Are we validating enough our MRI markers? Cell-specific challenges to dissect the neurobiology of microstructural MRI

Motivation: Validation of MRI-extracted biomarkers is seldom performed, and when available, Is normally underpowered and based on correlation. Goal(s): Here we present an innovative framework for validating microstructural MRI biomarkers by eliciting cell-specific responses. Approach: The framework is based on injection of neurotoxins in rats, followed by MRI exploration and histology. Results: We successfully isolated conditions associated to neurodegenerative, demyelinating and inflammatory pathologies and demonstrated sensitivity and specificity of MRI- derived biomarkers. Impact: This framework impulse a much-needed change in paradigm for MRI validation by challenging the biological content of MRI derived biomarkers, refine and test new models for microstructural imaging and bridge the gap between advances in MRI physics and clinical applications.