Identifying the signature of glia in multi-dimensional MRI

Glia are immune-responsive brain cells that act as early biomarkers of neuroinflammation and pathology, making them important targets for intervention. Where current clinical imaging of neuroinflammation relies on PET and exposes patients to harmful radiation, MRI could offer a powerful non- invasive alternative. Diffusion and relaxation MRI -methods that are sensitive to morphological and chemical cellular properties respectively- hold great promise for imaging glia. However, current methods probing the diffusion and relaxation properties separately have failed to reliably distinguish glia from neuronal components. I will combine diffusion-relaxation MRI into a single joint method to provide a new glia-specific biomarker. First, I will identify the MR “fingerprint” of glia by comparing extensive diffusion-relaxation MRI to cellular microscopy from the same brain. This fingerprint will then inform simulations with a microscopy-derived “digital twin” of brain tissue to engineer optimised MRI protocols that provide an in vivo biomarker for glia. Extensive validation will be performed in rodents (using MRI and microscopy), in healthy volunteers, across MR hardware, and through comparisons with gold- standard PET in patients. This will deliver a validated MR biomarker that promises major impact. Towards the project’s end, translation to patient populations will be explored, paving the way for improved neuroinflammation diagnostics.