INTRODUCTION — Contrast-enhanced ultrasound (CEUS) is a well-established technique [1-6]. CEUS is most often used for liver imaging, but it is also used for imaging other gastrointestinal organs and non-gastrointestinal organs (eg, heart, spleen, kidneys, and breast) [5] (see "Contrast echocardiography: Clinical applications" and "Contrast echocardiography: Contrast agents, safety, and imaging technique"). It is used in most of Europe and Asia and in many other countries worldwide, and guidelines for its use are available [7-9]. One contrast agent (Lumason) that is used for CEUS of the liver has been approved by the US Food and Drug Administration (FDA) [10]; however, its use in the United States for gastrointestinal disorders has been mainly limited to research settings [1,2,11]. (See "Contrast echocardiography: Clinical applications" and "Contrast echocardiography: Contrast agents, safety, and imaging technique".)
This topic will review the use of CEUS in the pancreas, hepatobiliary system, and gastrointestinal tract. The use of CEUS for the evaluation of liver lesions is discussed separately. (See "Contrast-enhanced ultrasound for the evaluation of liver lesions".)
GENERAL PRINCIPLES — CEUS uses ultrasound contrast agents to improve visualization and characterization of anatomic structures and lesions. Ultrasound contrast agents are microbubbles that are 1 to 10 microns in size (equal to or smaller than red blood cells), which permit visualization of both the larger blood vessels and the microvasculature. CEUS permits real-time visualization of contrast-enhancement patterns during the arterial and venous phases, and in the case of the liver, the portal-venous phase [12]. The general principles behind CEUS, as well as advantages of CEUS over conventional B-mode ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), are discussed in detail elsewhere. (See "Contrast-enhanced ultrasound for the evaluation of liver lesions", section on 'General principles' and "Contrast-enhanced ultrasound for the evaluation of liver lesions", section on 'Advantages of CEUS'.)
TECHNICAL ASPECTS — CEUS can be performed using a traditional transcutaneous approach or in combination with endoscopic ultrasound (typically done for the evaluation of pancreatic lesions). Only small amounts of ultrasound contrast agents are required for CEUS. For non-liver indications, a dose of 2.4 mL is often sufficient.
Transcutaneous contrast-enhanced ultrasound — Prior to performing CEUS, a conventional transcutaneous (B-mode) ultrasound examination is performed. The ultrasound contrast agent is then injected and imaging is obtained from the arterial to the venous phases. The arterial phase is marked by the first visualization of the contrast agent (typically 10 to 20 seconds after contrast injection). Enhancement increases progressively through the early arterial phase to a short peak enhancement. The venous phase starts approximately 30 to 45 seconds after contrast injection and can be described as a phase of low enhancement. However, for parenchymal organs, a longer and higher parenchymal/venous phase enhancement is visible followed by a progressive decrease in enhancement until the microbubbles are no longer seen. Different enhancement patterns can help identify a lesion’s vascular composition, which can assist with lesion identification.
Contrast-enhanced endoscopic ultrasound — Endoscopic ultrasound (EUS) overcomes some of the disadvantages of transcutaneous ultrasound techniques, including limited visualization of the pancreas in many patients. As with transcutaneous CEUS, the addition of a contrast agent when performing EUS (CE-EUS) can help delineate and identify lesions based on their pattern of vascular enhancement [13-17]. (See "Endoscopic ultrasound in chronic pancreatitis" and "Endoscopic ultrasound in the staging of exocrine pancreatic cancer".)
Two different techniques are used for CE-EUS [5]. The first is contrast-enhanced high-mechanical index (MI) EUS (CEHMI-EUS). In CEHMI-EUS, ultrasound contrast agents are used to enhance Doppler signals [18,19]. The advantages of this technique are that it does not require contrast-specific software and that it only adds an additional three to four minutes to the standard EUS examination [20]. However, Doppler ultrasound is limited by artifacts, poor spatial resolution, and low sensitivity to low flow [21].
The other technique, contrast-enhanced low-MI EUS, does require contrast-specific software, allows continuous scanning, and provides a detailed, high-resolution examination of the vascular architecture of parenchymal tissue to help characterize a lesion [22].
Contrast agent dosing — The dose of the ultrasound contrast agent (ie, SonoVue/Lumason) for non-liver indications is typically 2.4 mL [5,23]. The dose may be adjusted based on the sensitivity of the equipment being used, the type of transducer, and the organ under investigation. The dose can be increased to 4.8 mL when using higher frequency transducers, including those used for CE-EUS.
