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Salafia C.M.,Placental Analytics, Llc | Yampolsky M.,University of Toronto | Shlakhter A.,University of Toronto | Mandel D.H.,Placental Analytics, Llc | Schwartz N.,University of Pennsylvania
Placenta | Year: 2012

Objectives: Observational and empirical evidence suggest that the average placental shape is round with a centrally inserted umbilical cord. Yet variability of shape is common. When in pregnancy do shape and cord insertion variations originate? Materials and methods: Placental measures from published datasets obtained ultrasonographically at 11-14 weeks and/or at term were correlated. Results: Significant correlations were found between the normalized distance of cord insertion to the margin at 11-14 weeks with the same quantity at delivery (r = 0.509, p < 0.0001). First trimester cord marginality was not correlated with two measures of roundness of the delivered placenta (p = 0.448, and p = 0.812). There was a strong correlation between delivered placental thickness and first trimester cord marginality (r = -0.368, p = 0.009). There was a significant relationship between the cord marginality at 11-14 weeks and the mean chorionic vascular density at delivery (r = -0.287, p = 0.015). Placental position in the uterine cavity influences cord marginality at delivery. Modeling suggests that placental growth in the first trimester is non-round. Placental shape at 11-14 weeks is found to be irregular. This irregularity is not correlated with the roundness of the delivered placenta. Both empirically, and in the context of IVF pregnancies, deformation of the vasculogenic zone yields a bi-lobate placental shape. Conclusions: Our findings strongly support the hypothesis that abnormal cord insertion and a multi-lobate shape result from early influences on the placental growth, such as the shape of the vasculogenic zone, or placental position in the uterus, rather than trophotropism later in pregnancy. © 2011 Elsevier Ltd. All rights reserved.

Yampolsky M.,University of Toronto | Salafia C.M.,Placental Analytics, Llc | Misra D.P.,Wayne State University | Shlakhter O.,Alberta Health Services | Gill J.S.,Imperial College London
Placenta | Year: 2013

The mean surface shape of placenta is round [1,2] and common abnormalities of shape are associated with vascular abnormalities and reduced placental functional efficiency. A long-standing approach is to describe shapes as elliptic, and to quantify them by "length" and "breadth". We test this description in two cohorts: National Collaborative Perinatal Project and Pregnancy, Infection and Nutrition Study. We conclude that quantifying placental shape as elliptic is ambiguous and problematic. The "breadth" of the placenta should be interpreted as a combination of two different measurements: placental size and irregularity of the placental surface. It has no intrinsic functional significance. © 2013 Elsevier Ltd. All rights reserved.

Serov A.S.,CNRS Condensed Matter Physics Laboratory | Salafia C.,Placental Analytics, Llc | Grebenkov D.S.,CNRS Condensed Matter Physics Laboratory | Filoche M.,CNRS Condensed Matter Physics Laboratory
Journal of Applied Physiology | Year: 2016

The performance of the placenta as a gas exchanger has a direct impact on the future health of the newborn. To provide accurate estimates of respiratory gas exchange rates, placenta models need to account for both the physiology of exchange and the organ morphology. While the former has been extensively studied, accounting for the latter is still a challenge. The geometrical complexity of placental structure requires use of carefully crafted approximations. We present here the state of the art of respiratory gas exchange placenta modeling and demonstrate the influence of the morphology description on model predictions. Advantages and shortcomings of various classes of models are discussed, and experimental techniques that may be used for model validation are summarized. Several directions for future development are suggested. Copyright © 2016 the American Physiological Society.

Gill J.S.,Imperial College London | Salafia C.M.,Placental Analytics, Llc | Grebenkov D.,Ecole Polytechnique - Palaiseau | Vvedensky D.D.,Imperial College London
Journal of Theoretical Biology | Year: 2011

Oxygen transport from maternal blood to fetal blood is a primary function of the placenta. Quantifying the effectiveness of this exchange remains key in identifying healthy placentas because of the great variability in capillary number, caliber and position within the villus-even in placentas deemed clinically "normal". By considering villous membrane to capillary membrane transport, stationary oxygen diffusion can be numerically solved in terminal villi represented by digital photomicrographs. We aim to provide a method to determine whether and if so to what extent diffusional screening may operate in placental villi. Segmented digital photomicrographs of terminal villi from the Pregnancy, Infection and Nutrition study in North Carolina 2002 are used as a geometric basis for solving the stationary diffusion equation. Constant maternal villous oxygen concentration and perfect fetal capillary membrane absorption are assumed. System efficiency is defined as the ratio of oxygen flux into a villus and the sum of the capillary areas contained within. Diffusion screening is quantified by comparing numerical and theoretical maximum oxygen fluxes. A strong link between various measures of villous oxygen transport efficiency and the number of capillaries within a villus is established. The strength of diffusional screening is also related to the number of capillaries within a villus. Our measures of diffusional efficiency are shown to decrease as a function of the number of capillaries per villus. This low efficiency, high capillary number relationship supports our hypothesis that diffusional screening is present in this system. Oxygen transport per capillary is reduced when multiple capillaries compete for diffusing oxygen. A complete picture of oxygen fluxes, capillary and villus areas is obtainable and presents an opportunity for future work. © 2011 Elsevier Ltd.

