Quantitative mapping of trimethyltin injury in the rat brain using magnetic resonance histology.
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The growing exposure to chemicals in our environment and the increasing concern over their impact on health have elevated the need for new methods for surveying the detrimental effects of these compounds. Today's gold standard for assessing the effects of toxicants on the brain is based on hematoxylin and eosin (H&E)-stained histology, sometimes accompanied by special stains or immunohistochemistry for neural processes and myelin. This approach is time-consuming and is usually limited to a fraction of the total brain volume. We demonstrate that magnetic resonance histology (MRH) can be used for quantitatively assessing the effects of central nervous system toxicants in rat models. We show that subtle and sparse changes to brain structure can be detected using magnetic resonance histology, and correspond to some of the locations in which lesions are found by traditional pathological examination. We report for the first time diffusion tensor image-based detection of changes in white matter regions, including fimbria and corpus callosum, in the brains of rats exposed to 8 mg/kg and 12 mg/kg trimethyltin. Besides detecting brain-wide changes, magnetic resonance histology provides a quantitative assessment of dose-dependent effects. These effects can be found in different magnetic resonance contrast mechanisms, providing multivariate biomarkers for the same spatial location. In this study, deformation-based morphometry detected areas where previous studies have detected cell loss, while voxel-wise analyses of diffusion tensor parameters revealed microstructural changes due to such things as cellular swelling, apoptosis, and inflammation. Magnetic resonance histology brings a valuable addition to pathology with the ability to generate brain-wide quantitative parametric maps for markers of toxic insults in the rodent brain.
Diffusion Magnetic Resonance Imaging
Diffusion Tensor Imaging
Dose-Response Relationship, Drug
Published Version (Please cite this version)10.1016/j.neuro.2014.02.009
Publication InfoBadea, Alexandra; Calabrese, Evan; Hedlund, Laurence W; Johnson, G Allan; Little, PB; & Qi, Y (2014). Quantitative mapping of trimethyltin injury in the rat brain using magnetic resonance histology. Neurotoxicology, 42. pp. 12-23. 10.1016/j.neuro.2014.02.009. Retrieved from http://hdl.handle.net/10161/10329.
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Associate Professor in Radiology
My interest lies primarily in using MR microscopy to image the rodent brain, including its vasculature, so as to provide comprehensive morphometric phenotyping. I study the morphometry of the rodent brain, its anatomical variability in normal states, and also in human disease models. These studies require several steps: imaging protocols for optimal contrast, brain segmentation, registration, statistical analysis, and atlasing. Ultimately we should be able to quantify changes during normal
Professor Emeritus of Radiology
Currently, major effort is devoted to developing and utilizing magnetic resonance (MR) microscopy for in vivo histologic studies of major organs systems in small animals such as rats and guinea pigs. This work takes two directions: 1. development of monitoring and physiologic and support systems and 2. examination of magnetic resonance correlates of the microscopic changes that occur in the lungs, liver, kidneys, brain and blood vessels. MR imaging at microscopic resolution in live s
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