Ultra-High field (UHF) MRI has been in continuous development as a new tool to investigate ultrastructural microscopic details in neuropathology. In this study we use UHF-MRI (17.6T) to investigate presymptomatic changes in the hippocampus of animal models of ALS (G93A-SOD1 mice). Using an ALS fluorescent transgenic mouse reporter and optical confocal microscopy, we demonstrated that microstructural changes detected by MRI diffusion can be related to very early alterations in axonal connectivity. This study constitutes a stepping stone for the application of more complex diffusion models in inhomogeneous brain tissue as a non-invasive exploration of neuropathology in ALS.
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