Sensitising brain MRI to cell type and shape

We propose to sensitise brain MRI to cell type numbers and shapes or morphologies. The goal in each case is to achieve cell specificity. We will do so by (1) enhancing diffusion MRS to provide tissue microstructure intracellularly to distinguish between neuronal, astrocyte, and microglia morphology, by (2) combining high resolution diffusion and quantitative MRI with 2D and 3D microscopy and spatial transcriptomics to generate models that can predict cell distribution, and by (3) developing novel molecular MRI contrasts that provide cell or molecule specific signatures read out through the widely used BOLD signal. Each of these three classes of methods will be important on their own, but it is in their integration that we expect to achieve cellular specificity and spatial resolution in vivo. At the end of the eight year project we will have significantly advanced our ability to use MRI as a cell-specific readout of brain architecture and provided key insights into how variation in the cellular architecture of the brain leads to variation in risk and resilience in mental health.