Fixel-Based Analysis Effectively Identifies White Matter Tract Degeneration in Huntington’s Disease

Abstract

Microstructure damage in white matter might be linked to regional and global atrophy in Huntington’s Disease (HD). We hypothesize that degeneration of subcortical regions, including the basal ganglia, is associated with damage of white matter tracts linking these affected regions. We aim to use fixel-based analysis to identify microstructural changes in the white matter tracts. To further assess the associated gray matter damage, diffusion tensor-derived indices were measured from regions of interest located in the basal ganglia. Diffusion weighted images were acquired from 12 patients with HD and 12 healthy unrelated controls using a 3 Tesla scanner. Reductions in fixel-derived metrics occurs in major white matter tracts, noticeably in corpus callosum, internal capsule, and the corticospinal tract, which were closely co-localized with the regions of increased diffusivity in basal ganglia. These changes in diffusion can be attributed to potential axonal degeneration. Fixel-based analysis is effective in studying white matter tractography and fiber changes in HD.

Early whole-body mutant huntingtin lowering averts changes in proteins and lipids important for synapse function and white matter maintenance in the LacQ140 mouse model

“…Changes in white matter detected through imaging are one of the first signs of disease in people with HD (PwHD) (Rosas et al, 2006;Paulsen et al, 2008;Paulsen, 2009;Hobbs et al, 2010;Di Paola et al, 2012;Phillips et al, 2013;Singh et al, 2013;Matsui et al, 2015;Odish et al, 2015;Poudel et al, 2015;Faria et al, 2016;Bourbon-Teles et al, 2019;Tereshchenko et al, 2019;Sweidan et al, 2020;Oh et al, 2021). Morphometric studies of postmortem HD brain showed reduced cross-sectional area of white matter in addition to gray matter atrophy (de la Monte et al, 1988;Vonsattel and DiFiglia, 1998).…”

Early whole-body mutant huntingtin lowering averts changes in proteins and lipids important for synapse function and white matter maintenance in the LacQ140 mouse model

“…Changes in white matter detected through imaging are one of the first signs of disease in people with HD (PwHD) ( Bourbon-Teles et al, 2019 ; Di Paola et al, 2012 ; Faria et al, 2016 ; Hobbs et al, 2010 ; Matsui et al, 2015 ; Odish OF et al, 2015 ; Oh et al, 2021 ; Paulsen, 2009 ; Paulsen et al, 2008 ; Phillips et al, 2013 ; Poudel et al, 2015 ; Rosas et al, 2006 ; Singh et al, 2013 ; Sweidan et al, 2020 ; Tereshchenko et al, 2019 ). Morphometric studies of postmortem HD brains showed reduced cross-sectional area of white matter as well as gray matter atrophy ( de la Monte et al, 1988 ; Vonsattel and DiFiglia, 1998 ).…”

The contribution of preclinical magnetic resonance imaging and spectroscopy to Huntington’s disease

“…Fixel-based analysis in early-phase HD patients allowed to detect specifically affected fiber bundles with reduced cross-section (FC) but stable fiber density (FD) (Adanyeguh et al, 2021). Though, FD reduction was observed in the fornix (Oh et al, 2021). Interestingly, the same kind of analysis applied to corticostriatal and cortico-thalamic tracts was able to detect reduction of the fiber density and cross section (FDC) parameter in gene carriers 11 years from onset, while they were still preserved 25 years from onset (Zeun et al, 2022), highlighting the ability of diffusion-MRI to visualize the progression of the disease.…”