TY - JOUR
T1 - Structure-function relationships in the feto-placental circulation from in silico interpretation of micro-CT vascular structures
AU - Byrne, Monika
AU - Aughwane, Rosalind
AU - James, Joanna L
AU - Hutchinson, Ciaran
AU - Arthurs, Owen
AU - Sebire, Neil
AU - Ourselin, Sebastien
AU - David, Anna L
AU - Melbourne, Andrew
AU - Clark, Alys R
N1 - Funding Information:
This research was supported by a Royal Society of New Zealand Rutherford Discovery Fellowship (14-UOA-032), the Wellcome Trust (210182/Z/18/Z, 203145Z/16/Z; 203148/Z/16/Z) and the Engineering and Physical Sciences Research Council (EPSRC) (NS/A000027/1; NS/A000050/1; NS/A000049/1). This research was supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London and a University of Auckland Bioengineering Masters Scholarship (Byrne).
Publisher Copyright:
© 2021 Elsevier Ltd
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5/21
Y1 - 2021/5/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85101796488&partnerID=8YFLogxK
U2 - 10.1016/j.jtbi.2021.110630
DO - 10.1016/j.jtbi.2021.110630
M3 - Article
C2 - 33607145
SN - 0022-5193
VL - 517
SP - 110630
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
M1 - 110630
ER -