Contrast-enhanced ultrasound (CEUS) of the abdominal vasculature
Vascular diseases account for a significant proportion of abdominal pathology and represent a common referral source for abdominal ultrasonographic examinations. B-mode, color Doppler, and spectral Doppler analyses are well-established in the evaluation of abdominal blood vessels although they may occasionally be limited by lower sensitivity for slow flow visualization or the deeper location of abdominal vascular structures. The introduction of microbubbles as ultrasonographic contrast agents has rendered contrast-enhanced ultrasound (CEUS), a valuable complementary ultrasonographic technique, which is capable of addressing clinically significant problems and guiding patient management. The purpose of this pictorial review is to analyze the use of CEUS in the evaluation of abdominal vascular pathology and illustrate such applications by presenting representative images. Pathology discussed includes abdominal aortic aneurysm, post-endovascular treatment aorta, portal vein thrombosis, abdominal vascular trauma, and organ transplantation along with its complications.
KeywordsContrast-enhanced ultrasound Aorta Portal vein Aneurysm Endoleak Trauma
Ultrasonography (US) is a well-established first-line modality for the evaluation of abdominal symptoms. Vascular diseases account for a significant part of abdominal abnormalities comprising a wide spectrum of conditions including arterial and venous diseases, diseases affecting native organs, post-operative surveillance and detection of complications, benign and malignant entities, and follow-up of transplantation. Its widespread use is based on numerous advantages, including low cost, repeatability, potential to be performed at any location from the patient’s bedside to the operating room, good patient tolerability, and the absence of contraindications. Nevertheless, US has inherent limitations and in some cases may not successfully address all clinical demands. Inappropriate body habitus, the presence of overlying gas-containing intestinal loops, deep position of abdominal organs, and vascular structures are important limitations for the ultrasonographic evaluation of abdominal abnormalities. When it comes to abdominal vascular diseases, color and power Doppler techniques along with spectral analysis are essential for diagnosis but again have inherent limitations like Doppler angle dependency, limited sensitivity to slow flow, and aliasing or blooming artifact . These limitations are usually accommodated by the performing physician but may hinder proper diagnosis in challenging conditions like the detection of a small or delayed endoleak or the identification of neovascularization within a malignant portal venous thrombus. Computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are currently the reference methods for diagnostic evaluation of abdominal vascular abnormalities, overcoming US limitations, and meeting clinical imaging needs. However, there are situations where CTA and MRA should be avoided, including patients with renal impairment, cardiac pacemakers, and metallic foreign bodies. In a number of patients, US will be the sole imaging modality.
Recent significant technological advances in US with the introduction of elastography and contrast-enhanced ultrasound (CEUS) have expanded capabilities, with the term multiparametric ultrasound (MPUS) used to encompass all the facets of US . Contrast-enhanced ultrasound, using microbubble as ultrasonographic contrast agents (UCA), has gained wide acceptance in many clinical scenarios, culminating in the publication of numerous official recommendations . The recent Food and Drug Administration (FDA) approval for an UCA for characterization of focal liver lesions in adult and pediatric patients is expected to further increase the use of CEUS in the United States . With regard to abdominal vascular pathology, CEUS has been investigated in many applications although considered particularly valuable in the detection and characterization of aortic endoleaks, identification of aortic dissection and rupture, and for differential diagnosis of neoplastic vs. bland thrombus in the portal vein and inferior vena cava (IVC) [1, 4]. Beyond the unenhanced ultrasonographic technique’s inherent advantages previously described, CEUS is also characterized by improved flow visualization even in extremely small-caliber vessels, for example, in tumor neovessels, superior spatial and temporal resolution in real-time evaluation, and increased contrast between blood flow and avascular tissues. This relies on the unique property of UCA to strictly remain within the vascular tree, incapable of diffusion through the vessel wall as their size does not permit this. Moreover, CEUS advantages include dispensing of any prior laboratory tests, excellent safety profile, and limited contraindications [1, 3, 5].
