Comparison of subcortical regions in macaque and marmoset monkeys using multimodal MRI and histology

2149 

Abstract Submission 

Kadharbatcha Saleem¹, Alexandru Avram¹, Vincent Schram¹, Peter Basser¹

¹Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892

Kadharbatcha Saleem  
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH
Bethesda, MD 20892

Alexandru Avram  
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH
Bethesda, MD 20892

Vincent Schram  
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH
Bethesda, MD 20892

Peter Basser  
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH
Bethesda, MD 20892

Subcortical nuclei play essential roles in regulating the central and peripheral nervous systems. However, the cross-species comparison of these deep brain structures has yet to be thoroughly investigated using MRI and histology. Here, we combined multimodal MRI data and matched histology sections with multiple stains derived from the same marmoset and macaque brains to investigate if there are any MR signal intensity or neuropil staining differences in different subcortical regions between these two species ex-vivo.

We scanned two adult perfusion-fixed marmoset brains and one macaque brain on a 7T scanner using mean apparent propagator (MAP)-MRI [1,2] with 150 μm and 200 μm resolution, respectively. We acquired 112 or 256 diffusion-weighted images with multiple b-values (bmax=10000s/mm2), diffusion gradient pulse duration δ=6 or 8 ms, and diffusion time Δ=28 or 20 ms. In each voxel, we estimated the MAP and computed microstructural diffusion tensor imaging (DTI) and MAP parameters: fractional anisotropy (FA); mean, axial, and radial diffusivities (MD, AD, and RD, respectively); propagator anisotropy (PA), return-to-origin probability (RTOP), return-to-axis probability (RTAP), return-to-plane probability (RTPP), non-gaussianity (NG), and the non-diffusion attenuated (amplitude) image, which provides a T2W contrast. We also estimated the fiber orientation distribution functions (fODFs) [3] in each voxel.

Following MRI acquisition, we prepared both brain specimens for histological processing with multiple stains [4,5]. An alternating series of 50 μm thick coronal sections were processed with AchE, Prussian blue (iron stain), and Nissl or antibodies against neurofilament protein (SMI-32), parvalbumin, NeuN, and ChAT. The high-resolution images of these stained sections were manually registered to corresponding maps of MRI volumes to allow analysis in histologically defined subcortical regions.

We found distinct MR signal intensity differences between the marmoset and macaque monkeys in some subcortical regions. For example, the subregions of the basal ganglia (pallidum and substantia nigra) and the deep cerebellar nuclei exhibited significantly more hypointense signals in the T2W images of macaque than in the marmoset (Fig. 1). The MRI studies in primates have interpreted this hypointense signal to a high level of intracellular iron deposit [6,7]. We confirmed this finding in the histology sections derived from the same macaque and marmoset brains stained with Perls Prussian blue. In the macaque, the neuropil of the basal ganglia subregions and the deep cerebellar nuclei stained intensely with Prussian blue confirm the presence of a high-level iron. The spatial location of these intensely stained regions matched well with the hypointense signal intensity found in these deep brain structures in macaque T2W images. In contrast, these subregions in the marmoset revealed very faint staining with Prussian blue, confirming a very weak iron deposit, and it corresponded well with the significantly less hypointense signal in T2W images (Fig. 1A-F).

We also found other differences in the subcortical white matter in T2W images. For example, the anterior limb of the internal capsule, cerebral peduncle, anterior commissure, and the deep cerebellar white matter exhibited more hypointense signal in the marmoset than in the macaque (Fig 2A, B). In MAP-MRI (DEC-FOD) [8], we found alternating bands of fiber bundles with different orientations in the fascia dentata (FD) of the macaque hippocampus but not in the marmoset (Fig. 2C, D). In contrast, the hippocampal CA1 of the marmoset revealed more mediolaterally oriented fibers than in the macaque (Fig. 2E).

High-resolution multimodal MRI combined and correlated with histology can elucidate structures that were previously invisible radiologically and offer a roadmap toward identifying subcortical nuclei and their subregions based on differences in microstructural and chemoarchitectonic properties.

Anatomy and Functional Systems

Subcortical Structures ¹

White Matter Anatomy, Fiber Pathways and Connectivity

Diffusion MRI

Multi-Modal Imaging ²

Brainstem

CHEMOARCHITECTURE

Cross-Species Homologues

Data analysis

HIGH FIELD MR

MRI

STRUCTURAL MRI

Sub-Cortical

White Matter

WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC