A molecular map of the living human brain from quantitative MRI
Authors list
Melissa Grant-Peters George EC Thomas Daan van Kruining Louise A Huuki-Myers Ruth Zhang Jonathan W Brenton Hemanth Nelvagal Angeliki Zarkali James Evans Christina E Toomey Aine Fairbrother-Browne Ivelina Dobreva Kelsey D Montgomery Joanne Lachica Naomi Hannaway Nicholas Wood Sonia Gandhi Martina F Callaghan Frances Platt Zane Jaunmuktane Karin Shmueli Leonardo Collado-Torres Kristen R Maynard Rimona S Weil Mina RytenThis article is a preprint. Preprints have not been peer-reviewed.
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Abstract
Profiling dynamic molecular processes in neurodegeneration in vivo remains a major clinical challenge. Limited brain tissue accessibility especially limits the development and effective deployment of emerging disease modifying therapies, highlighting the need for non-invasive methods for profiling molecular disease processes. We introduce a non-invasive imaging framework that integrates ultra-high-resolution 7T quantitative MRI (qMRI) with spatially-resolved transcriptomics (SRT) to infer cell-type and pathway-specific molecular features within the cortical grey matter. We demonstrate that our method predicts from qMRI data disease-associated changes to cell type proportions and molecular pathways within the grey matter cortex which are corroborated by orthogonal datasets, including bulk RNA sequencing, single nucleus RNA sequencing and high-performance liquid chromatography. This proof-of-concept establishes the integration of qMRI and SRT as a scalable, non-invasive platform for molecular profiling in neurodegeneration, with significant potential for precision therapeutic monitoring, drug development and clinical trials.
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