Probabilistic atlas of the mesencephalic reticular formation, isthmic reticular formation, microcellular tegmental nucleus, ventral tegmental area nucleus complex and caudal-rostral linear raphe nuclei complex in living humans from 7 Tesla MRI.

INTRODUCTION The mesencephalic reticular formation, isthmic reticular formation, microcellular tegmental nucleus, ventral tegmental area nuclei and linear raphe nuclei are small brainstem regions crucially involved in arousal, sleep, and reward. Yet, these nuclei are difficult to identify in magnetic resonance imaging (MRI) of living humans. In the current work we developed a probabilistic atlas of these brainstem nuclei in living humans, using non-invasive ultra-high field MRI. METHODS In 12 healthy subjects we acquired single-subject multi-contrast (diffusion and T2-weighted) 1.1mm-isotropic resolution 7 Tesla MRI images. After pre-processing and alignment to stereotactic space, these images were used to delineate in each subject the nuclei of interest based on the image contrast as well as on neighboring nuclei and landmarks. Nuclei labels were averaged across subjects to yield probabilistic labels. The latter were further validated by assessment of the label inter-rater agreement, internal consistency and volume. RESULTS Labels were delineated for each nucleus with good overlap across subjects. The inter-rater agreement and internal consistency were below (p < 10-8) the linear spatial imaging resolution (1.1 mm), thus validating the generated probabilistic atlas labels. The volume of our labels did not differ from literature volumes (p < 0.05) further validating our atlas. DISCUSSION AND CONCLUSION The probabilistic atlas of these five mesopontine nuclei expands current in vivo brainstem nuclei atlases and can be used as a tool to identify the location of these areas in conventional (e.g. 3Tesla) images. This might serve to unravel the brainstem structure to function link and thus improve clinical outcome.