The aim of my thesis was to examine the use of placental magnetic resonance imaging in preeclampsia and chronic hypertension. Placental magnetic resonance imaging techniques are currently in development and there is a paucity of data for their use and application in hypertensive disorders of pregnancy. The objectives of my research were to firstly optimise placental magnetic resonance imaging and associated measures in women with preeclampsia and chronic hypertension and to describe potential unexpected findings in magnetic resonance imaging performed for research during pregnancy. Secondly, I set out to provide an approach to visual assessment of the placenta in uncomplicated pregnancies using T2-weighted imaging. Thirdly I investigated placental changes in preeclampsia for an insight into the pathophysiology of preeclampsia and then investigated placental changes in chronic hypertension for an insight into the heterogeneity of pregnancy outcomes. Lastly, I explored changes in associated placental biomarkers Placental Growth Factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), vascular adhesion molecule (VCAM) and hyaluronan in women with preeclampsia and chronic hypertension and described them in the context of placental T2* values obtained from magnetic resonance imaging. These objectives were achieved through performing a prospective, observational study, embedded within the National Institutes of Health (NIH) funded Placenta imaging Project, which aimed to develop a novel magnetic resonance approach to assess growth and development of the human placenta in health and disease. The focus of my project related specifically to evaluating placental magnetic resonance imaging in women with chronic hypertension and preeclampsia. In this thesis, the optimisation and application of advanced magnetic resonance imaging techniques have provided detailed placental imaging in women with preeclampsia and chronic hypertension. These techniques have enabled qualitative visual assessment and quantitative assessment of placental structure and function. Optimised T2-weighted imaging sequences have led to the development of a comprehensive approach to visual assessment of the placenta in uncomplicated pregnancies and are subsequently used as a reference for assessing women with preeclampsia and chronic hypertension. Quantitative assessment of the placenta has included the development of T2* mapping and diffusion sequences, culminating in an optimised combined diffusion-relaxometry sequence which provides regionally matched diffusion and T2* values in a reasonably fast and acceptable scan time compared to conventional sequences. Methods assessing placental T2* maps to quantify the visual variation seen are explored and detect variability within such maps. These measures include lacunarity as well as histogram derived measures of kurtosis and skewness, in addition to mean T2*. These advanced sequences of T2-weighted imaging, T2* mapping and diffusion weighted imaging have been applied to women with preeclampsia and chronic hypertension in order to explore the spectrum of placental phenotypes in these hypertensive disorders of pregnancy. In pregnancies complicated by preeclampsia, T2-weighted imaging showed substantial areas of low signal intensity, advanced lobularity and high granularity within lobules with a reduced entire placental mean T2* for gestational age and higher lacunarity values compared to uncomplicated pregnancies. In pregnancies complicated by chronic hypertension, T2-weighted imaging showed a varied visual appearance compared to gestation matched controls with some showing features similar to those with preeclampsia and some indistinguishable from those in the control group. Not all women with mean T2* values outside of the normal range developed adverse pregnancy outcomes and conversely not all women with normal mean T2* values had uncomplicated pregnancies. This suggest a more complex interaction between the placenta and maternal or fetal response, while the timing of imaging (in relation to delivery) may be crucial. Finally, T2* mapping was explored in conjunction with placental biomarkers of PlGF, sFlt-1, hyaluronan and VCAM to further elucidate mechanisms underlying preeclampsia and chronic hypertension. These biomarkers have been found to provide complementary mechanistic information of placental phenotypes seen with T2* mapping.
Magnetic resonance imaging to identify a placental phenotype in hypertensive disorders and its association with clinical, ultrasound and biomarker variables
Ho, A. (Author). 1 Jun 2021
Student thesis: Doctoral Thesis › Doctor of Philosophy