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Contribution of Magnetic Resonance Microscopy in the 12-Week Neurotoxicity Evaluation of Carbonyl Sulfide in Fischer 344 Rats
Robert C. Sills
Laboratory of Experimental Pathology, sills{at}niehs.nih.gov
Daniel L. Morgan
Laboratory of Molecular Toxicology, NIEHS, Research Triangle Park, North Carolina 27709, USA
David W. Herr
Neurotoxicology Division, ORD/NHEERL, U.S. EPA, Research Triangle Park, North Carolina 27711, USA
Peter B. Little
Pathology Associates, Division of Charles River Laboratories, Durham, North Carolina 27713, USA
Nneka M. George
Laboratory of Experimental Pathology
Thai Vu Ton
Laboratory of Experimental Pathology
Nancy E. Love
Veterinary Centers of America
Robert R. Maronpot
Laboratory of Experimental Pathology
G. Allan Johnson
Center for In Vivo Microscopy, Duke University Medical Center, Durham, North Carolina 27701, USA
In this carbonyl sulfide (COS) study, magnetic resonance microscopy (MRM) and detailed light microscopic evaluation effectively functioned in parallel to assure that the distribution and degree of pathology in the brain was accurately represented. MRM is a powerful imaging modality that allows for excellent identification of neuroanatomical structures coupled with the ability to acquire 200 or more cross-sectional images of the brain, and the ability to display them in multiple planes. F344 rats were exposed to 200—600 ppm COS for up to 12 weeks. Prior to MRM, rats were anesthetized and cardiac perfused with McDowell Trump's fixative containing a gadolinium MR contrast medium. Fixed specimens were scanned at the Duke Center for In Vivo Microscopy on a 9.4 Tesla magnetic resonance system adapted explicitly for microscopic imaging. An advantage of MRM in this study was the ability to identify lesions in rats that appeared clinically normal prior to sacrifice and the opportunity to identify lesions in areas of the brain which would not be included in conventional studies. Other advantages include the ability to examine the brain in multiple planes (transverse, dorsal, sagittal) and obtain and save the MRM images in a digital format that allows for postexperimental data processing and manipulation. MRM images were correlated with neuroanatomical and neuropathological findings. All suspected MRM images were compared to corresponding H&E slides. An important aspect of this study was that MRM was critical in defining our strategy for sectioning the brain, and for designing mechanistic studies (cytochrome oxidase evaluations) and functional assessments (electrophysiology studies) on specifically targeted anatomical sites following COS exposure.
Key Words: Carbonyl sulfide • brain • neurotoxicity • magnetic resonance microscopy • auditory system
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Toxicologic Pathology, Vol. 32, No. 5,
501-510 (2004)
DOI: 10.1080/01926230490493918
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