Curing with Sound - Radiotherapie

Curing with Sound
Inaugural address by Prof. C.T.W. Moonen
University Medical Center Utrecht
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Contents
Introduction
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Centre for Image-Controlled Oncological Interventions
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MRI-controlled ultrasound for cancer care
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MRI-controlled ultrasound and chemotherapy
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MRI-controlled ultrasound and immunotherapy
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MRI-controlled ultrasound and stem cells
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Action Plan for developing MRI-controlled ultrasound
20
Conclusions
20
Acknowledgements
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Curing with Sound
Inaugural address by Prof. C.T.W. Moonen
Speech given on Friday 18 October, 2013
Imaging Division
University Medical Centre, Utrecht
3
Rector Magnificus,
my colleagues from the Netherlands, Europe and North America,
my family and friends,
and all those listening,
1 Introduction
I am not talking about the positive influence that music by artists such as Mozart,
George Brassens or Beppie Kraft can have on the human psyche. This is about
pressure waves, comparable to musical vibrations, but then at greater intensities
and higher frequencies that can no longer be perceived by humans or animals.
Pressure waves such as these penetrate the human body, where we can put them
to therapeutic use. In this context, we are talking about ultrasound that typically has
frequencies of about 1MHz, one million waves per second, at an amplitude of a few
micrometres and a wavelength of one millimetre. It has been known for a long time
that ultrasound vibrations are absorbed by the tissue, with the extent of absorption
and reflection depending on the type of tissue. These principles are used in what is
known as ultrasound imaging or ultrasonography (Figure 1).
Figure 1: An ultrasound image
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When sound waves are absorbed, the mechanical energy of that pressure wave is
converted into thermal energy. This is negligible or unnoticeable in ultrasonography,
but at greater intensities the tissue becomes warmer. If we then take several
transmitters rather than one and ensure that the sound waves are all in phase at a
specific location, we get vibrations with the greatest amplitude at that point and also
- after a while - the greatest temperature elevation (Figure 2).
Figure 2: An ultrasound source with multiple
independent transmitters, showing the vibration
path for each transmitter separately in red. Taken
together, the beams create a focal point in the
same way as an optical lens can concentrate
sunlight at its focal point.
We call this high-intensity focused ultrasound, abbreviated to HIFU. The dimensions
of the focal point of the sound waves will be of the same order of magnitude as the
wavelength, i.e. approximately 1 mm for this type of ultrasound. As I said, the physical
principles have been known for some time. The potential for medical applications
has also been suspected for some time, because the transmitters can be placed
outside the body. During the 1950s and 1960s, the Fry brothers in Illinois developed
an ultrasound device for treating brain tumours (Figure 3).
The idea was wonderful, but in those days it was not possible to see clearly exactly
where the focal point of the sound waves was located with respect to the brain
structures. Moreover, it was not really clear just how warm the tissue actually became.
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Figure 3: Prof. William J. Fry, Bio-acoustic Research Laboratory, University of Illinois, IL, United States. The first
HIFU system with four independent transmitters for treating brain conditions.
A major step towards clinical applications was taken during the 1990s in Lyon by
Dominique Cathignol’s group. Prostate cancer was treated using an endorectal
ultrasound transmitter. The positioning of the device was verified using ultrasound
imaging. However, the temperature could not yet be measured, or at any rate not
non-invasively.
Magnetic resonance imaging, generally abbreviated to MRI, was invented in the
seventies, long after the invention of focused ultrasound. The development of MRI
and its medical applications went extremely rapidly, and MRI is now seen as the best
way of demonstrating the presence of abnormalities in soft tissue (Figure 4).
A generally less well-known fact is that MRI is also capable of indicating temperature
changes (Figure 5). This is because temperature changes can affect the forces
between neighbouring water molecules inside tissues, and that can be seen in the
MRI signal. Temperature measurements using MR make it possible for us to adjust the
heating effect, in the same way as a thermostat does.
