phosphocreatine and Liver-Diseases

The purpose of this study was to determine the intracellular pH of the whole head and in voxels localized to the basal ganglia in patients with chronic liver disease using phosphorus-31 magnetic resonance spectroscopy (31P MRS). The study group compromised 82 patients with biopsy-proven cirrhosis (43 Child's grade A, 25 Child's grade B and 14 Child's grade C). Eleven subjects showed no evidence of neuropsychiatric impairment on clinical, psychometric and electrophysiological testing, 37 showed evidence of minimal hepatic encephalopathy and 34 had overt hepatic encephalopathy. Unlocalized 31P MRS of the whole head was performed in 48 patients and 10 healthy volunteers. Localized 31P MRS of the basal ganglia was performed in the 34 patients and in 20 healthy volunteers. The intracellular pH values were calculated from the chemical shift difference between the inorganic phosphate (P) and phosphocreatine (PCr) resonances. The percentage inorganic phosphate (%Pi), phosphocreatine (%PCr) and betaNTP signals, relative to the total 31P signal, and peak area ratios of inorganic phosphate and phosphocreatine, relative to betaNTP were also measured. There were no differences between patients and volunteers in intracellular pH in 31P MR spectra measured from the whole head or the basal ganglia. There was no correlation between the severity of encephalopathy (West Haven criteria) or liver dysfunction (Child score) and intracellular pH values. There was also no significant change in the inorganic phosphate, phosphocreatine or betaNTP resonances in spectra acquired from the whole head. However, in spectra localized to the basal ganglia, there was a significant increase in mean P/NTP (p=0.02) and PCr/NTP (p=0.009). The mean %Pi and mean %PCr were also increased (p=0.06; p=0.05, respectively), but there was no significant change in mean %betaNTP. When the patient population was classified according to the severity of encephalopathy, those with overt disease had a higher mean P/NTP and %Pi (p=0.03; p=0.01), compared to the reference population. Our results suggest that there are detectable bioenergetic abnormalities in patients with minimal hepatic encephalopathy or stable, overt chronic hepatic encephalopathy, but any associated intracellular pH change is probably a secondary, rather than a primary phenomenon.

Topics: Adult; Aged; Brain; Brain Damage, Chronic; Female; Humans; Hydrogen-Ion Concentration; Liver Diseases; Magnetic Resonance Imaging; Male; Middle Aged; Phosphates; Phosphocreatine; Phosphorus Isotopes

Proton magnetic resonance (MR) spectroscopy of the brain was performed in 11 patients with chronic hepatic encephalopathy (CHE), and the results were compared with those of patients with liver disease but without CHE; clinical control subjects with diabetes, uremia, or cortical atrophy; and healthy subjects. The technique of water-suppressed stimulated-echo hydrogen-1 MR spectroscopy for detection of cerebral glutamate, glutamine, glucose, N-acetylaspartate, choline metabolites, (phospho)creatine, and myo-inositol is described. Specific changes in the brain of CHE patients included the anticipated elevation in cerebral glutamine levels (P less than or equal to .0001), a 23% reduction in choline metabolite levels (P less than or equal to .0001), and a more than 50% reduction in cerebral myo-inositol levels (P less than or equal to .0001). In four of the 15 patients with liver disease but without clinical CHE, a significant reduction in the myo-inositol level was detected, and in two of these patients an elevation in the glutamine concentration was also observed. These findings indicate a role for image-guided H-1 MR spectroscopy in the diagnosis and monitoring of both overt and preclinical CHE.

Topics: Aspartic Acid; Brain; Choline; Female; Glucose; Glutamates; Glutamic Acid; Glutamine; Hepatic Encephalopathy; Humans; Inositol; Liver Diseases; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine; Reproducibility of Results

Spatially resolved 31P magnetic resonance spectroscopy (MRS) at 4.7 T was applied to noninvasively assess liver phosphorus metabolites in a biochemically well-characterized model of hepatotoxicity induced by injection of a sublethal dose of D-galactosamine (galN). A newly developed hybrid method based on spectral localization with B0 and B1 gradients was employed to obtain multivoxel spectra in intact anesthesized rats. Spatially localized in vivo spectra were recorded 0 to 26 h after galN injection of female rats. In response to galN exposure, diphosphodiester peaks ascribed to UDP-hexosamines became detectable by 4 h and persisted up to 26 h. A metabolite coresonating with inorganic phosphate increased rapidly in intensity by 2 h after galN and returned to baseline by 18 h; this resonance was shown not to be Pi and was assigned to galN-1-phosphate by subsequent high resolution MRS experiments on extracts prepared from these livers. These results confirmed in vivo the metabolic perturbations described previously for this model of hepatotoxicity following biochemical studies based on classical extraction methods. Unlike the in vitro studies, however, these noninvasive experiments provided additional information on the time course of metabolic alterations on the same animal.

Topics: Adenosine Triphosphate; Animals; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Female; Galactosamine; Liver Diseases; Magnetic Resonance Spectroscopy; Phosphocreatine; Phosphoric Diester Hydrolases; Phosphoric Monoester Hydrolases; Phosphorus; Rats; Rats, Inbred Strains

Topics: Acidosis; Adenosine Triphosphate; Alanine Transaminase; Alcoholism; Aspartate Aminotransferases; Catalase; Cholinesterases; Coenzymes; Fatty Acids; Fructose-Bisphosphate Aldolase; Hepatitis; Hepatitis A; Humans; Hyperlipidemias; Hyponatremia; Liver Cirrhosis; Liver Diseases; NAD; Pathology; Peroxidases; Phosphocreatine