In vivo Assessment of Brain Microstructure in Patients with Huntington's Disease Using Quantitative MRI

ObjectivesUtilizing the quantitative magnetic resonance imaging (MRI) technique, multiparametric mapping (MPM), we assessed the integrity of cortical and subcortical regions across different Huntingtons disease (HD) stages, relating the derived findings to genetic modifiers and clinical measures. MethodsSixteen premanifest patients with HD (PwHDpre), ten manifesting PwHD (PwHDman), and forty-two healthy controls (HC) underwent clinical examinations and an MRI session at 3T. We derived quantitative MPM maps and performed voxel-based quantification (VBQ) and voxel-based morphometry (VBM). We assessed the group differences between the combination of PwHDpre and PwHDman (PwHDtotal), PwHDpre and PwHDman, compared with matched HC. Using correlation analysis, we investigated the link between MPM-derived findings, CAG repeat length, and clinical scores. ResultsPwHDman presented with reductions in all four quantitative MPM maps across bilateral caudate nucleus, frontal, parietal, temporal, and occipital gyri. We observed spatial overlap between VBQ- and VBM-derived findings, demonstrating widespread volume loss in PwHDman. PwHDpre presented with reductions in some quantitative maps within frontal and temporal regions. Reduced MPM values correlated with clinical scores of HD severity. InterpretationThe observed reductions across four MPM modalities in PwHDman are consistent with demyelination and neuronal loss, supported by observations of widespread volume loss. While the observed reductions in PwHDpre are indicative of early demyelination and inflammation. In this study, we demonstrated the utility and clinical relevance of MPM for detecting microstructural alterations across different stages of HD. MPM can serve as a non-invasive biomarker of neurodegeneration in HD, with insights into pathological events underlying the observed neuronal loss.