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Figure 4: An MRI-image
On the left in figure 5, you can see the localised heating by ultrasound in the muscle of
a laboratory animal, with the diagram showing the desired temperature progression
in red; the MR thermometry data is in black. This heating study was carried out
without intervention by the researcher. For the first time, this made it possible to
raise the temperature locally in the tissue and control it, fully automatically and noninvasively. MRI is currently the only method available for measuring temperature
changes inside the body non-invasively. This is important for the treatment. After all,
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Figure 5: Temperature regulation using MRI-controlled sound waves
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we have to make allowances for variable perfusion, variable absorption of ultrasound
and variable thermal insulation. At the beginning of the nineties, heating by focused
sound waves plus the very precise imaging and thermometry capabilities of MRI led
to combination MRI that also used focused sound waves, better known as MRI-HIFU.
Kullervo Hynynen, Ferenc Jolesz and John Mallard in particular played key roles in this.
The first medical applications involved benign swellings in the uterus. This procedure
is now routinely used in numerous countries, including here in Utrecht.
I have also been investigating the possibilities of this technology since 1994, first
at the American National Institutes of Health, then at CNRS and the University of
Bordeaux, and for the last few years at the University Medical Centre in Utrecht.
In the rest of my lecture, I hope to convince you of the extensive opportunities
offered by MRI-controlled ultrasound in medical care and I shall be sketching out
how we hope to develop research in the years to come.
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Centre for Image-Controlled Oncological Interventions
Before I start talking about medical interventions, I am going to take you on a small
diversion through the world of the military. This is not because I am a particular fan
of it, but because there is a considerable similarity to medical interventions that are
controlled using imaging. You may perhaps have seen the following video clip in the
news on TV. The fragment shows how images are first used to define the target and
then how a laser-guided projectile hits the target very precisely (Video 1).
And now back to medical interventions and the context of this research: the Centre
for Image-Controlled Oncological Interventions at the University Medical Centre,
Utrecht. The techniques that we will be using in the Centre do indeed resemble those
from the military world: localising the target precisely using imaging and then using
images as a guide to ensure that the target is hit very precisely. The central theme of
the Centre for Image-Controlled Oncological Interventions is indeed to use guiding
images to develop non-invasive or minimally invasive treatments and apply them in
oncology. This goal is expressed as “see what you’re treating, and treat what you’re
seeing”, as well as the theme of “surgery without cutting” or “surgery without a scalpel”.
The University Medical Centre in Utrecht has invested heavily in the Centre for ImageControlled Oncological Interventions and has high expectations that this will result in
better patient care, less damage to the body and better therapeutic results. The next
slide shows you the new building for the Centre for Image-Controlled Oncological
Interventions, which we have just started using (Figure 6).
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Video 1: Target determination and laser-guided bombardment
Figure 6: Building for the Centre for Image-Controlled Oncological Interventions
As I said earlier, guidance by means of images plays a central role at the Centre
for Image-Controlled Oncological Interventions. The Centre for Image-Controlled
Oncological Interventions is concentrating primarily on MRI as the imaging
technique. MRI-controlled focused ultrasound therefore fits in beautifully with
these developments. Other developments within the Centre for Image-Controlled
Oncological Interventions are MRI-controlled radiotherapy and the use of radioactive,
MRI-detectable granules for internal irradiation of liver tumours after they have been
injected via the hepatic artery.
The next slide (Figure 7) shows you the idea for an MRI-controlled linear accelerator,
developed by my colleagues Jan Lagendijk and Bas Raaymakers and their team,
working with Philips and Elekta. The patient lies inside the magnet, while the
accelerator goes round the MRI and shoots through the magnet into the tumour. The
idea here is once again that the MRI is producing continuous images, thereby making
it possible to guide the highly energetic photon beam. The first prototype has now
been installed in the Centre for Image-Controlled Oncological Interventions and we
anticipate being able to use it in clinical applications within two years.
