Biology subjects

Saleem, K. S.

Publications and source records attributed to Saleem, K. S..

7 recordsLinked to original sources

bioRxiv2026

Nonuniform scaling of cerebellar cortical-nuclear architecture across primates revealed by cross-species atlases

The cerebellum shapes distributed motor and association networks through precisely organized pathways linking the cerebellar cortex to the deep cerebellar nuclei (DCN), its principal output structures. Whether these cortical and nuclear compartments scale proportionally across primates and how their relative expansion influences large-scale brain organization remains unclear. We generated multimodal, high-resolution cross-species 3D cerebellar atlases in marmoset, macaque, and human, integrating iron-sensitive magnetic resonance contrast with complementary histological markers to delineate DCN subdivisions in detail. Comparative volumetric analyses reveal nonuniform scaling of cerebellar cortical-nuclear architecture: cortical expansion markedly outpaces enlargement of the DCN, indicating disproportionate growth of input relative to output structures. This divergence parallels preferential expansion of posterior hemispheric territories, particularly lobules VI-IX and Crus I/II linked to higher-order association networks, whereas DCN subdivisions show selective rather than uniform scaling. Together, these findings establish nonuniform cortical-nuclear scaling as a systems-level organizational principle that reshapes cerebellar contributions to distributed brain networks.

neuroscience↗

bioRxiv2024

Direct segmentation of cortical cytoarchitectonic domains using ultra-high-resolution whole-brain diffusion MRI

We assess the potential of detecting cortical laminar patterns and areal borders by directly clustering voxel values of microstructural parameters derived from high-resolution mean apparent propagator (MAP) magnetic resonance imaging (MRI), as an alternative to conventional template-warping-based cortical parcellation methods. We acquired MAP-MRI data with 200{micro}m resolution in a fixed macaque monkey brain. To improve the sensitivity to cortical layers, we processed the data with a local anisotropic Gaussian filter determined voxel-wise by the plane tangent to the cortical surface. We directly clustered all cortical voxels using only the MAP-derived microstructural imaging biomarkers, with no information regarding their relative spatial location or dominant diffusion orientations. MAP-based 3D cytoarchitectonic segmentation revealed laminar patterns similar to those observed in the corresponding histological images. Moreover, transition regions between these laminar patterns agreed more accurately with histology than the borders between cortical areas estimated using conventional atlas/template-warping cortical parcellation. By cross-tabulating all cortical labels in the atlas- and MAP-based segmentations, we automatically matched the corresponding MAP-derived clusters (i.e., cytoarchitectonic domains) across the left and right hemispheres. Our results demonstrate that high-resolution MAP-MRI biomarkers can effectively delineate three-dimensional cortical cytoarchitectonic domains in single individuals. Their intrinsic tissue microstructural contrasts enable the construction of whole-brain mesoscopic cortical atlases.

neuroscience↗

bioRxiv2024

The Subcortical Atlas of the Marmoset (SAM) monkey based on high-resolution MRI and histology

A comprehensive three-dimensional digital brain atlas of cortical and subcortical regions based on MRI and histology has a broad array of applications for anatomical, functional, and clinical studies. We first generated a Subcortical Atlas of the Marmoset, called the "SAM," from 251 delineated subcortical regions (e.g., thalamic subregions, etc.) derived from the high-resolution MAP-MRI, T2W, and MTR images ex vivo. We then confirmed the location and borders of these segmented regions in MRI data using matched histological sections with multiple stains obtained from the same specimen. Finally, we estimated and confirmed the atlas-based areal boundaries of subcortical regions by registering this ex vivo atlas template to in vivo T1- or T2W MRI datasets of different age groups (single vs. multisubject population-based marmoset control adults) using a novel pipeline developed within AFNI. Tracing and validating these important deep brain structures in 3D improves neurosurgical planning, anatomical tract tracer injections, navigation of deep brain stimulation probes, fMRI and brain connectivity studies, and our understanding of brain structure-function relationships. This new ex vivo template and atlas are available as volumes in standard NIFTI and GIFTI file formats and are intended for use as a reference standard for marmoset brain research.

neuroscience↗

bioRxiv2023

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

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.

neuroscience↗

bioRxiv2022

COnstrained Reference frame diffusion TEnsor Correlation Spectroscopic (CORTECS) MRI: A practical framework for high-resolution diffusion tensor distribution imaging

