· Hepatocellular carcinoma (HCC) is the second leading cause of cancer death in the world and most rapidly growing cause of cancer death in the United States

· Magnetic resonance imaging (MRI) plays a critical role in the management of patients with or at risk for HCC. In such patients, MRI can be used to make the non-invasive diagnosis of HCC without confirmatory biopsy. Major treatment decisions such as resection, liver transplantation, use of embolic or ablative therapy, and administration of chemotherapy may be made without tissue sampling.

· The Liver Imaging Reporting And Data System (LI-RADS) is a system of standardized terminology, interpretation, and reporting for imaging examinations of the liver [1].

o It has been developed with the support of the American College of Radiology

o It is the only radiologic system for HCC developed by a radiology organization

o It applies to patients with patients at risk for development of HCC (cirrhosis, chronic hepatitis B viral infection, current or prior HCC)

o It addresses both extracellular and hepatobiliary contrast agents

· LI-RADS categorizes observations from LR-1 to LR-5, reflecting probability of benignity or HCC in at-risk patients. Smaller observations must satisfy stricter criteria to be assigned equivalent categories.

· Observations with features suggestive of non-HCC malignancy are categorized LR-M.

· Observations associated with tumor in vein are categorized LR-5V.

· LR-5 applies to observations with imaging features diagnostic of HCC.

o The imaging criteria have high specificity but modest sensitivity for HCC.

o Imaging features relevant for LR-5 categorization are diameter, arterial phase hyper-enhancement, washout appearance, capsule appearance, and threshold growth.

· Extracellular agents and hepatobiliary agents may be used in LI-RADS categorization.

· Both types of agents have advantages and disadvantages for LI-RADS categorization.

As a result of the information presented in this case-based presentation, learners will be able to:

· Understand the need for standardized interpretation and reporting of MR imaging examinations done for diagnosis or staging of HCC in patients with cirrhosis or other risk factors for HCC

· Become familiar with and understand key LI-RADS terminology and concepts

· Apply LI-RADS v2014 algorithm to categorize observations in patients with or at risk for HCC

Untreated observations that are neither definitely nor probably benign and lack features of non-HCC malignancy or tumor in vein may be categorized LR-3, LR-4, or LR-5. Appropriate categorization of such observations depends on the presence of major features. Major features are those that have been shown in prior studies to permit reliable diagnosis of HCC or that have been endorsed by other leading organizations such AASLD or OPTN. Major features include: arterial phase hypo- or iso-enhancement, arterial phase hyper-enhancement, diameter, washout appearance (“washout”), capsule appearance (“capsule”), and threshold growth. Each of these major features is defined in Table 1.

A few key concepts and caveats are emphasized here. The text below is nearly verbatim from ref [2].

LI-RADS requires that observations unequivocally enhance more than background liver AND be hyperintense in the arterial phase to meet criteria for arterial phase hyperenhancement. Thus, observations that enhance from hypointense pre-contrast to isointense in the arterial phase do not meet current LI-RADS criteria for arterial phase hyperenhancement.

Peripheral or rim-like arterial phase hyper-enhancement is a feature favoring intrahepatic cholangiocarcinoma (ICC) over HCC. Observations that exhibit rim-like arterial phase hyperenhancement usually should be categorized LR-M rather than LR-3, LR-4, or LR-5.

Washout appearance should be strictly defined by temporal reduction in enhancement from an earlier to a later phase, not by simple comparison of the signal intensities between the observation and surrounding liver in a single post-arterial phase such as the portal venous or delayed phase. The phases appropriate for assessing washout appearance depend on the gadolinium based contrast agent (GBCA) used.

For gadoxetate disodium, washout appearance should be assessed by comparing the portal venous phase to the arterial phase. After the portal venous phase, the hepatic parenchyma continues to progressively enhance due to uptake of gadoxetate disodium by hepatocytes. Thus, relative hypointensity of an observation after the portal venous phase (e.g., in the transitional phase) may be due to rapid transit of contrast, lack of functional hepatocytes, or a combination of the two. Given this uncertainty, transitional phase hypointensity does not have the same diagnostic implication as washout appearance and so should not be used to categorize an observation LR-5. Similarly, the hepatobiliary phase should not be used to gauge washout appearance.

For gadobenate dimeglumine, washout appearance can be assessed by comparing either the portal venous phase or the delayed phase to the arterial phase. Although gadobenate dimeglumine has mild hepatocellular uptake that permits hepatobiliary imaging at a delay of about 1-3 hours, this uptake has negligible impact on enhancement of liver and liver observations during the dynamic phases after its administration. Thus, these phases can be interpreted in the same fashion as with extracellular agents. As with gadoxetate disodium, the hepatobiliary phase should not be used to gauge washout appearance.

For extracellular GBCAs, washout appearance can be assessed by comparing either the portal venous phase or the delayed phase to the arterial phase, as these agents have negligible hepatocelluar uptake.

Capsule appearance may be difficult to assess when gadoxetate disodium is used. Uptake of gadoxetate disodium by hepatocytes leads to progressive enhancement of background liver parenchyma in the transitional phase, which is speculated to obscure any delayed rim enhancement.

Note that many of the features required for LR-5 categorization are features of progressed HCC (which characteristically is “hypervascular”), not of early HCC (which characteristically is “hypovascular”).

Once an observation has been categorized, radiologists at their discretion may apply ancillary features to adjust the category. Ancillary features are imaging features that modify likelihood of HCC. In isolation, these features do not permit reliable categorization of observations and hence are considered ancillary.

(See Figure 4)

(See Table 3)

*Although diffuse T1 hyper-intensity and hepatobiliary phase T1 hyper-intensity are not typical features of HCC, they do not occur in ICC; thus their presence favors a diagnosis of HCC over ICC.

Diagnostic of tumor in vein: enhancing soft tissue in lumen of vein Suggestive but not diagnostic of tumor in vein:

· Occluded vein with any of the following:

· Moderately to markedly expanded lumen

· Ill-defined walls

· Restricted diffusion

· Contiguity with LR-5 observation

· Obscured, partially visualized vein

· Heterogeneous enhancement of vein not attributable to mixing artifact