Imaging in Interventional Radiology: Applications of Contrast-Enhanced Ultrasound

Abstract

This review explores the applications of contrast-enhanced ultrasound (CEUS) in interventional radiology, focusing on its role in endoleak detection after endovascular abdominal aortic aneurysm repair (EVAR), periprocedural thermal ablation guidance, and transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). CEUS offers a dynamic assessment for the detection of endoleak following EVAR, facilitating accurate diagnosis and classification. In periprocedural thermal ablation, CEUS enhances target lesion delineation with the visualization of real-time perfusion changes, optimizing treatment strategies and reducing residual tumor rates. Finally, CEUS has demonstrated efficacy in intraprocedural evaluation and postprocedural follow-up in TACE for HCC, offering early detection of residual tumor enhancement and providing an alternative for patients with contraindications to contrast-enhanced computed tomography or magnetic resonance imaging. Overall, CEUS is a versatile and valuable tool with many applications to offer interventional radiologists enhanced diagnostic capabilities and improved patient management.

Keywords

contrast-enhanced ultrasound - endoleak - thermal ablation - transarterial chemoembolization - interventional radiology

Contrast-enhanced ultrasound (CEUS) has emerged as a pivotal diagnostic tool by leveraging the use of intravascular contrast agents through the form of microbubbles to enhance visualization of blood flow and tissue perfusion. While its use as a diagnostic tool is routine in many parts of the world (e.g., CEUS LI-RADS,[1] contrast-enhanced echocardiography, and contrast-enhanced voiding urosonography), new and novel applications of CEUS for an “interventional” application are constantly emerging.

In the United States, three main contrast agents are predominantly utilized in CEUS: sulfur hexafluoride (Lumason), perflutren lipid microspheres (Definity), and perflutren protein-type A microspheres (Optison).

Lumason (Bracco Diagnostics, Princeton, NJ; marketed as Sonovue in Europe), a sulfur hexafluoride microbubble-based contrast agent, is encapsulated within a phospholipid shell, allowing for prolonged circulation and sustained enhancement during imaging. It is primarily utilized in the assessment of vascular structures related to solid organs. Its high echogenicity and consistent enhancement make it particularly valuable in delineating vascular abnormalities and characterizing lesions.

Definity (Lantheus Medical Imaging, North Billerica, MA), composed of perflutren lipid microspheres, exhibits rapid clearance from the bloodstream and is thus well suited for dynamic imaging studies including the assessment of myocardial perfusion and the evaluation of cardiac function.

Optison (GE Healthcare AS, Oslo, Norway), containing perflutren protein-type A microspheres, is unique in its albumin-based shell, and its compatibility with harmonic imaging techniques is particularly advantageous in echocardiography, facilitating the evaluation of intracardiac shunts, valvular regurgitation, and myocardial perfusion defects.[2]

Of the aforementioned three agents, only Lumason does not require refrigeration and can be reconstituted via three-way stopcock mixing immediately prior to use. Additionally, Lumason is the only FDA-approved agent for both liver lesion characterization and contrast-enhanced voiding urosonography (radiation-free alternative to voiding cystourethrography).

The versatility of CEUS has demonstrated a myriad of diagnostic and interventional applications. We will review several of its applications in this article with the attention to endoleak diagnosis and classification, periprocedural thermal ablation, and other investigational uses such as intra-arterial administration to evaluate for lesion coverage in transarterial chemoembolization (TACE).

Applications of Contrast-Enhanced Ultrasound in Endoleak Detection and Classification

Currently, the endovascular aneurysm repair (EVAR) technique accounts for over 56% of all abdominal aortic aneurysm (AAA) repairs in the United States.[3] Between 20 and 50% of these patients treated with EVAR develop endoleak—some requiring reintervention within the first 30 days after placement.[4] [5] [6]

CEUS offers several advantages in the detection and characterization of endoleak after endovascular AAA repair. Its improved visualization, ability to detect small endoleak, and noninvasive nature make it a valuable tool in clinical practice.[7]

