General Sonopathology (Signs of benign and malignant cystic and

ECBSE General Sonopathology
19.11.2013 1
EFSUMB Course Book
Student Edition
Editors: Jan Tuma, Radu Badea, Christoph F. Dietrich
General Sonopathology (Signs of
benign and malignant cystic and
solid lesions)
Dieter Nürnberg1, Vito Cantisani 2
1
2
Medizinisches Zentrum,Ruppiner Kliniken Charite Berlin, Germany
University of Rome “La Sapienza”, Italy
Corresponding author:
Dr. Vito Cantisani
Department of Radiology,University of Rome "La Sapienza",Policlinico Umberto I, Viale
Regina Elena 244, 00161, Rome,Italy
Tel.: (39) 06-4455602
Fax.: (39) 06-490243
E mail: [email protected]
Acknowledgment: Mattia Di Segni, Hektor Grazhdani, Francesco Maria Drudi
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Content
Introduction ..................................................................................................................... 2
Cystic lesions .................................................................................................................. 2
Criteria of normal cysts ............................................................................................... 2
Signs of pathological cysts ......................................................................................... 4
CEUS in differentiation of cystic lesions .................................................................. 10
Solid lesions .................................................................................................................. 11
Signs of pathological solid lesions............................................................................ 11
Ultrasound features indicating malignancy of solid lesion ....................................... 11
Stones ........................................................................................................................... 21
Free fluid and gas ......................................................................................................... 22
References/Recommended readings .......................................................................... 24
Introduction
While ultrasound waves in liquids and therefore also in cysts are transmitted almost
without hindrance and consequently with no echo, in solid structures, such as
tumours, the waves encounter many structures with different densities compared to
the surrounding tissue. This leads to a different echogenicity. Cysts are generally
black or echo-free in an ultrasound image, while solid tumours have a range of
densities leading to a range of echos, from hypoechoic, to isoechoic, to hyperechoic.
Cysts have typically features, which are explained in the following text.
Cystic lesions
Criteria of normal cysts
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smooth wall (regular contour)
round form
echo free content
posterior acoustic features (dorsal echo plus)
tangential phenomenon / side shadowing
While ultrasound waves in liquid and therefore also cysts, are transmitted almost
without hindrance and consequently without an echo, in solid structures such as
tumours the waves encounter many structures with different densities compared to
the surrounding tissue. This leads to a different echogenicity. Cysts are generally
black or echo-free in an ultrasound image, while solid tumours have a range of
densities leading to a range of echos, from hypoechoic, to isoechoic, to hyperechoic.
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Cysts have typical features, which are explained in the following text.
Figure 1 Cystic and solid lesion in liver. Cysts or encapsulated liquid
structures can be very easily differentiated by ultrasound to
circumscribed solid lesions. In figure 1 a ventral echo-free harmless
cyst can be detected. Further dorsal a small hyperechoic solid lesion
can be seen. The sonographical picture suggests a capillary
haemangioma (see Liver Chapter). While the cyst, as a fluid-filled
structure shows no echo or is almost echo-free, a solid tumorous
structure shows a more or less homogenous echo.
Figure 2 Normal cyst. The image shows a round, echo-free structure with a
smooth surface surrounded by homogenous liver tissue.
Theperipheral echo-free structures are vessel sections. The cyst
shows the typical phenomenon of distal sound amplification, an
echoincrease at the distal part of the cyst, visible as a light dorsal ray.
Laterally to the sound amplification, two hypoechoic, dark lines are
visible, that originates from the lateral cusps of the cyst and
delineatesthe amplification laterally. This is an artefact called the
tangential phenomenon / side shadowing.
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Signs of pathological cysts
Criteria of an abnormal cystic lesion
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irregular wall / irregular contour / calcifications
not round form
echogenic content and internal structures, solid parts
no posterior acoustic features / no dorsal echo plus
Irregular wall:
While normal cysts, without any pathological findings, have a smooth wall, an
irregular wall [Figure 3a, 3b, 3c, 3d] and intramural calcifications are considered
pathological signs. These can contribute information, e.g. to the origination of the
cyst. Genuine cysts have a smooth configuration, secondary cysts show an irregular
configuration, e.g. haemangioma, parasitic cysts, abscesses and pseudo-cysts.
