Cytoarchitecture of the mouse brain as defined by magnetic resonance histology
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1
Duke University, United States
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2
Drexel University, College of Medicine, United States
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3
Drexel University School of Biomedical Engineering , United States
Introduction: Magnetic resonance histology has become a routine method for quantitative morphologic evaluation of mouse phenotypes(1). The use of active staining allows acquisition of images at spatial resolution @ 10x10x10 um (voxel volume of 1 pl), ~ 1,000,000 X higher resolution than a routine clinical MRI(2). At this spatial resolution, the cytoarchitecture of the brain is clearly visible. This presentation will focus on the contrast mechanisms that allow 3D differentiation of fine scale neuroanatomical regions in the actively stained mouse brain.
Methods: Specimens were actively stained to enhance the signal to noise over that seen in unstained (formalin fixed) specimens (3). Three imaging protocols were devised to optimize contrast based on T1, T2, and T2 * differences. The whole brain (in the skull) was imaged at 21.5 um isotropic resolution for the T1 and T2 * protocol and 43 um for the T2 protocol. The same specimens were then processed for Nissl histology and the resulting images were registered to the MR data. Higher resolution MR histology images (to 10 um isotropic resolution) were acquired over limited fields of view to help interpret the cytoarchitecture seen.
Results: The contrast in the T1 and T2* images is consistent with that in the Nissl data: the contrast in the T2 images is generally reversed. We have identified most of the cellular layers in the olfactory bulb, hippocampus and cortex in the T1 and T2* images. The benefit of the T2 scan lies in identifying nuclei borders, from amygdala to thalamus and midbrain.
Conclusion: A number of investigators have shown lower resolution MR images of formalin fixed specimens. Active staining allows acquisition of much higher resolution in which finer detail of the cytarchitecture is clearly visible. But the staining process alters the contrast. This work provides the foundation knowledge for three optimized protocols and the relationship to more traditional histologic images that will continue to expand the utility of MR histology for morphologic phenotyping in the mouse brain.
References
1. Johnson GA, Ali-Sharief A, Badea A, et al. High-throughput morphologic phenotyping of the mouse brain with magnetic resonance histology. NeuroImage 2007; 37:82-89
2. Nouls JC, Izenson MG, Greeley HP, Johnson GA. A superconducting volume coil for magnetic resonance microscopy of the mouse brain. Journal of Magnetic Resonance 2008; 191:231-238
3. Johnson GA, Cofer GP, Gewalt SL, Hedlund LW. Morphologic phenotyping with magnetic resonance microscopy: the visible mouse. Radiology 2002; 222:789-793
Conference:
Neuroinformatics 2008, Stockholm, Sweden, 7 Sep - 9 Sep, 2008.
Presentation Type:
Oral Presentation
Topic:
Live Demonstrations
Citation:
Johnson
A,
Badea
A,
Bertrand
L,
Burstein
PD,
Cofer
GP,
Fubara
B and
Nissanov
J
(2008). Cytoarchitecture of the mouse brain as defined by magnetic resonance histology.
Front. Neuroinform.
Conference Abstract:
Neuroinformatics 2008.
doi: 10.3389/conf.neuro.11.2008.01.120
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Received:
25 Jul 2008;
Published Online:
25 Jul 2008.
*
Correspondence:
Allan Johnson, Duke University, Durham, United States, gaj@orion.duhs.duke.edu