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Figure 7: MRI-controlled linear accelerator
The potential synergy in the development of MRI-controlled sound waves and the
MRI-controlled linear accelerator, both technically and in terms of their fields of
application, make the University Medical Centre in Utrecht an exceptional location,
even at the world level. The development of image-guided interventions has been
going on for some time at major research centres, as we have also seen today during
the international symposium. We have seen some wonderful examples from Harvard
Medical School, from Toronto’s Sunnybrook Hospital, from the Edouard Herriot Hospital in
Lyon and other well-known centres. However, the broad scale at which the University
Medical Centre in Utrecht is investing in image-controlled, non-invasive oncological
care therapies can genuinely be called unique. On the one hand, these studies in
demand a great deal of investment in technology and infrastructure; on the other,
they do also offer opportunities for commercialisation. Public-private partnership is
therefore a crucially important aspect of the Centre for Image-Controlled Oncological
Interventions. Close cooperation with Philips has played a key role in the rapid
progress made by MRI-controlled ultrasound over recent years. Cooperation with
Philips at the research level has long been intensive, but the decision to develop
MRI-controlled ultrasound waves as a product was only taken eight years ago. The
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governmental authorities have made a major contribution by encouraging publicprivate partnerships through government subsidies. At this point I would particularly
like to mention the CTMM, the Centre for Translational Molecular Medicine, which has
played (and is still playing) a key role in the development of MRI-controlled sound
waves at Utrecht. Because of the high expectations for patient care, the Centre
for Image-Controlled Oncological Interventions is also playing a large part in the
discussions about in-depth cooperation with the Antoni van Leeuwenhoek Hospital.
After all, it is ultimately all about transforming our new techniques into improved
treatments for patients.
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MRI-controlled ultrasound for cancer care
Back to MRI-controlled ultrasound for cancer care. Where are we now? After the
radical technological advances, a number of clinical studies have been performed
worldwide over recent years into the use of this new technology in treating breast,
liver, kidney, bone and brain tumours. This has also been discussed in depth today at
the international symposium on MRI-controlled sound waves here in the Geertekerk.
This research is taking place in Japan, China, Korea, the United States and Canada,
and within Europe primarily in France, Switzerland, Italy, the United Kingdom,
Germany, the Netherlands and now also in Norway and Denmark. The amount of
research is still increasing. It is currently only a licensed treatment in Europe - that
is to say that the therapy has been approved by the European authorities - for the
palliative treatment of bone metastases. The costs are however not yet reimbursed
by the insurance companies. Acceptance of new medical technologies is always a
lengthy process. It must for instance be demonstrated that a new technique is better
than the existing methods, or that the technique has added value in some other way.
And that costs time and money. Another reason is the regulation of medical studies;
very necessary regulation, by the way. The organisation of medical care in hospital
departments is also important. For MRI-controlled ultrasound, the question also
arises of which department such therapy should belong in: interventional radiology,
radiotherapy, oncology or surgery? The answer depends a great deal on where the
research is being done and where it was started. The radiotherapy and radiology units
at the University Medical Centre, Utrecht, are united in a single Imaging Division. This
is unusual both at the national and international levels - the exception rather than
the rule. It seems to me to be no coincidence that the major developments in imageguided oncological interventions have taken place in close cooperation between
radiology, interventional radiology and radiotherapy within the Imaging division at
the University Medical Centre, Utrecht.
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Back to cancer care. If we heat cancerous tissue for a certain time, the tissue will
die off once what we refer to in professional jargon as the ‘lethal thermal dose’ has
been exceeded. It dies off almost immediately as a result of damage to proteins
and membranes; we then refer to that as ‘ablation’. It does sometimes happen more
slowly, sometimes even several days after heating, if biochemical reactions have to
take place first. This is referred to as ‘apoptosis’. We use MRI-controlled ultrasound
to heat the tumour locally. As we have just seen, we follow or control that using
MRI. We stop the treatment when the heating has gone comfortably beyond the
lethal thermal dose. Let’s take a recent example from an experimental breast cancer
treatment performed in the University Medical Centre, Utrecht, by Maurice van den
Bosch, in close cooperation with the technical team and with Philips.
You can see an MRI image here that clearly shows where the tumour is located (Figure
8). The following video clip (Video 2) shows the tumour being heated by ultrasound,
monitored by MRI temperature measurements. You can see the temperature rising, in
this case going above 60 degrees. You can also see the temperature distribution, and
it is all in real time, i.e. the temperature information is available less than 100 ms after
the MRI has made a new image.
