Wilson’s Disease and Clinical MR Imaging Application layer, parenchymal heterogeneity with multiple nodules, and the absence of caudate lobe hypertrophy. It also suggested that US seemed to be the best imaging modality for the demonstration of early parenchymal alteration. In this study, hypointense nodules on T2-weighted images, surface nodularity of the liver, and gallbladder fossa widening were common MR imaging findings in patients with Wilson’s disease, and these correlated with severity of hepatic dysfunction. Among the patients with normal or mild hepatic dysfunction (Child-Pugh class A), the MR findings were more common in patients with the neurologi- cal manifestations than the non-neurological manifestations of Wilson’s disease. Therefore, it is postulated that neurological dysfunction, which was not associated with symptomatic liver disease, might be related with hepatic copper accumulation and subsequent hepatic parenchymal changes. Hepatic nodules in Wilson’s disease are considered as a result of copper deposition. On MR imaging, these lesions typically appear as hypointense on T2-weighted images and hyperintense on T1-weigthed images (9, 14). In this study, multiple hypointense nodules were commonly noted on T2-weighted images (50%). The paramagnetic effect of ionic copper has been implicated as a cause of hypointen- sity, as was observed on T2-weighted images and hyperin- tensity as observed on T1-weighted images. However, the T1-shortening and T2-shortening effect of copper deposi- tion may be nullified by elevated T1 and T2 values in advanced cirrhosis (17). Multiple hypoinstense nodules of the liver were noted in 33% of patients with early stage of hepatic dysfunction (Child-Pugh class A) before advanced cirrhosis. In patients with advanced hepatic dysfunction (Child-Pugh classes B and C), hypointense nodules of the liver were noted in 93% (13 of 14) of the patients and 50% of the nodules were macronodular (> 3 mm in diameter) and were observed as hyperintense on T1- weighted images. Contour abnormalities of the liver due to parenchymal necrosis, regeneration, and scarring that suggest cirrhosis were correlated with hepatic dysfunction in this study. The expanded gallbladder fossa sign has been reported to be a highly specific MR sign for the diagnosis of cirrhosis, and consists of the enlargement of the pericholecystic space (i.e., the gallbladder fossa) (21). This is comparable to the finding of a thickened perihepatic fat layer as described by Akhan et al. (10). A normal caudate to right lobe ratio has been reported as a unique feature of cirrhosis in Wilson’s disease (14). In this study, caudate hypertrophy was less common (20% of patients) relative to other imaging features that were suggestive of cirrhosis. However, an explanation is not postulated for the mechanism of lobar Korean J Radiol 11(6), Nov/Dec 2010 dysmorphism of the liver in these patients. Reversibility of copper deposition after copper chelating therapy is noteworthy. Kim et al. (22) reported that MR imaging of the brain depicts the reversible changes of the involved brain parenchyma after copper chelating therapy. Reversible changes of copper deposition in the liver have been rarely reported (12, 14, 23). In this study, follow-up MR images of the liver demonstrated improved intrahep- atic nodules in 47% (8 of 17) of patients after copper chelating therapy with clinical improvement of liver function. Follow-up MR examinations also demonstrated aggravated nodular infiltrations and progressed contour abnormalities of cirrhosis in four patients with rapidly progressive hepatic dysfunction. From this point of view, MR imaging may be used as an indicator of therapeutic response in Wilson’s disease. This study has several limitations. First, clinical grading of Wilson’s disease has not yet been fully established. The Child-Pugh classification was used in the evaluation of clinical status of Wilson’s disease, which only reflects hepatic dysfunction. Serum ceruloplasmin and copper levels, as well as the 24-hour urinary copper level were not considered. Although 50 patients with Wilson’s disease were included in the study, most of the patients were Child-Pugh class A, and only 25% of the patients were Child-Pugh class B or C. Therefore, an error in the statisti- cal analysis was inevitable. Second, the MR protocol could not be uniformly assumed, as the study included retrospec- tive data collection for a 10-year span. Third, interobserver or intraobserver variance analyses were not performed for the MR imaging interpretation. In conclusion, MR imaging of the liver in Wilson’s disease demonstrated multiple, hypointense nodules on T2-weighted images, as well as contour abnormalities of the liver suggestive of cirrhosis. These imaging features correlated with the severity of hepatic dysfunction and clinical presentation. MR imaging also demonstrated reversible parenchymal changes after clinical improve- ment. References 1. Gitlin JD. Wilson disease. Gastroenterology 2003;125:1868- 1877 2. Bull PC, Thomas GR, Rommens JM, Forbes JR, Cox DW. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat Genet 1993;5:327-337 3. Tanzi RE, Petrukhin K, Chernov I, Pellequer JL, Wasco W, Ross B, et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet 1993;5:344-350 4. Seo JK. Wilson disease: an update. Korean J Hepatol 2006;12:333-363 [Korean] 5. Ala A, Schilsky ML. Wilson disease: pathophysiology, diagnosis, 671