PANCREAS — CEUS techniques (transcutaneous CEUS and contrast-enhanced endoscopic ultrasound [CE-EUS]) can be used to evaluate pancreatic neoplasia and inflammatory lesions [5]. Advantages of CEUS of the pancreas include high-detail resolution and real-time imaging, which permit visualization of intrapancreatic vessels and microvessels [24]. The findings associated with specific pancreatic lesions are similar for both methods, but CE-EUS may permit visualization of a lesion that cannot be seen adequately with transcutaneous CEUS [24-27].
The enhancement pattern of a focal pancreatic lesion is usually compared with the adjacent (healthy) pancreatic tissue. Healthy pancreatic parenchyma typically has a strong, homogenous enhancement pattern that begins immediately after aortic enhancement and lasts from 10 to 30 seconds (arterial phase). After the arterial phase, there is a transient venous phase that lasts from approximately 30 to 120 seconds after contrast injection [4,5]. In patients with pancreatitis, the comparison of the enhancement pattern is more complicated because inflamed pancreatic tissue is hypervascular compared with healthy pancreatic tissue and areas of necrosis appear as nonenhancing.
Indications and efficacy — CEUS in the pancreas is often used to differentiate pancreatic ductal adenocarcinoma from other solid tumors and to differentiate among pancreatic cystic lesions. It has a sensitivity of approximately 90 percent and a specificity of 90 to 100 percent for diagnosing malignancy [28-30].
CEUS can be used to [5,9,31]:
●Further evaluate a focal pancreatic lesion that is indeterminate on computed tomography (CT) or magnetic resonance imaging (MRI)
●Characterize a solid pancreatic lesion as:
•Pancreatic ductal adenocarcinoma
•A hyperenhancing solid pancreatic lesion (eg, a neuroendocrine tumor)
•Mass-forming chronic pancreatitis
•Autoimmune pancreatitis
●Characterize a cystic lesion as:
•A fluid collection or walled-off pancreatic necrosis
•A serous cystadenoma
•A mucinous cystic neoplasm
•A mucinous cystadenocarcinoma
•An intraductal papillary mucinous neoplasm (IPMN)
●Identify areas of necrosis in acute pancreatitis
●Define the dimensions and margins of a neoplastic lesion, including its relationship with adjacent vessels, which is important for staging purposes and determining resectability
CEUS has also been studied for monitoring treatment response in patients with pancreatic tumors after chemoradiotherapy (CRT) or high-intensity focused ultrasound (HIFU) [32,33].
One of the largest studies to look at the ability of CEUS to diagnose pancreatic lesions was the Pancreatic Multicenter Ultrasound Study [29]. It included 1439 patients with pancreatic lesions. The findings on CEUS were compared with the final pathologic diagnoses. For solid lesions, the sensitivity for diagnosing adenocarcinoma was 88 percent and the specificity was 88 percent. The sensitivity and specificity for diagnosing a neuroendocrine tumor were 74 and 93 percent, respectively. For cystic lesions, the sensitivity for diagnosing a neoplasm was 78 percent and the specificity was 100 percent. Finally, the sensitivity and specificity for diagnosing a pseudocyst were 93 and 99 percent, respectively. In a second study that focused on cystic pancreatic lesions, CEUS had a sensitivity for diagnosing pseudocysts of 94 percent and a specificity of 77 percent [21].
Solid lesions — The most common solid primary pancreatic neoplasm is ductal adenocarcinoma [23]. Pancreatic ductal adenocarcinoma is typically hypoenhancing in all phases, whereas other solid lesions, especially neuroendocrine tumors, are hyperenhancing in the arterial phase.
In addition to enhancement patterns, other findings noted during CEUS can help diagnose a pancreatic ductal adenocarcinoma. One finding that helps differentiate ductal adenocarcinoma from other solid pancreatic lesions is dilation of the main pancreatic duct. It is often dilated in patients with ductal adenocarcinoma but not in patients with pancreatic neuroendocrine tumors. Another feature associated with ductal adenocarcinoma is blurred mass margins (by contrast, they are sharply delineated in neuroendocrine tumors and in metastases from renal cell carcinoma).