Figure 3a Liver cyst with irregular wall. The wall of the cyst is only partially
smooth. There is a calcification visible in the wall with the typical
acoustical shadow.
The sonic waves cannot penetrate the
calcification. Calcifications are more often in secondary liquid
lesions following a hematoma.
Figure 3bCystic lesion with a very irregular wall and echogenic content. The
wall of the cyst is very irregular and frayed. The relative homogenous
content is a collection of pus. A large liver abscess is depicted here.
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Figure 3c Cyst with irregular wall of the pancreas- pancreatic pseudocyst.
The ventral wall of the cyst is very irregular in this case.This is not a
genuine cyst, but a pseudo cyst emerging after anacute
pancreatitis.The ventral wall of the cyst is multiple millimetres thick.
Such a cysthas to be differentiated from a cystic tumour through
clinical signs,patient history and further imaging techniques.
Endosonography and contrast agent enhanced ultrasound play a
significant role.
Figure 3d Cyst with irregular wall and internal structure of the kidney- atypical
renal-cyst. Deviated atypical cyst of the kidney, which has to be
differentiated from a partly cystic tumour or cystic wall tumour.
Imaging techniques are to be used, especially contrast enhanced
ultrasound.
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Echogenic content and internal structures:
Echogenic content and solid structures (septa) within the cyst are conspicuous
signsthat should be pursued further. If the content is echogenic, it could be blood
after a haemorrhage or pus in an infected cyst [Figure 4]. Pancreatic pseudocysts
can accumulate detritus or partly solid tissue (sequestrum). Septs in a cyst (internal
structures) are suggestive of a tumour, but occur also in parasitic cysts (e.g.
ecchinococcus).
Figure 4a Big cyst of pancreas with internal structures. The internal structures
showed a blood circulation in contrast enhanced ultrasound. This
facilitated the indication to an operation which led to the diagnosis of a
macro-cystic, serous pancreas tumour (benign cystoadenoma).
Figure 4b
Partial cystic tumour of pancreas. There solid partsare more
numerous than the liquid parts in this mucinous cystic adenoma
of the pancreas. This is a benign pancreas tumour that can
normally be identified by endoscopic ultrasound.
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Figure 4c Big cyst of left kidney with internal structures – ecchinococcus cyst.
Normally, ecchinococcous cyst occur more frequent in the liver than
in the kidney, as shown here. In this ecchinococcous cyst septs and
even round cystic structures are visible within a large cyst. (“cysts
within a cyst”). By courtesy of G.v. Klingräf
Figure 4d
Big cyst of liver with internal structures – haemorrhagic cyst. A
primary echo-free cyst in the liver appears diffuse hyperechoic
aftera painful event. It bled into the cyst. The bleeding stops
spontaneously (self-tamponade). There is an increased risk of
secondary infections.
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Figure 4e Big cystic lesion of spleen with internal structures – spleen
hematoma. While under anticoagulation a minor accident
occurredand led to the discovery of this large liquid structure in the
spleen. The septs are caused by parenchyma bridges. Also a
hematoma during organization can cause these septs. The rupture of
the spleen exceeded more than 50% of the organ, leading to a
splenectomy. By courtesy of H. Pannwitz
Figure 4f
Cystic lesion of pancreatic tail with echogenic content – infected
pancreatic pseudo cyst. ¾ of the cyst are filled with
echogeniccontent. During the examination of the spleen the tail of
the pancreas is well visible. In case of an infection an intervention
(puncture or drainage) must follow.
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Figure 4g Big cystic formation with hypoechic content and gas – paracolic
abscess. The combination of liquid content (hypoechoic, fluctuating)
and gas (marker) proves the diagnosis of an abscessor an infection,
respectively.
There are very hypoechoic, mainly hypervascular solid tumours that almost appear
echo-free. This also applies to hypoechoic enlarged lymph nodes. The typical dorsal
acoustical shadow that would occur in cysts is missing [Figure 5]. The echogenicity of
the lesion is often visible, if the signal is increased (increase the gain!).
Figure 5Very echopoor (nearly echofree!) lesions without dorsal acoustic
features. Especially enlarged lymph nodes in malignant lymphomas
or in an acute lymphadenitis can appear almost cystic in nature and
be misinterpreted. The image above shows mesenteric lymph nodes
in a patient with Non-Hodgkin Lymphoma.
