In vivo brain microstructure mapping for clinical neuroimaging
Description: None of the current microscopy techniques are usable on human living subjects. Yet characterizing the microstructure of human brain over the course of development, aging and disease withholds tremendous value for neurobiology and diagnostics. Diffusion MRI has emerged in recent years as a highly promising “super-resolution” technique which can provide sub-pixel information about tissue microstructure. In an MRI experiment, water molecules diffuse over a few microns and their path is mainly influenced by cellular membranes and other features of tissue architecture encountered over that distance. The main challenge in the field of Microstructural MRI is to decode the information contained in the diffusion-weighted signal to retrieve these specific features of microstructure, by combining dedicated measurements with biophysical modeling. The ultimate goal is to bring MRI to the level of a non-invasive in vivo microscope. The past years has been pivotal to the establishment of white matter microstructure mapping, which is now validated and used in clinical studies of disease. Given the numerous neurodegenerative and psychiatric diseases that involve substantial gray matter damage, there is growing interest in mapping gray matter microstructure. The main challenge that has stalled Microstructural MRI in gray matter so far is establishing the relevant biophysical model for this tissue. We have recently taken up that challenge and showed that the main mechanism that needs to be specifically accounted for is membrane permeability of neurites and glial processes. We have developed the framework for a new model (NEXI – Neurite EXchange Imaging) that has been successfully implemented in the rat cortex in vivo. Importantly, NEXI is translatable to clinical MRI systems.The project is articulated around the following objectives: (i) Bring human gray matter microstructure mapping to the same level of maturity as white matter mapping; (ii) Develop “dynamic” microstructure mapping; (iii) Translate microstructure mapping tools to clinical studies, and bring new insights into disease mechanisms and progression, with a particular focus on biomarkers of early psychosis.The Microstructural MRI tools proposed are meant to have a dramatic impact on our understanding of virtually all normal and pathological processes. They can be adapted for both animal and clinical studies, giving them outstanding potential for fundamental neuroscience and in translational research. Finally, they can be used to uncover relationships between brain structure and function at a new mesoscale, and potentially revolutionize brain network modeling.
Amount: CHF 1,727,000
Funding type: fellowship
Funder scheme: Eccellenza
Start date: 2021-09-01
End date: 2026-08-31
Investigator: Jelescu, Ileana
Institution: University of Lausanne – LA
Funded outputs count: 44
Funder award ID: 194260
OpenAlex ID: G8259175753