Ductal adenocarcinoma (hypoenhancing) — Because most ductal adenocarcinomas are characterized by a relatively low mean vascular density, they appear hypoenhancing in all phases (seen in approximately 90 percent of the cases) (image 1) [23,34-36]. This also applies to the very small (ie, ≤15 mm) solid pancreatic lesions [37].
Hyperenhancing lesions — Unlike ductal adenocarcinomas, almost all other solid pancreatic lesions are hyperenhancing because they are hypervascular [28,30,34-36,38-40]. These lesions include neuroendocrine tumors, serous microcystic neoplasia, hamartomas, focal pancreatitis, autoimmune pancreatitis, intrapancreatic accessory spleen, metastases, and other rare neoplasia and focal pancreatic lesions.
Neuroendocrine tumors — Neuroendocrine tumors typically appear as focal pancreatic lesions that are well defined and hyperenhancing in the early arterial phase because of abundant arterial vascularization. The enhancement pattern is homogenous in small lesions, whereas larger lesions show a peripherally dominated pattern [28,30,41,42]. In larger tumors, necrotic avascular areas lead to inhomogeneous enhancement (comparable to the findings in hepatic metastases of neuroendocrine tumors) (image 2) [43]. There are also cystic forms of neuroendocrine tumors with variable appearances [44].
During the venous phase, rapid wash-out resulting in a hypoechoic appearance has been reported [41]. Functioning neuroendocrine tumors are associated with endocrine symptoms. Such tumors are often smaller than 1.5 cm in 50 percent of the cases. This may be useful in differentiating them from solid pseudopapillary tumors, which are usually large and asymptomatic and present with characteristic peripheral rim isoenhancement [45].
Solid pseudopapillary tumors — Solid pseudopapillary tumors of the pancreas have patterns of enhancement that help differentiate them from other solid pancreatic tumors. Peripheral rim isoenhancement, internal heterogeneous enhancement with "fast-in and fast-out" enhancement, and nonenhancing zones due to necrotic and hemorrhagic areas are characteristic [46]. The heterogeneous internal enhancement and the isoenhancing capsule are important diagnostic indicators of a solid pseudopapillary tumor because these features are rarely found in other pancreatic neoplasms [47]. Ultrasound contrast agents (UCA) are blood pool agents that remain within the intravascular space. Due to this property, wash-out of solid pseudopapillary tumors during the venous phase can be seen with CEUS [41,48]. By contrast, CT and MRI show a progressive fill-in due to the late enhancement of the fibrous tissue caused by rapid clearance of contrast agent from the intravascular space into the extravascular space. Thus, only CEUS can accurately show blood flow of these lesions, reflecting their vascular features.
Nonfunctioning islet cell tumors — These tumors are found more often in older adults. They present on CEUS with rapid and intense hyperenhancement during the early arterial phase with nonenhancing necrotic areas [42].
Cystic lesions — CEUS can help differentiate pseudocysts and walled-off pancreatic necrosis (WOPN) from neoplastic cysts (eg, serous and mucinous cystadenomas, IPMNs). CEUS identifies areas that are perfused (septa, nodules) and areas that are nonperfused (debris, clots) [23]. Cystic neoplasms typically show neovascularization of intralesional septa and parietal nodules, whereas pseudocysts and WOPN do not [21,25]. Pseudocysts and WOPN typically contain nonvascularized, completely non-enhancing material (debris, clot) [5,49-51]. However, in the early stages of pseudocyst formation, traversing (large) vessels may be seen that are hyperenhancing [23]. The walls of pseudocysts may be highly vascularized if the cyst is "young" (few weeks of age) and poorly vascularized if the cyst is "old" (few months of age) [52].
CEUS findings associated with specific lesions include:
●Serous cystadenoma – Serous cystadenomas are composed of microcysts. They typically have a lobulated appearance with thin walls, centrally located arteries, and highly vascularized fibrotic septae with a spoke-like pattern [23,44,53]. The vascularized areas are hyperenhancing on CEUS (image 3). Small lesions can be confused with solid pancreatic lesions, including intrapancreatic accessory spleens, because of their abundant arterial vascularization [28,30,41,42].
●Mucinous cystadenoma – Mucinous cystadenomas are macrocystic lesions with wall thickening, visible (enhancing) nodules and septae, and no duct involvement [44].
●Mucinous cystadenocarcinoma – Mucinous cystadenocarcinomas consist of large cysts and solid areas that are poorly vascularized and thus hypoenhancing [52].
