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Non-invasive monitoring of blood oxygenation in human placentas via concurrent diffuse optical spectroscopy and ultrasound imaging

Abstract

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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Fig. 1: Integrated FD-DOS/US placenta instrumentation and three-layer modelling.
Fig. 2: Three-layer model reconstruction algorithm and phantom-validation experiments.
Fig. 3: Placental haemoglobin properties during stability test measurements and the maternal left-tilt experiment.
Fig. 4: Continuous monitoring of placental haemoglobin properties during maternal hyperoxia.
Fig. 5: Static (baseline) and dynamic (during maternal hyperoxia) placental haemoglobin properties for participants with NPO or APO.
Fig. 6: Static (baseline) and dynamic (during maternal hyperoxia) placental haemoglobin properties for participants with NPP or MVM.

Data availability

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.

Code availability

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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Acknowledgements

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.

Author information

Authors and Affiliations

Authors

Contributions

L.W., A.G.Y. and N.S. designed the study. L.W. and T.K. developed the instrument with assistance from W.B.B., K.A., L.H., D.R.B. and V.K. L.W. and J.M.C. developed the three-layer reconstruction algorithm and conducted the computer simulations. L.W. and T.K. performed phantom experiments with help from W.B.B. and L.H. K.A. designed the optical probe with input from L.W. and W.B.B. L.W. collected and analysed the optical data. S.P. and N.S. advised on human participant data interpretation. N.S. collected and analysed the ultrasound data. R.L.L. performed placental histopathologic analysis. L.W., A.G.Y. and N.S. wrote the paper with input from all authors.

Corresponding author

Correspondence to Lin Wang.

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Nature Biomedical Engineering thanks Carolyn Bayer, Christopher Contag and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1

Detailed schematic of the custom heterodyne FD-DOS instrument.

Supplementary information

Reporting Summary

Supplementary dataset 1

Optically measured placental data for the 24 participants.

Supplementary dataset 2

Clinically monitored variables for the 24 participants.

Supplementary tables

Supplementary Tables 1–6.

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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

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