Imaging and MRS protocols

All magnetic resonance acquisitions were carried out on a 3 T whole-body Siemens Magnetom Prisma scanner (Siemens Medical Solutions, Erlangen, Germany) with a standard Siemens transmit body coil and 64-channel receive head-neck coil array. A three-dimensional T₁-weighted image (T_R: 2300 ms, T_E: 4.18 ms, T_I: 900 ms, field-of-view (FOV): 256 × 240 mm², slice thickness: 1 mm) was acquired to allow for positioning of the volume of interest (VOI) and for volumetric analysis. Diffusion-weighted 2D spin-echo echo planar imaging (b values: 2500 s/mm² (60 directions), 900 s/mm² (32 directions) and 300 s/mm² (8 directions), FOV: 208 × 208 mm², T_E: 71 ms, T_R: 2910 ms, slice thickness: 2 mm, multiband acceleration factor: 3) was acquired to evaluate the brain microstructure in HD. Similar acquisitions were performed but with opposite phase-encode blip for distortion correction. The diffusion acquisitions were interleaved with several non-diffusion-weighted reference images for motion correction.

DW-MRS was performed in a 15 × 32 × 8 mm³ VOI positioned on the anterior part of the corpus callosum (Fig. 3b) using a semi-localized by adiabatic selective refocusing (sLASER) sequence coupled with bipolar diffusion weighting gradients (T_E: 120 ms, T_R: 3000 ms, gradient duration: 18 ms)³⁴. Diffusion weighting was applied in two orthogonal directions that were parallel (b values: 0, 482, 772, 1737 and 3088 s/mm², 48 spectra per b value) and perpendicular (b values: 0, 964, 1544, 3474, 6176 s/mm², 48 spectra per b value) to the callosal fibers. FAST(EST)MAP³⁵ was used to perform B₀ shimming in the VOI. The variable pulse power and optimized relaxation delays³⁶ were used for water suppression after determining the power needed for maximum water suppression. A reference scan, with no water suppression, was acquired for each b value and direction and used for eddy current correction. Cardiac gating was performed for all DW-MRS acquisitions using a peripheral pulse unit to reduce signal fluctuations induced by physiological motion.