Investigating Perfusion of the Human Placenta

Placental insufficiency is a significant cause of morbidity and mortality, accounting for one third of antenatal stillbirths. It occurs when the maternal spiral arteries fail to remodel normally in early pregnancy, leading to inadequate maternal perfusion of the placenta. The fetus becomes hypoxic and if not delivered prematurely may ultimately die. Assessing the placenta is therefore clinically important, to diagnose placental insufficiency in vivo, and investigate poor pregnancy outcome ex vivo. Ex vivo placental assessment relies on subjective histological analysis of a small proportion of the placenta, looking for features such as oedema, inflammation and the presence of avascular villi. Regional variation and heterogeneity are not defined. In utero clinical assessment is via ultrasound Doppler measurements, looking for increased resistance in the uterine arteries, suggesting poor spiral artery remodeling, and increased resistance within the umbilical artery, suggesting inadequate development of the feto-placental microcirculation. There is therefore an urgent need to develop new ways to evaluate the perfusion of the placenta both in and ex vivo. In this thesis I investigate two imaging modalities with the potential to improve our understanding of placental perfusion. Ex vivo I develop a placental perfusion and micro-CT imaging technique, to directly visualise the feto-placental microcirculation, before applying the technique to investigate heterogeneity within a cohort of normal term placentae. I investigate differences in vascular density through the placenta at multiple scales. In vivo I investigate a novel Magnetic Resonance Imaging model of placental perfusion, that combines diffusion weighted imaging with T2 relaxometry, to estimate maternal and fetal placental perfusion. I develop this technique, exploring MRI parameters relating to perfusion in normally grown and growth restricted pregnancies. This work is important as the techniques developed improve our ability to investigate and understand placental perfusion, and provide potential new parameters of placental function in vivo

A review of feto-placental vasculature flow modelling

The placenta provides the vital nutrients and removal of waste products required for fetal growth and development. Understanding and quantifying the differences in structure and function between a normally functioning placenta compared to an abnormal placenta is vital to provide insights into the aetiology and treatment options for fetal growth restriction and other placental disorders. Computational modelling of blood flow in the placenta allows a new understanding of the placental circulation to be obtained. This structured review discusses multiple recent methods for placental vascular model development including analysis of the appearance of the placental vasculature and how placental haemodynamics may be simulated at multiple length scales

PIPPI2021: An Approach to Automated Diagnosis and Texture Analysis of the Fetal Liver & Placenta in Fetal Growth Restriction

Fetal growth restriction (FGR) is a prevalent pregnancy condition characterised by failure of the fetus to reach its genetically predetermined growth potential. 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. We applied the Intravoxel Incoherent Motion Model and 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 (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. 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. Moreover, we explored the use of deep learning to regress the latter three variables. 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

Photoacoustic imaging of the human placental vasculature

Minimally invasive fetal interventions require accurate imaging from inside the uterine cavity. Twin‐to‐twin transfusion syndrome (TTTS), a condition considered in this study, occurs from abnormal vascular anastomoses in the placenta that allow blood to flow unevenly between the fetuses. Currently, TTTS is treated fetoscopically by identifying the anastomosing vessels, and then performing laser photocoagulation. However, white light fetoscopy provides limited visibility of placental vasculature, which can lead to missed anastomoses or incomplete photocoagulation. Photoacoustic (PA) imaging is an alternative imaging method that provides contrast for hemoglobin, and in this study, two PA systems were used to visualize chorionic (fetal) superficial and subsurface vasculature in human placentas. The first system comprised an optical parametric oscillator for PA excitation and a 2D Fabry‐Pérot cavity ultrasound sensor; the second, light emitting diode arrays and a 1D clinical linear‐array ultrasound imaging probe. Volumetric photoacoustic images were acquired from ex vivo normal term and TTTS‐treated placentas. It was shown that superficial and subsurface branching blood vessels could be visualized to depths of approximately 7 mm, and that ablated tissue yielded negative image contrast. This study demonstrated the strong potential of PA imaging to guide minimally invasive fetal therapies. [Image: see text

Placenta Imaging Workshop 2018 report:Multiscale and multimodal approaches

The Centre for Medical Image Computing (CMIC) at University College London (UCL) hosted a two-day workshop on placenta imaging on April 12th and 13th 2018. The workshop consisted of 10 invited talks, 3 contributed talks, a poster session, a public interaction session and a panel discussion about the future direction of placental imaging. With approximately 50 placental researchers in attendance, the workshop was a platform for engineers, clinicians and medical experts in the field to network and exchange ideas. Attendees had the chance to explore over 20 posters with subjects ranging from the movement of blood within the placenta to the efficient segmentation of fetal MRI using deep learning tools. UCL public engagement specialists also presented a poster, encouraging attendees to learn more about how to engage patients and the public with their research, creating spaces for mutual learning and dialogue

Placental MRI and its Application to Fetal Intervention

OBJECTIVE: Magnetic Resonance Imaging (MRI) of placental invasion has been part of clinical practice for many years. The possibility of being better able to assess placental vascularization and function using MRI has multiple potential applications. This review summarises up-to-date research on placental function using different MRI modalities. METHOD: We discuss how combinations of these MRI techniques have much to contribute to fetal conditions amenable for therapy such as singletons at high risk for FGR; and monochorionic twin pregnancies for planning surgery and counselling for selective growth restriction and transfusion conditions. RESULTS: The whole placenta can easily be visualized on MRI, with a clear boundary against the amniotic fluid, and a less clear placental-uterine boundary. Contrasts such as Diffusion Weighted Imaging, Relaxometry, Blood Oxygenation Level Dependent MRI and flow and metabolite measurement by Dynamic Contrast Enhanced MRI, Arterial Spin Labeling or spectroscopic techniques are contributing to our wider understanding of placental function. CONCLUSION: The future of placental MRI is exciting, with the increasing availability of multiple contrasts and new models that will boost the capability of MRI to measure oxygen saturation and placental exchange, enabling examination of placental function in complicated pregnancies

Developments in functional imaging of the placenta

The placenta is both the literal and metaphorical black box of pregnancy. Measurement of the function of the placenta has the potential to enhance our understanding of this enigmatic organ and serve to support obstetric decision making. Advanced imaging techniques are key to supporting these measurements. This review summarises emerging imaging technology being used to measure the function of the placenta and new developments in the computational analysis of this data. We address three important examples where functional imaging is supporting our understanding of these conditions: fetal growth restriction, placenta accreta, and twin-twin transfusion syndrome