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

The effects of maternal position, in late gestation pregnancy, on placental blood flow and oxygenation: An MRI study

KEY POINTS: Maternal supine sleep position in late pregnancy is associated with an increased risk of stillbirth. Maternal supine position in late pregnancy reduces maternal cardiac output and uterine blood flow. Using MRI, this study shows that compared to the left lateral position, maternal supine position in late pregnancy is associated with reduced uteroplacental blood flow, oxygen transfer across the placenta with an average 6.2% reduction in oxygen delivery to the fetus and an average 11% reduction in fetal umbilical venous blood flow. ABSTRACT: Maternal sleep position in late gestation is associated with an increased risk of stillbirth though the pathophysiological reasons for this are unclear. Studies using MRI have shown that compared with lateral positions, lying supine causes a reduction in cardiac output, reduced abdominal aortic blood flow and reduced vena caval flow which is only partially compensated for by increased flow in the azygos venous system. Using functional MRI techniques, including an acquistion termed Diffusion-Relaxation Combined Imaging of the Placenta (DECIDE), which combines diffusion weighted imaging and T2 relaxometry, blood flow and oxygen transfer were estimated in the maternal, fetal and placental compartments when subjects were scanned both supine and in left lateral positions. In late gestation pregnancy, lying supine caused a 23.7% (p <0.0001) reduction in total internal iliac arterial blood flow to the uterus. In addition, lying in the supine position caused a 6.2% (p = 0.038) reduction in oxygen movement across the placenta. The reductions in oxygen transfer to the fetus, termed delivery flux, of 11.2% (p = 0.0597) and in fetal oxygen saturation of 4.4% (p = 0.0793) did not reach statistical significance. It is concluded that even in healthy late gestation pregnancy, maternal position significantly affects oxygen transfer across the placenta and may in part provide an explanation for late stillbirth in vulnerable fetuses. This article is protected by copyright. All rights reserved

Structure-function relationships in the feto-placental circulation from in silico interpretation of micro-CT vascular structures

A well-functioning placenta is critical for healthy fetal development, as the placenta brings fetal blood in close contact with nutrient rich maternal blood, enabling exchange of nutrients and waste between mother and fetus. The feto-placental circulation forms a complex branching structure, providing blood to fetal capillaries, which must receive sufficient blood flow to ensure effective exchange, but at a low enough pressure to prevent damage to placental circulatory structures. The branching structure of the feto-placental circulation is known to be altered in complications such as fetal growth restriction, and the presence of regions of vascular dysfunction (such as hypovascularity or thrombosis) are proposed to elevate risk of placental pathology. Here we present a methodology to combine micro-computed tomography and computational model-based analysis of the branching structure of the feto-placental circulation in ex vivo placentae from normal term pregnancies. We analyse how vascular structure relates to function in this key organ of pregnancy; demonstrating that there is a 'resilience' to placental vascular structure-function relationships. We find that placentae with variable chorionic vascular structures, both with and without a Hyrtl's anastomosis between the umbilical arteries, and those with multiple regions of poorly vascularised tissue are able to function with a normal vascular resistance. Our models also predict that by progressively introducing local heterogeneity in placental vascular structure, large increases in feto-placental vascular resistances are induced. This suggests that localised heterogeneities in placental structure could potentially provide an indicator of increased risk of placental dysfunction

Texture-Based Analysis of Fetal Organs in Fetal Growth Restriction

Fetal growth restriction (FGR) is common, affecting around 10% of all pregnancies. Growth restricted fetuses fail to achieve their genetically predetermined size and often weigh &lt;10th centile for gestation. However, even appropriately grown fetuses can be affected, with the diagnosis of FGR missed before birth. Babies with FGR have a higher rate of stillbirth, neonatal morbidity such as breathing problems, and neurodevelopmental delay. FGR is usually due to placental insufficiency leading to poor placental perfusion and fetal hypoxia. MRI is increasingly used to image the fetus and placenta. Here we explore the use of novel multi-compartment Intravoxel Incoherent Motion Model (IVIM)-based models for MRI fetal and placental analysis, to improve understanding of FGR and quantify abnormalities and biomarkers in fetal organs. In 12 normally grown and 12 FGR gestational-age matched pregnancies (Median 28+ 4 wks±3+ 3 wks) we acquired T2 relaxometry and diffusion MRI datasets. Decreased perfusion, pseudo-diffusion coefficient, and fetal blood T2 values in the placenta and fetal liver were significant features distinguishing between FGR and normal controls (p-value &lt;0.05). This may be related to the preferential shunting of fetal blood away from the fetal liver to the fetal brain that occurs in placental insufficiency. These features were used to predict FGR diagnosis and gestational age at delivery using simple machine learning models. Texture analysis was explored to compare Haralick features between control and FGR fetuses, with the placenta and liver yielding the most significant differences between the groups. This project provides insights into the effect of FGR on fetal organs emphasizing the significant impact on the fetal liver and placenta, and the potential of an automated approach to diagnosis by leveraging simple machine learning models

