C-MORPH · Noninvasive cell specific morphometry in neuroinflammation and degeneration

Brain structure determines function. Disentangling regional microstructural properties and understanding how these properties constitute brain function is a central goal of neuroimaging of the human brain and a key prerequisite for a mechanistic understanding of brain diseases and their treatment. Using magnetic resonance (MR) imaging, previous research has established links between regional brain microstructure and inter-individual variation in brain function, but this line of research has been limited by the non-specificity of MR-derived markers. This hampers the application of MR imaging as a tool to identify specific fingerprints of the underlying disease process.Exploiting state-of-the-art ultra-high field MR imaging techniques, I have recently developed two independent spectroscopic MR methods that have the potential to tackle this challenge: Powder averaged diffusion weighted spectroscopy (PADWS) can provide an unbiased marker for cell specific structural degeneration, and Spectrally tuned gradient trajectories (STGT) can isolate cell shape and size. In this project, I will harness these innovations for MR-based precision medicine. I will advance PADWS and STGT methodology on state-of-the-art MR hardware and harvest the synergy of these methods to realize Cell-specific in-vivo MORPHOMETRY (C-MORPH) of the intact human brain. I will establish novel MR read-outs and analyses to derive cell-type specific tissue properties in the healthy and diseased brain and validate them with the help of a strong translational experimental framework, including histological validation. Once validated, the experimental methods and analyses will be simplified and adapted to provide clinically applicable tools. This will push the frontiers of MR-based personalized medicine, guiding therapeutic decisions by providing sensitive probes of cell-specific microstructural changes caused by inflammation, neurodegeneration or treatment response.