in vivo longitudinal imaging unravels the origin of neuromelanin-MRI contrast in a rat model of Parkinson’s disease

Motivation: Neuromelanin-MRI contrast is a promising biomarker for Parkinson's disease, but still needs investigation as the biological and physical origins of the contrast are still unclear. Goal(s): The objective was to unravel the mechanisms behind neuromelanin-MRI contrast, both biologically and physically, and to better understand the role of neuromelanin in Parkinson's disease. Approach: We performed in vivo longitudinal neuromelanin-MRI coupled with quantitative multiparametric imaging on a rat model of Parkinson's disease based on accumulation of neuromelanin, with histological validation. Results: Results show that contrast increases with neuromelanin accumulation and decreases with neuronal loss. The contrast arises from T1 reduction due to paramagnetic neuromelanin-iron complexes. Impact: We provide first in vivo validation and better understanding of neuromelanin-MRI as a biomarker of neuronal loss in Parkinson's disease. Results also suggest a pathogenic threshold of neuromelanin accumulation triggering neurodegeneration. Investigating this hypothesis may lead to new therapeutic window.