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Qualitative and Quantitative Neuropathology Approaches Using Magnetic Resonance Microscopy (Diffusion Tensor Imaging)
Robert C Sills1, G Allan Johnson2, Robert J Anderson2
1Division of the National Toxicology Program, 6857National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Abstract:
It is well established that hexachlorophene, which is used as an antibacterial agent, causes intramyelinic edema in humans and animal models. The hexachlorophene myelinopathy model, in which male Sprague-Dawley rats received 25 to 30 mg/kg hexachlorophene by gavage for up to 5 days, provided an opportunity to compare traditional neuropathology evaluations with magnetic resonance microscopy (MRM) findings. In addition, stereology assessments of 3 neuroanatomical sites were compared to quantitative measurements of similar structures by MRM. There were positive correlations between hematoxylin and eosin and luxol fast blue stains and MRM for identifying intramyelinic edema in the cingulum of corpus callosum, optic chiasm, anterior commissure (aca), lateral olfactory tracts, pyramidal tracts (py), and white matter tracts in the cerebellum. Stereology assessments were focused on the aca, longitudinal fasciculus of the pons, and py and demonstrated differences between control and treated rats, as was observed using MRM. The added value of MRM assessments was the ability to acquire qualitative 3-dimensional (3-D) images and obtain quantitative measurements of intramyelinic edema in 26 neuroanatomical sites in the intact brain. Also, diffusion tensor imaging (fractional anisotropy [FA]) indicated that there were changes in the cytoarchitecture of the white matter as detected by decreases in the FA in the treated compared to the control rats. This study demonstrates creative strategies that are possible using qualitative and quantitative assessments of potential white matter neurotoxicants in nonclinical toxicity studies. Our results lead us to the conclusion that volumetric analysis by MRM and stereology adds significant value to the standard 2-D microscopic evaluations.
Insights
Magnetic Resonance Microscopy (MRM) effectively detects hexachlorophene-induced white matter damage in rats, correlating with traditional methods. This advanced imaging offers valuable quantitative insights into neurotoxicant effects on brain cytoarchitecture.
Area of Science:
- Neuroscience
- Toxicology
- Biomedical Imaging
Background:
- Hexachlorophene (antibacterial agent) is known to cause intramyelinic edema in humans and animal models.
- Traditional neuropathology methods are used to evaluate toxicant-induced white matter injury.
Purpose of the Study:
- To compare traditional neuropathology with Magnetic Resonance Microscopy (MRM) findings in a hexachlorophene myelinopathy model.
- To assess the value of MRM and stereology in quantifying neurotoxicant effects on white matter.
Main Methods:
- Male Sprague-Dawley rats were administered hexachlorophene (25–30 mg/kg) for up to 5 days.
- Neuropathology (H&E, LFB stains) and stereology were compared with MRM and diffusion tensor imaging (fractional anisotropy [FA]).
- Quantitative volumetric analysis of 26 neuroanatomical sites was performed using MRM.
Main Results:
- MRM showed positive correlations with traditional stains for identifying intramyelinic edema in multiple white matter tracts.
- Stereology and MRM demonstrated significant differences in neuroanatomical sites between control and hexachlorophene-treated rats.
- Decreased FA values in diffusion tensor imaging indicated white matter cytoarchitecture changes in treated rats.
Conclusions:
- MRM provides valuable qualitative 3-D images and quantitative measurements of intramyelinic edema in intact brains.
- Volumetric analysis by MRM and stereology significantly enhance standard 2-D microscopic evaluations for assessing white matter neurotoxicants.
- MRM and diffusion tensor imaging offer creative strategies for nonclinical toxicity studies of white matter toxicants.
