Imaging checklist holds the key to hepatocellular carcinoma prediction

March 10, 2009

Mountaineering metaphors provided the framework for Sunday’s Josef Lissner honorary lecture: Ode to the liver.

Mountaineering metaphors provided the framework for Sunday's Josef Lissner honorary lecture: Ode to the liver.

"The liver, in my opinion, is for radiologists what the Matterhorn is for alpinists. It is a sort of litmus test for measuring your skills," said Prof. Carlo Bartolozzi, chair of the radiology department at the University of Pisa in Italy.

Bartolozzi began by acknowledging that he was not the first to compose an ode to the liver. Pablo Neruda, winner of the Nobel Prize for Literature in 1971, described the liver's pathophysiology in a poem that ended with a prayer to the organ: "Do not betray me! Work on!"

Returning to the mountaineering theme, Bartolozzi observed that before climbing any peak, alpinists should be aware of the possible pathways, risks, and complexities ahead. The same is true when exploring an organ as complex as the liver, he noted. Radiologists need to understand what is going on.

The liver is the central homeostatic organ in the body and the site of at least 100 functional processes. Its uniqueness derives from having peculiar cellularity, double vascularity, and a biliary system.

The portal vein is responsible for 70% of the vascular supply in the normal liver. The remaining 30% comes indirectly from the portal artery via the peribiliary arterial plexus. Functional changes to the liver, such as sinusuidal fibrosis, thrombosis, and capillarization cause a change in vascularity, with the portal flow decreasing and the arterial supply increasing.

This can be observed on perfusion imaging with CT and/or MRI, Bartolozzi said. Parameters such as hepatic blood volume and hepatic blood flow will drop, while mean transit time and hepatic arterial fraction will rise.

"It is very interesting to see how these parameters are related to the degree of fibrosis," he said.

Delegates were also shown the stepwise development of hepatocarcinogenesis in the cirrhotic liver. Starting with large, regenerative nodules (benign), the sequence progresses through low-grade dysplastic nodules (benign), high-grade dysplastic nodules (premalignant), and early HCC (premalignant), before ending with overt HCC.

"Neoangiogenesis is fundamental in making a diagnosis of HCC," Bartolozzi said. "The question is: How do we explore the ‘grey zone' of these equivocal nodules?"

The answer may lie with pathology. Certain precancerous pathological features can now be identified using noninvasive radiological techniques.

One pathological sign of premalignancy is a change to clear cells, that is, cells rich in glycogen. Because glycogen causes a strong T1 shortening on MRI, these can be identified on T1-weighted imaging. Comparison with out-of-phase MR images will confirm whether the suspect cells contain glycogen and not fat. Other premalignant features include iron-free nodules, impaired biliary function, and cholestasis.

Bartolozzi showed a series of MR images that could be used to diagnose a high-grade dysplastic nodule. The signs to look out for are T1 and T2 shortening (glycogen content), no wash-in/wash-out on contrast-enhanced imaging (no neoangiogenesis), and hyperintensity in the hepatobiliary phase (cholestasis).

Overt HCC, on the other hand, will show prolonged T1 and T2 relaxation (hypercellularity), contrast wash-in/wash-out (neoangiogenesis), and hypointensity in the hepatobiliary phase (loss of hepatobiliary function).

"All pathological features have a corresponding imaging feature. So in practice, when we acquire images of patients suffering from cirrhosis, we have to follow this sort of checklist," Bartolozzi said.