Placental vascular abnormalities causing deficient placental perfusion contribute to common complications of human pregnancy including preeclampsia and intrauterine growth restriction (IUGR). Blood flow pulsatility, quantified using the Doppler Resistance index, is often elevated in the uterine and/or umbilical circulations in preeclamptic or growth restricted pregnancies. This change in hemodynamics is associated with placental vascular abnormalities which presumably elevate vascular resistance and thereby impair perfusion. However, the causes of placental vascular abnormalities in human pregnancy as well as the relationships between structural and hemodynamic changes are poorly understood. In our lab, we are using genetically-altered mice as new models to explore the etiology of abnormalities in placental vascularization and hemodynamics. We are using ultrasound biomicroscopy (30-40 MHz; Vevo770, VisualSonics, Canada) to non-invasively image and record Doppler blood velocity waveforms of isoflurane-anesthetized pregnant mice. We have monitored blood velocity in the uterine artery and intraplacental arterial canals of the mother, and in the yolk sac and umbilical circulations of the embryo both in normal pregnancy and in mouse models of intrauterine growth restriction (IUGR). Dr. Junwu Mu has shown that peak (PSV) and end-diastolic velocities (EDV) in the uterine artery increase and the uterine arterial Doppler Resistance Index (RI= (PSV-EDV)/PSV) decreases during gestation in mouse as in human pregnancy. PSV in the umbilical artery increases progressively from the day the heart starts to beat (E8.5) until term (E18.5) whereas PSV in the vitelline artery to the yolk sac increases until E13.5, and then remains stable. In the umbilical artery, EDV increases from zero to become detectable as early as E15.5 and is detectable in nearly all embryos at term. Umbilical waveforms are similar to those observed in first trimester human pregnancy. Similar to findings in human IUGR, Dr. Junwu Mu and Ms. Shathiyah Kulandavelu observed elevated resistance indices in the umbilical and uterine arteries of two mouse models of IUGR; eNOS knockouts from Jackson Laboratories, and transgenics with perinatal hepatic overexpression of IGFBP-1 created by Drs. Victor Han and Carole Watson. In collaboration with Dr. John Sled (Mouse Imaging Centre, Toronto), Ms. Monique Rennie and Ms. Kathie Whiteley are using X-ray micro-computed tomography (µCT) to image and quantify vascular branching patterns in the utero-placental and umbilico-placental circulations following the installation of an X-ray opaque contrast agent. Preliminary results suggest this method can be used to detect normal developmental changes in placental vascularity as well as vascular defects in IUGR models. We conclude that ultrasound biomicroscopy and µCT provide viable methods for quantifying placental hemodynamics and vascularity throughout pregnancy in mice. Our early results show that there are strong parallels in placental structure and hemodynamics between mice and humans in both normal and IUGR pregnancies.