●Intraductal papillary mucinous neoplasm (IPMN) – IPMNs are divided into main-duct and side-branch types [5]. Main-duct IPMN has a characteristic endoscopic appearance (dilated pancreatic duct, fish-mouth papilla). Thus, their diagnosis typically does not require CEUS. If CEUS is performed, the appearance is one of irregular wall thickening and dilatation of the pancreatic duct (image 4) [44]. Side-branch IPMNs at an early stage often appear as small cystic lesions connected to the side branches of the main pancreatic duct (duct of Wirsung). More advanced side-branch IPMNs may have a grape-like configuration of small cysts and have additional findings, such as septae, nodules, and wall thickening.
In the mixed-type IPMN, features of main pancreatic duct dilation and side branch cysts are combined.
Pancreatitis
Acute pancreatitis — In acute pancreatitis, organ failure and infected necrosis are the predominant prognostic features. CEUS can help identify necrotic areas since these areas do not enhance [52,54]. In patients who require repeat imaging, CEUS is an attractive option because it does not have the radiation exposure associated with CT scanning.
Chronic pancreatitis — Early in the course of chronic pancreatitis, the pancreatic parenchyma may appear normal or hyperechoic because of fatty infiltration and fibrosis. With more advanced disease, it develops heterogenous echogenicity, and in addition, heterogeneous enhancement on CEUS. Other findings include irregular contour, intraductal and parenchymal calcifications, and pancreatic ductal dilation and strictures.
Mass-forming pancreatitis — Focal pancreatitis appears as a mass-like lesion that might be confused with neoplasia [38]. It typically occurs in patients with a history of chronic pancreatitis. In patients with mass-forming pancreatitis, CEUS typically shows a similar or stronger enhancement pattern than the normal pancreatic parenchyma since both arterial and venous vessels are present (unlike ductal adenocarcinoma, which is typically hypoenhancing because only arterial vessels are present) [20,55].
Autoimmune pancreatitis — There are three recognized patterns of autoimmune pancreatitis: diffuse, focal, and multifocal [56]. Focal disease is often located within the pancreatic head and might mimic pancreatic malignancy [57]. Both focal and diffuse autoimmune pancreatitis typically show hyperenhancement on CEUS or CE-EUS. CEUS contributes to the differentiation of hypoenhancing ductal adenocarcinoma from hyperenhancing focal autoimmune pancreatitis [58,59]. For better visualization of vascular patterns, three-dimensional reconstruction might be useful [60].
BILIARY TRACT — CEUS has been used to evaluate the gallbladder and the biliary tree. CEUS can be used in the following clinical situations:
●To differentiate nonenhancing sludge, debris, and parasites from enhancing neoplasia
●To detect infiltration of surrounding structures by a tumor
Gallbladder — CEUS in the gallbladder and biliary tree is mainly helpful in differentiating nonenhancing sludge, debris, and parasites from enhancing neoplasia [5,61]. The benefit of using high frequency linear transducers has been shown [62,63]. The vascular phases seen in the gallbladder wall are different from those of the liver because the blood supply is provided entirely by the cystic artery and not by portal vein branches [5,64]. As a result, the arterial phase is followed directly by the venous phase [5].
CEUS has been used to detect gallbladder cancer and to detect complications of cholecystitis:
●Gallbladder carcinomas are typically hyperenhancing in the arterial phase and hypoenhancing in the venous phase (image 5). The imaging also shows disruption of gallbladder wall layer structure. The absence of enhancement in biliary sludge allows differentiation from a tumor [5]. In addition to suggesting a diagnosis of gallbladder carcinoma, CEUS can detect infiltration of the surrounding liver parenchyma or liver metastases [23].
●In patients with cholecystitis, interruption of the gallbladder wall suggests perforation. This can be confirmed by noting a lack of enhancement of the perforated wall. CEUS can also be used to look for abscess formation in the adjacent liver parenchyma [65,66].
Biliary tree — CEUS may have a role in evaluating patients with cholangiocarcinoma. Promising findings have been observed in studies of patients with extrahepatic cholangiocarcinoma. CEUS (predominantly contrast-enhanced endoscopic ultrasound) has been able to determine the depth of tumor infiltration and to detect involvement of surrounding tissue [23,64,67].