Figure 8: Tumour location.
The following slide shows you the details of this ultrasound device (Figure 9), built
into the bed of the MRI, with the holder that the breast is placed in and the ultrasound
transmitters around it. An initial prototype was built by our laboratory; this is the
second prototype, made by Philips.
We are now in a so-called Phase I study with ten patients. Despite the very promising
initial results, we expect that we will still need about three years before we have
proved that this technique works at least as well as alternative techniques. As I said,
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a
b
c
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Video 2: Heating a breast tumour by MRI-controlled sound waves
Figure 9: Prototype ultrasound device for breast cancer treatment
such proof is a requirement if the technique is to be fully accepted. There are several
alternatives for breast cancer, but the approach using MRI-controlled sound waves
has the great benefit of being entirely non-invasive. We therefore expect that there
will be far fewer negative side effects. After being treated, patients can go back home
the same day. We hope to start a Phase I study into the treatment of liver tumours
shortly. We are now putting the finishing touches to development of treatment
protocols. You can see an example of an experiment using laboratory animals on the
next slide (Figure 10).
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Figure 10: MRI-controlled sound waves: developing a therapeutic protocol for liver treatment.
On the left here, you can see temperature images overlaid in colour on anatomical
images in grey taken during the treatment. The ultrasound enters the body from the
left and you can see the greatest temperature change at the focal point. On the right,
you can see images that were taken after the ultrasound therapy. An MRI contrast
agent can be used to let us see whether the therapy has actually been effective.
You can see the lesions, with a dark core and a high signal around them. The core is
dark because the MRI contrast agent can no longer penetrate it. This tells us that the
tissue there is no longer perfused with blood. At the edge, it is the other way round.
The blood flow increases there and we can see an elevated concentration of the
contrast agent. After the therapy, we are therefore once again able to use imaging to
determine whether the therapy has worked and if it did so sufficiently throughout
the tumour. In short, imaging is an essential element in the planning, execution and
evaluation of treatment.
Ultrasound applications in the liver are technically more difficult because of the
movements caused by respiration and the heartbeat, as well as by the fact that the
ribs partially reflect or absorb sound waves. We need new techniques to provide
solutions to these problems. One important aspect is the interaction between the
MRI part and the ultrasound part of the device. Both are computer-controlled, using
independent operating systems. Nevertheless, we need MRI information in order
to guide the sound waves to the tumour. During the treatment, we also have to
include the degree of heating when adjusting to the correct power, so that the tissue
receives the correct thermal dose throughout. This is demands the real-time control
that I mentioned earlier, making the device more complex. Special algorithms have
to be developed and the information processing speed is a crucial parameter. The
enormous advances in interactive computer games have led to graphics cards
that process data amazingly quickly. We are able to make good use of this massive
progress.
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We must naturally be able to guarantee the safety of the system for medical
applications, despite the complexity. It should be obvious that MRI-controlled
ultrasound requires physicists and computer experts in addition to physicians. Similar
cooperation between doctors and physicists is already fully accepted; there are for
instance legal provisions for radiotherapy because of its use of ionising radiation. MRIcontrolled ultrasound is only in its infancy and the tight-knit interaction between
physicists and doctors is not yet organised well enough. We have therefore started
discussions with various bodies, including the National Cancer Institute and American
Association of Physicists in Medicine from the USA in order to obtain an international
consensus about quality control and the physics knowledge needed for this new
technology.
At the University Medical Centre in Utrecht, we are working not only on the treatment
of breast and liver tumours, but also on the palliative treatment of painful bone
metastases. People are working assiduously elsewhere on the treatment of kidney,
pancreas and brain tumours.