Summary of CEUS applications for various abdominal vascular systems
Specific strengths over CTA
Delineation of mural thrombus blood flow within an aneurysm
Detection of active extravasation in ruptured AAA
Detection of aorto-caval fistulas
Detection of aortic dissection
Detection of rupture signs in the emergency department
However, an MDCTA should always be performed when available
Detection and characterization (classification) of endoleaks
Quantification of aneurysm enhancement
Better characterization of endoleaks
Lack of nephrotoxic contrast agent and ionizing radiation, suitable for long-term follow-up
Improved detection of portal vein thrombus
Characterization of portal vein thrombosis as benign or malignant
Increased spatial and temporal resolution within the field-of-view
Improved detection of neovessels
Improvement of renal arteries evaluation with Doppler technique
Improvement of mesenteric artery evaluation
Detection of parenchymal injuries
Detection of vascular pathology like pseudoaneurysm or active bleeding
Prolonged continuous scanning
Detection of vascular complications like hepatic artery and portal vein thrombosis or stenosis
Prolonged continuous scanning
Technique and safety
CEUS is performed with the intravenous administration of a bolus dose of the UCA, and essentially always performed after a complete unenhanced ultrasonographic examination. This allows the examiner to identify the area of interest, establish an initial opinion, ascertain the viability of a subsequent CEUS examination and plan the procedure to maximize the diagnostic outcome. Once the unenhanced ultrasonographic protocol is complete, having appreciated the gray-scale, color, power Doppler, and spectral analysis findings, an intravenous catheter can be placed in the antecubital fossa. It is best to insert the intravenous catheter following the baseline US to avoid unnecessary cannulation if the CEUS examination is not deemed useful. In general, the amount of UCA administered varies depending on the ultrasound machine’s sensitivity and the product used. SonoVue™ (Bracco SpA, Milan, Italy) is the most widely used contrast agent in Europe and consists of microbubbles containing an inert gas (sulfur hexafluoride) encapsulated by a phospholipid shell, marketed as Lumason™ (Bracco SpA, Milan, Italy) in the United States. A dose of 2.4 mL of Lumason™/SonoVue™ per injection is considered adequate for the liver and other abdominal vascular procedures. A second dose of 2.4 mL can be administered if needed. UCA are strict intravascular agents, large enough (10 μm) to preclude passage through the vascular endothelium, but small enough to circulate through small capillaries. Crucially, the metabolism of UCA renders them independent of renal excretion, the phospholipid shell is metabolized by the liver and the contained inert gas is exhaled by the lungs. As a result, CEUS can be safely performed in patients with renal impairment. In order to achieve optimal visualization of the UCA, a contrast-specific ultrasonographic technique should be applied. Pulse inversion and amplitude-modulation techniques which in general suppress echogenic signals originating from static tissues while visualizing echogenic signals produced by oscillating microbubbles are used. This results in the optimal echogenicity distinction between UCA and static tissues and offers the best spatial and temporal resolution. Two valuable techniques in vascular CEUS include the replenishment mode after a high-Mechanical Index pulse and the Temporal Maximum Intensity Projection (MIP) mode. In the first technique, a high-MI ultrasound pulse is used to disrupt all the microbubbles lying within the imaging field with replenishment allowing observation of the enhancement pattern of structures. In the second technique, the ultrasound device aggregates bright echoes of the UCA and creates cumulative images which illustrate the vascular pattern or architecture of structures under investigation [1, 3, 4, 6].
Among its advantages, CEUS can be performed without any prior laboratory examination as impaired renal function is not a contraindication for administration of UCA, contrary to CTA and MRA. The contraindications for CEUS are limited and include known history of allergic reaction to the UCA itself, severe pulmonary hypertension and pregnancy. The contraindication of right-to-left shunt has been recently discontinued [1, 7]. SonoVue™ has been extensively investigated for adverse reactions and has an excellent safety profile. Serious adverse reactions occurred in only 0.0086% of patients and treatment was necessary in only four patients. This adverse reaction rate is considered comparable to the rate of MR contrast agents and lower than CT contrast agents [1, 8, 9]. CEUS is a safe technique; however, given the very small likelihood of adverse reactions, resuscitation equipment should be available in every US Department where CEUS examinations are performed.
