Multimodal anatomical mapping of subcortical regions in Marmoset monkeys using high-resolution MRI and matched histology with multiple stains.

Abstract

Subcortical nuclei and other deep brain structures play essential roles in regulating the central and peripheral nervous systems. However, many of these nuclei and their subregions are challenging to identify and delineate in conventional MRI due to their small size, hidden location, and often subtle contrasts compared to neighboring regions. To address these limitations, we scanned the whole brain of the marmoset monkeys in ex vivo using a clinically feasible diffusion MRI method, called the mean apparent propagator (MAP)-MRI, along with T2W and MTR (T1-like contrast) images acquired at 7 Tesla. Additionally, we registered these multimodal MRI volumes to the high-resolution images of matched whole-brain histology sections with seven different stains obtained from the same brain specimens. At high spatial resolution, the microstructural parameters and fiber orientation distribution functions derived with MAP-MRI can distinguish the subregions of many subcortical and deep brain structures, including fiber tracts of different sizes and orientations. The good correlation with multiple but distinct histological stains from the same brain serves as a thorough validation of the structures identified with MAP-MRI and other MRI parameters. Moreover, the anatomical details of deep brain structures found in the volumes of MAP-MRI parameters are not visible in conventional T1W or T2W images. The high-resolution mapping using novel MRI contrasts, combined and correlated with histology, can elucidate structures that were previously invisible radiologically. Thus, this multimodal approach offers a roadmap toward identifying salient brain areas in vivo in future neuroradiological studies. It also provides a useful anatomical standard reference for the region definition of subcortical targets and the generation of a 3D digital template atlas for the marmoset brain research (Saleem et al., 2023). Additionally, we conducted a cross-species comparison between marmoset and macaque monkeys using results from our previous studies (Saleem et al., 2021). We found that the two species had distinct patterns of iron distribution in subregions of the basal ganglia, red nucleus, and deep cerebellar nuclei, confirmed with T2W MRI and histology.