Yampolsky M.,University of Toronto | Salafia C.M.,Placental Analytics, Llc | Shlakhter O.,Alberta Health Services
Placenta | Year: 2013

Introduction While the mean shape of human placenta is round [1] with centrally inserted umbilical cord, significant deviations from this ideal are fairly common, and may be clinically meaningful [1]. Traditionally, they are explained by trophotropism. We have proposed a hypothesis explaining typical variations in placental shape by randomly determined fluctuations in the growth process of the vascular tree. It has been recently reported that umbilical cord displacement in a birth cohort has a log-normal probability distribution, which indicates that the displacement between an initial point of origin and the centroid of the mature shape is a result of accumulation of random fluctuations of the dynamic growth of the placenta. To confirm this, we investigate statistical distributions of other features of placental morphology. Methods In a cohort of 1023 births at term digital photographs of placentas were recorded at delivery. Excluding cases with velamentous cord insertion, or missing clinical data left 1001 (97.8%) for which placental surface morphology features were measured. Best-fit statistical distributions for them were obtained using EasyFit. Results and discussion The best-fit distributions of umbilical cord displacement, placental disk diameter, area, perimeter, and maximal radius calculated from the cord insertion point are of heavy-tailed type, similar in shape to log-normal distributions. This is consistent with a stochastic origin of deviations of placental shape from normal. Conclusions Deviations of placental shape descriptors from average have heavy-tailed distributions similar in shape to log-normal. This evidence points away from trophotropism, and towards a spontaneous stochastic evolution of the variants of placental surface shape features.

Gasperowicz M.,University of Calgary | Yampolsky M.,University of Toronto | Salafia C.M.,Placental Analytics, Llc
Placenta | Year: 2013

Human birth weight does not scale linearly with the weight of the placenta: placental mass (PM) is proportional to the fetal mass (FM) raised to the scaling exponent of 0.75 (PM ∼ FM0.75) [1,2]. The mouse is a common model for studying genetic and physiological backgrounds of placental development, function and pathologies. However, to date it has not been known how placental weight scales relative to embryo weight in mice. We analyzed E12.5 litters of CD1 wild-type mice, and found that the mouse placental weight demonstrates a power-law scaling relationship with fetal weight; the value of the scaling exponent is approximately 0.72. © 2013 Elsevier Ltd. All rights reserved.

Placental Analytics, Llc | Date: 2012-07-03

Software for processing digital images of the anatomy for diagnosis and treatment.

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 135.07K | Year: 2015

DESCRIPTION provided by applicant Placental measures of roundness cord insertion centrality volume shape and thickness are biomarkers of maternal fetal growth Deviations from expected placental morphology even as early as weeks are related to placental dysfunction and pregnancy complications such as preeclampsia pregnancy hypertension gestational diabetes mellitus and fetal chromosomal defects The common occurrence of these deviations reveals the need for mathematical models to quantify deviations in placental morphology and assess risk of adverse pregnancy outcomes early in pregnancy To meet this need we have assembled a leading team of experts in placental morphology mathematics computer science and obstetrics and gynecology to develop and validate mathematical models that predict placental dysfunction and pregnancy complications from placental morphology measurements obtained early in pregnancy The algorithm will be developed from a large database comprised of D ultrasound placental images from pregnancies with known outcomes providing objective criterion in which andquot healthyandquot and potentially andquot at riskandquot patterns of placental growth can be established A prototype for clinical software will be advanced to house the proposed models allow for inputting of individual patient data and generate estimates for increased risk for adverse outcomes thereby indicating patients for further investigation The proposed models will classify individualized pregnancy risks providing a foundation for a personalized plan to manage each pregnancy PUBLIC HEALTH RELEVANCE Abnormal placental growth is related to numerous adverse pregnancy outcomes such as preeclampsia fetal growth restriction and gestational diabetes mellitus The proposed project will apply multi site state of the art three dimensional ultrasound to mathematical models of the placenta delineating normal and `at riskandapos placental growth patterns The models offer a feasible scalable and non invasive method to ascertain pregnancy risks early in gestation