GASTROINTESTINAL TRACT — In the gastrointestinal tract, CEUS has primarily been used to evaluate the bowel wall and peri-intestinal structures. In addition, extravascular (intracavitary) use has been described. The normal gastrointestinal wall measures less than 2 mm in thickness and shows homogenous contrast enhancement [68]. For gastrointestinal tract examination, higher frequency transducers (7.5 MHz) and higher contrast doses (eg, 2.4 to 4.8 mL) are used. The arterial phase lasts until 30 to 40 seconds after injection, when peak enhancement is reached. Then, a venous phase follows, lasting until approximately 120 seconds [5,69].
Inflammatory bowel disease — In patients with inflammatory bowel disease (IBD), CEUS is helpful in distinguishing abscesses from (peri-) intestinal vascularized inflammatory masses, including fistulas (image 6) [5,23,70,71]. CEUS can also help distinguish between fibrous and inflammatory strictures since active inflammation enhances strongly, whereas a fibrotic stricture enhances poorly [72]. In some countries outside of the United States, intestinal ultrasound has been introduced in daily praxis [73-77]. However, in the United States and United Kingdom, evaluation with CT or MRI is more commonly performed for the evaluation of IBD.
CEUS can be used to study disease activity in IBD, using bowel wall thickness and CEUS enhancement as markers of inflammation, but the role of CEUS for treatment initiation and monitoring has not yet been determined [71]. The use of an oral anechoic contrast solution (iso-osmolar polyethylene glycol) enhances the ability of CEUS to evaluate inflammatory activity and decreases the interobserver variability [78-80].
CEUS can be used in the following clinical situations:
●Identification of and differentiating between a fistula and abscess
●Estimation of disease activity in IBD
●Discerning between fibrous and inflammatory strictures in Crohn disease
CEUS has been used to quantify bowel wall vascularity, which is considered to be a marker of inflammatory activity in patients with Crohn disease [75,81,82]. Enhancement in different wall layers can be evaluated and quantified and correlates well with clinical activity indices [81,83,84] and with MRI findings [85,86]. Time-intensity curve analysis (contrast kinetics) may further quantify disease activity [5]. In a study with 104 patients with Crohn disease examined by CEUS with respect to the disease activity index, it was found that the pattern of contrast enhancement and the ratio of enhanced to entire wall thickness had a sensitivity of 81 percent and a specificity of 63 percent for detecting active disease [81].
In a second study with 105 patients with Crohn disease, CEUS was compared with magnetic resonance enterography (MRE) for detecting terminal ileal inflammation (using ileoscopy as the gold standard for assessing disease activity) [87]. CEUS was technically feasible in 98 percent of patients and MRE in 100 percent. CEUS was more sensitive than MRE (100 versus 87 percent), with similar specificity (92 versus 100 percent) for detecting active inflammation in the terminal ileum. MRE detected 16 ileal strictures and five fistulas. CEUS identified 11 of the strictures but none of the fistulas.
CEUS may also provide prognostic data in patients receiving biologic therapies [88], but this has not yet been evaluated in detail. A limitation of CEUS is that the entire intestine cannot be assessed.
Neoplasia — A role for CEUS in the diagnosis of gastrointestinal cancer has not been established [89,90]. Gastrointestinal stromal tumors (GISTs) and other subepithelial lesions show typical arterial hyperenhancement [91]. Enhancement of small GISTs (<20 mm) and larger low-risk GISTs may be homogeneous, whereas almost all malignant GISTs show heterogeneous enhancement and avascular areas, independent of their size. Central necrosis may be seen in GISTs using CEUS and contrast-enhanced endoscopic ultrasound. Central necrosis is often not seen with other subepithelial lesions (eg, leiomyoma, schwannoma), which show homogeneous enhancement.
OTHER USES — CEUS can be used in adults and pediatric patients with suspected trauma-related laceration and/or bleeding of parenchymal organs (eg, spleen, liver, and kidney) [92-96]. CEUS can also be used to characterize focal splenic lesions and the spleen in general [97-99] and also to evaluate peritoneal bleeding [95].
Evaluation with CEUS has been supported by society guidelines, and CEUS has been approved by regulatory agencies for use in pediatric populations [100-102].
EXTRAVASCULAR CONTRAST ADMINISTRATION — Numerous reports on extravascular or intracavitary administration of ultrasound contrast agents have been published, but large prospective studies are lacking [103-105]. The contrast agent can be injected into physiologic cavities (eg, the gallbladder) or into non-physiologic spaces such as fistulas. The examination of the course of fistulas in Crohn disease is a typical extravascular application.