Diffusion MRI studies with resolutions of a few hundred micrometers have consistently shown that in the cortex water diffusion occurs preferentially along radial and tangential orientations with respect to the cortical surface, in agreement with histology. These dominant orientations do not change significantly even if the relative contributions from microscopic water pools to the net voxel signal vary across studies that use different diffusion times, b-values, TEs, and TRs. With this in mind, we propose a practical new framework for measuring non-parametric diffusion tensor distribution (DTD) MRI by constraining the microscopic diffusion tensors of the DTD to be diagonalized using the same orthonormal reference frame of the mesoscopic voxel. In each voxel, the constrained DTD (cDTD) is completely determined by the correlation spectrum of the microscopic principal diffusivities associated with the axes of the voxel reference frame. Consequently, all cDTDs are inherently limited to the domain of positive definite tensors and can be reconstructed efficiently with numerical methods for solving Inverse Laplace Transform problems. Moreover, cDTDs can be measured using only data acquired with conventional single diffusion encoding, which can be obtained more efficiently than measurements with multiple diffusion encoding. In tissues with radial symmetry, such as the cortex, we can further constrain the cDTD to contain only cylindrically symmetric diffusion tensors and measure the 2D correlation spectra of radial and tangential diffusivities. To demonstrate this framework, we perform numerical simulations and analyze high-resolution dMRI data. We image 2D cDTDs in the cortex and derive marginal distributions of radial and tangential diffusivities, distributions of the microscopic fractional anisotropies and mean diffusivities, as well as their 2D correlation spectra to quantify the shape-size characteristics of the microscopic diffusion tensors. Signal components corresponding to specific bands in the measured correlation spectra show high specificity to cortical laminar structures observed with histology. Our framework drastically simplifies the measurement of non-parametric DTDs and may be applied retrospectively to analyze existing high-resolution dMRI data. Moreover, the framework provides a non-parametric generalization of DTI and subsumes existing diffusion signal representations and tissue models, enabling their harmonization, cross-validation, and optimization in specific clinical applications characterizing tissue changes.

biophysics↗

bioRxiv2021

High-resolution mapping and digital atlas of subcortical regions in the macaque monkey based on matched MAP-MRI and histology

Subcortical nuclei and other deep brain structures are known to play an important role in the regulation of the central and peripheral nervous systems. It can be difficult to identify and delineate many of these nuclei and their finer subdivisions in conventional MRI due to their small size, buried location, and often subtle contrast compared to neighboring tissue. To address this problem, we applied a multi-modal approach in ex vivo non-human primate (NHP) brain that includes high-resolution mean apparent propagator (MAP)-MRI and five different histological stains imaged with high-resolution microscopy in the brain of the same subject. By registering these high-dimensional MRI data to high-resolution histology data, we can map the location, boundaries, subdivisions, and micro-architectural features of subcortical gray matter regions in the macaque monkey brain. At high spatial resolution, diffusion MRI in general, and MAP-MRI in particular, can distinguish a large number of deep brain structures, including the larger and smaller white matter fiber tracts as well as architectonic features within various nuclei. Correlation with histology from the same brain enables a thorough validation of the structures identified with MAP-MRI. Moreover, anatomical details that are evident in images of MAP-MRI parameters are not visible in conventional T1-weighted images. We also derived subcortical template "SC21" from segmented MRI slices in three-dimensions and registered this volume to a previously published anatomical template with cortical parcellation (Reveley et al., 2017; Saleem and Logothetis, 2012), thereby integrating the 3D segmentation of both cortical and subcortical regions into the same volume. This newly updated three-dimensional D99 digital brain atlas (V2.0) is intended for use as a reference standard for macaque neuroanatomical, functional, and connectional imaging studies, involving both cortical and subcortical targets. The SC21 and D99 digital templates are available as volumes and surfaces in standard NIFTI and GIFTI formats.

neuroscience↗

bioRxiv2017

A population MRI brain template and analysis tools for the macaque

The use of standard anatomical templates is common in human neuroimaging, as it facilitates data analysis and comparison across subjects and studies. For non-human primates, previous in vivo templates have lacked sufficient contrast to reliably validate known anatomical brain regions and have not provided tools for automated single-subject processing. Here we present the \"National Institute of Mental Health Macaque Template\", or NMT for short. The NMT is a high-resolution in vivo MRI template of the average macaque brain generated from 31 subjects, as well as a neuroimaging tool for improved data analysis and visualization. From the NMT volume, we generated maps of tissue segmentation and cortical thickness. Surface reconstructions and transformations to previously published digital brain atlases are also provided. We further provide an analysis pipeline using the NMT that automates and standardizes the time-consuming processes of brain extraction, tissue segmentation, and morphometric feature estimation for anatomical scans of individual subjects. The NMT and associated tools thus provide a common platform for precise single-subject data analysis and for characterizations of neuroimaging results across subjects and studies.

neuroscience↗