Manuscript
In an emergency setting, ultrasound (US) imaging is the first-line approach, and it
has a fundamental role in detecting and diagnosing various acute abdominal
pathologies [1]
[2]
[3]. The many applications of US imaging in the study
of abdominal diseases make US examination a versatile modality. Nevertheless,
standard US imaging has several limitations in characterizing anatomic structures
and vascularized lesions. Contrast-enhanced ultrasound (CEUS) is a technique that
uses specific contrast agents that can improve the characterization of anatomical
structures through the visualization of small vessels and microcirculation [4]
[5]
[6]
[7].
CEUS contrast agents are microbubbles made of a gas core and a stabilized biological
shell. The second generation of sonography contrast media is a solution prepared
very quickly and it is immediately administrable. CEUS has the benefit of a high
temporal resolution and the operator can detect the contrast transit in the
arterial, portal-venous, and late phase. The arterial phase starts 10 sec
after injection and lasts 25−30 sec. The portal-venous phase starts
immediately after the arterial one. Furthermore, these contrast agents have a short
half-life, are excreted rapidly from the lungs, and are very well tolerated. In
fact, they can be injected into patients with renal insufficiency, hypotension,
shock, without further preliminary laboratory tests, and are also indicated in
critical patients [4]
[5]
[8]. CEUS contrast media are safe with a very low
incidence of side effects. There are no cardio-, nephro- or hepato-toxicities and
life-threatening anaphylactic reactions in abdominal applications have been reported
with a rate of 0.001% in the study of O’Connor et al. [9]. In Europe, CEUS has only been approved for a
limited number of non-traumatic abdominal pathologies in adults, focusing especially
on liver disease. Various studies have shown it to be an excellent imaging technique
also for non-hepatic applications. A fundamental practical approach is described in
the EFSUMB Guidelines [10]
[11]
[12]. CEUS application in children is currently still
“off-label” except for a few indications including vesico-uereteral
reflux, but it could be a very useful method in the non-ionizing imaging of young
patients [6]
[13]
[14]
[15]
[16]
[17].
Today, in the emergency setting, CEUS is used predominantly in the study of blunt
or
penetrating traumatic lesions, especially for the diagnosis and follow-up of the
solid parenchymal organ (so-called “non-operative management”) [8]
[18]
[19]
[20]
[21]
[22]. Often CEUS is used after a baseline US
examination, in an attempt to avoid radiation exposure a computed tomography (CT)
examination, especially in hemodynamically stable minor trauma. Furthermore, CEUS
is
a valid method that can help the radiologist make rapid decisions in case of an
unstable major trauma that cannot be moved to the radiology emergency department and
needs immediate surgical treatment [8]
[19]
[20]
[23]
[24].
The experience with CEUS in abdominal non-traumatic pathology is still limited. In
fact, the purpose of this article is to review the possibilities and limitations of
CEUS in the acute abdominal setting, focusing on various scenarios (inflammation,
ischemia, and hemorrhage) and their related radiological images.
Intra-abdominal hemorrhage
Intra-abdominal hemorrhage can be caused by spontaneous bleeding, for example
during anticoagulant therapy, spontaneous rupture of a solid mass, a
hepatocellular carcinoma, an aortic aneurysm, or a hemorrhage within cystic
lesions ([Fig. 1]) [5]
[25]. It can be secondary also to diagnostic
procedures or therapies such as biopsy or femoral artery puncture in
interventional maneuvers. Baseline US can detect the collection of bloody in the
peritoneal or extraperitoneal space. Performing CEUS exam helps to recognize the
real site of bleeding, through the direct visualization of the contrast leakage
(similar to in angiography or during CT exam after contrast injection) [26]. On CEUS, the operator sees active contrast
extravasation directly from a vessel (in a continuous or pulsatile form), like
in the case of a spontaneous rupture of an abdominal vessel. The extravasation
is seen as enhancing blood passing through the arterial wall defect and adjacent
pooling [27]. CEUS may have difficulties in
differentiating active free bleeding from a pseudoaneurysm. In this case, the
differential diagnosis must be made through angiography or CT ([Fig. 2]) [26]
[28]
[29]
[30]. In the case of a ruptured abdominal mass,
CEUS examination can detect the contrast bleeding within the tumor or into the
adjacent hematoma ([Fig. 3]) [31]. Also, in the case of patients with a
complicated abdominal cystic mass or a vesical hemorrhage, CEUS can depict the
bleeding site and differentiate it from active contrast extravasation or
endoluminal clots (for example, in the case of massive hematuria). However, CEUS
exam cannot depict small, deep, and multiple hemorrhages, especially those
located outside the scanned area. In these cases, CT with contrast media
injection is the main radiological examination to be performed, because of its
panoramic and direct visualization of the exact bleeding vessel [32]. Moreover, it has to be remembered that
clinical evaluation is fundamental. For example, with both B-mode and CEUS it is
not possible to differentiate between a spontaneous or traumatic splenic
rupture, because the imaging findings are the same [33]
[34].