Cancer care is not the only field in which MRI-controlled ultrasound may result in a
new therapy. The technique has also been used recently in the treatment of essential
tremor (or action tremor) in Canada and the United States. This condition often starts
with mild trembling in the hands and arms and may progress to a serious problem
in which normal, everyday things such as keeping hold of a cup can become very
difficult. It is a neurological disorder in which the hands, head and/or voice tremble
rhythmically, or much less commonly the legs or torso. The treatment of essential
tremor by MRI-controlled sound waves has recently been described by Elias et al. in
the leading medical journal The New England Journal of Medicine.
This video clip (Video 3), recorded in Toronto at a well-known centre for MRIcontrolled sound waves, shows how MRI-controlled sound waves are used to treat
part of the thalamus. Immediately after the operation, this patient was able to hold a
glass of water and drink it unaided for the first time in ten years.
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Video 3: Treatment of hand tremor by a small ablation in the thalamus (part of the brain).
4
MRI-controlled ultrasound and chemotherapy
So far I have been talking about using ultrasound for eliminating tissue by heating it
up. There are other possibilities too. At the Centre for Image-Controlled Oncological
Interventions, we are aiming to use sound waves to develop improved forms of
chemotherapy. How is that being done? Before going into more detail, it would be a
good idea to explain a little about current developments in pharmacology. The ideal
remains a so-called ‘magic bullet’, in other words influencing a specific biochemical
pathway by direct interaction between the medicine and its ‘target’. Tumours closely
resemble normal cells, which makes it difficult for medicines to react specifically
against cancer cells. In addition to this general problem, it is important to concentrate
sufficient amounts of the medicine while restricting systemic toxicity. Even when we
succeed in developing specific medicines (which thankfully is happening more and
more often), we have to keep in mind that those medicines face a number of barriers
before they can reach their ‘target’ from the bloodstream. They have to get to the
tumour despite the high pressure around that tissue, cross the epithelial layer (the
layers of cells around the blood vessels), and then get through the cell membrane
(because their ‘target’ is generally intracellular). Sound waves can help in various
ways, and this is the theme of a recent subsidy from the European Research Council
to the Sound Pharma project. Firstly, we can once again utilise the temperature
increase that occurs when sound waves are absorbed. In this case, we are aiming
for an increase of just a few degrees; not lethal in its own right, but sufficient to
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increase the perfusion locally, as well as the vascular permeability - how easily the
blood vessel walls can be crossed - and the toxic effect of the medicines. We can
also utilise the direct mechanical aspect of the vibrations that are induced by the
sound waves. These vibrations can also lead to increased vascular permeability and
this can be further enhanced by contrast agents that are used in ultrasonography.
These are small bubbles of gas that can swell and shrink under the influence of sound
waves, a phenomenon known as ‘cavitation’. It is now known that cell membranes
can temporarily become porous - leaky - during this process, creating a pathway
for the medicines. Moreover, we can create miniature medicine compartments, at
the nanometre scale, which open up under the influence of sound waves. This is
illustrated by the following video clip about nanocarriers, which are heat-sensitive.
They open up at a temperature of 41 degrees, just a little bit above normal body
temperature. This video was made by Philips (Video 4).
We are working on this with Philips Research Eindhoven, the National Institutes of Health,
and an American company called Celsion. The Imaging Division has been working for
some time now with the Pharmaceutical Sciences faculty of Utrecht University, in the
context of the Centre for Image-Controlled Oncological Interventions. Gert Storm, an
expert in the field of nanoparticles with medical applications, works one day a week
on image-controlled chemotherapy at the Centre for Image-Controlled Oncological
Interventions. As Nathan McDannold showed today, it is possible to use sound waves
to temporarily open up the blood-brain barrier locally. The blood-brain barrier is one
of the biggest problems preventing effective medicines from getting into the brain,
thereby making it one of the largest obstacles in the fight against Alzheimer’s disease,
for example. Here you can see how the blood-brain barrier is locally made to ‘leak’
Video 4: Nanocarriers en MRI-geluidsgolven
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temporarily by sound waves. We measure this using MRI contrast agents. They are not
normally able to cross the blood-brain barrier, but after ultrasound treatment with
gas bubbles, we can see uptake of contrast agent as an increase in intensity, but only
at the places where the blood-brain barrier is leaking.
