E005 In vivo quantification of basal ganglia microstructural abnormalities in Huntington’s disease with soma and neurite density imaging
Year: 2024
Type: conference-paper
Study design: Observational Study
Abstract: Background Huntington’s Disease (HD) causes loss of motor functions largely due to atrophy in the basal ganglia (BG). Soma and Neurite Density Imaging (SANDI)1 is a novel biophysical model yielding estimates of soma and neurite density and soma size that may inform about the pathological processes in the BG in HD. Aims To characterise HD-related pathological abnormalities in BG microstructure with SANDI indices and evaluate the associations between SANDI-derived measures and speeded tapping motor performance. Methods T1-weighted (1mm3) and multi-shell diffusion-weighted-imaging (2mm3, 6 b-values from 0 - 6,000 s/mm,2 254 directions) data were acquired on an ultra-strong gradient (300 mT/m) 3T Siemens Connectome system in n = 30 individuals with premanifest and manifest HD and n = 30 age- and sex-matched healthy controls. The caudate, putamen, pallidum, and thalamus were segmented bilaterally from T1-weighted images using FreeSurfer v6. Median values of proxy soma density, soma size, and extracellular water were extracted for each subcortical region and compared between the groups. SANDI measures were correlated with Q-motor2 speeded tapping performance. Results HD was associated with increased extracellular water and soma size and reduced soma density in the BG but not the thalami (figure 1) consistent with ex vivo morphometric evidence of neuronal soma loss and astrocyte swelling in the HD brain.3 Speeded tapping correlated negatively with soma density and positively with soma size and extracellular water (figure 2). Conclusion SANDI-derived measurements may provide in vivo biomarkers of cellular BG changes that are associated with the loss of motor function in HD. References Palombo M, Ianus A, Guerreri M, et al. SANDI: a compartment-based model for non-invasive apparent soma and neurite imaging by diffusion MRI. Neuroimage 2020;215:116835. doi: 10.1016/j.neuroimage.2020.116835 [published Online First: 20200411] Reilmann R, Schubert R. Motor outcome measures in Huntington disease clinical trials. Handb Clin Neurol 2017;144:209–25. doi: 10.1016/B978-0-12-801893-4.00018-3. Rajkowska G, Selemon LD, Goldman-Rakic PS. Neuronal and glial somal size in the prefrontal cortex: a postmortem morphometric study of schizophrenia and Huntington disease. Arch Gen Psychiatry 1998;55(3):215–24. doi: 10.1001/archpsyc.55.3.215.
Institutions: Cardiff University, George Huntington Institute
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4402373677