Department of Circulation and Medical Imaging

Transcription

Foto: Geir Mogen
EVALUATION OF RESEARCH IN BIOLOGY, MEDICINE AND HEALTH IN NORWAY 2010–2011
Self-assessment
Department of Circulation
and Medical Imaging
• PANEL 2:
• Exercise Training in Health and Disease
• Extreme Environments and Health
• PANEL 4A:
• Cardiovascular Clinical and
Translational Science
• PANEL 4B:
• Ultrasound Innovation in Diagnosis
and Therapy
• Magnetic Resonance in Diagnosis
and Therapy
• Image Guided Therapy and Minimally
Invasive Interventions
Introduction
The Research Council of Norway is responsible for conducting evaluations of Norwegian
research. In 2010 the Council launched a comprehensive evaluation of biology, medicine and
the health sciences, including psychology. Included in the evaluation were Norwegian
universities, university hospitals, relevant research institutes and relevant university colleges.
The results will be available in the autumn of 2011.
The objectives of the evaluation are to:
•
•
•
•
•
perform a critical review of research in biology, medicine and the health sciences in an
international perspective;
obtain feedback on how Norwegian research can meet future challenges, especially in
relation to new interdisciplinary research fields and social challenges;
provide recommendations for measures to increase the quality and effectiveness of
research;
serve as a tool for institutions’ strategic planning and scientific development activities;
strengthen the basis for the Research Council’s research policy input to government
authorities.
Internal evaluations by the institutions/units under review
Each institution included in the evaluation was asked to carry out an internal evaluation to
provide the panels with information about the institution’s organisation, strategic goals,
research activity, infrastructure and other relevant factors.
The research groups of the Faculty of Medicine at NTNU and the St.Olavs HospitalTrondheim University Hospital was evaluated together, since their research and innovation
activities are highly integrated. The research groups were divided into 28 evaluation units.
Self-assessments including information about the organization and resources, as well as future
plans, was provided by each of the evaluation units.
This document presents the self-assessments that were produced by the research groups at the
Department of Circulation and Medical Imaging, the Faculty of Medicine.
Trondheim January 2011
Content
1.1.Institutional level:
1.1.1 Organisation of the department……………………………………………………p.1
1.1.2 Research leadership……………………………………………………………......p.2
1.1.3 Strategy…………………………………………………………………………….p.4
1.1.4 Scientific quality – Strong and weak research areas……………………………... .p.7
1.1.5 Resource situation………………………………………………………………. ...p.7
1.1.6 Training, mobility and career path……………………………………………… …p.9
1.1.7 Research collaboration, including interdisiplinarity……………………………… .p.10
1.1.8 Other information of relevance to the evaluation…………………………………..p.10
Attachment: Fact sheet, including organization chart
1.2 Research group/evaluation unit: Exercise Training in Health and Disease
1.2.1 Organisation, research leadership, strategy and resource situation…………….. ..p.1
1.2.2 Research activities, including interdisciplinary research and research impact……p.3
1.2.3 Training, mobility and career path………………………………………………..p.5
1.2.4 Research collaboration (national, international, industry/public sector), including
interdisiplinarity…………………………………………………………………..p.6
Attachment: List of publications
1.2 Research group/evaluation unit: Extreme Environments and Health
1.2.1 Organisation, research leadership, strategy and resource situation…………….. .p.1
1.2.2 Research activities, including interdisciplinary research and research impact….. p.2
1.2.3 Training, mobility and career path………………………………………………..p.4
interdisiplinarity…………………………………………………………………..p.5
1.2 Research group/evaluation unit: Cardiovascular Clinical and Translational Science
1.2.1 Organisation, research leadership, strategy and resource situation……………… .p.1
1.2.2 Research activities, including interdisciplinary research and research impact…... p.2
1.2.3 Training, mobility and career path………………………………………………...p.4
interdisiplinarity…………………………………………………………………...p.5
1.2.5 Other information of relevance to the evaluation………………………………….p.5
1.2 Research group/evaluation unit: Ultrasound Innovation in Diagnosis and Therapy
1.2 Research group/evaluation unit: Magnetic resonance in Diagnosis and Treatment
1.2 Research group/evaluation unit: Image Guided Therapy and Minimally Invasive
Interventions
Content
1.1.Institutional level (level 1): Department of Circulation and Medical Imaging
1.1.1 Organisation of the institution……………………………………………………… p.1
1.1.2 Research leadership……………………………………………………………........ p.2
1.1.3 Strategy……………………………………………………………………………... p.4
1.1.4 Scientific quality – Strong and weak research areas……………………………….. p.7
1.1.5 Resource situation………………………………………………………………….. p.7
1.1.6 Training, mobility and career path…………………………………………………. p.9
1.1.7 Research collaboration, including interdisiplinarity………………………………...p.10
1.1.8 Other information of relevance to the evaluation…………………………………... p.10
Attachment: Fact sheet, including organization chart (and CVs for level 1)
1.2 Evaluation unit (level 2): Exercise Training in Health and Disease
1.2.1 Organisation, research leadership, strategy and resource situation………………… p.1
1.2.2 Research activities, including interdisciplinary research and research impact…….. p.3
interdisiplinarity……………………………………………………………………. p.6
Attachments: List of publications
Curriculum vitae for the evaluation unit
1.2 Evaluation unit (level 2): Extreme Environments and Health
1.2.1 Organisation, research leadership, strategy and resource situation………………… p.1
1.2.2 Research activities, including interdisciplinary research and research impact…….. p.2
interdisiplinarity……………………………………………………………………. p.5
Attachments: List of publications
Curriculum vitae for the evaluation unit
1. Institutional level (level 1) – Department of Circulation and Medical Imaging
1.1.1 Organisation of the department
The Department of Circulation and Medical Imaging is one of five academic
departments under the Faculty of Medicine. It was established in September 2002 as part of
the reorganisation of the Faculty of Medicine, and is responsible for teaching, research,
innovation and dissemination of popular science in the disciplines: anaesthesiology,
biomedical engineering, cardiology, cardiopulmonary physiology, cardiothoracic surgery,
exercise physiology, pulmonary medicine, radiology and vascular surgery.
Since the reorganisation, the department has successfully implemented its strategic
plan for 2002-2010, to exploit the ongoing revolution in biosciences and medical technology.
A central action has been to stimulate the creation of research groups with a critical mass for
performing research on a high international level. The department has focused on
interdisciplinary collaboration between clinical medicine, translational biomedical research
and medical technology. Close collaboration with the relevant clinical departments at St.
Olavs Hospital has been an important tool. The research units have been very successful at
obtaining external research funding from a wide variety of sources. Much of this funding is
relatively short term and the department has a strong focus on helping its research groups to
stay winners at competitive calls based on scientific excellence and relevance for health care.
The Department of Circulation and Medical Imaging currently hosts several large to
medium size interdisciplinary collaborations and other common infrastructure. The MI Lab
(Medical Imaging Laboratory) was established as a Centre of Research-based Innovation in
2007 with funding from the Research Council of Norway and industry. It joined the forces
and formed a common strategic focus of successful research groups in magnetic resonance,
ultrasound innovation and image guided surgery. MI Lab is one of three such centres within
Medicine and Health in Norway and has a total budget of 240 MNOK over 8 years. By
November 2010 MI Lab has 30 PhD students and postdoctoral fellows.
The National Centre of 3D ultrasound and image guided surgery is the cornerstone in
a research and innovation network, which includes the Future Operating Room at St Olavs
Hospital and several industrial partners. As described under the specific research units, other
strong projects are emerging in relation to exercise, metabolomics, clinical cardiology and
professional diving, as a result of prioritising larger collaborative efforts. The Department of
Circulation and Medical Imaging provides a fertile environment for multidisciplinary and
interdisciplinary collaborations called for by today's scientific, technical and medical
community. Its strong tradition of medical innovation contributes to an inherently interactive
place where engineers, research scientists and clinicians may easily exchange ideas and
collaborate on a daily basis, facilitating efforts to improve health care technologies and
services. An example of success is Vscan, the new pocket-size hand-held ultrasound scanner
from the MI Lab partner GE Vingmed Ultrasound. The research behind Vscan was performed
as a collaboration between GE Vingmed Ultrasound and the research group of Professor Hans
Torp at the Department of Circulation and Medical Imaging. Further R&D on clinical
application and technology devlopment is an important focus for MI Lab. Vscan was voted
the 14th most important invention worldwide by the readers of Time magazine after its
international release in 2009. Its pioneer technology may become a universal tool for
physicians similar to the stethoscope. The first scientific study using Vscan in general practice
has been performed in three GP offices in the Trondheim area.
Moving into the new University Hospital in January-April 2010 represented a major
leap forward implementing the strategic decision of full integration of clinical service,
translational medical research and medical technology within the Emergency and
Cardiopulmonary Medicine Centre. The departments of anaesthesiology, cardiology,
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cardiothoracic surgery, pulmonary medicine and vascular surgery are now located in the same
building as the staff offices and the laboratories for biomedical engineering, ultrasound,
exercise physiology and translational research. Magnetic resonance imaging research
laboratories and animal research facilities are located in adjacent buildings. Such a dense colocalisation of personnel involved in routine clinical service, innovation and translational
research yields a unique opportunity for facilitating and managing synergy effects. The
Operational Team of the Department and the leadership of its adjunct clinical departments
meet regularly in a common forum for research strategy.
At the reorganisation in 2002 the Department of Circulation and Medical Imaging was
organised in sections. The purpose was to coordinate research activities in larger units and to
serve as a link for two-way information and cooperation between the staff and the Operative
Management Team. This strategy led to more networking within the department, yielding
higher levels of collaboration and accomplishment.
A first example of the success of this strategy was the creation of MI Lab by
amalgamating magnetic resonance and ultrasound imaging. Another was combining
translational exercise research and environmental physiology into a section that developed
close collaboration with cardiology, pulmonary medicine, ultrasound technology and
magnetic resonance imaging. Today the section for ultrasound and magnetic resonance and
the section for exercise and extreme environments are successful translational research units
that combine basic biomedical research, medical technology innovation and clinical research.
In patient-oriented clinical research the department faces a challenge with some small groups
below or close to critical mass in related fields, that have yet to identify common goals, either
mutually or with other more established units. Some of the researchers are successfully
integrated in the inter-departmental unit for Opioids, Symptom Management and Palliation, as
reported under the Department of Molecular Medicine and Cancer Research. Others join in
the emerging unit of Cardiovascular Clinical and Translational Science, as reported here.
1.1.2 Research leadership
Strategic research leadership of the department is anchored in an Operative
Management Team that collaborates closely on strategy and staffing with the Faculty of
Medicine through the Dean, and with the research groups through the Section Leaders. The
ongoing process of integration with the University Hospital aims at transforming informal
contacts regarding career development and research projects between Heads of academic and
adjunct clinical departments into closer and more binding strategic action.
The Department of Circulation and Medical Imaging is led by the Head of Department,
who is appointed by the Dean of the Faculty of Medicine for a four year term, and who may
be re-appointed for another four years. Øyvind Ellingsen, MD, PhD, Professor of Cellular
Cardiology, serves his first term as appointed Head of Department (2009-2013). He is an
accomplished translational scientist in heart failure and exercise training and was the former
Deputy Head (2006) and elected Head of Department (2007-2009), has international
leadership experience chairing the Section of Exercise Basic and Translational Research
within the European Association for Cardiovascular Prevention and Rehabilitation (20082010), and currently chairs the European SMARTEX-HF multicenter study.
The department is managed by an Operative Management Team that meets every 2-3
weeks, and by administrative staff who run the day to day buiness. The Operative
Management Team includes the Head and the Deputy Head of Department, three Section
Leaders (appointed by the Head of Department), the director of MI Lab, the Chief executive
officer, an elected student representative and two elected staff member representatives (one
for technical staff and one for PhD students and postdoctoral fellows). Its present composition
secures a broad range of diverse interests and priorities in technological and translational
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research and innovation. Strengthening clinical research expertise representation and
leadership is an important goal for the ongoing process towards reorganisation of the sections;
a limiting factor is the small number of clinical scientists in full time university positions.
The Operative Management Team decides how to implement and practice the
department’s strategies, plans and policies for research, teaching, innovation, staffing and
economy. Every semester, the Operative Management Team is supplied by two external
representatives appointed by the Dean to constitute the Department Council. Institutional
matters of major and principal significance, including strategic priorities, economy and budget,
are discussed. The Operative Management Team and the Department Council function as
advisory bodies; decision power and responsibility lies with the Head of Department, who
reports directly to the Dean. As indicated above (1.1.1) the role of the Section Leaders is to
coordinate research activities in larger units and to serve as a link for two-way information
and cooperation between the staff and the Operative Management Team. Project leaders
(principal investigators) enjoy an extensive degree of freedom to choose projects within their
field of expertise and a correspondingly high degree of autonomy and responsibility in
running their projects according to budgets and plans, since a major part of research activities
are funded independent of the department budget (see below, 1.1.5). All project applications
to internal and external funding bodies and to the Ethics Committee must be approved by the
Head of Department before submission.
Allocation of research funding is largely dependent on external sources. Salaries for
PhD students, postdoctoral fellows and other temporary employed research staff, and other
running costs related to research projects come from competitive grants from the Research
Council of Norway, the Central Norway Regional Health Authority and other public and
private national and international sources. An important strategic priority is therefore to help
the research groups to stay winners at competitive calls based on scientific excellence and
relevance for health care, and to leave a large degree of autonomy to successful project
leaders. In contrast, tenure of faculty, technical and administrative staff lies with the Dean,
and is largely funded by NTNU. Implementing strategic research priorities in the recruitment
of new professors, engineers and officers therefore involves close collaboration with the Dean
to achieve common goals.
As described below, 35-40% of the department’s budget of about 6 MNOK constitute
its intrinsic strategic leeway after basic running costs (1.1.5). About 1/5 of this is given to
faculty as research funding, rewarding PhD and master degree supervision, publication in
peer-reviewed journals, and selected teaching and administrative activities. The remaining 4/5
are allocated to research projects by the Operational management after internal competition
based on strategic goals; small or medium size projects with potential to eventually attract
external funding is prioritised, based on scientific excellence and relevance.
Division of work time between research, innovation, teaching, clinical work, and
scientific advice to the governing authorities, scientific journals, funding organisations and
other external institutions is highly dependent on type of appointment, research training and
achievements. Typically, university faculty have 40-60% of their time dedicated to research,
whereas hospital researchers have 5-20%. The Faculty of Medicine and St Olavs Hospital
offer generous opportunities for 1-year or 4-months sabbatical research terms on full salary
every five years, respectively.
Faculty with a high scientific output often get reduced teaching duties and more time
for research, whereas those who neither publish nor attract research funding have to take on
larger teaching responsibilities. Advisory activity, leadership in professional organisations and
involvement in peer-review is generally encouraged, since they usually contribute to a high
level of competence and often involve networking that is highly beneficial for research
activity and public standing of the university.
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Insufficient time for research because of pressing patient related duties is a prevalent
symptom of structural factors that contribute to scientific under-performance in some clinical
disciplines. As detailed in the following sections (1.1.3-1.1.6) a major strategic challenge for
the department is the limited opportunity for experienced physicians to participate in research
activities. This requires common strategic goals and close practical collaboration with St
Olavs Hospital at all levels of leadership. The health care systems in the rich countries,
Norway included, face the challenge of escalating costs, and there is a tendency towards less
opportunity within the hospitals for allocating protected time for research. The Faculty of
Medicine has together with St Olavs Hospital established a flexible system for coemployment between university and hospital, and the department uses this for hiring
physicians with the best possible combination of research and clinical work for the benefit of
the research units and projects. Within this framework it is still an important task for the
hospital and university leadership to secure sufficient protected time for high quality research.
1.1.3 Strategy
After the previous evaluation in 2003, the department has successfully followed the
recommendations and implemented its resulting strategic plans in the following ways:
• The department has extended its strategic position as a “resource centre” of medical
technology for the whole NTNU where engineers, translational scientists, clinical
scientists and industrial innovators collaborate across disciplines to meet health care
needs. Establishing the MI Lab has formed a template for interdisciplinary research
and innovation that cover the whole chain from idea to clinical application. This
consortium has the potential to develop into a centre for innovation. Using the success
of carrying basic research results in acoustics through patenting to state of the art
ultrasound scanners has formed a powerhouse that utilises the potential to crosslink
with new disciplines. Several steps have been taken to exploit the potential of
molecular biology and nano-medicine. The department has invested in state of the art
high-field MR systems as a basis for collaboration with strong groups of molecular
genomics of breast and prostate cancer. A project for ultrasound mediated drug
delivery won an NTNU-funded interdisciplinary medical technology grant in
collaboration with the departments of biophysics and chemistry.
• The department has made a strategic effort of carrying research results and
innovations all the way from idea to clinical applications by strengthening the patientoriented aspect. As already mentioned (1.1.1) the department is carrying out studies to
evaluate the usefulness of the pocket-size ultrasound scanner (Vscan) by employing
clinical postdoctoral fellows and PhD students as part of the innovative industrial team.
It also chairs the steering committee, is the coordinating centre and runs the
echocardiography core-lab of a European multicenter study of exercise training in
heart failure (SMARTEX-HF), thus testing whether superiority of high intensity
interval training in experimental studies and small size feasibility studies applies in a
randomised clinical trial large enough to affect standard practice. Other examples
provide similar opportunities for clinicians in to participate in cutting edge projects,
sometimes involving “internal” or adjacent departments, sometimes involving external
institutions, depending on capacity and training.
• The department has taken several strategic steps to support concrete projects to exploit
data from the HUNT population surveys and the samples from its biobank. It took
advantage of the high quality translational research in exercise physiology and
initiated a Fitness Project in collaboration with experts in epidemiology at the
Department of Community Medicine. A sample of 4500 respondents across ages13-80
was tested for peak oxygen uptake by ergospirometry and for endothelial function by
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•
ultrasonography of brachial artery flow-mediated dilation. The first cross-sectional
studies of associations with self-reported questionnaire-based data on physical activity
are being submitted for publication. Molecular genomics studies of aerobic capacity
are in progress, and prospective follow-up studies on fitness, aerobic capacity and
mortality will be carried out when observation time permits. Examinations of 1350
respondents by echocardiography and 1000 by cerebral magnetic resonance imaging
(MRI-HUNT) yield unique information on the variation of heart and brain phenotypes
across age groups in a healthy population. A total of 10-15 PhD projects are expected
to result from baseline and follow-up studies.
The department has made several strategic investments to develop a strong group of
translational research on exercise in medicine. One of the successful postdoctoral
fellows from the group, Ulrik Wisløff, was appointed full professor of Cardiovascular
Physiology at a young age, in stiff competition with several international applicants. In
response, and the department has prioritised funds for state of the art laboratories of
cellular cardiology, including confocal imaging, epifluorescence microscopy and
patch clamp electrophysiology, in order to support his efforts to identify cellular and
molecular mechanisms of enhanced cardiac function in response to exercise training.
It has also recruited an internationally recognised expert in electrophysiological and
optical techniques, Professor Godfrey L. Smith, University of Glasgow, as adjunct
professor to support these activities. Facilities for exercise testing and training have
been established for translational and clinical science. These investments have resulted
in high impact publications in Circulation, Science and Nature Medicine, and as
already mentioned, a fruitful translation into a European multicenter study on a novel
exercise training programme for heart failure patients.
Main strengths of the department
Professional
• An adequate number of key faculty experienced in translational biomedical science
and innovation
• Some key faculty with a good track record of international publication and patenting,
researcher training and dissemination
• State of the art infrastructure and equipment
• Well established local, national and international interdisciplinary networks
Financial
• Ability to generate a large amount of projects within strategic goals by external
funding from regional and national sources
Organisational
• A successful research strategy that helps research groups stay winners at competitive
calls based on scientific excellence and relevance for health care
• Appointed leadership with a strong strategic mandate and close collaboration with the
Dean regarding staffing
• Well functioning research groups that prioritise the right number of projects within an
adequate strategic focus
Main weaknesses of the department
Professional
• Lack of critical mass for strategic research activities in some clinical disciplines, i.e.
insufficient capacity and/or training
• Severe limitations in Norwegian hospitals’ ability to allocate protected time for
research, i.e. drastic measures to reduce escalating health care costs
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Financial
• Lack of flexibility to hire professors and technicians on temporary contracts according
to needs related to short and medium term projects
• Renewal of costly equipment (e.g. MRI scanners) that can mainly be obtained through
external funding
Organisational
• Some research initiatives below a critical mass that need to combine mutually or with
a larger, well established unit to realise their potential
Research strategies and plans
The research strategy of the department coincides with currents trends and
developments within the field by exploiting the ongoing revolution in biosciences and
technology within the three main research strategic areas of the Faculty of Medicine:
• Medical Technology
• Translational Research
• Health Surveys and Biobanking
The strategic vision is an academic department working in concerted action with its
adjacent clinical counterparts – where clinicians, technologists, translational scientists, and
industrial innovators collaborate closely in interdisciplinary projects to meet the needs of the
health care sector.
To realise this vision, the department will pursue the following main goals of its 20022010 strategy for research and innovation:
Overarching priorities
• Joint strategies with adjacent clinical departments and concerted action anchored with
leadership to strengthen patient-oriented clinical research
• Exploiting the potential of translational research in clinical disciplines
• Innovation for improved patient outcomes and cost-effective health care
• Research units with critical mass to sustain strategic action, including translational and
interdisciplinary collaboration, grant writing and other organisational needs
Medical Technology
• Magnetic resonance and ultrasound for innovation, clinical diagnosis and treatment
• Image guided therapy and minimally invasive interventions
Translational research
• Excercise training for prevention, treatment and rehabilitation in cardiopulmonary
disease
• Clinical cardiovascular problems in anaesthesiology, cardiology and cardiothoracic
surgery
• Diving safety and bubble formation
Health Surveys and Biobanking
• Collaborative epidemiology of the North-Trøndelag Health Survey (HUNT),
especially the Fitness Project
• Functional genomics with the HUNT Biobank, within the department’s translational
research areas, e.g. MRI-HUNT and the Fitness Project
The goals will be adjusted according to an ongoing strategic process at the University –
NTNU and at the University Hospital – St Olavs Hospital. A revised NTNU strategy is
scheduled to be approved by its Board in March 2011. The Faculty of Medicine has suggested
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that Health is included as a main Focus of NTNU; the main research foci of the Faculty
remain as listed above. The Dean has also initiated a joint process with the director of the St
Olavs Hospital in order to further integrate clinical and academic departments’ strategies and
organisation. The Operative Management Team of the Department of Circulation and Medical
Imaging has initiated regular meetings with Heads of adjacent clinical departments in order to
identify and develop joint strategies and concerted action for research and innovation.
1.1.4 Scientific quality – Strong and weak research areas
A majority of faculty are part of productive collaborations within one of the six main
research units reported under the Department of Circulation and Medical Imaging:
1. Exercise Training in Health and Disease (Panel 2) has evolved into an internationally
recognized unit of translational research. Its main focus is the beneficial effects of exercise
training in cardiovascular disease and the metabolic syndrome, including the whole research
chain of cellular, molecular, clinical and epidemiological aspects.
2. Extreme Environments and Health (Panel 2) is a rapidly growing unit with international
competence on bubble formation during decompression and the occupational risk related to
diving.
3. Cardiovascular Clinical and Translational Science (Panel 4a) comprises a network of key
persons well established in adjacent clinical fields that are likely to benefit mutually by
developing and pursuing common goals within a firmer organisational structure.
The following three units: 4. Ultrasound Innovation in Diagnosis and Therapy; 5. Magnetic
Resonance in Diagnosis and Therapy; and 6. Image Guided Therapy and Minimally Invasive
Interventions (Panel 4b) constitute a highly successful interdisciplinary research network of
engineers, research scientists and clinicians with a strong focus on medical innovation to
improve health care technologies and services. Activities, strengths and weaknesses of the
specific units are detailed below (1.2). Some researchers are part of a successful unit for
Opioids, Symptom Management and Palliation, reported under the Department of Molecular
Medicine and Cancer Research. All units represent networks of faculty who regularly publish
in peer-reviewed international journals; some of the works represent high impact science or
cutting edge innovation internationally.
Pulmonary medicine is at a developmental stage where faculty with limited research
time are pursuing different sub-disciplines. Two staff members are collaborating within units
of exercise training and image guided therapy, and are represented with CVs, respectively.
Two part time clinical researchers working on chronic obstructive pulmonary disease, Anne
Hildur Henriksen and Malcolm Sue-Chu, have yet to amalgamate into a larger unit and are
represented with CVs directly under the department. Helge Bjørnstad Pettersen holds a full
time university position and has been dedicated to teaching and clinical work (CV listed under
department).
The department adheres to a policy of encouraging publication of all studies in peerreviewed international journals. All publication-dependent allocation of funding in the
department’s budget is distributed to authors according to number and impact; national level 2
journal articles yield triple weight. Research groups involved in research focused towards
innovation tend to be under-represented in number and scientific impact of publications.
Heavy work loads and delay related to patenting, and highly specialised fields of interest are
reasons why the output of innovative research may not be accurately assessed solely by
counting scientific articles.
1.1.5 Resource situation
The new University Hospital represents a major upgrade of structural resources for the
department. Not only has it set the stage for functional amalgamation with its adjacent clinical
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departments in the Emergency and Cardiopulmonary Medicine Centre. With new buildings
came also generous funding for renewal of research equipment (see list below). The last five
years have seen a substantial increase in funding for PhD students, postdoctoral fellows and
small to medium sized research projects and infrastructure, especially from the Central
Norway Regional Health Authority and from the Research Council of Norway through MI
Lab. In contrast there is no growth in permanent positions for professors and technicians.
Consequently the number and capacity of people with sufficient time and know-how to write
and run competitive grants is becoming a rate limiting factor for further development. This is
particularly true for clinical research carried out by faculty with extensive clinical
commitments. As already mentioned (1.1.2) insufficient and/or fragmented time is a major
limitation for patient-oriented research in clinical disciplines. A major cause is the position
structure, where a majority of clinical faculty is hired mainly for teaching, on contracts with
5-20% research time. Research time is typically spread out, with little protection from
pressing patient related duties. However, for some of the physicians the scientific output
volume and quality is very good compared to resources available.
Academic staff of the department has high competence (see above, 1.1.3, strengths and
weaknesses). There is a good mix of ages and relevant backgrounds, including physicians,
technologists and basic scientists, but there are few women in senior ranks. However, there is
excellent recruitment of women researchers among PhD students and postdoctoral fellows.
The department has a policy of encouraging women to apply for faculty positions; in 2010 it
has appointed Charlotte Bjørk Ingul as senior researcher (UNIKARD) and it has nominated
Professor Ingrid Gribbestad for a tenured chair in MR technology. Full time faculty positions
as well as PhD stipends and postdoctoral fellowships are advertised internationally whenever
feasible. Since Scandinavian language requirements may be a limiting factor, the department
finances NTNU courses in Norwegian from beginners to advanced level. A Swede is being
recruited for a full professorship in vascular surgery.
The following table describes available research infrastructure at the department. The
faulty of Medicine is establishing a funding system to replace small to medium equipment.
Renewal of more costly MR equipment is highly dependent on external sources. The
department complies with the Faculty’s policy to establish and utilise common core facilities.
Investments in equipment > 1 mill. NOK at ISB, DMF, NTNU (All prices ex. VAT.)
Name/type of equipment
Location
Price
NOK
Servicecosts/year Year
of
(estimated) acquisition
2 photon confocal microscope
Fluorescense microscope, inverted
Upgrade package for Patch Clamp
Confocal microscope
Confocal microscope
Patch Clamp for fluorescense
microscope
Fluorescense microscope, inverted
Pressurechamber with controlsystem
Fluostar Omega, Plate reader
photometer
Ergospirometry equipment for
humans, Jaeger
342.03.022
342.03.034A
342.03.063
342.03.063
342.03.063
5 000 000
2 000 000
1 500 000
2 600 000
2 000 000
70 000
30 000
0
30 000
30 000
Spring 2011
2009
2010
2010
2004
342.03.071
342.03.071
342.03.055
2 000 000
2 600 000
1 900 000
40 000
30 000
10 000
2010
2005
2008
342.03.K15
1 500 000
25 000
2010
343.01.027
1 000 000
25 000
2008
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Ultrasound,
echo-doppler
for
heartexamination
Ultrasound,
echo-doppler
for
heartexamination
Ultrasound
scanners
for
experimental research (2 scanners)
Ultrasound scanner for small
animals VEVO 2100 (9-70 MHz)
Relaxometer with gradient
High resolution NMR 14,1 Tesla
(2 scanners)
High resolution NMR 11,7 Tesla
Clinical 3 Tesla
Animal scanner 7 Tesla
Total
343.01.015
2 000 000
15 000
2010
343.01.021
2 000 000
15 000
2010
342.03.006
Animal
Facility
MR Centre
1 500 000
50 000
2010
1 700 000
1 500 000
25 000
25 000
2010
2008
MR Centre
MR Centre
Neuro Centre
MR Centre
9 600 000
1 500 000
20 000 000
13 000 000
450 000
150 000
1 000 000
400 000
2010
1995
2006
2004
72 900 000 2 420 000
The department is involved in two major national research infrastructures, including
NORBRAIN and NorMIT. The former is in neuroscience and comprises the Kavli Institute
for Systems Neuroscience in Trondheim, MI Lab and the Centre of Molecular Biology and
Neuroscience in Oslo. The latter is a collaboration between the Operating Room of the Future
at St. Olavs Hospital and the Intervention Centre at Oslo University Hospital. Both are on the
Research Council of Norway roadmap for large-scale national research infrastructures.
1.1.6 Training, mobility and career path
The Department of Circulation and Medical Imaging has been steadily increasing the
number of PhD students, postdoctoral fellows and research scientists over the past five years,
according to the strategy. It is committed to gender equality and adheres to NTNU’s policies.
When recruiting, gender is taken into consideration if candidates have relatively equivalent
qualifications. As shown in the table below, the percentage of women is very satisfactory and
the number of international candidates increases. Women researchers seem to attract larger
proportions of women recruits, even in medical technology, which is still dominated by men.
Age balance in academic positions is not a problem; the department adheres to NTNU’s
general policy of facilitating staying employed to age 70 for everyone who wishes.
PhD
Women
Students
Men
Postdoctoral Women
Fellows
Men
Research
Women
Scientists
Men
Total
International
2005 2006 2007 2008 2009
11
10
18
21
26
18
22
28
27
36
5
8
7
13
12
3
2
6
9
12
0
0
3
3
5
4
5
5
7
12
41
47
67
80
103
4
4
7
14
17
Recruitment of highly skilled and motivated candidates is very satisfactory in most
disciplines of the department. Medical imaging is popular with engineering and medical
students, thanks to courses and hands on laboratory exposure given in early years. Exercise
and diving is often associated with an exuberant life style that attracts interest from science
9
students of many disciplines. Difficulties in recruiting physicians into research are prevalent
in many Western countries, including Norway; overall this is not the case for most fields of
the department. A 12-week student thesis and an imbedded first PhD year research track
attract highly motivated medical students to the department, and the majority pursues research
towards completing a PhD. Patient-oriented clinical projects are quite popular, and these
activities should be a good source of recruiting future faculty.
To stimulate interest in medical imaging research, the MI Lab leader Olav Haraldseth
is the promoter and current leader of the Norwegian Research School in Medical Imaging
(www.ntnu.no/medicalimaging). It is a collaboration of the universities in Trondheim, Oslo,
Bergen and Tromsø, one of five research schools funded by the Research Council of Norway,
with a total budget of 24 MNOK over 8 years. Its aim is to improve the quality of medical
imaging research in Norway, and this will be achieved by enhancing national collaboration,
multi-disciplinary research, quality of PhD training, and recruitment of the best students.
An increasing number of PhD students spend part of their time abroad. This requires
highly coordinated projects and close collaboration with the sponsoring institution. Some
examples are given in section 1.2.3. Medical imaging offers excellent opportunities for
exposure to future-oriented industrial research challenges through its partners, including
innovators and adjunct professors in MI Lab and other projects.
PhD students and postdoctoral fellows are supported to become independent
researchers by acting as co-supervisors for medical students and master students, but time
constraints (3 year-funding for PhD, 2-3 for posts-doc) sometimes render this difficult. Postdocs may be main supervisors for PhD students, given there is a backup plan involving senior
faculty if they should leave. They are also involved in co-writing larger grant applications and
are sometimes encouraged to submit independent smaller grant applications. Since 2006, three
postdoctoral fellows from the exercise group have been appointed to senior research
positions; Ulrik Wisløff as tenured professor at the department in 2008, Ole J. Kemi as Senior
Lecturer at the University of Glasgow from 2006, and Jan P. Loennechen as an associate
professor at the department in 2006.
1.1.7 Research collaboration, including interdisciplinarity
The Department of Circulation and Medical Imaging provides a fertile environment
for multi- and inter-disciplinary collaborations called for by today's scientific, technical and
medical community. Its strong tradition of medical innovation contributes to an inherently
interactive place where engineers, research scientists and clinicians may easily exchange ideas
and collaborate on a daily basis, facilitating efforts to improve health care technologies and
services. Most units have extensive national and international networks and this is reflected in
a large proportion of co-publication with international universities (1.2). Projects in progress
are presented for the whole department in monthly meetings, and on 1-2-day yearly seminars.
The department has six adjunct professors from other universities to complement its expertise
and facilitate exchange, including Anders Dale (University of California, San Diego), Arend
Heerschap (Radboud University Nijmegen), Sverre Holm (University of Oslo), Kjell
Kristoffersen (GE Vingmed Ultrasound), Henrik Larsson (Glostrup University Hospital) and
Godfrey Smith (University of Glasgow). These appointments have been successfully used to
supplement the expertise within the faculty, thus improving scientific output volume and
quality. As described above, the department actively pursues translational research and
innovation in collaboration with industry as some of its core strategic goals (1.1.3).
1.1.8 Other information of relevance to the evaluation
None
10
The Regional Centre for
Child and Adolescent
Mental Health (RBUP)
Cardiovascular
Clinical and
Clinical Microbiology
and Infectious
Disease
Orthopedics
Image Guided Therapy
and Minimally Invasive
Interventions
Neurodevelopmental
Disorders and
Brain Imaging
Adult Psychiatry
Magnetic Resonance
in Diagnosis
and Therapy
Obstetrics
Gastroenterology
Mobility Disorders
Ultrasound Innovation
in Diagnosis
and Therapy
Community Health
and Social Medicine
Gynecology
Immunology and
Hematological
Cancer
Headache Disorders
Extreme Environments
and Health
General Practice
and Primary Health
Tumor Biology
Research Group
Opioids, Symptom
Management and
Palliation
Neurodegenerative
Diseases
Exercise Training in
Health and Disease
Epidemiology and
Health Services
Research
Clinical
Pharmacology and
Toxicology
DNA Repair and
Genome Stability
University
Organisation Chart
Centre for the
Biology of Memory
(CBM)
CBM / KISN
Centre of Excellence
Dept. of
Neuroscience
Dept. of
Circulation and
Medical Imaging
Dept. of
Public Health and
General Practice
Faculty
Departments
Evaluation Units
The Norwegian EHR
Research Centre
(NSEP)
Dept. of Laboratory
Medicine, Children’s
and Women’s Health
Dept. of Cancer
Research and
Molecular Medicine
Faculty of Medicine
Dean
NTNU
Faculty of Medicine
Rector
Board
NTNU
Board
www.ntnu.edu/dmf
Panel 2
EVALUATION OF RESEARCH IN BIOLOGY, MEDICINE AND HEALTH IN NORWAY 2010 – 2011
Self-assessment – Level 2
Exercise Training
in Health and Disease
1.2 Evaluation unit (level 2): Exercise Training in Health and Disease
1.2.1 Organisation, research leadership, strategy and resource situation
The primary objective of the unit is to utilise the beneficial effects of exercise training in
prevention, treatment and rehabilitation of cardiovascular disease, metabolic syndrome, and other
major non-communicable conditions, by developing evidence-based exercise training programmes
and by identifying underlying cellular and molecular mechanisms. The major focus of the unit is
translational cardiovascular science, including the whole research chain of cellular, molecular,
experimental, clinical and epidemiological aspects. The unit runs a two-year research based Master
of Science programme in Exercise Physiology and Sport Sciences that studies the application of
scientific principles and techniques with the aim of improving performance. The research of the
unit is organised in two groups:
1. Cardiac Exercise Research, led by Professor Ulrik Wisløff
2. Exercise Physiology and Sport Sciences, led by Professor Jan Helgerud and Professor Jan
Hoff.
Professor Wisløff is Section Leader and represents the unit in the Operative Management Team.
Cardiac Exercise Research (www.ntnu.edu/isb/cerg)
Professor Ulrik Wisløff runs the majority of the projects in this group, with 80% time for
research and 20% for teaching and administration. He was awarded a 4-year Young Outstanding
Investigator Grant from the Research Council of Norway in 2007. Wisløff has recently been
granted a K.G. Jebsen Centre of Exercise in Medicine of 4 million NOK for 4 years, starting in
2011, which releases even more funding from NTNU and the Central Norway Regional
Authorities. He has also been awarded a major 4-year grant from the Research Council of Norway,
starting in 2011. The total of these grants will support research for over 10 million NOK per year,
spent on improved cardiovascular health. Professor Øyvind Ellingsen and Associate Professor
Sigurd Steinshamn combine 20% time for research with full time positions as Head of the
Department of Circulation and Medical Imaging and Senior Consultant at the Department of
Pulmonary Medicine, respectively. Professor Stig A. Slørdahl has combined his position as Dean
of the Faculty of Medicine with supervising PhD projects. The researchers have successfully
established an interval training programme for patients with cardiovascular disease. They have also
developed and characterised experimental models of exercise and cardiovascular disease to study
cellular and molecular adaptations to exercise.
The Cardiac Exercise Research Group currently comprises 7 post-docs, 18 PhD students and
2 master students. Three of the post-docs and 10 of the PhD students are women. There are 2
international PhD students, from Brazil and Pakistan, respectively, and 1 international Master
Student. The group has one international Adjunct Professor, Godfrey L. Smith from the University
of Glasgow, and 2 engineers.
The researchers publish a large proportion their work in high-ranked cardiovascular journals,
and have established an international reputation for high quality research within the field. Over the
last 10 years the group has developed strong regional, national and international scientific
collaborations, thereby providing a broad spectre of forefront methodology. This strategy is
essential to ensure that the research remains internationally competitive in identifying the
mechanisms of myocardial adaptive processes associated with exercise. Articles from the group
are frequently cited and are featured by the media both nationally and internationally. In Norway
the research is highlighted on Norwegian television 3-8 times each year and senior faculty are
frequently invited to present at international conferences (for examples see “Media Attention”
www.ntnu.edu/isb/cerg).
1
Exercise Physiology and Sport Sciences (www.ntnu.no/studier/msport/default)
Professor Jan Helgerud and Professor Jan Hoff carry out a major part of their research with
students of the 2-year international Master of Science program in Exercise Physiology and Sport
Sciences. Ten students per year graduate, and their work is published as part articles in good to
excellent peer-reviewed journals. The master program has an engineer dedicated to its laboratories,
who also contribute significantly to teaching ad research. The group has currently 2 PhD students.
Resources
Funding medical research has increasingly become a priority of the Central Norway Regional
Health Authority over the past decade, and financial resources to employ research fellows and
post-docs have improved substantially. As international reputation has increased, the Cardiac
Exercise Research Group has obtained grant funding from external sources such as the Research
Council of Norway, the Norwegian Council on Cardiovascular Diseases, the British Heart
Foundation (in collaboration with Prof. Mark Boyett, Manchester UK), and the National Institute
of Health (in collaboration with Professor Steven L. Britton, University of Michigan, USA). It is
also part of a consortium that recently applied for funding from the EU (FP7, in collaboration with
Professor Burkert M. Pieske, Phillips University of Marburg, Germany). As part of the new
integrated university hospital development, the Department of Circulation and Medical Imaging
has state of the art laboratories and research equipment for basic and clinical research. The
laboratories provided are of the highest quality and the Department still has funding to upgrade or
buy new equipment through 2013. The challenge during the next years will be to maintain and
expand staff in order to capitalise on the new infrastructure.
A particular challenge is to find funding to support the best local and international scientific
talent and to attract the best international post-docs and clinical scientists. As the number of
permanent positions has been reduced over the last 5 years, the administrative burden of each
academic has increased, thus leaving less time for research activities. This increases the need for
experienced PhD and post-doctoral fellows to support the research. Despite these limitations,
performance in terms of quality and quantity of research as very high, and it is likely that the unit
will remain competitive for major grants.
As described in section 1.1, co-localisation with the clinical departments in the new
University Hospital provides excellent facilities for interdisciplinary collaboration in translational
and clinical research, with easy access to patients and human tissue samples. The Faculty of
Medicine is host to five PhD programs, all with extensive teaching curricula to ensure excellent
training for current students.
Investment the last 5 years with value more than 1 000 000 NOK
Small animal ultrasound scanner (VEVO, Visual Sonics US)
Ergospirometry for humans (Jaeger, Germany)
Patch-Clamp system (Cairn Instruments UK)
Fluorescence microscopes (x3) for study of isolated cardiomyocytes (Cairn Instruments)
Confocal microscope from Zeiss (Germany)
Spinning disc confocal microscope (Cairn Instruments UK)
The research unit has an extensive network of collaborators worldwide. As part of these
collaborations some tissue samples and datasets are analysed at other institutions. This
complements local expertise and capacity. Training of research staff frequently entails visiting and
using specialised equipment in other institutions. For example, over the past 2 years, members of
the research staff has visited the laboratory of Professor Godfrey L. Smith at the University of
Glasgow to train in single cell electrophysiological techniques and to review the technique of 2photon confocal microscopy and wide-field imaging of heart muscle cells.
