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

Abstract

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.

Corticosterone potentiates DFP-induced neuroinflammation and affects high-order diffusion imaging in a rat model of Gulf War Illness

“…Furthermore, what we have demonstrated here is that this neuroinflammatory response results in subtle, but differentiable changes in diffusion MRI, which highlights the ability to detect inflammatory-induced changes in MRI patterns early and without the requirement of severe damage to the brain tissue. Recent studies using similar diffusion parameters also reported successful discrimination of microstructural changes in neuronal or glial cell elements (Johnson et al, 2014, Blumenfeld-Katzir et al, 2011). In addition, high-order diffusion MRI successfully captured statistically significant changes in diffusion indices in a rat model of mild traumatic brain injury as early as 2 h post-injury (Zhuo et al, 2012).…”

Magnetic resonance imaging of leukoencephalopathy in amnestic workers exposed to organotin

“…In rats exposed to TMT orally, early swelling and thickening of the optic fiber layer were observed in some segments of the retina (Chang and Dyer, 1983b). In addition, intraperitoneal exposure of rats to TMT resulted in changes in white matter regions of their brains, including the fimbria and corpus callosum, as well as hippocampal neuron, on diffusion tensor images (Johnson et al 2014). All these findings suggest that white matter lesions can be observed in TMT intoxication.…”

Long-term effects of curcumin in the non-human primate brain

“…In GFA mapping, the left middle frontal gyrus ROI (#213) in the curcumin group revealed significant pattern differences against the controls. In previous studies, it has been shown that the impact of aging in area 46 (overlaps to #213), is likely due to loss of dendritic arborization or synaptic integrity (reviews for Peters and Kemper, 2012), which can decrease complexity in the medium and enhance either radial or tangential diffusion components (Johnson et al, 2014; Zhuo et al, 2012). If this is the case, then lowered GFA in the frontal cortex of curcumin treated animals can be postulated as an increased complexity due to intactness of subneuronal components.…”