title: Ultrasound detection of altered placental vascular morphology based on hemodynamic pulse wave reflection.
abstract: Abnormally pulsatile umbilical artery (UA) Doppler ultrasound velocity waveforms are a hallmark of severe or early onset placental-mediated intrauterine growth restriction (IUGR), whereas milder late onset IUGR pregnancies typically have normal UA pulsatility. The diagnostic utility of these waveforms to detect placental pathology is thus limited and hampered by factors outside of the placental circulation, including fetal cardiac output. In view of these limitations, we hypothesized that these Doppler waveforms could be more clearly understood as a reflection phenomenon and that a reflected pulse pressure wave is present in the UA that originates from the placenta and propagates backward along the UA. To investigate this, we developed a new ultrasound approach to isolate that portion of the UA Doppler waveform that arises from a pulse pressure wave propagating backward along the UA. Ultrasound measurements of UA lumen diameter and flow waveforms were used to decompose the observed flow waveform into its forward and reflected components. Evaluation of CD1 and C57BL/6 mice at embryonic day (E)15.5 and E17.5 demonstrated that the reflected waveforms diverged between the strains at E17.5, mirroring known changes in the fractal geometry of fetoplacental arteries at these ages. These experiments demonstrate the feasibility of noninvasively measuring wave reflections that originate from the fetoplacental circulation. The observed reflections were consistent with theoretical predictions based on the area ratio of parent to daughters at bifurcations in fetoplacental arteries suggesting that this approach could be used in the diagnosis of fetoplacental vascular pathology that is prevalent in human IUGR. Given that the proposed measurements represent a subset of those currently used in human fetal surveillance, the adaptation of this technology could extend the diagnostic utility of Doppler ultrasound in the detection of placental vascular pathologies that cause IUGR.NEW & NOTEWORTHYHere, we describe a novel approach to noninvasively detect microvascular changes in the fetoplacental circulation using ultrasound. The technique is based on detecting reflection pulse pressure waves that travel along the umbilical artery. Using a proof-of-principle study, we demonstrate the feasibility of the technique in two strains of experimental mice.
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anum
authors.initials: A
authors.lastname: Rahman
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Yu-Qing
authors.initials: YQ
authors.lastname: Zhou
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Yee
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Jun
authors.initials: J
authors.lastname: Dazai
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Cahill
authors.affiliation: Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada.|Mount Sinai Hospital, Toronto, Ontario, Canada; and.
authors.forename: John
authors.initials: J
authors.lastname: Kingdom
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.|Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Macgowan
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada; john.sled@utoronto.ca.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.|Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada.|Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: John G
authors.initials: JG
authors.lastname: Sled
mesh_terms: D000465:Algorithms; D000818:Animals; D001808:Blood Vessels / Q000000981:diagnostic imaging; D047108:Embryonic Development; D005260:Female; D005317:Fetal Growth Retardation / Q000000981:diagnostic imaging*; D017709:Fractals; D006439:Hemodynamics; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000000981:diagnostic imaging*; D021041:Placental Circulation; D011247:Pregnancy; D063177:Pulse Wave Analysis; D018608:Ultrasonography, Doppler; D016216:Ultrasonography, Prenatal
keywords: intrauterine growth restriction; placenta; ultrasound; umbilical artery; wave reflection