The term abdominal aortic aneurysm (AAA) refers to an irreversible enlargement of the abdominal aorta of more than 3 cm or 50% of reference diameter . US is excellent for screening or diagnostic evaluation and follow-up of AAA with high sensitivity and specificity and excellent intra- and inter-observer agreement . The use of UCA adds little to the evaluation of an uncomplicated AAA, although it will readily and accurately delineate mural thrombus and differentiate this from slow blood flow, often not visualized with conventional US techniques [1, 4, 12, 13]. Rupture of an AAA; associated with high mortality, necessitates early and accurate diagnosis with immediate treatment [10, 14]. Rupture risk increases with increasing aneurysm diameter rising to > 30% for aneurysms larger than 7 cm . Patients presenting with abdominal pain of acute onset and low blood pressure or decrease of hematocrit may signify an AAA rupture, and US can exclude the presence of an AAA. US has limited accuracy for detection of rupture, . The use of UCA significantly increases the sensitivity for detection of several findings of AAA rupture. With the intravascular nature of the UCA, CEUS is able to visualize active extravasation and dependent pooling of the UCA in the retroperitoneum or peritoneal cavity. Although these findings closely correlate with those provided by CTA, CEUS has the potential to be performed at the bedside in the Emergency Department, prompting accurate diagnosis with earlier treatment [16, 17].
AAA rupture may rarely be complicated by the formation of an aorto-caval fistula, which needs specific management. Although CTA is the reference method for the evaluation of aorto-caval communications, CEUS has the potential to delineate such communication with high accuracy in a real-time and dynamic manner [18, 19]. Arterial-venous communications have also been demonstrated with UCA in different vascular systems including the femoral vessels .
Dissection usually affects both thoracic and abdominal aorta, with isolated abdominal aortic dissection being rare . Symptoms like asymmetric blood pressure, pain of acute onset, and signs of organ dysfunction secondary to ischemia should point toward the diagnosis of aortic dissection [21, 22]. CTA remains the primary modality for emergency evaluation of the whole aorta including the iliac arteries. If US findings are inconclusive but suspicious of dissection, UCA can be used. Suspicious conventional US findings include an intimal flap and bidirectional color flow signals within the lumen of aorta. The administration of UCA readily and accurately visualizes intimal flaps, establishing the diagnosis of dissection. Moreover, CEUS helps identify re-entry points and discriminate true and false lumen as the enhancement of the former precedes that of the later [13, 19, 23, 24, 25].
US offers a cost effective, well-tolerated option for imaging surveillance of the post-EVAR aorta, but limited by body habitus, operator experience, and technical artifacts. The diagnostic accuracy varies; studies reporting a 45% positive predictive value and 86% sensitivity for endoleak detection  with US detecting more endoleaks requiring intervention compared to CT, with a 90% sensitivity and 81% specificity , compared to color Doppler with a sensitivity of 33%–63% and specificity of 63%–93% [36, 37].
CEUS has been widely investigated for accuracy in detecting endoleaks. Optison™ (Mallinckrodt, St Louis, Mo) was found to accurately classify endoleaks as type 1 or 2, enabling US to detect more endoleaks than delayed-phase CTA . The diagnostic accuracy of CEUS with Optison™ for the diagnosis of endoleaks is reported at a sensitivity of 100% and specificity of 65% . CEUS with SonoVue™ has demonstrated variable results, with a sensitivity of 80%–100% and a specificity of 82%–100% in diagnosing endoleaks, outperforming color Doppler US [36, 37, 40, 41, 42]. Some studies have concluded that CEUS may even outperform CTA, the current gold standard for evaluation of endoleaks, primarily attributable to the dynamic and real-time nature of imaging . According to a meta-analysis, CEUS pooled sensitivity and specificity for diagnosis of endoleak is 91.4% and 78.2%, respectively, although significant heterogeneity of studies was noted, potentially limiting the accuracy for specificity . Beyond subjective assessment of endoleak presence, CEUS also provides the potential for objective quantitative analysis of aneurysmal sac enhancement. Studies using time–intensity curves have demonstrated that CEUS is 99% sensitive and 93% specific for detection of endoleaks, compared with CTA, with a significant difference between the enhancement level of aneurysms with and without endoleak . If a four-dimensional technique is applied, CEUS has equivalent accuracy to CTA for evaluation of post-operative aortic aneurysm diameter, volume, and endoleak detection in patients with fenestrated endografts . According to a systematic review, CEUS and MRA have superior diagnostic accuracy compared to CTA for identification of post-EVAR endoleaks, although being equivalent to CTA for characterization of endoleaks type 1 and 3 . CEUS was also found to outperform CTA for the diagnosis of delayed type II endoleak .
