Background Magnetisation transfer imaging (MTI) has the potential to quantify pathological changes in CNS disorders before conventional MRI sequences can detect abnormalities. This makes MTI an attractive technique to apply in both premanifest and manifest HD as an addition to volumetric measures.

Aim To investigate MTI parameters and their clinical correlates in premanifest and manifest HD.

Method From the TRACK-HD study, 78 participants (28 controls, 25 premanifest gene carriers and 25 manifest HD) were scanned using MTI and T1 weighted MRI. Brain regions were segmented using FSL's automated tools FAST and FIRST on T1 images. This approach yields separate segmentations of grey matter, white matter, caudate nucleus, putamen, pallidum, thalamus, amygdala and hippocampus, of which individual magnetic transfer ratio (MTR) values were calculated. Regression analysis with clinical measures of motor (UHDRS total motor score, speeded tapping, tongue force), cognitive (MMSE, SDMT, Stroop, TMT, Verbal fluency), behavioural functioning (BDI, FrSBe, PBA-s) and the disease burden was performed on gene carriers.

Results MTR peak height was reduced in both grey (p<0.004) and white matter (p<0.006) in manifest HD compared with controls. Mean MTR was also reduced in grey matter (p<0.001) and showed a trend in white matter (p<0.052) in manifest HD. No differences between premanifest gene carriers and controls were found. The deep grey matter structures showed a uniform pattern of significantly reduced MTR values in manifest HD (p<0.05) but not in premanifest HD. MTR values correlated with disease burden, motor and cognitive impairment.

Conclusion Throughout the brain, disturbances in MTI parameters are apparent in manifest HD and are homogeneous across (subcortical) grey and white matter. The correlation of MTI with clinical features indicates the potential to act as a disease monitor in future clinical trials.