Poster 19: Basal Ganglia Pathology in Preclinical and Early Symptomatic Huntington's Disease: Diffusion Tensor Imaging, Magnetic Resonance Spectroscopy, and Volumetric Measures—Which Imaging Modality Is More Sensitive?

Abstract

Background Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder characterized by motor, psychiatric, and cognitive dysfunction. One of the main focuses of clinical research now is to define valid and reliable biomarkers of disease onset and progression that can be of use in future treatment trials. Various neuropathological and neuroimaging studies have indicated early involvement of various components of the basal ganglia. Aim In this study, we examined the sensitivity of three magnetic resonance techniques in detecting basal ganglia pathology. Diffusion tensor imaging (DTI) is an MRI technique that measures indices of passive water diffusion, which is believed to reflect the tissue fiber density, fiber architecture, and uniformity of nerve fiber direction. Proton MRS (1H-MRS) is a non-invasive technique that allows the detection of brain chemicals that contain hydrogen, such as N-Acetyl-aspartate (NAA), choline-containing compounds (CHO), creatine/phosphocreatine (CRE), glutamine, glutamate, myoinositol (mI), and lactate (LAC). Volumetric measures of caudate and putamen can be obtained from structural MRI scans. Method We examined 25 HD gene carriers (13 preclinical and 12 early symptomatic) and 20 matched gene negative controls. The three imaging modalities were performed on each subject using a GE Signa 1.5T scanner during one scan session. Six HD gene carriers and two control subjects were scanned twice, two years apart. Clinical measures were also collected. Results The H-MRS revealed increased choline/creatine and myoinositol/creatine ratios in the basal ganglia in the symptomatic group and decreased glutamate+glutamine/creatine ratios in the preclinical group. Preliminary DTI analyses suggest reduced anisotropy, measured as fractional anisotropy in the basal ganglia. More detailed DTI results and volumetric data will be presented at the meeting. The sensitivity, limitations of, and relationship between the three MRI imaging modalities in detecting basal ganglia pathology in HD will be discussed. The combination of all three techniques may provide a more powerful tool to predict aspects of the clinical presentation.