Role of MRI in Detection of Minimal Hepatic Encephalopathy
Role of MRI in Detection of Minimal Hepatic Encephalopathy
Introduction Liver cirrhosis (LC) is irreversible fibrosis of the liver (1) and it remains a
 public health problem. One of the complications of the cirrhosis is hepatic encephalopathy
 (HE) which is defined as brain dysfunction caused by liver insufficiency. Pathophysiological
 mechanisms of HE are complex and multifactorial. Recognition of beginning stages of HE, such
 as minimal HE (mHE) is of most importance.

 Objectives and originality of the project Diagnosis of mHE can be challenging, time-consuming
 and, at least to some extent, subjective. This project will assess the role of magnetic
 resonance (MR) in mHE diagnosis with emphasis on multimodal imaging technique. With advanced
 magnetic resonance (MR) techniques, in-vivo detection of intracellular water content,
 estimation pH and metabolites levels with millimolar concentrations can be easily performed.
 This will offer to explore possible pathophysiological mechanisms of HE and to evaluate the
 results from previous, studies that were mainly performed on animal models or cell cultures.

 By our best knowledge, multimodal MR approach as the investigators propose in this
 application has not been yet performed. The investigators will use advanced MR techniques
 which are currently not available in the clinical setting and require multicenter
 collaboration.

 Methods The investigators will include 10-20 patients of both genders with hyperammonemia and
 mHE and 10-20 patients of both genders with HE. Diagnosis of HE will be made based on results
 of validated neuropsychiatric test. Age-matched and gender-matched control group with no
 gastrointestinal, neurological or psychiatric complaints and normal levels of ammonia in the
 blood. Patients with mHE/HE will be included from outpatient clinic of the Department of
 gastroenterology, University Medical Centre (UMC) Ljubljana. Healthy controls (HC) will be
 invited to join via internet advertisement. Contraindications for HC will include
 gastrointestinal (emphasis on liver disease), neurological or psychiatric complaints. Grade
 of mHE/HE will be classified according to West-Haven (WH) classification. Patients with
 different degree of liver cirrhosis, which will be scored with the Child-Pugh (CP) score, and
 with no contraindications for MR (e.g. presence of metal in body) will be included. Blood
 levels of liver enzymes and ammonia will be measured in all participants. MR scanning will
 include: T1- and T2-weighted MR, MRS (MEGA-PRESS and PRESS) in two voxels: striatum and
 cerebellum. Location will be double-checked by voxel position screenshots. Analysis, with
 voxel-positioning error compensation will be performed in Gannet (www.gabamrs.com). Moreover,
 high resolution diffusion weighted imaging (DWI), diffusion kurtosis imaging (DKI),
 quantitative susceptibility mapping (QSM) will be performed in brain as well. Liver QSM will
 be executed to assess iron load.
Inclusion Criteria:

 -  Known liver disease/cirrhosis

 Exclusion Criteria:

 -  Pregnancy, non compatible material with MRI