It is therefore possible to use MRI-controlled ultrasound to open up the blood-brain
barrier on a very localised scale (Figure 11). It is interesting to see that we can now
also use MRI to determine not only where the blood-brain barrier has been opened
up, but also for how long and for what sizes of molecules it has become permeable.
To date, this is all only preclinical studies; we do hope however that this will indeed
bear fruit in clinical terms.
Figure 11: Blood-brain barrier being opened
up in a laboratory animal (slide from Nathan
McDannold, Harvard University). It can be seen
to have been opened up at the locations marked
with the arrows.
Sound waves are also able to make a contribution in the field of specific antibodies,
which are receiving a great deal of attention from the pharmaceutical industry. The
high molecular weights of antibodies means that they only diffuse slowly towards the
target. Ultrasound vibrations, supported by slight temperature increases if necessary,
could improve the diffusion and the transport.
A variety of medicines are now known that enhance the effect of radiotherapy. I could
mention gemcitabine and doxorubicin, but there are many others. Chemoradiation,
as it is known, is already being used in clinical practice. However, the combination of
sound waves, radiotherapy and medicines has hardly been touched upon. The Centre
for Image-Controlled Oncological Interventions will also find plenty of promising
material in this field.
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5
MRI-controlled ultrasound and immunotherapy
Are there also possibilities for deploying sound waves once the tumour has
already started to spread? Until now, I have spoken about high-precision sound
waves that can be guided by MRI very accurately to their ‘target’. So how can we
still make effective use of sound waves once the tumour has metastasized? There
are opportunities there as well, in this case via the effects on the immune system.
Together with Professor Gosse Adema of the Radboud UMC and Professor Theo Ruers
of the Antoni van Leeuwenhoek Hospital, we proposed using ultrasound vibrations to
release antigens from the primary tumour. These can be used in turn by the dendritic
cells, the ones that act as the teachers within the immune system, as it were, training
the workers - the T-cells - how to recognise the foreign cells. This allows us to use the
primary tumour to ‘train’ the immune system, enhancing that effect with ultrasound.
Moreover, there are numerous possibilities for improving this immunological effect
of the vibrations by locally depositing medicines that specifically stimulate the
immune system and counteract the inhibitory immunological effect of the tumour
cells. That may all be ‘pie in the sky’ at the moment, but we do hope to develop this
theme further over years to come at the Centre for Image-Controlled Oncological
Interventions. In the European context, discussions have already been started with
Professor De Smedt of the Pharmacological Sciences faculty in Ghent and Professor
Thielemans of the Vrije Universiteit in Brussels.
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MRI-controlled ultrasound and stem cells
There are also intriguing possibilities for making use of ultrasound in regenerative
medicine. We have for instance demonstrated in the past that it is possible to
encourage expression of the associated gene locally using a combination of localised
heating with MRI-controlled sound waves plus the use of a heat-sensitive gene
promoter. The main purpose of our research was to use this as a way of locally creating
differentiation factors for stem cells, thereby forcing the stem cells to differentiate in
a particular direction. As an example, I will take the production of bone cells from
mesenchymatic stem cells. The requisite differentiation factors and the associated
concentrations to force cell differentiation in a specific direction are becoming
increasingly well known. There is also the possibility of giving an additional antitumour function to haematopoietic stem cells after a bone marrow transplant and
then ‘switching it on’ locally after the immune system has recovered. This ‘switching
on’ can once again be done by localised heating with MRI-controlled sound waves.
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7
Action Plan for developing MRI-controlled ultrasound
It should be clear by now that there are numerous opportunities for MRI-controlled
ultrasound. So is it simply a question from now on of getting everyone singing from
the same hymn sheet, or do we have to keep listening carefully for any discordant
notes? For a number of applications, such as the ablation of breast cancer, the
technique is already fairly well defined. A number of practical issues do demand a
special approach. It is for example difficult to get sound waves to go through bone.
Gas and air also cause problems, making applications in the lungs very awkward. MRI
temperature measurements are tricky when there is not much free water present in
the tissue.