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CEUS in differentiation of cystic lesions
Figure 6 Contrast enhanced ultrasound helps to differentiate between
a cyst and a tumour. If a conspicuous wall lesion or echogenic content
is detected in B-mode (marker), that cannot be detected in contrast
enhanced
ultrasound
(no
enhancement), the material
is
amorphousand has no blood circulation. This way, the differentiation
between pseudocysts and cystic tumours is possible e.g. in the
pancreas.
Solid lesions
Signs of pathological solid lesions
Criteria of malignant solid lesions are:
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the invasion of surrounding structures
irregular wall / irregular margins
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not round form, taller than wide lesion
inhomogeneous echogenic content and internal structures
posterior acoustic shadowing
microcalcifications
hypervascularity (elevated RI index)
New signs: Hypoenhancement during the portal and late phases at contrast
enhanced ultrasound
Stiff lesions at US elastography
Ultrasound features indicating malignancy of solid lesions
Any new mass found in any organ at ultrasound examination, should be viewed with
suspicion and the bigger the mass and the more solid component in it, the more
attention should be paid. If the mass presents with an irregular form, it is highly
suspicious for an infiltrating malignancy. On the other hand, however, a regular, round
or oval form does not warrant tranquility and good knowledge of pathology and
ultrasound signs of malignancies in the particular organ are required for the operator
[8].
As a rule of the thumb, suspicion for malignancies should always be kept high in a
new found nodule or mass. Of course, a purely cystic mass is rarely malignant, but in
certain organs like the ovaries, yearly follow up is required if the cyst is bigger than 3
cm in a postmenopausal woman and bigger than 5 cm in a woman in her
reproductive age. A palpable and painful mass in the breast that alarms the woman,
when found at ultrasound to be a simple cyst, should warrant the operator to calm the
patient by saying that the mass is only liquid and to suggest follow-up.
Decompression aspiration of the cyst resolves the pain and also the anxiety of the
subject. A cystic mass that presents thickened walls and internal septa is
denominated a complex cyst and it should be evaluated with greater attention when
found in the ovary, kidney or pancreas. The more solid the component in walls and
septa, the more the mass is suspected for malignancy. In the ovary, signs of
vascularity at color-Doppler in the solid component increase the suspicion. When a
complex ovarian cyst is found, the operator should check the abdomen for free fluid
or peritoneal nodularity, which are both, in this clinical situation, sure signs of
malignant peritoneal spread of ovarian cancer (peritoneal carcinomatosis). In the
kidney and pancreas, a complex cystic mass requires computed-tomography
evaluation and eventual surgery.
In certain cases a cyst is not anechoic at ultrasound, but presents as hypoechoic and
has to be differentiated from a solid nodule which must be evaluated with attention
and followed with repeated examinations when in the breast or thyroid. A cyst is
complicated when containing debris, haemorrhage or infection and in these cases
presents as hypoechoic at ultrasound. Ballottement with the probe, i.e. pushing
sharply and releasing, may help detecting a complicated cyst in the breast.
Ultrasound elastography shows a characteristic artifact in fluids and makes diagnosis
of cysts, and on the other hand if the lesion is solid elastography would show the
signs of a soft or hard solid tissue.
A solid mass or nodule with irregular shape, spiculated margins [see Figure 19] and
heterogeneity is generally suspicious.
Malignancy is almost certain if the mass has interrupted the organ's capsule and
invades adjacent tissues such as in the case of a prostate, thyroid or salivary gland
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nodule, or a renal or liver mass. Vascular invasion is also a sure sign of malignancy
and is seen with hepatocellular carcinomas (HCC) that invade the portal vein, with
pancreatic carcinomas that encase and invade the mesenteric artery and vein, and
with renal carcinomas that form intravascular malignant thrombi in the renal vein. If
an intravascular echoic image containing internal Doppler signal is present in an
enlarged vein, it is qualified as a neoplastic thrombus [see Figure 11 and 12].
Furthermore, a solid mass or nodule that is associated with prominent and unusually
large regional lymph nodes is highly suspicious for malignancy and the nodes are
suspicious for lymphatic spread (N1).
