Using LI‐RADS With Contrast‐Enhanced Ultrasound

Abstract

Contrast-enhanced ultrasound (CEUS) uses intravenously administered microbubbles to evaluate the enhancement characteristics of focal lesions visible on ultrasound. In 2016, the US Food and Drug Administration approved the use of sulfur hexafluoride lipid type A microspheres (Lumason, Bracco Diagnostics Inc., Monroe Township, NJ, USA) for the evaluation of a focal liver lesion in a pediatric or adult patient. Subsequently, the American College of Radiology (ACR) Liver Imaging Reporting and Data System (LI-RADS) published CEUS LI-RADS and updated it in 2017.1, 2 CEUS LI-RADS, like computed tomography/magnetic resonance (MR) imaging (CT/MRI) LI-RADS, is a framework for classifying untreated liver observations with different likelihood levels in patients at high risk for hepatocellular carcinoma (HCC). The components of CEUS LI-RADS, accuracy of CEUS for diagnosing HCC, and indications for CEUS LI-RADS are highlighted in this review. Primary liver cancer is the sixth leading cause of cancer worldwide and the fourth leading cause of cancer-related mortality.3 Accurate characterization of early-stage HCC allows appropriate treatment and improves patient survival. Per-observation CEUS LI-RADS categories range from LR-1 through LR-5 and also include LR-M (probably malignant but not HCC specific), LR-TIV (tumor in vein), and LR-NC (not characterizable because of image omission or degradation). LR-1 and LR-2 represent definitely and probably benign, respectively. LR-3 indicates an intermediate probability for HCC, and LR-4 and LR-5 represent probably and definitely HCC, respectively. Major criteria for CEUS LI-RADS include: (1) size of lesion; (2) presence or absence of arterial phase hyperenhancement (APHE) (nonrim; nondiscontinuous peripheral nodular enhancement); and (3) presence or absence of, as well as degree of, washout (mild or marked/punched out) and timing of washout, if present (early or late). APHE and mild, late washout (>60 seconds) are typical for HCC, whereas early (<60 seconds) or marked washout (<2 minutes) typically occurs in intrahepatic cholangiocarcinoma (ICC) and other nonhepatocellular malignancies. Please refer to the ACR CEUS LI-RADS website for further details.1 CEUS LI-RADS has a high positive predictive value for diagnosing HCC in patients with cirrhosis and other high-risk patients without cirrhosis, comparable with CT/MRI LI-RADS. The overarching goal of CEUS LR-5 diagnosis is high specificity for HCC and exclusion of non-HCC malignancy, including ICC and combined HCC/ICC. Because LR-5 designation is intended to guide management without biopsy, the sensitivity for diagnosing HCC is sacrificed to maintain a high specificity, resulting in some HCCs characterized as LR-M, LR-4, or rarely, LR-3. A review of 21 pathologically proved ICCs, published in 2010 (prior to CEUS LI-RADS), claimed CEUS was unable to differentiate ICC from HCC,4 resulting in removal of CEUS from a 2011 American Association for the Study of Liver Diseases (AASLD) practice guideline for HCC management.5 However, subsequent research has shown that ICC can be effectively differentiated from HCC by assessing the timing and degree of onset of washout, and thus the importance of these features in CEUS LI-RADS.6, 7 Additional recent retrospective reviews have shown sensitivity of CEUS LR-5 for diagnosing HCC ranging between 62% and 75%, positive predictive values of 97% and 98.5%, and specificity of 96%,8-10 equivalent to CT/MRI LI-RADS. In these studies, HCC represented between 48% and 75% of all LR-M observations. The latest AASLD guidance document now includes CEUS as a recommended diagnostic tool to characterize observations suspicious for HCC.11 However, at this time, Organ Procurement and Transplantation Network (OPTN) does not recognize CEUS for transplant considerations. Multiphase contrast-enhanced CT or MRI may be necessary to verify a CEUS LR-5 observation in liver transplant candidates. Incongruent CT/MRI and CEUS cases may require discussion and/or appeal to the regional review board. Some drawbacks of CEUS are listed in Table 1. In brief, the small field of view renders CEUS best for focused examinations and not for staging. Other limitations may include: (1) CEUS of an observation or nodule occult on grayscale ultrasound; in this scenario, the sonographer can use anatomic landmarks to evaluate the area of interest and perform an initial injection to help localize the observation; if APHE or washout is observed, a repeat injection can be performed to further assess enhancement characteristics; (2) CEUS of an observation or nodule deep in the liver, or in a background of severe hepatic steatosis; and a (3) large body habitus. If the observation or nodule is difficult to visualize on grayscale ultrasound, it will likely be difficult to evaluate with CEUS. CEUS LI-RADS currently evaluates nodules visible on grayscale ultrasound. Future versions of CEUS may include: (1) how to evaluate nodules occult on grayscale imaging, (2) assessment of treatment response, (3) use in liver HCC screening, and (4) use of Kupffer cell–specific contrast agents. LI-RADS now includes a system for performance and interpretation of CEUS in patients at risk for HCC. The CEUS LI-RADS algorithm has high positive predictive value and specificity for diagnosing HCC and differentiating from non-HCC malignancy. An invaluable imaging tool and problem solver in the patient at risk for HCC, CEUS particularly excels in characterizing indeterminate CT/MRI liver observations and improves patient care.