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Gary Cofer

Possible papers associated with this exact author name in Arrow. This page groups case-insensitive exact name matches and is not a full identity disambiguation profile.

6 papers

1 author row

YNIMG Journal 2022 Journal Article

Resolution and b value dependent structural connectome in ex vivo mouse brain

Stephanie Crater
Surendra Maharjan
Yi Qi
Qi Zhao
Gary Cofer
James C. Cook
G. Allan Johnson
Nian Wang

Diffusion magnetic resonance imaging has been widely used in both clinical and preclinical studies to characterize tissue microstructure and structural connectivity. The diffusion MRI protocol for the Human Connectome Project (HCP) has been developed and optimized to obtain high-quality, high-resolution diffusion MRI (dMRI) datasets. However, such efforts have not been fully explored in preclinical studies, especially for rodents. In this study, high quality dMRI datasets of mouse brains were acquired at 9. 4T system from two vendors. In particular, we acquired a high-spatial resolution dMRI dataset (25 μm isotropic with 126 diffusion encoding directions), which we believe to be the highest spatial resolution yet obtained; and a high-angular resolution dMRI dataset (50 μm isotropic with 384 diffusion encoding directions), which we believe to be the highest angular resolution compared to the dMRI datasets at the microscopic resolution. We systematically investigated the effects of three important parameters that affect the final outcome of the connectome: b value (1000s/mm2 to 8000 s/mm2), angular resolution (10 to 126), and spatial resolution (25 µm to 200 µm). The stability of tractography and connectome increase with the angular resolution, where more than 50 angles is necessary to achieve consistent results. The connectome and quantitative parameters derived from graph theory exhibit a linear relationship to the b value (R2 > 0. 99); a single-shell acquisition with b value of 3000 s/mm2 shows comparable results to the multi-shell high angular resolution dataset. The dice coefficient decreases and both false positive rate and false negative rate gradually increase with coarser spatial resolution. Our study provides guidelines and foundations for exploration of tradeoffs among acquisition parameters for the structural connectome in ex vivo mouse brain.

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YNIMG Journal 2021 Journal Article

A multicontrast MR atlas of the Wistar rat brain

G. Allan Johnson
Rick Laoprasert
Robert J. Anderson
Gary Cofer
James Cook
Forrest Pratson
Leonard E. White

We describe a multi-contrast, multi-dimensional atlas of the Wistar rat acquired at microscopic spatial resolution using magnetic resonance histology (MRH). Diffusion weighted images, and associated scalar images were acquired of a single specimen with a fully sampled Fourier reconstruction, 61 angles and b=3000 s/mm2 yielding 50 um isotropic spatial resolution. The higher angular sampling allows use of the GQI algorithm improving the angular invariance of the scalar images and yielding an orientation distribution function to assist in delineating subtle boundaries where there are crossing fibers and track density images providing insight into local fiber architecture. A multigradient echo image of the same specimen was acquired at 25 um isotropic spatial resolution. A quantitative susceptibility map enhances fiber architecture relative to the magnitude images. An accompanying multi-specimen atlas (n=6) was acquired with compressed sensing with the same diffusion protocol as used for the single specimen atlas. An average was created using diffeomorphic mapping. Scalar volumes from the diffusion data, a T2* weighted volume, a quantitative susceptibility map, and a track density volume, all registered to the same space provide multiple contrasts to assist in anatomic delineation. The new template provides significantly increased contrast in the scalar DTI images when compared to previous atlases. A compact interactive viewer based on 3D Slicer is provided to facilitate comparison among the contrasts in the multiple volumes. The single volume and average atlas with multiple 3D volumes provide an improved template for anatomic interrogation of the Wistar rat brain. The improved contrast to noise in the scalar DTI images and the addition of other volumes (eg. QA, QSM, TDI ) will facilitate automated label registration for MR histology and preclinical imaging.

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YNIMG Journal 2020 Journal Article

Cytoarchitecture of the mouse brain by high resolution diffusion magnetic resonance imaging

