Evaluation of brain development using 1H-MRS-Detectable metabolites as biomarkers in children with liver desease

PURPOSE: Proton Magnetic Resonance Spectroscopy (1H-MRS) is a non-invasive imaging technique that enables quantitication of neurochemicals in vivo with potential diagnostic value and facilitating investigations of brain development. This study evaluated the extent to which 1H-MRS can add information to the study of children with liver disease pre- and post-transplant (Tx) by revealing abnormalities in cerebral metabolism, and to evaluate if performance on measures of cognitive ability is related to concentrations of 1H-MRS-detectable neurometabolites. METHOD:In a sample of 23 children with liver desease (pre-Tx n=13, mean age 13.1; post Tx=10 mean age 15.1) and 11 healthy controls (mean age 12.2), single voxel 1H-MRS in occipitoparietal and frontal cortical white matter was used to assay concentrations of four principles metabolities:N acetyl aspartate, choline, myo-Inositol and glutamate-glutamine, in parallel with assessments of Full-scale IQ (FSIQ). RESULTS: No differences in cerebral metabolites were observed between the pre- and post-Tx groups, nor between these patients and age-matched healthy controls. This suggests that neurodevelopment, assayed by surrogate neurometabolite markers detected by 1H-MRS, is normal in the liver disease patient cohort and is unaffected by Tx intervention. No correlations were observed between any of the metabolite measures and FSIQ CONCLUSION: 1H-MRS may supplement neuropsychological tests to enable evaluation of the patient’s progress before and after transplantation and holds promise as a screening tool for biomarkers in liver disease because of the increased precision gained through using continuous measures rather than ordinal or categorical ones. The use of 1H-MRS is still largely exploratory and further normative 1H-MRS metabolite values are required to provide context for the clinical data.