Computational protocol: Structural and molecular myelination deficits occur prior to neuronal loss in the YAC128 and BACHD models of Huntington disease

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Protocol publication

[…] YAC128 HD mice: 16 mice (8 WT; and 8 YAC128; 50% male) were scanned at 1.5, 3, 6, 9 and 12 months old. The mice were anaesthetized using 1–3% isoflurane mixed with oxygen and air (1:1 ratio) through a nose cone during preparation and MRI scanning. Respiration rate was maintained at 80 ± 10 bpm and temperature at 36–37°C with an MRI-compatible heater (SAII, NY). MRI was conducted on a 7T scanner (ClinScan, Bruker BioSpin, Germany) with four-channel mouse brain array coils. DTI was acquired using a spin-echo EPI sequence with eight averages of 30 diffusion sensitizing directions, b = 1500 s/mm2, repetition time (TR) = 10000 ms, echo time (TE) = 40 ms and 0.2 × 0.2 × 0.5 mm3 voxel resolution. The acquisition time was 45.5 min. High-resolution structural MRI was acquired with fast spin-echo with TR = 2760 ms, TE = 43 ms and voxel size = 0.1 × 0.1 × 0.3 mm3. After eddy current distortion and motion correction, tensor fitting was carried out using the weighted least squares method with FDT (FMRIB's Diffusion Toolbox, FSL, Oxford; http://fsl.fmrib.ox.ac.uk/fsl/, last accessed April 28, 2016) to obtain FA. For each time point, one animal with the highest signal-to-noise ratio was chosen to be the initial target, and the remaining animals' FA images were non-linearly registered to it using FNIRT (FMRIB’s nonlinear image registration tool). The registered images were then averaged to create time point-specific FA templates. Another round of non-linear registration was carried out to align all FA images to the corresponding FA template. After in-plane Gaussian smoothing of 0.3 mm full-width at half maximum, voxel-wise group analysis was conducted on the FA map using two-sample t-tests in SPM8 (http://www.fil.ion.ucl.ac.uk/spm/, last accessed April 28, 2016). The statistical analysis was restricted to WM regions with FA > 0.175 on the template. Family wise correction was performed with a cluster threshold of P < 0.05 determined by a Monte-Carlo simulation using 3DClustSim in AFNI (NIH; http://afni.nimh.nih.gov/, last accessed April 28, 2016). Based on the results of the voxel-wise analysis, regions of interest were manually drawn in the anterior CC, posterior CC, AC, EC and CG on the templates (B). The average FA values in those regions were calculated.BACHD rats: Diffusion tensor images were acquired using an echo planar imaging with 256 directions (b = 0,1000s/mm2, 54×21 mm field of view, 128×52 mm matrix, twenty-six 1 mm slices, 60/5500ms TE/TR). FA images were generated using Inveon Acquisition Workplace. Inveon Research Workplace software was used for the image analysis, where a volume of interest approach was implemented on anterior and posterior CC, the CG and the EC. FA values were compared between male BACHD rats and WT controls at 12 months of age (TG5:WT = 14:13 for EC, TG5:WT = 11:10 for the remaining areas). […]

Pipeline specifications

Software tools SPM, AFNI
Applications Magnetic resonance imaging, Functional magnetic resonance imaging
Organisms Mus musculus, Rattus norvegicus