ABSTRACT
Putaminal metabolites examined using cross-sectional magnetic resonance spectroscopy (MRS) can distinguish pre-manifest and early Huntington's Disease (HD) individuals from controls. An ideal biomarker, however, will demonstrate longitudinal change over short durations. The objective here was to evaluate longitudinal in vivo brain metabolite profiles in HD over 24 months. Eighty-four participants (30 controls, 25 pre-manifest HD, 29 early HD) recruited as part of TRACK-HD were imaged at baseline, 12 months, and 24 months using 3T MRS of left putamen. Automated putaminal volume measurement was performed simultaneously. To quantify partial volume effects, spectroscopy was performed in a second, white matter voxel adjacent to putamen in six subjects. Subjects underwent TRACK-HD motor assessment. Statistical analyses included linear regression and one-way analysis of variance (ANOVA). At all time-points N-acetyl aspartate and total N-acetyl aspartate (NAA), neuronal integrity markers, were lower in early HD than in controls. Total NAA was lower in pre-manifest HD than in controls, whereas the gliosis marker myo-inositol (MI) was robustly elevated in early HD. Metabolites were stable over 24 months with no longitudinal change. Total NAA was not markedly different in adjacent white matter than putamen, arguing against partial volume confounding effects in cross-sectional group differences. Total NAA correlations with disease burden score suggest that this metabolite may be useful in identifying neurochemical responses to therapeutic agents. We demonstrate almost consistent group differences in putaminal metabolites in HD-affected individuals compared with controls over 24 months. Future work establishing spectroscopy as an HD biomarker should include multi-site assessments in large, pathologically diverse cohorts.
Subject(s)
Biomarkers/metabolism , Brain/metabolism , Huntington Disease/metabolism , Huntington Disease/pathology , Adult , Analysis of Variance , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Cross-Sectional Studies , Female , Humans , Inositol/metabolism , Longitudinal Studies , Magnetic Resonance Spectroscopy , Male , Middle Aged , Putamen/pathology , Statistics as Topic , Time Factors , White Matter/pathologyABSTRACT
Myelin water imaging, a magnetic resonance imaging technique capable of resolving the fraction of water molecules which are located between the layers of myelin, is a valuable tool for investigating both normal and pathological brain structure in vivo. There is a strong need for pulse sequences which improve the quality and applicability of myelin water imaging in a clinical setting. In this study, we validated the use of a fast multi echo T(2) relaxation sequence for myelin water imaging. Using a multiple combined gradient and spin echo (GRASE) technique, we attain whole cerebrum myelin water images in under 15 minutes. Region of interest analysis indicates that this fast GRASE imaging sequence produces results which are in good agreement with pure spin echo measurements (R(2)=0.95, p<0.0001). This drastic improvement in speed and brain coverage compared to current spin echo standards will allow increased inclusion of myelin water imaging in neurological research protocols and opens up the possibility of applications in a clinical setting.
