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

• Three groups of SD rats (N = 8/group): control, 8 mg/kg and 12 mg/kg trimethyltin.
• MR histology with GRE and diffusion tensor imaging at 39- and 78-micron resolution.
• Automated registration and voxel-based analysis for statistical parametric maps.
• Quantitative assessment of regional changes in volume and fractional anisotropy.

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.

Magnetic resonance histology can provide multiple metrics to assess central nervous system injuries. Different image contrasts (GRE, and diffusion weighted images, or DWI) were acquired from rats exposed to trimethyltin (TMT), as well as controls. Voxel-based analysis, comparing controls against TMT-treated rats, identified distinct regions where TMT exposure induced statistically significant changes in volume and diffusion tensor image-based parameters, such as fractional anisotropy. These regions can be referenced relative to a 3D MR atlas of the rat brain.Figure optionsDownload high-quality image (90 K)Download as PowerPoint slide