Simulations of the Vascular Network Growth Process for Studying Placenta Structure and Function Associated with Autism
Placenta chorionic surface vascular networks differ in individuals at-risk for autism compared to controls in terms of longer, straighter, thicker vessels; less branching; smaller changes in flow directions; and better coverage to the placental boundary. What mechanism(s) could drive these differences and how these mechanisms would impact blood transport has not been widely investigated. We used a Monte-Carlo simulation to mimic three mechanisms for controlling vascular growth: vessels grow faster and longer, terminate more frequently before branching, and flow directions are more tightly controlled in the at-risk simulations. For each mechanism, we analyzed simulated vascular networks based on structural properties and blood flow, assuming Poiseuille’s law and distensible vessels. Our simulations showed that none of these mechanisms alone could reproduce all structural properties of vascular networks in placentas identified as at-risk for autism. Terminating vessels more frequently or growing longer vessels could each reproduce longer vessels and less branching, but not greater boundary coverage or smaller changes in flow directions. As for their influence on blood flow, longer vessels and less branching have large, opposing effects on network function. Networks with longer vessels are less efficient in terms of slower flow rates and higher total network volume; in contrast, networks with less branching are more efficient. Our results suggest either these mechanisms work together to drive observed differences in vascular networks of at-risk individuals by balancing their impacts on network function; or another mechanism not considered here might drive these differences.
KeywordsPlacentas Autism Vascular networks Blood flow Simulations
The work described in this chapter was initiated during the Association for Women in Mathematics collaborative workshop Women Advancing Mathematical Biology hosted by the Mathematical Biosciences Institute (MBI) at Ohio State University in April 2017. Funding for the workshop was provided by MBI, NSF ADVANCE “Career Advancement for Women Through Research-Focused Networks” (NSF-HRD 1500481), Society for Mathematical Biology, and Microsoft Research.
- 2.A. Angelidou, S. Asadi, K.-D. Alysandratos, A. Karagkouni, S. Kourembanas, T.C. Theoharides, Perinatal stress, brain inflammation and risk of autism-review and proposal. BMC Pediatr. 12(1), 89 (2012)Google Scholar
- 4.J.-M. Chang, H. Zeng, R. Han, Y.-M. Chang, R. Shah, C.M. Salafia, C. Newschaffer, R.K. Miller, P.J. Katzman, J. Moye, M. Fallin, C.K. Walker, L. Croen, Autism risk classification using placental chorionic surface vascular network features. BMC Med. Inform. Decis. Mak. 17(1), 162 (2017)Google Scholar
- 8.K Coward, D. Wells, Textbook of Clinical Embryology (Cambridge University Press, Cambridge, 2013)Google Scholar
- 13.C.J. Newschaffer, L.A. Croen, M.D. Fallin, I. Hertz-Picciotto, D.V. Nguyen, N.L. Lee, C.A. Berry, H. Farzadegan, H.N. Hess, R.J. Landa, S.E. Levy, M.L. Massolo, S.C. Meyerer, S.M. Mohammed, M.C. Oliver, S. Ozonoff, J. Pandey, A. Schroeder, K.M. Shedd-Wise, Infant siblings and the investigation of autism risk factors. J. Neurodev. Disord. 4, 1–16 (2012)CrossRefGoogle Scholar
- 16.C.M. Salafia, Placental vascular tree as biomarker of autism/ASD risk. Annual report for U.S. Army Medical Research and Materiel Command at Fort Detrick, Maryland 21702-5012 W81XWH-10-1-0626, Research Foundation for Mental Hygiene (2014), http://www.dtic.mil/dtic/tr/fulltext/u2/a575079.pdf.
- 18.C.M. Salafia, T. Girardi, M. Yampolsky, O. Shlakhter, C. Newschaffer, D. Fallin, C. Walker, C. Stodgell, P. Katzman, J. Culhane, P. Landrigan, S. Szabo, N. Thieux, J. Swanson, N. Dole, M. Varner, J. Moye, R. Miller, Chorionic vascular structure and placental functional efficiency (beta) differ in high and low autism risk placental cohorts. Placenta 34, A72 (2013)CrossRefGoogle Scholar
- 19.C.M. Salafia, C. Platt, T. Girardi, R. Shah, G. Merz, D.P. Misra, Placental structure in ASD: does the placenta mirror the diagnosis? in 2014 International Meeting for Autism Research, page Abstract No. 17578 (2014)Google Scholar