Background Aberrant myelination may contribute or even precede neurodegeneration. White matter (WM) abnormalities have been widely reported in Huntington’s disease (HD), and are detectable in the pre-manifest stage, prior to symptom onset, using diffusion-weighted (DW) MRI. However, standard DW MRI metrics (e.g. fractional anisotropy (FA)) are non-specific indices of underlying biological changes. Quantitative magnetization transfer (qMT) imaging is a more sensitive measure of myelin content in white matter, as indexed by the macromolecular proton fraction (MPF). MPF is lower in early-stage HD and is related to WM abnormalities measured with DW MRI (Bourbon-Teles et al, 2017).

Aims To assess whether myelin breakdown can be detected in pre-manifest HD gene carriers using qMT and DW MRI.

Methods/techniques MRI was performed on a Siemens PRISMA 3T MRI Scanner at Cardiff University Brain Research Imaging Centre (CUBRIC). Eight pre-HD participants (Disease burden score; 229–299), and eight matched controls were recruited and scanned. A 3D MT-weighted fast spoiled gradient recalled-echo (SPGR) sequence was used to obtain qMT data for estimation of myelin. DW MRI was acquired and manual tractography of the cortico-spinal tract (CST), corpus callosum (CC), anterior thalamic radiation (ATR) and SMA-putamen was performed in Explore-DTI v 4.8.3.

Results/outcome We will present a group-wise comparison between MPF and FA, radial and axial diffusivity (RD and AD) across all WM tracts, in line with the methods of (Bourbon-Teles et al, 2017). Planned analysis to assess group differences in diffusion metrics will be used to infer microstructural differences in WM properties including myelin content, white matter integrity and axonal damage in pre-manifest participants.

Conclusions This is the first study to apply qMT MRI to measure myelin content in a pre-manifest cohort. Reduced myelination in this cohort could help inform the development of new drug treatments that aim to tackle HD in the earliest stages. Further analysis will combine this with volumetric data, to probe the early relationship between myelination and grey matter atrophy.