Linking MRI and microscopy for multi-scale neuroscience: mechanisms, diagnostics and anatomy

Magnetic resonance imaging (MRI) measures water, which exists in virtually every tissue in the body, including the brain. Although MRI images have 1 mm pixels, they have the potential to reveal information about tissue on the order of a micrometer which is 1,000 times smaller. This is because water is very sensitive to microscopic spaces and biological molecules. This enables MRI to detect subtle changes in brain disease happening at the microscopic scale. While these methods have exquisite sensitivity, they lack specificity; a given change measured with MRI could come from several plausible changes to brain tissue.

This research aims to improve our ability to interpret MRI by improving our understanding of how underlying microscopic properties of tissues alter the MRI signal. We will develop methods to link MRI at millimeter resolution to direct measurements using microscopes. By scanning brains after death, we can directly compare MRI and microscopy data in the same tissue to reveal their relationship. We will use these techniques to study brain anatomy at a very fine scale, to provide MRI microscopy markers in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and study how the brain rewires itself to learn new skills.