This proposal is designed to test the general hypothesis that fetal ultrasound exposure at clinically relevant frequencies, intensities, and dwell times is capable of heating the rat fetus by several degrees Celsius, and that this heating, if appropriately timed, is sufficient to cause neural tube defects. It initially examines the thermal environment of the pregnant rat and re-examines the issue of the teratogenic effect of maternal heating by immersion to serve as a positive control. Then it will determine the ultrasound dosimetry necessary to raise fetal temperature 5, 3, and 1 degree Celsius in an acute preparation followed by a randomized dosing sequence designed to raise fetal temperature by those amounts for 1, 5, or 10 minutes to evaluate teratogenic effect. Finally, a series of in vitro experiments using rat sarcoma cells and a clonogenic assay will be used to determine the cell killing effects of each of these thermal exposures.
|Miller, Morton W; Church, Charles C (2013) Arrhenius thermodynamics and birth defects: chemical teratogen synergy. Untested, testable, and projected relevance. Birth Defects Res C Embryo Today 99:50-60|
|Miller, Morton W; Dewey, William C (2003) An extended commentary on ""Models and regulatory considerations for transient temperature rise during diagnostic ultrasound pulses"" by Herman and Harris (2002). Ultrasound Med Biol 29:1653-9; author response 1661-2|
|Miller, M W; Nyborg, W L; Dewey, W C et al. (2002) Hyperthermic teratogenicity, thermal dose and diagnostic ultrasound during pregnancy: implications of new standards on tissue heating. Int J Hyperthermia 18:361-84|