2
1.2.2 Research activities, including interdisciplinary research and research impact
Cardiac Exercise Research
The Cardiac Exercise Research Group has an internationally established record for
translational research. To exemplify, we demonstrated in a rat model that aerobic interval training
may be a potent modifier of post-infarction heart failure. Based upon these results, we
demonstrated the efficacy of aerobic interval training in enhancing cardiovascular fitness and
reversing myocardial remodelling in heart failure patients (Wisløff et al Circulation 2007). At
present, the group runs a multicenter phase-II type clinical trial (SMARTEX-HF, clinical Trials
Record #090309) in 7 European centres, and serves as the coordinating center. This study is
aiming to extend previous findings and establish safety in a larger and more heterogeneous
population of heart failure patients. Further studies in the rat model have increased our
understanding of some of the molecular mechanisms behind improved cardiac function after
aerobic interval training.
By close collaboration with the Department of Cardiology and Department of Cardiothoracic
Surgery, the group has recently been able to isolate cardiomyocytes from biopsies taken from the
left ventricular myocardium of patients with or without post-infarction heart failure during
coronary artery bypass grafting. We are among the first groups to report contractile function,
calcium handling and mechanisms of impaired contractile function in isolated cardiomyocytes
from such patients. These procedures open a new window of opportunity for detailed and
quantitative assessments of cellular physiology of the human myocardium before it enters endstage in heart failure, in a manner that few groups have access to internationally. This make it
possible to conduct controlled experiments to identify molecular targets that may rescue cardiac
pump function and prevent it from progressing into the end-stage of heart failure. Our preliminary
data demonstrates that cardiomyocytes from patients with heart failure have somewhat preserved
contractile capacity at rest, but a reduced ability to increase contractile capacity at higher heart
rates, such as during physical activity. Furthermore, reduced control of intracellular diastolic
calcium (Ca2+) in heart failure patients probably explains the increased frequency of spontaneous
contraction which may lead to ventricular arrhythmias and sudden death. Central mechanisms
underpinning the deterioration in Ca2+ cycling and hence cardiac function has been linked to
reduced activity of the protein sarcoplasmic reticulum (SR) Ca2+ ATPase 2a (SERCA-2a), which
recycles Ca2+ back to its storage in the SR during diastole. We also found a loss of transverse
tubules that are important for Ca2+ auto-regulation and synchronous activation of Ca2+ release
during systole (Figure 1).
Cell shortening
Calcium release
SERCA-2a function
Transverse tubule
6
4
2+
2
0
0.5
1.0
1.5
Stimulation frequency (Hz)
2.0
p<0.01
0.30
0.25 p<0.01
0.20
p<0.01
0.15
0.10
0.05
0.00
20
0.2
0.1
1.0
1.5
Stimulation frequency (Hz)
2.0
15
10
5
0
0.0
0.5
(Vmax, pmole/s/mg)
NS
p<0.01
0.3
Rate of calcium uptake
8
p=0.07
0.35
T-tubule density whole cell
10
Ca
Cell shortening (%)
p<0.001
transient amplitude (F340/380)
p<0.01
12
Heart Failure
Normal EF
Normal EF
Heart Failure
Figure 1. Impaired cardiac cell shortening in patients with heart failure (Ejection Fraction,
EF<35%) (red) compared to controls (EF>60%) (blue) was explained by less calcium release during
systole. Mechanisms of reduced calcium release were related to a reduced density of transverse
tubules in failing hearts. SERCA-2a function assessed as SR calcium uptake in separate biopsies of
the LV myocardium was lower in failing hearts. To the left, an example of a single isolated
cardiomyocyte from a heart failure patient stained with DI-8-ANEPPS to detect transverse tubules.
3
Another example of translational research from the Cardiac Exercise Research Group is the
use of animal models with inborn low or high aerobic capacity (e.g. Wisløff et al, Science 2005).
To determine whether there are more than a statistical link between maximal oxygen uptake
(VO2max) and cardiovascular disease, the research team hypothesised that artificial selection of rats
based on Low and High intrinsic Capacity for Running (LCR/HCR rats, respectively) would yield
models that contrast for risk factors related to cardiovascular disease. In summary, LCR rats had
all characteritics of the metabolic syndrome as observed in man, along with a 28-45% shorter
lifespan than HCR rats, which developed a healthy profile. These contrasting models provide the
first demonstration that an intrinsic component of oxidative energy metabolism is inherently
connected with longevity. Based upon these data our group has conducted two clinical studies in
patients with metabolic syndrome (Tjønna et al, Circulation 2008) and in obese adolescents and
adults, followed by prospective epidemiological studies of more than 23 800 men and 25 991
women related to physical activity and prognoses for developing metabolic syndrome. Finally,
these studies formed the basis for the research group to initiate a Fitness Project as a part of the
third wave of one of the largest population based studies (www.ntnu.no/hunt/english) in an
unselected, free living population. The group used direct measurements of VO2max to assess
objective reference values for cardiorespiratory fitness, and studied its relation to levels of
conventional cardiovascular risk factors in healthy men (n=2368) and women (n=2263) aged 20-90
years. Each 5 ml·kg-1·min-1 lower VO2max corresponded to approximately 55% higher prevalence
of metabolic syndrome in both genders. These data demonstrates the high clinical relevance of
preserved VO2max and provides the largest reference material for aerobic capacity in both genders.
Exercise Physiology and Sport Sciences
The research activities in the Exercise Physiology and Sport Sciences Group are diverse. The
main direction is the use of specific exercise training interventions to prevent and treat inactivity
related diseases and other conditions where exercise training interventions might alter
cardiovascular, neural or muscular properties in a favourable manner. The group has contributed to
basic knowledge by studying the limiting factors for oxygen transport in man. Oxygen transport from
air to mitochondria in healthy subjects is closely related to the heart’s stroke volume. In some
conditions, patients’ limitation to oxygen transport is local and muscular. The group has also shown
how angiogenesis and muscular changes may be normalised. These results have given rise to
mechanistic studies, partly carried out at NTNU, and may be applied in prevention and treatment of
inactivity related diseases. As shown in the publication lists, the researchers have a high publication
rate.
Interdisciplinarity; scientific complementarities
All participants and collaborators within the Cardiac Exercise Research Group have been
chosen on the basis of a) identified needs for the strategy as a whole and b) individual expertise,
excellence and commitment. With the resources in the research group and from regional, national
and international collaborators we have access to a broad spectrum data ranging from well defined
animal model that reflects human physiology to patients and human tissue as well as population
based data from the HUNT study. Most of the collaborators have long-standing and ongoing
projects with the research group, assuring a coordinated research action. All active researchers
have well defined roles in the group with no redundancies in research activities or expertise. The
researchers have a broad spectrum of scientific backgrounds, with biophysicists, biologists,
physiologists, exercise physiologists, physicians, cardiologists, thoracic surgeons, bioengineers and
technical engineers working together. Some partners contribute to basic and clinical research by
providing a well established fundament for translational research with a large potential for further
development.
4
Research coherence with trends and developments in the field
The research activities of the unit are in coherence with trends in the field of research for
prevention and management of non-communicable diseases (NCDs) by exercise training, as well
as by identifying basic mechanisms of cardiovascular disease. The consequence of physical
inactivity has major impact on reduced quality of life, invalidity, premature death, and
socioeconomic problems. Physical inactivity has been identified as the fourth leading risk factor
for global mortality (6% of deaths globally). This follows high blood pressure (13%), tobacco use
(9%) and high blood glucose (6%). Overweight and obesity are responsible for 5% of global
mortality. Levels of physical inactivity are rising in many countries with major implications for the
general health of people worldwide and for the prevalence of NCDs, such as cardiovascular
disease, diabetes and cancer, as well as and their identified risk factors such as hypertension,
hyperglycaemia and obesity. Physical inactivity is estimated as being a principal cause for
approximately 21–25% of breast and colon cancer burden, 27% of diabetes, and approximately
30% of ischaemic heart disease. In addition, NCDs now account for nearly half of the overall
global burden of disease. It has been estimated that currently 6 of every 10 deaths are attributable
to NCD.
Societal relevance of the research
An overall research goal of the unit is to develop new therapeutic strategies for patients with
cardiovascular disease, thereby reducing the global burden of disease. It has been shown that
participation in regular physical activity reduces the risk of coronary heart disease and stroke,
diabetes, hypertension, colon cancer, breast cancer and depression. Furthermore, physical activity
is a key determinant of energy expenditure, and is thus fundamental to energy balance and weight
control. The unit aims to identify effective exercise programs for large populations as well as
specific patients and risk groups in order to develop effective tools for prevention, treatment, and
rehabilitation, and to provide detailed exercise training recommendations that will improve overall
health. This effort will contribute to European research strategies to change health behaviour for
improving health and quality of life of the large population of patients with cardiovascular disease,
including diabetes, metabolic syndrome, myocardial infarction and heart failure, which have a
large economic impact on our society.
Strengths and weaknesses
The main strength of the unit is a successful research strategy with an interdisciplinary
approach handling a variety of methods from genomic level to human/patient training intervention
studies as well as health surveys, through collaboration with epidemiologists, clinicians, basic
scientist, molecular biologist etc. The unit has state of the art infrastructure and all equipment
necessary for improving scientific efforts in the years to come. The main weaknesses are few
permanent positions, vulnerability to achieve funding to keep the most talented researchers and
thereby maintaining expert skills in research methodology.
Publication rate
As demonstrated by the CVs, all researchers in the unit have a relatively high publication rate
in international journals with medium to high impact, whereas some smaller projects are published
in journals with low impact.
During the evaluation period, the unit has trained a total of 22 PhD students, and currently 20
PhD students and 7 post-doctoral fellows are working within the unit. A majority of the research
fellows are recruited as undergraduate students, and then unit aims to recruit international students
as funding schemes permit. Due to the focus of the research, the students’ educational background
5
is diverse and include physicians, biologists, exercise physiologist, epidemiologists etc. The
recruitment of students to the unit is in accordance with the institution’s policy for recruitment.
The Department aims to recruit 50% of both genders, and within the unit this goal has been
achieved for PhD and post-docs. So far tenured faculty only consists of men. The recruitment of
young motivated PhD students is good, and during the recent 5 years regional funding has
increased the number of available postdoctoral research positions, which allows the most talented
students a longer career within the unit. This policy has increased the level of research that can be
achieved, compared to units consisting of masters and PhD students only. At present, permanent
academic positions at NTNU almost exclusively become available as vacancies related to
retirement, rendering the age and gender balance fixed for the foreseeable future.
Mobility and career path
The unit has an extensive international collaboration (as can be seen from the CVs) and most
PhD and post-doctoral research fellows visit laboratories around the world for short periods of
time (1-3 months) to learn new techniques. In order to stimulate PhD and post-docs to become
independent researchers and research leaders, the unit has a tradition of letting PhD students be
main (or co-) supervisors for master students and similarly post-docs to be main (or co-)
supervisors for PhD students. The principal investigators involve the students in grant writing as
much as possible in order to teach them this important skill.
1.2.4 Research collaboration (national, international, public sector)
As described above, the unit has established strong regional, national and international
collaborations evidenced by co-publication over several years. This includes interactive and strong
collaboration between scientist ranging from epidemiologists via clinicians and basic scientists
across several departments and faculties within NTNU. It also has extensive collaborations with
the other Norwegian universities and relevant industry, e.g. test of new ultrasound probes or
software, test of potential new drugs etc. Foremost, the unit has been able to establish productive
collaborations with outstanding researchers at several international leading universities as can be
seen from the publication lists. Excellent international collaborations are an important factor for
maintaining a high level of quality and relevance. The international collaborators provide specialist
facilities and assays to enhance the range of data associated with each paper, and contribute
significantly to the publishing process by ensuring the optimum impact of the data and the correct
context of the study. For example, Professor Godfrey L. Smith has internationally recognized
expertise in biophysical techniques. His appointment supports a number of research projects with
electrophysiological and optical techniques that has been successfully utilised in a large number of
studies form the unit. Other examples are Professor Steven Britton, Professor Gianluigi Condorelli,
Professor Sonia Najjar and Professor Russel Richardsson.
6
List of publications for the unit Exercise Training in Health and Disease
(period 1.1.2005 - 30.6.2010)
2010:
Fimland MS, Helgerud J, Gruber M, Leivseth G, Hoff J. Enhanced neural drive after maximal
strength training in multiple sclerosis patients. Eur J ApplPhysiol. 2010 Sep;110(2):435-43.
Epub 2010 May 30. PubMed PMID: 20512584.
Harstad I, Heldal E, Steinshamn SL, Garåsen H, Winje BA, Jacobsen GW. Screening and
treatment of latent tuberculosis in a cohort of asylum seekers in Norway. Scand J Public
Health. 2010 May;38(3):275-82. Epub 2009 Nov 13. PubMed PMID: 19914972.
Hiller A, Helvik AS, Kaasa S, Slørdahl SA. Psychometric properties of the Norwegian
MacNew Heart Disease health-related quality of life inventory. Eur J Cardiovasc Nurs. 2010
Sep;9(3):146-52. Epub 2010 Feb 4. PubMed PMID: 20133205.
Tyldum EV, Romundstad PR, Slørdahl SA. Pre-pregnancy physical activity and preeclampsia
risk: a prospective population-based cohort study. Acta Obstet Gynecol Scand. 2010
Mar;89(3):315-20. PubMed PMID: 19961274.
Husby VS, Helgerud J, Bjørgen S, Husby OS, Benum P, Hoff J. Early postoperative maximal
strength training improves work efficiency 6-12 months after osteoarthritis-induced total hip
arthroplasty in patients younger than 60 years. Am J Phys Med Rehabil. 2010 Apr;89(4):30414. PubMed PMID: 20134307.
Helgerud J, Støren O, Hoff J. Are there differences in running economy at different velocities
for well-trained distance runners? Eur J Appl Physiol. 2010 Apr;108(6):1099-105. Epub 2009
Dec 19. PubMed PMID: 20024579.
Husby VS, Bjørgen S, Hoff J, Helgerud J, Benum P, Husby OS. Unilateral vs. bilateral total
hip arthroplasty - the influence of medial femoral head offset and effects on strength and
aerobic endurance capacity. Hip Int. 2010 Apr-Jun;20(2):204-14. PubMed PMID: 20544648.
Helgerud J, Bjørgen S, Karlsen T, Husby VS, Steinshamn S, Richardson RS, Hoff J.
Hyperoxic interval training in chronic obstructive pulmonary disease patients with oxygen
desaturation at peak exercise. Scand J Med Sci Sports. 2010 Feb;20(1):e170-6. Epub 2009
May 26. PubMed PMID: 19793218.
Støren O, Helgerud J, Hoff J. Running Stride Peak Forces Inversely Determine Running
Economy in Elite Runners. J Strength Cond Res. 2010 Jan 21. [Epub ahead of print] PubMed
PMID: 20093965.
Fimland MS, Helgerud J, Knutsen A, Ruth H, Leivseth G, Hoff J. No effect of prior caffeine
ingestion on neuromuscular recovery after maximal fatiguing contractions. Eur J Appl
Physiol. 2010 Jan;108(1):123-30. Epub 2009 Sep 17. PubMed PMID: 19760253.
Leenders JJ, Wijnen WJ, Hiller M, van der Made I, Lentink V, van Leeuwen RE, Herias V,
Pokharel S, Heymans S, de Windt LJ, Høydal MA, Pinto YM, Creemers EE.Regulation of
cardiac gene expression by KLF15, a repressor of myocardin activity. J Biol Chem. 2010 Aug
27;285(35):27449-56. Epub 2010 Jun 21. PubMed PMID: 20566642; PubMed Central
PMCID: PMC2930743.
Arum CJ, Kodama Y, Rolim N, Widerøe M, Anderssen E, Viset T, Otterlei M, Lundgren S,
Chen D, Zhao CM. A rat model of intravesical delivery of small interfering RNA for studying
urinary carcinoma. World J Urol. 2010 Aug;28(4):479-85. Epub 2010 Apr 8. PubMed PMID:
20376453.
Wong PL, Lau PW, Mao DW, Wu YY, Behm DG, Wisløff U. Three Days of Static Stretching
Within a Warm-Up Does Not Affect Repeated-Sprint Ability in Youth Soccer Players. J
Strength Cond Res. 2010 Jun 23. PubMed PMID: 20581698.
Gutvik CR, Wisløff U, Brubakk AO. Use of heart rate monitoring for an individualized and
time-variant decompression model. Eur J Appl Physiol. 2010 Jun 25. PubMed PMID:
20577757.
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Electrophysiol. 2007 Aug;18(8):854-61. Epub 2007 Jun 6. PubMed PMID: 17553077.
Klauke N, Smith G, Cooper JM. Microfluidic systems to examine intercellular coupling of
pairs of cardiac myocytes. Lab Chip. 2007 Jun;7(6):731-9. Epub 2007 May 17. PubMed
PMID: 17538715.
Walker NL, Burton FL, Kettlewell S, Smith GL, Cobbe SM. Mapping of epicardial activation
in a rabbit model of chronic myocardial infarction:. J Cardiovasc Electrophysiol. 2007
Aug;18(8):862-8. Epub 2007 May 30. PubMed PMID: 17537208.
Reddy SL, Grayson AD, Smith G, Warwick R, Chalmers JA. Methicillin resistant
Staphylococcus aureus infections following cardiac surgery: incidence, impact and identifying
adverse outcome traits. Eur J Cardiothorac Surg. 2007 Jul;32(1):113-7. Epub 2007 Apr 16.
Klauke N, Smith GL, Cooper JM. Microfluidic partitioning of the extracellular space around
single cardiac myocytes. Anal Chem. 2007 Feb 1;79(3):1205-12. PubMed PMID: 17263355.
Caldwell JC, Smith GL, Cobbe SM. How does thrombolysis increase defibrillation success?
Med Hypotheses. 2007;68(5):1183-4. Epub 2006 Nov 22. PubMed PMID: 17118568.
Völkers M, Loughrey CM, Macquaide N, Remppis A, DeGeorge BR Jr, Wegner FV,
Friedrich O, Fink RH, Koch WJ, Smith GL, Most P. S100A1 decreases calcium spark
frequency and alters their spatial characteristics in permeabilized adult ventricular
cardiomyocytes. Cell Calcium. 2007 Feb;41(2):135-43. Epub 2006 Aug 21. PubMed PMID:
16919727.
Ferreira JC, Rolim NP, Bartholomeu JB, Gobatto CA, Kokubun E, Brum PC. Maximal lactate
steady state in running mice: effect of exercise training. Clin Exp Pharmacol Physiol. 2007
Aug;34(8):760-5. PubMed PMID: 17600553.
Tyvold SS, Solligård E, Lyng O, Steinshamn SL, Gunnes S, Aadahl P. Continuous
monitoring of the bronchial epithelial lining fluid by microdialysis. Respir Res. 2007 Nov
1;8:78. PubMed PMID: 17976234; PubMed Central PMCID: PMC2169243.
Sørhaug S, Steinshamn S, Haaverstad R, Nordrum IS, Martinsen TC, Waldum HL.
Expression of neuroendocrine markers in non-small cell lung cancer. APMIS. 2007
Feb;115(2):152-63. PubMed PMID: 17295682.
Rolim NP, Medeiros A, Rosa KT, Mattos KC, Irigoyen MC, Krieger EM, Krieger JE, Negrão
CE, Brum PC. Exercise training improves the net balance of cardiac Ca2+ handling protein
expression in heart failure. Physiol Genomics. 2007 May 11;29(3):246-52. Epub 2007 Jan 23.
Høydal K, Helgerud J, Karlsen T, Støylen A, Steinshamn S, Hoff J. Patients with coronary
artery- or chronic obstructive pulmonary disease walk with mechanical inefficiency.
Scandinavian Cardiovascular Journal. 2007;41, 405- 410.
Haseler L, Lin A, Hoff J, Richardson RS (2007) Oxygen availability and PCr recovery rate in
untrained human calf muscle: Evidence of metabolic limitation in normoxia. American
Journal of Physiology, Regul Integr Comp Physiol. 2007;293, 2046-2051.
Helgerud J, Høydal K, Wang E, Karlsen T, Berg P, Bjerkaas M, Simonsen T, Helgesen C,
Hjorth N, Bach R, Hoff J. (2007) Aerobic high-intensity intervals improve VO2max more
than moderate training. Medicine & Science in Sports & Exercise; 39(4):665-71.
Hoff J, Tjønna AE, Høydal M, Richardson R, Steinshamn S, Helgerud J. (2007) Maximal
strength training of the legs in COPD: a therapy for mechanical inefficiency. Medicine & Science
in Sports & Exercise ;39(2):220-6.
Kemi OJ, Høydal MA, Haram PM, Garnier A, Fortin D, Ventura-Clapier R, Ellingsen O.
Exercise training restores aerobic capacity and energy transfer systems in heart failure treated
with losartan. Cardiovasc Res. 2007 Oct 1;76(1):91-9. Epub 2007 Jun 19. PubMed PMID:
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Schroen B, Leenders JJ, van Erk A, Bertrand AT, van Loon M, van Leeuwen RE, Kubben N,
Duisters RF, Schellings MW, Janssen BJ, Debets JJ, Schwake M, Høydal MA, Heymans S,
Saftig P, Pinto YM. Lysosomal integral membrane protein 2 is a novel component of the
cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy. J Exp Med.
2007 May 14;204(5):1227-35. Epub 2007 May 7. PubMed PMID: 17485520; PubMed
Central PMCID: PMC2118572.
Carè A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P, Bang ML, Segnalini P, Gu Y,
Dalton ND, Elia L, Latronico MV, Høydal M, Autore C, Russo MA, Dorn GW 2nd, Ellingsen
O, Ruiz-Lozano P, Peterson KL, Croce CM, Peschle C, Condorelli G. MicroRNA-133
controls cardiac hypertrophy. Nat Med. 2007 May;13(5):613-8. Epub 2007 Apr 29. PubMed
PMID: 17468766.
Høydal MA, Wisløff U, Kemi OJ, Ellingsen O. Running speed and maximal oxygen uptake in
rats and mice: practical implications for exercise training. Eur J Cardiovasc Prev Rehabil.
2007 Dec;14(6):753-60. PubMed PMID: 18043295.
Kemi OJ, Ellingsen O, Ceci M, Grimaldi S, Smith GL, Condorelli G, Wisløff U. Aerobic
interval training enhances cardiomyocyte contractility and Ca2+ cycling by phosphorylation
of CaMKII and Thr-17 of phospholamban. J Mol Cell Cardiol. 2007 Sep;43(3):354-61. Epub
2007 Jul 10. PubMed PMID: 17689560.
Wisløff U, Støylen A, Loennechen JP, Bruvold M, Rognmo Ø, Haram PM, Tjønna AE,
Helgerud J, Slørdahl SA, Lee SJ, Videm V, Bye A, Smith GL, Najjar SM, Ellingsen Ø,
Skjaerpe T. Superior cardiovascular effect of aerobic interval training versus moderate
continuous training in heart failure patients: a randomized study. Circulation. 2007 Jun
19;115(24):3086-94. Epub 2007 Jun 4. PubMed PMID: 17548726.
Carè A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P, Bang ML, Segnalini P, Gu Y,
Dalton ND, Elia L, Latronico MV, Høydal M, Autore C, Russo MA, Dorn GW2nd, Ellingsen
O, Ruiz-Lozano P, Peterson KL, Croce CM, Peschle C, Condorelli G. MicroRNA-133
controls cardiac hypertrophy. Nat Med 2007 May; 13(5)613-18
Høydal MA, Wisløff U, Kemi OJ, Britton SL, Koch LG, Smith GL, Ellingsen Ø. Nitric oxide
synthase type-1 modulates cardiomyocyte contractility and calcium handling: association with
low intrinsic aerobic capacity. Eur J Cardiovasc Prev Rehabil. 2007 Apr;14(2):319-25.
Amundsen BH, Wisløff U, Slørdahl SA. [Exercise training in cardiovascular diseases].
Tidsskr Nor Laegeforen. 2007 Feb 15;127(4):446-8. Review. Norwegian. PubMed PMID:
17304273.
Wong PL, Chamari K, Mao de W, Wisløff U, Hong Y. Higher plantar pressure on the medial
side in four soccer-related movements. Br J Sports Med. 2007 Feb;41(2):93-100. Epub 2006
Dec 18. PubMed PMID: 17178776; PubMed Central PMCID: PMC2658934.
Adams V, Linke A, Wisloff U, Döring C, Erbs S, Kränkel N, Witt CC, Labeit S, MüllerWerdan U, Schuler G, Hambrecht R. Myocardial expression of Murf-1 and MAFbx after
induction of chronic heart failure: Effect on myocardial contractility. Cardiovasc Res. 2007
Jan 1;73(1):120-9. Epub 2006 Nov 1. PubMed PMID: 17145048.
Wong PL, Chamari K, Chaouachi A, Mao de W, Wisløff U, Hong Y. Difference in plantar
pressure between the preferred and non-preferred feet in four soccer-related movements. Br J
Sports Med. 2007 Feb;41(2):84-92. Epub 2006 Nov 30. PubMed PMID: 17138639; PubMed
Central PMCID: PMC2658925.
Obad A, Palada I, Valic Z, Ivancev V, Baković D, Wisløff U, Brubakk AO, Dujić Z. The
effects of acute oral antioxidants on diving-induced alterations in human ardiovascular
function. J Physiol. 2007 Feb 1;578(Pt 3):859-70. Epub 2006 Nov 16. PubMed PMID:
2006:
Cheng W, Klauke N, Sedgwick H, Smith GL, Cooper JM. Metabolic monitoring of the
electrically stimulated single heart cell within a microfluidic platform. Lab Chip. 2006
Nov;6(11):1424-31. Epub 2006 Sep 14. PubMed PMID: 17066165.
Colotti G, Zamparelli C, Verzili D, Mella M, Loughrey CM, Smith GL, Chiancone E. The
W105G and W99G sorcin mutants demonstrate the role of the D helix in the Ca(2+)dependent interaction with annexin VII and the cardiac ryanodine receptor. Biochemistry.
2006 Oct 17;45(41):12519-29. PubMed PMID: 17029407.
Smith G, Macquaide N. Swallowing a spider to catch a fly: Ca-calmodulin dynamics in adult
cardiomyocytes. J Mol Cell Cardiol. 2006 Sep;41(3):416-7. Epub 2006 Jul 25. PubMed
PMID: 16870208.
Klauke N, Smith GL, Cooper J. Extracellular recordings of field potentials from single
cardiomyocytes. Biophys J. 2006 Oct 1;91(7):2543-51. Epub 2006 Jul 14. PubMed PMID:
Smith GL, Elliott EE, Kettlewell S, Currie S, Quinn FR. Na(+)/Ca(2+) exchanger expression
and function in a rabbit model of myocardial infarction. J Cardiovasc Electrophysiol. 2006
May;17 Suppl 1:S57-S63. PubMed PMID: 16686683.
Kemi OJ, Arbo I, Høydal MA, Loennechen JP, Wisløff U, Smith GL, Ellingsen Ø. Reduced
pH and contractility in failing rat cardiomyocytes. Acta Physiol (Oxf). 2006 Nov-Dec;188(34):185-93. PubMed PMID: 17054658.
Lundsett N, Wisløff U, Hjelde A, Brubakk AO. The effect of endurance training on the rate of
nitrogen elimination in women. Undersea Hyperb Med. 2006 Jul-Aug;33(4):281-9. PubMed
PMID: 17004415.
Wisløff U, Nilsen TI, Drøyvold WB, Mørkved S, Slørdahl SA, Vatten LJ. A single weekly
bout of exercise may reduce cardiovascular mortality: how little pain for cardiac gain? 'The
HUNT study, Norway'. Eur J Cardiovasc Prev Rehabil. 2006 Oct;13(5):798-804. PubMed
PMID: 17001221.
Løset A Jr, Møllerløkken A, Berge V, Wisløff U, Brubakk AO. Post-dive bubble formation in
rats: effects of exercise 24 h ahead repeated 30 min before the dive. Aviat Space Environ
Med. 2006 Sep;77(9):905-8. PubMed PMID: 16964738.
Dujić Z, Palada I, Valic Z, Duplancić D, Obad A, Wisløff U, Brubakk AO. Exogenous nitric
oxide and bubble formation in divers. Med Sci Sports Exerc. 2006 Aug;38(8):1432-5.
Haram PM, Adams V, Kemi OJ, Brubakk AO, Hambrecht R, Ellingsen O, Wisløff U. Timecourse of endothelial adaptation following acute and regular exercise. Eur J Cardiovasc Prev
Rehabil. 2006 Aug;13(4):585-91. PubMed PMID: 16874149.
Møllerløkken A, Berge VJ, Jørgensen A, Wisløff U, Brubakk AO. Effect of a short-acting NO
donor on bubble formation from a saturation dive in pigs. J Appl Physiol. 2006
Dec;101(6):1541-5. Epub 2006 Jul 20. PubMed PMID: 16857861.
Kirkeby-Garstad I, Wisløff U, Skogvoll E, Stølen T, Tjønna AE, Stenseth R, Sellevold OF.
The marked reduction in mixed venous oxygen saturation during early mobilization after
cardiac surgery: the effect of posture or exercise? Anesth Analg. 2006 Jun;102(6):1609-16.
Aetiology-specific patterns in end-stage heart failure patients identified by functional
annotation and classification and classification of microarray data. Beisvag V, Lehre PK,
Midelfart H, Aass H, Geiran O, Sandvik AK, Laegreid A, Komorowski J, Ellingsen O. Eur J
Heart Fail. 2006 Jun; 8(4):381-9. PMID 16753336.
Dujić Z, Ivancev V, Valic Z, Bakovic D, Marinović-Terzić I, Eterović D, Wisløff U.
Postexercise hypotension in moderately trained athletes after maximal exercise. Med Sci
Sports Exerc. 2006 Feb;38(2):318-22. PubMed PMID: 16531901.
Hoff J, Kähler N, Helgerud J. (2006) Training sowie Ausdauer- und Krafttests von
professionellen Fußballspielern. Training and testing physical capacities for elite football
players. Deutsche Zeitschrift für Sportmedizin 56(5): 6-14.
Richardson RS, Duteil S, Wary C, Wray DW, Hoff J, Carlier P (2006) Human skeletal muscle
intracellular oxygenation: the impact of ambient oxygen availability. Journal of Physiology
1:571:415-24.
Brum PC, Rolim NP, Bacurau AV, Medeiros A. Neurohumoral activation in heart failure: the
role of adrenergic receptors. An Acad Bras Cienc. 2006 Sep;78(3):485-503. Review. PubMed
PMID: 16936938.
Rolim NP, Mattos KC, Brum PC, Baldo MV, Middlekauff HR, Negrão CE. The decreased
oxygen uptake during progressive exercise in ischemia-induced heart failure is due to reduced
cardiac output rate. Braz J Med Biol Res. 2006 Feb;39(2):297-304. Epub 2006 Feb 2.
Sørhaug S, Steinshamn S, Nilsen OG, Waldum HL. Chronic inhalation of carbon monoxide:
effects on the respiratory and cardiovascular system at doses corresponding to tobacco
smoking. Toxicology. 2006 Dec 7;228(2-3):280-90. Epub 2006 Sep 29. PubMed PMID:
17056171.
Sørhaug S, Langhammer A, Waldum HL, Hveem K, Steinshamn S. Increased serum levels of
chromogranin A in male smokers with airway obstruction. Eur Respir J. 2006 Sep;28(3):5428. Epub 2006 May 17. PubMed PMID: 16707514.
Amundsen BH, Helle-Valle T, Edvardsen T, Torp H, Crosby J, Lyseggen E, Støylen A, Ihlen
H, Lima JA, Smiseth OA, Slørdahl SA. Noninvasive myocardial strain measurement by
speckle tracking echocardiography: validation against sonomicrometry and tagged magnetic
resonance imaging. J Am Coll Cardiol. 2006 Feb 21;47(4):789-93. Epub 2006 Jan 26.
2005:
Malm S, Frigstad S, Helland F, Oye K, Slordahl S, Skjarpe T. Quantification of resting
myocardial blood flow velocity in normal humans using real-time contrast echocardiography.
A feasibility study. Cardiovasc Ultrasound. 2005 Jun 16;3:16. PubMed PMID: 15958173;
Ingul CB, Torp H, Aase SA, Berg S, Stoylen A, Slordahl SA. Automated analysis of strain
rate and strain: feasibility and clinical implications. J Am Soc Echocardiogr. 2005
May;18(5):411-8. PubMed PMID: 15891750.
Ingul CB, Stoylen A, Slordahl SA. Recovery of stunned myocardium in acute myocardial
infarction quantified by strain rate imaging: a clinical study. J Am Soc Echocardiogr. 2005
May;18(5):401-10. PubMed PMID: 15891749.
Dybdahl B, Slørdahl SA, Waage A, Kierulf P, Espevik T, Sundan A. Myocardial ischaemia
and the inflammatory response: release of heat shock protein 70 after myocardial infarction.
Heart. 2005 Mar;91(3):299-304. PubMed PMID: 15710705; PubMed Central PMCID:
PMC1768748.
Moe IT, Hoven H, Hetland EV, Rognmo O, Slørdahl SA. Endothelial function in highly
endurance-trained and sedentary, healthy young women. Vasc Med. 2005 May;10(2):97-102.
Sørhaug S, Steinshamn SL, Waldum HL. Octreotide treatment for paraneoplastic intestinal
pseudo-obstruction complicating SCLC. Lung Cancer. 2005 Apr;48(1):137-40. PubMed
PMID: 15777981.
Kohl P, Camelliti P, Burton FL, Smith GL. Electrical coupling of fibroblasts and myocytes:
relevance for cardiac propagation. J Electrocardiol. 2005 Oct;38(4 Suppl):45-50. Review.
Sharma AK, Smith G, Smith D, Sinha S, Rustom R, Sells RA, Hammad A, Bakran A.
Clinical outcome of cadaveric renal allografts contaminated before transplantation. Transpl
Int. 2005 Jul;18(7):824-7. PubMed PMID: 15948862.
Currie S, Quinn FR, Sayeed RA, Duncan AM, Kettlewell S, Smith GL. Selective downregulation of sub-endocardial ryanodine receptor expression in a rabbit model of left
ventricular dysfunction. J Mol Cell Cardiol. 2005 Aug;39(2):309-17. PubMed PMID:
15921690.
Miller SL, Currie S, Loughrey CM, Kettlewell S, Seidler T, Reynolds DF, Hasenfuss G,
Smith GL. Effects of calsequestrin over-expression on excitation-contraction coupling in
isolated rabbit cardiomyocytes. Cardiovasc Res. 2005 Sep 1;67(4):667-77. PubMed PMID:
15913577.
Kemi OJ, Ellingsen O. Trans-sodium crocetinate does not affect exygen uptake in rats during
treadmill running. Scand J Clin Lab Invest. 2005; 65(7) 577-84
Klauke N, Smith GL, Cooper JM. Stimulation of isolated ventricular myocytes within an open
architecture microarray. IEEE Trans Biomed Eng. 2005 Mar;52(3):531-8. PubMed PMID:
15759583.
Hoff J. (2005) Training and testing physical capacities for elite soccer players. Invited review.
Journal of Sport Sciences 23(6): 573 – 582.
Østerås H, Hoff J, Helgerud J. (2005) Effects of high-intensity endurance training on maximal
oxygen consumption in healthy elderly people. Journal of Applied erontology 24(5): 377-87.
Slørdahl S, Wang E, Hoff J, , Kemi OJ, Amundsen B, Helgerud J. (2005) Aerobic endurance
training in patients with Intermittent Claudication: Effects of high and low intensity.
Scandinavian Cardiovascular Journal 39(4):244-9.
Hoff J, Kemi OJ, Helgerud J. (2005) Physiological Characteristics of Elite and Junior Elite Ice Hockey
Players. (2004) International Journal of Sports Medicine 25:1-5
McMillan K, Helgerud J, Macdonald R, Hoff J. (2005) Physiological adaptations to soccerspecific endurance training in professional youth soccer players. British Journal of Sports
Medicine, 39(5):273-7.
McMillan K, Helgerud J, Grant S, Newell J, Hoff J. (2005) Lactate threshold responses to a
season of professional British youth soccer. British Journal of Sports Medicine. 39(7): 432-6.
Valic Z, Duplancić D, Baković D, Ivancev V, Eterović D, Wisløff U, Brubakk AO, Dujić Z.
Diving-induced venous gas emboli do not increase pulmonary artery pressure. Int J Sports
Med. 2005 Oct;26(8):626-31. PubMed PMID: 16158366.
Stølen T, Chamari K, Castagna C, Wisløff U. Physiology of soccer: an update. Sports Med.
2005;35(6):501-36. Review. PubMed PMID: 15974635.
Brubakk AO, Duplancic D, Valic Z, Palada I, Obad A, Bakovic D, Wisloff U, Dujic Z. A
single air dive reduces arterial endothelial function in man. J Physiol. 2005 Aug 1;566(Pt
3):901-6. Epub 2005 Jun 16. PubMed PMID: 15961424; PubMed Central PMCID:
PMC1464788.
Kemi OJ, Haram PM, Loennechen JP, Osnes JB, Skomedal T, Wisløff U, Ellingsen Ø.
Moderate vs. high exercise intensity: differential effects on aerobic fitness, cardiomyocyte
contractility, and endothelial function. Cardiovasc Res. 2005 Jul 1;67(1):161-72. Epub 2005
Apr 20. PubMed PMID: 15949480.
Berge VJ, Jørgensen A, Løset A, Wisløff U, Brubakk AO. Exercise ending 30 min pre-dive
has no effect on bubble formation in the rat. Aviat Space Environ Med. 2005 Apr;76(4):3268. PubMed PMID: 15828630.
Chamari K, Moussa-Chamari I, Boussaïdi L, Hachana Y, Kaouech F, Wisløff U. Appropriate
interpretation of aerobic capacity: allometric scaling in adult and young soccer players. Br J
Sports Med. 2005 Feb;39(2):97-101. PubMed PMID: 15665205; PubMed Central PMCID:
PMC1725118.
Wisløff U, Najjar SM, Ellingsen O, Haram PM, Swoap S, Al-Share Q, Fernström M, Rezaei
K, Lee SJ, Koch LG, Britton SL. Cardiovascular risk factors emerge after artificial selection
for low aerobic capacity. Science. 2005 Jan 21;307(5708):418-20. PubMed PMID: 15662013.
Chamari K, Hachana Y, Kaouech F, Jeddi R, Moussa-Chamari I, Wisløff U. Endurance
training and testing with the ball in young elite soccer players. Br J Sports Med. 2005
Jan;39(1):24-8. PubMed PMID: 15618335; PubMed Central PMCID: PMC1725014
Panel 2
Extreme Environments and Health
1.2. Evaluation unit (level 2): Extreme Environments and Health
Extreme environments can be defined as natural or man-made environments that
require significant adaptation for survival and maintenance of health, and sometimes
behavioural and protective measures for survival. Diving is of particular importance to the
Norwegian oil industry and there is considerable concern that diving may lead to long term
injury. The unit for Extreme Environments and Health has systematically studied bubble
formation during decompression using a translational approach and has established one of the
world’s leading laboratories within this field. Its work forms the basis for procedures used by
divers as well as for establishing the mechanisms of injury.
The unit was established in 1988 and is headed by Professor Alf O. Brubakk. He is
retiring in January 2011, but will still be involved in research as Professor Emeritus. His
successor as Professor of Applied Physiology is being sought internationally. The unit is
rapidly growing, and currently comprises 16 persons. Three are faculty (see table below), 1
and ten (63%) are under 35 years of age. Decision-making is based on discussions, where all
are invited to contribute, and a level structure, where all participants may develop their
expertise and follow their interests.
Composition of competence and background, age, sex, and nationality of the academic staff
Name
Position
Alf O. Brubakk
Professor
Alndreas Møllerløkken
Post Doc
Ingrid Eftedal
Researcher
Astrid Hjelde
Technician
PhD/Dr Philos/MSc students
Christian Gutvik
Kim Vidar Rasdal
Arve Jørgensen
Svein Erik Gaustad
Martin Skrove
Marianne Bjordal Havnes
Yonne Tangelder
Michael Lang
Yara Bernaldo de Quireos
Kristin Svee
Yvonne Kerlefsen
Technical staff
Arnfinn Sira
Qualification
MD, Dr med
Phd
Dr. Scient
PhD
Age
69
36
45
59
Sex
M
M
F
F
Nationality
NO
NO
NO
NO
MSc Eng
MD
MD
Msc Physiol
MD
Msc Physiol
MSc Psychol.
MSc mar biol
MSc mar biol
Bachelor
Bachelor
34
29
32
32
30
30
27
53
27
26
28
M
M
M
M
M
F
F
M
F
F
F
NO
NO
NO
NO
NO
NO
NL
USA
ESP
NO
NO
Cand Scient
54
M
NO
1
Astrid Hjelde has been included into the unit because of her background and the fact that she
represents the its statistical expertise.
1
Strategy for publication and dissemination, including popular science
During the evaluation period 2005-2010, the unit published 29 papers in peerreviewed international journals (see publication list). Professor Brubakk has contributed to the
following books and book chapters:
Diving and Hyperbaric Medicine, Elsvier, 5th ed, Editor and chapter
The Future of Diving, Smithsonian Institution, Editor and papers
Endothelial Biomedicine, Cambridge University Press, W.C. Aird (ed), chapters:
Endothelium and diving and Exercise and the endothelium.
