Diffusion MRI shows increased water apparent diffusion coefficient in the brains of cirrhotics R. Lodi, MD; C. Tonon, MD; A. Stracciari, MD; M. Weiger, PhD; V. Camaggi, MD; S. Iotti, PhD; G. Donati, MD; M. Guarino, MD; L. Bolondi, MD; and B. Barbiroli, MD Abstract—Background: Brain edema and increased intracranial pressure worsen prognosis in patients with end-stage chronic cirrhosis. Objective: To use diffusion-weighted imaging (DWI) to quantify water apparent diffusion coefficient (ADC) in different brain regions of patients with chronic liver failure with or without hepatic encephalopathy. Methods: The authors studied 14 patients with viral liver cirrhosis and 12 sex- and age-matched healthy volunteers. Seven patients had no clinical evidence of hepatic encephalopathy; six had grade I hepatic encephalopathy; and one had grade II hepatic encephalopathy. Brain DWI was obtained using a single-shot echo-planar imaging sequence, and four gradient strengths (b values = 0, 300, 600, and 900 s/mm 2 ) were applied to calculate the average diffusivity maps. Results: Mean ADC values in the brains of patients with cirrhosis were significantly increased in all selected regions of interest (caudate, putamen, and pallidus nuclei; occipital, parietal, and frontal lobe white matter) except in the thalamus. Venous ammonia was linearly related to ADC values in deep gray and white matter regions of interest. Conclusions: Brain water apparent diffusion coefficient is increased in patients with chronic liver disease and may be useful in monitoring patients with hepatic encephalopathy. NEUROLOGY 2004;62:762–766 Brain edema and increased intracranial pressure, a major complication of fulminant hepatic failure, 1 also occur in patients with end-stage cirrhosis and ad- versely affect prognosis. 2 There is no effective treat- ment for brain edema in patients with cirrhosis, and liver transplantation is the only successful interven- tion. 2 More recently, the presence of mild brain edema even in patients with cirrhosis with no evi- dence of encephalopathy has been hypothesized based on increased T2-weighted signal intensity 3 and reduced magnetization transfer ratios 4 in the hemi- spheric white matter (WM). MR spectroscopy (MRS) studies have identified neurometabolic abnormalities that could well con- tribute to brain edema development in patients with cirrhosis. 5-8 MRS studies of the brains of patients with cirrhosis with clinical and subclinical hepatic en- cephalopathy (HE) consistently found an increase in glutamine 5-7 associated with a reduction in glutamate 7 and myo-inositol, a cerebral osmolyte. 6 Glutamine in- crease, the result of ammonia detoxification in astro- cytes, has been implicated as the central event determining cell swelling and increased brain water content in patients with HE. 9 Diffusion-weighted imaging (DWI) allows the as- sessment of the water apparent diffusion coefficient (ADC), a measure of tissue water diffusivity. ADC depends on the interactions between water mole- cules and the chemical environment and the struc- tural barriers at the cellular and subcellular level hindering their motion in vivo. 10 Given the limited efficacy of therapy when the stage of overt cerebral edema and intracranial hy- pertension is reached, detection of early signs of brain edema or changes in water distribution at the microscopic level can be critical for the treatment of patients with chronic liver disease. 2 In the present study, we used DWI to assess water ADC in different brain regions in patients with chronic liver failure either with or without clinical evidence of HE. Methods. Patients. Fourteen patients with viral liver cirrhosis and 12 sex- and age-matched healthy volunteers (9 men; aged 58  8 years) were studied (table). Patients with a history of drug abuse and those with neurologic or psychiatric diseases unrelated to liver failure were excluded. Etiology was hepatitis C virus (HCV) in eight patients, hepatitis B virus (HBV) in five patients, and HBV and hepatitis D virus (HDV) in one. Based on Parsons- Smith criteria, HE was grade 0 in seven patients, grade I in six patients, and grade II in one patient. No patients with cirrhosis with severe HE (grades III or IV) were included in the study. The degree of liver failure was moderate in five patients (Child–Pugh B) and severe in nine patients (Child–Pugh C). Laboratory screen- ing, which included albumin, bilirubin, prothrombin time, and serum venous ammonia levels, was performed the same day as the MRI scans. MRI. MRI was performed using a 1.5-T GE Signa Horizon LX system (Milwaukee, WI) equipped with a birdcage head radiofre- From the Departments of Clinical Medicine and Applied Biotechnology (Drs. Lodi, Tonon, Weiger, Iotti, and Barbiroli), Neurology (Drs. Stracciari and Guarino), and Internal Medicine and Gastroenterology (Drs. Camaggi, Donati, and Bolondi), Policlinico S. Orsola-Malpighi, University of Bologna, Italy. Supported by EU contract QLK4 –2002– 01763 (V Framework), Fondazione Cassa di Risparmio in Bologna, and Progetto Pluriennale di Ricerca E.F. 2000. Received July 30, 2003. Accepted in final form October 6, 2003. Address correspondence and reprint requests to Dr. Raffaele Lodi, Dipartimento di Medicina Clinica e Biotecnologia Applicata “D. Campanacci,” Universita’ di Bologna, Policlinico S. Orsola, Via Massarenti 9, 40138 Bologna, Italy; e-mail: raffaele.lodi@ unibo.it 762 Copyright © 2004 by AAN Enterprises, Inc.