Voxel-wise normative models for abnormality-driven contrast of microstructural MRI

COEX 

Microstructural magnetic resonance imaging (MRI) can be used to measure brain tissue properties in vivo and has been used extensively in scientific research to derive biomarkers sensitive to disease pathology and progression, like normal-appearing white matter alterations in multiple sclerosis (MS) [1] and small vessel disease (SVD) [2] and iron accumulation in the subcortical grey matter in Parkinson's disease (PD) [3]. However, these biomarkers have been seldom implemented in clinical practice. We posit that this limited clinical translation is due, in part, to the difficult interpretability of raw microstructural maps to detect subtle pathological tissue alterations distinct from normal variations. For example, white matter deterioration and subcortical grey matter iron accumulation are both normal age-related phenomena [4,5]. Here, we constructed voxel-wise normative models of microstructural MRI and produced subject-wise z-scored maps of microstructural abnormality relative to these age- and sex-specific averages. These maps bring important context regarding normal brain tissue integrity and permit intuitive visual assessment of brain tissue abnormalities at first glance.