Appearances in public media
Participation in “Schroedinger’s Cat” (Popular Science TV program) and Newton
(Children’s educational TV). The unit has also arranged two international conferences at
NTNU with participation of leading researchers in the fields of diving medicine and
environmental physiology:
In December 2008 “The Future of Diving: 100 years of Haldane and beyond”,
InDecember 2010 “Man in Extreme Environments – applied physiology from subsea to
space”.
Resources (human, monetary, time)
The financial situation of the unit has been quite satisfactory based on support mainly
from industry. Lately, financing has come from Statoil with further support from the Central
Norwegian Regional Health Authority and the Research Council of Norway. Joint plans for
future funding starting in 2012 include grants of 5-6 million NOK yearly for 5 years
supported by the Research Council of Norway, the Oil Industry Council and the Norwegian
Department of Industry.
The unit has access to several hyperbaric chambers and to NTNU exercise facilities for
small animals (mice, rats and rabbits) and pigs. It also has a one man hyperbaric chamber, and
has recently participated in acquiring a six man hyperbaric chamber. General laboratory
facilities are state of the art, with access to ultrasonography equipment to detect gas bubbles
in the circulatory system. The laboratories have a specialized blood gas analyser for
hyperbaric conditions, and have access to high capacity equipment for biochemical and
genetic analyses at core laboratories. The Department has MRI scanners for animals and
humans, which are important research tools for the unit. The new laboratories at St Olavs
Hospital and within the Department are well equipped for standard analyses in molecular
medicine. The Department for Circulation and Medical Imaging recently (2010) moved into
new facilities in the Emergency and Cardiopulmonary Medicine Centre at the new St. Olavs
Hospital, with considerable investments in equipment and infrastructure. At present the unit
has no need for major additional investments in infrastructure.
Use of research infrastructure at other institutions
The unit collaborates with experts at other institutions in order to get access to methodology
that is not established within the Department.
Diving and hyperbaric medicine is a small research field world wide, but an area of
considerable commercial interest. In addition to the extensive output by the US Navy, the
activity of the unit is a significant source of knowledge. A recent review may be seen in:
http://viewer.zmags.com/showmag.php?magid=311142#/page30/ pp 30-37, in Norwegian.
2
Diving is also important in many developing countries, but here the procedures are
often very unsatisfactory with high risks of injury. To contribute to amelioration of this and to
perform research into the actual diving practices, the unit has initiated an international
program called Harvest Divers Improvement Program. In this program there are participants
from USA, Australia, Mexico, Croatia and Norway. The initial investigators are medical
students; with two teams studying lobster fishermen on Isla Mujeres, Yucatan, two teams in
Galapagos, Ecuador and one student in Thailand. A continuation of the program is planned.
Research activities and the research profile of the unit
During recent years the main focus of the unit has been to study how decompression,
the effects of pressure reduction, affects the body. By understanding the basic mechanisms,
better and safer procedures can be developed. Decompression effects and gas bubble
formation are major health hazards in diving and many of the basic mechanisms are not well
understood. Furthermore, decompression injury may play a significant role in possible long
term effects of diving. The main working hypothesis of the unit is that endothelial dysfunction
and damage is the main cause of serious (neurological) decompression sickness. Conceivably
the amount of vascular bubble formation is an indication of decompression stress and that
procedures that reduce bubble formation is desirable.
The unit is using a translational approach, combining in-vitro methods with animal
and human studies. In addition to this, development of computer models of diving and
decompression is an important tool. One important problem in decompression is the
significant variability of response both inter- and intra-individually. To address this problem
the unit uses an epigenetic approach as well as studies of the modifying effects of physical
exercise. In compliance with the strategy of the Department of Circulation and Medical
Imaging, the unit is founded on competence in both technology and medicine, with a staff
consisting of engineers, physiologist, biologists and physicians.
Research coherence with trends and development in the field
During recent years, there is an increased awareness of the importance of endothelial
dysfunction in the development of decompression and diving injuries. This is an approach that
the unit has pursued since the early 1980s. The translational approach is increasingly being
accepted as an important contribution to the field.
Research contributions to basic research and/or vice versa
One of the most important contributions of the unit is showing that high intensity
aerobic exercise is inversely related to vascular gas bubble production and injury after diving.
Its studies have documented that this is related to the production of nitric oxide, indicating
that pharmacological prevention of decompression injury may be possible. Another important
contribution is to show that the application of heat prior to the dive may reduce the risk of
injury, and pre-treatment is now an important and active research field.
The unit has developed and evaluated a computer model of decompression
(Copernicus) that establishes an important tool for basic understanding of the decompression
process. This understanding will have implications for procedures, and it will eventually be
incorporated into a new dive computer for recreational and occupational diving.
Societal relevance of the research and other ways research has contributed to innovation
The unit is presently engaged in a study on evaluation of dive computers supported by
the Norwegian Labour Directorate. The aim is to establish a European Standard for evaluation
of dive computers, in collaboration with other European researchers and with the US-Navy
Experimental Diving Unit. The unit has established methods for evaluating decompression
3
using ultrasonic images; the development of improved ultrasonic equipment is being
developed at the Department of Circulation and Medical Imaging.
For 20 years the unit has arranged and hosted the course “Enjoy the Cold” held at
Svalbard. The agenda of this course is to promote knowledge of safe working in cold
environments, and it has attracted considerable international participation. A course for diving
medical specialists following European guidelines, is in preparation.
Alf Brubakk has been chairman of the Diving Medical Advisory Committee (DMAC,
1999-2002) who gives advice on commercial diving in the North Sea. He is currently a
member of the Medical Board of the European Diving Technology Committee (EDTC) that
gives advice on training programs for diving medical personnel in Europe.
Strengths and weaknesses of the unit
The main strength of the unit is the ability to initiate programs that interest young
researchers and trigger their enthusiasm. This is reflected in the composition of the research
staff and also by the fact that it is attracting a significant number of leading researchers in the
field to its symposia.
The main weakness is Professor Brubakk’s imminent retirement. He is one of the
leaders in his field, and he is the senior editor of the main textbook in diving medicine:
Physiology and Medicine of Diving. His leadership of the unit has been instrumental in
making the unit on of the leaders in diving research. However, the human resources,
infrastructure and future funding of the group are excellent. Brubakk will contribute to the
research as a Professor Emeritus and prospects of recruiting an internationally recognised
candidate for the professorship should be very good.
Distribution of scientific results / publications among the researchers
The unit has a large number of PhD students that are well on the path to a PhD. The
projects are continuously being prepared for publication in peer-reviewed journals. In
addition, the researchers participate at relevant national and international meetings and
conferences.
One of the former PhD students, who has both a technical and medical degree, is the
present Head of Diving Medicine in Statoil. Over the past five years, PhD students have been
recruited among medical students as well as students with biological and engineering
background. The unit supervises Master and Bachelor theses amongst students in addition to
recruiting medical research students. Senior researches encourage and help PhD students to
apply for post-doc grants to continue their academic career, and the strategy coheres well with
the Department’s policy of interdisciplinary recruitment from several NTNU faculties. In line
with NTNU’s strategy following the Bologna process, the unit has established a Cotutelleagreement with NTNU and the University of Texas.
Gender equality and the balance between men and women in academic positions
At present, there are two women and two men in academic positions; among students
are five women and six men.
4
Age balance in academic positions and how the policy is followed up
At the moment the main effort will be to recruit a new professor. A professorship in
applied physiology will be announced. The unit has good access to excellent candidates for
PhD.
Policy for mobility and career path
One of the PhD students has spent one year at the Medical College of Wisconsin, and
the Mayo Clinic, USA, and at the University of Split, Croatia. Another has spent 6 months at
the University of Texas and at NASA.
International recruitment
At present, the unit has one researcher from the Netherlands, one PhD student from
USA and is co-supervising a PhD student from Spain.
Opportunities related to future oriented research challenges
The unit is taking part in a Marie Curie scholarship program (Phypode) involving 10
European sites from 2011. Another important collaboration is Department of Physiology,
University of Tromsø, Department of Arctic Biology and the Norwegian Polar Institute,
where the unit takes part in a collaborative project on effects of cold and diving. Two medical
students will be recruited.
1.2.4 Research collaboration (national, international, industry (public sector), including
interdisciplinary
National collaboration
The most important collaboration is with the Cardiac Exercise Research Group within
the Department. This has pointed to a totally new way of preventing decompression injuries
and has given new insight into the basic mechanisms of bubble formation in the vasculature.
There are also local collaborative projects with the Department of Bacteriology, NTNU /
SINTEF for the study of antibodies and their effects on the endothelium and with the MR
laboratory for the study of brain injury induced by decompression. The unit also collaborates
with NUI (Norwegian Underwater Intervention Inc) for studies of the effect of pressure and
oxygen on decompression in cell cultures.
International collaboration
The most important international collaboration is with the Department of Physiology,
University of Split, Croatia. Numerous studies on the effect of diving on the human body
have resulted in excellent co-publications.
The unit has a joint PhD program with the Department of Physiology, Medical College
of Wisconsin, USA and with the Department of Physiology and Biophysics at the Mayo
Clinic. Svein Erik Gaustad is about to complete his PhD thesis as the first candidate in the
program.
The unit also has a collaboration with the Department of Pulmonary and Critical Care
Medicine, University of Texas Medical Branch, and with NASA, Houston for the study of
decompression in space. One PhD student (Arve Jørgensen) recently studied here for the
academic year 2009-2010 on a Fulbright Grant. A cotutelle agreement has been signed.
These collaborative efforts allow us to learn new techniques and methods, and they
give us important contacts that are crucial in a specialized and limited field.
5
Industry
Since 2007 the unit has participated in a competence program for diving financed by
Statoil and Exxon Mobile. The main aim of this program is to train researchers in diving
medicine and physiology. Internationally, the unit has have collaborated with Uwatech AG,
Switzerland in the development of a new decompression computer model.
Public sector
The unit is presently involved in a research project, PDC (Personal Dive Computer),
financed by the Norwegian Labour Department. The aim is to establish acceptance criteria for
commercially used dive computers.
6
List of publications for the unit Extreme Environments and Health
(period 1.1.2005 – 30.6.2010)
1. Ljubkovic M, Gaustad SE, Marinovic J, Obad A, Ivancev V, Bilopavlovic N,
Breskovic T, Wisløff U, Brubakk AO, Dujic Z. Ultrasonic evidence of acute
interstitial lung edema after SCUBA diving is resolved within 2-3 h. Respir Physiol
Neurobiol 2010 Apr 30;171(2): 165-70. Epub 2010 Feb 24.
2. Gaustad SE, Rolim N, Wisløff U. A valid and reproducible protocol for testing
maximal oxygen uptake in rabbits. Eur J Cardiovasc Prev Rehabil. 2010 Feb; 17(1):
83-8.
3. Gutvik CR, Wisløff U and Brubakk AO. Use of heart rate monitoring for an
individualized and time-variant decompression model. Euro J Appl Physiol 2010 Nov;
110(5): 885-92. Epub 2010 Jun 25.
4. Gutvik CR, Dunford RG, Dujic Z and Brubakk AO. Parameter estimation of the
Copernicus decompression model with venous gas emboli in human divers. Med Biol
Eng Comput 2010 Jul 48(/): 625-636. Epub 2010 Apr 23.
5. Djurhuus R, Nossum V, Lundsett N, Hovin W, Svardal AM, Havnes MB, Fismen L,
Hjelde A, Brubakk AO. Simulated diving after heat stress potentiates the induction of
heat shock protein 70 and elevates glutathione in human endothelial cells. Cell Stress
Chaperones 2010 Jul: 15(4):405-14. Epub 2009 Nov 19.
2009:
6. Rasdal KV, Hjelde A, Møllerløkken A, Lundsett N, Brubakk AO. Aortic function in
rats after decompression without ultrasonically detectable bubble formation. Aviat
Space Environ Med 2009 Dec; 80(12): 1006-11.
7. Brubakk AO, Møllerløkken A. The role of intra-vascular bubbles and the vascular
endothelium in decompression sickness. DHM 2009 Sept; 39(3): 162-170.
8. Jørgensen A, Berge VJ, Brubakk AO, Wisløff U. A reliable and valid protocol for
measuring maximal oxygen uptake in pigs. Eur J Cardiovasc Prev Rehabil 2009 Oct;
16(5):628-32.
9. Gutvik CR, Brubakk AO. A dynamic two-phase model for vascular bubble formation
during decompression of divers. IEEE Trans Biomed Eng. 2009 Mar; 56(3): 884-9.
10. Glavas D, Bakovic D, Obad A, Palada I, Breskovic T, Valic Z, Brubakk AO, Dujic Z.
Effects of tetrahydrobiopterine on venous bubble grade and acute diving-induced
changes in cardiovascular function. Clin Physiol Funct Imaging 2009 Apr; 29(2): 1007. Epub 2008 Dec 4.
11. Brubakk AO, Lang MA. J.S. Haldane, the First Environmental Physiologist. In: Lang
MA and Brubakk AO (eds). The Future of Diving: 100 years of Haldane and beyond.
Smithsonian Institution Scholary Press 2009, 3-5.
12. Møllerløkken A, Eftedal I. Individual Risk of Decompression Sickness: Possible
Effects of Genomic or Epigenomic Variation Altering Gene Expression. In: Lang MA
and Brubakk AO (eds). The Future of Diving: 100 years of Haldane and beyond.
13. Havnes MB, Widerøe M, Thuen M, Møllerløkken A, Brubakk AO. Lack of Signs of
Brain Injury in Rats on MRI after Decompression. In: Lang MA and Brubakk AO
(eds). The Future of Diving: 100 years of Haldane and beyond. Smithsonian
Institution Scholary Press 2009, 65-71.
14. Eftedal OS. Ultrasound for Evaluationg Decompression. In: Lang MA and Brubakk
AO (eds). The Future of Diving: 100 years of Haldane and beyond. Smithsonian
15. Løvstakken L, Møllerløkken A, Måsøy SE. Current Trends in Ultrasound Imaging
Technology, SURF Imaging, and Decompression Induced Microbubbles. In: Lang
16. Lang MA and Angelini S. The Future of Dive Computers. In: Lang MA and Brubakk
17. Brubakk AO. Baromedical and Environmental Physiology Group (BAREN). In: Lang
18. Lang MA. Parameters of Extreme Environment Diving. In: Lang MA and Brubakk
2008:
19. Bakovic D, Glavas D, Palada I, Breskovic T, Fabijanic D, Obad A, Valic Z, Brubakk
AO, Dujic Z. High-grade bubbles in left and right heart in an asymptomatic diver at
rest after surfacing. Aviat Space Envirn Med 2008 Jun; 79(6): 626-8.
20. Glavas D, Markotic A, Valic Z, Kovacic N, Palada I, Martinic R, Breskovic T,
Bakovic D, Brubakk AO, Dujic Z. Expression of endothelial selectin ligands on
human leukocytes following dive. Exp Biol Med 2008 Sep; 233(9): 1181-8.
21. Dujic Z, Valic Z, Brubakk AO. Beneficial role of exercise on scuba diving. Exerc
Sport Sci Rev. 2008 Jan; 36(1):38-42.
22. Havnes MB, Møllerløkken A, Brubakk AO. The effect of two consecutive dives on
bubble formation and endothelial function in rats. Diving and Hyperbaric Medicine
2008; 38 (1): 29-33.
2007:
23. Obad, A; Valic, Zoran; Palada, Ivan; Brubakk, Alf O; Modun, D; Dujic, Z.
Antioxidant pretreatment and reduced arterial endothelial dysfunction after diving.
Aviation, Space and Environmental Medicine 2007;78(12):1114-1120
24. Obad A, Palada I, Ivancev V, Valic Z, Fabijanic D, Brubakk AO, Dujic Z.
Sonographic detection of intrapulmonary shunting of venous gas bubbles during
exercise after diving in a professional diver. J Clin Ultrasound 2007 Oct; 35(8): 473-6.
25. Møllerløkken A, Gutvik C, Berge VJ, Jorgensen A, Loset A, Brubakk AO.
Recompression during decompression and effects on bubble formation in the pig.
Aviat Space Environ Med. 2007;78(6):557-60.
26. Møllerløkken A, Nossum V, Hovin W, Gennser M, Brubakk AO. Recompression with
oxygen to 160 kPa eliminates vascular bubbles, bue does not prevent endothelial
damage. Eur J Underwater Hyperbar Med 2007;8:11-16.
27. Eftedal OS, Lydersen S, Brubakk AO. The relationship between venous gas bubbles
and adverse effects of decompression after air dives. Undersea Hyperb Med.
2007;34(2):99-105.
28. Eftedal OS, Tjelmeland H, Brubakk AO. Validation of decompression procedures
based on detection of venous gas bubbles: A Bayesian approach. Aviat Space Environ
Med. 2007;78(2):94-9.
29. Obad A, Palada I, Valic Z, Ivancev V, Bakovic D, Wisloff U, Brubakk AO, Dujic Z.
The effects of acute oral antioxidants on diving-induced alterations in human
cardiovascular function. J Physiol. 2007; Feb; 78(2):94-9.
30. Brubakk AO, Eftedal O, Wisloff U. Endothelium and diving In: Aird W. (ed).
Endothelial Biomedine, Cambridge University Press 2007.
31. Wilsoff U, Haram PM, Brubakk AO. Exercise and the endothelium. In: Aird W. (ed).
Endothelial Biomedicine, Cambridge University Press 2007.
2006:
32. Lundsett N, Wisløff U, Hjelde A, Brubakk AO. The effect of endurance training on
the rate of nitrogen elimination in women. Undersea Hyperb Med 2006 Jul-Aug;
33(4): 281-9.
33. Løset A Jr, Møllerløkken A, Berge V, Wisløff U, Brubakk AO. Post-dive bubble
formation in rats: effects of exercise 24h ahead repeated 30 min before the dive. Aviat
Space Environ Med 2006 Sept; 77(9): 905-8.
34. Dujic Z, Palada I, Valic Z, Duplancic D, Obad A, Wisløff U, Brubakk AO. Exogenous
nitric oxide and buble formation in divers. Med Sci Sports Exerc. 2006 Aug; 38(8):
1432-5.
35. Haram PM, Adams V, Kemi OJ, Brubakk AO, Hambrecht R, Ellingsen O, Wisløff U.
Time-course of endothelial adaptation following acute and regular exercise. Eur J
Cardiovasc Prev rehabil. 2006 Aug; 13(4): 585-91.
36. Møllerløkken A, Berge VJ, Jørgensen A, Wisløff U, Brubakk AO. Effects of a shortacting NO donor on bubble formation from a saturation dive in pigs. J Appl Physiol
2006 Dec; 101(6): 1541-5.
37. Dujic Z, Obad A, Palada I, Valic Z, Brubakk AO. A single open sea air dive increases
pulmonary artery pressure and reduces right ventricular function in professional
divers. Eur J Appl Physiol 2006 Jul; 97(4): 478-85.
2005:
38. Hjelde A, Gerderaas AO, Krokan HE, Brubakk AO. Lack of effect of hyperoxia on
photodynamic therapy and lipid peroxidation in three different cancer cell lines. Med
Sci Monit 2005 Oct; 11(10):BR351-6.
39. Valic Z, Duplancic D, Bakovic D, Ivancev V, Eterovic D, Wisløff U, Brubakk AO,
Dujic Z. Diving-induced venous gas emboli do not increase pulmonary artery
pressure. Int J Sports Med 2005 Oct; 26(8): 626-31.
40. Westin AA, Asvall J, Idrovo G, Denoble P, Brubakk AO. Diving behaviour and
decompression sickness among Galapagos underwater harvesters. Undersea Hyperb
Med 2005 May-Jun; 32(3): 175-84.
41. Brubakk AO, Duplancic D, Valic Z, Palada I, Obad A, Bakovic D, Wisløff U, Dujic Z.
A single air dive reduces arterial endothelial function in man. J Physiol 2005 Aug
1;566(pt3): 901-6.
42. Dujic Z, Palada I, Obad A, Duplancic D, Brubakk AO, Valic Z. Exercise-induced
intrapulmonary shunting of venous gas emboli does not occur after open-sea diving. J
Appl Physiol 2005 Sep; 99(3): 944-9.
43. Berge VJ, Jørgensen A, Løset A, Wisløff U, Brubakk AO. Exercise ending 30 min
pre-dive has no effect on bubble formation in the rat. Aviat Space Environ Med 2005
Apr; 76(4): 326-8.
Panel 4A
Cardiovascular Clinical and
1.2 Evaluation unit (level 2): Cardiovascular Clinical and Translational Science
The unit comprises a network of well established clinicians who are active in teaching
and research in anaesthesiology, emergency medicine, cardiology, cardiothoracic surgery and
immunology. The majority combine full-time consultant positions at St Olavs Hospital with
20% teaching positions at the Department of Circulation and Medical Imaging. Compared to
available time and resources, scientific output is adequate. Co-localisation in a new
Emergency and Cardiopulmonary Medicine Centre in 2010 represents an opportunity to
benefit mutually by developing and pursuing common strategic goals within a firmer
organisational structure. The potential to attract more external funding is good.
The Section Leader, Professor Olav FM Sellevold, represents the unit as member of
the Operational Management Team of the Department, where resources from NTNU are
allocated. Due to the diversity of projects there is a high degree of autonomy and
responsibility of the researchers regarding funding from external sources. The majority of the
academic staff is male Norwegians, with a good age distribution from 40-60. As apparent
from section 1.2.2 and the publication list, there is a strong interest and ability to make
cooperative studies within the clinical departments and in collaboration with translational
researchers. The clinical wards and laboratories provide excellent arenas for recruitment of
patients and healthy volunteers for studies. In addition, a research ward staffed with specially
trained research assistants/nurses has recently opened, providing common facilities for closely
monitored out-patient studies.
As mentioned in 1.1.2, insufficient and/or fragmented time is a major limitation for
patient-oriented research in some clinical disciplines. A major cause is the position structure,
where a majority of clinical faculty is hired mainly for teaching, on contracts with 5-20%
research time. Research time is typically spread out, with little protection from pressing
patient related duties. However, for some of the physicians the scientific output volume and
quality is very good compared to resources available.
The new University Hospital represents a major upgrade of structural resources for the
clinical and academic departments. Financial responsibility for infrastructure for research and
innovation is dual and follows ownership, i.e. St Olavs Hospital for wards and clinical
laboratories and NTNU for translational and experimental research facilities, respectively. As
described in section 1.1, the Operational Team of the Department and the leadership of its
adjunct clinical departments meet regularly in a common forum for research strategy, in order
to optimise joint allocation of resources. Proximity between clinical departments and research
laboratories has further lowered the threshold for collaboration with innovation and
translational research, especially within the Department of Circulation and Medical imaging,
but also with the Department of Laboratory Medicine, Children’s and Women’s Health.
The cardiology laboratories for echocardiography, angiography and arrhythmia are
very well equipped and constitute a state of the art basis for projects. Several clinical
researchers have long standing cooperation with ultrasound innovation, which is described in
the report to Panel 4B. After co-localisation, a high strategic priority for researchers in
cardiothoracic anaesthesia and intensive care is to intensify their use of 3D trans-oesophagus
echocardiography to monitor cardiac surgery patients. For this purpose facilities for a
perioperative physiological laboratory have been allocated within the intensive care unit, and
funding of 1 million NOK in equipment is being applied for. These assessments will combine
excellently with an extensive database of clinical data from cardiothoracic surgery patients, as
detailed below (1.2.2).
The unit has access to an excellent facility for advanced experimental models in pigs,
where projects originating from clinical staff and collaborating technologists are carried out. It
1
provides infrastructure for echo-Doppler assessment of ventriculo-arterial coupling, epicardial
echoprobes for quality control of coronary anastomoses, visualization of myocardial function
in experimental heart failure, effects of drug therapy etc.
Pathophysiology in sepsis, trauma, major surgery, cardiovascular interventions and
postoperative pathophysiology (Aadahl, Solligård, Gunnes)
Work in this field has been going for years, and is reflected in the relevant publication
list. Multi Organ Dysfunction (MODS) is the most important cause of death after serious
conditions like sepsis, trauma and major surgery. Hypoperfusion of the splanchnic region is
thought to initiate inflammatory responses leading to MODS, and organ cross-talk between
the intestine and the lungs is important. The neuroendocrine system is recently described as a
possible trigger. In collaboration with Dr. Gustafsson at the Department of Cancer and
Molecular Medicine and Dr. Kidd at Yale University, mechanisms underlying this response
are indentified by detecting early alterations in the intestine and the lung. Focus is on organ
dysfunction during ischaemia and reperfusion (remote organ failure), flow and ultrasound
integration (fluid dynamics), and biosensors for tight glucose control.
Human Bronchial Microdialysis in Open Aortic Aneurysm Repair (Gunnes, Dahl, Aadahl)
This project examines the airway reaction to open surgery on the aorta and whether it
is possible to predict pulmonary complications after open surgery for abdominal aortic
lesions. Examination of the bronchial epithelial lining fluid by microdialysis and analysis of
multiple inflammation markers by flow cytometry has previously been done in cooperation
with professor Espevik at the Department of Cancer and Molecular Medicine together with
researchers at Uppsala and Århus Universities. Clinical outcomes reflect postoperative
respiratory failure; need of non-invasive ventilation, hypoxia, pulmonary infiltrates, infection,
and length of intensive care.
Clinical course in cardiac surgery patients (Stenseth, Sellevold, Videm)
For the last 17 years more than 300 preoperative, perioperative and postoperative data
points have been registered in all cardiac surgery patients. The database now contains more
than 12 000 cases, and allows investigation of perioperative indices in relation to mortality
and postoperative complications. Blood samples and clinical variables have been registered
prospectively in another 1000 patients, in which genetic polymorphisms and inflammatory
markers will be related to postoperative complications. Ongoing in vitro studies focus on the
mechanisms for neutrophil activation upon contact with artificial surfaces such as in
cardiopulmonary bypass.
Clinical anaesthesia (Fasting, Gisvold)
The focus has been on continuous quality assurance and improvement by routine
monitoring of complications during anaesthesia and intensive care. This registry has been in
operation for almost 30 years.
Postoperative bleeding in cardiac surgery (Stenseth, Pleym, Wahba)
There has been extensive characterization and prevention of postoperative bleeding in
cardiac surgery. Collaboration with researchers in Inflammation and Biocompatibility has led
to studies on various aspects of haemostasis and inflammation during cardiopulmonary
bypass. The Institute of Immunology (Prof. T.E. Mollnes) and the Department of Thoracic
2
and Cardiovascular Surgery at Oslo University Hospital (Prof. L. Svennevig, A. Fiane) have
been heavily involved.
Postoperative fatigue following cardiac surgery (Kirkeby-Garstad, Nordhaug, Sellevold,
Aadahl)
This research focuses on oxygen transport and metabolism in skeletal muscle
following extracorporeal circulation in cardiac surgery, in collaboration with ultrasound
researchers at the department. A clinical study assessing the effect of moderate and high
intensity interval training on the clinical course in patients with atrial fibrillation starts within
the next months.
Bed-rest after aortic valve surgery (Sellevold)
Physiological changes occur during mobilization after cardiac valve surgery. A
randomized study of patients mobilized the day after surgery compared with a group of
patients staying in bed for two days has been completed, in cooperation with St. Orsola
University Hospital in Bologna, Italy (Professor Martinelli, Dr. Grillone).
Myocardial contractile reserve in patients with an unstable haemodynamic state (KirkebyGarstad, Nordhaug, Aadahl)
A model has been developed for instantaneous capture of flow-profiles obtained by
ultrasound and arterial pressure measured in aorta. At present, the model is validated in a
large-animal experimental model in cooperation between the NTNU researchers in fluid
dynamics (Prof. Hellevik) and an ultrasound researcher at the Department (Løvstakken).
Emergency medicine (Skogvoll, Gisvold)
The research focus has been on cardiopulmonary resuscitation either in-hospital or
out-of-hospital, pre-hospital and in-hospital triage in trauma, and emergency air and ground
ambulances. In close cooperation with emergency researchers at the University of Oslo (Prof.
Steen) and signal analysts at the University of Stavanger (Prof. Eftestøl), dynamic models for
analysis of patients’ state development during cardiac arrest are currently studied.
Collaboration now is extended to the Resuscitation Study Group at the University of Chicago,
USA (Dr. Edelson). The underlying causes of cardiac arrest are studied in cooperation with
the ultrasound researchers at the Department of Circulation and Medical Imaging (Assoc.
Prof. B.O. Haugen) and clinicians at the Department of Pathology and Medical Genetics of St.
Olavs Hospital.
Imaging and intervention in cardiovascular and pulmonary disease (Wiseth, Videm)
Despite high workload on the attending physicians, the department has high potential
for using its new clinical laboratories in improving and extending research. The department
has included more 1000 patients in the ongoing NORSTENT trial, and runs a substudy on
dysglycaemia. Planned projects include high-intensity interval training and the composition of
intracoronary plaques assessed with intracoronary ultrasound and virtual histology.
Measurement of inflammatory markers is included as a translational aspect
Electrophysiology (Loennechen, Rossvoll)
Clinical studies have investigated the risk of ventricular arrhythmias in patients with
myocardial infarction, and in patients with catecholaminergic polymorphic ventricular
tachycardia mutations. Both involve cooperation with Dr. Haugaa, Rikshospitalet, Oslo. Two
registry studies evaluate radiofrequency ablation and atrial fibrillation treatment at St Olavs
Hospital.
3
Inflammation in cardiovascular disease (Videm, Wiseth)
Present translational projects related to the innate immune system in cardiovascular
medicine comprise studies on oxidative stress and inflammatory response during
revascularization procedures. Relations between atherosclerotic disease, dysglycaemia and
novel inflammatory markers are assessed. Other topics include the impact of diabetes on risk
for fatal coronary artery disease, based on data from the population-based North-Trøndelag
Health Survey. Inflammation and cardiovascular disease in HUNT patients with rheumatoid
arthritis or ankylosing spondilitis is done in collaboration with Drs. Thomas and Brown,
University of Queensland, Brisbane, Australia. A specially designed “Immunochip”,
permitting genotyping of 200 000 relevant SNPs will be employed. Linking to the national
Norwegian Cause of Death Registry has been established.
Remote ischemic preconditioning, including preoperative training on the myocardium in
patients (Nordhaug, Kirkeby-Garstad)
The preconditioning mechanisms are investigated by preoperatively harvesting human
myocardial biopsies from patients that have performed preoperative exercise. Mitochondrial
respiration, membrane structure, and calcium handling are assessed in collaboration with the
unit for Exercise training in Health and Disease (Prof. Wisløff).
Myocardial cell structure and function in atrial fibrillation (Wahba Loennechen)
Patients scheduled for surgical ablation of atrial fibrillation provide preoperative
specimens, and tissue from cardiac surgery patients without atrial fibrillation is taken for
comparison. Mitochondrial respiration, membrane structure, and calcium handling are
assessed in collaboration with the unit for Exercise training in Health and Disease (Prof.
Wisløff).
Strengths and weaknesses
The major strength of the unit is its broad interdisciplinary network and the heavy
involvement of clinicians in research. Cooperation with translational researchers is another
asset. A tradition of interdisciplinary projects at the Department facilitates the combination of
new ideas coming from clinical problems and systematic mechanistic research that takes
advantage of the resources from other disciplines.
The most obvious weaknesses of the unit are limited protected time for research and
lack of common strategic goals. Fortunately these challenges are being recognised by the
leadership and most of the researchers. As detailed in section 1.1.3, the Faculty of Medicine
and St. Olavs Hospital are addressing these issues in their common strategy for an integrated
University Hospital, both at the top institutional level and in the academic and clinical
departments. With many resources and strengths, the unit is likely to expand its external
project funding substantially by working within the institutional strategic framework.
Recruitment of PhD students is mainly done by supervising medical students from the
science track, offering an extra research year imbedded in medical school. The majority of
these candidates want to get a PhD as a starting point in their clinical career. They start with
small projects and pursue a path for PhD completion. Junior physicians who are interested in
research, typically start clinical projects and apply for combined research positions. The
clinical departments have some combined half-time research / half-time clinical specialization
positions that have been attractive because they provide clinical and scientific training. For a
majority of physicians within the field, a clinical career is most popular in terms of financial
and professional outcome. This limits the number of physicians wanting to enter into a full-
4
time research position. A strategic goal is to integrate research and clinical work by
establishing more combined 50%/50% research/clinical positions, and to pursue the
recruitment of medical students. As the PhD candidates finish their degrees, more effort will
be invested in obtaining post-doctoral positions.
The majority of the research staff is male, but with higher numbers of women in
medical school the recruitment of women researcher is increasing (1.1.6). The department is
following the NTNU policy of gender equality, and there is successful recruitment of women
researchers as PhD students in clinical disciplines.
In general, age distribution of faculty is satisfactory. However, a number of
researchers in cardiothoracic anaesthesia and intensive care are approaching retirement within
5-10 years, and an active recruiting policy has been pursued over the past years. Emergency
medicine has been successful in recruiting PhD students among clinical fellows. Mobility of
Norwegian physicians and clinical PhD students to institutions abroad is relatively low. This
is probably partly due to certification requirements abroad and favourable domestic working
conditions. Most PhD students have spouses and children, which require extra time and
financial resources. Nevertheless, exchange with international institutions is encouraged and
the unit has a broad network that facilitates mobility where possible. Postdoctoral fellows and
clinicians with a doctorate degree are encouraged to serve as main supervisors of PhD
students.
interdisciplinary.
Most researchers within the unit have a large potential for collaborative research, and
several faculty are involved in longstanding productive networks, as evidenced by copublication. Some examples have already been mentioned (1.2.2). Within emergency
medicine, the R&D Department of the Norwegian Air ambulance Foundation (Professor Hans
M. Lossius) provides access to an international research network. The Foundation is one of
the largest Norwegian patient organizations, reflecting high public awareness and funding.
1.2.5 Other information of relevance to the evaluation
The unit comprises a network of key persons well established in adjacent clinical fields that
are likely to benefit mutually by developing and pursuing common goals within a firmer
organisational structure. An important asset of the unit is ideas that emerge from managing
patients and confronting real life clinical problems.
Senior members of the unit
1. Sven Erik Gisvold, PhD
2. Olav FM Sellevold, PhD
3. Eirik Skogvoll PhD
4. Vibeke Videm, PhD
5. Alexander Wahba, PhD
6. Rune Wiseth, PhD
7. Petter Aadahl, PhD
8. Sigurd Fasting, PhD
9. Sigurd Gunnes, PhD
10. Bjørn Olav Haugen, PhD
11. Jan Pål Loennechen, PhD
12. Dag Ole Nordhaug, PhD
13. Erik Solligård, PhD
14. Roar Stenseth, PhD
Professor II
Professor II/ Section Leader
Professor II
Professor
Professor II
Professor
Professor
Associate Professor II
Associate Professor
Associate Professor
Associate Professor
Researcher
5
15. Idar Kirkeby-Garstad, PhD Researcher
Adjunct members of the unit, solely affiliated with St. Olavs Hospital
16. Hilde Pleym, PhD,
Senior Consultant, Anaesthesiology
17. Ane Dale, PhD
Senior Consultant, Cardiology
6
List of publications for the unit Cardiovascular Clinical and Translational Science
2010
1. Bergum D, Skogvoll E. Continuous chest compressions: encouraging but unusual.
Scand J Trauma Res Emerg Med 2010,18:20.
2. Bjerkelund CE, Christensen P, Dragsund S, Aadahl P. How to secure free airway?
Tidsskr Nor Laegeforen. 2010; 130: 507-510
3. Eggum R, Ueland T, Mollnes TE, Videm V, Fiane AE, Aukrust P, Lindberg HL.
Perfusion temperature, thyroid hormones and inflammation during pediatric cardiac
surgery. Interact Cardiovasc Thorac Surg 2010;10: 76-80.
4. Fasting S. Risk in anaesthesia. Tidsskr Nor Laegeforen. 2010; 130: 498-502.
5. Gjeilo KH, Klepstad P, Wahba A, Lydersen S, Stenseth R. Chronic pain after cardiac
surgery: a prospective study. Acta Anaesthesiol Scand. 2010; 54:70-78.
6. Haugaa KH, Leren IS, Berge KE, Bathen J, Loennechen JP, Anfinsen OG, Früh A,
Edvardsen T, Kongsgård E, Leren TP, Amlie JP. High prevalence of exercise-induced
arrhythmias in catecholaminergic polymorphic ventricular tachycardia mutationpositive family members diagnosed by cascade genetic screening. Europace. 2010;12:
417-423.
7. Haugaa KH, Smedsrud MK, Steen T, Kongsgaard E, Loennechen JP, Skjaerpe T,
Voigt JU, Willems R, Smith G, Smiseth OA, Amlie JP, Edvardsen T. Mechanical
dispersion assessed by myocardial strain in patients after myocardial infarction for risk
prediction of ventricular arrhythmia. JACC Cardiovasc Imaging. 2010; 3: 247-256.
8. Hjelde H, Sundstrøm S, Ødegård A, Hatlinghus S, Abusland AB, Haaverstad R.
Recurrence and survival after surgical treatment of lung cancer. [Norwegian] Tidsskr
Nor Laegeforen. 2010; 130:25-28.
9. Krüger A, Skogvoll E, Castren M, Kurola J, Lossius HM. Scandinavian pre-hospital
physician-manned Emergency Medical Services – same concept across borders?
Resuscitation 2010;81:427-433
10. Larsen K, Uleberg O, Skogvoll E. Difference in trauma team activation criteria among
Norwegian hospitals. Scand J Trauma Res Emerg Med 2010, 18:21.
11. Mostad U, Fasting S. Paediatric intensive care. Tidsskr Nor Laegeforen. 2010;130:4043. [Norwegian]
12. Nordgaard H, Swillens A, Nordhaug D, Kirkeby-Garstad I, Van Loo D, Vitale N,
Segers P, Haaverstad R, Lovstakken L. Impact of competitive flow on wall shear
stress in coronary surgery: computational fluid dynamics of a LIMA-LAD model.
Cardiovasc Res 2010; 88:512-519.
13. Nordgaard HB, Vitale N, Astudillo R, Renzulli A, Romundstad P, Haaverstad R.
Pulsatility index variations using two different transit-time flowmeters in coronary
artery bypass surgery. Eur J Cardiothorac Surg. 2010; 37: 1063-1067.
14. Nyrnes SA, Løvstakken L, Skogvoll E, Torp HE, Haugen BO. Does a new ultrasound
low modality improve visualisation of neonatal pulmonary veins? Echocardiography
2010; 27:1113-1119
15. Poldermans D, Bax JJ, Boersma E, De Hert S, Eeckhout E, Fowkes G, Gorenek B,
Hennerici MG, Iung B, Kelm M, Kjeldsen KP, Kristensen SD, Lopez-Sendon J, Pelosi
P, Philippe F, Pierard L, Ponikowski P, Schmid JP, Sellevold OF, Sicari R, Van den
Berghe G, Vermassen F, Hoeks SE, Vanhorebeek I, Vahanian A, Auricchio A, Bax JJ,
Ceconi C, Dean V, Filippatos G, Funck-Brentano C, Hobbs R, Kearn P, McDonag T,
McGregor K, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Vardas P,
Widimsky P, De Caterina R, Agewall S, Al Attar N, Andreotti F, Anker SD, BaronEsquivias G, Berkenboom G, Chapoutot L, Cifkova R, Faggiano P, Gibbs S, Hansen
HS, Iserin L, Israel CW, Kornowski R, Eizagaechevarria NM, Pepi M, Piepoli M,
Priebe HJ, Scherer M, Stepinska J, Taggart D, Tubaro M; Guidelines for pre-operative
cardiac risk assessment and perioperative cardiac management in non-cardiac surgery:
the Task Force for Preoperative Cardiac Risk Assessment and Perioperative Cardiac
Management in Non-cardiac Surgery of the European Society of Cardiology (ESC)
and endorsed by the European Society of Anaesthesiology (ESA). Eur J Anaesthesiol
2010; 27: 92-137.
16. Reid BO, Skogvoll E. Pitfalls with the "chest compression-only" approach: The
challenge of detecting an unusual cause. Scand J Trauma Res Emerg Med 2010, 8:45
doi:10.1186/1757-7241-18-452010 [Case report]
17. Sellevold OF, Stenseth R. Non-cardiac surgery in patients with cardiac disease.
Tidsskr Nor Laegeforen. 2010;130:623-7. [Norwegian]
18. Sellevold OF, Bratlid D. Is Tidsskriftet's publishing time too long? Tidsskr Nor
Laegeforen. 2010 Jun 17; 130: 1228-1231. [Norwegian]
19. Sellevold OFM, de Hert S, Pelosi P. A major step forward: guidelines for the
management of cardiac patients for non-cardiac surgery - the art of anaesthesia. Eur J
Anaesthesiol 2010; 27:89-91.
20. Sellevold OF, Guarracino F. Transcutaneous aortic valve implantation: recent
advances and future. Curr Opin Anaesthesiol 2010; 23:67-73.
21. Vanke P, Nordseth T, Loennechen JP, Mostad DH, Skjærpe T, Sellevold OFM. Young
woman with cardiac arrest. Tidsskr Nor Legeforen 2010; 130:47-50. [Norwegian]
22. Thiara AS, Andersen VY, Videm V, Mollnes TE, Fiane AE. Comparable
biocompatibility of Phisio- and Bioline-coated cardiopulmonary bypass circuits
indicated by the inflammatory response. Perfusion 2010;25(1):9-16.
23. Vanke P, Nordseth T, Loennechen JP, Mostad DH, Skjaerpe T, Sellevold OF. A
young woman with cardiac arrest. Tidsskr Nor Laegeforen. 2010; 130: 47-50.
