Contribution of Magnetic Resonance Microscopy in the 12-Week Neurotoxicity Evaluation of Carbonyl Sulfide in Fischer 344 Rats

Abstract

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.

Mass spectrometric analysis of rat cerebrospinal fluid proteins following exposure to the neurotoxicant carbonyl sulfide

“…In this study, we use proteomics in an effort to identify markers of neurological disease following environmental exposure to carbonyl sulfide (COS) in rats . We focused on carbonyl sulfide which is a low molecular weight, colorless gas that originates from a variety of sources.…”

“…In the rat model, exposure to 500 ppm COS for 6 h per day for 2 days resulted in no microscopic lesions in the brain. By the third day of COS exposure, bilateral symmetrical necrosis was present in the posterior colliculus of all rats exposed to 500 ppm . The time points of 1,2 and 3 days of exposure to 500 ppm COS were selected to examine possible predictors/biomarkers of neuronal necrosis and inflammation in the CSF.…”

Quantitative mapping of trimethyltin injury in the rat brain using magnetic resonance histology

“…It has helped elucidate the pathogenesis of carbonyl sulfide (Morgan, et al . 2004; Sills, et al . 2004), and has become routine for structural neuroanatomical phenotyping (Badea, et al .…”

“Current Pathology Techniques” Symposium Review: Advances and Issues in Neuropathology

“…Like their human counterparts, the small animal instruments are noninvasive and can, in most cases, be used to study the same animal at multiple times over a protracted period. Neurobiology has been a particularly fruitful arena for investigation, particularly with respect to MRI (Benveniste et al 2000;Hesselbarth et al 1998;Kornguth et al 1994;Sills et al 2004) and PET (Suehiro et al 1993;Toyama et al 2005) applications. One major advantage of MRI is that the entire brain can be scanned for lesions without disrupting the tissue integrity for subsequent light microscopic evaluations .…”