Magnetic resonance imaging and volumetric analysis: novel tools to study the effects of thyroid hormone disruption on white matter development.

Humans and wildlife are exposed to environmental pollutants that have been shown to interfere with the thyroid hormone system and thus may affect brain development. Our goal was to expose pregnant rats to propylthiouracil (PTU) to measure the effects of a goitrogen on white matter development in offspring using magnetic resonance imaging (MRI) and volumetric analysis. We exposed pregnant Sprague Dawley (SD) rats to 3 or 10 ppm PTU from gestation day 7 (GD7) until postnatal day 25 (P25) to determine the effects on white matter (WM), gray matter (GM), and hippocampus volumes in offspring. We sacrificed offspring at P25 but continued the life of some offspring to P90 to measure persistent effects in adult animals. P25 offspring exposed to 10 ppm PTU displayed lowered levels of triiodothyronine (T3) and thyroxine (T4); cerebral WM, GM, and total brain volumes were significantly lower than the volumes in control animals. P90 adults exposed to 10 ppm PTU displayed normal T3 levels but lowered T4 levels; WM, GM, total brain, and hippocampal volumes were significantly lower than the volumes in control adults. Both P25 and P90 rats exposed to 10 ppm PTU displayed significant reductions in percent WM as well as heterotopias in the corpus callosum. Exposure to 3 ppm PTU did not produce any significant effects. These results suggest that MRI coupled with volumetric analysis is a powerful tool in assessing the effects of thyroid hormone disruption on white matter development and brain structure. This approach holds great promise in assessing neurotoxicity of xenobiotics in humans and wildlife.