In conclusion, CEUS offers a beneficial alternative to CTA especially for patients with impaired renal function. Moreover, CEUS is also a suitable alternative for younger patients with EVAR reducing the cumulative exposure to ionizing radiation, with the need for lifelong imaging surveillance with CTA. CEUS could be incorporated in diagnostic algorithms for the detection of endoleak as a second step after initial US examination, in order to increase the technique’s diagnostic accuracy. In cases of negative results, the patient could be safely discharged and referred for follow-up imaging. Further imaging with CTA could be reserved for cases with positive results or continued suspicion of endoleak [28, 31, 36, 47].
Portal vein thrombosis
CEUS in abdominal trauma has been evaluated with promising results. Traumatic parenchymal lesions appear as non-enhancing hypoechoic areas and showing variance with the otherwise normally perfused parenchyma. CEUS can readily identify and characterize lacerations, contusions, and intra-parenchymal or sub-capsular hematomas affecting all solid organs of the abdominal cavity. Based on studies comparing US and CEUS with CT as the reference standard in patients sustaining blunt abdominal trauma, CEUS was found to outperform US in terms of sensitivity and specificity for the diagnosis of solid organ injury, with CEUS demonstrating 69% sensitivity and 99% specificity for diagnosing renal trauma, 84% sensitivity and 99% specificity for liver trauma, and 93% sensitivity and 99% specificity for splenic trauma [1, 55, 56].
US is routinely performed for monitoring of transplanted organs during the post-operative period for early detection of complications, including arterial occlusion or stenosis and venous thrombosis. The unenhanced techniques of B-mode, color Doppler, and spectral analysis are an invaluable tool for screening for these complications. However, sensitivity is limited with inconclusive results. Further imaging is often warranted either with a non-invasive type of angiography (CTA or MRA) or with interventional angiography. CEUS is well-established for the evaluation of both micro-vasculature and macro-vasculature, acting as a potential alternative to CTA or MRA.
It has been established that the administration of UCA increases the diagnostic accuracy of US for the detection of ischemic areas of both native and transplanted organs, demonstrating areas of ischemia with increased tissue contrast, depicted as non-enhancing areas within the normally perfused parenchyma. Color Doppler provides only a subjective assessment of tissue vascularity based on the color flow signals [58, 59, 60, 61].
CEUS following renal transplantation can be used to identify acute cortical necrosis, demonstrating the peripheral rim sign, as seen on CT and MR imaging . Functional information related to the transplanted kidney can be obtained with quantification of parenchymal signal intensity on CEUS. This technique produces time–intensity curves and dynamic variables like time-to-peak and peak intensity. Good inter-observer agreement was demonstrated with this type of analysis, while the quantitative variables obtained have been correlated with glomerular filtration rate 3 months after transplantation .
Other abdominal vessels
The use of UCA for the evaluation of other aortic branches is limited to the superior and inferior mesenteric artery. Definity™ (Lantheus Medical Imaging, Billerica, Massachusetts) offers increased sensitivity for the identification of celiac and mesenteric artery stenosis and occlusion . Others have investigated the use of UCA for evaluation of mesenteric transit time in Crohn’s disease, and even though visual and software-based assessment of the time of maximum UCA enhancement in the superior mesenteric artery and vein correlated well, there was no significant correlation with disease activity .
CEUS has also been used to detect liver metastasis by evaluating hepatic artery and vein enhancement based on the arrival times to hepatic artery and vein and transit time between artery and vein; shorter with an increased level of enhancement in both vessels in patients with liver metastases. Based on these results, a functional ultrasonographic technique performed with only 0.6 mL of SonoVue™ can be used to detect micrometastases in the liver .
The introduction of UCA has significantly expanded the role of US in the investigation of abdominal vascular diseases. CEUS is superior to conventional US techniques in term of tissue contrast, spatial, and temporal resolution and its dynamic and real-time nature in assessment of tissue perfusion and vascular lumen opacification. Experience has shown that CEUS plays a key role in certain clinical scenarios such as evaluation of abdominal trauma, diagnosis of organ ischemia, imaging surveillance of post-EVAR aorta or the differential diagnosis of malignant vs. benign portal vein thrombosis in patients with liver cirrhosis and hepatocellular carcinoma. CEUS is also useful in assisting ultrasonographic evaluation of other blood vessels, although the widespread availability of CTA and MRA has limited its role in the renal arteries and mesenteric arteries.
