Diffusion imaging in Huntington's disease: comprehensive review

Area of Science:

• Neuroimaging
• Neuroscience
• Genetics

Background:

• Huntington's disease (HD) is a monogenic disorder with 100% penetrance.
• Early, premanifest stages of HD exhibit detectable brain changes.
• Investigating microstructural alterations offers insights into brain organization and neurodegeneration.

Purpose of the Study:

• To investigate microstructural brain changes in early and premanifest Huntington's disease using diffusion MRI.
• To understand the pattern and progression of white matter degeneration in HD.
• To assess the utility of diffusion MRI in clinical trials for HD.

Main Methods:

• Diffusion MRI techniques including voxelwise analysis, region of interest, and tractography.
• Analysis of white matter degeneration patterns.
• Application of advanced techniques like multitissue compartment models and connectomics.

Main Results:

• Diffusion MRI reveals a centrifugal pattern of white matter degeneration in HD, starting in deep brain areas.
• Degeneration affects the corpus callosum, long white matter tracts, and densely connected networks like the sensorimotor network early in premanifest stages.
• Diffusion analyses show potential as a biomarker for tracking disease progression and treatment effects.

Conclusions:

• Diffusion MRI is a valuable tool for detecting and tracking microstructural brain changes in Huntington's disease, even in premanifest stages.
• Understanding the pattern of degeneration aids in comprehending HD's neurodegenerative process.
• Diffusion MRI analyses should be considered for inclusion in clinical trials to enhance understanding of treatment efficacy.