What is it about?

The work presents the highest resolution MRI/DTI images of the mouse brain ever acquired. Postmortem specimens were scanned on a specially constructed 9.4T mouse connectome scanner at spatial resolution of 15 microns. Diffusion tensor imaging (DTI) allows one to map the connections in the brain. Spatial resolution was extended using a super resolution technique to 5 micron voxels with volume that is 64 million times smaller than the standard clinical scan. The method was paired with light sheet microscopy allowing whole brain studies of cells and circuits to study a wide range of neurodegenerative diseases- Alzheimer's, Parkinson's etc.

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Why is it important?

The method is transformative for the neuro science community as it provides a comprehensive whole mouse brain images at microscopic resolution. As clinical MRI has revolutionized patient care, this method will enable basic scientists to study mouse models of disease in unprecedented detail. Since the brain remains in the skull, its morphology remains in tact. The light sheet images are registered to the in skull specimen making accurate measures of cell density possible. Diffusion tensor tractography provides insight into changes in brain connectivity in early development, aging, neuro degeneration, and exposure to neuro toxins.

Perspectives

The final sentence in Paul Lauterbur's Nobel Prize winning paper describing MRI says that "imaging techniques should have many useful applications in studies of internal structure and composition of microscopic objects". Fifty years of relentless work in engineering, physics, and biology have made his vision a reality. By merging MRI with light sheet microscopy in the whole brain we can now explore the exquisite complexity of the brain (and many other tissues) in tact. The data can uncover mechanisms and evolution of terrible diseases, the details of neuro development and neuro degeneration, the impact of genetics. The rich multidimensional data will provide ready material for AI discovery in neuroscience.

G Allan Johnson
Duke University

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This page is a summary of: Merged magnetic resonance and light sheet microscopy of the whole mouse brain, Proceedings of the National Academy of Sciences, April 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2218617120.
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