Magnetic Resonance Imaging Biomarkers for Diagnosing Placentas with Abnormal Diffusional Exchange

Babies born too small are at much greater risk of being handicapped or of dying soon after birth. Also, people who were small babies have an increased chance of developing heart disease or diabetes as adults. The placenta is responsible for transferring nutrients from mother to baby during pregnancy and so does have a key role in controlling growth. A variety of research has now led us to better understanding of the defects in the placenta that can cause babies to grow too slowly. We believe that this knowledge of the placenta could allow us to diagnose babies who are growing poorly in the womb. Here we will investigate whether magnetic resonance imaging, a non-invasive method of studying the internal organs of the body, may be used to examine the placenta in the womb and determine which ones are abnormal and so may be causing abnormal growth of the baby. If we could diagnose abnormal placentas in this way and so identify babies growing too slowly, we will be able to focus medical care with a consequent greater chance of the pregnant woman delivering a healthy baby. Furthermore, better diagnostic tools could lead to new ways of treating the woman with an abnormally growing baby during her pregnancy. We have a strong track record of explaining our work to the public through newspaper interviews, radio and television and will continue to do this. The University of Manchester provides support for a variety of events aimed at increasing public understanding of science, including Open Days and regular `Cafe Scientifique meetings.

The birth of a baby who is abnormally small, because its growth has been restricted in utero (i.e. suffered intrauterine growth restriction, IUGR) complicates 3-10% of all first time births. The perinatal mortality rate of the IUGR fetus is 4-10 times higher than that of normally grown babies and they also have increased risk of neonatal, and later, morbidity. Despite these severe consequences of IUGR, the ability of the obstetrician to diagnose and treat the disease in utero is still severely limited. Failure of the placenta to supply adequate nutrients to the fetus is one cause of IUGR. There is now good knowledge of the variety of structural and functional defects in this organ associated with IUGR. We have postulated that assessment of these placental phenotypes of IUGR could be used to diagnose IUGR in utero at early stages of the disease. Here we will test the hypothesis that the blood flow in the maternal and fetal circulations of the placenta, and the passive permeability and related exchange barrier characteristics of the placenta can be assessed together in utero by Magnetic Resonance Imaging (MRI) and that such measurements can be used to distinguish small normal babies from those with IUGR due to placental insufficiency. The work will be in two phases. In phase 1 we will (a) Characterise and validate the MRI techniques for examining placental structure/function in normal human pregnancies. We will measure blood flow using FAIR arterial spin labelling (ASL) methods and assess placental exchange barrier characteristics by relaxation time and quantitative magnetisation transfer (qMT) measurements and analysis of texture and homogeneity. (b) Set up and validate a method to measure the passive permeability of the placenta in utero at the time of Caesarean section, using inert, hydrophilic tracers of increasing molecular weight. In phase 2 we will proceed to test whether the MRI measurements of placental phenotypes can be used to distinguish between women having normal pregnancies from those with a fetus suffering from IUGR, and how well they correlate with direct measurements of placental permeability and exchange barrier dimensions (as measured by morphometric analysis of placentas post delivery). If successful the project will allow us to design a prospective randomised control trial of the use of MRI analysis of placental phenotypes in diagnosing IUGR during pregnancy.