Direct assessment of blood oxygenation in the human placenta can provide information about placental function. However, the monitoring of placental oxygenation involves invasive sampling or imaging techniques that are poorly suited for bedside use. Here we show that placental oxygen haemodynamics can be non-invasively probed in real time and up to 4.2 cm below the body surface via concurrent frequency-domain diffuse optical spectroscopy and ultrasound imaging. We developed a multimodal instrument to facilitate the assessment of the properties of the anterior placenta by leveraging image-reconstruction algorithms that integrate ultrasound information about the morphology of tissue layers with optical information on haemodynamics. In a pilot investigation involving placentas with normal function (15 women) or abnormal function (9 women) from pregnancies in the third trimester, we found no significant differences in baseline haemoglobin properties, but statistically significant differences in the haemodynamic responses to maternal hyperoxia. Our findings suggest that the non-invasive monitoring of placental oxygenation may aid the early detection of placenta-related adverse pregnancy outcomes and maternal vascular malperfusion.
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The main data supporting the results in this study are available within the paper and its supplementary information. All optical data generated in this study, including source data and the data used to make the figures, are available from figshare with identifiers at https://doi.org/10.6084/m9.figshare.19451882, https://doi.org/10.6084/m9.figshare.19451879 and https://doi.org/10.6084/m9.figshare.19451876. The raw clinical and ultrasound data are available from the corresponding author, subject to approval from the Institutional Review Board of the University of Pennsylvania.
The custom code employed for processing the optical data and for performing the statistical analysis are available from figshare with identifiers at https://doi.org/10.6084/m9.figshare.19451882, https://doi.org/10.6084/m9.figshare.19451879 and https://doi.org/10.6084/m9.figshare.19451876. The LabVIEW code and simulation code are also available from the corresponding author on request.
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The work was supported by NIH U01HD087180. J.M.C. was partially supported by NIH P41EB015893. T.K. was partially supported by NIH F31HD085731 and NIH T32HL007915. W.B. was partially supported by R01NS113945. A.G.Y. acknowledges partial support from NIH R01NS060653 and NIH P41EB015893. We thank D. Licht, B. White, J. Strauss and Y. H. Ong for useful discussions, advice and support, as well as the clinic research coordinators of the Maternal and Child Health Research Center at Perelman School of Medicine, University of Pennsylvania.
The authors declare no competing interests.
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Wang, L., Cochran, J.M., Ko, T. et al. Non-invasive monitoring of blood oxygenation in human placentas via concurrent diffuse optical spectroscopy and ultrasound imaging. Nat. Biomed. Eng 6, 1017–1030 (2022). https://doi.org/10.1038/s41551-022-00913-2