Merged magnetic resonance and light sheet microscopy of the whole mouse brain

We demonstrate the highest-resolution MR images ever obtained of the mouse brain. The diffusion tensor images (DTI) @ 15 μm spatial resolution are 1,000 times the resolution of most preclinical rodent DTI/MRI. Superresolution track density images are 27,000 times that of typical preclinical DTI/MRI. High angular resolution yielded the most detailed MR connectivity maps ever generated. High-performance computing pipelines merged the DTI with light sheet microscopy of the same specimen, providing a comprehensive picture of cells and circuits. The methods have been used to demonstrate how strain differences result in differential changes in connectivity with age. We believe the methods will have broad applicability in the study of neurodegenerative diseases.