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. Here, 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.

Sex differences in modulation of fetoplacental vascular resistance in growth-restricted mouse fetuses following betamethasone administration: comparisons with human fetuses

“…30 This technique uses high-frequency ultrasound to measure pulse pressure waves that travel both with and counter to the direction of blood flow along the UA, providing additional information about the fetoplacental vasculature than can be obtained by measuring UA PI alone. 31 The UA diameter, UA blood flow, and wave reflection coefficient were significantly elevated in the BMZ-treated mice compared with saline-treated controls, suggesting a significant decrease in placental vascular resistance. In this study, we investigated the changes in UA wave reflection metrics after BMZ administration in fetuses exposed to chronic, late-gestation maternal hypoxia, an established model of FGR.…”

“…Ultrasound imaging was performed using a high-frequency ultrasound system with a 40 MHz linear array transducer (Vevo 2100, Visualsonics, Inc, Toronto, Canada) as previously described. 30,31 Briefly, dams were anesthetized with isoflurane (2.5% for maintenance in 11% O 2 for the hypoxia group and 21% O 2 for the controls). The imaging session was limited to 30 minutes to maintain a physiological maternal heart rate.…”

“…The ultrasound image analysis has been described in detail previously. 30,31 Briefly, the near and far walls in the Mmode time series and the mean velocity waveforms in the Doppler velocity spectra were automatically outlined, smoothed, divided into cardiac cycles by selection of the onset of systole, temporally aligned, and averaged together. It is unclear why some growth-restricted fetuses do not show improvements in umbilical artery (UA) pulsatility index after corticosteroid administration.…”

“…Original Research datasets passed this preprocessing quality control, further postprocessing criteria based on the work of Chirinos et al 40 were applied to the M-mode traces: datasets were excluded if (1) >35% of the total aligned waveforms were outside the bands representing AE20% of the average area change (at this threshold, the area waveforms separated visually into 2 distinct clusters representing datasets with low and high variations between the individual waveforms) 31 or (2) there were not enough individual area traces to average (<4 area traces).…”

Advances in imaging feto-placental vasculature: new tools to elucidate the early life origins of health and disease

“…With regard to experimental models, preclinical microultrasound has provided useful insight into placental haemodynamics in models commonly used to understand early life origins of adult disease. 18,52,101,102,[145][146][147][148][149][150][151][152] For example, using preclinical high-resolution ultrasound, there is evidence for perturbed umbilical cord blood flow and velocity in 11β-HSD2 -/mice. 18 However, this was ameliorated by pravastatin administration and also improved fetal cardiac function.…”