MRI-based in vivo histology of Multiple Sclerosis

• Applicant: Dr. Evgeniya Kirilina
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Biophysics ; Medical Physics, Biomedical Technology ; Pathology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 550054922

Multiple sclerosis (MS) is a complex neurological disease involving inflammation, demyelination and neurodegeneration throughout the central nervous system (CNS). While white matter lesion in MS has been intensively studied, less is known about cortical pathology in MS despite its well-accepted contribution to accumulation in disease related disability in MS. Current diagnostic and treatment decisions in MS are based on conventional MRI, which lacks sensitivity for cortical pathology and cannot differentiate between overlapping pathological processes. This proposal aims to address these limitations by using advanced neuroimaging techniques and histopathological analysis within an international multidisciplinary research team including MRI physicists, neuropathologists and clinical MS specialists. We will exploit recent advances in ultra-high field, ultra-high resolution quantitative MRI and biophysical modelling of MRI contrasts to develop a sensitive and specific diagnostic tool to assess multiple pathological processes in the MS cortex. We will perform a large multimodal histopathological study combining ultra-high field ultra-high resolution MRI, comprehensive histopathology and advanced tissue characterization on post-mortem brains from MS patients. We will characterize histopathological features of cortical remyelination, diffuse chronic inflammation and identify determinants of qMRI changes in MS brains. We will develop a generative model linking neuropathological changes to qMRI parameters and validate it in post-mortem tissue. Based on this model, we will establish sensitive qMRI biomarkers of cortical pathology for in vivo assessment of disease progression and apply them in a group of MS patients in a longitudinal study to quantify disease progression. Successful completion of this project will provide new insights into cortical pathology in MS and novel neuroimaging markers of MS progression to guide treatment decisions and inform clinical trials of targeted therapies. This precision medicine approach will improve diagnostic accuracy, monitor disease progression and facilitate personalized treatment strategies, ultimately improving outcomes for people with MS.

• DFG Programme: Research Grants
• International Connection: Austria, Belgium
• Partner Organisation: Fonds National de la Recherche Scientifique - FNRS; Fonds zur Förderung der wissenschaftlichen Forschung (FWF)
• Cooperation Partners: Dr. Simon Hametner, Ph.D.; Professor Pierre Maquet, Ph.D.