Giving you five: A neuroimaging atlas of the nigrosomes in the substantia nigra based on 3D histology

ABSTRACT Nigrosomes are formed by clusters of pigmented dopaminergic cells in the substantia nigra that critically contribute to dopaminergic function. The ever-increasing resolution of ultra-high-field MRI brings clinical imaging of these clusters into reach, promising unprecedented insight into the functional role of the nigrosomes and their early degeneration in Parkinson’s disease. However, due to the nigrosomes’ small extents and intricate shapes, they are not included in current MRI brain atlases, preventing nigrosome-specific MRI data analysis. We provide a comprehensive 3D histological atlas of the five nigrosomes co-aligned to the widely-used MNI152 2009b space. This atlas is based on 3D-reconstructed, ultra-high-resolution block-face images and gold-standard nigrosome delineations in calbindin-D28K immunohistochemistry. We validated the atlas’s accuracy using the multimodal ultra-high-resolution post mortem BigBrain dataset and demonstrated its consistency with qualitative nigrosome atlases based on classical 2D histology. We provide detailed usage instructions for applying our atlas to ultra-high-resolution and -field MRI data. The openly available atlas enables neuroimaging studies of the nigrosomes, opening a new avenue toward understanding the differential involvement of the nigrosomes in the healthy and diseased brain and the development of neuroimaging biomarkers of dopaminergic neurodegeneration.