Compliance with ethical standards
Conflict of interest
Authors VR and CF declare that they have no potential conflict of interest. Author GY has received lecture fees from Bracco. Author DH has received fees from Bracco for providing a training workshop on CEUS. Author PS has received lecture fees from Bracco, Siemens, Samsung, Philips, and Hitachi.
This article does not contain any studies with human participants or animals performed by any of the authors.
Online Resource 1 Video clip of CEUS examination showing an endoleak type 1. Supplementary material 1 (AVI 446553 kb)
Online Resource 2 Video clip of CEUS examination showing an endoleak type 2. Supplementary material 2 (AVI 66479 kb)
- 5.Piscaglia F, Bolondi L, Italian Society for Ultrasound in M, Biology Study Group on Ultrasound Contrast A (2006) The safety of Sonovue in abdominal applications: retrospective analysis of 23188 investigations. Ultrasound Med Biol 32:1369–1375. doi: 10.1016/j.ultrasmedbio.2006.05.031 CrossRefPubMedGoogle Scholar
- 42.Pfister K, Rennert J, Uller W, et al. (2009) Contrast harmonic imaging ultrasound and perfusion imaging for surveillance after endovascular abdominal aneurysm repair regarding detection and characterization of suspected endoleaks. Clin Hemorheol Microcirc 43:119–128. doi: 10.3233/ch-2009-1226 PubMedGoogle Scholar
- 43.Chung J, Kordzadeh A, Prionidis I, Panayiotopoulos Y, Browne T (2015) Contrast-enhanced ultrasound (CEUS) vs. computed tomography angiography (CTA) in detection of endoleaks in post-EVAR patients. Are delayed type II endoleaks being missed? A systematic review and meta-analysis. J Ultrasound 18:91–99. doi: 10.1007/s40477-014-0154-x CrossRefPubMedPubMedCentralGoogle Scholar
- 44.Jung EM, Rennert J, Fellner C, et al. (2010) Detection and characterization of endoleaks following endovascular treatment of abdominal aortic aneurysms using contrast harmonic imaging (CHI) with quantitative perfusion analysis (TIC) compared to CT angiography (CTA). Ultraschall Med 31:564–570. doi: 10.1055/s-0028-1109811 CrossRefPubMedGoogle Scholar
- 45.Gargiulo M, Gallitto E, Serra C, et al. (2014) Could four-dimensional contrast-enhanced ultrasound replace computed tomography angiography during follow up of fenestrated endografts? Results of a preliminary experience. Eur J Vasc Endovasc Surg 48:536–542. doi: 10.1016/j.ejvs.2014.05.025 CrossRefPubMedGoogle Scholar
- 46.Guo Q, Zhao J, Huang B, et al. (2016) A systematic review of ultrasound or magnetic resonance imaging compared with computed tomography for endoleak detection and aneurysm diameter measurement after endovascular aneurysm repair. J Endovasc Ther 23:936–943. doi: 10.1177/1526602816664878 CrossRefPubMedGoogle Scholar
- 49.Tarantino L, Francica G, Sordelli I, et al. (2006) Diagnosis of benign and malignant portal vein thrombosis in cirrhotic patients with hepatocellular carcinoma: color Doppler US, contrast-enhanced US, and fine-needle biopsy. Abdom Imaging 31:537–544. doi: 10.1007/s00261-005-0150-x CrossRefPubMedGoogle Scholar
- 59.Bertolotto M (2009) Contrast-enhanced ultrasound: past, present, and future. In: Dogra V (ed) Advances in ultrasound, an issue of ultrasound clinics. Philadelphia: Saunders, pp 339–367Google Scholar
- 62.Claudon M, Dietrich CF, Choi BI, et al. (2013) 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. Ultraschall Med 34:11–29. doi: 10.1055/s-0032-1325499 CrossRefPubMedGoogle Scholar
- 66.Sidhu PS, Shaw AS, Ellis SM, Karani JB, Ryan SM (2004) Microbubble ultrasound contrast in the assessment of hepatic artery patency following liver transplantation: role in reducing frequency of hepatic artery arteriography. Eur Radiol 14:21–30. doi: 10.1007/s00330-003-1981-x CrossRefPubMedGoogle Scholar
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.