[Norwegian]
24. Veel T, Bugge JF, Kirkebøen KA, Pleym H. Anaesthesia in adult open heart surgery.
Tidsskr nor Laegeforen 2010; 130: 618-22. [Norwegian]
25. Vengen IT, Dale AC, Wiseth R, Videm V. Lactoferrin is a novel predictor of fatal
ischemic heart disease in diabetes mellitus type 2. Long-term follow-up of the HUNT
1 study. Atherosclerosis. 2010; 212: 614-20.
2009
1. Beisvag V, Kemi OJ, Arbo I, Loennechen JP, Wisløff U, Langaas M, Sandvik AK,
Ellingsen Ø. Pathological and physiological hypertrophies are regulated by distinct
gene programs. Eur J Cardiovasc Prev Rehabil. 2009;16: 690-697.
2. Berg KK, Madsen HO, Garred P, Wiseth R, Gunnes S, Videm V.The additive
contribution from inflammataory genetic markers on the severity of cardiovascular
disease. Scand J Immunol 2009;69:36-42.
3. Dale AC, Midthjell K, Nilsen TIL, Wiseth R, Vatten LJ. Glycemic control in newly
diagnosed diabetes patients and mortality from ischemic heart disease: 20-year followup of the HUNT Study in Norway. Eur Heart J 2009; 30:1372-1377.
4. Erglis A, Kumsars I, Niemelä M, Kervinen K, Maeng M, Lassen JF, Gunnes P,
Stavnes S, Jensen JS, Galløe A, Narbute I, Sondore D, Mäkikallio T, Ylitalo K,
Christiansen EH, Ravkilde J, Steigen TK, Mannsverk J, Thayssen P, Hansen KN,
Syvänne M, Helqvist S, Kjell N, Wiseth R, Aarøe J, Puhakka M, Thuesen L; Nordic
PCI Study Group. Randomized comparison of coronary bifurcation stenting with the
crush versus the culotte technique using sirolimus eluting stents: the Nordic stent
technique study. Circ Cardiovasc Interv. 2009; 2: 27-34.
5. Chronic pain after cardiac surgery: a prospective study. Gjeilo KH, Klepstad P, Wahba
A, Lydersen S, Stenseth R. Acta Anaesthesiol Scand. 2009; 54(1):70-8.
6. Hoel TN, Thiara AS, VidemV, Fiane AE, Mollnes TE, Castellheim A, Svennevig JL.
In vitro evaluation of Phisio-coated sets for pediatric cardiac surgery. Scand Cardiovasc
J 2009; 43: 129-135.
7. Kolseth SM, Nordhaug DO, Stenseth R, Sellevold O, Kirkeby-Garstad I, Wahba A.
Prophylactic treatment with levosimendan: a retrospective matched-control study of
patients with reduced left ventricular function. Eur J Cardiothorac Surg.
2009;36:1024-1030.
8. Kvaløy JT, Skogvoll E, Eftestøl T, Gundersen K, Kramer-Johansen J, Olasveengen
TM, Steen PA: Which factors influence state transitions during resuscitation?
Resuscitation 2009 Aug; 80(8):863-869.
9. Moholdt TT, Amundsen BH, Wahba A, Løvø KT, Gullikstad L, Bye A, Skogvoll E,
Wisløff U, Slørdahl SA. Aerobic interval training versus continuous moderate exercise
after coronary artery bypass surgery: A randomised study of cardiovascular effects and
quality of life. American Heart Journal 2009; 158:1031-1037.
10. Myhre HO, Ødegård A, Winnerkvist A, Stenseth R. Thoracic abdominal aneurysms-open surgery and endovascular treatment. Tidsskr Nor Laegeforen 2009; 129: 21272130. [Norwegian]
11. Nordgaard H, Vitale N, Haaverstad R. Transit-time blood flow measurements in
sequential saphenous coronary artery bypass grafts.Ann Thorac Surg. 2009; 87:140915.
12. Nordgaard H, Nordhaug D, Kirkeby-Garstad I, Løvstakken L, Vitale N, Haaverstad R.
Different graft flow patterns due to competitive flow or stenosis in the coronary
anastomosis assessed by transit-time flowmetry in a porcine model. Eur J
Cardiothorac Surg. 2009; 36:137-42.
13. Pleym H. 4.2.2.3 Fibrinolysehemmere: Tranexamsyre, og 4.2.2.4 Rekombinant faktor
VIIa (rFVIIa). I: Heier HE (red.). Håndbok i transfusjonsmedisin. Oslo:
Helsedirektoratet, 2009. http://www.helsedirektoratet.no/sykehus/blodbanker
14. Poldermans D, Bax JJ, Boersma E, De Hert S, Eeckhout E, Fowkes G, Gorenek B,
Hennerici MG, Lung B, Kelm M, Kjeldsen KP, Kristensen SD, Lopez-Sendon J,
Pelosi P, Philippe F, Pierard L, Ponikowski P, Schmid JP, Sellevold OF, Sicari R, Van
den Berghe G, Vermassen F, Hoeks SE, Vanhorebeek I; ESC Committee for Practice
Guidelines (CPG). Guidelines for pre-operative cardiac risk assessment and
perioperative cardiac management in non-cardiac surgery: the Task Force for
Preoperative Cardiac Risk Assessment and Perioperative Cardiac Management in
Non-cardiac Surgery of the European Society of Cardiology (ESC) and European
Society of Anaesthesiology (ESA).Eur Heart J 2009;30:2769-812.
15. Prot V, Haaverstad R, Skallerud B. Finite element analysis of the mitral apparatus:
annulus shape effect and chordal force distribution. Biomech Model Mechanobiol.
2009;8: 43-55.
16. Røe OD, Anderssen E, Helge E, Pettersen CH, Olsen KS, Sandeck H, Haaverstad R,
Lundgren S, Larsson E. Genome-wide profile of pleural mesothelioma versus parietal
and visceral pleura: the emerging gene portrait of the mesothelioma phenotype. PLoS
One. 2009; 4: e6554.
17. Tjønna AE, Stølen T, Bye A, Slørdahl S, Ødegård R, Skogvoll E, Wisløff U. Aerobic
interval training reduce cardiovascular risk factors more than a multi treatment
approach in overweight adolescents. Clinical Science (Lond). 2009;116:317-326
18. Tyldum GA, Schjerve IE, Tjønna AE, Kirkeby-Garstad I, Stølen TO, Richardson RS,
Wisløff U. Endothelial dysfunction induced by post-prandial lipemia: complete
protection afforded by high-intensity aerobic interval exercise J Am Coll Cardiol.
2009; 53: 200-206.
19. Vegsundvåg J, Holte E, Wiseth R, Hegbom K, Hole T. Transthoracic
echocardiography for imaging of the different coronary artery segments: a feasibility
study. Cardiovasc Ultrasound. 2009; 7: 58.
20. Vengen IT, Dale AC, Wiseth R, Midthjell K, Videm V. Neopterin predicts the risk for
fatal ischemic heart disease in type 2 diabetes mellitus. Long-term follow-up of the
HUNT 1 study. Atherosclerosis 2009; 207: 239-244.
21. Videm V, Olsen GD. No relationship between neutrophil granulocyte activation and
the myeloperoxidase gene -129 G>A and -463 G>A promoter polymorphisms:
implications for investigations of cardiovascular disease. Coronary Artery Disease
2009; 20: 446-452.
22. Wahba A. Cardioblate surgical ablation system.. Expert Rev Med Devices 2009;6:
469-75.
23. Christensen E, Skogvoll E, Viset T, Warloe T, Sundstrøm S. Photodynamic therapy
with 5-aminoleavulinic acid, dimethylsulfoxide and curettage in basal cell carcinoma –
a 6 year clinical and histological follow up. Journal of the European Academy of
Dermatology and Venereology 2009; 23:58-66.
2008
1. Castellheim A, Hoel TN, Videm V, Fosse E, Pharo A, Svennevig JL, Fiane AE, Mollnes
TE. Biomarker profile in off-pump and on-pump coronary artery bypass grafting surgery
in low-risk patients. Ann Thorac Surg 2008; 85:1994-2002.
2. Christensen E, Gudmundsdottir I, Bofin A, Skogvoll E. Cytological diagnosis of
basalcell carcinoma and actinic keratosis, using Papanicolaou and May-GrunvaldGiemsa stained cutaneous tissue smear. Cytopathology 2008;19: 316-322.
3. Dale AC, Vatten LJ, Nilsen TIL, Midthjell K, Wiseth R. Secular decline in mortality
from coronary heart disease in adults with diabetes mellitus: cohort study. BMJ. 2008;
337:a236. doi: 10.1136/bmj.39582.447998.BE
4. Dale O, Nilsen T, Bjørgaas T, Borkamo A, Aadahl P The time course of exhaled ethane in six
intensive care cases. Acta Anaesthesiol Scand. 2008; 52: 869-71.
5. Juel IS, Solligård E, Tvedt KE, Skogvoll E, Jynge P, Beisvag V, Erlandsen SE,
Sandvik AK, Aadahl P, Grønbech JE. Post-ischaemic restituted intestinal mucosa is
more resistant to further ischaemia than normal mucosa in the pig. Scand J Clin Lab
Invest. 2008; 68 :106-116 .
6. Eggum R, Ueland T, Mollnes TE, Videm V, Aukrust P, Fiane AE, Lindberg HL. Effect
of perfusion temperature on the inflammatory response during pediatric cardiac surgery.
Ann Thorac Surg 2008; 85: 611-617.
7. Garner OB, Yamaguchi Y, Esko JD, Videm V. Small changes in lymphocyte
development and activation in mice by tissue-specific alteration of heparan sulfate.
Immunology 2008; 125: 420-429.
8. Gjeilo KH, Wahba A, Klepstad P, Lydersen S, Stenseth R. The role of sex in healthrelated quality of life after cardiac surgery: a prospective study. Eur J Cardiovasc Prev
Rehabil 2008;15: 448-5.
9. Graven T, Loennechen JP, Leren TP. Brugada syndrome. Tidsskr Nor Laegeforen.
2008; 128: 2828-31. [Norwegian]
10. Hayashi SY, Seeberger A, Lind B, Gunnes S, Alvestrand A, do Nascimento MM,
Lindholm B, Brodin LA. Acute effects of low and high intravenous doses of
furosemide on myocardial function in anuric haemodialysis patients: a tissue Doppler
study. Nephrol Dial Transplant. 2008:1355-1361.
11. Ibrahim K, Vitale N, Kirkeby-Garstad I, Samstad S, Haaverstad R. Narrowing effect
of off-pump CABG on the LIMA-LAD anastomosis: epicardial ultrasound
assessment. Scand Cardiovasc J. 2008;42:105-109.
12. Ibrahim KS, Vitale N, Tromsdal A, Kirkeby-Garstad I, Fraser AG, Haaverstad R.
Enhanced intra-operative grading of ascending aorta atheroma by epiaortic ultrasound
vs echocardiography. Int J Cardiol. 2008;128:218-223.
13. Jensen JS, Galløe A, Lassen JF, Erglis A, Kumsars I, Steigen TK, Wiseth R et al.
Safety in simple versus complex stenting of coronary artery bifurcation lesions. The
nordic bifurcation study 14 mont follow-up results. EuroIntervention 2008; 2: 229-33.
14. Juel IS, Solligård E, Lyng O, Bakkelund K, Tvedt K, Skogvoll E, Aadahl P, Grønbech JE.
Postischaemic restituted intestinal mucosa is more resistant to further ischaemia than normal
mucosa in the pig. Scand J Clin Lab Invest. 2008;68(2):106-16.
15. Ljøstad U, Skogvoll E, Eikeland R, Midgard R, Skarpaas T, Berg Å, Mygland Å. Oral
Doxycycline versus IV Ceftriaxone for European Lyme Neuroborreliosis: A
multicenter randomised double-blind placebo-controlled trial. Lancet Neurology
2008;7: 690-695.
16. Lovstakken L, Ibrahim KS, Vitale N, Henriksen ST, Kirkeby-Garstad I, Torp H,
Haaverstad R. Blood flow imaging: a new two-dimensional ultrasound modality for
enhanced intraoperative visualization of blood flow patterns in coronary anastomoses.
J Am Soc Echocardiogr. 2008; 21: 969-975.
17. Pleym H, Wahba A, Bjella L, Stenseth R. Sonoclot analysis in coronary artery
surgery: a comparison between patients with unstable coronary artery disease treated
with enoxaparin before surgery and patients with stable coronary artery disease not
treated with enoxaparin. J Cardiothorac Vasc Anesth 2008;22:670-674.
18. Pleym H, Wahba A, Bjella L, Stenseth R. Sonoclot-analysis in elderly compared to younger
patients undergoing coronary surgery. Acta Anaesthesiol Scand 2008;52:28-35.
19. Pleym H. Drugs for reduction of blood transfusions during surgery. Tidsskr Nor Laegeforen 2008;
128: 829-30. [Norwegian]
20. Rasmussen LS, Gisvold SE. New author guidelines. Acta Anaesthesiol Scand. 2008;
52: 594-595.
21. Roth K, Nilsen TI, Hatlen E, Sørensen KS, Hole T, Haaverstad R. Predictors of long
time survival after lung cancer surgery: a retrospective cohort study.BMC Pulm Med.
2008;8: 22.
22. Schjerve IE, Tyldum GA, Tjønna AE, Stølen TO, Loennechen JP, Hansen HE, Haram
PM, Heinrich G, Bye A, Najjar SM, Smith GL, Slørdahl SA, Kemi OJ, Wisløff U.
Both aerobic endurance and strength training programs improve cardiovascular health
in obese adults. Clin Sci (Lond). 2008; 115: 283-93
23. Skogvoll E, Gundersen K, Eftestøl T, Kvaløy JT, Kramer-Johansen J, Olasveengen M,
Steen PA. Dynamics and State Transitions during Resuscitation in Out-of-Hospital
Cardiac Arrest. Resuscitation 2008; 78: 30-37.
24. Skogvoll E, Nordseth T. The early minutes of in-hospital cardiac arrest: Shock or
CPR? A population-based prospective study. Scan J Trauma Resus Emerg Med 2008,
16:11
25. Solligård E, Juel IS, Spigset O, Romundstad P, Grønbech JE, Aadahl P. Gut luminal
lactate measured by microdialysis mirrors permeability of the intestinal mucosa after
ischemia. Shock 2008;29:245-25.
26. Sellevold OFM, Pelosi P. Lots of enthusiasm and good will but little resources. Tidsskr Nor
Legeforen 2008: 128:1428-1429. [Norwegian]
27. Tyvold. SS, Solligard E, Gunnes S, Steinshamn S, Aadahl P. Continuous monitoring of the
bronchial epithelial lining fluid by microdialysis. Respir Res. 2007; 8:78.
28. Tjønna AE, Lee SJ, Rognmo Ø, Stølen TO, Bye A, Haram PM, Loennechen JP, AlShare QY, Skogvoll E, Slørdahl SA, Kemi OJ, Najjar SM, Wisløff U. Aerobic interval
training versus continuous moderate exercise as a treatment for the metabolic
syndrome: a pilot study. Circulation. 2008;118: 346-54.
29. Tyldum EV, Madssen E, Skogvoll E, Slørdahl SA. Repeated image analyses improve
accuracy in assessing arterial flow-mediated dilatation. Scand Cardiovasc J 2008; 42:
310-315.
30. Velle HO, Kolnes K, Høgalmen G, Gudim LP, Wiseth R, Rødevand O. Computer
tomography coronary angiography. Tidsskr Nor Lægeforen 2008;128:2177-80.
[Norwegian]
31. Videm V, Albrigtsen M. Soluble ICAM-1 and VCAM-1 as markers of endothelial
activation. Scand J Immunol 2008; 67: 523-531.
32. Videm V. Neutrophil-Biomaterial interactions Wnek G, Bowlin GE (eds):
Encyclopedia of Biomaterials and Biomedical Engineering, 2nd edition, pp 19341941. Informa Healthcare, New York, May 2008. ISBN 9781 42007 8022.
DOI:10.3109/E-EBBE-120041672. (Book chapter).
33. Wahba A. Intraaortic balloon pump placement in various patient populations.
Interactive Cardiovascular and Thoracic Surgery 2008; 7 389-395.
34. Wahba A, Flobak F, Stakkevold TI, Sellevold OM, Greiff G, Wiseth R. A 76-year old
man with cardiac murmur after myocardial infarction. Tidsskr Nor Legeforening 2008;
128: 46-8. [Norwegian]
35. Åsberg AE, Mollnes TE, Videm V. Complement activation by neutrophil granulocytes.
Scand J Immunol 2008; 67: 354-361.
36. Åsheim P, Spigset O, Aasarød K, Walstad RA, Uggen PE, Zahlsen K, Aadahl P.
Pharmacokinetics of peritoneally instilled aminophylline, terbutaline and tobramycin
in pigs. Acta Anaesthesiol Scand. 2008; 52: 243-248.
2007
1. Brattli OS, Nystuen K, Sæther OD, Aadahl P, Grønbech JE and Myhre HO: Regional
distribution of blood flow during proximal aortic cross-clamping: An Experimental
Study using Coloured Microspheres. Scand J Clin Lab Invest. 2007; 67: 526-535.
Castberg I, Skogvoll E, Spigset O. Pharmacokinetics of quetiapine: Evidence from a
routine therapeutic drug monitoring service. J Clin Psych 2007; 68: 1540-1545.
2. Dale AC, Nilsen TI, Vatten L, Midthjell K, Wiseth R. Diabetes mellitus and risk of
fatal ischaemic heart disease by gender: 18 years follow-up of 74,914 individuals in
the HUNT 1 study. Eur Heart J 2007; 28: 2924-2929.
3. Gisvold SE. Challenges in scientific publishing--reflections after 14 years as Editor-inChief. Acta Anaesthesiol Scand. 2007 Sep;51(8):975-8.
4. Gisvold SE. There is much to learn from history. Acta Anaesthesiol Scand. 2007;
51:965.
5. Gjeilo KH, Stenseth R, Wahba A, Lydersen S, Klepstad P. Validation of the Brief Pain
Inventory in Patients Six Months After Cardiac Surgery. J Pain Symptom Manage
2007;34:648-56.
6. Haaverstad R, Vitale N, Tromsdal A, Hegbom K, Karevold A. Intermittent incomplete
closure of Medtronic Advantage aortic valve leaflets causes unnecessary reoperation. J
Thorac Cardiovasc Surg. 2007;134:791- 792.
7. Haaverstad R, Latto PN, Vitale N. Right subclavian catheter perforation of the aorta
due to an incorrect external landmark-guided insertion technique. CJEM. 2007; 9: 4345.
8. Haaverstad R, Vitale N, Karevold A, Cappabianca G, Tromsdal A, Olsen PS, Köber L,
Ihlen H, Rein KA, Svennevig JL. Clinical and echocardiographic assessment of the
Medtronic Advantage aortic valve prosthesis: the Scandinavian multicentre,
prospective study. Heart. 2007;93:500-505.
9. Heimstad R, Skogvoll E, Mattson L-Å, Johansen OJ, Eik-Nes S, Salvesen K.
Induction or antenatal monitoring in post-term pregnancy? A randomised, controlled
trial. Obstetrics & Gynecology 2007;109: 609-617.
10. Holte E, Vegsundvåg J, Wiseth R. Direct visualization of of a significant stenosis of
the right coronary artery by transthoracic echocardiography. A case report.
CardiovascUltrasound 2007;5: 33.
11. Hauso Ø, Gustafsson BI, Loennechen JP, Stunes AK, Nordrum I, Waldum HL. Longterm serotonin effects in the rat are prevented by terguride. Regul Pept. 2007;143: 3946.
12. Hoel TN, Saatvedt K, Videm V, Mollnes TE, Brosstad F, Seem E, Fosse E, Svennevig
JL. Off-pump cardiac surgery abolishes complement activation. Perfusion 2007;22:251256.
13. Kjøs HO, Lande TM, Eriksson U, Nordhaug D, Karevold A, Haaverstad R. [Thoracic
injuries at a regional trauma centre].Tidsskr Nor Laegeforen. 2007;127:1496-1499.
[Norwegian]
14. Lund JA, Wibe A, Sundstrom SH, Haaverstad R, Kaasa S, Myrvold HE. Anal
carcinoma in mid-Norway 1970-2000.Acta Oncol. 2007; 46: 1019-1026.
15. Ibrahim KS, Løvstakken L, Kirkeby-Garstad I, Torp H, Vik-Mo H, Haaverstad R.
Effect of the cardiac cycle on the coronary anastomosis assessed by ultrasound. Asian
Cardiovasc Thorac Ann. 2007;15: 86-90.
16. Juel IS, Solligård E, Skogvoll E, Aadahl P, Gronbech JE. Lactate and glycerol
released to the intestinal lumen reflect mucosal injury and permeability changes
caused by strangulation obstruction. Eur Surg Res. 2007;39:340-49
17. Kjørstad KE, Nordhaug DO, Korvald C, Müller S, Steensrud T, Myrmel T.Mechanical
restitution curves: a possible load independent assessment of contractile function. Eur
J Cardiothorac Surg. 2007;3: 677-84.
18. Kvaløy JT, Skogvoll E. Modelling seasonal and weather dependency of cardiac arrests
using the covariate order method. Statistics in Medicine 2007; 26: 3315-3329.
19. Manstad-Hulaas F, Ommedal S, Tangen GA, Aadahl P, Hernes TN. Side-branched
AAA stent graft insertion using navigation technology: a phantom study. Eur Surg
Res. 2007; 39: 364-371.
20. Pleym H. Drugs in Anaesthesia. In Nordeng H, Spigset O (eds.). Drugs and their use.
Oslo: Gyldendal, 2007. Book chapter [Norwegian]
21. Randeberg LL, Winnem AM, Langlois NE, Larsen EL, Haaverstad R, Skallerud B,
Haugen OA, Svaasand LO. Skin changes following minor trauma.Lasers Surg Med.
2007; 39:403-13.
22. Reimers A, Kutschera-Sund J, Skogvoll E, Spigset O. Lamotrigine in children and
adolescents: The impact of age on its serum concentrations and the extent of drug
interactions. Eur J Clin Pharmacol 2007; 63: 687-92.
23. Riley CF, Moen MH, Videm V. Inflammatory markers in endometriosis: Reduced
peritoneal neutrophil response in minimal endometriosis. Acta Obst Gyn Scand 2007; 86:
877-881.
24. Schirmer-Mikalsen K, Vik A, Gisvold SE, Skandsen T, Hynne H, Klepstad P. Severe
head injury: control of physiological variables, organ failure and complications in the
intensive care unit. Acta Anaesthesiol Scand. 2007; 51:1194-1201.
25. Sellevold OF, Fasting S, Stenseth R, Gisvold SE. Do medical errors occur only in
Trondheim? Tidsskr Nor Laegeforen. 2007;127: 1535. [Norwegian]
26. Skjold A. Amundsen BH, Wiseth R, Støylen A, Haraldseth O, Larsson HBW, Jynge P.
Manganese dipyridoxyl-diphosphate (MnDPDP) as a viability marker in patients
with myocardial infarction. J Magn Reson Imaging 2007;26: 720-727.
27. Solligård E, Wahba A, Skogvoll E, Stenseth R, Grønbech JE, Aadahl P. Rectal lactate
levels in endoluminal microdialysate during routine coronary surgery. Anaesthesia
2007; 62:250-258.
28. Stenseth R, Nilsen T, Haaverstad R, Vitale N, Dale O. Frequent sampling allows
detection of short and rapid surges of exhaled ethane during cardiac surgery. Perfusion
2007;22:391-396.
29. Støen R, Breivik H, Grimstad J, Sellevold OFM, Stenseth R. Central Neurological
Blocades in patients with increased bleeding tendency. 2007. [Norwegian]
http://nafweb.no/index.php?option=com_content&task=view&id=104&Itemid=27
30. Sørhaug S, Steinshamn S, Haaverstad R, Nordrum IS, Martinsen TC, Waldum HL.
Expression of neuroendocrine markers in non-small cell lung cancer.APMIS. 2007;
115: 152-63.
31. Tyvold SS, Solligård E, Lyng O, Steinshamn SL, Gunnes S, Aadahl P. Continuous
monitoring of the bronchial epithelial lining fluid by microdialysis. Respiratory
Research; 2007; 1: 78.
32. Uleberg O, Vinjevoll OP, Eriksson U, Aadahl P, Skogvoll E. Overtriage in trauma what are the causes? Acta Anaesth Scand 2007; 51: 1178-1183.
33. Videm V, Wiseth R, Gunnes S, Madsen HO, Garred P. Multiple inflammatory
markers in patients with significant coronary artery disease.. International J Cardiol
2007; 118: 81-87.
34. Wisløff U, Støylen A, Loennechen JP, Bruvold M, Rognmo Ø, Haram PM, Tjønna
AE, Helgerud J, Slørdahl SA, Lee SJ, Videm V, Bye A, Smith GL, Najjar SM,
Ellingsen Ø, Skjaerpe T. Superior cardiovascular effect of aerobic interval training
versus moderate continuous training in heart failure patients: a randomized study.
Circulation. 2007; 115: 3086-94.
35. Ødegård A, Aasland J, Myhre HO, Mollnes TE, Videm V. The inflammatory response
to stent grafting of the thoracic aorta. Int Angiol 2007; 26: 219-227.
36. Åsberg AE, Videm V. Inhibition of platelet receptors involved in neutrophil-platelet
interaction reduces biomaterial-induced inflammation in modell CPB. Artificial
Organs 2007; 31: 617-626.
37. Åsheim P, Uggen PE, Aasarød K, Aadahl P. A 58.year old woman with short bowel
syndrome and nutrition failure. Tidsskr Nor Laegeforen. 2007; 127: 1370-1371.
[Norwegian]
2006
1. Aghajani E, Muller S, Kjørstad KE, Korvald C, Nordhaug D, Revhaugand A, Myrmel
T. The pressure-volume loop revisited: Is the search for a cardiac contractility index a
futile cycle? Shock 2006; 25: 370-376.
2. Berg K, Haaverstad R, Astudillo R, Bjørngaard M, Skarra S, Wiseth R, Basu S, Jynge
P. Oxidative stress during coronary artery bypass operations: Importance of surgical
trauma and drug treatment. Scand Cardiovasc J 2006; 40: 291-297.
3. Bugten, V. Nordgaard, S. Skogvoll, E. Steinsvåg, S. Effects of non-absorbable
packing in middle meatus after sinus surgery. The Laryngoscope 2006; 116(1):83-88
4. Eide TO, Romundstad P, Stenseth R, Aadahl P, Myhre HO. Spinal fluid dynamics
during thoracic- and thoracoabdominal aortic surgery. Int Angiol 2006;25:46-51.
5. Fykse V, Solligård E, Bendheim MØ, Chen D, Grønbech JE, Sandvik AK,
WaldumHL. ECL cell histamine mobilization and parietal cell stimulation in the rat
stomach studied by microdialysis and electron microscopy. Acta Physiol.
2006;186:37-43.
6. Grawe RW, Falloon IRH, Widen JH, Skogvoll E. Two-years of continued early
treatment for recent-onset schizophrenia: a randomised controlled study. Acta Psych
Scand 2006; 114: 328-36.
7. Gustafsson B, Westbroek I, Waarsing J, Waldum HL, Solligård E, Brunsvik A,
Dimmen S, Leeuwen J van, Weinans H, Syversen U. Long-term serotonin
administration leads to higher bone mineral density, affects bone architecture, and
leads to higher femoral bone stiffness in rats. J Cell Biochem. 2006; 97:1283-1291.
8. Gjeilo KH, Wahba A, Klepstad P, Lydersen S, Stenseth R. Health-related quality of
life three years after coronary surgery: A comparison with the general population.
Scand Cardiovasc J 2006; 40: 29-36.
9. Haaverstad R, Myrmel T. Waiting time for surgery of lung cancer must be shortened.
Tidsskr Nor Laegeforen. 2006; 126:1893. [Norwegian]
10. Heimstad R, Dahloe R, Laache I, Skogvoll E, Schei B. Fear of childbirth and history
of abuse: implications for pregnancy and delivery. Acta Obstet Gynecol Scand. 2006;
85: 435-40.
11. Ibrahim K, Tjomsland O, Halvorsen D, Wiseth R, Wahba A, Karevold A, Haaverstad
R. Effect of clopidogrel on midterm graft patency following off-pump coronary
revascularization surgery. Heart Surg Forum 2006; 9: E 851-6.
12. Kirkeby-Garstad I, Sellevold OFM. Early mobilization after aortic valve surgery. Surg Technol
Int. 2006; 15:198-204.
13. Kirkeby Garstad I, Wisløff U, Skogvoll E, Stølen T, Tjønna AE, Stenseth R, Sellevold
OFM. The marked reduction in mixed venous oxygen saturation during early
mobilization after cardiac surgery; the effect of posture or exercise? Anesthesia and
Analgesia 2006; 102:1609-16.
14. Kemi OJ, Arbo I, Høydal MA, Loennechen JP, Wisløff U, Smith GL, Ellingsen Ø.
Reduced pH and contractility in failing rat cardiomyocytes. Acta Physiol (Oxf). 2006;
188: 185-93.
15. Kolnes K, Ose Velle H, Hareide S, Hegbom K, Wiseth R. Multislice computed
tomography coronary angiography at a local hospital: Pitfalls and potential. Acta
Radiol 2006;47:680-686.
16. Løvstakken L, Bjaerum S, Kristoffersen K, Haaverstad R, Torp H. Real-time adaptive
clutter rejection filtering in color flow imaging using power method iterations. IEEE
Trans Ultrason Ferroelectr Freq Control. 2006;53:1597-1608.
17. Madssen E, Hære P, Wiseth R. Radial artery diameter and vasodilatory properties after
transradial coronary angiography. Ann Thoracic Surg 2006; 82;1698-1702.
18. Malm S, Frigstad S, Torp H, Wiseth R, Skjærpe T. Quantitative adenosine real-time
myocardial contrast echocardiography for detection of angiographically significant
coronary artery disease. J Am Soc Echocardiogr 2006;19: 365-72.
19. Pleym H, Wahba A, Videm V, Åsberg, A, Lydersen S, Bjella L, Dale O, Stenseth R.
Increased fibrinolysis and platelet activation in elderly patients undergoing coronary
bypass surgery. Anesth Analg 2006;102:660-7
20. Pleym H, Videm V, Wahba A, Åsberg, A, Amundsen T, Bjella L, Dale O, Stenseth R.
Heparin resistance and increased platelet activation in coronary surgery patients
treated with enoxaparin preoperatively. Eur J Cardiothorac Surg 2006;29:933-940.
21. Randeberg LL, Haugen OA, Haaverstad R, Svaasand LO. A novel approach to age
determination of traumatic injuries by reflectance spectroscopy. Lasers Surg Med.
2006; 38: 277-289.
22. Steigen TK, Maeng M, Wiseth R, Erglis A, Kumsars I, Narbute I, Gunnes P,
Mannsverk J, Meyerdierks O, Rotevatn S, Niemelä M, Kervinen K, Jensen JS, Galløe
A, Nikus K, Vikman S, Ravkilde J, James S, Aarøe J, Ylitalo A, Helqvist S, Sjögren I,
Thayssen P, Virtanen K, Puhakka M, Airaksinen J, Lassen JF, Thuesen L; Nordic PCI
Study Group. Randomized study on simple versus complex stenting of coronary
artery bifurcation lesions: the Nordic bifurcation study Circulation 2006, 114:19551961.
23. Stenvik M, Tjomsland O, Lien S, Gunnes S, Kirkeby-Garstad I, Astudillo R. Effect of
subcutaneous suture line and surgical technique on wound infection after
saphenectomy in coronary artery bypass grafting: a prospective randomised study.
Scand Cardiovasc J. 2006; 40: 234-237.
24. Videm V, Wiseth R, Gunnes S, Madsen HO, Garred P. Multiple inflammatory
markers in patients with significant coronary artery disease. Int J Cardiol. 2007; 118:
81-87.
25. Wahba A, Nordhaug DO. What are the long-term results of cardiac valve
replacements endocarditis with a history of i.v. drug abuse? Interactive
CardioVascular and Thoracic Surgery 2006; 5: 608-610.
26. Wahba A. Centrifugal blood pump use in routine cardiac surgery. ICVTS 2006; 5: 299
- 300.
27. Wiseth R.Cardiac Disease. Tidsskr Nor Lægeforen 2006;126:94. [Norwegian]
28. Wiseth R, Hegbom K, Slette M, Åsberg A, Vik-Mo H. Incidence of procedural related
myocardial infarction following percutaneous coronary intervention. A matter of
definitions. Euro Interv 2006; 2: 351-355.
29. Yavuz Y, Aadahl P, Mårvik R, Grønbech JE. Hemodynamic and tissue blood flow responses to
long-term pneumoperitoneum and hypercapnia in the pig. Surg Endosc 2006; 20: 1394-1401.
30. Zaglavara T, Karvounis HI, Haaverstad R, Pillay TM, Hamilton JR, Hasan A,
Parharidis GE, Louridas GE, Dark JH, Kenny A. Dobutamine stress echocardiography
is highly accurate for the prediction of contractile reserve in the early postoperative
period, but may underestimate late recovery in contractile reserve after
revascularization of the hibernating myocardium. J Am Soc Echocardiogr. 2006; 19:
300-306.
31. Åsberg AE, Videm V. Neutrophil dysfunction after biomaterial contact in an in vitro
model of cardiopulmonary bypass. Eur J Cardio-Thoracic Surg 2006; 30: 744-748.
32. Åsberg AE, Videm V. Concentration-dependent effect of abciximab on platelets and
neutrophils in model cardiopulmonary bypass. Perfusion 2006:21:343-352.
2005
1. Berge S D, Berg-Utby C, Skogvoll E. Helicopter transport of sick neonates. A 14year, population-based study. Acta Anaesth Scand 2005; 49: 999-1003.
2. Berg K, Jynge P, Bjerve K, Skarra S, Basu S, Wiseth R. Oxidative stress and
inflammatory response during and following coronary interventions for acute
myocardial infarction. Free Radic Res 2005; 39: 629-36.
3. Gustafsson BI, Tømmerås K, Nordrum I, Loennechen JP, Brunsvik A, Solligård E,
Fossmark R, Bakke I, Syversen U, Waldum H.Long-term serotonin administration
induces heart valve disease in rats. Circulation. 2005 Mar 29;111(12):1517-1522.
4. Hilton CJ, Hamilton JR, Vitale N, Haaverstad R. Effects of 'Bristol' on surgical
practice in the United Kingdom. Interact Cardiovasc Thorac Surg. 2005;4:197-199.
5. Kirkeby-Garstad I, Stenseth R, Sellevold OF. Post-operative myocardial dysfunction
does not affect the physiological response to early mobilization after coronary artery
bypass grafting. Acta Anaesthesiol Scand 2005; 49: 1241-1247.
6. Kirkeby-Garstad I, Sellevold, OFM, Stenseth, R, Skogvoll, E. Mixed venous oxygen
desaturation during early mobilization after coronary artery bypass surgery. Acta
Anaest Scand 2005; 49: 827-834.
7. Kemi OJ, Haram PM, Loennechen JP, Osnes JB, Skomedal T, Wisløff U, Ellingsen Ø.
Moderate vs. high exercise intensity: differential effects on aerobic fitness,
cardiomyocyte contractility, and endothelial function. Cardiovasc Res. 2005; 67:16172.
8. Kjørstad KE, Nordhaug DO, Korvald C, Steensrud T, Myrmel T. Mechanical
restitution curves reflect post-ischemic stunning in pigs. Scand Cardiovasc J. 2005; 39:
107-114.
9. Nordseth T, Skogvoll E, Gisvold SE. Emergency in-hospital anaesthesia assistance.
Tidsskr Nor Laegeforen. 2005; 125: 3124-3126. [Norwegian]
10. Papadopoulos CE, Zaglavara T, Karvounis HI, Haaverstad R, Parharidis GE, Louridas
GE, Kenny A. QT dispersion is determined by the relative extent of normal,
hibernating, and scarred myocardium in patients with chronic ischemic
cardiomyopathy. A dobutamine stress echocardiography study before and after
surgical revascularization. J Electrocardiol. 2006; 39:103-109.
11. Pleym H, Tjomsland O, Åsberg A, Lydersen S, Wahba A, Bjella L, Tromsdal A, Dale
O, Stenseth R. Effects of autotransfusion of mediastinal shed blood on biochemical
markers of myocardial damage in coronary surgery. Acta Anaesthesiol Scand 2005:
49; 1248-1254.
12. Reimers A, Skogvoll E, Sund JK, Spigset O. Drug Interactions between lamotrigine
and psychoactive drugs: Evidence from a therapeutic drug monitoring service. J Clin
Psychopharm 2005; 25:342-348.
13. Rygnestad T, Moen S, Wahba A, Lien S, Ingul CB, Schrader H, Kapstad SE.Severe
poisoning with sotalol and verapamil. Recovery after 4 h with CPR followed by
extracorporeal heart lung assist. Acta Anaesthesiol Scand 2005, 49: 1378-80.
14. Solligård E, Juel IS, Bakkelund K, Jynge P, Tvedt KE, Johnsen H, Aadahl P, Grønbech JE. Gut
luminal microdialysis of glycerol as a marker of intestinal ischemic injury and recovery. Crit Care
Med. 2005; 33: 2278-2785. Erratum in: Crit Care Med. 2007; 35:333.
15. Salvesen RS, Mostad U, Aadahl P. Care for children with tracheostomy. Tidsskr Nor Laegeforen.
2005; 125: 907-909.
16. Sellevold OF. Frontiers in Scandinavian anaesthesiology. Acta Anaesthesiol Scand.
2005; 49: 891-893. (Editorial)
17. Wiseth R, Haaverstad R, Vitale N, Karevold A. Prosthetic valve hemodynamics
assessed by the left ventricular outflow tract area utilization index: A randomized
study of the CarboMedics Reduced versus the Medtronic Hall valve. J Heart Valve
Dis 2005;14:518-22.
18. Wiseth R. Cardiogenic shock. Tidsskr Nor Lægeforen 2005;125:1493.
19. Zaglavara T, Pillay T, Karvounis H, Haaverstad R, Parharidis G, Louridas G, Kenny
A. Heart. Detection of myocardial viability by dobutamine stress echocardiography:
incremental value of diastolic wall thickness measrement. Heart. 2005 May;91(5):6137.
20. Åsberg AE, Videm V. Activation of neutrophil granulocytes in an in vitro model of
cardiopulmonary bypass. Artificial Organs 2005; 29: 927-936.
21. Aasland J, Lundbom J, Eide TO, Ødegård A, Aadahl P, Romundstad P, Myhre HO. Recovery
following treatment of descending thoracic aortic disease. A comparison between endovascular
repair and open surgery. Int Angiol. 2005; 24: 231-237.
Panel 4B
Ultrasound Innovation
in Diagnosis and Therapy
1.2 Evaluation unit (level 2): Ultrasound Innovation in Diagnosis and Therapy
The ultrasound research group was founded by the landmark research of Liv Hatle and
Bjørn Angelsen in the late 1970s, and has remained an interdisciplinary group with close cooperation between technologists and clinical cardiologists. It is a long-time close
collaboration between the cardiologists at the Department of Cardiology at the University
Hospital and the engineers at the Faculty of Medicine (previously in a separate Department of
Biomedical Engineering and after the reorganisation in 2002 part of Department of
Circulation and Medical Imaging). The group has a long and successful history of interdisciplinary research and of collaboration between university, industry and hospital, and is an
excellent arena for translational research with an iterative process between technology
innovation and clinical feasibility studies, and with closeness to the patients’ needs and the
demands of the clinicians.
A recent success is Vscan, the new pocket-sized and hand-held ultrasound scanner
from the MI Lab partner GE Vingmed Ultrasound, and with international release in October
2009. The research behind Vscan was performed as a collaboration between GE Vingmed
Ultrasound and the research group of Professor Hans Torp. Further R&D on clinical
application and further technology improvements will be a new focus area for MI Lab. Vscan
was voted the 14th most important invention worldwide by the readers of Time magazine.
Vscan is pioneer technology and may become a universal tool for medical doctors inside and
outside the hospital, similar to the stethoscope. The first scientific study using Vscan in
general practice has been performed in three GP (general practitioner) offices in the
Trondheim area. Furthermore, in 2010 there was a new spin-off company from the Ultrasound
innovation group, SURF technology AS which will market a new breakthrough technology
(with acronym SURF, Second Order UltRasound Field Imaging) which have significant
benefits compared to present technology for image noise suppression and for improved
sensitivity for ultrasound contrast agents.
Recently, the unit has moved to the third floor of the Emergency and Cardiopulmonary
Medicine Centre in the new fully integrated St. Olavs Hospital, and is now co-located with the
cardiology unit, as well as cardiothoracic and vascular surgery units, which have their wards,
operation theatres and outpatient clinics on the floors above and below. Also co-localized on
the same floor is an R&D unit of GE Vingmed Ultrasound (which has main offices in Horten,
Norway). This opens the potential for even further daily integration between scientific
researchers, clinicians and product developers from university, hospital and industry.
