Abstract

Fetal growth restriction (FGR) is a prevalent pregnancy condition characterised by failure of the fetus to reach its genetically predetermined growth potential. The multiple aetiologies, coupled with the risk of fetal complications - encompassing neurodevelopmental delay, neonatal morbidity, and stillbirth - motivate the need to improve holistic assessment of the FGR fetus using MRI. We hypothesised that the fetal liver and placenta would provide insights into FGR biomarkers, unattainable through conventional methods. Therefore, we explore the application of model fitting techniques, linear regression machine learning models, deep learning regression, and Haralick textured features from multi-contrast MRI for multi-fetal organ analysis of FGR. We employed T2 relaxometry and diffusion-weighted MRI datasets (using a combined T2-diffusion scan) for 12 normally grown and 12 FGR gestational age (GA) matched pregnancies (Estimated Fetal Weight below 3rd centile, Median 28+/-3wks). We applied the Intravoxel Incoherent Motion Model, which describes circulatory properties of the fetal organs, and analysed the resulting features distinguishing both cohorts. We additionally used novel multi-compartment models for MRI fetal analysis, which exhibit potential to provide a multi-organ FGR assessment, overcoming the limitations of empirical indicators - such as abnormal artery Doppler findings - to evaluate placental dysfunction. The placenta and fetal liver presented key differentiators between FGR and normal controls, with significant decreased perfusion, abnormal fetal blood motion and reduced fetal blood oxygenation. This may be associated with the preferential shunting of the fetal blood towards the fetal brain, affecting supply to the liver. These features were further explored to determine their role in assessing FGR severity, by employing simple machine learning models to predict FGR diagnosis (100% accuracy in test data, n=5), GA at delivery, time from MRI scan to delivery, and baby weight. We additionally explored the use of deep learning to regress the latter three variables, training a convolutional neural network with our liver and placenta voxel-level parameter maps, obtained from our multi-compartment model fitting. Image texture analysis of the fetal organs demonstrated prominent textural variations in the placental perfusion fractions maps between the groups (p<0.0009), and spatial differences in the incoherent fetal capillary blood motion in the liver (p<0.009). This research serves as a proof-of-concept, investigating the effect of FGR on fetal organs, measuring differences in perfusion and oxygenation within the placenta and fetal liver, and their prognostic importance in automated diagnosis using simple machine learning models.