Adapting and Optimizing CBV-MRI and MEGAPRESS-MRS to Measure Slow Functional Changes in Normal and Abnormal Brains

Description

Functional brain changes occur rapidly by alterations in synaptic activity, or more slowly, typified by changes in synaptic density and functional neurochemistry. Functional MRI has focused more on the prior than the latter, even though slow brain changes are important for normal brain function and for many brain disorders. With this in mind, I have adapted and optimized MRI-based tools in mice designed to measure ‘slow functional’ changes in the brain - slow changes in linked to synaptic density or slow changes in functional neurochemistry. First, I developed and optimized a series of tools that can map cerebral blood volume (CBV) across the cortical mantle and within cortical layers. I show that this reflects the known functional architecture of the mouse brain and use a whisker-cutting paradigm to show that this approach is sensitive to slow changes in synaptic density. Second, I demonstrate the utility of this approach for mapping slow changes in the brain associated with disease, by pinpointing changes in synaptic density in a novel mouse model of Alzheimer’s disease. Third, I implemented and optimized in mice an MR spectroscopy technique designed to measure changes in two neurotransmitters, GABA, and glutamate. I then demonstrate the translational capabilities of this approach by identifying glutamate abnormalities in the brains of patients in the prodromal stages of schizophrenia.

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