Fig. 1 Hemorrhagic corpus luteum. A young girl 14 y.o. with
pelvic pain arrives at the emergency department and the US examination
shows the presence of an enlarged left ovary compared to the
contralateral. The CEUS exam shows the presence of anechoic (internal)
cystic formation with an enhancing wall and an interruption of the
peripheral profile (white arrow), findings compatible with rupture of
the corpus luteum. It is also associated with free fluid in the
pelvis.
Fig. 2 Splenic pseudoaneurysm. Young male patient 18 y.o. arrives
at the emergency department with upper-left quadrant pain. Baseline US
(arrows in a–b) demonstrates the presence of at least two
parenchymal anechogenic lesions with peripheral vascular signal at
Doppler exam. CEUS (d–e) and CT (C) confirm the presence
of two vascular lesions within the splenic parenchyma referable to
pseudoaneurysm. The diagnosis of certainty and treatment were then made
with angiography and embolization of pseudoaneurysms (f).
Fig. 3 Spontaneous HCC rupture. Case of spontaneous bleeding from
an unknown liver lesion in a patient without additional comorbidities,
which turned out to be hepatocellular carcinoma. CT with contrast medium
(a–b–d–e) highlights the bleeding
lesion in the left lobe, then confirmed by the CEUS examination (arrow
in f) where there is a subcapsular arterial blush indicative of
bleeding in progress, which also extends into the adjacent peritoneal
cavity. Angiography confirms the presence of active bleeding (c),
embolized and no longer evident in angiographic (h) and CEUS
controls (g).
Parenchymal ischemia and infarction
In the case of parenchymal ischemia and infarction, CEUS can easily demonstrate
the non-vascularized area, especially in solid organs like the spleen, liver,
and kidney (that are also effectively examined by ultrasonography examination)
[33]
[34]. Suspected hypoechoic areas due to
hypoperfusion already detected on baseline US can be confirmed with CEUS, which
effectively shows the presence of microcirculation alterations. In fact, the
alterations in perfusion after the administration of the ultrasound contrast
medium appear as clearly visible hypoperfused areas due to the high intrinsic
lesion-to-parenchyma contrast of CEUS [5]. In
these cases, CEUS can be used instead of CT to reach a correct diagnosis and
evaluate the extent of the damage. It is a valid method to perform noninvasive
follow-up especially if the infarction is treated conservatively. A recent
review by Tedesco et al. shows the diagnostic approach of CEUS in infarctions of
the kidney, spleen and pancreas. This affirms that CEUS can replace CT in
specific situations [10]
[35]
[36]. Furthermore, the study by Setola et al.
describes the important role of CEUS in confirming suspected renal infarction on
baseline US ([Fig. 4]) [37]. The same CEUS semeiotics can be seen in testicular or ovarian
torsion and infarction, torsion of the spermatic cord and epididymis, as
described in the study by Badea et al. ([Fig. 5]
[6]) [12]
[38]
[39]
[40]
[41]. An advantage of CEUS in the pediatric
population is the lack of radiation exposure. CEUS has also been reported useful
in evaluating intestinal ischemia and small bowel infarction [42]
[43]. Hata et al. reported a sensitivity of
85–100% and a specificity of 98–100% in
diagnosing intestinal infarction with CEUS, from various etiologies [44].