MI Lab (Medical Imaging Laboratory, www.ntnu.no/milab) was established by the
Norwegian Research Council in 2007 as one of three Centres for Research-based Innovation
(SFI) in the area of medicine and health in Norway. This is a new construction where eight
industrial partners, St. Olavs Hospital, SINTEF and NTNU are working together in an open
research and innovation environment. MI Lab has a budget of ~ 240 MNOK (80 MNOK from
the Research Council of Norway) for the 8-years period 2007-2014, and covers research in
ultrasound, MR and image-guided surgery, and by November 2010 MI Lab has 30 PhD
students and postdoctoral fellows allocated to these three areas of research. MI Lab acts as an
instrument for improved integration and collaboration for the entire medical imaging research
environment in Trondheim and is an important part of the MR research group. MI Lab is
organised with its own board that meets 2-3 times a year. The vision of MI Lab is to facilitate
cost efficient health care and improved patient outcome through innovation in medical
imaging, and to exploit the innovations to create industrial enterprise in Norway. MI Lab has
updated its research plan for 2011-2014, and based on advice from its Scientific Advisory
Board it decided to have an increased focus on basic ultrasound technology, integrating
1
research on hardware, software and transducer arrays. In the coming years breakthroughs in
ultrasound technology will cause major improvements of ultrasound image quality, and MI
Lab wants to be one of the world leaders in this research area. Research on the next
generation ultrasound technology will have long-term benefit for all the MI Lab ultrasound
industrial partners as well as the university and hospital research groups involved in clinical
applications of ultrasound. The MI Lab research on hardware, software and transducer arrays
will be tailored to the specific challenges and goals for each industrial partner and research
group. This activity will include research on transducer arrays, ultrasound probe electronics,
software beam-forming, parallel imaging & compressed sensing, minimum diffractive wave
imaging, model powered acquisition and new technology for flow imaging / quantification,
and will also include a transducer workshop. This research will be performed in the
Ultrasound innovation group, and MI Lab funded 7 new PhD students in 2010.
Organisation
The research activities are organized in 4 project groups, one dealing with long term
ultrasound technology research, and 3 interdisciplinary groups, working with technology
development for blood flow imaging, pocket size ultrasound, and cardiac ultrasound. Each
project group is led by two senior researchers, one clinician and one technologist, and there
are regular follow-up meetings for all group members, including clinical staff and
collaborating staff in industry. Important decisions are made by the leader of each group,
after discussions among the group members. Recently, some of the postdoctoral researchers
in the unit have been appointed as main supervisor for PhD-students, which means that some
decisions are also made at the intermediate level. However, advice from senior staff is always
appreciated.
Staff
The unit has a strong technology profile with 3 senior, 8 post-docs and 16 PhD
students with background in electrical engineering, physics, and computer science, and 2
senior, 3 post-docs, and 9 PhD students with background in cardiology. The number of
women researchers is low, but growing: 1 post-doc and 7 PhD students. International staff: 2
post-docs, 6 PhD-students.
Publication strategy
The unit has concentrated on a few, specialized scientific journals in the field of
ultrasound technology and echocardiography for publications. The most frequently used
journal “IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control” which is
the leading international journal for ultrasound technology innovations. In clinical feasibility
studies, with joint effort of engineers and clinicians, journals that accept a substantial part of
technology content are preferred. Examples include “Ultrasound in medicine”, Journal of the
American Society of Echocardiography, The European Journal of Echocardiography and
Echocardiography. However, the unit has also a few (less than 10%) publications in high
impact journals ( JASA, Circulation, J Am Coll Cardiol).
All members of the group are encouraged to present their work in international
scientific meetings; minimum 1 per year. The IEEE Ultrasonic symposium is the most
important annual meeting for the technologists; but of equal importance for the unit are
clinical meetings with a “technology-profile”, like EUROECHO, which is an excellent
meeting place for engineers and clinicians.
The unit has a good track record in popular science. This includes several public
demonstrations of ultrasound technology per year, for students and general public, and
participation in TV programs, and newspaper. In 2009 there was much media coverage of
2
Vscan, the new pocket-sized ultrasound scanner from the industry partner GE Vingmed
Ultrasound. The main daily news program (Dagsrevyen), in the Norwegian State
Broadcasting (NRK) featured a news story including a patient investigation in the MI Lab
research project on Vscan in a general practitioner office in Trondheim. Vscan was also
presented in Time magazine, and ranked by their readers as 14th most important invention
world-wide in 2009.
Resources and scientific production
The 4 senior researchers in the group are funded 100% by NTNU, 3 of them have
permanent positions; the other 36 staff members are funded by external sources. Through the
collaboration with GE-Vingmed Ultrasound, the unit has participated in several industrial
research programs, giving funding of PhD-students, as well as free access and technical
support of ultrasound equipment. Other important sources for external funding include the
Central Norway Regional Health Authority and the Research Council of Norway. The most
important contribution to the growth of the unit since 2007 is MI Lab, which is a Researchbased Center of Innovation at NTNU. Through MI Lab, the unit has acquired 4 of its best
PhD-candidates, and two candidates from international universities for post-doc positions.
This made it possible to increase the number of PhD-students significantly. By the end of
2010 the unit will have 13 PhD-students funded by MI Lab. MI Lab has also given
substantial access to engineering resources, as well as equipment through MI Lab’s industrial
partners.
Research infrastructure
The unit’s laboratory facilities includes water tank setup for ultrasound field
measurements, research scanners and probes for in vitro and in vivo testing, ultrasound
examination laboratory for clinical studies, and workshop for prototype transducer
production.
Through the MI Lab program, the unit has access to 4 ultrasound scanners including probes
from GE-Vingmed Ultrasound. These are used for development of new imaging modalities, in
vitro testing, and small clinical feasibility studies. The agreement with GE-Vingmed
Ultrasound also includes free, continuous support and software / hardware upgrade to state-ofthe-art. One research scanner (Ultrasonix) has been rebuilt for dual frequency operation, and
is used in development of SURF imaging
The unit has recently acquired a 40 MHz high resolution ultrasound scanner for animal
studies of tumor imaging with the new methods and ultrasound mediated drug delivery.
Professor Catharina de Lange Davies, Dept. of Physics, NTNU, has a well developed optical
imaging laboratory for studies of targeted contrast agents and drug delivery in vitro and in
small animals which will be used for comparisons with high resolution ultrasound imaging.
The unit has the 2 fully equipped examination labs, including exercise ultrasound and
3D ultrasound scanners for clinical research. Both scanners will require replacement as the
scanners are worn down as well as replacement with newer models. An agreement with GEVingmed Ultrasound also includes free access to commercial analysis software, as well as
experimental software that is tested in the programming environment. MR imaging facilities
at St. Olavs Hospital are frequently used for reference measurements.
The ultrasound technology laboratory is organized for flexible experiments for
ultrasound technology development and ultrasound acoustic wave propagation. The
instrumentation includes a water tank with hydrophone measurements controlled by a high
precision 3D robot, for basic research on wave propagation and for acoustic material
characterization. It is also used for measurements of acoustic output for patient safety
evaluation.
3
The target of the transducer workshop, which has recently been established, is to test
limited realizations of novel transducer ideas. The workshop is equipped with the
fundamental tools to make piezoelectric transducer stacks, including dicing saw, lapping
machine, equipment for cleaning materials, and curing polymer glues. For characterization
and test: Electrical impedance analyzer, and linear wideband power amplifier for transducer
excitation. The group has collaboration with the transducer company Parallel Design in Nice,
France, to establish procedures for production of transducers.
The research is organized in 4 project groups, one dealing with long term ultrasound
technology research, and 3 interdisciplinary groups, working with technology development
for beam-forming and blood flow imaging and its clinical applications, pocket size
ultrasound, and cardiac ultrasound. Some of the research activities of the 4 project groups are
detailed below.
1. Ultrasound basic research
Head: B. Angelsen, T. Johansen
3 post-docs (S. Måsøy, R. Hansen, M. Voormolen), 8 PhD students, 2 engineers, 3 master
students
The group has a tight focus on fundamental aspects of ultrasound wave propagation
and scattering in tissue to develop fundamental knowledge for improved image quality and
new clinical applications, including ultrasound mediated drug delivery.
The new methods require new transducer technology which is also a focus of the
group. The new imaging methods compensates for multiple scattering noise and wave front
aberrations due to spatial variations in wave propagation velocity, which improves spatial
resolution with reduced noise for better differentiation of tissue properties. Particularly
promising are imaging methods that use dual band pulse complexes with a ratio of 1:10 for
the center frequencies of the two bands. Special designs for dual frequency ultrasound
transducer arrays have been carried through.
SURF Imaging denotes Second Order UltRasound Field Imaging, and is a new method
for ultrasound imaging recently developed by the group. In SURF Imaging, two pulses are
transmitted simultaneously; a standard imaging pulse, and manipulation pulse. Typically, the
frequency difference between the two pulses is a factor 7-10, e.g. an imaging pulse of 10 MHz
and a manipulation pulse of 1 MHz. The low-frequency manipulation pulse affects both the
propagation and scattering properties of the high-frequency imaging pulse due to the fact that
both these properties become dependent of the manipulation pulse pressure. This opens up a
range of new possibilities for ultrasound imaging. The new imaging method compensates for
multiple scattering noise and wave front aberrations due to spatial variations in wave
propagation velocity, which improves spatial resolution with reduced noise for better
differentiation of tissue properties. The group founded a new company, SURF Technology
AS, in March 2010 in order to industrialize new dual frequency imaging technology and drug
delivery methods developed by the group. A prototype ultrasound linear array has been built,
which shows improved performance over the experimental testing probes. The algorithms
have been further improved with substantially enhanced detection of tumors, and also
atherosclerotic plaque in the carotid artery. The company has been granted one patent for the
ultrasound transducer arrays, and one patent for the methodology and instrumentation. In
addition, 3 patent applications have been filed and are under examination. The dual frequency
imaging technology bears promise of improved image contrast for tumor tissue and
atherosclerotic tissue relative to normal tissue, both in the fundamental tissue image, in
4
visualization of neo-angiogenesis with contrast agents, and in visualization of microcalcifications. Ultrasound molecular imaging in tissue using molecularly targeted microbubbles is under development.
The dual frequency ultrasound technique is also useful for ultrasound mediated drug
delivery, using liposomal encapsulated drugs (diam. ~ 100nm). A fairly high ultrasound
frequency (1.5 – 10 MHz) is used for heating tissue to improve blood flow for increased
delivery of nano-particles to the tumor tissue, and also to produce increased pO2 in the tumor
that increases sensitivity to radiation and chemo-therapy. Switching to a lower frequency with
increased mechanical index is used to break the nano-particles for focused release of the drugs
in the tumor with reduced toxicity for the rest of the body. The effect of the ultrasound on the
tissue is monitored with MR imaging. The MR group at the department of Circulation and
Medical Imaging is well equipped to support with MR guidance for ultrasound mediated drug
delivery in small animals. Computer simulation programs are developed based on the
mathematical models for detailed studies of wave propagation and scattering, ultrasound
transducer designs, and signal processing algorithms. The methods and simulation programs
are also tested for identification of porous rock in collaboration with the Department of
Petroleum Engineering, NTNU.
Transducer design and production: Ultrasound probe design can be divided in two: design of
the probe’s aperture (array shape) and design of the probe’s transducer. Annular arrays have
been a research activity, while linear type arrays have been designed for special application
probes. Testing new probe designs has been a lengthy process, as the arrays have been
produced by commercial companies. Therefore, the group has developed a simulation tool,
xTrans, to study 1D models of transducers based on piezoelectric plates. Through design work
on probes, several transducer ideas have been developed, and a transducer workshop has been
established. In the workshop, transducer designs of simple stacks and arrays with a limited
number of elements will be tested. The first research objective is to make dual layer
transducers for multi frequency transducers.
1 D modelling of transducer vibration is efficient for the first cycle of the design
process, but a more realistic simulation must be carried out for the array. The Finite Element
Method (FEM) is commonly used for such simulations. The multipurpose FEM program
COMSOL has been chosen for this purpose, which in several projects has proved to be a
flexible and accurate tool.
2. Beam-forming and blood flow imaging
Head: H. Torp (Technology), B. Haugen (Clinical)
Post doc: L. Løvstakken, T. Hergum, T. Bjåstad,
PhD students (8 technology, 2 clinical)
Adjunct Professor: K.Kristoffersen (GE Vingmed Ultrasound), S. Holm (UiO),
Associate Professor: S. Samstad (cardiologist, PhD)
Beam-forming and Doppler imaging can be described as image formation at the most
basic data level in the ultrasound system. Beam-forming is the art of combining returned
ultrasound echoes from the hundreds or thousands of receiver elements in order to focus the
energy to provide spatial resolution and tissue contrast. Doppler imaging deals with detecting
and estimating the movement of blood and tissue, which are important information in
cardiovascular disease. Improving these techniques may lead to an overall improvement of all
further image processing and analysis, which in the end may provide a more certain diagnosis
during patient examinations. There is a long tradition and high competence for investigating
these topics at the Department of Circulation and Medical Imaging, indeed the very beginning
5
of ultrasound research at the department was based on the technical and clinical development
of Doppler ultrasound techniques in the mid 1970s.
Current research activities are focused on real time 3D ultrasound imaging and plane
wave imaging, both of which are recent trends in ultrasound technology. These techniques are
explored both for fundamental beam-forming problems, and for specialized Doppler
applications. Real time 3D ultrasound poses several challenges with regard to maintaining the
image quality and frame rate after moving from 2D to 3D acquisition. Recently, several
approaches to solve this challenge have been published by the group, and one patent
application has been filed. 3D ultrasound has also enabled solutions to the long-standing
problem of quantification of leaking heart valves. One patent application for this proposal has
been submitted, and two more are under preparation, and the first proof-of-concept clinical
trial with 27 patients has been conducted.
Future research challenges include adaptive beam-forming strategies to account for
phase aberrations, and provide resolutions beyond the diffraction limit. In vivo experiments
require recording of raw channel data from matrix array transducers, and this will become
available within the next year.
The other main focus, plane wave imaging, enables several novel Doppler methods. In
particular it enables high frame rate color flow imaging and increased frame rate with Doppler
spectral estimates. High frame rate color flow is very useful for imaging neonatal hearts, as
their heart rate is two-three times that of an adult. This method is currently tested in a clinical
trial at St. Olavs Hospital and Oslo University Hospital.
A new real time ultrasound flow imaging modality called blood flow imaging (BFI) is
able to visualize blood flow in any direction of the image and is not limited by velocity
aliasing. The method is developed at the department, and is currently being tested in a small
clinical trial to investigate its usefulness in diagnosing openings between the left and right
atrium (atrial septum defect = ASD). This project is a co-operation with Oslo University
Hospital. Trans-thoracic echocardiography is essential to select patients for trans-catheter
device closure of ASD, and trans-esophageal echocardiography is important to guide the
device deployment procedure. In this study the plan is to compare BFI with the established
reference BSD (balloon stretched diameter) to measure ASD size. In addition, comparison of
BFI and X-ray angiography are under development, which is regarded as the ”gold standard”
in the visualization of the pulmonary veins.
Technical research is partly performed in collaboration with industry partners such as
GE Vingmed Ultrasound and Medistim ASA. In the last 5 years the group has been granted 1
patent, and 4 patent applications are under processing.
3. Pocket size ultrasound
Head: H. Torp (Technology), B. Haugen (Clinical)
PhD students: (1 technology, 2 clinical)
Industry contact: S. Frigstad, GE-Vingmed Ultrasound
This activity started in 2006 when GE Vingmed Ultrasound realized that some of the
new technology and inventions for 3D ultrasound obtained through the research collaboration
between GE Vingmed Ultrasound and the Ultrasound research group in Trondheim could be
used to make a pocket-size hand-held ultrasound scanner with high image quality and userfriendliness. The R&D on the final product was performed through an industry research
collaboration project (BIA) with GE-Vingmed Ultrasound financed from the Research
Council of Norway. The task of the NTNU group was to perform research on probe
technology and automatic image analysis, including the crucial new invention of an algorithm
that enables recording of the heartbeats without an ECG signal. Until now cardiac ultrasound
6
had required ECG recording, and it would be a significant problem for user-friendliness to
have to carry around ECG leads and perform ECG recordings in the context of a hand held
ultrasound scanner. The new scanner, Vscan, had its international release in October 2009,
and the GE global CEO Jeff Immelt decided to do the release himself in person. The readers
of Time magazine ranked Vscan as the 14th most important invention worldwide in 2009.
Most ultrasound scanners are located in hospitals and operated by a limited number of trained
personnel. The development of pocket-size user-friendly ultrasound scanners might extend the
use of ultrasound to general practitioners and paramedics. Clinical research on Vscan is now a
focus area for MI Lab, and the group consists of engineers and clinicians (4 clinical PhD
students and post doc fellows) that work in close collaboration with industry. The main aims
are to evaluate new applications of pocket-size ultrasound for improved hospital workflow; to
validate the use of pocket-size ultrasound among non-expert and expert users in a variety of
clinical settings in the hospital, in general practice, and in emergency medicine; and to train
medical students in the use of pocket-size ultrasound. An important part of the project is
further technology refinements directed at improving user-friendliness through software
programs for automatic quality assessment and quantitative analysis. Miniaturization of
ultrasound equipment is a recent international trend with an increasing number of scientific
publications.
The first scientific study using Vscan in general practice has been performed in three
general practitioner offices in the Trondheim area. An ongoing trial at the Hospital in
Levanger, validates if the use by non-expert and expert users will change diagnosis and
treatment among patients admitted to a medical department. Finally, an ongoing study at St.
Olavs Hospital validates whether the use of pocket-size ultrasound during resuscitation in
hospitals will help identifying reversible causes. The algorithm that enables recording of a
heartbeat without an ECG signal was developed by one of the former technical PhD students
in the group. This algorithm is implemented in the Vscan and the inventor is now an
employee in GE Vingmed Ultrasound. The medical PhD students will be future consultant
cardiologists working in hospitals, some with affiliation with NTNU. A major strength of the
group is the high level of integration of engineering and clinical research that has become an
important part of NTNU culture for medical technology innovation.
4. Cardiac ultrasound
Head: H. Torp (technology), A. Støylen (Clinical)
Post.doc (technology): S. Aase, G. Kiss
Post.doc (clinical): B. Amundsen , C. Ingul
Phd-students (2 tehnology, 4 clinical)
Guest researcher: J. D’Hooge, Leuven, Belgium.
Industry contact: O. Gerald, F. Orderud, GE Vingmed Ultrasound
The cardiac ultrasound group is a multidisciplinary group of technologists and
clinicians, working on improving data acquisition, analysis and display, within the fields of
tissue Doppler, flow imaging, 3D ultrasound and integration with magnetic resonance
imaging. The aim is to improve ultrasound methods applied in coronary artery disease, heart
failure and valve pathology. The work consists of technical development, evaluation of
feasibility in healthy subjects and patients, validation, and clinical testing in diagnostics. The
close proximity of technical and clinical competence means that clinicians are involved in all
steps of the process, with next-door proximity to the technical expertise in the early stages of
testing. This is a major strength of the group. The close integration with the university
hospital ensures access to the patient base for clinical studies. New developments have been
taken into larger population studies as well as into the field of exercise physiology and cardiac
7
rehabilitation, in cooperation with the unit for exercise physiology.
The unit works closely with GE Vingmed Ultrasound in development of new methods,
under the regulations of MI Lab, where GE Vingmed Ultrasound is a partner. During the last
5 years 3 patents has been granted, and 3 more patent applications are under processing.
The research focus is on new ultrasound methods for evaluation of myocardial
function. Myocardial strain imaging was invented by this group some years ago, and it
presently focuses on 3D strain imaging to obtain the full description of myocardial
deformation in the left ventricle. This includes both in silico and in vivo validation studies.
The group also works on more accurate and automated measurements of left ventricular
volumes and ejection fraction by 3D echocardiography. With a new MI Lab invention in 2010
(filed as patent under the name of “Ultrasound imaging using curved beams“), it is possible to
obtain a frame rate of at least 500 images per second in 3D imaging of the left ventricle, and
this opens entirely new possibilities for a more thorough description of cardiac function. The
method will be used to study myocardial mechanics, especially the iso-volumic phases and
diastolic function, where high temporal resolution is vital. The method may also improve the
assessment of myocardial tissue properties, and hopefully detect changes in myocardial
stiffness due to fibrosis, which is a common pathological pathway along with hypertrophy and
remodelling in heart failure. There are no good non-invasive diagnostic tools for assessment
of myocardial stiffness and fibrosis today. The goal is to quantify active deformation and
passive tissue properties, and use this to better understand changes in myocardial function and
the cause of symptoms in common cardiac diseases like aortic stenosis, hypertensive
myocardial hypertrophy, diabetic cardiomyopathy and heart failure. Establishing cardiac
magnetic resonance imaging as a reference method for myocardial deformation, volumes,
viability and flow has increased the impact of our results.
After finishing their PhD theses, technology students typically proceed into further
research at the university, industry or college positions. Medical PhD students usually go into
the clinical specialty of cardiology, often in combined positions at hospital and university.
Currently the unit’s activities would benefit from even better recruitment of well trained
physicians as PhD-students.
Strenghts
The main strengths of the ultrasound innovation unit are:
• A long and successful history of interdisciplinary research
• A long and successful history of collaboration between university, industry and
hospital and between technologists and medical doctors/physicians
• Excellent arena for translational research with an iterative process between technology
innovation and clinical feasibility studies
•
Sufficient size of research groups to cover competence and experience in a wide range
of ultrasound technology.
Publications
The researchers in the project groups on Beam-forming and Doppler and Cardiac
ultrasound have a high number of publications in the last five years. These are well
established research areas in the unit, where long term scientific effort and technology
development has prepared the ground for documented research activity.
The project group on Ultrasound Basic Research has to a high extent focused on
development and industrial foundation based on a completely novel ultrasound imaging
technique that has recently shown encouraging results. This effort includes patent
applications that delay scientific publications.
Scientific publication for the project group on Pocket size Ultrasound has just begun.
8
During the first 2-3 years, a considerable effort was spent on developing an “electronic
stethoscope” with limited success. This activity has now been terminated, and emphasis is
put on automatic image analysis and ongoing clinical trials, with promising results.
Recruiting the best students to PhD and post doc positions is one of the most important
success factors for scientific output and quality. However, both technology and medicine are
areas where there is stiff competition with industry and health care, respectively, for the best
PhD candidates. For the technology PhD calls, MI Lab had several very high quality
applicants in 2009 and 2010. The recruitment of clinicians, including consultant cardiologists
has been increasing. The option of combining a clinical fellowship in cardiology with a PhD
research project within a maximum 6 years has been a success. Medical PhD students will
usually go into the clinical specialty of cardiology as consultants, often with combined
positions at hospital and university.
To stimulate interest in medical imaging research and to improve the quality of the
PhD training MI Lab leader Olav Haraldseth initiated and is the current leader of the
Norwegian Research School in Medical Imaging (see: www.ntnu.no/medicalimaging). The
Research Council of Norway had an open call for post graduate researcher training
programmes [“forskerskoler”] in 2008, and the Norwegian Research School in Medical
Imaging was one of the five appointed (the only in the area of medicine and health and the
only at NTNU). This effort is in collaboration with the universities in Oslo, Bergen and
Tromsø, and the total budget is 24 million NOK over 8 years. The researcher school is for all
Norwegian PhD students in the area of medical imaging (including MR, ultrasound, PET,
image guided surgery, optical imaging and bionanotechnology), and the main aim is to
improve the quality of medical imaging research in Norway. This will be achieved through
improving national collaboration, multi-disciplinary research, quality of PhD training, and
recruitment of the best students (also international recruitment). The research school will also
be used as a tool to establish organized collaboration with international universities in the area
of PhD training and exchange.
Recruitment of women is also a challenge as the number of female students with
relevant background is limited. However, in 2009 and 2010, the unit has been able to recruit 3
top quality female PhD students. An interesting new opportunity is to use the Norwegian
Research School in Medical Imaging (described above) as a tool to improve female
recruitment to MI Lab. There are good reasons to believe that this type of organized
researcher schools have special appeal to women master students who are in doubt of whether
to start on a PhD or not.
At NTNU the Faculty of Medicine hosts a PhD programme in Medical Technology
headed by Professor Hans Torp, who is also one of the key professors in the ultrasound
research group.
The Ultrasound research group and MI Lab are excellent arenas for collaboration
between academia and industry, and many PhD students in the MR research group work with
industry related PhD projects. The collaboration with GE Vingmed Ultrasound AS is very
close, and most of the key personnel in the company has had PhD and/or post doc periods in
the Ultrasound research group environment. There are also three small and medium sized
ultrasound companies in MI Lab (Medistim ASA, Sonowand AS and Aurotech Ultrasound
AS), and several PhD and postdoctoral projects in the ultrasound research group are either
short-term research on improving their current products or long-term research directed
towards next generation technology and/or new markets for these companies.
Until recently, the primary target for PhD students was Norwegian master candidates.
However, all calls are international, and during the 2005-2009 years the unit has also recruited
9
some top level international PhD students. For post-docs, there is a stronger focus on
recruiting international students from the best universities, in addition to PhD-candidates with
long term experience from the unit.
PhD-students have a high level of responsibility for the day-to-day activities according
to a detailed plan made by the student and his supervisor. The post doc’s are encouraged to
take responsibility as main supervisors for PhD-students. This is in accordance with the
Faculty of Medicine, which encourage some post-docs to be main supervisor, provided that a
senior researcher act as co-supervisor. PhD-students are also encouraged to supervise master
students related to their project. Master students in technology are recruited through an
international master program in medical technology, and by giving master courses in medical
imaging at the technology faculties at NTNU.
interdisiplinarity
The unit has extensive local, national and international networks. The research
collaborations are based on the needs of interdisciplinary projects and usually end up in copublication. Typically the collaboration partner add competence or access to patients, animal
models or infrastructure. The unit’s organisation in multidisciplinary research groups
facilitates co-publication; 30 out of the 81 scientific publications listed are joint work between
technologists and clinicians within the unit.
A long term collaboration with GE Vingmed Ultrasound has given access to cutting
edge ultrasound technology for adaption to new clinical applications. The company has a
R&D group co-located with the unit, with engineers taking actively part in the unit’s research
projects. The chief engineer for ultrasound in GE, K. Kristoffersen holds an adjunct professor
position at NTNU, and is currently main supervisor for one PhD student in the unit. Through
MI Lab, the unit also has common projects with several smaller companies, including
MediStim, Sonowand, Aurotech Ultrasound, and SURF Technology.
Collaboration with the University of Bergen has given access to their cardiovascular
circulation model, which has been successfully utilized to test a new method for
quantification of valve regurgitation. Collaboration with Professor T. Marwick, Brisbane,
Australia / Cleveland, USA, has resulted in a large evaluation study on strain rate imaging,
and ongoing clinical evaluation of 3D Doppler method for assessment of mitral valve
regurgitation. Collaboration with Professor P. Segers, Ghent on biomechanics of blood
vessels has resulted in a joint PhD (cotutelle) at Ghent University, Belgium and NTNU.
Professor Stuart Foster, University of Toronto, is helping to build up targeted drug delivery in
small animals.
With support from MI Lab, the unit has attached 3 international professors and
researchers in 20% positions as guest professors and guest researchers:
• Jan D’hooge, University of Leuven, Belgium, strengthened activity in 3D myocardial
strain, as well as computer simulations of ultrasound field.
• Jean-Francois Gelly, Parallel Design SA, France is helping to build up the transducer
design/production activity. Professor Sverre Holm, University of Oslo. Supervision
of Phd-students in the unit within adaptive beam-forming
• Professor Stuart Foster, Medical Imaging Research Center, Sunnybrook Hospital,
Univ of Toronto, who is helping to build up a targeted drug delivery.
For clinical studies the group has strong collaboration with St. Olavs Hospital, Trondheim:
Professor Torbjørn Dahl for carotid atherosclerosis, Professor Anders Angelsen for prostate
cancer, Professor Sturla Eik-Nes for fetal and gynecology imaging, and Haukeland Hospital,
Bergen: Professors Odd Helge Gilja and Svein Ødegård in Gastroenterology.
10
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2008:
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echocardiography in patients with myocardial infarction shows lack of diastolic,
but not systolic, reserve: a tissue Doppler study. Eur J Echocardiogr. 2009
Jun;10(4):503-8. Epub 2008 Dec 6. PubMed PMID: 19060314.
36: Crosby J, Amundsen BH, Hergum T, Remme EW, Langeland S, Torp H. 3-D speckle
tracking for assessment of regional left ventricular function. Ultrasound Med
Biol. 2009 Mar;35(3):458-71. Epub 2008 Dec 4. PubMed PMID: 19056164.
37: Søfteland Sandvei M, Amundsen BH, Olav Haugen B, Støylen A, Slørdahl SA, Vik
A. Left ventricular function during the acute phase of a subarachnoid
page 5
haemorrhage. Scand Cardiovasc J. 2008 Nov 22:1-7. [Epub ahead of print] PubMed
PMID: 19031170.
38: Oddershede N, Løvstakken L, Torp H, Jensen JA. Estimating 2-D vector
velocities using multidimensional spectrum analysis. IEEE Trans Ultrason
Ferroelectr Freq Control. 2008 Aug;55(8):1744-54. PubMed PMID: 18986918.
39: Nestaas E, Støylen A, Fugelseth D. Optimal types of probe, and tissue Doppler
frame rates, for use during tissue Doppler recording and off-line analysis of
strain and strain rate in neonates at term. Cardiol Young. 2008 Oct;18(5):502-11.
Epub 2008 Aug 28. PubMed PMID: 18752713.
40: Amundsen BH, Crosby J, Steen PA, Torp H, Slørdahl SA, Støylen A. Regional
myocardial long-axis strain and strain rate measured by different tissue Doppler
and speckle tracking echocardiography methods: a comparison with tagged magnetic
resonance imaging. Eur J Echocardiogr. 2009 Mar;10(2):229-37. Epub 2008 Jul 23.
41: Karlsen T, Hoff J, Støylen A, Skovholdt MC, Gulbrandsen Aarhus K, Helgerud J.
Aerobic interval training improves VO2 peak in coronary artery disease patients;
no additional effect from hyperoxia. Scand Cardiovasc J. 2008 Oct;42(5):303-9.
42: Crosby J, Amundsen BH, Helle-Valle T, Steen PA, Torp H. A new tissue Doppler
method for examination of left ventricular rotation. Ultrasound Med Biol. 2008
Nov;34(11):1741-51. Epub 2008 Jun 10. PubMed PMID: 18547711.
43: Masoy SE, Standal O, Nasholm P, Johansen TF, Angelsen B. SURF imaging: in
vivo demonstration of an ultrasound contrast agent detection technique. IEEE
Trans Ultrason Ferroelectr Freq Control. 2008 May;55(5):1112-21. PubMed PMID:
18519219.
44: Aase SA, Torp H, Støylen A. Aortic valve closure: relation to tissue
velocities by Doppler and speckle tracking in normal subjects. Eur J
Echocardiogr. 2008 Jul;9(4):555-9. Epub 2008 Mar 20. PubMed PMID: 18490310.
45: Amundsen BH, Rognmo Ø, Hatlen-Rebhan G, Slørdahl SA. High-intensity aerobic
exercise improves diastolic function in coronary artery disease. Scand Cardiovasc
J. 2008 Apr;42(2):110-7. PubMed PMID: 18365893.
46: Ibrahim K, Vitale N, Kirkeby-Garstad I, Samstad S, Haaverstad R. Narrowing
page 6
effect of off-pump CABG on the LIMA-LAD anastomosis: epicardial ultrasound
assessment. Scand Cardiovasc J. 2008 Apr;42(2):105-9. PubMed PMID: 18365892.
47: Lovstakken L, Ibrahim KS, Vitale N, Henriksen ST, Kirkeby-Garstad I, Torp H,
Haaverstad R. Blood flow imaging: a new two-dimensional ultrasound modality for
enhanced intraoperative visualization of blood flow patterns in coronary
anastomoses. J Am Soc Echocardiogr. 2008 Aug;21(8):969-75. Epub 2008 Mar 20.
48: Chérin E, Brown J, Måsøy SE, Shariff H, Karshafian R, Williams R, Burns PN,
Foster FS. Radial modulation imaging of microbubble contrast agents at high
frequency. Ultrasound Med Biol. 2008 Jun;34(6):949-62. Epub 2008 Feb 21. PubMed
PMID: 18294758.
2007:
49: Høydal KL, Helgerud J, Karlsen T, Støylen A, Steinshamn S, Hoff J. Patients
with coronary artery- or chronic obstructive pulmonary disease walk with
mechanical inefficiency. Scand Cardiovasc J. 2007 Dec;41(6):405-10. PubMed PMID:
17963154.
50: Vasseljen O, Fladmark AM, Westad C, Torp HG. Onset in abdominal muscles
recorded simultaneously by ultrasound imaging and intramuscular electromyography.
J Electromyogr Kinesiol. 2009 Apr;19(2):e23-31. Epub 2007 Sep 25. PubMed PMID:
17897842.
51: Nyrnes SA, Løvstakken L, Torp H, Haugen BO. Blood flow imaging-a new
angle-independent ultrasound modality for the visualization of flow in atrial
septal defects in children. Echocardiography. 2007 Oct;24(9):975-81. PubMed PMID:
17894577.
52: Skjold A, Amundsen BH, Wiseth R, Støylen A, Haraldseth O, Larsson HB, Jynge
P. Manganese dipyridoxyl-diphosphate (MnDPDP) as a viability marker in patients
with myocardial infarction. J Magn Reson Imaging. 2007 Sep;26(3):720-7. PubMed
PMID: 17729351.
53: Wisløff U, Støylen A, Loennechen JP, Bruvold M, Rognmo Ø, Haram PM, Tjønna
AE, Helgerud J, Slørdahl SA, Lee SJ, Videm V, Bye A, Smith GL, Najjar SM,
Ellingsen Ø, Skjaerpe T. Superior cardiovascular effect of aerobic interval
training versus moderate continuous training in heart failure patients: a
randomized study. Circulation. 2007 Jun 19;115(24):3086-94. Epub 2007 Jun 4.
page 7
54: Solberg OV, Lindseth F, Torp H, Blake RE, Nagelhus Hernes TA. Freehand 3D
ultrasound reconstruction algorithms--a review. Ultrasound Med Biol. 2007
Jul;33(7):991-1009. Epub 2007 May 18. Review. PubMed PMID: 17512655.
55: Soma J, Eriksen M, Amundsen BH. [A 50-year old woman with cor triatriatum].
Tidsskr Nor Laegeforen. 2007 Apr 19;127(8):1056-7. Norwegian. PubMed PMID:
17469211.
56: Brekke S, Rabben SI, Støylen A, Haugen A, Haugen GU, Steen EN, Torp H. Volume
stitching in three-dimensional echocardiography: distortion analysis and
extension to real time. Ultrasound Med Biol. 2007 May;33(5):782-96. Epub 2007 Apr
16. PubMed PMID: 17434669.
57: Ingul CB, Stoylen A, Slordahl SA, Wiseth R, Burgess M, Marwick TH. Automated
analysis of myocardial deformation at dobutamine stress echocardiography: an
angiographic validation. J Am Coll Cardiol. 2007 Apr 17;49(15):1651-9. Epub 2007
58: Ibrahim KS, Løvstakken L, Kirkeby-Garstad I, Torp H, Vik-Mo H, Haaverstad R.
Effect of the cardiac cycle on the coronary anastomosis assessed by ultrasound.
Asian Cardiovasc Thorac Ann. 2007 Apr;15(2):86-90. PubMed PMID: 17387187.
59: Løvstakken L, Bjaerum S, Torp H. Optimal velocity estimation in ultrasound
color flow imaging in presence of clutter. IEEE Trans Ultrason Ferroelectr Freq
Control. 2007 Mar;54(3):539-49. PubMed PMID: 17375823.
60: Varslot T, Måsøy SE, Johansen TF, Angelsen B. Aberration in nonlinear
acoustic wave propagation. IEEE Trans Ultrason Ferroelectr Freq Control. 2007
Mar;54(3):470-9. PubMed PMID: 17375817.
61: Hergum T, Bjåstad T, Kristoffersen K, Torp H. Parallel beamforming using
synthetic transmit beams. IEEE Trans Ultrason Ferroelectr Freq Control. 2007
Feb;54(2):271-80. PubMed PMID: 17328324.
62: Bjork Ingul C, Rozis E, Slordahl SA, Marwick TH. Incremental value of strain
rate imaging to wall motion analysis for prediction of outcome in patients
undergoing dobutamine stress echocardiography. Circulation. 2007 Mar
13;115(10):1252-9. Epub 2007 Feb 26. PubMed PMID: 17325245.
63: Amundsen BH, Wisløff U, Slørdahl SA. [Exercise training in cardiovascular
diseases]. Tidsskr Nor Laegeforen. 2007 Feb 15;127(4):446-8. Review. Norwegian.
page 8
64: Bjåstad T, Aase SA, Torp H. The impact of aberration on high frame rate
cardiac B-mode imaging. IEEE Trans Ultrason Ferroelectr Freq Control. 2007
Jan;54(1):32-41. PubMed PMID: 17225798.
65: Nestaas E, Stoylen A, Sandvik L, Brunvand L, Fugelseth D. Feasibility and
reliability of strain and strain rate measurement in neonates by optimizing the
analysis parameters settings. Ultrasound Med Biol. 2007 Feb;33(2):270-8. PubMed
PMID: 17207903.
2006:
66: Løvstakken L, Bjaerum S, Kristoffersen K, Haaverstad R, Torp H. Real-time
adaptive clutter rejection filtering in color flow imaging using power method
iterations. IEEE Trans Ultrason Ferroelectr Freq Control. 2006
Sep;53(9):1597-608. PubMed PMID: 16964910.
67: Vasseljen O, Dahl HH, Mork PJ, Torp HG. Muscle activity onset in the lumbar
multifidus muscle recorded simultaneously by ultrasound imaging and intramuscular
electromyography. Clin Biomech (Bristol, Avon). 2006 Nov;21(9):905-13. Epub 2006
Jul 5. PubMed PMID: 16822599.
68: Brekke S, Ingul CB, Aase SA, Torp HG. Increasing frame rate in ultrasound
imaging by temporal morphing using tissue Doppler. IEEE Trans Ultrason
Ferroelectr Freq Control. 2006 May;53(5):936-46. PubMed PMID: 16764448.
69: Blaas HG, Taipale P, Torp H, Eik-Nes SH. Three-dimensional ultrasound volume
calculations of human embryos and young fetuses: a study on the volumetry of
compound structures and its reproducibility. Ultrasound Obstet Gynecol. 2006
Jun;27(6):640-6. PubMed PMID: 16710882.
70: Malm S, Frigstad S, Torp H, Wiseth R, Skjarpe T. Quantitative adenosine
real-time myocardial contrast echocardiography for detection of angiographically
significant coronary artery disease. J Am Soc Echocardiogr. 2006
Apr;19(4):365-72. PubMed PMID: 16581474.
71: Løvstakken L, Bjaerum S, Martens D, Torp H. Blood flow imaging--A new
real-time, 2-D flow imaging technique. IEEE Trans Ultrason Ferroelectr Freq
Control. 2006 Feb;53(2):289-99. PubMed PMID: 16529103.
72: Amundsen BH, Helle-Valle T, Edvardsen T, Torp H, Crosby J, Lyseggen E,
page 9
Støylen A, Ihlen H, Lima JA, Smiseth OA, Slørdahl SA. Noninvasive myocardial
strain measurement by speckle tracking echocardiography: validation against
sonomicrometry and tagged magnetic resonance imaging. J Am Coll Cardiol. 2006 Feb
21;47(4):789-93. Epub 2006 Jan 26. PubMed PMID: 16487846.
73: Malm S, Frigstad S, Stoylen A, Torp H, Sagberg E, Skjarpe T. Effects of
ultrasound contrast during tissue velocity imaging on regional left ventricular
velocity, strain, and strain rate measurements. J Am Soc Echocardiogr. 2006
Jan;19(1):40-7. PubMed PMID: 16423668.
74: Aase SA, Stoylen A, Ingul CB, Frigstad S, Torp H. Automatic timing of aortic
valve closure in apical tissue Doppler images. Ultrasound Med Biol. 2006
Jan;32(1):19-27. PubMed PMID: 16364793.
2005:
75: Pettersen V, Bjørkøy K, Torp H, Westgaard RH. Neck and shoulder muscle
activity and thorax movement in singing and speaking tasks with variation in
vocal loudness and pitch. J Voice. 2005 Dec;19(4):623-34. PubMed PMID: 16301107.
76: Helle-Valle T, Crosby J, Edvardsen T, Lyseggen E, Amundsen BH, Smith HJ,
Rosen BD, Lima JA, Torp H, Ihlen H, Smiseth OA. New noninvasive method for
assessment of left ventricular rotation: speckle tracking echocardiography.
Circulation. 2005 Nov 15;112(20):3149-56. PubMed PMID: 16286606.
77: Rygnestad T, Moen S, Wahba A, Lien S, Ingul CB, Schrader H, Knapstad SE.
Severe poisoning with sotalol and verapamil. Recovery after 4 h of normothermic
CPR followed by extra corporeal heart lung assist. Acta Anaesthesiol Scand. 2005
Oct;49(9):1378-80. PubMed PMID: 16146479.
78: Slørdahl SA, Wang E, Hoff J, Kemi OJ, Amundsen BH, Helgerud J. Effective
training for patients with intermittent claudication. Scand Cardiovasc J. 2005
Sep;39(4):244-9. PubMed PMID: 16118073.
79: Ingul CB, Torp H, Aase SA, Berg S, Stoylen A, Slordahl SA. Automated analysis
of strain rate and strain: feasibility and clinical implications. J Am Soc
Echocardiogr. 2005 May;18(5):411-8. PubMed PMID: 15891750.
80: Ingul CB, Stoylen A, Slordahl SA. Recovery of stunned myocardium in acute
myocardial infarction quantified by strain rate imaging: a clinical study. J Am
Soc Echocardiogr. 2005 May;18(5):401-10. PubMed PMID: 15891749.
page 10
81: Måsøy SE, Varslot T, Angelsen B. Iteration of transmit-beam aberration
correction in medical ultrasound imaging. J Acoust Soc Am. 2005
Jan;117(1):450-61. PubMed PMID: 15704438.
