Photoacoustic imaging for in vivo quantification of placental oxygenation in mice

Abstract

Accurate analysis of placental and fetal oxygenation is critical during pregnancy. Photoacoustic imaging (PAI) combines laser technology with ultrasound in real time. We tested the sensitivity and accuracy of PAI for analysis of placental and fetal oxygen saturation (sO) in mice. The placental labyrinth (L) had a higher sO than the junctional zone plus decidua region (JZ+D) in C57Bl/6 mice. Changing maternal O from 100 to 20% in C57Bl/6 mice lowered sO in these regions. C57Bl/6 mice were treated with the NO synthase inhibitor L-N-nitroarginine methyl ester (L-NAME) from gestational day (GD) 11 to GD18 to induce hypertension. L-NAME decreased sO in L and JZ+D at GD14 and GD18 in association with fetal growth restriction and higher blood pressure. Hypoxia-inducible factor 1α immunostaining was higher in L-NAME control mice at GD14. Fetal sO levels were similar between l-NAME and control mice at GD14 and GD18. In contrast to untreated C57Bl/6, L-NAME decreased placental sO at GD14 and GD18 GD10 or GD12. Placental sO was lower in fetal growth restriction in an angiotensin-converting enzyme 2 knockout mouse model characterized by placental hypoxia. On phantom studies, patterns of sO measured directly correlated with those measured by PAI. In summary, PAI enables the detection of placental and fetal oxygenation during normal and pathologic pregnancies in mice.-Yamaleyeva, L. M., Sun, Y., Bledsoe, T., Hoke, A., Gurley, S. B., Brosnihan, K. B. Photoacoustic imaging for quantification of placental oxygenation in mice.

Non-invasive determination of murine placental and foetal functional parameters with multispectral optoacoustic tomography

“…Optoacoustic (OA) imaging emerged in the early 2000s as a novel non-invasive imaging method harnessing the advantages of optical and US imaging modalities to provide high-contrast characteristic responses of functional and molecular attributes without sacrificing resolution (for depths of millimetres to centimetres) in highly optically scattering biological tissues 7,8 . After several years of continuous technological developments, the use of OA in pre-clinical research and, more recently, in clinical studies has widely spread, with applications including characterization of cerebral hemodynamic responses upon external stimuli 9 , multi-scale whole-body imaging of small animals 10,11 , cell tracking 12,13 , assessments of tumour growth and progression 14,15 and visualization of cardiovascular dynamics 16 .…”

“…OA structural phenotyping of mammalian embryos has been shown to be feasible by either imaging mice embryos ex vivo 26 or using relatively slow scanning-based systems 27,28 . More recent studies have focused on monitoring placental and foetal oxygenation at different developmental stages with real-time OA systems based on linear arrays 2,7,29 . However, these systems are strongly affected by so-called limited-view effects and hence offer sub-optimal imaging performance and very limited quantification capabilities 30 .…”

β3-Adrenoceptors as Putative Regulator of Immune Tolerance in Cancer and Pregnancy

“…However, the oxygenation of the murine placenta does not undergo particular variations in the period between 10 and 18 days of pregnancy ( 118 ). In contrast, the lowest oxygen values appear to be observed around the eighteenth day of pregnancy ( 119 ). These observations therefore legitimize our choice of intervention timing.…”

Oxygen and lack of oxygen in fetal and placental development, feto–placental coupling, and congenital heart defects

“…Blood oxygen level dependent (BOLD) MRI has been used to investigate O 2 saturations during gestation in larger animals and humans (Sorensen et al, ), but is not routinely applicable, especially in smaller laboratory animals. Photo‐acoustic imaging (PAI) was recently developed and tested in rat and mouse pregnancies (Arthuis et al, ; Yamaleyeva et al, ). PAI combines the optical contrast of photoacoustic laser technology with the low acoustic scattering and high spatial resolution of microultrasound (reviewed in the study by Beard, ).…”

“…PAI allows accurate estimates of oxygen saturation (sO 2 ) due to differences in absorption spectra for oxygenated blood detected at 850 nm versus deoxygenated blood detected at 750 nm. A recent PAI study of E10‐18 pregnant mice using the LZ250 probe and Vevo2100 ultrasound assayed placental and fetal sO 2 with a resolution of ~75 μm; sensitivity and accuracy were excellent as determined by in vitro and in vivo validation (Yamaleyeva et al, ). The placental labyrinth appeared to have higher sO 2 than decidual and junctional zones, while there was no change in placental sO2 through normal development (E10‐18).…”