An optimised framework for relating microstructural MRI to multi-stain histology metrics in the mouse brain

Motivation: Voxel-wise MRI-histology comparisons routinely rely on manual segmentations of ROIs and subjective quantitative histological metrics, an error-prone and labour-intensive process. Goal(s): We developed an automated framework for investigating relationships between multiple MRI metrics and immunostains. Approach: We used MRI and histology protocols optimised for ex-vivo mouse brains. We co-registered this data and derived quantitative histological metrics. We conducted voxel-wise correlations in grey and white matter between MRI (diffusion, R2* and susceptibility) and immunohistochemistry (myelin, neurofilament and extracellular matrix proteins). Results: Our framework successfully recapitulated known relationships for myelin and neurofilaments and, interestingly, demonstrated new relationships between MRI metrics and extracellular matrix protein stains. Impact: Our optimised framework combines openly-shared software and MRI-histology protocols, addressing current challenges, such as obtaining high-quality histology data, MRI-to-histology registration and automatic extraction of quantitative histological metrics. This can benefit future MRI-histology studies in mouse brains prepared for ex-vivo MRI.