Advanced Quantitative Magnetic Properties Mapping of Tissue Microstructure

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Motivation The advent of ultra high field (UHF > 3 Tesla) MRI technologies, both hardware and MRI sequence physics, has introduced the possibility of visualizing in vivo changes in human tissue structure with an unprecedented level of accuracy. Accordingly, an ultra-high resolution mapping of MRI voxel-level microstructure would be highly impactful for providing a more nuanced understanding of neurodevelopment, brain plasticity and cellular aging This proposal aims to extend quantitative magnetic susceptibility and relaxometry-based MRI models of brain tissue microstructure to create intermediate resolution microstructure maps, based on 7 Tesla (T) MRI data. Specifically, by using an intermediate resolution of 50 150 m isotropic voxel sizes, presently achievable with 7 T animal MRI, the proposed work will seek to create reproducible assessments of myelin bilayer, axon and neuroglia magnetic susceptibility properties. MRI measurements will be related to underlying biological features by using computational models of realistic cell geometries and myelin volume fraction within an imaging voxel. Overall Objective This proposal aims to formulate a reproducible, quantitative microstructure MRI method to measure both myelin volume fraction and the amount of ferritin iron stored in neuroglial cells in mouse brain. The MRI method will be developed and validated using 7 T MRI of cuprizone (CPZ)-fed mice as a highly controllable biological system for estimating myelin volume fraction and the amount ferritin iron in brain white matter. Impact: While traditional MRI contrasts can reliably depict contrast in human brain tissue, they lack quantitative specificity. This is particularly relevant for MRI studies of fundamental brain neuroanatomy in basic and developmental neuroscience. A non-invasive, spatially resolved quantification of critical microstructural features in the brain would significantly enhance MRI as a tool for neurodevelopmental, neuroscience and brain aging research. Equally important, the proposed program will provide excellent training opportunities for highly qualified personnel, as well as set the basis for increased understanding of the microstructural organization of mouse brain tissue, with the ultimate goal of translating these findings/methods to human imaging.