Fig. 4 Kidney infarct. Right cortical mesorenal infarction with
triangular morphology, poorly visualized at baseline US (a) but
without enhancement at CEUS (white arrow - b) compared to the
remaining vascularized parenchyma.
Fig. 5 Acute testicular infarct. Segmental ischemia of a testicle
visualized as a diffusely hypoechoic area with poor Doppler
representation (white arrow in a–b–c). The
infarcted part of the testicle is not vascularized or enhanced on CEUS
(d).
Fig. 6 Acute ovarian torsion. Young girl 10 y.o. comes to the
emergency department complaining of constant pain during defecation. The
first US examination (a–b) demonstrates the presence of a
coarse cystic mass within the right ovary, with slightly thickened walls
with poor peripheral vascularization. CEUS (d) demonstrates the
presence of a cystic lesion with poorly enhanced walls and with solid
endoluminal parietal projections. The patient completed the diagnostic
procedure with MRI (axial c, sagittal e and coronal
f T2-weighted scans) which confirmed the presence of the
adnexal lesion (arrow). Note the perfect agreement between the
ultrasound images, CEUS, and MRI. The lesion turned out to be a cystic
teratoma.
Abdominal inflammation
Similar to ischemia and infarction, in inflammation and phlogosis, there is a
higher lesion-to-parenchyma contrast ratio in CEUS examination where the
hyperemia corresponds to increased parenchymal microcirculation. CEUS in
inflammatory disease has a key role in differentiating between an acute
phlogosis and a real abscess or phlegmon or inflammation from a gangrenous
evolution [10]
[45]
[46]. This principle is applied to any acute
abdominal inflammatory disease from cholecystitis to appendicitis, pancreatitis,
pyelonephritis, or diverticulitis. In particular, in acute cholecystitis, CEUS
can very easily detect the evident mural enhancement and any possible gangrenous
evolution. In the last case, the lack of mural enhancement is a sign of
perforation indicating the need for immediate surgical treatment ([Fig. 7]) [47]
[48]. Similarly, in acute appendicitis, CEUS
improves the detection rate of the disease achieving 98% accuracy and
100% sensitivity in the diagnosis, as reported by Incesu et al. [49]. This method can be used especially in the
pediatric population after baseline US, avoiding a CT examination. CEUS has been
shown to have sufficient accuracy to determine complications (such as perforated
or phlegmonous and gangrenous appendicitis) [13]
[49]. Another cause of abdominal pain that can
mimic appendicitis is epiploic appendagitis. Also, in this case, CEUS may help
the diagnosis by highlighting rounded enhancement in the abdominal fatty tissue
within a necrotic center, which is a typical finding in the disease [50]. In the case of acute pancreatitis, CEUS could
be used to define the area of higher vascularization within the parenchyma. This
technique is not used in routine daily work, first of all, because patients with
acute pancreatitis have pain and it is not easy to examine the whole pancreas on
US [10]
[51]. In this case, CT exam performed in the
emergency department is the gold standard and helps to grade the process [52].
Fig. 7 Acute complicated cholecystitis. On the baseline US images
(a and c) there are recognizable signs of
cholecystitis with a gallbladder filled with sludge and microcalculi
(arrow). CEUS highlights the evident enhancement of the gallbladder
wall, which appears very thickened (c and d), without
showing signs of complication such as an abscess or perforation.
In the case of acute gastrointestinal inflammation caused by diverticulitis,
appendicitis, or inflammatory bowel disease (IBD – like Crohn disease),
CEUS can improve the detection of their complications, such as abscess and
phlegmon ([Fig. 8]
[9]) [53]
[54]
[55]. Abscess appears as a non-enhancing rounded
lesion with hyperemic borders, while phlegmons are mass-like with a
non-homogeneous pattern of enhancement ([Fig.