CEUS can identify and differentiate endoleak more accurately than computed tomography (CT) angiography with the analysis of flow direction and velocity with sensitivity of 98% and specificity of 88%.[8] It is radiation free, avoids the need for iodinated contrast, and allows for real-time, dynamic detection of endoleak after EVAR. Diagnostic assessment is continuous and can visualize vascular flow along multiple minutes—as opposed to the few, static images in time obtained in multiphasic CT and magnetic resonance angiography. Compared with conventional US, CEUS provides good sensitivity despite technically difficult conditions caused by the patient's body habitus and the presence of bowel gas.[9] The absence of metal streak artifacts on US also allows for the detection of endoleak with high spatial resolution, especially after prior endoleak repair. Ultimately, it is the dynamic nature of CEUS which allows for accurate diagnosis and classification of endoleak, as the contrast microbubbles can be visualized flowing along their preferred path and entering the excluded aneurysm.

Technical Approach to CEUS in EVAR Surveillance

To minimize bowel gas and its associated comet-tail artifact, patients are instructed not to eat or drink anything the morning prior to the CEUS examination. Peripheral intravenous access of at least 22 gauge is obtained to administer the contrast microbubbles.

A standardized non-contrast diagnostic sonographic evaluation of the aortic endograft and the aneurysm sac is performed prior to contrast injection. The abdominal aorta and iliac arteries, including the endograft and excluded aneurysm, are evaluated in their entirety in both transverse and sagittal planes—noting optimal sonographic windows for the endograft and aneurysm sac for the upcoming contrast administration. The flow and waveforms in the peripheral endograft limbs are assessed with color and spectral Doppler. Additionally, color and spectral Doppler are used to assess the excluded aneurysm sac for residual flow and interrogate vessels that commonly cause type II endoleak, such as a patent inferior mesenteric artery or lumbar arteries.

For the contrast-enhanced portion of the exam, dual screen monitoring is performed with B-mode on one side—to guide anatomic landmarks—and contrast display mode on the other side—to assess for enhancement. The focal zone is set at the deep margin of the aorta. For adequate signal intensity at this focal length, the mechanical index (MI) can be increased but should be balanced against the consequences of increased contrast microbubble destruction. Ideally, the MI should remain less than 0.2, except in extremely difficult evaluations. Prior to contrast injection, the gain should be lowered to have the aorta slightly below detection on the contrast view. Subsequently, a bolus dose of 1.5 mL of Lumason (Bracco Diagnostics) or 0.2 mL of Definity (Lantheus Medical Imaging) is injected intravenously and flushed with 10 mL of saline. Alternative contrast injection protocols have also been described.

It is beneficial to start a timer when injecting the intravenous contrast, as the enhancement timing of the aneurysm sac relative to the endograft lumen is important for distinguishing endoleak etiology. Endoleak types I, III, and IV can be diagnosed by synchronous enhancement of the endograft lumen and aneurysm sac and are differentiated by direct visualization of where contrast can be seen extruding from the graft ([Fig. 1]). Delayed leaks (e.g., types II and V) are suggested by delayed enhancement of the aneurysm sac relative to the endograft lumen ([Fig. 2]). Dual-screen B-mode and contrast mode interrogation is continued for 5 to 7 minutes after contrast injection in order to evaluate for slow-flow and delayed endoleak. If delayed enhancement of the aneurysm sac is identified, the operator should allow for the contrast to be physiologically cleared (approximately 10 minutes), and a repeat bolus can be administered to attempt to visualize the arterial source and direction of the endoleak.[10]

Fig. 1 (a) Routine monitoring CT abdomen and pelvis without contrast due to decreased renal function in a patient with AAA repaired with Endologix graft over 10 years ago shows an enlargement of the aneurysm compared to (b) CT scan from 1 year prior. (c) B-mode US shows the endograft (arrowhead) within the aneurysm (arrow). (d) Dual-screen CEUS shows type III endoleak with the synchronous enhancement of the endograft (arrowhead) and the aneurysm sac (arrow).

Fig. 2 (a) Color Doppler ultrasound shows a partially thrombosed right common iliac artery aneurysm after Endologix endovascular repair with the question of type II endoleak from the right hypogastric artery (arrow). (b) CEUS demonstrates filling of the right limb of the endograft (arrowhead) and (c) subsequent delayed opacification of the right hypogastric artery (arrow), confirming type II endoleak.