Ref. no 30 and 36 are duplicates
Two paper not found in Pubmed:
T. Varslot and S.-E. Måsøy, Forward propagation of acoustic pressure pulses in 3D soft biological
tissue, Modeling, Identification and Control, Vol. 27, No. 3, pp. 181-200, 2006
S.-E. Måsøy, T. Varslot, and B. Angelsen, Variance analysis of arrival time and amplitude estimates
from random speckle signal, Journal of the Acoustical Society of America, Vol. 121, No. 1, p. 286-297,
January 2007. This article also appears in the Virtual Journal of Biological Physics Research, Vol. 13,
No. 2, 2007 (http://www.vjbio.org/)..
Reviews and Book Chapters
1. Moholdt T, Støylen A, Tyni-Lenné R, Cider Å, Schaufelberger M, Wisløff U. Trening
ved hjertesvikt. Aktivitetshåndboken. Oslo 2009. Helsedirektoratet. IS-1592.
2. Michael A. Lang, and Alf O. Brubakk, The Future of Diving: 100 Years of Haldane
and Beyond, Chapter: Lasse Løvstakken, Andreas Møllerløkken, Svein-Erik Måsøy,
New Ultrasonic Techniques for Decompression Evaluation, Smithsonian Institution
Scholarly Press, Washington, D. C. 2009. ISBN-13: 978-0-9788460-5-3
3. Amundsen BH, Slørdahl SA, Ståhle A, Cider Å. Koronarsykdom. In
Aktivitetshåndboken. Oslo 2009. Helsedirektoratet. IS-1592.
4. Støylen, Asbjørn. Three-dimensional reconstruction of strain measurements and
measurement of strain in three dimensions.. In: Marwick TH, Yu C-M and Sun JP
(Ed.). Myocardial Imaging. Massachusetts USA, Oxford UK, Victoria Australia:
Blackwell Publishing 2007. ISBN 978-1-4051-6113-8. s. 265-272
5. Støylen, Asbjørn. Strain Echocardiography. In: Shiota T (Ed.). 3D Echocardiography.
Hampshire UK: Informa Healthcare 2007. ISBN 1-84184-632-5. s. 141-151
6. Ingul, Charlotte Bjørk; Aase, Svein Arne. Automated strain and strain rate. I:
Myocardial Imaging. Blackwell Publishing 2007 ISBN 978-1-4051-6113-8. s. 278287
Panel 4B
Magnetic Resonance
in Diagnosis and Therapy
1.2 Evaluation level (level 2): Magnetic Resonance in Diagnosis and Therapy
The magnetic resonance (MR) research is organized as one large research group
integrating researchers from several departments at NTNU and St. Olav’s University Hospital.
The main participants are from the Departments of Circulation and Medical Imaging and
Neuroscience at NTNU and the Department of Radiology at St. Olav’s University Hospital.
The main focus is on neuroscience/brain disorders and prostate/breast cancer. The
activity is translational and interdisciplinary research with full integration between population
based imaging, clinical research on patients, research with animal models (transgenic mice,
rat models of disease, regenerative medicine), and basic research. Also integrated is
innovation on new MR methods and applications, new MR technology, and multi-functional
nanoparticles for imaging. The research activity has the dual goal of: 1) MR used as a
research tool to obtain new knowledge about disease processes and new therapies; 2)
innovation of new MR technology and methods for enhanced patient care and to obtain
improved patient outcome and a more cost-effective health care.
The MR research group also acts as core facility and centre of competence locally and
nationally for MR Imaging and MR Spectroscopy methods and applications. There are two
National centre of competence appointed by the Norwegian Ministry of Health in functional
MRI and in clinical MR Spectroscopy respectively (the former collaboration with Haukeland
University Hospital in Bergen), and a national FUGE technology platform in molecular
imaging (MIC Trondheim) appointed by the Research Council of Norway. Professor Olav
Haraldseth leads the “whole animal imaging network” in the NorMIC (Norwegian Molecular
Imaging) consortium. There is also an MR Metabolomics Laboratory which serves the
function as a national core facility, however, without formal appointment or national funding.
MI Lab (Medical Imaging Laboratory, www.ntnu.no/milab) was appointed by the
Research Council of Norway in 2007 as one of three Centres for Research-based Innovation
[SFI] in the area of medicine and health in Norway. This is a new construction where eight
industrial partners, St. Olav’s University Hospital, SINTEF and NTNU are working together
in an open research and innovation environment. MI Lab has a budget of ~ 240 MNOK (80
MNOK from the Research Council of Norway) for the 8-years period 2007-2014, and covers
research in MR, ultrasound and image-guided surgery, and by November 2010 MI Lab has 30
PhD students and postdoctoral fellows allocated to these three areas of research. MI Lab acts
as an instrument for improved integration and collaboration for the entire medical imaging
research environment in Trondheim and is an important part of the MR research group. MI
Lab is organised with its own board that meets 2-3 times a year. The vision of MI Lab is to
facilitate cost efficient health care and improved patient outcome through innovation in
medical imaging, and to exploit the innovations to create industrial enterprise in Norway.
Professor Olav Haraldseth in the MR research group is leader of MI Lab.
The key senior personnel in the MR research group are:
•
•
•
•
Professor PhD Ingrid S. Gribbestad, Dept. of Circulation and Medical Imaging: Leader of the
MR Cancer Group, the National Centre of Competence in Clinical MR Spectroscopy, and the MR
Metabolomics Laboratory
Professor MD, PhD Asta Håberg, Dept. of Neuromedicine and St. Olav’s University Hospital:
Leader of the Trondheim fMRI Group and the National Centre of Competence in Functional MRI
Professor MD, PhD Olav Haraldseth, Dept. of Circulation and Medical Imaging and St. Olav’s
University Hospital: Leader of MI Lab and the MIC (Molecular Imaging Centre) Trondheim
Professor PhD Ursula Sonnewald, Dept. of Neuromedicine: Leader of the Metabolic
Neuroscience group
1
•
Associate professor and consultant in Radiology, MD, PhD Kjell Arne Kvistad, Dept. of
Circulation and Medical Imaging and St. Olav’s University Hospital
It is a challenge to establish a good organisation and leadership for the MR research
group as it covers two departments at the Faculty of Medicine, St. Olav’s University Hospital
and several centres of competence and technology platforms. It was chosen not to establish
the group as a formal separate entity; it functions as an integrated research group based on
extensive sharing of competence, joint projects and co-publication, collaboration on research
funding activities and collaboration on the infrastructure. The senior academic staff
(professors and senior post doc fellows) meets regularly for activity updates and discussion of
strategies and infrastructure challenges. The group agrees on priorities for new equipments,
positions and other types of funding activities, and work together to obtain these goals
through the different departmental and institutional affiliations of the key senior researchers.
The MR research group consists presently of 65 persons including professors, research
scientists, post doc fellows, PhD students and medical students in the medical school research
program [forskerlinjen], and in this group app. 50 % are women. The group is
multidisciplinary; with backgrounds from medicine, physics, biophysics, mathematics,
computer science, chemistry, biotechnology, biology, physiology, molecular biology,
psychology and neuroscience. The five key senior researchers are relatively young (43, 49,
50, 54 and 58 years old), and 3 of the 5 are female (Ursula Sonnewald, Ingrid S. Gribbestad
and Asta Håberg). There are 15% international PhD students, 20% international post doc
fellows and 4 adjunct/guest professors from foreign universities connected to the MR research
group. The MR research group is also part of the large medical imaging research environment
in Trondheim, an integrated activity between NTNU, St. Olav’s University Hospital and
SINTEF, with a total of 150 persons in ultrasound, MR and image-guided therapy research.
The main strategy for publication and dissemination is to publish all important scientific
results as quickly as possible through presentation at international scientific meetings and as
full scientific papers in international scientific journals with peer review. Enclosed is a
publication list from the MR research group for 2005 - June 2010 with 110 full scientific
papers published in international journals with peer review (all to be found in the PubMed
database). Of these papers, 33% were published in level 2 journals (according the official
Norwegian system for result based funding of the universities), and 51% of the papers have
co-authors from foreign universities. There are publications in high impact journals such as
Journal of Neuroscience, Nature Reviews Neuroscience, Nature Biotechnology, Neuroimage,
Radiology, Journal of Cerebral Blood Flow and Metabolism, Brain, and Neurosurgery.
July-December 2010 was a productive period for the MR research group with a further
24 printed papers, however, the enclosed publication list is only until June 2010..
Scientific results with direct impact on patient treatment and diagnostics are
communicated to the relevant medical and hospital environments. For this purpose the two
National Centres of Competence appointed by the Norwegian Ministry of Health in functional
MRI and in Clinical MR spectroscopy are excellent tools. A main task for these centres is to
spread new knowledge of clinical relevance to the Norwegian health care system through
hands-on training, courses and seminars.
The fMRI and MR cancer groups have also been active with popular science
communication to the public through Norwegian media, with several presentations in the
science program ”Schrødingers katt” in Norwegian State Broadcasting (NRK), and in major
Norwegian newspapers (VG, Dagbladet, Adresseavisen).
The MR research group has a critical size sufficient for keeping the broad competence
and experience necessary for fulfilling the tasks and activities described in this document. The
group is heavily dependent on external funding, and this is a continuous challenge.
Furthermore, MR technology is expensive, and due to rapid technology development frequent
2
upgrades and purchases is necessary in order to have access to state-of-the-art technology at
all times. However, the group has been successful in obtaining sufficient funding from
external sources, and is presently in a period of steady growth. The scientific output is good
compared to available resources, documented through the quality and quantity of publications.
The MR research infrastructure includes two 3 Tesla clinical MR scanners (one Siemens
Trio is owned by NTNU and 100% dedicated to research), one 7 Tesla animal models
research scanner (Bruker Biospec), and two 600 MHz spectrometers (Bruker, one fitted with
cryoprobe and the other optimized for high throughput MR metabolomics of intact tissue
samples). The 3T Siemens scanner was purchased in 2006 (app. 20 MNOK), the 7T animal
scanner in 2004 (app. 13 MNOK), and the two 600 MHz spectrometers in 2010 (app.10
MNOK). The annual operating expenses are app. 3 MNOK per year.
The Kavli Institute for Systems Neuroscience in Trondheim (headed by Professor
Edvard Moser), MI Lab and the Centre of Molecular Biology and Neuroscience (CMBN) in
Oslo, have initiated the establishment of a national research infrastructure in neuroscience
called NORBRAIN. The aim is to achieve a vertical integration from cellular biology (main
focus of CMBN) through systems neuroscience research in animal models (main focus of the
Kavli Institute) to research on patients and human volunteers with advanced MR technology
(MI Lab). NORBRAIN is on the Research Council of Norway roadmap for large-scale
national research infrastructures (as investment ready), and the MI Lab part is funding of a
clinical 7 Tesla clinical MR system for human research with planned installation in 2013
(planned budget of app. 70 MNOK). With this technology the spatial resolution of 0.1 mm for
anatomy and 0.5 mm for functional studies will be possible.
MI Lab leads the medical imaging activity in the new national “EATRIS Centre
Norway” which is a node in the European research infrastructure EATRIS (European
Advanced Translational Research Infrastructure). EATRIS is part of the ESFRI (European
Strategy Forum on Research Infrastructure) programme, and is now entering the construction
phase. The MR research group will have important tasks in “EATRIS Centre Norway” in drug
development and new imaging biomarkers and tracers for preclinical and clinical research.
The main focus is on neuroscience/brain disorders and prostate/breast cancer, and the
activity is translational and interdisciplinary research with integration between population
based imaging, clinical research, research with animal models, and basic research. The
research activity has the dual goal of: 1) MR used as a research tool to obtain new knowledge
about disease processes and new therapies; 2) innovation of new MR technology and methods
for improved patient outcome and a more cost-effective health care system.
Trondheim fMRI group (Professor Asta Håberg)
The aim of Trondheim fMRI group is to elucidate the relationship between brain
structure and function in the diseased and healthy human brain. These goals are pursued via
three pathways: clinical MRI, human memory and population based imaging.
Clinical MRI: The aim is to assess brain structure and function using different MRI
techniques to increase out understanding of brain-behaviour relationships in selected patient
groups. In recent years the main patient groups studied have been traumatic brain injury (in
collaboration with Robert Asarnow’s laboratory at UCLA and Professors Robert T. Knight
and Mark D'Esposito at University of California, Berkeley), stroke (Professor Bent
Indredavik, Stroke Unit, St. Olav’s University Hospital), and children/adolescents born
prematurely with very low birth weight (Professor Ann Mari Brubakk, St. Olav’s University
Hospital). The overriding aim of these projects is to establish MRI methods and protocols that
allow for better patient care. One example is to select patients for follow-up with cognitive
3
and/or motor training based on functional and/or structural MRI measurements. A new
activity is the study of mild cognitive impairment with focus on memory and odor
identification as early indicators of incipient dementia with the goal of establishing methods
for subclinical diagnosis and monitoring of disease progression and treatment efficacy.
Human memory: This activity focuses on functions of the medial temporal lobe (MTL);
memory, spatial navigation and olfaction. The aims are to elucidate the functional role of
subregions in the MTL and how they are implicated in brain disease, in particular dementia.
This work is collaboration with the Kavli Institute for Systems Neuroscience/Centre for the
Biology of Memory in Trondheim (Professors. Edvard Moser and Menno Witter). The group
has developed methodology which allows flexible investigation of encoding and retrieval of
different types of stimuli, combined with fMRI of high spatial resolution (see below) enabling
detailed ecologically valid studies of MTL function in humans. We have been able to show
that there is a functional segregation along the longitudinal axis of the hippocampus, which is
linked to specific operations based on level of detail and abstraction rather than input
modality, encoding or retrieval processes. Some specific projects are: 1) navigation in space
using virtual reality when inside the MR scanner (collaboration with Prof. Richard Morris at
Centre for Cognitive and Neural Systems, University of Edinburgh); 2) context memory for
multimodal stimuli (visual, tactile, auditory and olfactory in order to investigate more
ecological valid encoding experiences and also explore how such multi modal stimuli are
processes in different subregions in MTL, and study the interaction between modality and
process (collaboration with Prof. Scott Small, Columbia University, NY, USA). Such studies
will bring us from the now often animal based hypothesis on human memory to develop
human centred hypothesis necessary in order for us to understand and treat human memory
dysfunction. For significant improvement of fMRI in MTL the group is exploring the use of
non-BOLD contrast based fMRI and new image acquisition and reconstruction techniques
(collaborations with Dr. Karla Miller, University of Oxford and Prof. Anders Dale, UCSD).
Population based imaging of brain structure and function. The Nord-Trøndelag health
study (HUNT) is one of the largest health studies ever performed. It is a unique database of
personal and family medical histories collected at three time points between 1984 and 2008.
MRI-HUNT is a cohort of 1006 HUNT participants who have undergone MRI (including DTI
and quantitative morphometrics). Gene sequencing of the total cohort has been funded and
will be performed at Translational Genomics Research Institute, Phoenix, Arizona
(collaboration with Dr. Matthew J Huentelman). Some specific projects based on the MRIHUNT cohort are: 1) Explore the impact for risk factors for or presence of cardiovascular
disease on gray and white matter structure using clinical data (blood pressure, HDL, LDL,
TG, weight, blood glucose etc.) and questionnaire data from 1984-6, 1995-7, and 2006-8
(collaboration with Professor Gene Alexander, University of Arizona and Professor Mark van
Buchem, University of Leiden, the Netherlands); 2) the cohort will undergo detailed testing
for different types of episodic memory with an internet based test battery (at present being
validated in a different HUNT cohort) (in collaboration with McKnight Brain Institute,
University of Arizona). Combined with neuroimaging, clinical, genetic, and questionnaire
data this detailed testing of a range of memory abilities will offer the possibility of studying
the distribution of memory abilities on specific types of episodic memory tests. Large scale
epidemiological data from a homogenous population with clinical data going back 25 years is
unique for studies on the relationship between lifestyle factors, risk factors, and genetics on
brain structure and cognition. Norway is an excellent country for nationwide MRI studies, and
on the national level the group is involved three large scale patient studies: the BRAIN and
TOP studies led by Professor Ole Andreassen (University of Oslo) and PRODE led by Prof.
Knut Engedal (University of Oslo) aiming to uncover the relationship between brain structure
and schizophrenia and brain structure and depression in the young and elderly, respectively.
4
The MR Cancer Group (Professor Ingrid S. Gribbestad):
The MR Cancer Group (https://www.ntnu.no/MRCancer) has focused on research and
implementation of MR methods for breast cancer diagnosis and treatment, later also for
prostate cancer. The projects combine the use of advanced MR Imaging (MRI), in vivo MR
Spectroscopy (MRS) and ex vivo MRS of intact cancer specimens (MR metabolomics) to
obtain functional and molecular tumour information for improved patient stratification.
Clinical studies: Dynamic-contrast enhanced MRI in combination with in vivo MRS has
shown a high sensitivity and specificity for differential diagnosis of breast cancer. Work
performed within the MR Cancer group was among the first to use these methods to
distinguish benign and malign breast cancer. Patients diagnosed with locally advanced breast
cancer have a poor prognosis, and are usually treated with neoadjuvant chemotherapy before
surgery. Recent work has proven that DCE-MRI can be used for early monitoring of treatment
response and prediction of overall survival. New methodology such as diffusion MRI has
been implemented. Excellent reproducibility of both diffusion MRI and in vivo MRS was
obtained by repeated examinations in a breast cancer patient cohort.
Current approaches for prostate cancer diagnosis are still inaccurate for patient
diagnosis and prognosis. The main goal of the multimodal MR prostate cancer project is to
evaluate if combined in vivo MRI, in vivo MRSI (collaboration Prof. Arend Heerschap) and
ex vivo MR metabolomics (see below) of tissue (collaboration Prof. John Kurhanewicz,
UCSF) can facilitate improved diagnosis, and thereby treatment, of prostate cancer patients.
Recently, spatially localized ex vivo MR metabolomics (and other molecular analyses) were
combined with co-localized functional MRI and in vivo MRS images for the very first time in
a cohort of prostate cancer patients undergoing prostatectomy.
Preclinical studies (MRI/MRS): The molecular imaging activity using different breast
cancer xenografts aims at tumour characterization and mapping of treatment effects, with a
careful histopathological validation (Prof. Lars Akslen, Haukeland University Hospital). The
main approach is to combine MRI (DCE-MRI, DW-MRI, MRS) with molecular diagnostics
(transcriptomics, metabolomics, histopathology) for improved treatment stratification. Early
chemotherapeutic and hormonal effects have been monitored in the well-established MCF-7
xenografts. New directly grafted orthotopic xenograft models that have retained the original
patient characteristics have been established at Oslo University Hospital. These models are
representing basal-like and luminal-like breast cancer gene expression profiles, and significant
differences have been demonstrated with MRI, in vivo MRS and molecular biology methods
(Prof. Anne-Lise Børresen-Dale). Ex vivo metabolomics metabolic profiles of the two models
are representative for human breast cancer samples, providing a relevant model system for
monitoring effect of new anticancer drugs targeting the inflicted pathways which is now being
tested. New MR methodologies to test the effect of anti-cancer drugs are being implemented;
hyperpolarized carbon-13 MRS will be performed through collaboration with the Cancer
Research UK Royal Marsden (Prof. Martin Leach), while phosphorous-31 MRS are being
performed at Radboud University Nijmegen (Prof. Arend Heerschap). Several breast cancer
xenografts are now examined (collaboration with Institute Curie, Paris) to map variation in
molecular and MR imaging profiles in different gene subgroups.
MR metabolomics: Metabolic profiling of intact cancer tissue specimens was
implemented by the MR Cancer Group as one of the first sites word-wide. Recently, the very
first study merging transcriptomics and metabolomics of the same cancer samples were
published in collaboration with Oslo University Hospital (Prof. Anne-Lise Børresen-Dale),
showing further stratification beyond gene expression based on the MR metabolic profiles.
The technology (High resolution Magic Angle Spinning (HR MAS) MRS) for intact tissue
analyses has been optimized and implemented at NTNU, as the first research group to do
thorough and large-scale characterization of intact breast cancer tissue samples. A breast
5
cancer tissue biobank with samples from 750 patients has been established in collaboration
with St. Olav’s University Hospital and local hospitals in Mid-Norway. Collaborative projects
with Oslo University Hospital (Prof. Rolf Kåresen Oslo II-biobank) and Haukeland
University Hospital (Prof. Per E. Lønning) involves additional breast tissue samples from app.
1100 patients. Metabolomics studies have shown that the molecular profiles correlate to
clinical parameters such as histopathological grade and hormone status. Possible correlations
to lymph node status and overall patient survival have also been demonstrated. Furthermore,
serum collected during HUNT2 will be studied for detection of early risk parameters for
cardiac heart disease.(Prof. Lars Vatten, NTNU).
In summary, combined molecular and multimodal MR imaging investigations in
xenograft models and patients have demonstrated an exciting approach for early changes of
different treatments and patient stratification. Future work will combine ex vivo and in vivo
MR metabolomics with other molecular methodologies to address molecular pathways and
targeted treatment approaches.
The Metabolic Neuroscience Group (Professor Ursula Sonnewald)
The main focus of this group is to obtain knowledge about how metabolic processes are
coupled to brain function/dysfunction and anatomy with special emphasis on glial/neuronal
interactions in conditions such as epilepsy, schizophrenia and Alzheimer`s disease. 13C
nuclear magnetic resonance spectroscopy (MRS) and mass spectrometry (MS) are carried out
on brain cell culture extracts, rodent brain and tissue extracts, after incubation/injection of 13C
labelled substrates. Careful balance of excitation by glutamate and inhibition by GABA is
required for proper brain functioning, including intellectual activities, memory and motor
skills. Imbalance may result in functional impairments, confusion, loss of memory, seizures
and excitotoxic cell damage, which in turn can cause neurological and psychiatric diseases
including dementia, epilepsy and psychosis. Information about biochemical pathways, i.e. the
activity of enzymes which are a result of gene expression can be gained by analyzing the
labelling of key substances by 13C MRS. Using appropriately 13C labelled precursors it is
possible to analyze neuronal and astrocytic metabolism and metabolic interactions between
these two major cell types in brain. 13C MRS analysis will shed light on essential metabolic
pathways in the brain and thus shed light on the underlying mechanisms leading to the known
activational differences in for instance prefrontal cortices seen in patients with dementia and
schizophrenia compared to healthy volunteers. Also, evaluation of the effect of
pharmaceutical intervention can be explored in vivo and insight into mechanisms responsible
for improvement can be understood. Thus, the groundwork for increased understanding of the
pathological processes and possible ways to attack the process can be obtained.
Molecular Imaging Centre (MIC) Trondheim (Professor Olav Haraldseth)
MIC Trondheim is a national technology platform for molecular imaging with MR, and
is involved in a broad range of projects dependent on the biomedical and medical research
problems presented by the collaborators. However, the platform has also in collaboration with
MI Lab established some self-initiated activities where the main focus has been Manganese
enhanced MR Imaging (MEMRI), regenerative medicine, multi-functional nanoparticles for
imaging (including image-guided drug delivery) and MRI of cardiac function in transgenic
mice established as a model system for studies of the effect of different genes on heart
function. Molecular imaging is at present mainly preclinical research in animal models,
however, with the potential of future translation to clinical use. In the case of MEMRI we
have performed clinical studies on patients with myocardial infarction and we found selective
uptake of manganese only in viable cardiac tissue, which supported the concept that MEMRI
has the potential of in-vivo detection of stunned and hibernating myocardium in humans.
6
In regenerative medicine, one project example is transplant-mediated repair on brain
white matter injury integrating scaffolding cells (Olfactory Ensheathing Cells) and alginate
scaffolds and using MR imaging for monitoring and guidance of the white matter regeneration
in two rat models of optical nerve and spinal chord injury. There is also collaboration on stem
cell research in with Professor Joel Glover at the Norwegian Stem Cell Centre in Oslo.
One nanoparticles project uses “oil-in-water nanoemulsions” (collaboration with Dr.
Willem Mulder at Mount Sinai Medical School, NY, USA) as a flexible synthesis platform
for multi-functional and multi-modal nanoparticles. Nanoparticles with bi-modality for MR
and optical imaging (fluorescence) are studied in a window chamber model of rat tumours to
allow excellent co-localization between the MR and optical images. The goal is to study some
basic mechanisms: the ability and the reproducibility of the nanoparticles to cross biological
barriers between the main tissue compartments, mechanisms for binding to the receptors, and
the relation between particle size and MR sensitivity, and furthermore to use this knowledge
to design nanoparticles with optimal properties tailored to different purposes.
MIC Trondheim also participates in the EU 7th FP project “Luminescent polymers for in
vivo imaging of amyloid signatures”. Novel contrast agents (based on luminescent conjugated
polymers, LCPs) and methods tailored to in-vivo diagnostic imaging of amyloid plaques (a
potential biomarker for Alzheimer’s disease) have been developed. The contrast agents are
multi-modal for optical imaging (fluorescence) and MR Imaging to combine high sensitivity
(fluorescence) with good anatomical localization (MRI).
MI Lab - Medical Imaging Laboratory (Professor Olav Haraldseth):
MI Lab acts as part of the MR research group through collaboration on specific research
projects and the main activities are described above in the MR cancer group, Trondheim fMRI
group and MIC Trondheim subchapters.
All the described activities are considered to be within the major international trends in the
different fields. Some examples that illustrate this are:
• MR in population imaging is a novel tool for elucidating the early structural and
functional brain changes accompanying common health problems/diseases and combined
with imaging genetics, the research may reveal imaging biomarkers for assessment of risk
for different brain disorders and early (subclinical) diagnosis.
• MR metabolomics of intact tissue samples
• Combined molecular (genomics, transcriptomics, histopathology) and MR imaging
diagnostics of cancer, stratification of cancer patients for individualized treatment
• Multimodal and multifunctional nanoparticles for imaging, and including image-guided
drug delivery
• MR imaging used as a tool for obtaining new knowledge about brain functions in the
medial temporal lobe (memory, navigation and olfaction), as typical early functional
impairments in aging and in diseases such as dementia and neurodegenerative disorders.
•
•
•
The main societal impact of the research is found on three levels:
Basic and clinical research using MR imaging to obtain new knowledge about disease
mechanisms, new therapeutic targets and new innovative therapies
Population based epidemiology research using MR imaging and MR metabolomics to
obtain knowledge about risk factors for disease and imaging biomarkers for disease
occurrence and progression
Innovation on MR imaging and technology for clinical use in the hospitals with a main
focus on early (subclinical) diagnosis, therapy tailored to the individual patient
7
(personalized medicine concept), monitoring of therapy response and stratification of
subgroups that will benefit from rehabilitation programs.
Furthermore, the research and innovation may help the health care system to find costeffective solutions through early diagnosis, better and quicker treatment decisions, and
imaging used to delineate risk groups for disease.
The MR research group has a long and successful history of interdisciplinary research
and of collaboration between university and hospital and between technologists and medical
doctors. It has been proven that the MR research group is an excellent arena for translational
research with an iterative process between technology R&D and clinical feasibility studies,
and between basic biomedical research and clinical research. The group combines curiositydriven basic research with closeness to the patients’ needs and the demands of the health care.
Innovation obtained through high-quality research is the defined task for MI Lab, and MI Lab
has two MR companies (both SMEs) as partners: Nordic NeuroLab (NNL) located in Bergen
and CorTechs Labs located in San Diego, USA. The MR research group collaborates with
NNL in the area of new methods and applications of functional MR technology in clinical
studies of brain tumours, brain vasoreactivity and traumatic brain injury, the latter also
including resting state fMRI and new innovative paradigms for assessment of brain activity
linked to attention. In the case of CorTechs the research collaboration is in the area of early
(subclinical) diagnosis of brain degeneration and monitoring of disease progression through
follow-up of changes in quantitative morphology over time compared to a validated control
group of normal brain ageing. MI Lab, MIC Trondheim and the MR Cancer group are also
active in a new strategic innovation focus in Trondheim on multi-modal and multi-functional
nanoparticles for imaging and image-guided drug delivery, and this includes also participation
in the EUs 7th framework project LUPAS with partners from 7 countries. Furthermore, the
research activities in MR metabolomics and MR in the HUNT population study have great
potential for innovation in the area of biomarkers. In this context collaboration with NTNU
Technology Transfer and HUNT Biosciences is established. MI Lab leader Olav Haraldseth
also initiated (together with the Centre for Molecular Biology and Neuroscience in Oslo) the
Nansen Neuroscience Network which is a new national innovation cluster between industry
and academia, and that will be an important instrument for innovation and industry
collaboration in the area of neuroscience and brain disorders.
The main strengths of the MR research group are:
• long and successful history of interdisciplinary research
• long and successful history of collaboration between university and hospital and between
technologists and medical doctors/physicians in the hospital departments
• excellent arena for translational research with an iterative process between technology
R&D and clinical feasibility studies, and between basic research, animal models and
clinical research
• scientific production and publications of high quality
• sufficient size of research group to cover competence and experience in a wide range of
areas of MR technology and applications from basic research to clinical research and
population based imaging
• sufficient size of research group to handle the situations when experienced researchers
with unique competence and experience leave the group
• excellent gender equality
Weaknesses:
• the broadness of the activities is a problem for continuous funding of new expensive
equipment to obtain state-of-the-art infrastructure in all the research subfields
8
•
dependence on external funding and after a long period of continuous growth the
consolidation on the high level of activity is a challenge
The 5 key senior researchers in the MR research group all have an active scientific
production and in the enclosed publication list for 2005- June 2010 (only full scientific
papers) they are co-author on a number of papers: Ursula Sonnewald 45, Ingrid Gribbestad
19, Asta Håberg 16, Olav Haraldseth 19, Kjell Arne Kvistad 11.
Recruiting the best students to PhD and post doc positions is one of the most important
success factors for the research. The MR research group is satisfied with the recruitment
during the last five years, and has obtained an excellent interdisciplinary mix. The MR
research group has a history of successful recruitment of women at all levels, and there is
about a perfect 50-50 balance between the genders both on PhD, post doc and senior professor
level. Noteworthy is that 3 out of the 5 key senior researchers are female.
To stimulate interest in medical imaging research and improve the quality of the PhD
training MI Lab leader Olav Haraldseth initiated and is the current leader of the Norwegian
Research School in Medical Imaging (see: www.ntnu.no/medicalimaging). The Research
Council of Norway had an open call for post graduate researcher training programmes
[forskerskoler] in 2008, and the Norwegian Research School in Medical Imaging was one of
the five appointed (the only in the area of medicine and health). This school is collaboration
with the universities in Oslo, Bergen and Tromsø, and the total budget is 24 million NOK
over 8 years. The researcher school is multidisciplinary and covers all areas of medcial
imaging research including bionanotechnology. The main aims are to improve the quality of
the research, the quality of PhD training, and improve recruitment of the best students (also
foreign recruitment). The research school will also organize collaboration with foreign
universities in the area of PhD training and exchange.
Also important for recruitment to the MR research group is the PhD and master
programmes in neuroscience at Faculty of Medicine, NTNU. These programs attract top level
students because the internationally leading Kavli Institute for Systems Neuroscience and
Centre for the Biology of Memory are located at the Faculty of Medicine at NTNU. The MR
Research group collaborates closely with these research groups, and recruits many top quality
master and PhD students for neuroscience research with MR methods (described above).
The MR research group has a focus on recruiting PhD students and post doc fellows
from high quality foreign universities, and all job opportunity calls are international. During
the 2005-2009 period some top level foreign PhD students and post doc fellows have been
recruited, and at present the MR research group has 15% foreign PhD students and 20%
foreign post doc fellows.
MI Lab has recruited four top foreign scientists for adjunct professor/guest researcher for
the activities in the MR research group:
• Prof. Anders M. Dale, Multimodal Imaging Lab., Univ. of California San Diego, USA
• Prof. Arend Heerschap, Radboud University Medical Centre, Nijmegen, the Netherlands
• Prof. Henrik Larsson, Glostrup University Hospital, Copenhagen, Denmark
• Guest Researcher Kim Mouridsen, Centre of Functionally Integrative Neuroscience,
Århus, Denmark
Several PhD students and post doc fellows from the MR research group have spent time
at excellent institutions abroad, such as John Hopkins School of Medicine, Baltimore USA;
University of California San Fransisco (UCSF) USA; Radboud Univ. Medical Centre,
Nijmegen Netherlands; The Erwin L. Hahn Institute for MR Imaging, Essen, Germany;
Martinos Centre for Biomedical Imaging at Harvard/MIT/MGH in Boston.
9
MI Lab is an excellent arena for collaboration between academia and industry and many
PhD students in the MR research group work with industry related PhD projects. During
recent years some PhD candidates from the MR research group have found job opportunities
with research related tasks in industry (Philips and GE). Similarly, many PhD candidates and
post doc fellows from the MR research group are now employed in MR research related
positions at the university hospitals in Oslo, Bergen, Tromsø and Stavanger.
In the MR research group the general policy is that the PhD students and post doc
fellows have a high level of responsibility for the day-to-day activities in their own projects.
Some post doc fellows are encouraged to participate as main supervisors and co-supervisors
for PhD students (the Faculty of Medicine allows post docs as main supervisors when one of
the professors is co-supervisor). Some of the senior post doc fellows are encouraged to build
an academic carrier, and they apply for their own grants, are senior authors on scientific
papers, follow NTNU mentor programmes and are trained in project leadership.
interdisciplinarity
All the MR research group activities have large local, national and international
networks. During recent years the MR research group has had collaboration activities and/or
co-publication with: 55 foreign universities, 3 Norwegian Centres of Excellence (one in
Trondheim and two in Oslo), the universities and university hospitals in Oslo, Bergen and
Tromsø, 19 departments and sections at St. Olav’s University Hospital, 7 departments at
NTNU (from three different faculties), and 14 industrial companies. The international
collaboration is well documented through co-publication. In the enclosed publication list for
2005- June 2010 51% of the 110 published papers have one co-author or more from a foreign
university or foreign industrial company.
Examples of the most important ongoing international collaboration partners are
mentioned in the text above (especially the research activities on pages 3-7).
Examples of other international institutions with ongoing or planned collaboration
activities are:
in USA: Martinos Centre for Biomedical Imaging at Harvard/MIT/MGH, Boston; Weill
Cornell Medical College of Cornell University, New York; Burke Medical Research Institute,
New York; McKnight Brain Institute and Division of Neural Systems, Memory and Aging,
University of Arizona, Tucson.
In UK: Wellcome Trust Centre for Neuroimaging, University College of London (UCL);
In the Netherlands: Donders Institute for Brain, Cognition and Behaviour, Radboud
University, Nijmegen; Dept. of Anatomy and Neurosciences, VU University Medical Centre,
Amsterdam; Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam.
In Germany: The Erwin L. Hahn Institute for MR Imaging, University of Essen
In France: INSERM U 666 Faculté de Médecine, Strasbourg.
In order to obtain new knowledge of high international significance within medical
research, it is necessary to study the biomedical/clinical research problem from many different
angles, with different methods and with different types of competence. For the MR research
group this can only be achieved through national and international collaboration and the group
continuously strive to find the right partners with the right synergies in competence and for
access to infrastructure, animal models, image analysis software etc. The MR research group
has been successful in this context, and this has contributed to the quality of the research and
has also been important for building more competence and experience within the MR research
group. In some projects national and international collaboration is necessary in order to obtain
patient inclusion (multicentre clinical studies) and patient material (e.g. cancer biopsies) of
sufficient size and statistical power for testing the study hypothesis.
10
Magentic Resonance in Diagnosis and Therapy
PUBLICATION LIST 2005-June 2010
Limited to printed full scientific papers and review articles in international journals with referee,
and only papers registered in the PubMed database.
2010
1.
Xu J, Evensmoen HR, Lehn H, Pintzka CW, Håberg AK. Persistent posterior and transient anterior medial
temporal lobe activity during navigation. Neuroimage. 2010 Jun 2. [Epub ahead of print]. PMID: 20685394
2.
Palmer HS, Garzon B, Xu J, Berntsen EM, Skandsen T, Håberg AK. Reduced fractional anisotropy does not
change the shape of the hemodynamic response in survivors of severe traumatic brain injury. J
Neurotrauma. 2010 May;27(5):853-62. PMID: 20199173
3.
Hak S, Reitan NK, Haraldseth O, de Lange Davies C. Intravital microscopy in window chambers: a unique
tool to study tumor angiogenesis and delivery of nanoparticles. Angiogenesis. 2010 Jun;13(2):113-30.
PMID: 20623252
4.
Reitan NK, Thuen M, Goa PE, de Lange Davies C. Characterization of tumor microvascular structure and
permeability: comparison between magnetic resonance imaging and intravital confocal imaging. J Biomed
Opt. 2010 May-Jun;15(3):036004. PMID: 20615006
5.
Berntsen EM, Gulati S, Solheim O, Kvistad KA, Torp SH, Selbekk T, Unsgård G, Håberg AK. Functional
magnetic resonance imaging and diffusion tensor tractography incorporated into an intraoperative 3dimensional ultrasound-based neuronavigation system: impact on therapeutic strategies, extent of resection,
and clinical outcome. Neurosurgery. 2010 Aug;67(2):251-64. Epub 2010 Jun 25. PMID: 20644410
6.
Sitter B, Bathen TF, Singstad TE, Fjøsne HE, Lundgren S, Halgunset J, Gribbestad IS. Quantification of
metabolites in breast cancer patients with different clinical prognosis using HR MAS MR spectroscopy.
NMR Biomed. 2010 May;23(4):424-31. PMID: 20101607
7.
Wijnen JP, van Asten JJ, Klomp DW, Sjobakk TE, Gribbestad IS, Scheenen TW, Heerschap A. Short echo
time 1H MRSI of the human brain at 3T with adiabatic slice-selective refocusing pulses; reproducibility and
variance in a dual center setting. J Magn Reson Imaging. 2010 Jan;31(1):61-70. PMID: 20027568
8.
Giskeødegård GF, Grinde MT, Sitter B, Axelson DE, Lundgren S, Fjøsne HE, Dahl S, Gribbestad IS,
Bathen TF. Multivariate modeling and prediction of breast cancer prognostic factors using MR
metabolomics. J Proteome Res. 2010 Feb 5;9(2):972-9. PMID: 19994911
9.
Jensen LR, Huuse EM, Bathen TF, Goa PE, Bofin AM, Pedersen TB, Lundgren S, Gribbestad IS.
Assessment of early docetaxel response in an experimental model of human breast cancer using DCE-MRI,
ex vivo HR MAS, and in vivo (1)H MRS. NMR Biomed. 2010 Jan;23(1):56-65. PMID: 19650073
10. Arum CJ, Kodama Y, Rolim N, Widerøe M, Anderssen E, Viset T, Otterlei M, Lundgren S, Chen D, Zhao
CM. A rat model of intravesical delivery of small interfering RNA for studying urinary carcinoma. World J
Urol. 2010 Aug;28(4):479-85. Epub 2010 Apr 8. PMID: 20376453
11. Leke R, Bak LK, Anker M, Melø TM, Sørensen M, Keiding S, Vilstrup H, Ott P, Portela LV, Sonnewald U,
Schousboe A, Waagepetersen HS. Detoxification of Ammonia in Mouse Cortical GABAergic Cell Cultures
Increases Neuronal Oxidative Metabolism and Reveals an Emerging Role for Release of Glucose-Derived
Alanine. Neurotox Res. 2010 May 18. [Epub ahead of print] PMID: 20480276
12. Podo F, Buydens LM, Degani H, Hilhorst R, Klipp E, Gribbestad IS, Van Huffel S, van Laarhoven HW,
Luts J, Monleon D, Postma GJ, Schneiderhan-Marra N, Santoro F, Wouters H, Russnes HG, Sørlie T,
Tagliabue E, Børresen-Dale AL; FEMME Consortium. Triple-negative breast cancer: present challenges
and new perspectives. Mol Oncol. 2010 Jun;4(3):209-29. Epub 2010 Apr 24. Review. PMID: 20537966
2009
13. Lehn H, Steffenach HA, van Strien NM, Veltman DJ, Witter MP, Håberg AK. A specific role of the human
hippocampus in recall of temporal sequences. J Neurosci. 2009 Mar 18;29(11):3475-84. PMID: 19295153
14. van Strien NM, Cappaert NL, Witter MP. The anatomy of memory: an interactive overview of the
parahippocampal-hippocampal network. Nat Rev Neurosci. 2009 Apr;10(4):272-82. Review. PMID:
19300446
15. Johansen R, Jensen LR, Rydland J, Goa PE, Kvistad KA, Bathen TF, Axelson DE, Lundgren S, Gribbestad
IS. Predicting survival and early clinical response to primary chemotherapy for patients with locally
advanced breast cancer using DCE-MRI. J Magn Reson Imaging. 2009 Jun;29(6):1300-7. PMID: 19472387
16. Martinussen M, Flanders DW, Fischl B, Busa E, Løhaugen GC, Psychol C, Skranes J, Vangberg TR,
Brubakk AM, Haraldseth O, Dale AM. Segmental Brain Volumes and Cognitive and Perceptual Correlates
in 15-Year-Old Adolescents with Low Birth Weight. J Pediatr. 2009 Dec;155(6):848-853.e1. PMID:
19683725
17. Skranes J, Lohaugen GC, Martinussen M, Indredavik MS, Dale AM, Haraldseth O, Vangberg TR, Brubakk
AM. White matter abnormalities and executive function in children with very low birth weight.
