Brain scanner maps Huntington damage at cell level

Huntington’s disease targets specific brain regions, particularly the basal ganglia (a group of structures deep in the brain that regulate movement and cognition). Cells die, and tissue shrinks. Until now, scans could measure that shrinkage but could not clearly distinguish what changes at the cellular level. Soma and Neurite Density Imaging (SANDI) is a technique based on diffusion MRI that differentiates between cell bodies (soma) and cellular extensions (neurites). The study, published in eLife, applied SANDI to 56 people with Huntington’s disease and 57 age- and sex-matched controls.

In people with Huntington’s, the density of cell bodies in the basal ganglia was lower than in controls. At the same time, the cell bodies that remained were larger, and there was more space between cells. This combination points to active cell loss alongside changes in surviving cells. Notably, neuritic extensions of the cells did not differ significantly between groups, suggesting that loss of cell bodies is the earliest detectable sign of damage in this region.

Link to motor decline

SANDI measurements correlated with results on standardized motor tests. Greater scan abnormalities were associated with worse motor performance. SANDI values explained up to 63% of the variance in brain volume loss. This makes the technique potentially useful as a biomarker in clinical trials, allowing early measurement of whether a treatment is having an effect.

Relevance for neurodegenerative aging

Huntington’s is primarily genetically determined, but the mechanisms of cell loss in the basal ganglia are also relevant to other neurodegenerative conditions associated with aging. SANDI could in the future help detect age-related brain damage earlier and more precisely. Whether the technique is broadly applicable for that purpose requires further research.

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