Applications of Contrast-Enhanced Ultrasound in Periprocedural Thermal Ablation

Thermal ablation techniques are increasingly utilized for the treatment of various solid tumors, and CEUS can provide several periprocedural advantages. CEUS provides accurate delineation of an ablation target, particularly in focal lesions that are difficult to appreciate with standard B-mode US.[11] CEUS often improves visualization of ill-defined tumors by demonstrating arterial-phase hyperenhancement and/or tumor washout ([Fig. 3]). Furthermore, CEUS may delineate viable areas of tumor in large tumors with necrosis. Accurate delineation of the ablation target allows clinicians to strategize the ablation approach, ensuring adequate coverage of the target lesion while minimizing damage to adjacent structures.

Fig. 3 (a) Subtle region of hypoechogenicity on B-mode (arrow), which is (b) well delineated after intravenous contrast injection (arrow). (c) Successful placement of the ablation electrode (arrowhead) through the target lesion with (d) visualization of the treatment zone (arrow).

CEUS can be used to guide probe placement and provide real-time monitoring of tissue perfusion changes.[12] Procedures are typically done with two injections, or an infusion can be performed (∼1 mL/min) when prolonged contrast-enhancement is required. Post-ablation CEUS can also be performed, thereby facilitating immediate assessment of adequate treatment coverage by evaluating changes in tumor vascularity and perfusion patterns. This allows for rapid identification of residual tumors, enabling performance of re-ablation in the same session and reduction of reintervention in up to 31% of patients.[13] [14]

The efficacy of periprocedural CEUS has been further demonstrated in other studies. For example, patients with hepatocellular carcinoma (HCC) poorly imaged by grayscale US and selected for radiofrequency ablation demonstrated complete response with a single session of treatment in 95.2% of the patients treated by CEUS guidance versus 32% in patients treated by grayscale US guidance alone.[15]

Applications of Contrast-Enhanced Ultrasound in Transarterial Chemoembolization

HCC is the most common type of primary liver cancer and its incidence and mortality rates have been rising for the last decade.[16] Transarterial embolization therapies rely on localized catheter delivery of embolic agents via hepatic arteries. For example, TACE is performed by the injection of chemotherapeutic drugs mixed with lipiodol or drug-eluting beads containing doxorubicin. CEUS has been demonstrated to be effective for both intraprocedural evaluation and postprocedural follow-up with several advantages.

Shiozawa et al described a study including 39 HCC lesions treated with DEB-TACE with intraprocedural intra-arterial US (IAUS) guidance. US contrast was injected intra-arterially via the microcatheter in order to sonographically appreciate vascular supply to the tumor and lesion coverage prior to DEB-TACE administration (conceptually analogous to cone beam CT performed during mapping angiography). Following administration of therapy, 13 of the 39 lesions were identified as incompletely treated on IAUS, as evidenced by persistent enhancement characteristics, allowing for further administration of drug-eluting microspheres.[17]

Per Society of Interventional Radiology guidelines, follow-up imaging is typically performed 4 to 6 weeks postprocedure with either contrast-enhanced CT or contrast-enhanced magnetic resonance imaging. The delay in evaluation is thought to allow for differentiation of peritumoral inflammation and viable tumor, but also to minimize artifact from intraparenchymal lipiodol on CT.[18] CEUS has an excellent safety profile with data suggesting residual tumor enhancement accurately detected as early as 1-week post embolization due to the purely intravascular nature of US contrast agents and lack of lipiodol artifact on US.[19] When evaluated with CEUS, residual, viable tumors would manifest as internal residual enhancement or nodular peripheral enhancement. A tumor that is completely treated by TACE should demonstrate smooth tumor margins without internal flow in any enhancement phase.[20] CEUS can also be considered as an alternative for follow-up in patients who have contraindications to contrast-enhanced CT/contrast-enhanced magnetic resonance.

Conclusion

CEUS has many useful applications and substantial advantages in interventional radiology, including precise detection and classification of endoleak after EVAR, periprocedural guidance for thermal ablation, and the evaluation of real-time lesion perfusion changes in TACE for HCC. With its excellent safety profile and ability to provide detailed, dynamic, real-time imaging, CEUS is a valuable tool with the ability to enhance patient care by improving diagnostic accuracy, treatment efficacy, and patient outcomes.

Conflict of Interest

The authors have no conflict of interest to disclose.

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Publication History

Article published online:
19 August 2024