In the spectrum of nodule characteristics, on the opposite side of an irregular shape
mass, with spiculated margins and internal heterogeneity, lies a nodule with
homogeneous echotexture, regular margins, and oval or round shape. Such a
nodule, however, is considered attentively in the context of the organ where it is
presented; for example, in the testicle, pancreas and kidney it is a common
presentation for malignancies, and it is therefore suspicious when found in the liver
and salivary glands. Whereas such a nodule in the uterus is a benign leiomyoma and
unless it is symptomatic (haemorrhage when prominent in the cavity with endometrial
irritation), it requires no particular attention. A nodule of salivary gland cannot be
differentiated as benign or malignant either by ultrasound or by any other imaging
modality. Thus, in the absence of helpful ultrasound signs, evaluation with knowledge
of the pathology of the specific organ is required in such cases.
In a newly found nodule, further imaging work-up is needed with computed
tomography or magnetic resonance, as in the case of nodule in the kidney, pancreas
or liver. Ultrasound is diagnostic in the case of a testicular nodule, but traditional
ultrasound is not capable of distinguishing a benign from a malignant lesion in the
liver. A solid nodule in the liver is always suspicious for metastases or a primitive
neoplasm (HCC), especially in the appropriate clinical context. However, on the other
hand, benign liver lesions can be found in healthy subjects (haemangioma, follicular
nodular hyperplasia and adenoma). The recent developments in ultrasound, with
contrast agent studies and elastography techniques, are currently being established
as valid adjunct tools. The EFSUMB guidelines indicate for liver lesions at
contrastenhanced ultrasound, that hypoenhancement in the late and post-vascular
phases, corresponding to the wash out phenomenon, characterizes malignancies
[Figure 7, 8]. Almost all metastases show this feature, regardless of their
enhancement pattern in the arterial phase. Very few exceptions to this rule have
been reported, mainly in atypical hepatocarcinoma.
Figure 7 On the left side at contrastenhanced ultrasound two hypoechoic
lesions during the late phase are clearly presented; on the right the
lesions at Baseline-ultrasound appeared markedly hypoechoic
(hepatic metastases).
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On the left side at contrastenhanced ultrasound one hypoechoic
lesion during the late phase; and at the right side the lesion at
Baseline-ultrasound appeared markedly heterogeneous with tiny
hypoechoic capsule. (Hepatic adenocarcinoma, hepatocarcinoma).
Ultrasound is the primary imaging modality for the diagnosis of thyroid cancer. 5060% of the population developsthyroid nodules during the life span and only 5-7 % of
them are malignant. In a thyroid nodule, if the presence of one suspicious sign is
found, fine-needle aspiration cytology (FNAC) is required. These signs are:
microcalcifications, interrupted thyroid capsule by the nodule invasion, suspicious
loco-regional lymph nodes, marked hypoechogenicity, irregular form and irregularity
in the margins with spiculations and / or microlobulations, deeper than wide shape in
the transverse scan, vivid internal hypervascularity at color-Doppler, and interval
growth greater than 20% in two dimensions of the nodule[Figure 9].
US elastography is a valuable additional tool in the evaluation of thyroid nodules
aiding in the decision making: to proceed to FNAC or to simply follow up. The
nodules are suspicious when they present as hard, with high stiffness at the various
elastography methods: at real time elastography (RTE) the score 3 or even more at
score 4 [Figure 10], at strain ratio elastography a value greater than 2 and at the
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recent quantitative elastography techniques, high measured elasticity values (at
shear wave elastography SWE >35 – 66 kPa, at acoustic radiation force impulse
ARFI > 2,6 m/sec).
Figure 9
On the left side (B-mode ultrasound) an hypoechoic, fairly
marginatedthyroid lesion is visible; on the right side
(ultrasoundStrain elastography) a completely stiff lesion was
evidenced.
A breast lesion ultrasound assessment is always required after an abnormal
mammography or a non diagnostic mammography. Suspicious ultrasound features of
breast nodules are: hypoechogenicity, irregular shape and irregular margins
(spiculation, angular margins, micro or macro lobulations, duct extension and branch
pattern), microcalcifications, echogenic halo, oval form but taller than wide, posterior
acoustic shadowing [Figure 10], internal vascularity.
Figure 10
A hypoechoic lesion with internal part of shadowing shown. In
thecenter of the measured lesion there is a portion that limits the
through transmission, as shown by the distal shadow.