And ultrasound equipment is rather expensive, as is the MRI hardware. MRIcontrolled ultrasound is a new technique within oncological care and there is
little or no reimbursement of it by the health insurers. This technique will therefore
provisionally have to be funded by subsidies, which is becoming more and more
awkward in these difficult economic times. The scientist’s task is thus not only to
study and use science, but also increasingly to search for financial backing for that
science. The industrialisation of this new technology also has a key part to play. There
is an essential role for industry in the development of good and - above all - safe
equipment. Healthcare cutbacks are leading to a slowdown in sales, which in turn
is reducing the amounts of money that the industrials are investing in research and
development.
Despite these problems, which may hopefully turn out only to be temporary, the
patient remains the focal point of our research. After all, being able to cure people is
the most important driving force behind our efforts.
8Conclusions
In conclusion, I would like to run through the main points for you again. Focusing
ultrasound presents a huge range of possibilities in medical care. Planning, controlling
and evaluating this by means of MRI makes the technique more precise and allows
us to measure the effect. Local heating of tumours by ultrasound waves can kill off
the tumour. The technique is only in its infancy and is still only being tested clinically
at a small scale. MRI-controlled ultrasound also has numerous potential applications
in chemotherapy, in combination with radiotherapy and also in future in the use of
stem cells and for stimulation of the immune system. The University Medical Centre
in Utrecht has invested heavily in the Centre for Image-Controlled Oncological
Interventions in order to make this research possible.
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9Acknowledgements
I would therefore like to thank the Board of Directors of UMC Utrecht and the
Management Committee of Utrecht University for the confidence they have shown
in me. I am also grateful to the Imaging Division, the Divisional Board and the
management team - Martin Hendriks, Hans Bouwer, Max Viergever and Jan Lagendijk
- for their vision and their initiative in developing the Centre for Image-Controlled
Oncological Interventions, and for their enthusiasm for this research.
I would very specifically like to mention Willem Mali here; he played a major role
in the decision to come to UMC Utrecht. Peter Luijten, Maurice van den Bosch and
Marco van Vulpen have also played important parts. I have already worked closely
with Peter, a Philips man at the time, when I moved from the National Institutes of
Health to Bordeaux. That role was if anything even greater in the move to Utrecht,
not only as the scientific director of the CTMM there, which I have already mentioned,
but also as a new colleague in the Imaging Division and as the leader of the main
MRI research field. Jan Lagendijk, head of Radiotherapy Physics in Utrecht, has been
a vital force in setting up the Centre for Image-Controlled Oncological Interventions.
His optimism is infectious. As regards the clinical applications, our group is working
very closely with Maurice van den Bosch and his team. We are very much looking
forward to intensifying this cooperation even further. The presence of Marco van
Vulpen means that the clinical applications in radiotherapy will increase. Being able
to work in this direct way with the medical staff is very pleasurable and extremely
motivational.
I would also like to express my thanks to my group for their efforts and enthusiasm,
particularly to the French delegation who have dared to take the step of moving
to the Low Countries with me. And also to the staffers Clemens Bos, Mario Ries and
Wilbert Bartels, who have also dared to make the move to the Centre for ImageControlled Oncological Interventions and with whom I work closely on a daily basis.
Furthermore, I would like to thank the many research groups with whom I have
worked - both within the Imaging Division and elsewhere, in nuclear medicine,
image processing, radiotherapy and radiology - and the lab techs and the students
and the secretaries for their enthusiasm and patience with this invasion from France.
You make coming to work a pleasure.
I would also very much like to thank the Focused Ultrasound Surgery Foundation
from the United States; they have been putting in a great deal of effort to get MRIcontrolled sound waves into the clinics in practice. They are working extremely well
with both the researchers and the patients’ organisations.
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My dear friends of HIFU, I thank you all for your enormous contributions to this field, and of
course for coming to Utrecht and making this day such a special one.
A thank-you to my family as well; they have kept supporting me throughout my
scientific career, both through the interest they have shown and in other ways. And
finally I would like to thank you all for being here and for listening.
“Ik heb gezegd.”
(Formal conclusion: lit. “I have spoken”)
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