Nian Wang
Leonard E. White
Yi Qi
Gary Cofer
G. Allan Johnson

MRI has been widely used to probe the neuroanatomy of the mouse brain, directly correlating MRI findings to histology is still challenging due to the limited spatial resolution and various image contrasts derived from water relaxation or diffusion properties. Magnetic resonance histology has the potential to become an indispensable research tool to mitigate such challenges. In the present study, we acquired high spatial resolution MRI datasets, including diffusion MRI (dMRI) at 25 μm isotropic resolution and quantitative susceptibility mapping (QSM) at 21.5 μm isotropic resolution to validate with conventional mouse brain histology. Diffusion weighted images (DWIs) show better delineation of cortical layers and glomeruli in the olfactory bulb than fractional anisotropy (FA) maps. However, among all the image contrasts, including quantitative susceptibility mapping (QSM), T1/T2∗ images and DTI metrics, FA maps highlight unique laminar architecture in sub-regions of the hippocampus, including the strata of the dentate gyrus and CA fields of the hippocampus. The mean diffusivity (MD) and axial diffusivity (AD) yield higher correlation with DAPI (0.62 and 0.71) and NeuN (0.78 and 0.74) than with NF-160 (-0.34 and -0.49). The correlations between FA and DAPI, NeuN, and NF-160 are 0.31, -0.01, and -0.49, respectively. Our findings demonstrate that MRI at microscopic resolution deliver a three-dimensional, non-invasive and non-destructive platform for characterization of fine structural detail in both gray matter and white matter of the mouse brain.

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YNICL Journal 2018 Journal Article

Postmortem diffusion MRI of the entire human spinal cord at microscopic resolution

Evan Calabrese
Syed M. Adil
Gary Cofer
Christian S. Perone
Julien Cohen-Adad
Shivanand P. Lad
G. Allan Johnson

The human spinal cord is a central nervous system structure that plays an important role in normal motor and sensory function, and can be affected by many debilitating neurologic diseases. Due to its clinical importance, the spinal cord is frequently the subject of imaging research. Common methods for visualizing spinal cord anatomy and pathology include histology and magnetic resonance imaging (MRI), both of which have unique benefits and drawbacks. Postmortem microscopic resolution MRI of fixed specimens, sometimes referred to as magnetic resonance microscopy (MRM), combines many of the benefits inherent to both techniques. However, the elongated shape of the human spinal cord, along with hardware and scan time limitations, have restricted previous microscopic resolution MRI studies (both in vivo and ex vivo) to small sections of the cord. Here we present the first MRM dataset of the entire postmortem human spinal cord. These data include 50 μm isotropic resolution anatomic image data and 100 μm isotropic resolution diffusion data, made possible by a 280 h long multi-segment acquisition and automated image segment composition. We demonstrate the use of these data for spinal cord lesion detection, automated volumetric gray matter segmentation, and quantitative spinal cord morphometry including estimates of cross sectional dimensions and gray matter fraction throughout the length of the cord.

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YNIMG Journal 2010 Journal Article

Waxholm Space: An image-based reference for coordinating mouse brain research

G. Allan Johnson
Alexandra Badea
Jeffrey Brandenburg
Gary Cofer
Boma Fubara
Song Liu
Jonathan Nissanov

We describe an atlas of the C57BL/6 mouse brain based on MRI and conventional Nissl histology. Magnetic resonance microscopy was performed on a total of 14 specimens that were actively stained to enhance tissue contrast. Images were acquired with three different MR protocols yielding contrast dependent on spin lattice relaxation (T1), spin spin relaxation (T2), and magnetic susceptibility (T2*). Spatial resolution was 21. 5 μm (isotropic). Conventional histology (Nissl) was performed on a limited set of these same specimens and the Nissl images were registered (3D-to-3D) to the MR data. Probabilistic atlases for 37 structures are provided, along with average atlases. The availability of three different MR protocols, the Nissl data, and the labels provides a rich set of options for registration of other atlases to the same coordinate system, thus facilitating data-sharing. All the data is available for download via the web.

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YNIMG Journal 2007 Journal Article

High-throughput morphologic phenotyping of the mouse brain with magnetic resonance histology

G. Allan Johnson
Anjum Ali-Sharief
Alexandra Badea
Jeffrey Brandenburg
Gary Cofer
Boma Fubara
Sally Gewalt
Laurence W. Hedlund

The Mouse Biomedical Informatics Research Network (MBIRN) has been established to integrate imaging studies of the mouse brain ranging from three-dimensional (3D) studies of the whole brain to focused regions at a sub-cellular scale. Magnetic resonance (MR) histology provides the entry point for many morphologic comparisons of the whole brain. We describe a standardized protocol that allows acquisition of 3D MR histology (43-μm resolution) images of the fixed, stained mouse brain with acquisition times <30 min. A higher resolution protocol with isotropic spatial resolution of 21. 5 μm can be executed in 2 h. A third acquisition protocol provides an alternative image contrast (at 43-μm isotropic resolution), which is exploited in a statistically driven algorithm that segments 33 of the most critical structures in the brain. The entire process, from specimen perfusion, fixation and staining, image acquisition and reconstruction, post-processing, segmentation, archiving, and analysis, is integrated through a structured workflow. This yields a searchable database for archive and query of the very large (1. 2 GB) images acquired with this standardized protocol. These methods have been applied to a collection of both male and female adult murine brains ranging over 4 strains and 6 neurologic knockout models. These collection and acquisition methods are now available to the neuroscience community as a standard web-deliverable service.

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