DTI And ~1H-MRS: Micro-structural And Neurochemical Assessments Of Brain Damage In Patients With Hepatolenticular Degeneration

Background Hepatolenticular degeneration(HLD)was a rare autosomal recessivedisorder for which diagnosis is critical because an effective treatment is available.,Also called Wilson diseases(WD).Diagnosis of WD is based on clinical findings,biochemical investigations and presence of Kayser-Fleischer(KF)ring on ophthalmological examination.It has a poor prognosis due to patients with decompensated cirrhosis of the liver and/or severe nervous system symptoms.The keys to the prognosis are early discovery and early treatment.It is difficult to early diagnose HLD since the symptoms associated in this syndrome are often bizarre and varying.Conventional MRI has an important role in diagnosis,treatment and followed up for patients with HLD.Technology of DTI and MRS of brain were new approach developed in the resent years.It based on the principle of magnetic resonance which had higher sensitivity than conventional MRI.MRS measurements are determined by biochemical profiles of the underlying pathologies,whereas DTI is more sensitive to structural differences.Using the MRS and DTI technology to HLD was less reported,and studies have yielded conflicting results.Objective The objective of this study was to assess the clinical application of proton magnetic resonance spectroscopy(~1H-MRS)and diffusion tensor imaging(DTI)in detecting micro-structural impairments of the white matter and deep gray matter nuclei and neurochemical abnormalities in patients with hepatolenticular degeneration(HLD).To explore the value of DTI in judging microscopic lesions in normal appearing white matter of HLD patient.FA,ADC,E1,E2,E3 value,and relative ratio of NAA /Cr,Cho/Cr and NAA/Cho in the HLD group and healthy controls were compared.To study the correlation between FA value and relative ratio of NAA /Cr in HLD.ROC curve was drawed by DTI and MRS quantitative data,and than evaluate their diagnostic performance.Methods 26 patients with HLD and 20 volunteers underwent DTI and ~1H-MRS exams.FA,ADC,E1,E2,E3 value,and relative ratio of NAA /Cr,Cho/Cr and NAA/Cho of bilateral thalamus,bilateral putamens,bilateral frontal cerebral white matter and splenium of corpus callosum from the two groups were obtained and processed with statistical methods.Pearson's correlation was used in analyzing the relation of values.ROC curve was drawn with clinical diagnosis results as the gold standard.Taking P<0.05 for the difference was statistically significant.Results The HLD patients group had higher FA and ADC values in bilateral putamen and thalamus compared to the volunteer group.The differences of FA and ADC values in bilateral putamen between the HLD group and the volunteer group were statistically significant(P<0.05).However,there were no statistically significant differences of FA and ADC values in bilateral thalamus between the two groups(P>0.05).Mean ADC values of bilateral frontal white matter and corpus callosum of the HLD patients group was higher than that of the volunteer group.Mean FA values of Bilateral frontal white matter and corpus callosum from the HLD patients group were lower compared with that from the volunteers group,and the differences were statistically significant(P<0.05).The mean Eigenvalue values of all ROI of the HLD groups were higher than that of the volunteer group.Differences were found in bilateral putamen(E1,E2,E3 value),bilateral thalamus(E1 value),bilateral frontal white matter and corpus callosum(E2,E3 value)and all the differences were statistically significant(P<0.05).Bilateral putamen,bilateral thalamus and corpus callosum of the HLD group had lower NAA/Crin ratios compared with the volunteer group,and the differences were statistically significant.FA value were positive correlated to NAA/Cr ratio(P < 0.05)on Bilateral thalami,frontal white matter and thecorpus callosum.FA value has favorable effective functions for the diagnosis on the right side of the putamen.The sensitivity and specificity were separately 80% and 76.9% used diagnostic value of 0.160(10-3 was/s).Combined analysis of FA value and NAA/Cr ratio demonstrated a sensitivity of 96.2% or a specificity of 90% for acute rejection.Conclusion DTI combined with ~1H-MRS can be used as quantitative indicators to assess micro-structural impairments and neurochemical abnormalities in HLD.These results showed that it can truly reflect the extent of brain damage of HLD patients.The putamen FA value increases maybe related with the excess iron accumulation in the region in patients with HLD.MRS was a noninvasive method that provides metabolic information about the brain.This study found a medium positive correlation between the FA value and NAA/Cr ratio in part of the ROI.DTI and MRS can provide quantitative data to response the real damage of brain tissue.The results show that the process possesses certain advantages and feasibility,have laid certain foundation for the further clinical research and the application.