A Web-Based Atlas Combining MRI and Histology of the Squirrel Monkey Brain

Abstract

The squirrel monkey (Saimiri sciureus) is a commonly-used surrogate for humans in biomedical research. In the neuroimaging community, MRI and histological atlases serve as valuable resources for anatomical, physiological, and functional studies of the brain; however, no digital MRI/histology atlas is currently available for the squirrel monkey. This paper describes the construction of a web-based multi-modal atlas of the squirrel monkey brain. The MRI-derived information includes anatomical MRI contrast (i.e., T2-weighted and proton-density-weighted) and diffusion MRI metrics (i.e., fractional anisotropy and mean diffusivity) from data acquired both in vivo and ex vivo on a 9.4 Tesla scanner. The histological images include Nissl and myelin stains, co-registered to the corresponding MRI, allowing identification of cyto- and myelo-architecture. In addition, a bidirectional neuronal tracer, biotinylated dextran amine (BDA) was injected into the primary motor cortex, enabling highly specific identification of regions connected to the injection location. The atlas integrates the results of common image analysis methods including diffusion tensor imaging glyphs, labels of 57 white-matter tracts identified using DTI-tractography, and 18 cortical regions of interest identified from Nissl-revealed cyto-architecture. All data are presented in a common space, and all image types are accessible through a web-based atlas viewer, which allows visualization and interaction of user-selectable contrasts and varying resolutions. By providing an easy to use reference system of anatomical information, our web-accessible multi-contrast atlas forms a rich and convenient resource for comparisons of brain findings across subjects or modalities. The atlas is called the Combined Histology-MRI Integrated Atlas of the Squirrel Monkey (CHIASM). All images are accessible through our web-based viewer ( https://chiasm.vuse.vanderbilt.edu /), and data are available for download at ( https://www.nitrc.org/projects/smatlas/ ).

Histologically derived fiber response functions for diffusion MRI vary across white matter fibers—An ex vivo validation study in the squirrel monkey brain

“…Different response functions can lead to different tractography results. A, Tractography is compared with an atlas of known connections (atlas and histology described in References and ; see Figure from reference and Figure B from reference for visualization of the ground truth pathways), by calculating the true positive and true negative rate of connections to various regions of interest. B, C, the sensitivity and specificity of the tractography results from Figure are plotted in a receiver operating characteristic curve using the default FOD threshold (B) and no FOD threshold (C).…”

“…The atlas contains 71 white matter and gray matter ROIs, 44 of which are known to be connected to the left hemisphere primary motor cortex and 27 of which are not connected (ie do not show evidence of tracer after injection into the primary motor cortex). Following procedures similar to References 48 and 49, tractography results were binarized, and the presence or absence of streamlines in each ROI (both white and gray matter) was determined. We measured the sensitivity (the ability to detect true connections) and specificity (the ability to avoid false connections) of the various tractographic implementations derived using different response kernels.…”

Learning 3D White Matter Microstructure from 2D Histology

“…There are several potential improvements to the current study, as well as future areas of exploration. The next step will be to include additional slices from the same monkey, as well as incorporate, test, or train on multiple subjects from existing atlases or databases [18,19]. Successful generalization to new subjects would lend significant confidence in applying this to unseen brains or new species, for example the human brain.…”

“…MRI experiments, histological methods, and data registration were performed on an ex vivo squirrel monkey brain following the procedures described in [18,19]. Briefly, ex vivo imaging was performed a Varian 9.4 T magnet, with diffusion weighted scans acquired using a PGSE multi-shot spin-warp imaging sequence (TR = 4.6 s, TE = 42 ms, 32 gradient directions, b ≈ 1000s/mm 2 , 300 μm voxel, 192×128×115 matrix).…”

“…Finally, a multistep registration procedure was utilized [22] that involves 2D affine and 2D non-rigid transformations to an intermediate "frozen tissue block space", followed by 3D affine and 3D non-rigid transformations to MRI data. Deformation fields produced by registration steps allow transfer of any set of data to any desired space for comparisons [18], in this study, we chose to process dMRI data in histology space, resulting in high resolution myelin images aligned with corresponding dMRI derived FoDs.…”