Journal article
Shape Matters: Predicting Huntington’s Disease using Progression Modelling
Computer methods and programs in biomedicine, Vol.277, 109250
04/2026
DOI: 10.1016/j.cmpb.2026.109250
PMID: 41564629
Abstract
•A deep learning pipeline for extracting descriptors of brain subcortical shape from MRI scans.•Compared to conventional volumetric measures, shape features are strongly associated with HD progression and better capture within-stage variability across the disease continuum.•Integration of shape descriptors into a conditional generative model improves forecasting of biomarkers of disease progression.
Despite evidence of group-level differences in striatal morphometry among persons with Huntington’s Disease (PwHD), current models of HD progression used for participant selection and assessment of treatment outcomes in clinical trials do not leverage shape information.
We first validated the capability of a discriminative deep neural network to derive descriptors of shape from all subcortical structures affected by HD, utilizing 2,932 brain scans in 615 PwHD across three longitudinal datasets (TRACK-HD, PREDICT-HD, and IMAGE-HD). We then trained a conditional generative model that used shape descriptors, alongside conventional volumetric, genetic, as well as composite cognitive, motor, and functional features at baseline to predict biomarkers of disease progression at subsequent time points.
We observed that the anatomical shapes of subcortical structures, including putamen, lateral ventricle, pallidum, caudate, thalamus, and accumbens, exhibited strong associations with HD progression, as measured by a commonly used prognostic score. Furthermore, within-stage heterogeneity, along the continuum of disease progression, was better captured: when shape descriptors were aggregated using principal component analysis, they showed a high correlation with disease stage (Spearman’s correlation: ρ = 0.72), compared to volumetric measurements in cubic millimetres (ρ = 0.45). Finally, incorporating subcortical shape into the generative model improved predictive performance, compared to the same model that relied solely on brain volumes.
This study demonstrates that subcortical brain shape is associated with HD progression, enables capturing fine-grained within-stage variability, and improves the predictability of characteristic biomarkers. The findings could potentially optimize future clinical trials through more targeted participant recruitment and more objective post-intervention assessments of treatment efficacy.
Details
- Title: Subtitle
- Shape Matters: Predicting Huntington’s Disease using Progression Modelling
- Creators
- Mohsen Ghofrani-Jahromi - Monash UniversitySusmita Saha - Monash UniversityAdeel Razi - Monash UniversityPubu M. Abeyasinghe - Monash UniversityGovinda R. Poudel - Australian Catholic UniversityJane S. Paulsen - University of Wisconsin–MadisonSarah J. Tabrizi - University College LondonNellie Georgiou-Karistianis - Monash University
- Resource Type
- Journal article
- Publication Details
- Computer methods and programs in biomedicine, Vol.277, 109250
- DOI
- 10.1016/j.cmpb.2026.109250
- PMID
- 41564629
- NLM abbreviation
- Comput Methods Programs Biomed
- ISSN
- 0169-2607
- eISSN
- 1872-7565
- Publisher
- Elsevier B.V
- Grant note
- CHDI Foundation: A-3433 National Health and Medical Research Council (NHMRC) Australia: 606650 NCATSNIH: R01-NS040068, U01-NS105509, U01-NS103475
TRACK-HD and TrackON-HD were supported by the CHDI Foundation, a not-for-profit organisation dedicated to finding treatments for Huntington's disease. IMAGE-HD was supported by CHDI Foundation research agreement A-3433 and the National Health and Medical Research Council (NHMRC) Australia grant 606650 (N.G.-K.). The PREDICT-HD study was funded by the NCATS and the NIH (NIH; R01-NS040068, U01-NS105509, U01-NS103475).
- Language
- English
- Electronic publication date
- 01/15/2026
- Date published
- 04/2026
- Academic Unit
- Psychiatry
- Record Identifier
- 9985130242302771
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