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Ultrasound lymph node assessment is often requested by the clinician and
furthermore a patient may present for a first examination with a mass that is found at
ultrasound to be a metastatic lymph node or a primary or secondary lymphoma. A
lymph node that presents as big, hypoechoic with a round or irregular shape, is
evidently malignant. However, in many common cases, differentiating the normal
reactive lymph nodes from the malignant ones is often a challenging task. Suspicious
signs are short axis dimensions greater than 1 cm as a general rule, the absence of
the hyperechoic fibro-fatty vascular medullary sinus, heterogeneity in internal texture,
shape that is tending toward round and away from oval, and cortical vascularity at
color-Doppler (normally the vascularity is only hilar with internal branching). A ratio
short axis to long axis (in transverse scan) major than 0,5 is suspicious, showing a
lymph node that is becoming round. Various authors report measured dimensions
that serve as reliable cut-off values, as for example malignancy is suggestive by the
following: in the lateral neck short axis greater than 5 mm, in the submandibular
region short axis >8 mm, in axillary cavity lymph nodes with a focal cortical thickening
greater than 3 mm, Cystic and calcific changes of any kind in a lymph node are signs
of malignancies as they represent degenerative necrosis of malignant tissue.
Keeping in mind the general picture of the clinical condition of the patient is
indispensable when evaluating a solid nodule or mass. If the patient has a primary
neoplasm or has been treated for it, the suspicionsare always high despite few and
slight ultrasound signs. Any new lesion in the liver is a metastasis, a minimally
enlarged lymph node is suspicious and subcutaneous nodes are skin metastatic
spread in such cases.
The main feature indicating malignancy is the invasion of surrounding structures:
 vessels (e.g portal branches for hepatocarcinoma, mesenteric vessels for
pancreatic neoplasms, renal vein for renal carcinoma); the presence of an
intravascular echoic image [Figure 11] with internal Doppler signal is qualified
as neoplastic thrombus or the evidence of direct invasion of a mass with
echogenicity similar to the primary tumour is indicating as infiltrating neoplastic
lesions [Figure 12];
Figure 11
At baseline ultrasound a renal lesion invading the ipsilateral vein
is seen.
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Figure 12 A neoplastic thrombus (some colour-flow signals are evident) is
detected within inferior vena cava.
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organ capsule (e.g. prostate cancer or thyroid nodules), seen as a subtle
extension over it or infiltration of adjacent structures, with associated
limitations of physiologic movements in adrenal malignancies [Figure 13].
Figure 13
Ultrasound shows an heterogenous, mainly hypoechoic,
with an antero-posterior diameter longer than the
transverse, with irregular margins in the left thyroid lobe and
infiltrates the capsule.
Lymph node metastases, another highly valuable feature, is surely best indicated by
hypoechoic round or inhomogeneously echotextured [Figure 14] nodes with
extensively altered vascularization and loss of the fatty hilum or with presence of
focal hypoechoic areas; anyway, the most precocious feature – though non specific for lymph node metastases is the enlargement of lymph nodes located on the typical
lymphatic drainage pathways for the organ.
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Figure 14
Baseline ultrasound shows an heterogeneous thyroid lesion
(Thyroid Carcinoma) with adjacent hetereogeneous, hypoechoic
Lymph node (metastasis).
Figure 15
Baseline ultrasound shows an hyperechoic lymph node with a
peripheral hypoechoic area (metastasis).
Figure 16
Baseline ultrasound shows an heterogeneous, hypoechoic lymph
node with tiny and irregular hylum.
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Figure 17
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At power-Doppler the lymph node appears hypervascular.
Echogenicity is rarely considered as a feature indicative of the nature of the nodules
in organs other than the thyroid – where it must be associated to solid echotexture.
The possible exceptions that can be considered are liver hemangiomas and renal
angiomyolipomas.
Echotexture, when inhomogeneous, is not a direct sign of malignancy – rather
meaning the overgrowth compared to the feeding ability of the vascular background
[Figure 18].
Figure 18
An inhomogeous, hypo-hyperechoic lesion at lower pole of the
kidney is detected
Ill defined margins– applied when more than 50% of lesion borders are not well
demarcated is a common descriptor. In thyroid lesions it was reported to have a
sensitivity ranging between 53-89% and a specificity ranging 15-59%.
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Margins irregularity – appearing as jagged lesion border image – is also considered a
sign of malignancy in many lesions.
Figure 19
At baseline ultrasound the hypoechoic lesion, presented irregular
margins.