Uses — Extravascular CEUS can be used in the following clinical situations involving gastrointestinal organs:
●Differentiating between a fistula and abscess
●Assisting in interventional procedures (eg, abscess drainage) [106]
●Determining the route of a fistula
●Diagnosing Zenker's diverticulum [107]
●Diagnosing hepatic hydrothorax
●Percutaneous transhepatic cholangiography and drainage [108,109]
●Percutaneous transhepatic and endoscopic-guided gallbladder drainage [110,111]
In addition to diagnosing abscesses, the combined use of intravenous and intracavitary CEUS can guide abscess treatment. Contrast agents are given intravenously for better delineation of the abscess and are injected into the abscess cavity during intervention to detect communication between septated cavities. The combined approach is also used for follow-up examinations to evaluate the treatment response and detect complications [5,106].
Other clinical applications include evaluation of diverticula, gastroesophageal reflux disease, bile ducts, and intestinal stenosis. Functional ultrasound (eg, determining gastric emptying) can also be performed using intraluminal contrast [112]. Extravascular CEUS is most commonly used in settings when standard diagnostic techniques are inconclusive, not suitable for a particular patient, are associated with high risk (eg, moving a patient out of an intensive care unit), or are not available [113].
Technique — No standard dose of ultrasound contrast agent has been established for intracavitary (extravascular) injection. The range of reported doses is 0.1 mL to 1 mL (most commonly just a few drops) diluted in 10 mL or more of 0.9 percent saline; a higher content of contrast agent may be needed for high-frequency ultrasound probes (eg, those used for contrast-enhanced endoscopic ultrasound) [3,114].
If the aim of the investigation is to detect a connection between two cavities (eg, when evaluating fistulas or diagnosing hepatic hydrothorax), a dose of 1 to 2 mL appears to be effective. If the aim of the investigation is to demonstrate the exact anatomy of a cavity, a lower dose must be given to avoid shadowing that may result in poor image quality and missing or false information [109,115]. One suggested dose in this setting is 0.1 mL of the ultrasound contrast agent in 20 mL saline [114].
SUMMARY
●Background – Contrast-enhanced ultrasound (CEUS) is a well-established technique for imaging the liver and other organs. It is used in most of Europe and Asia, and in many other countries worldwide. The contrast agent Lumason that is used for CEUS of the liver has also been approved by the US Food and Drug Administration. (See 'Introduction' above.)
●CEUS uses ultrasound contrast agents to improve visualization and characterization of anatomic structures and lesions. CEUS permits real-time visualization of contrast-enhancement patterns during the arterial and venous phases, and in the case of the liver, the portal-venous phase. (See "Contrast-enhanced ultrasound for the evaluation of liver lesions", section on 'General principles' and "Contrast-enhanced ultrasound for the evaluation of liver lesions".)
●Pancreatic imaging – CEUS in the pancreas is often used to differentiate pancreatic ductal adenocarcinoma from other solid tumors, such as neuroendocrine tumors. It is also used to differentiate pancreatic cystic lesions (eg, intraductal papillary mucinous neoplasm, mucinous cystadenomas, serous cystadenomas, organized pancreatic necrosis, and pseudocysts). (See 'Pancreas' above.)
●Biliary tract imaging – In the gallbladder and biliary tree, CEUS has been used in the following clinical situations (see 'Biliary tract' above):
•To differentiate non-enhancing sludge and debris from enhancing neoplasia
•To detect infiltration of surrounding structures by a tumor
●Intestinal imaging – In patients with inflammatory bowel disease (IBD), CEUS can help to distinguish abscesses from (peri-) intestinal vascularized inflammatory masses, including fistulas. CEUS can also help characterize fibrous versus inflammatory strictures since active inflammation enhances strongly, whereas a fibrotic stricture enhances poorly. (See 'Gastrointestinal tract' above.)
●Use of extravascular contrast – In extravascular CEUS, the contrast agent is injected into physiologic cavities (eg, the gallbladder) or into non-physiologic spaces and fistulas. Extravascular CEUS can be used in the following clinical situations (see 'Extravascular contrast administration' above):
•Differentiating between a fistula and abscess
•Determining the route of a fistula
•Diagnosing hepatic hydrothorax
•Facilitating percutaneous drainage procedures
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