Robust MR-based approaches to quantifying white matter structure and structure/function alterations in Huntington's disease

BACKGROUND Huge advances have been made in understanding and addressing confounds in diffusion MRI data to quantify white matter microstructure. However, there has been a lag in applying these advances in clinical research. Some confounds are more pronounced in HD which impedes data quality and interpretability of patient-control differences. This study presents an optimised analysis pipeline and addresses specific confounds in a HD patient cohort. METHOD 15 HD gene-positive and 13 matched control participants were scanned on a 3T MRI system with two diffusion MRI sequences. An optimised post processing pipeline included motion, eddy current and EPI correction, rotation of the B matrix, free water elimination (FWE) and tractography analysis using an algorithm capable of reconstructing crossing fibres. The corpus callosum was examined using both a region-of-interest and a deterministic tractography approach, using both conventional diffusion tensor imaging (DTI)-based and spherical deconvolution analyses. RESULTS Correcting for CSF contamination significantly altered microstructural metrics and the detection of group differences. Reconstructing the corpus callosum using spherical deconvolution produced a more complete reconstruction with greater sensitivity to group differences, compared to DTI-based tractography. Tissue volume fraction (TVF) was reduced in HD participants and was more sensitive to disease burden compared to DTI metrics. CONCLUSION Addressing confounds in diffusion MR data results in more valid, anatomically faithful white matter tract reconstructions with reduced within-group variance. TVF is recommended as a complementary metric, providing insight into the relationship with clinical symptoms in HD not fully captured by conventional DTI metrics.