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ABSTRACT: Introduction
There is a lack of effective therapeutic interventions for preeclampsia. A central factor in the etiology of the disease is the development of placental hypoxia due to abnormal vascular remodeling. However, methods to assess the impact of potential therapies on placental growth and remodeling are currently lacking. Here, we develop and validate ultrasound-guided photoacoustic imaging methods to monitor the placental response to therapeutic intervention. Establishing non-invasive tools to image placental function opens up previously unachievable understandings of placental therapeutic response.Methods
Studies were performed in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. Preclinical research has identified tempol, a superoxide dismutase mimetic, and the phosphodiesterase inhibitor sildenafil as potential therapeutics for preeclampsia, as both improve in vivo maternal outcomes. PA images of the placental environment were acquired in RUPP rats receiving tempol (n = 8) or sildenafil (n = 8) to assess the longitudinal effects of treatment on placental oxygenation and vascular remodeling. Imaging measurements were validated with ex vivo histological analysis.Results
Spectral photoacoustic imaging non-invasively measured placental hypoxia and impaired vascular growth two days after the RUPP procedure was implemented. Sildenafil significantly improved (p < 0.05) placental oxygenation and promoted vascular remodeling in RUPP animals, while RUPP animals treated with tempol had a diminished placental therapeutic response.Discussion
We demonstrate that photoacoustic imaging provides in vivo measures of placental oxygenation and vascular remodeling, a previously unobtainable assessment of preeclamptic therapeutic response. These imaging tools have tremendous potential to accelerate the search for effective therapies for preeclampsia.
SUBMITTER: Lawrence DJ
PROVIDER: S-EPMC10236486 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature

Lawrence Dylan J DJ Bayer Carolyn L CL
Placenta 20220621
<h4>Introduction</h4>There is a lack of effective therapeutic interventions for preeclampsia. A central factor in the etiology of the disease is the development of placental hypoxia due to abnormal vascular remodeling. However, methods to assess the impact of potential therapies on placental growth and remodeling are currently lacking. Here, we develop and validate ultrasound-guided photoacoustic imaging methods to monitor the placental response to therapeutic intervention. Establishing non-inva ...[more]