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



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.



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.



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.
Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Park Place, Cardiff CF10 3AT, UK; Brain Repair Group, Life Science Building, 3rd Floor, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK; Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Cathays, Cardiff CF24 4HQ, UK. Electronic address: steventonjj@cardiff.ac.uk.
Jessica J
JJ
Steventon
Brain Repair Group, Life Science Building, 3rd Floor, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK; School of Biomedical Sciences, Queen's Medical Centre, Nottingham University, Nottingham NG7 2UH, UK.
Rebecca C
RC
Trueman
Brain Repair Group, Life Science Building, 3rd Floor, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK; Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Cathays, Cardiff CF24 4HQ, UK; Institute of Psychological Medicine and Neurology, School of Medicine, Hadyn Ellis Building, Maindy Road, Cathays, Cardiff CF24 4HQ, UK.
Anne E
AE
Rosser
Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Park Place, Cardiff CF10 3AT, UK; Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis Building, Cathays, Cardiff CF24 4HQ, UK.
Derek K
DK
Jones
D000465:Algorithms; D016477:Artifacts; D015331:Cohort Studies; D003337:Corpus Callosum / Q000000981:diagnostic imaging*; D017281:Cost of Illness; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D056324:Diffusion Tensor Imaging; D005260:Female; D005385:Fingers / Q000503:physiopathology; D006801:Humans; D006816:Huntington Disease / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009929:Organ Size; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D066127:White Matter / Q000000981:diagnostic imaging*
Corpus callosum; DTI; Diffusion MRI; Disease burden; Huntington's disease; Tractography