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 175.95K | Year: 2011

DESCRIPTION (provided by applicant): The development of the placenta is a principal determinant of pregnancy outcome including prematurity, preeclampsia and fetal growth/ birth weight. In turn, next-pregnancy (maternal) risks as well as (newborn) risks ofa wide variety of childhood and adult health outcomes have been reported to be predicted by pregnancy outcomes, with these outcomes serving as proxies for the adequacy (or not) of the intrauterine environment. We propose comprehensive measurement of the placental shape as a more direct assessment of the intrauterine environment, and have developed image analysis software tools for this task. Evidence suggests that major public health issues such as prematurity and preeclampsia have their origin in early gestation, in subclinical pathology that sets the stage for an irrevocable outcome. A growing body of epidemiologic evidence links placental growth to childhood and adult health outcomes, but these studies are limited to the traditional measures of placental weight and its derivatives (e.g. fetoplacental weight ratio) and have not reported consistent findings. The current gold standard measures of placental shape include dichotomous descriptions of placenta shape (as round /oval and irregular ), and take only a single pair of surface diameters, one thickness measure of the placental disk, and the distance of the cord insertion to the nearest disk edge. The most complex placental shapes, with off-center cords, irregular perimeters and variable disk thicknesses are those in which growth may have been most precarious during pregnancy; yet these most poorly measured by current gold standards may be the placentas most germane to the fetal origins debate and to understanding the genesis of disorders such as preeclampsia and prematurity that appear to have their roots in early pregnancy. Our recent work has demonstrated that: 1) abnormal placental shape is correlated with reduced placental efficiency and may be determined early in gestation; 2) different shapes appear to be caused by perturbations in placental development at different times in gestation; and 3) chorionic plate features measured by ultrasound at 11-14 weeks are significantly correlated to similar features observed at term. Our software tool takes the measurements of the delivered placenta and rewinds the movie to identify the timing and magnitude of a gestational stressor(s) that causes deviation(s) from normal placental growth. It more comprehensively captures complex placental shapesand vascular structures using digital .jpg photographs of placental chorionic surface and slices that can be prepared in any hospital with a digital camera and a sharp knife, and are detailed but still compact enough to be readily emailed to a central diagnostic facility for analysis. Such an approach promises to be reproducible across patients and institutions and valid. Another clinical use would be in pre-conceptual counseling and surveillance of subsequent pregnancies, as preeclampsia and prematurity can recur. The goals of this Phase 1 SBIR are to complete the development of our image analysis software tool and to validate it using a subsample of approximately 700 cases each from the Pregnancy, Infection and Nutrition Study of the University of North Carolina-Chapel Hill (UNC PIN) data set and 675 cases from the U.S. National Children's Study (NCS) Vanguard placental project. This proposal differs from our part of the NCS Formative Research Proposal in that this proposal is confined to developing software and modeling methods derived solely from (2D) digital images, while the NCS proposal is focused on studying the 3D shape obtained from a 3D scanner. PUBLIC HEALTH RELEVANCE: Complicated pregnancies of any type carry risks of recurrence in subsequent pregnancies as well as lifelong health risks for the child, but they most commonly occur in clinically healthy women. Deformed placental shapes can be, but are not currently, measured accurately and reliably at birth to serve as a record to identify, time and quantify what are currently undetectable clinically gestational stressors, especially in those pregnancies that reflect the most problematic intrauterine environments and potentially greatest maternal and/or infant risk. Placental Analytics, LLC, proposes to optimize models of whole placental shape based on well-established methodologies in mathematics (Fourier analysis) and physics (statistical thermodynamics) that are based on data derived from digital images of the placental chorionic surface and slices that could be collected in any hospital with a digital camera and a sharp knife, and validate them in data sets with maternal and newborn outcomes, the essential next step before bringing such diagnostic tools to market.

Placental Analytics, Llc | Date: 2010-02-26

A method for analyzing the placenta in two or three dimensions comprising: selecting one or more placental samples to be analyzed; obtaining a digital image of each placental sample; and performing an analysis on the digital images, wherein a mathematical algorithm is applied to the digital image. Three dimensional scanning is also used to measure the 3-D placental shape. The results of the analysis are correlated with data on health outcomes in infants, children, or adults and are used to assess future health risks to a patient.

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