Sensitising brain MRI to cell type and shape

We propose to sensitise brain Magnetic Resonance Imaging (MRI) to cell type numbers, shapes, and connectivity. The goal in each case is to achieve cell specificity. We will do so by (1) developing novel molecular MRI contrasts that provide cell or molecule specific signatures read out through the widely used Blood Oxygen Level Dependent (BOLD) signal, (2) enhancing diffusion Magnetic Resonance Spectroscopy (MRS) to provide tissue microstructure intracellularly to distinguish between neuronal, astrocyte, and microglia morphology, and (3) combining high resolution diffusion and quantitative MRI with 2D and 3D histology and transcriptomics to generate models that can predict cell distribution and optimise mesoscopic brain connectivity. Our project will significantly advance our ability to use MRI as a cell-specific readout of brain architecture. Timecourses of our metrics will then allow us to provide key insights into how variation in the cellular architecture of the brain leads to variation in risk and resilience in mental health.