Neuroreport. 2009 Feb 18;20(3):263-6. PMID: 19444947
18. Thuen M, Olsen O, Berry M, Pedersen TB, Kristoffersen A, Haraldseth O, Sandvig A, Brekken C.
Combination of Mn(2+)-enhanced and diffusion tensor MR imaging gives complementary information
about injury and regeneration in the adult rat optic nerve. J Magn Reson Imaging. 2009 Jan;29(1):39-51.
PMID: 19097077
19. Askim T, Indredavik B, Vangberg T, Håberg A. Motor network changes associated with successful motor
skill relearning after acute ischemic stroke: a longitudinal functional magnetic resonance imaging study.
Neurorehabil Neural Repair. 2009 Mar-Apr;23(3):295-304. PMID: 18984831
20. Håberg AK, Qu H, Sonnewald U. Acute changes in intermediary metabolism in cerebellum and
contralateral hemisphere following middle cerebral artery occlusion in rat. J Neurochem. 2009 May;109
Suppl 1:174-81. PMID: 19393025
21. Kristoffersen A. Diffusion measurements and diffusion tensor imaging with noisy magnitude data. J Magn
Reson Imaging. 2009 Jan;29(1):237-41. PMID: 19097102
22. Eide KR, Ødegård A, Myhre HO, Lydersen S, Hatlinghus S, Haraldseth O. DynaCT during EVAR--a
comparison with multidetector CT. Eur J Vasc Endovasc Surg. 2009 Jan;37(1):23-30. Epub 2008 Nov 17.
PMID: 19010697
23. Lund TM, Risa O, Sonnewald U, Schousboe A, Waagepetersen HS. Availability of neurotransmitter
glutamate is diminished when beta-hydroxybutyrate replaces glucose in cultured neurons. J Neurochem.
2009 Jul;110(1):80-91. PMID: 19457063
24. Shi Q, Risa Ø, Sonnewald U, Gibson GE. Mild reduction in the activity of the alpha-ketoglutarate
dehydrogenase complex elevates GABA shunt and glycolysis. J Neurochem. 2009 May;109 Suppl 1:21421. PMID: 19393030
25. Bak LK, Walls AB, Schousboe A, Ring A, Sonnewald U, Waagepetersen HS. Neuronal glucose but not
lactate utilization is positively correlated with NMDA-induced neurotransmission and fluctuations in
cytosolic Ca2+ levels. J Neurochem. 2009 May;109 Suppl 1:87-93. PMID: 19393013
26. Kondziella D, Eyjolfsson EM, Saether O, Sonnewald U, Risa O. Gray matter metabolism in acute and
chronic hydrocephalus. Neuroscience. 2009 Mar 17;159(2):570-7. PMID: 19171182
27. Risa O, Melø TM, Sonnewald U. Quantification of amounts and (13)C content of metabolites in brain tissue
using high- resolution magic angle spinning (13)C NMR spectroscopy. NMR Biomed. 2009 Apr;22(3):26671. PMID: 19012315
28. Bathen TF, Christensen Løhaugen GC, Brubakk AM, Gribbestad IS, Axelson DE, Skranes J. Combining
clinical assessment scores and in vivo MR spectroscopy neurometabolites in very low birth weight
adolescents. Artif Intell Med. 2009 Oct;47(2):135-46. PMID: 19411169
29. Gulati S, Berntsen EM, Solheim O, Kvistad KA, Håberg A, Selbekk T, Torp SH, Unsgaard G. Surgical
resection of high-grade gliomas in eloquent regions guided by blood oxygenation level dependent functional
magnetic resonance imaging, diffusion tensor tractography, and intraoperative navigated 3D ultrasound.
Minim Invasive Neurosurg. 2009 Feb;52(1):17-24. PMID: 19247900
30. Vaaler AE, Morken G, Linaker OM, Sand T, Kvistad KA, Bråthen G. Symptoms of epilepsy and organic
brain dysfunctions in patients with acute, brief depression combined with other fluctuating psychiatric
symptoms: a controlled study from an acute psychiatric department. BMC Psychiatry. 2009 Sep 30;9:63.
PMID: 19793395
31. Berntsen EM, Gulati S, Solheim O, Kvistad KA, Lindseth F, Unsgaard G. Integrated pre- and intraoperative
imaging in a patient with an arteriovenous malformation located in eloquent cortex. Minim Invasive
Neurosurg. 2009 Apr;52(2):83-5. PMID: 19452415
32. Widerøe M, Olsen Ø, Pedersen TB, Goa PE, Kavelaars A, Heijnen C, Skranes J, Brubakk AM, Brekken C.
Manganese-enhanced magnetic resonance imaging of hypoxic-ischemic brain injury in the neonatal rat.
Neuroimage. 2009 Apr 15;45(3):880-90. PMID: 19138750
2008
33. Larsson HB, Hansen AE, Berg HK, Rostrup E, Haraldseth O. Dynamic contrast-enhanced quantitative
perfusion measurement of the brain using T1-weighted MRI at 3T. J Magn Reson Imaging. 2008
Apr;27(4):754-62. PMID: 18383268
34. Hammer J, Alvestad S, Osen KK, Skare Ø, Sonnewald U, Ottersen OP. Expression of glutamine synthetase
and glutamate dehydrogenase in the latent phase and chronic phase in the kainate model of temporal lobe
epilepsy. Glia. 2008 Jun;56(8):856-68. PMID: 18381650
35. Sjøbakk TE, Johansen R, Bathen TF, Sonnewald U, Juul R, Torp SH, Lundgren S, Gribbestad IS.
Characterization of brain metastases using high-resolution magic angle spinning MRS. NMR Biomed. 2008
Feb;21(2):175-85. PMID: 17542042
36. Bathen TF, Holmgren K, Lundemo AG, Hjelstuen MH, Krokan HE, Gribbestad IS, Schønberg SA. Omega3 fatty acids suppress growth of SW620 human colon cancer xenografts in nude mice. Anticancer Res. 2008
Nov-Dec;28(6A):3717-23. PMID: 19189655
37. Tessem MB, Swanson MG, Keshari KR, Albers MJ, Joun D, Tabatabai ZL, Simko JP, Shinohara K, Nelson
SJ, Vigneron DB, Gribbestad IS, Kurhanewicz J. Evaluation of lactate and alanine as metabolic biomarkers
of prostate cancer using 1H HR-MAS spectroscopy of biopsy tissues. Magn Reson Med. 2008
Sep;60(3):510-6. PMID: 18727052
38. Seierstad T, Røe K, Sitter B, Halgunset J, Flatmark K, Ree AH, Olsen DR, Gribbestad IS, Bathen TF.
Principal component analysis for the comparison of metabolic profiles from human rectal cancer biopsies
and colorectal xenografts using high-resolution magic angle spinning 1H magnetic resonance spectroscopy.
Mol Cancer. 2008 Apr 25;7:33. PMID: 18439252
39. Berntsen EM, Samuelsen P, Lagopoulos J, Rasmussen IA Jr, Håberg AK, Haraldseth O. Mapping the
primary motor cortex in healthy subjects and patients with peri-rolandic brain lesions before neurosurgery.
Neurol Res. 2008 Nov;30(9):968-73. PMID: 18671900
40. Rasmussen IA, Xu J, Antonsen IK, Brunner J, Skandsen T, Axelson DE, Berntsen EM, Lydersen S, Håberg
A. Simple dual tasking recruits prefrontal cortices in chronic severe traumatic brain injury patients, but not
in controls. J Neurotrauma. 2008 Sep;25(9):1057-70. PMID: 18729718
41. Myran R, Kvistad KA, Nygaard OP, Andresen H, Folvik M, Zwart JA. Magnetic resonance imaging
assessment of the alar ligaments in whiplash injuries: a case-control study. Spine (Phila Pa 1976). 2008 Aug
15;33(18):2012-6. PMID: 18708935
42. Thuen M, Berry M, Pedersen TB, Goa PE, Summerfield M, Haraldseth O, Sandvig A, Brekken C.
Manganese-enhanced MRI of the rat visual pathway: acute neural toxicity, contrast enhancement, axon
resolution, axonal transport, and clearance of Mn(2+). J Magn Reson Imaging. 2008 Oct;28(4):855-65.
PMID: 18821627
43. Olsen Ø, Thuen M, Berry M, Kovalev V, Petrou M, Goa PE, Sandvig A, Haraldseth O, Brekken C. Axon
tracing in the adult rat optic nerve and tract after intravitreal injection of MnDPDP using a semiautomatic
segmentation technique. J Magn Reson Imaging. 2008 Jan;27(1):34-42. PMID: 18157895
44. Kondziella D, Sonnewald U, Tullberg M, Wikkelso C. Brain metabolism in adult chronic hydrocephalus. J
Neurochem. 2008 Aug;106(4):1515-24. PMID: 18419769
45. Alvestad S, Hammer J, Eyjolfsson E, Qu H, Ottersen OP, Sonnewald U. Limbic structures show altered
glial-neuronal metabolism in the chronic phase of kainate induced epilepsy. Neurochem Res. 2008
Feb;33(2):257-66. PMID: 17710539
46. Bogen IL, Risa O, Haug KH, Sonnewald U, Fonnum F, Walaas SI. Distinct changes in neuronal and
astrocytic amino acid neurotransmitter metabolism in mice with reduced numbers of synaptic vesicles. J
Neurochem. 2008 Apr 9. [Epub ahead of print] PMID: 18346203
47. Schousboe A, Bak LK, Sickmann HM, Sonnewald U, Waagepetersen HS. Energy substrates to support
glutamatergic and GABAergic synaptic function: role of glycogen, glucose and lactate. Neurotox Res. 2007
Dec;12(4):263-8. Review. PMID: 18201953
2007
48. Skjold A, Amundsen BH, Wiseth R, Støylen A, Haraldseth O, Larsson HB, Jynge P. Manganese
dipyridoxyl-diphosphate (MnDPDP) as a viability marker in patients with myocardial infarction. J Magn
Reson Imaging. 2007 Sep;26(3):720-7. PMID: 17729351
49. Hagen AI, Kvistad KA, Maehle L, Holmen MM, Aase H, Styr B, Vabø A, Apold J, Skaane P, Møller P.
Sensitivity of MRI versus conventional screening in the diagnosis of BRCA-associated breast cancer in a
national prospective series. Breast. 2007 Aug;16(4):367-74. PMID: 17317184
50. Skranes J, Vangberg TR, Kulseng S, Indredavik MS, Evensen KA, Martinussen M, Dale AM, Haraldseth O,
Brubakk AM. Clinical findings and white matter abnormalities seen on diffusion tensor imaging in
adolescents with very low birth weight. Brain. 2007 Mar;130(Pt 3):654-66. PMID: 17347255
51. Alvestad S, Goa PE, Qu H, Risa Ø, Brekken C, Sonnewald U, Haraldseth O, Hammer J, Ottersen OP,
Håberg A. In vivo mapping of temporospatial changes in manganese enhancement in rat brain during
epileptogenesis. Neuroimage. 2007 Oct 15;38(1):57-66. PMID: 17822925
52. Xu J, Rasmussen IA, Lagopoulos J, Håberg A. Diffuse axonal injury in severe traumatic brain injury
visualized using high-resolution diffusion tensor imaging. J Neurotrauma. 2007 May;24(5):753-65. PMID:
17518531
53. Rasmussen IA Jr, Lindseth F, Rygh OM, Berntsen EM, Selbekk T, Xu J, Nagelhus Hernes TA, Harg E,
Håberg A, Unsgaard G. Functional neuronavigation combined with intra-operative 3D ultrasound: initial
experiences during surgical resections close to eloquent brain areas and future directions in automatic brain
shift compensation of preoperative data. Acta Neurochir (Wien). 2007;149(4):365-78. PMID: 17308976
54. Xu J, Rasmussen IA, Berntsen EM, Moss K, Shnier R, Lagopoulos J, Malhi GS. A growth in bipolar
disorder? Acta Psychiatr Scand. 2007 Mar;115(3):246-50. PMID: 17302626
55. Kristoffersen A. Optimal estimation of the diffusion coefficient from non-averaged and averaged noisy
magnitude data. J Magn Reson. 2007 Aug;187(2):293-305. PMID: 17572124
56. Eide KR, Ødegård A, Myhre HO, Haraldseth O. Initial observations of endovascular aneurysm repair using
Dyna-CT. J Endovasc Ther. 2007 Feb;14(1):50-3. PMID: 17291152
57. Lovatt D, Sonnewald U, Waagepetersen HS, Schousboe A, He W, Lin JH, Han X, Takano T, Wang S, Sim
FJ, Goldman SA, Nedergaard M. The transcriptome and metabolic gene signature of protoplasmic
astrocytes in the adult murine cortex. J Neurosci. 2007 Nov 7;27(45):12255-66. PMID: 17989291
58. Kondziella D, Alvestad S, Vaaler A, Sonnewald U. Which clinical and experimental data link temporal lobe
epilepsy with depression? J Neurochem. 2007 Dec;103(6):2136-52. Review. PMID: 17887964
59. Melø TM, Sonnewald U, Bastholm IA, Nehlig A. Astrocytes may play a role in the etiology of absence
epilepsy: a comparison between immature GAERS not yet expressing seizures and adults. Neurobiol Dis.
2007 Nov;28(2):227-35. PMID: 17719229
60. Santos SS, Leite SB, Sonnewald U, Carrondo MJ, Alves PM. Stirred vessel cultures of rat brain cells
aggregates: characterization of major metabolic pathways and cell population dynamics. J Neurosci Res.
2007 Nov 15;85(15):3386-97. PMID: 17628504
61. Yudkoff M, Daikhin Y, Melø TM, Nissim I, Sonnewald U, Nissim I. The ketogenic diet and brain
metabolism of amino acids: relationship to the anticonvulsant effect. Annu Rev Nutr. 2007;27:415-30.
Review. PMID: 17444813
62. Olstad E, Olsen GM, Qu H, Sonnewald U. Pyruvate recycling in cultured neurons from cerebellum. J
Neurosci Res. 2007 Nov 15;85(15):3318-25. PMID: 17304574
63. Brenner E, Sonnewald U, Schweitzer A, Andrieux A, Nehlig A. Hypoglutamatergic activity in the STOP
knockout mouse: a potential model for chronic untreated schizophrenia. J Neurosci Res. 2007 Nov
15;85(15):3487-93. PMID: 17304567
64. Olstad E, Qu H, Sonnewald U. Long-term kainic acid exposure reveals compartmentation of glutamate and
glutamine metabolism in cultured cerebellar neurons. Neurochem Int. 2007 Jun;50(7-8):1004-13. PMID:
17196710
65. Sjøbakk TE, Johansen R, Bathen TF, Sonnewald U, Kvistad KA, Lundgren S, Gribbestad IS. Metabolic
profiling of human brain metastases using in vivo proton MR spectroscopy at 3T. BMC Cancer. 2007 Jul
27;7:141.PMID: 17662122
66. Jensen LR, Berge K, Bathen TF, Wergedahl H, Schønberg SA, Bofin A, Berge RK, Gribbestad IS. Effect of
dietary tetradecylthioacetic acid on colon cancer growth studied by dynamic contrast enhanced MRI. Cancer
Biol Ther. 2007 Nov;6(11):1810-6. PMID: 18287814
67. Lyng H, Sitter B, Bathen TF, Jensen LR, Sundfør K, Kristensen GB, Gribbestad IS. Metabolic mapping by
use of high-resolution magic angle spinning 1H MR spectroscopy for assessment of apoptosis in cervical
carcinomas. BMC Cancer. 2007 Jan 17;7:11. PMID: 17233882
68. Bathen TF, Jensen LR, Sitter B, Fjösne HE, Halgunset J, Axelson DE, Gribbestad IS, Lundgren S. MRdetermined metabolic phenotype of breast cancer in prediction of lymphatic spread, grade, and hormone
status. Breast Cancer Res Treat. 2007 Aug;104(2):181-9. PMID: 17061040
69. Håberg A, Qu H, Hjelstuen MH, Sonnewald U. Effect of the pyrrolopyrimidine lipid peroxidation inhibitor
U-101033E on neuronal and astrocytic metabolism and infarct volume in rats with transient middle cerebral
artery occlusion. Neurochem Int. 2007 Jun;50(7-8):932-40. PMID: 17241701
2006
70. Skjold A, Kristoffersen A, Vangberg TR, Haraldseth O, Jynge P, Larsson HB. An apparent unidirectional
influx constant for manganese as a measure of myocardial calcium channel activity. J Magn Reson Imaging.
2006 Nov;24(5):1047-55. PMID: 17024667
71. Vangberg TR, Skranes J, Dale AM, Martinussen M, Brubakk AM, Haraldseth O. Changes in white matter
diffusion anisotropy in adolescents born prematurely. Neuroimage. 2006 Oct 1;32(4):1538-48. PMID:
16843682
72. Huszthy PC, Brekken C, Pedersen TB, Thorsen F, Sakariassen PO, Skaftnesmo KO, Haraldseth O, Lønning
PE, Bjerkvig R, Enger PO. Antitumor efficacy improved by local delivery of species-specific endostatin. J
Neurosurg. 2006 Jan;104(1):118-28. PMID: 16509155
73. Brekke C, Lundervold A, Enger PØ, Brekken C, Stålsett E, Pedersen TB, Haraldseth O, Krüger PG,
Bjerkvig R, Chekenya M. NG2 expression regulates vascular morphology and function in human brain
tumours. Neuroimage. 2006 Feb 1;29(3):965-76. PMID: 16253523
74. Kondziella D, Brenner E, Eyjolfsson EM, Sonnewald U. How do glial-neuronal interactions fit into current
neurotransmitter hypotheses of schizophrenia? Neurochem Int. 2007 Jan;50(2):291-301. Review. PMID:
17084946
75. Olstad E, Qu H, Sonnewald U. Glutamate is preferred over glutamine for intermediary metabolism in
cultured cerebellar neurons. J Cereb Blood Flow Metab. 2007 Apr;27(4):811-20. PMID: 17033695
76. Bak LK, Waagepetersen HS, Melø TM, Schousboe A, Sonnewald U. Complex glutamate labeling from [U13C]glucose or [U-13C]lactate in co-cultures of cerebellar neurons and astrocytes. Neurochem Res. 2007
Apr-May;32(4-5):671-80. PMID: 17021949
77. Mutkus L, Aschner JL, Syversen T, Shanker G, Sonnewald U, Aschner M. Mercuric chloride inhibits the in
vitro uptake of glutamate in GLAST- and GLT-1-transfected mutant CHO-K1 cells. Biol Trace Elem Res.
2006 Mar;109(3):267-80. PMID: 16632895
78. Melø TM, Nehlig A, Sonnewald U. Neuronal-glial interactions in rats fed a ketogenic diet. Neurochem Int.
2006 May-Jun;48(6-7):498-507. PMID: 16542760
79. Melø TM, Sonnewald U, Touret M, Nehlig A. Cortical glutamate metabolism is enhanced in a genetic
model of absence epilepsy. J Cereb Blood Flow Metab. 2006 Dec;26(12):1496-506. PMID: 16538229
80. Eyjolfsson EM, Brenner E, Kondziella D, Sonnewald U. Repeated injection of MK801: an animal model of
schizophrenia? Neurochem Int. 2006 May-Jun;48(6-7):541-6. PMID: 16517016
81. Sonnewald U, Kortner TM, Qu H, Olstad E, Suñol C, Bak LK, Schousboe A, Waagepetersen HS.
Demonstration of extensive GABA synthesis in the small population of GAD positive neurons in cerebellar
cultures by the use of pharmacological tools. Neurochem Int. 2006 May-Jun;48(6-7):572-8. PMID:
16516347
82. Bak LK, Schousboe A, Sonnewald U, Waagepetersen HS. Glucose is necessary to maintain
neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons. J Cereb Blood
Flow Metab. 2006 Oct;26(10):1285-97. PMID: 16467783
83. Santos SS, Gibson GE, Cooper AJ, Denton TT, Thompson CM, Bunik VI, Alves PM, Sonnewald U.
Inhibitors of the alpha-ketoglutarate dehydrogenase complex alter [1-13C]glucose and [U-13C]glutamate
metabolism in cerebellar granule neurons. J Neurosci Res. 2006 Feb 15;83(3):450-8. PMID: 16416424
84. Kondziella D, Brenner E, Eyjolfsson EM, Markinhuhta KR, Carlsson ML, Sonnewald U. Glial-neuronal
interactions are impaired in the schizophrenia model of repeated MK801 exposure.
Neuropsychopharmacology. 2006 Sep;31(9):1880-7. PMID: 16395297
85. McKenna MC, Waagepetersen HS, Schousboe A, Sonnewald U. Neuronal and astrocytic shuttle
mechanisms for cytosolic-mitochondrial transfer of reducing equivalents: current evidence and
pharmacological tools. Biochem Pharmacol. 2006 Feb 14;71(4):399-407. Review. PMID: 16368075
86. Sjøbakk TE, Lundgren S, Kristoffersen A, Singstad T, Svarliaunet AJ, Sonnewald U, Gribbestad IS.
Clinical 1H magnetic resonance spectroscopy of brain metastases at 1.5T and 3T. Acta Radiol. 2006
Jun;47(5):501-8. PMID: 16796315
87. Bathen TF, Sjöbakk TE, Skranes J, Brubakk AM, Vik T, Martinussen M, Myhr GE, Gribbestad IS, Axelson
D. Cerebral metabolite differences in adolescents with low birth weight: assessment with in vivo proton MR
spectroscopy. Pediatr Radiol. 2006 Aug;36(8):802-9. PMID: 16703344
88. Sitter B, Lundgren S, Bathen TF, Halgunset J, Fjosne HE, Gribbestad IS. Comparison of HR MAS MR
spectroscopic profiles of breast cancer tissue with clinical parameters. NMR Biomed. 2006 Feb;19(1):3040. PMID: 16229059
89. Håberg A, Qu H, Sonnewald U. Glutamate and GABA metabolism in transient and permanent middle
cerebral artery occlusion in rat: importance of astrocytes for neuronal survival. Neurochem Int. 2006 MayJun;48(6-7):531-40. Epub 2006 Feb 28. PMID: 16504342
90. Vik A, Kvistad KA, Skandsen T, Ingebrigtsen T. [Diffuse axonal injury in traumatic brain injury]. Tidsskr
Nor Laegeforen. 2006 Nov 16;126(22):2940-4. Review. Norwegian. PMID: 17117192
91. Brurberg KG, Thuen M, Ruud EB, Rofstad EK. Fluctuations in pO2 in irradiated human melanoma
xenografts. Radiat Res. 2006 Jan;165(1):16-25. PMID: 16392958
92. Tessem MB, Bathen TF, Löfgren S, Saether O, Mody V, Meyer L, Dong X, Söderberg PG, Midelfart A.
Biological response in various compartments of the rat lens after in vivo exposure to UVR-B analyzed by
HR-MAS 1H NMR spectroscopy. Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5404-11. PMID: 17122130
93. Fris M, Tessem MB, Saether O, Midelfart A. Biochemical changes in selenite cataract model measured by
high-resolution MAS H NMR spectroscopy. Acta Ophthalmol Scand. 2006 Oct;84(5):684-92. PMID:
16965502
94. Tessem MB, Midelfart A, Cejková J, Bathen TF. Effect of UVA and UVB irradiation on the metabolic
profile of rabbit cornea and lens analysed by HR-MAS 1H NMR spectroscopy. Ophthalmic Res.
2006;38(2):105-14. PMID: 16374053
2005
95. Martinussen M, Fischl B, Larsson HB, Skranes J, Kulseng S, Vangberg TR, Vik T, Brubakk AM,
Haraldseth O, Dale AM. Cerebral cortex thickness in 15-year-old adolescents with low birth weight
measured by an automated MRI-based method. Brain. 2005 Nov;128(Pt 11):2588-96. PMID: 16123146
96. Thuen M, Singstad TE, Pedersen TB, Haraldseth O, Berry M, Sandvig A, Brekken C. Manganese-enhanced
MRI of the optic visual pathway and optic nerve injury in adult rats. J Magn Reson Imaging. 2005
Oct;22(4):492-500. PMID: 16161073
97. Brenner E, Kondziella D, Håberg A, Sonnewald U. Impaired glutamine metabolism in NMDA receptor
hypofunction induced by MK801. J Neurochem. 2005 Sep;94(6):1594-603. PMID: 16045441
98. Mutkus L, Aschner JL, Syversen T, Shanker G, Sonnewald U, Aschner M. In vitro uptake of glutamate in
GLAST- and GLT-1-transfected mutant CHO-K1 cells is inhibited by the ethylmercury-containing
preservative thimerosal. Biol Trace Elem Res. 2005;105(1-3):71-86. PMID: 16034155
99. Morken TS, Sonnewald U, Aschner M, Syversen T. Effects of methylmercury on primary brain cells in
mono- and co-culture. Toxicol Sci. 2005 Sep;87(1):169-75. PMID: 15958655
100. Waagepetersen HS, Qu H, Sonnewald U, Shimamoto K, Schousboe A. Role of glutamine and neuronal
glutamate uptake in glutamate homeostasis and synthesis during vesicular release in cultured glutamatergic
neurons. Neurochem Int. 2005 Jul;47(1-2):92-102. PMID: 15921825
101. Melø TM, Nehlig A, Sonnewald U. Metabolism is normal in astrocytes in chronically epileptic rats: a (13)C
NMR study of neuronal-glial interactions in a model of temporal lobe epilepsy. J Cereb Blood Flow Metab.
2005 Oct;25(10):1254-64. PMID: 15902201
102. McKenna MC, Sonnewald U. GABA alters the metabolic fate of [U-13C]glutamate in cultured cortical
astrocytes. J Neurosci Res. 2005 Jan 1-15;79(1-2):81-7. PMID: 15593283
103. Qu H, Eloqayli H, Sonnewald U. Pentylenetetrazole affects metabolism of astrocytes in culture. J Neurosci
Res. 2005 Jan 1-15;79(1-2):48-54. PMID: 15562439
104. Waagepetersen H, Melø T, Schousboe A, Sonnewald U. Homeostasis of neuroactive amino acids in
cultured cerebellar and neocortical neurons is influenced by environmental cues. J Neurosci Res. 2005 Jan
1-15;79(1-2):97-105. PMID: 15558763
105. Martinez I, Bathen T, Standal IB, Halvorsen J, Aursand M, Gribbestad IS, Axelson DE. Bioactive
compounds in cod (Gadus morhua) products and suitability of 1H NMR metabolite profiling for
classification of the products using multivariate data analyses. J Agric Food Chem. 2005 Aug
24;53(17):6889-95. PMID: 16104816
106. Nygaard ØP, Kolstad F, Kvistad KA, Zwart JA, Solberg T, Lied B, Myrseth E, Helseth E, Baardsen R.
[Chronic whiplash syndrome is no indication for craniocervical fixation]. Tidsskr Nor Laegeforen. 2005
Nov 3;125(21):2939-41. Review. Norwegian. PMID: 16276376
107. Kolstad F, Myhr G, Kvistad KA, Nygaard OP, Leivseth G. Degeneration and height of cervical discs
classified from MRI compared with precise height measurements from radiographs. Eur J Radiol. 2005
Sep;55(3):415-20. PMID: 16129250
108. Saether O, Krane J, Risa Ø, Cejková J, Midelfart A. High-resolution MAS 1H NMR spectroscopic analysis
of rabbit cornea after treatment with dexamethasone and exposure to UV-B radiation. Curr Eye Res. 2005
Dec;30(12):1041-9. PMID: 16354617
109. Risa O, Saether O, Kakar M, Mody V, Löfgren S, Söderberg PG, Krane J, Midelfart A. Time dependency of
metabolic changes in rat lens after in vivo UVB irradiation analysed by HR-MAS 1H NMR spectroscopy.
Exp Eye Res. 2005 Oct;81(4):407-14. PMID: 16185952
110. Tessem MB, Bathen TF, Cejková J, Midelfart A. Effect of UV-A and UV-B irradiation on the metabolic
profile of aqueous humor in rabbits analyzed by 1H NMR spectroscopy. Invest Ophthalmol Vis Sci. 2005
Mar;46(3):776-81. PMID: 15728530
Panel 4B
Image Guided Therapy and
Minimally Invasive Interventions
1.2 Evalutation unit (level 2) Image Guided Therapy and Minimally Invasive Interventions
1.2.1 Organization, research leadership, strategy and resource situation
St. Olavs Hospital, NTNU and SINTEF have a long and successful tradition of collaboration in
Image guided Therapy and Minimally Invasive Interventions since early 1990ties. The unit
Image Guided Therapy and Minimally Invasive Interventions is anchored in the National Centre
of 3D ultrasound and image guided surgery that was established by the Norwegian Government
in 1995 and also has strong collaboration with the MR and ultrasound groups in Trondheim. The
unit covers researchers from department of Medical Technology at SINTEF as well as several
departments at the Faculty of Medicine and St. Olavs Hospital. The unit consists of an
interdisciplinary core team of 35 people covering clinical and technological researchers and is
headed by an overall research director supported by a steering committee and an international
advisory board. The unit is participating in projects from basic to applied clinical and
technological translational research funded from the Government, EU, The Research Council of
Norway, own resources and industry. Dissemination is performed through scientific publication,
conference presentations, popular media and through courses and educational activities.
Strategy and aims of the research unit:
The overall aim of the unit is to improve patient care by research and development of medical
technology and methods for treatment, giving less trauma for patients, improved safety and
quality in treatment as well as shorter hospital stay and rehabilitation time, hence establishing
cost effective solutions for society and health care providers. Goals are also to improve quality
of academic translational and interdisciplinary research, spread of competence as well as
increase industrial exploitation and innovation (figure 1).
Figure 1: Relevance and impact/goal of research activities of the unit that affect the strategy
The strategy of the unit is to:
• Focus own research within ultrasound and image guided therapy that makes it possible to be
at a high national and international level and establish collaboration with other well
recognized research groups that give a good supplement to own research.
• Work in interdisciplinary teams of clinical personnel and researchers with technological
background, making it possible to develop technology meeting the demands in the clinic.
• Establish international collaboration through participation in EU projects and other
international collaborative projects.
• Ensure high quality and up to date research infrastructure for clinical and translational
research within medical technology and image guided interventions, making the unit an
attractive collaborator for national and international partners, including universities, research
institutes, academia and industry.
1
• Increase competence through education of both clinical and technological personnel through
PhD and courses as well as ensure presence of senior competent personnel.
• Disseminate results from the research activity and spread competence through scientific
journals as well as in other media nationally and internationally, which is in accordance with
St. Olavs Hospital, NTNU and SINTEF strategies.
Organization, management and decision-making:
The unit is anchored at the National Centre for 3D ultrasound and image guided surgery, which
is organized with an overall coordinator, Professor and Research Director Toril A Nagelhus
Hernes, who also has responsibility for the technological researchers in the unit.
Interdisciplinary teams of 5-10 persons within each clinical area, are headed by one responsible
clinician and one technological project leader. The coordinator together with the clinical and
technological project leaders within each clinical area, constitute the management team of the
unit. Technological and clinical PhDs/post docs and researchers are part of the teams that meet
on a daily basis in the operating rooms or in the laboratories, where the research activity is
performed. There are significant synergies within the clinical areas, making it possible to
develop technological research approaches for meeting the demands in various clinical areas.
Therefore, a pool of technological researchers cooperates closely with all clinical project teams.
Status reports from every clinical areas are outlined quarterly, including a summary of results
the foregoing 3 months, plans for the coming three months as well as explanations for any
changes in plans that may have occurred due to unpredictable events for example not available
patients, failure in achievements, further developments in one direction due to successful results
and/or initiation of new projects. The centre is directed by a steering committee, which has the
overall responsibility for deciding the budget and projects to be fulfilled the coming year by the
unit. The steering committee is represented by the collaborating organizations St. Olavs
Hospital, NTNU and SINTEF and meets once a year, typically in the autumn. In this meeting
the management team presents the results for the past year as well as the plans for the coming
year and the steering committee gives the direction for research, including budget decisions. The
unit also has an advisory board, that advices the centre about future strategies and research
activities. The advisory board meets every 1-2 year and consists of highly skilled clinical and
academic persons, who are international leaders within fields of research, relevant for the centre.
In addition, representatives from all Norwegian Regional Health Authorities are included in
order to ensure interaction with hospitals in Norway. Members of the advisory board are:
•
•
•
•
•
•
•
•
•
•
Vice Director Jan Eirik Thoresen, Oslo Univ. Hospital (leader advisory board)
Prof Jenny Dankelman, Delft University of Technology, The Netherlands
Prof Lars Norgren, University Hospital, and University of Örebro, Sweden
Prof Vera van Velthoven, Freiburg Universitetsklinikk, Germany (not 11Nov09)
Prof Odd Helge Gilja, Haukeland University Hospital, Bergen
Prof Einar Stranden, Oslo University Hospital, Aker, University of Oslo
Prof Bjørn Edwin, Oslo Univ. Hospital, Interventional Centre, University of Oslo
Prof Erik Fosse, Oslo Univ. Hospital, Interventional Centre, University of Oslo
Prof Roar Kloster, University Hospital of Northern Norway (UNN), Tromsø
Prof. and Research Director Siv Mørkved, St. Olavs Hospital, Trondheim
The complete research unit gathers once a year, typically in January, in a strategy workshop
where the results for the past year are summarized, new ideas are evaluated and plans for
projects the coming year are outlined. Decisions and selection of projects to be run are based on
direction from the steering committee and advisory board, funding sources (after applications)
as well as selection criteria covering: clinical benefit/user needs, technological challenges, risk
of failure/likelihood of success, market potential, strategic relevance within the field of research
of the unit as well competition, collaboration possibilities, trends and available resources. New
projects run in the unit are organized with a project leader and clinical and technical personnel
are included in accordance with the competence needed in order to fulfill the goals and
deliveries in the specific project.
2
Resources and personnel:
The unit is highly interdisciplinary with app 50/50 of technologists/clinical personnel
respectively and covers mainly research areas within neuro-, vascular- and laparoscopic surgery.
Clinical personnel are also dedicated to the ordinary patient treatment activity at the hospital.
Out of core team of 35 people about 25 person-years are estimated used for research, education
and dissemination activity, including PhD and post docs, project management and
administration. Personnel within the core team with CV attached are (in alphabetical order):
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
Ass. Prof, PhD Tore Amundsen, clinical responsible lung (St.Olav´sUniversity Hospital/NTNU)
Senior advisor, Innovation, Espen Aspnes, (SINTEF)
Ass. Prof. PhD, MD Torbjørn Dahl, vascular surgery (St. Olavs Hospital/NTNU)
Ass. Prof. Senior Researcher, technology, PhD Rune Hansen, PL vascular surgery (SINTEF/NTNU)
Prof.II, Research director and coordinator, PhD Toril A Nagelhus Hernes, technology (SINTEF/NTNU)
Senior Researcher, technology PhD, Thomas Langø, PL, Laparoscopic surgery (SINTEF)
Ass Prof. Senior Researcher, technology, PhD, Frank Lindseth, PL navigation (SINTEF/NTNU)
Researcher technology, PhD, Sebastien Muller (SINTEF)
Prof. Emeritius Hans Olav Myhre,clinical responsible,vascular surgery(St.Olav´sUniversity Hospital/NTNU)
Prof.II Ronald Mårvik, clinical responsible, laparoscopy (St. Olavs Hospital/NTNU)
Post Doc and Researcher, PhD technology, Ingerid Reinertsen (SINTEF/NTNU)
Research Manager Merete Rørvik (SINTEF/Innomed)
Prof II Warren Sandberg, clinical anesthesiology (NTNU)
Senior Researcher Tormod Selbekk, PL technology Neurosurgery (SINTEF)
Prof Sverre Torp, Pathology (NTNU)
Research Manager Else Thurmann-Nielsen (SINTEF/Unimed Innovation)
Prof.II Geirmund Unsgård, clinical responsible,neurosurgery (St.Olav´s University Hospital/NTNU)
MD, Senior Consult. Asbjørn Ødegård, Vascular therapy/radiology (St.Olav´sUniversity Hospital)
Technical staff at the Operating room of the Future (research infrastructure) and related
activities as Innomed (National program for innovation in health care) and Unimed Innovation
(administration of clinical trials in The Central Norway Regional Health Authority) adds up to
47 people. The background of the researchers in the core team are either clinical MD or
technological (MSc) within computer science, image and signal processing, physics, medical
technology, mathematics or cybernetics. 15 out of 35 have a PhD degree. 13 are PhD students, 7
are professors within the field, but no full time professor is employed working only with image
guided minimal invasive interventions. 20 % of the core team is women (2 of the women have
PhD). 2 persons are from outside Norway. Many of the researchers are employed at two places,
which encourage collaboration and translational clinical research. The role as National Centers
of Competence, is the most important activity and makes it possible to ensure long-term
competence development and a focused research strategy/activity within the unit.
Publication and dissemination
As a National centre of competence
within 3D ultrasound and image
guided surgery and as a National
Centre for advanced Laparoscopic
surgery, the unit has a role not only to
perform research, educate PhD degrees
and run courses, but also to spread
competence and to disseminate results
and new knowledge received from the
research activities. In the period 20052010: >100 publications in peer review
Figure 2: Dissemination and publication
journals and books relevant for the field of research, >268 conference presentations, >69
dissemination and other media presentations nationally and internationally and >30 courses
have been held. This is satisfying due to available resources and well in accordance with the
strategies of St. Olavs Hospital, NTNU and SINTEF.
3
Research Infrastructure:
The unit has through the years focused on
building up important infrastructures as a
platform for the research activity in the unit:
• Operating Room of the Future
• Platform: Image guided interventions
• Various prototypes and phantoms developed
on a project basis including algorithms,
visualization modules, ultrasound probes,
scanners and positioning technology
• Simulators:
Training
surgical
skills,
(National Centre for Advanced Laparoscopic Figure 3: Operating Room of the Future, St Olavs H.
6 operating rooms for research, innovation, education,
surgery, NSALK) and Ultrasound simulator
communicating with auditorium in knowledge center
The unit also works closely together with the medical imaging groups at NTNU and uses the
ultrasound and MR facilities when needed as well as visualization facilities established for
visualization of oil reservoir data at Inst of Petroleum technology. The navigation platform for
image guided interventions integrates navigation technology with intraoperative ultrasound
imaging, advanced visualization and display technology, making it possible to navigate inside
the body and improve outcome of patient treatment. The platform has been an important tool for
international and industrial collaboration as well as an important reason why the research unit is
internationally recognized. The Operating Room of the Future was opened in 2005 after own
investment of app 82 mill NOK of which 25 mill NOK was investment from industrial partners.
The facilities are now expanded to include one operating room dedicated for research activities
within each centre of St. Olavs Hospital (6 in all, figure 3,4). The Operating Room of the Future
has also established collaboration with Mass General Hospital in Boston and has a Prof II
related to the infrastructure (Warren Sandberg). The research Infrastructure has a leader group
and a scientific board, which reviews all projects that are applied for to use the infrastructure for
research. This ensures high quality protocols for the research and further that all research
projects are in conjunction with rules, ethical standards and regulations in Norway.
Due to rapid development, the
research facilities need to be
upgraded in order to fulfill the
needs and ambitions. St. Olavs
Hospital has therefore applied for
396,2 mill NOK of which 107, 6
mill NOK is funding from the
Research Council of Norway in
equipment and running costs
(2011-2020) to establish NorMIT:
Norwegian Centre for minimally
invasive therapy and
Figure 4: Clinical study of ultrasound guided navigated neurosurgery
medical technologies as National
research infrastructure for minimally invasive therapy, translational research and medical
technologies. NorMIT is a collaboration between Operating Room of the Future and The
Interventional Centre at Oslo University Hospital. The application got highest score,
exceptionally good, on all evaluation parameters (benefit to research, management and
applicant, research groups, feasibility, international collaboration, strategic importance, project
quality) and is now on the National map of Research Infrastructure in Norway. Hopefully,
funding will be achieved so the infrastructure for the research unit is secured for coming years.
4
Surgical interventions are changing dramatically as conventional open surgery is increasingly
being replaced with less invasive, non-invasive and endoscopic procedures. Minimally Invasive
Image guided Therapy (MIT) gives less trauma for patients and reduces hospital stay and costs.
The research unit was to our knowledge the first group in the world that in 1997 demonstrated
the possibility of deep-seated brain tumor resection guided by intraoperative navigated 3D
ultrasound (Grønningsaether et al, Neurosurgery, 2000/Unsgård et al, Neurosurgery 2002).
Based on the technology and innovation performed at the research unit, the spin off company
MISON (now Sonowand) was established in 1998. Since then the activity and usage of
ultrasound and image guided minimally invasive surgery has been explored in a variety of
clinical application areas as in laparoscopy (Langø et al, MITAT 2008/Solberg et al, MITAT
2009) and endovascular procedures (Brekken et al, J Endovasc Ther, 2008/ Manstad-Hulaas et
al, Eur Surg Res 2008). The group has also received a number of prices and awards based on the
innovation and research deliveries. The activity at the research unit is interdisciplinary covering
applied technological and clinical translational research in medical technologies and image
guided interventions. The unit covers international trends as well as national and international
political goals and challenges specified both in Norwegian governmental reports as well as in
EU 7 and 8 fp, emphasizing demands for research and innovation improving quality of health
care deliveries.
