Three-dimensional Subcortical Atlas of the Marmoset (“SAM”) based on MRI and histology

2204 

Abstract Submission 

Kadharbatcha Saleem¹, Alexandru Avram², Vincent Schram², Peter Basser², Daniel Glen³

¹NICHD/NIH, Rockville, MD, ²NICHD/NIH, Bethesda, MD, ³NIMH, Bethesda, MD

Kadharbatcha Saleem  
NICHD/NIH
Rockville, MD

Alexandru Avram  
NICHD/NIH
Bethesda, MD

Vincent Schram  
NICHD/NIH
Bethesda, MD

Peter Basser  
NICHD/NIH
Bethesda, MD

Daniel Glen  
NIMH
Bethesda, MD

Despite its importance as a model for human brain development and neurological disorders, the marmoset lacks a comprehensive MRI-histology-based parcellation and 3D atlas of brain areas. Here, we first generated a Subcortical Atlas of the Marmoset, called the SAM, from 251 delineated subcortical regions derived from the ex vivo high-resolution multimodal MRIs [1,2] and matched histology with multiple stains derived from the same brain specimen. Tracing and validating atlas-based brain regions is imperative for neurosurgical planning, anatomical tract tracer injections, deep brain stimulation probes navigation, functional imaging (fMRI) studies, and establishing brain structure-function relationships.

We scanned one adult male perfusion-fixed marmoset brain on a 7T scanner using MAP-MRI with 150 μm resolution. We acquired 256 diffusion-weighted images with multiple b-values (bmax=10000s/mm2), pulse duration δ=6 ms, and diffusion time Δ=28 ms. In each voxel, we estimated the MAP and computed microstructural DTI/MAP parameters: fractional anisotropy (FA); mean, axial, and radial diffusivities (MD, AD, and RD, respectively); propagator anisotropy (PA), non-gaussianity (NG), return-to-origin probability (RTOP), return-to-axis probability (RTAP), and return-to-plane probability (RTPP), along with the fiber orientation distribution functions (fODFs) [3]. The MT ratio (MTR) was computed from images acquired with and without MT preparation.

Following MRI acquisition, we prepared the brain specimens for histological processing with five different stains [4,5]. An alternating series of 50 μm thick coronal sections were processed with Nissl, Acetylcholinesterase, or immunohistochemically with antibodies against parvalbumin, neurofilament protein, and choline acetyltransferase. 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.

Using a combined ex vivo MAP-MRI with direction encoded color (DEC) map [6] derived from the fiber orientation distribution (FOD) functions and histology, we identified and segmented 211 gray matter subregions in the deep brain structures, including the basal ganglia, thalamus, hypothalamus, brainstem (midbrain, pons, and medulla), amygdala, bed nucleus of stria terminalis, and the basal forebrain. In addition, we also distinguished and segmented 40 fiber tracts of different sizes and orientations associated with the basal ganglia, thalamus, brainstem, and cerebellum. The examples in Figure 1 illustrate the subcortical gray and white matter regions in MAP-MRI (DEC-FOD) that are segmented with reference to matched histological sections for the 3D atlas. This newly segmented volume is called ex vivo "SAM," or the Subcortical Atlas of the Marmoset. The SAM atlas in Figure 2 shows the segmented subcortical regions on the 2D coronal, axial, and sagittal MRI and in 3D. This new digital atlas provides a practical standard template for neuroanatomical, functional (fMRI), clinical, and connectional imaging studies. The ex vivo digital template atlas is available as volume and surfaces in standard NIFTI and GIFTI formats.

We estimated, confirmed, and validated the atlas-based areal boundaries of subcortical areas by registering this ex vivo atlas template to in vivo T1W MRI datasets of different age groups (single vs. multisubject population-based marmoset control adults) using a novel pipeline developed within AFNI and SUMA. These results demonstrate that affine and nonlinear warpings are sufficient to distinguish and provide atlas-based estimates of areal boundaries of marmoset subjects in vivo.

The combined multimodal MRI and histology enabled detailed noninvasive segmentation of gray and white matter regions and the generation of a 3D digital template atlas. This comprehensive MRI/histology-based atlas provides a readily usable standard for region definition for the marmoset brain.

Image Registration and Computational Anatomy ²

Segmentation and Parcellation

Subcortical Structures

Brain Atlases ¹

Multi-Modal Imaging

Atlasing

Brainstem

CHEMOARCHITECTURE

MRI

Sub-Cortical

WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC

Other - Marmoset, Histology, Monkey, Primate