Assessment of Placental Blood Volume Flow and Function in IUGR Using a Transfer Function Model

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Abstract: The placenta is the conduit through which all fetal nourishment and oxygen delivery passes. Therefore, assessment of placental function is critical to understanding and monitoring the physiological state of the developing fetus. All nutrients and oxygen get to the fetus through placental communications between the maternal and fetal blood circulations. Hence, major factors for placental function are blood flow and perfusion. In this regard, we hypothesize that a new method for measuring umbilical arterial and venous flows can yield significant, new information about placental functional status. Since standard spectral Doppler studies can detect flow abnormalities related to IUGR, albeit generally late in gestation, we hypothesize that our new methods will be more sensitive to changes in placental function earlier than the present diagnostic techniques, including ultrasound Doppler measurements. We are expressing this optimism because we will use an angle-independent, flow profile independent volume flow measurement method, that we have validated in other settings, to make time-dependent blood flow measurements in the umbilical arteries and vein simultaneously. These will lead directly to a placental transfer function (PTF), which would be a totally benign method for analyzing placental function throughout gestation. If successful, our combined volume flow/transfer function methods can be quickly implemented on standard diagnostic ultrasound machines and moved into clinical use. Initially, we will use phantom studies to investigate how time-dependent umbilical cord flow is altered based on controlled changes in vascular resistance and compliance, and we will use this time-dependent flow information to create and validate a transfer function model of the phantom. In the phantom, we will have complete control of the flows, internal resistance/compliance, and pressure drops. We will be able to see how effectively the transfer function represents these parameters in the phantom. Once proven in phantoms, we will use a well-validated in-vivo pregnant sheep model of intrauterine growth restriction (IUGR), gestational testosterone treated sheep, to test how well flow and our transfer function model predict placental changes in IUGR.