Ex vivo 100 μm isotropic diffusion MRI‐based tractography of connectivity changes in the end‐stage R6/2 mouse model of Huntington's disease

Background: Huntington's disease is a progressive neurodegenerative disorder. Brain atrophy, as measured by volumetric magnetic resonance imaging (MRI), is a downstream consequence of neurodegeneration, but microstructural changes within brain tissue are expected to precede this volumetric decline. The tissue microstructure can be assayed non-invasively using diffusion MRI, which also allows a tractographic analysis of brain connectivity.
Methods: We here used ex vivo diffusion MRI (11.7T) to measure microstructural changes in different brain regions of end‐stage (14 weeks of age) wild type and R6/2 mice (male and female) modeling Huntington's disease. To probe the microstructure of different brain regions, reduce partial volume effects and measure connectivity between different regions, a 100 μm isotropic voxel resolution was acquired.
Results: Although fractional anisotropy did not reveal any difference between wild‐type controls and R6/2 mice, mean, axial, and radial diffusivity ...,

2.2 | MRI
For MR imaging, mouse heads were immersed into proton‐free FluorInert (Sigma) in a syringe to immobilize the head for long scanning times at a high resolution, where minimal movement between gradient directions can affect image quality. Images were acquired with a Bruker AV3 HD 11.7T/89mm vertical bore microimaging system, with a Micro 2.5 gradient insert (capable of up to 150 G/cm) in a 25 mm quadrature birdcage coil (Bruker). Sample temperature was maintained at 21 ± 0.1°C with a Bruker SmartCooler BCU‐1 40/50 air chiller and probe heater with a thermocouple feedback loop.39 Scanning parameters were defined in ParaVision 6.0. A 3D spin‐echo diffusion MRI scan was acquired (repetition time, TR = 700 ms, echo time, TE = 24 ms, diffusion time = 12 ms, diffusion encoding duration 5 ms, b value = 1401.57 s/mm2, with 12 non-collinear diffusion directions and one A0 image, number of averages, NA = 1, matrix 196 × 128 × 128, 100 μm isotropic resolution, and 31 h 3 min acquisitio..., DSI Studio