Quantifiable study of magnetic resonance super resolution reconstruction in Placenta Accreta Spectrum using Image Quality Metrics

Magnetic Resonance Images are increasingly being used for detection and diagnosis of Placental Complications1 . Here we apply this technology to reconstruction of placenta accreta spectrum. Super-Resolution Reconstruction (SRR) allows for a high-resolution 3D reconstruction from 2D MRI slices to allow for improved visibility of structures for future clinical use2 . The use of Image Quality metrics provides quantitative evaluation of the SRR images and allows comparisons to be drawn between the original 2D images and the SRR. These metrics are tested for statistical significance, providing an objective assessment of the SRR images

Micro-CT and histological investigation of the spatial pattern of feto-placental vascular density

Introduction: There are considerable variations in villous morphology within a normal placenta. However, whether there is a reproducible spatial pattern of variation in villous vascular density is not known. Micro-CT provides three-dimensional volume imaging with spatial resolution down to the micrometer scale. In this study, we applied Micro-CT and histological analysis to investigate the degree of heterogeneity of vascularisation within the placenta. Method: Ten term placentas were collected at elective caesarean section, perfused with contrast agent and imaged whole with Micro-CT. Eight full depth tissue blocks were then taken from each placenta and imaged. Sections were taken for histological analysis. Data was analysed to investigate vascular fill, and vascular density in relation to location from cord insertion to placental edge at each scale. Results: Whole placental imaging revealed no spatially consistent difference in villous vessel density within the main placental tissue, although there was a great degree of heterogeneity. Both block imaging and histological analysis found a large degree of heterogeneity of vascular density within placentas, but no strong correlation between villous vascular density and block location (rs = 0.066, p = 0.7 block imaging, rs = 0.06, p = 0.6 histological analysis). Discussion: This work presents a novel method for imaging the human placenta vascular tree using multiscale Micro-CT imaging. It demonstrates that there is a large degree of variation in vascular density throughout normal term human placentas. The three-dimensional data created by this technique could be used, with more advanced computer analysis, to further investigate the structure of the vascular tree

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

Visualization and Quantification of Placental Vasculature Using MRI

Visualization of the placental vasculature in vivo is important for parameterization of placental function which is related to obstetric pathologies such as fetal growth restriction (FGR). However, most analysis of this vasculature is conducted ex vivo after delivery of the placenta. The aim of this study was to determine whether in vivo MRI imaging can accurately quantify the feto-placental vasculature, and to determine the impact of MRI contrast on its identification. Six different MRI contrasts were compared across 10 different cases. Image quality metrics were calculated, and analysis of vasculature segmentations performed. Measures of assessment included the vessel radius distribution, vessel connectivity and the identification of vessel loops. T2 HASTE imaging performed the best both qualitatively, and quantitatively for PSNR and connectivity measures. A larger number of segmented branches at the smallest radii were observed, indicative of a richer description of the in vivo vascular tree. These were then mapped to MR perfusion fraction measurements from intra-voxel incoherent motion (IVIM) MRI. Mapped results were compared to measures extracted from gold-standard ex vivo micro-CT of the placenta and showed similar vessel density patterns suggesting that placental vessel analysis may be feasible in vivo

An automated localization, segmentation and reconstruction framework for fetal brain MRI

Reconstructing a high-resolution (HR) volume from motion-corrupted and sparsely acquired stacks plays an increasing role in fetal brain Magnetic Resonance Imaging (MRI) studies. Existing reconstruction methods are time-consuming and often require user interaction to localize and extract the brain from several stacks of 2D slices. In this paper, we propose a fully automatic framework for fetal brain reconstruction that consists of three stages: (1) brain localization based on a coarse segmentation of a down-sampled input image by a Convolutional Neural Network (CNN), (2) fine segmentation by a second CNN trained with a multi-scale loss function, and (3) novel, single-parameter outlier-robust super-resolution reconstruction (SRR) for HR visualization in the standard anatomical space. We validate our framework with images from fetuses with variable degrees of ventriculomegaly associated with spina bifida. Experiments show that each step of our proposed pipeline outperforms state-of-the-art methods in both segmentation and reconstruction comparisons. Overall, we report automatic SRR reconstructions that compare favorably with those obtained by manual, labor-intensive brain segmentations. This potentially unlocks the use of automatic fetal brain reconstruction studies in clinical practice