PROTON MR SPECTROSCOPIC MEASUREMENT OF NEUROMETABOLITES IN HEPATIC-ENCEPHALOPATHY DURING ORAL LACTULOSE THERAPY

BACKGROUND AND PURPOSE: MR imaging and MR spectroscopy are increasingl y being used to determine response to pharmacologic therapy. Hepatic e ncephalopathy (HE) is characterized by abnormal cerebral metabolites, yet the response to lactulose and other anti-HE measures is still prim arily determined by using arbitrary categorical clinical rating scales , rather than MR spectroscopy. The purpose of this study was to determ ine whether MR spectroscopy could demonstrate relevant neurometabolic changes associated with lactulose therapy and thereby provide further support for the use of MR spectroscopy in clinical trials. METHODS: Te n control subjects and 23 patients with grades I to III HE were studie d by proton MR spectroscopy with imaging parameters of 2000/26 (TR/TE) . Metabolic ratios were calculated for myo-inositol (mI)/creatine (Cre ), choline (Cho)/Cre, (glutamine + glutamate) (Glx)/Cre, N-acetylaspar tate (NAA)/Cre, and (Cho + mI)/Glx. A time series design trial was use d in which eight patients with HE were compared before and after lactu lose therapy (60 mL by mouth three times per day). RESULTS: Relative t o control subjects, HE was characterized by 43%, 64%, and 5% reduction s, respectively, in mI/Cre, (Cho + mI)/Glx, and Cho/Cre. In comparison , Glx/Cre was increased by 75% and NAA/Cre was not changed. Therapy wi th lactulose was associated,vith increases of 29%, 37%, and 7%, respec tively, in mI/Cre, (Cho + mI)/Glx, and Cho/Cre, as well as respective decreases of 15% and 42%, respectively, in Glx/Cre and HE grade. NAA/C re did not change with lactulose therapy. CONCLUSION: MR spectroscopy detects neurometabolic changes associated with pharmacologic therapy f or HE. The metabolic ratios mI/Cre and (Cho + mI)/Glx are the most sen sitive measures of lactulose effect. These data support the expanded u se of MR spectroscopy as an adjunctive technique in pharmaceutical dev elopment and clinical trials for HE.