10]) [53]
[56]. IBD is a lifelong chronic disease and
patients are often young. Currently, US and CEUS are similar to CT and magnetic
resonance imaging (MRI) in detecting active disease and follow-up of intestinal
lesions [57]
[58]. Detection and evaluation of vascular flow in
the bowel wall is an important factor in the diagnosis and management of IBD. On
baseline US, it may de difficult to distinguish the necrotic liquefied center of
an abscess, but after contrast injection, the presence of non-enhanced necrotic
central nucleus and a peripheral enhanced wall occasionally with internal septa
with perifocal hyperemia can be easily demonstrated, especially during the
arterial phase ([Fig. 11]).
Fig. 8 Acute diverticulitis. In a, the intestinal wall is
visualized an axial scan, highlighting a hypoechoic exophytic lesion
suggestive of a diverticulum. After administration of US contrast medium
b, the evident enhancement of the inflamed intestinal wall,
in the arterial phase (arrow).
Fig. 9 Abscess in diverticulitis. Pain in the left iliac fossa in
a man without further comorbidity. In the clinical suspicion of an
abscess, a CEUS (a–b) examination was performed directly:
it shows a nonhomogeneous constantly anechogenic fluid collection with
marked peripheral arterial enhancement, typical of an abscess. The
finding was confirmed by CT (c–d) which also makes small
air bubbles stand out better, in the context of a peri-diverticular
abscess.
Fig. 10 Abscess in Crohn’s disease. Similarly to [Fig. 9], this is a case of a 37-year-old
male patient with Crohn’s disease with an intestinal abscess
tightly attached to the abdominal wall (arrow).
Fig. 11 Renal abscess. CT a and US (b–c)
signs of a renal abscess in the upper right pole in an elderly patient
(arrow). The CEUS study (c) confirms the presence of an abscess
with an anechoic necrotic center and peripheral enhancement, as
demonstrated by the CT examination. The basic US scan b does not
allow complete visualization of the pathology.
Similarly, in patients with acute pyelonephritis, the inflammatory areas within
the cortical renal spaces are better depicted with CEUS than baseline US. These
areas appear as rounded or wedge-shaped hypoenhancing foci within the normally
enhancing renal parenchyma, with marginal hyperemia ([Fig. 12]) [62]. The presence of some
perfusion can differentiate acute renal infection from infarction. In the latter
scenario, the sonographic contrast signal is absent [63]
[64].
Fig. 12 Acute pyelonephritis. The basic US image in a
highlights a blurred hypoechoic area in the right kidney. After the
administration of contrast medium, the CEUS examination b
confirms the presence of a triangular area with reduced enhancement
compared to the remaining parenchyma: the finding refers to an area of
pyelonephritis (arrows). It is also associated with perirenal free fluid
collection. The images in c and d are images from a follow
up CEUS study after twenty days of antibiotic therapy.
Limits of CEUS
In an emergency setting, CEUS exam has several limitations, primarily related to
the intrinsic limitations of US, i. e., intestinal movement, obesity,
presence of free intraperitoneal air, and the inability of the patient to
maintain breath-hold. Moreover, it does not have panoramic view, unlike CT which
allows the complete visualization of the whole abdomen. CEUS may not diagnose
deep or localized bleeding in a poorly studied abdominal parenchyma, such as the
lower pole of the spleen or in the case of retroperitoneal collections. In these
cases, an abdominal CT scan should be performed urgently. Despite these
limitations, CEUS also has several advantages as explained in this review,
including its rapid availability in an emergency context, patients who are
bedridden, in intensive care units, or who are difficult to transport to the
radiology department for a CT scan.
In conclusion, use of CEUS in the acute non-traumatic setting is not yet
widespread, but it should be, especially because it is a simple and safe imaging
modality in the study of inflammatory, ischemic, and hemorrhagic pathologies of
the abdomen. Furthermore, CEUS improves the accuracy of baseline US imaging,
while limiting the use of CT and related radiation exposure, especially in
younger patients.
