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Chronic hypoxia in pregnant mice impairs the placental and fetal vascular response to acute hypercapnia in BOLD-MRI hemodynamic response imaging. | LitMetric

Chronic hypoxia in pregnant mice impairs the placental and fetal vascular response to acute hypercapnia in BOLD-MRI hemodynamic response imaging.

Placenta

The Goldyne Savad Institute of Gene Therapy and MRI Laboratory, Human Biology Research Center, Hadassah Hebrew University Medical Center, Ein Karem, And the Faculty of Medicine, Hebrew University, Jerusalem, Israel; The Wohl Institute for Translational Medicine, Hadassah Hebrew University Medical Center, Ein Karem, And the Faculty of Medicine, Hebrew University, Jerusalem, Israel.

Published: July 2021

AI Article Synopsis

  • A brief hypercapnic challenge during non-invasive BOLD-MRI imaging can detect acute placental hypoperfusion and reveal fetal brain sparing effects, proposing a new method to differentiate between normal and compromised pregnancies.
  • Eighteen pregnant ICR mice were tested under different oxygen conditions, and BOLD-MRI showed a significant reduction in signal for various organs in normoxic mice during hypercapnia, indicating impaired placental function.
  • The study found that both early- and late-onset hypoxia led to decreased growth and increased fetal neuroapoptosis, particularly in early-onset cases, highlighting the potential of BOLD-MRI to assess chronic fetal health issues related to placental insufficiency.

Article Abstract

Introduction: Brief hypercapnic challenge causes acute placental hypoperfusion with fetal brain sparing on BOLD-MRI. We hypothesize that this non-invasive imaging strategy can distinguish between normal pregnancy and chronic placental hypoperfusion (using the maternal hypoxia model).

Methods: Eighteen pregnant female ICR mice were randomized to three groups: normoxia, late-onset hypoxia (12%O;E13.5-17.5) and early-onset hypoxia (12%O;E10.5-17.5). On E17.5, animals were imaged in a 4.7-T Bruker-Biospec MRI scanner. Fast coronal True-FISP was performed to identify organs of interest (placenta and fetal heart, liver and brain). BOLD-MRI was performed at baseline and during a 4-min hypercapnic challenge (5%CO). %-change in placental and fetal signal was analyzed from T2*-weighted gradient echo MR images. Following MRI, fetuses and placentas were harvested, weighed and immuno-stained.

Results: In normoxic mice, hypercapnia caused reduction in BOLD-MRI signal in placenta (-44% ± 7%; p < 0.0001), fetal liver (-32% ± 7%; p < 0.0001) and fetal heart (-54% ± 12%; p < 0.002), with relative fetal brain sparing (-12% ± 5%; p < 0.0001). These changes were markedly attenuated in both hypoxia groups. Baseline fetal brain/placenta SI ratio was highest in normoxic mice (1.14 ± 0.017) and reduced with increasing duration of hypoxia (late-onset hypoxia: 1.00 ± 0.026; early-onset hypoxia: 0.91 ± 0.016; p = 0.02). Both hypoxic groups exhibited fetal growth restriction with prominent placental glycogen-containing cells, particularly in early-onset hypoxia. There was increased fetal neuro- and intestinal-apoptosis in early-onset hypoxia only.

Conclusions: BOLD-MRI with brief hypercapnic challenge distinguished between normoxia and both hypoxia groups, while fetal neuroapoptosis was only observed after early-onset hypoxia. This suggests that BOLD-MRI with hypercapnic challenge can identify chronic fetal asphyxia before the onset of irreversible brain injury.

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Source
http://dx.doi.org/10.1016/j.placenta.2021.05.006DOI Listing

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