Calcifications are readily detected with ultrasound presenting as echogenic (sound
absorption) with posterior acoustic shadow. The diagnostic significance of
calcifications is variable depending on the organ where they are found.
Microcalcifications:Being small do not cast acoustic shadow [Figure 19 and 20] and
they are a sign of malignancy in a thyroid nodule and in a breast lesion. Micro or
macro calcification in a neck lymph node is a sign of metastatic spread.
Figure 20
At baseline ultrasound the hypoechoic lesion, presented multiple
microcalcifications.
Vascularity and blood flow features: Doppler evaluation employs both qualitative
features, i.e the presence and distribution of blood flow; hypervascularity is a finding
to be taken in account since it is suggestive in majority of cases of malignancy.
Figure 21
The lesion presented some internal vascular flow signal.
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Quantitative features deriving from spectral analysis:
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Resistance Index, the ratio between the difference between systolic and
diastolic velocities and the systolic velocity; high-RI is suggestive of
malignancy
Figure 22
At color-Doppler the lesion presented RI >0.70
Stones
Ultrasound is the primary modality and the most sensitive one, for the detection of
biliary stones (gallstones) and the first line for the diagnosis of renal calculi.
Calcification absorbs the sound waves and the classical appearance of stones is that
of an echogenic structure which casts posterior acoustic shadow. [Figure 23 and 24]
Figure 23
At baseline ultrasound an hyperechoic focus with posterior
acoustic shadow is clearly visualized within the gall bladder.
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Figure 24
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At baseline ultrasound an hyperechoic focus with posterior
acoustic shadow is clearly visualized at middle pole of the kidney.
In some small renal stone without clear acoustic shadow, twinkle artifact at colorDoppler (ring-down artifact) is a helpful sign [Figure 25].
Figure 25
At color-Doppler ultrasound an hyperechoic focus with posterior
acoustic shadow twinkle artifact is clearly visualized within the
ureteral distal part.
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Salivary duct stones and eventual accompanying sialadenitis are promptly diagnosed
with ultrasound.
Free fluid and gas
Free fluid in the abdomen or in thorax is echo free. Normally we see the fluid only in
vessels, bile system, urinary system or gastrointestinal tract. In the situation of
pathological effusion the fluid is in abnormal locations like around the liver or between
the bowel.
In the situation of free gas we find the typical artefact of reverberation in atypical (or
wrong) places.
Figure 26a Echo free ascites surround the liver – transudate in situation of
decompensation of liver cirrhosis.
Figure 26b Echoic ascites with fibrin structures in the abdomen in situation of
necrotizing pancreatitis.
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Figure 27aNo organs are visible because of a curtain of gas or reverberations.
Free perforation caused by stomach ulcer.
Figure 27b Two big air bubbles between abdominal wall and liver are also signs
of perforation.
.
References/Recommended reading
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Schmidt G., Greiner L., Nürnberg D. Differential Sonography. Thieme. 2013.
Dietrich CF. EFSUMB - European Course Book. 2012.
Nuernberg D et al. Ultrasound in gastroenterology--liver and spleen.
Z.Gastroenterol. 44 (9):991-1000, 2006.
Will U et al. Interventional ultrasound-guided procedures in pancreatic
pseudocysts, abscesses and infected necroses - treatment algorithm in a large
single-center study. Ultraschall Med. 32 (2):176-183, 2011.
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Dietrich CF, Nuernberg D. Interventional Ultrasound. Stuttgart:Thieme, 2013.
Rumack C M, Wilson S R, Charboneau J W, Levine D. Diagnostic Ultrasound,
Mosby, New Jork, 4 edition, January 2011.
Claudon M, Dietrich CF, Choi BI et al. Guidelines and good clinical practice
recommendations for Contrast Enhanced Ultrasound (CEUS) in the liver - update
2012: A WFUMB-EFSUMB initiative in cooperation with representatives of
AFSUMB, AIUM, ASUM, FLAUS and ICUS. Ultrasound Med Biol. 2013
Feb;39(2):187-210. doi: 10.1016/j.ultrasmedbio.2012.09.002. Epub 2012 Nov 5.
Cooper D. et al 2009: Revised American Thyroid Association Management
Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer.
Thyroid, 1911:1167-214.
Cantisani V, Lodise P, Grazhdani H, et al. Ultrasound elastography in the
evaluation of thyroid pathology. Current status. Eur J Radiol. 2013 Jun 11.