Research profile of unit:
The
research
unit
has
deliveries and responsibilities
that are fulfilled in roles as
national centers of 3D
ultrasound and advanced
laparoscopic surgery, such as
course arrangements, dissemination and competence
exploration
activities
in
addition to research. The
activity of the unit covers
from
basic
to
applied
interdisciplinary
and
translational research as well
Figure 5: Research profile: The unit performs research through an iterative research
as technological research and
process based on state of the art technologies, adaptation, development and clinical
innovation activities. The
testing/translational interdisciplinary activity. Clinical pilot testing and redevelopment can
be performed in order to achieve technology that improves efficiency and efficacy of patient
work also is highly synergetic
treatment
with the research within MR
and ultrasound being performed by the other units at NTNU. The main way the research activity
is performed is through an iterative process evolved by identification of clinical demands,
research and development, prototyping and clinical translational research,- all performed in a
close interdisciplinary team (figure 5). The main research areas are (all interdisciplinary):
• Clinical research, feasibility and testing including identification of demands and
requirements of minimal invasive methods and technology for improved therapy
• Technological research within medical technology aiming at improving image guided
therapy: navigation, visualization, ultrasound for diagnostics and guidance of procedures,
ultrasound for contrast imaging and drug-delivery applications (nanomedicine), image
processing and visualization, calibration, positioning, micro-positioning systems, prototype
development based on user demands, simulations and training technology
5
•
•
Translational research bringing technology and prototype technology into clinical practice
Innovation and industrial exploration as recognized and exampled by development of
prototypes both on navigation technology and ultrasound simulators to be commercialized
by the Norwegian medical technology companies
The mix of various funding sources also makes the research unit robust and able to perform
basic research, applied research and innovative research in collaboration with the industry
(funding sources in % of total: 23% own, 35% government, 18 % The Research Council of
Norway, 10% EU, 14% industry). In addition the research unit is involved in various EU
projects as specified in the chapter of national and international collaboration.
Societal relevance, impact and innovation:
The activity in the unit for minimally invasive therapy and image-guided interventions has
impact on patients, academia, industry and the health sector as emphasized in figure 1. The
impact is recognized through the deliveries in the portfolio of projects run by the unit, covering
exploration of new knowledge, publications, prototype development of products meeting user
needs as well as studies testing new technology and medical devices in a clinical environment.
The research at the unit gives improved competence in the health care sector and ensures
product development meeting user demands as delivered by industry.
Impact on patient treatment
The new technologies made at the research unit make the treatment procedures more accurate,
safer and/or more user friendly by introduction of images and technology that makes it easier to
see remaining tumor tissue, detect vessels to avoid severe bleedings and display anatomy
making it possible to guide instruments and resection tools with better precision and accuracy.
New technology explored at the research unit also makes it possible to perform therapy of
patients by minimal access to the lesion and thereby decrease trauma for the patient. Some
example results from the research, demonstrating innovation of new technology improving
treatment and surgical approaches are (documented by technology/clinical feasibility studies
from the unit):
• Intraoperative 3D ultrasound and navigation improving delineation and resection of brain
tumors (Unsgård et al Acta Neurochirurgica, 2005/Rygh et al Acta Neurochirurgica 2008)
• Endovascular treatment of aortic disease versus open surgery (Myhre HO, TDnlf, 2009/
Aasland J, Int Angiol. 2005)
• New ultrasound and display technology for vessel detection and visualization in guidance of
surgical interventions (Lindseth et al, Neurosurgery, 2009/Hernes et al, International Journal
of Medical Robotics and Computer Assisted Surgery, 2006),
• New ultrasound technology for contrast imaging for better diagnosis and future
nanomedicine application (Hansen et al, Ferroelectrics and Frequency Control, 2009),
• Ultrasound strain imaging for improved tumor detection and delineation (Selbekk et al,
Ultrasound in Medicine & Biology, 2010),
• Vessel based registration for correction of brain shift improving guidance of brain surgery
(Reinertsen et al, Medical analysis, 2007),
• Navigation of endoscopes using intraoperative ultrasound (Rygh et al, Minim Invasive
Neurosurgery, 2006/Langø et al, MITAT 2008)
• New ultrasound probes for more accurate and safe surgery in for example transsphenoidal
surgery (Solheim et al, Neurosurgery, 2010)
As seen from the publication list, the scientific dissemination activity is performed by the core
personnel in the research unit, however spread relatively per person approximately due to the
amount of time spend for research in priority for other activities. The research unit is anchored
in the hospital and all research is therefore directly related to user and clinical demands. The
unit runs >20 projects and clinical trials/year (own initiated and external funded from EU, The
6
Research Council of Norway and industry), performs conference and workshop arrangements as
the international conference for the Society for Medical Innovation and Technology
(SMIT2010, Sept 2010), runs 13 ongoing PhDs (7 clinical, 6 technological) and 1 post doc, has
12 fulfilled PhDs and 2 fulfilled post docs from the research unit since 1992, runs >30 Course
for educational activity (2005-2010) and received 12 awards since 1995 based on the activity.
Example user and researcher driven large scale projects run within the unit at the moment are:
• National Centre of 3D ultrasound in minimally invasive therapy is funded by the Norwegian
Health Authorities. The centre consists of St. Olavs Hospital, NTNU and SINTEF, since 1995.
The research activity of the centre is related to methods and technology for minimally invasive
ultrasound and image guided interventions within neurosurgery, vascular surgery and
laparoscopic surgery. The Center houses 5 professor II, 13 PhD,1post doc students/year and uses
Operating Room of the Future as a core infrastructure. (Budget: app 10 mill NOK /year)
• National Center of Advanced Laparoscopic Surgery, Health Authority in Norway (NSALK St.
Olavs Hospital). NSALK has as its main tasks to perform education and training, research and
development with laparoscopy and image guided therapy. (Budget: app 2 mill NOK/year), >30
courses in the period 2005-2010.
• e-MIT, Enhanced Minimally invasive Therapy (FRIMED, Research Council, SINTEF, St.
Olavs Hospital, NTNU). The project aims at developing technology for minimally invasive
therapy for various clinical applications as lung, spine, vascular and laparoscopic procedures.
(Budget: app 3.5 mill NOK/year, 2010-2013).
• Cooperation Support Through Transparency (COSTT, VERDICT-NFR, NTNU), aiming at
improving efficiency and collaboration in health care through transparency of the process of
patient treatment, including industrial (Sonitor) and academic partners.
13 PhD projects and are involved in the National research school in medical imaging, NTNU
• NorMIT: Norwegian Centre for minimal invasive technology and medical technology,
appication to be established as a national research infrastructure. Collaboration with Oslo
University Hospital, The Interventional Centre.
• Strategic 4-year research project on nanomedicine 2010-2014: “Personalized diagnosis and
tumor specific therapy” own funding, app 8 mill NOK, NTNU and 24 mil NOK from SINTEF
and strategic project in nanomedicine/Nanotechnology for medical applications.
Impact on industry – innovation:
The projects run by the unit makes it possible to explore research ideas from the academic
perspectives as well as from industrial and user demands and needs. The activity has impact on
industrialization and innovation in developing new medical devices and medical technology to
be commercialized by Norwegian companies. The unit has developed >10 prototypes on a
project basis, some of which already have been commercialized. This includes prototypes within
navigation systems, visualization and display modules, integrated micro-positioning
technologies, ultrasound simulation algorithms, integrated ultrasound simulator, ultrasound
probes. The unit holds >8 patents/ applications since 1995 and established the spinn off MISON
in 1998. Examples of industry collaboration and ongoing user driven research projects aiming at
developing prototypes to be commercialized by the industrial partners are:
• Sonowand: Industry-user driven project (2008-2011): (BIP projects, The Research Council of
Norway): Research for developing prototype technology for future image guided therapy for
patients. Demonstrated on stands, SMIT2010 conference, Sept 2010.
• Simsurgery: Industry-user driven project (2010-2014): (BIP projects, The Research Council of
Norway): Research for developing prototype technology for training of surgical procedures.
• Laerdal Medical: Industry-user driven project (2008-2011): (BIP projects, The Research
Council of Norway): Research for development of an ultrasound simulator for training of
ultrasound diagnostics in emergency situations. Stands, SMIT2010 conference, Sept 2010.
• Center of research based Innovation (SFI), Medical Imaging Laboratory (MILab), 2007-2014,
7
NTNU, aiming at improving patient care through developments within MR, ultrasound and
image guided therapy. MI Lab acts as an instrument for improved integration and collaboration
for the entire medical imaging research environment in Trondheim and is an important part of
the research unit. MILab covers eight industrial and academic partners and is funded partly by
The Research Council of Norway and industry as well as own financing from NTNU, St
Olav´s University Hospital and SINTEF. www.ntnu.no/milab
• Through the research infrastructure Operating Room of the Future, the research unit has
collaboration with Siemens, Olympus, Sony and Covidien. These industrial collaborators have
funded PhDs and partly financed some of the equipment in the research facilities. In addition
industrial collaboration is established through the simulator centre at NSALK.
Strength and weakness of the research unit
Strengths
Weakness
• Well focused and specific strategy within image guided • No full time professor
interventions in response to trends and needs
in the group
• Internationally recognized, participation in international projects
• Still not funding for
upgrading
NorMIT
• Strong interaction with other research groups/large network both
research
nationally and internationally
infrastructure
• Highly interdisciplinary (clinical and technological)
• Cover basic to applied research, satisfying mix of basic, applied • Basic funding could
be better
research and innovation
• Few woman scientists
• Strong collaboration with both MR/ ultrasound group at NTNU
• Strong collaboration between St. Olavs Hospital, NTNU and
SINTEF on all levels
• Good collaboration with industry
• Several funding sources makes the unit robust
• Covers publication, dissemination, course and education – clear
insight in user needs/demands and clinical practice
• Involvement in educational activity at the university ensures
satisfying recruitment possibilities
• Very good research infrastructure: Operating Room of the future NorMIT national infrastructure good chance to be fulfilled
• Well organized research unit, in spite of many institutions
involved and various background of personnel
• Clear and transparent management structure both on unit level as
well as on the clinical areas and project level.
• Steering committee and advisory board with international
representatives ensures activity in relation to trends and needs.
• Training programs and practical project management possibilities
for young and more experienced researchers (project based
research).
• Transparent process in selection of projects
The unit´s career path strategy is constituted by that of St. Olavs Hospital, NTNU and SINTEF:
• NTNU aims at educating more PhD/post doc within medical technology, having a separate
PhD program for medical technology as well as a National Research School in Medical
Imaging. NTNU educates students from MSc to PhD to post doc and further to Ass Professor
and full Professor. However, few in the research unit are employed at NTNU after PhD and
8
all professors are professor II within the area.
• St. Olavs Hospital aims at having more clinical personnel with PhDs and more clinical
research. Many of the clinical PhDs have joint positions at NTNU/St. Olavs Hospital and
enter into clinical positions after PhD.
• SINTEF aims at having high competent researchers, many of them with PhD, who can
manage large-scale research project management constituting of teams of researchers with
both technological and clinical background. The career path is from MSc to Researcher to
Senior Researcher to Chief Researcher. Many PhD students are employed at SINTEF after
their PhD degree. In addition, many of the personnel who have PhDs, including young
researchers, are encouraged to manage large scale project of >1 mill NOK /year in order to
increase their competence, collaborate with industry as well as train themselves to become
independent researchers.
The research unit has had satisfying recruitment of PhD candidates and researchers. Researchers
at the unit participate in various arrangements as Researchers Night, TV programs as Newton
and Schrødingers Katt, as well as lecturing in various courses at the university, in order to
stimulate young researchers to join the activity. Only two of the personnel with PhD are women
(one of them is the coordinator/manager of the unit), although all three organizations encourage
women to take PhDs as well as to take responsibility of project management. Few of the PhDs
or researchers are staying long time abroad, but many have considerable collaboration with
other research groups internationally through projects. The research unit collaborates with many
other groups both nationally and internationally, especially through EU projects and has also
many visiting researchers/PhD students. All PhD projects are related to demands in health care,
are parts of the strategy of the unit and most PhD projects also have commercial exploitation
possibilities.
interdisciplinarity
The research unit is interdisciplinary in its nature and collaboration is an integrated part of the
strategy making it possible to focus own research with the aim at maintaining high quality of the
research. In this respect focusing own research and collaboration with others will make it easier
to fulfill the goals and ambitions. The group collaborates regionally, nationally as well as
internationally and between institutes, faculties and organizations. The collaboration is also
reflected in co-authorship on scientific publications as seen in the publication list attached.
Collaboration internationally is also recognized by inclusion of international representatives in
the advisory board and participation in EU projects in recent years, including several large
scaled integrated projects as well as Marie Curie Training program. Still much effort has been
put in initiating networks and projects, and much of this activity has been focusing on
development of new features and prototypes. The strategy is to strengthen scientific publication
in scientific journals as well as innovation based on results also from these applied research
projects. The projects specified below show the ability of the research units to initiate and
participate in international collaboration. In all projects there are both academic and industrial
partners included.
EU projects and international collaboration:
• FP7 Project: IIIOS – Integrated Intraoperative Imaging Operating System (10 partners incl
NTNU/IVS): The Marie Curie Initial Training Networks project IIIOS is initiated by prof
Andreas Meltzer at University of Dundee. IVS/ORF will be responsible for research and
training in MR and ultrasound guided cardiovascular procedures both as a clinical and
technological partner in this field. Research will include new concepts to improve the
intraoperative imaging through the development of new image guided navigation tools.
9
• FP7 Project 3 MICRON (Three modality contrast imaging using multi-functionalized microballoons, NMP-2009, 10 partners incl SINTEF): The main objective is to develop monodisperse multimodal bubbles with improved stability with shell properties opening for
ultrasound MR and SPECT/PET imaging, i.e. multi modal imaging and shell decoration with
antibodies or ligands opening for molecular imaging and incorporation of various drugs and
RNAs opening for local drug delivery and gene therapy induced by ultrasound improving
diagnostics and therapy of cancer and cardiovascular diseases.
• FP7 Project: FUSIMO - Patient specific modelling and simulation of focused ultrasound in
moving organs, ICT – 2010, 11 partners incl SINTEF. The project aims at developing
improved medical technology for patient treatment.
• FP6 Project: VECTOR - Versatile Endoscopic Capsule for gastrointestinal TumOr
Recognition and therapy (19 partners incl SINTEF): The objective of the VECTOR project is to
develop intelligent endoscopic capsules using innovations in micro- and nanotechnology. The
VECTOR project aims at investigating and developing a miniaturized robotic pill for advanced
diagnostics and therapy in the human digestive tract, making a significant contribution to the
diagnosis and treatment of digestive cancers and to strengthen the competitiveness of the
European biomedical industry through innovative technologies. The project was appointed as
STAR project by the EU commision.
• SMIT, Society for innovation and technology. A society that especially focuses medical
technology and minimally invasive procedures. 3 of the researcher in the research unit are in the
Steering Committee of SMIT. Conference 2010 was successfully arranged in Sept 2010.
• The research unit also collaborates with many universities and research groups both
nationally and internationally, many as partners in EU projects listed above.
• The unit was active in the foundation of EUROSTAR. This is an international register of
endovascular procedures for the treatment of aortic aneurymal disease. The register has been
used in several scientific publications, and PhD theses from the unit.
• ESVS-European Society for Vascular Surgery. The unit had the first president an presently
has the national council member. The annual meeting of 2009 was successfully arranged in
Oslo.
• Many collaborative projects together with universities and hospitals.
Related projects in the unit important in relation to clinical trials/research and innovation are:
• Innomed: InnoMed is Norway's competence network for need/user driven innovation in
health care. InnoMed is owned by the Norwegian Directorate of Health and is financed by The
Ministry of Health and Care Services and The Ministry of Trade and Industry. InnoMed has a
strategic role in a ten-year program launched by the authorities in promoting innovation
processes in the health sector in order to improve quality, efficiency and effectiveness, and also
create new business opportunities for industry. The Secretariat of InnoMed is situated at
SINTEF, Dept of Medical Technology, which is a part of the research unit, and is headed by
Research Manager Merete Rørvik. The secretariat performs the overall management of the
network, initiates and runs innovation projects as well as develops research methodology and
competence in how to disclose demands and performs innovation processes in health care. The
program aims at improving quality and efficiency in health care by development of new
solutions and medical technology. InnoMed has the strategic areas as ICT in health care,
medical technology, welfare technology and health services.
• Unimed Innovation: Unimed Innovation is responsible for administration of clinical trials,
which are performed on a project basis from the industry. The activity covers all hospitals in
Mid Norway. Clinical trials are performed in accordance with Good Clinical Practice. The
activity is headed by Research Manager Else Thurmann Nilsen, who is employed at Dept of
Medical Technology at SINTEF.
10
Image guided therapy and minimal invasive interventions
Papers in international scientific journals with referee
2010
1.
Bazilevs Y, Hsu M.-C., Zang W, Liang X, Kvamsdal Trond, Brekken Reidar,
Isaksen J.G. A fully-coupled fluid-structure interaction simulation of cerebral
aneurysms. Computational Mechanics 2010;46-3-16. Epub 2010 Jan 29.
2.
Rethy A, Langø T, Åsland J, Mårvik R. Development of a multimodal tumor
model for porcine liver. J Gastrointestinal Surgery, DOI: 10.1007/s11605-0101283-y, May 2010.
3.
Gjerald SU, Brekken R, Hernes TAN. Real-time ultrasound simulation for low cost
training simulators. Progress in Biomedical Optics and Imaging – Proceedings of
SPIE, Medical Imaging, San Diego, California, USA. Volume 7629, Article no:
76290B. February 13-18, 2010.
4.
Våpenstad C, Rethy A, Langø T, Selbekk T, Ystgaard B, Hernes TAN, Mårvik R.
Laparoscopic ultrasound: a survey of its current and future use, requirements, and
integration with navigation technology. Surg Endosc DOI 10.1007/s00464-0101135-6. Epub Jun 5.
5.
Selbekk T, Brekken R, Solheim O, Lydersen S, Hernes TAN, Unsgård G. Tissue
motion and strain in the human brain assessed by intraoperative ultrasound in
glioma patients. Ultrasound in Medicine & Biology, 2010; 36(1):2-10.
6.
Bø Lars Eirik, Gjerald Sjur Urdson, Brekken Reidar, Tangen Geir Arne, Hernes
Toril A Nagelhus. Efficiency of ultrasound training simulators: Method for
assessing image realism. MITAT - Minimally invasive therapy & allied
technologies, 2010; 19(2): 69-74.
7.
Solheim O, Selbekk T, Løvstakken L, Tangen GA, Solberg OV, Johansen TF,
Cappelen J, Unsgård G. Intrasellar ultrasound in transsphenoidal surgery - a novel
technique. Neurosurgery, 2010; 66:173-186.
8.
Hansen R, Måsøy SE, Johansen TF, Angelsen BA. Utilizing dual frequency band
transmit pulse complexes in medical ultrasound imaging. Journal of the Acoustical
Society of America (JASA), 2010; 127(1): 579-87.
9.
Seternes A, Myhre HO, Dahl T. Early results after treatment of abdominal
compartment syndrome with traction and vacuum assisted wound closure. Eur J
Vasc Endovacs Surg, 2010; 40(1): 60-64. Epub 2010 Mar 31.
10.
Hjelde H, Sundstrøm S, Odegård A, Hatlinghus S, Abusland AB, Haaverstad R.
Recurrence and survival after surgical treatment of lung cancer. Tidsskr Nor
Laegeforen. 2010 Jan 14;130(1):25-8.
1
2009
11.
Lindseth F, Løvstakken L, Rygh OM, Tangen GA, Torp H, Unsgård G. Blood
Flow Imaging -An angle-independent ultrasound modality for intraoperative
assessment of flow dynamics in neurovascular surgery. Neurosurgery, 2009;
65(ONS Suppl 1):149-157.
12.
Solheim O, Selbekk T, Lindseth F, Unsgaard G, Intraoperative navigated 3D
ultrasound in giant intracranial meningiomas. Acta Neurochirurgica, 2009;
151:1143-1151.
13.
Zhang Y, Wang W, Liang X, Bazilevs Y, Hsu MC, Kvamsdal T, Brekken R,
Isaksen J. High-Fidelity Tetrahedral Mesh Generation from Medical Imaging Data
for Fluid-Structure Interaction Analysis of Cerebral Aneurysms. CMES
2009;42(2):131-150
14.
Berntsen EM, Gulati S, Solheim O, Kvistad KA, Lindseth F, Unsgård. Integrated
pre- and intraoperative imaging in a patient with an arteriovenous malformation
located in eloquent cortex. Minim Invasive Neurosurg, 2009; 52: 83-85.
15.
Langø T, Nesbakken R, Færevik H, Holbø K, Reitan J, Yavuz Y, Mårvik R.
Cooling vest for improving surgeons’ thermal comfort: A multidisciplinary design
project. Minim Invasive Ther Allied Technol (MITAT), 2009; 18:1:20-29.
16.
Solberg OV, Langø T, Tangen GA, Mårvik R, Ystgaard B, Rethy A, Hernes TAN.
Navigated ultrasound in laparoscopic surgery. Minim Invasive Ther Allied Technol
(MITAT), 2009;18:1:36-53.
17.
Gulati S, Berntsen EM, Solheim O, Kvistad KA, Håberg A, Selbekk T, Lindseth F,
Torp SH, Unsgaard G. Surgical resection of high grade gliomas in eloquent regions
guided by blood oxygenation level dependent functional magnetic resonance
imaging, diffusion tensor tractography, and intraoperative navigated 3D ultrasound.
Minimally Invasive Neurosurgery, 2009; 52:1: 17-24.
18.
Hansen R and Angelsen BA. SURF imaging for contrast agent detection. IEEE
transactions on Ultrasonics, Ferroelectrics and Frequency Control, 2009;56:2:28090.
19.
Ravn-Eide K, Ødegaard A, Myhre HO, Lydersen S, Hatlinghus S, Haraldseth O.
Dyna-CT during EVAR - A Comparison with Multidetector CT. Eur J Vasc
Endovasc Surg, 2009;37:1:23-30.
20.
Eide KR, Ødegård A, Myhre HO, Lydersen S, Hatlinghus S, Haraldseth O. DynaCT during EVAR – A comparison with multidetector CT. Eur J Vasc Endovasc
Surg 2009; 37: 23-30
21.
Altreuther M, Ødegård A, Aasgaard F, Lange CA, Myhre HO. Endovascular
treatment of calcified plaque in the thoracic aorta after recurrent massive
embolization. Int Angiol 2009; 28: 500-2.
2
22.
Seim AR, Fagerhaug T, Ryen SM, Curran P, Sæther OD, Myhre HO, Sandberg,
WS. Causes of cancellations on day of surgery at two major university hospitals.
Surg Innov 2009; 16: 173-80.
23.
Myhre HO, Winnerkvist A, Ødegård A, Stenseth R. Torakoabdominale
aortaaneurismer. Åpen kirurgi og endovaskulær behandling. TDnlf nr. 20, 22. okt.
2009, s 2127-2130
24.
Myhre HO, Moen T, Ødegård A, Lange C, Nakken T, Egeland T, Torstensen K,
Johnsen R. Mulig assosiasjon mellom humant leukocyttantigen (HLA) og
abdominalt aortaaneurisme. Kirurgen 2009;1:26-27.
25.
Myhre HO, Jørgensen JJ. Karkirurgi i 2009. Lederartikkel TDnlf nr. 20, 22. okt.
2009, s. 2092
2008
26.
Enquobahrie A, Gobbi D, Turek MW, Cheng P, Yaniv Z, Lindseth F, Cleary K.
Designing tracking software for image-guided surgery applications: IGSTK
experience. International Journal of Computer Assisted Radiology and Surgery,
2008;3:5:395-403.
27.
Rygh OM, Selbekk T, Torp SH, Lydersen S, Hernes TAN, Unsgaard G.
Comparison of ultrasound findings with histopathology in subsequent phases of
glioblastoma resection. Acta Neurochir (Wien). 2008;150(10):1033-41.
28.
Brekken R, Dahl T, Hernes TAN, Myhre HO. Reduced strain in abdominal aortic
aneurysms after endovascular repair. J Endovasc Ther 2008;15:453-461.
29.
Langø T, Tangen GA, Mårvik R, Ystgaard B, Yavuz Y, Kaspersen JH, Solberg
OV, Hernes TAN. Navigation in laparoscopy – Prototype research platform for
improved image-guided surgery. Minim Invasive Ther Allied Technol (MITAT),
2008; 17:1:17-33.
30.
Solberg OV, Tangen G-A, Lindseth F, Sandnes S, Enquobahrie A, Ibáñez L, Gobbi
D, Cleary K. Integration of a real-time video grabber component with the open
source image-guided surgery toolkit IGSTK. Proceedings of Medical Imaging
2008: PACS and Imaging Informatics, San Diego, CA, USA: SPIE,
2008;6919:69190Z-69199.
31.
Isaksen JG, Bazilevs Y, Kvamsdal T, Zhang Y, Kaspersen JH, Waterloo K,
Romner B, Ingebrigtsen T. Determination of Wall Tension in Cerebral Artery
Aneurysms by Numerical Simulation. Stroke. 2008; 39:3172-8.
32.
Måsøy S-E, Standal Ø, Nasholm P, Johansen TF, Angelsen BA, Hansen R. SURF
imaging: In vivo demonstration of an ultrasound contrast agent detection technique.
IEEE transactions on Ultrasonics, Ferroelectrics and Frequency Control,
2008;55:5:1112-21.
3
33.
Dahl T, Cederin B, Myhre HO, Indredavik B. The prevalence of carotid artery
stenosis in an unselected hospitalized stroke population. Int Angiol, 2008;27:2:1425.
34.
Lange C, Aasland JK, Ødegård A, Myhre HO. The durability of EVAR – What are
the evidence and implications on follow-up? Scandinavian Journal of Surgery,
2008;97:2:205-12.
35.
Berge C, Haug ES, Romundstad PR, Lange C, Myhre HO. Improved long-term
survival following infrarenal abdominal aortic aneurysm repair. Scand Cardiovasc
J, 2008;42:5:354-9.
36.
Jensen SA, Vatten LJ, Myhre HO. The association between diabetes mellitus and
the prevalence of intermittent claudication. Vasc Med 2008; 13: 239-44
2007
37.
Reinertsen I, Lindseth F, Unsgaard G and Collins DL. Clinical validation of vessel
based registration for correction of brain-shift. Medical Image Analysis, 11:673-84,
2007.
38.
Rassmussen I-A, Lindseth F, Rygh OM, Berntsen EM, Selbekk T, Xu J, Hernes
TAN, Harg E, Håberg A, Unsgaard G. Improved neuronavigation by use of
combined intra-operative 3D ultrasound and brain shift corrected functional MRI
and DTI-based tractograms: Initial experiences during surgical resections close to
eloquent cerebrocortical areas. Acta Neurochir. 149:365-378, 2007.
39.
Manstad-Hulaas F, Ommedal S, Tangen GA, Aadahl P, Hernes TN. Side-Branched
AAA Stent Graft Insertion Using Navigation Technology: A Phantom Study. Eur
Surg Res, 39:6:364-371, 2007.
40.
Solberg OV, Lindseth F, Torp H, Blake RE, Hernes TAN. Freehand 3D ultrasound
reconstruction algorithms - A review. Ultrasound Med Biol, 33:7:991-1009, 2007.
41.
Enquobahrie A, Cheng P, Gary K, Ibanez L, Gobbi D, Lindseth F, Yaniv Z,
Aylward S, Jomier J, Cleary K. The Image-Guided Surgery Toolkit IGSTK: An
Open Source C++ Software Toolkit. J Digital Imaging, ISSN 0897-1889, 1618727X (Online), DOI 10.1007/s10278-007-9054-3.
42.
Brekken R, Kaspersen J, Tagen G, Dahl T, Hernes T, Myhre H. 3D visualization of
strain in abdominal aortic aneurysms based on navigated ultrasound imaging.
Proceedings of the SPIE Medical Imaging- Physiology, Function and Structure
from medical images, San Diego February, 6511-52, 2007.
43.
Ødegård A, Aasland J, Myhre HO, Mollnes TE, Videm V. The inflammatory
response to stentgrafting of the thoracic aorta. Int Angiol 2007; 26: 219-27.
4
44.
Eide KR, Ødegård A, Myhre HO, Haraldseth O. Initial observations in EVAR
using Dyna-CT. J Endovasc Ther 2007; 14: 50-53.
45.
Berge C, Ødegård A, Lange C, Myhre HO. Infrarenal abdominal aortic aneurysm
repair. Time-trends and results during a 20-year period. World J Surg,
2007;31:8:1682-6.
46.
Hagen AI, Bofin A, Møller P, Myhre HO, Kjellevold KH, Ytterhus B, Mæhle L.
Amplification of TOP2A and HER-2 genes in breast cancers occurring in patients
harbouring BRCA1 germline mutations. Acta Oncol 2007; 46: 199-203.
47.
Jensen, LP, Lepäntalo M, Fossdahl JE, Rohr N, Jensen BS, Jpesen J, Grenager O,
Fasting H, Myhre HO, Bækgaard N, Nielsen OM, Helgstrand U, Schroeder TV.
Dacron or PTFE for above-knee femoropopliteal bypass. A multicenter randomised
study. Eur J Vasc Endovasc Surg 2007; 34; 44-9
48.
Berge C, Haug ES, Romundstad PR, Lange C, Myhre HO. Infrarenal abdominal
aortic aneurysm repair. Time-trends and results during a 20-year period. World
Journal of Surgery 2007; 3: 1682-6
49.
Brattli OS, Nystuen K, Sæther OD, Aadahl P, Grønbech JE, Myhre HO. Regional
distribution of blood flow during proximal aortic cross-clamping. An experimental
study using coloured microspheres. Scand J Clin Lab Invest 2007; 67: 526-535
50.
Eide T, Romundstad P, Klepstad P, Myhre HO. Helserelatert livskvalitet hos
langtidsoverlevende etter kirurgi for torakoabdominalt aortaaneurisme. Sykepleien
forskning 01/07
51.
Norgren L, Myhre HO. Arteriell insuffisiens i beina. Tidsskr Nor Lægeforen, 2007;
127:123
2006
52.
Ottermo MV, Øvstedal M, Langø T, Stavdahl Ø, Yavuz Y, Johansen TA, Mårvik
R. The Role of Tactile Feedback in Laparoscopic Surgery. Surg Laparosc Endosc
Percutan Tech, Dec;16:6:390-400, 2006.
53.
Rygh OM, Selbekk T, Lindseth F, Müller TB, Hernes TAN, Unsgaard G.
Intraoperative navigated 3D ultrasound angiography in surgery. Surgical
Neurology, 66:581-592, 2006.
54.
Hernes TAN, Lindseth F, Selbekk T, Rygh OM, Tangen GA, Rasmussen I, Wollf
A, Rasmussen I Solberg OV, Harg E, Augdal S, Couweleers F, Unsgaard G.
Technical developments for improved 3D ultrasound guided neurosurgery Computer-assisted 3D ultrasound-guided neurosurgery: technological
contributions, including multimodal registration and advanced display,
demonstrating future perspectives. International Journal of Medical Robotics and
Computer Assisted Surgery, 2:1:45-59, 2006.
5
55.
Mårvik R, Nesbakken R, Langø T, Yavuz Y, Bjelland H, Ottermo MV, Stavdahl Ø.
Ergonomic design criteria for a novel laparoscopic tool handle with tactile
feedback. Minerva Chir, 61:5:435-44, 2006.
56.
Yavuz Y, Skogås JG, Güllüoğlu MG, Langø T, Mårvik R. Are cold light sources
really cold? Surg Laparosc Endosc Percutan Tech, 16:5:370-6, 2006.
57.
Yavuz Y, Rønning K, Bakkelund K, Lyng O, Aadahl P, Mårvik R, Grønbech JE.
Hemodynamic and tissue blood flow responses to long-term pneumoperitoneum
and hypercapnia in the pig. Surg Endosc, 20:9:1394-1401, 2006.
58.
Dahl T, Aasland J, Romundstad P, Johnsen HJ, Myhre HO. Carotid
endarterectomy: time-trends and results during a 20-year period. Int Angiol,
Sep;25:3:241-8, 2006.
59.
Dahl T, Myhre HO, Johnsen HJ. Surgical treatment of carotid stenosis in Norway.
Tiddsskr Nor Laegeforen, May:25;126:11:1466-9, 2006. (Norwegian)
60.
Dahl T, Rudjord K, Altreuther M, Myhre HO. Data quality of surgery for carotid
artery stenosis. Are the national vascular registries reliable? Eur J Vasc Endovasc
Surg. Apr;31:4:381-5. 2006.
61.
Kolstad F, Rygh OM, Selbekk T, Unsgaard G, Nygaards OP. Three-dimensional
ultrasonography navigation in spinal cord tumor surgery. Technical note. J
Neurosurg: Spine, 5:3:264-70,2006
62.
Mårvik R, Langø T. High-definition television in medicine. Editorial in Surg
Endosc, 20:3:349-50, 2006.
63.
Brekken R, Bang J, Ødegård A, Aasland J, Hernes TAN, Myhre HO. Strain
estimation in abdominal aortic aneurysms from 2D ultrasound. J Ultrasound Med
Biol, 32:1:33-42, 2006.
64.
Unsgaard G, Rygh OM, Selbekk T, Müller TB, Kolstad F, Lindseth F, Hernes
TAN. Intra-operative 3D ultrasound in neurosurgery. Acta Neurochirurgica,
148:3:235-53, 2006.
65.
Rygh OM, Cappelen J, Selbekk T, Lindseth F, Hernes TANH, Unsgård G.
Endoscopy guided by an intraoperative 3D ultrasound based neuronavigation
system. Minim Invasive Neurosurg, February, 49:1:1-9, 2006.
66.
Eide TO, Romundstad PR, Stenseth R, Aadahl P, Myhre HO. Spinal fluid
dynamics during thoracic- and thoracoabdominal aortic surgery. Int Angiol 2006;
25: 46-51.
67.
Myhre HO. Karkirurgien 1980-2005. Jubileumsnummer Tidsskr Nor Lægeforen nr
1, 2006; 100-101.
6
68.
69.
Jensen SA, Vatten LJ, Myhre HO. The prevalence of chronic critical lower limb
ischemia in a population of 20,000 subjects 40-69 years of age. Eur J Vasc
Endovasc Surg 2006; 32: 60-65. (Referert til i DailyUpdates)
Vik BJ, Angelsen A, Egey A, Myhre HO. Renal carcinoma extending into the
inferior vena cava. Vascular surgical aspects. Phlebology 2006; 21: 41-44.
70.
Dahl T, Johnsen HJ, Myhre HO. Kirurgisk behandling ved carotisstenose i Norge.
Tidsskr Nor Laegeforen 2006; 11: 1466-69.
71.
Norgren L, Jawien A, Matyas L, Rieger H, Arita K and the European MCI-9042
Study Group. Sarpogrelate, a 5-HT2A receptor antagonist in intermittent
claudication. A Phase II European study. Vasc Med 2006; 11: 75-83.
72.
Kulseng B, Myhre HO. Is insulin growth factor-1 (IGF-1) playing a role for
aneurysm formation in patients with pituitary gland tumor? Int Angiol 2006; 25:
433-5.
2005
73.
Eide TO, Aasland J, Romundstad P, Stenseth R, Saether OD, Aadahl P, Myhre HO.
Changes in hemodynamics and acid-base balance during cross-clamping of the
descending thoracic aorta. A study in patients operated on for thoracic and
thoracoabdominal aortic aneurysm. Eur Surg Res, Nov-Dec;37:6:330-4, 2005.
74.
Aasland J, Lundbom J, Eide TO, Odegard A, Aadahl P, Romundstad PR, Myhre
HO. Recovery following treatment of descending thoracic aortic disease. A
comparison between endovascular repair and open surgery. Int Angiol,
Sep;24:3:231-7, 2005.
75.
Haug ES, Romundstad P, Saether OD, Jorgenvag R, Myhre HO. Quality of data
reported on abdominal aortic aneurysm repair--a comparison between a national
vascular and a national administrative registry. Eur J Vasc Endovasc Surg.
Jun;29:6:571-8, 2005.
76.
Haug ES, Romundstad P, Aune S, Hayes TBJ, Myhre HO. Elective open operation
for abdominal aortic aneurysm in octogenarians – Survival analysis of 105 patients.
Eur J Vasc Endovasc Surg 2005; 29: 489-495.
77.
Unsgaard G, Selbekk T, Müller TB, Ommedal S, Torp SH, Myhr G, Bang J,
Nagelhus Hernes TA. Ability of navigated 3D ultrasound to delineate gliomas and
metastases - comparison of image interpretations with histopathology. Acta
Neurochirurgica, 147:12:1259-69, 2005.
78.
Hernes TANH, Selbekk T, Lindseth F, Rygh OM, Muller T, Unsgård G. Navigated
neurosurgery with intraoperative 3D ultrasound. Indian Clinical Neurosurgery, vol
5, 2005.
79.
Martin K, Ibanez L, Avila L, Barre S, Kaspersen JH. Integrating segmentation
methods from the Insight Toolkit into a visualization application. Med Image Anal,
9: 579-593.
7
80.
Mårvik R, Langø T, Tangen GA, Lindseth F, Yavuz Y, Hernes TAN. Imageguided laparoscopic surgery – Review and current status. Minerva Chirurgica,
October; 60:5:305-25, 2005.
81.
Unsgaard G, Ommedal S, Rygh O, Lindseth F. Operation of Arteriovenous
Malformations Assisted by Stereoscopic Navigation-controlled Display of
Preoperative Magnetic Resonance Angiography and Intraoperative Ultrasound
Angiography. Neurosurgery. 56(4) Operative Neurosurgery Supplement 2:281-290,
April 2005.
82.
Wollf A, Tangen GA, Solberg OV, Kaspersen JH, Langø T, Hernes TAN, Mårvik
R. Real-time endoscope and ultrasound integration in computer assisted navigated
surgery. In Proceedings of Computer Assisted Radiology and Surgery (CARS),
Berlin, Germany, June 22-25: 606-611, 2005.
83.
Mårvik R, Yavuz Y, Waage A, Kjæve JK, Bergamaschi R. Clinical Evaluation of a
new ultrasonic Doppler Instrument (SonoDoppler®) for the detection of blood flow
during laparoscopic procedures. J Minimally Invasive Therapy, 14:3:198-202,
2005.
84.
Mercier L, Langø T, Lindseth F, Collins L D. A review of calibration techniques
for freehand 3D ultrasound systems. J Ultrasound Med Biol; 31: 2: 143-165, 2005.
85.
Selbekk T, Bang J, Unsgaard G. Strain processing of intraoperative ultrasound
images of brain tumours: initial results. J Ultrasound Med Biol; 31: 1: 45-51, 2005.
86.
Pedersen MI, Aasland J, Kaspersen JH, Leira HO, Myhre HO. Teleradiologisk
oppfølging av pasienter behandlet med stentgraft i aorta. Tidsskr Nor Lægeforen,
10:1362-4, 2005.
87.
Kaspersen JH, Aasland J, Leira HO, Ødegård A, Nagelhus B, Størset G, Lundbom
J, Pedersen M, Rosenlund T, Tjora A, Myhre HO. Three-dimensional teleradiology
for surveillance following endovascular aortic aneurysm repair: A feasibility study.
J Endovasc Ther, 12:196-199, 2005.
88.
Lange C, Hobo R, Leurs LJ, Daenens K, Buth J, Myhre HO on behalf of the
EUROSTAR Collaborators. Results of Endovascular Repair of Inflammatory
Abdominal Aortic Aneurysms. A Report from the EUROSTAR Database. Eur J
Vasc Endovasc Surg, 2005; 29: 363-70.
89.
Jensen SA, Vatten LJ, Nilsen TIL, Romundstad PR, Myhre HO. Serum lipids and
anthropometric factors related to the prevalence of intermittent claudication. Eur J
Vasc Endovasc Surg 2005; 30: 582-587.
90.
Dahl T, Lange C, Ødegård A, Bergh K, Osen SS, Myhre HO. Ruptured abdominal
aortic aneurysm secondary to tuberculous spondylitis. Int Angiol 2005; 24: 98-101.
91.
Lange C, Leurs LJ, Buth J, Myhre HO. Endovascular repair of abdominal aortic
aneurysm in octogenarians. An analysis based on EUROSTAR data. J Vasc Surg
8
2005; 42: 624-9.
92.
Eide TO, Romundstad R, Klepstad P, Myhre HO. Health related quality of life in
long term-survivors following thoracoabdominal aortic aneurysm repair. J Vasc
Nurs 2005; 23: 88-94.
93.
Jensen SA, Vatten LJ, Nilsen TIL, Romundstad PR, Myhre HO. The association
between smoking and the prevalence of intermittent claudication. Vascular
Medicine 2005; 10: 257-263.
Scientific reports and books / book chapters
94.
Unsgård G. Book chapter: Ultrasound-guided neurosurgery. In vol II, Practical
Handbook of Neurosurgery - From Leading Neurosurgeons. Sindou, Marc (Ed.),
Springer, Wien-New York, 2009, ISBN: 978-3-211-84819-7.
95.
Kaspersen JH, Langø T, Lindseth F. Computer-Aided Interventions. Chapter 12, p
271-287, in: Information Technology Solutions for Healthcare, Zielinski K,
Duplaga M, Ingram D (eds). Health Informatics Series, Springer, London, 2006.
96.
Wesche J, Dahl T, Myhre HO. Acute axillary/subclavian vein thrombosis. In
“Vascular Surgery. Cases, questions and commentaries, Second Edition”.
Geroulakos, Urk, Hopson, Eds. Springer Verlag, London Ltd., 2006.
97.
Myhre HO, Haaverstad R. Prevention of postoperative paraplegia during
thoracoabdominal aortic surgery: pp 283-295 in Current techniques and results.
Sakalihasan N, Kuivaniemi H, Michel JB “Aortic Aneurysms, New insights into an
old problem”. Les Editions de l’Université de Liege, 2008
9

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