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Continuous monitoring of deep-tissue haemodynamics with stretchable ultrasonic phased arrays

Abstract

Stretchable wearable devices for the continuous monitoring of physiological signals from deep tissues are constrained by the depth of signal penetration and by difficulties in resolving signals from specific tissues. Here, we report the development and testing of a prototype skin-conformal ultrasonic phased array for the monitoring of haemodynamic signals from tissues up to 14 cm beneath the skin. The device allows for active focusing and steering of ultrasound beams over a range of incident angles so as to target regions of interest. In healthy volunteers, we show that the phased array can be used to monitor Doppler spectra from cardiac tissues, record central blood flow waveforms and estimate cerebral blood supply in real time. Stretchable and conformal skin-worn ultrasonic phased arrays may open up opportunities for wearable diagnostics.

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Fig. 1: Challenges of deep-tissue monitoring and mechanism of the stretchable ultrasonic phased array.
Fig. 2: Performance characterizations of the stretchable ultrasonic phased array.
Fig. 3: Cardiac activity monitoring.
Fig. 4: Central blood flow monitoring.

Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. Data generated in this study, including source data and the data used to produce the figures, are available from Harvard Dataverse at https://dataverse.harvard.edu/dataset.xhtml?persistentId=doi:10.7910/DVN/EPITIY.

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Acknowledgements

We thank Z. Wu and L. Chen for guidance on the ultrasonic imaging algorithm and data processing; S. Xiang for feedback on manuscript preparation; and Y. Hu and Z. Liu for advice on the cardiac tissue Doppler experiments. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH). All biological experiments were conducted in accordance with the ethical guidelines of the NIH and with the approval of the IRB of the University of California, San Diego (IRB number 170812). We acknowledge support from the NIH (grant 1R21EB027303-01A1) and the Center for Wearable Sensors at the University of California, San Diego.

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C.W., B.Q., M.L., Z.Z. and S.X. designed the research. C.W., B.Q., M.L., B.L. and Z.Z. performed the experiments. C.W., B.Q. and Z.Z. performed the simulations. C.W., Z.Z., B.Q. and M.L. analysed the data. C.W. and S.X. wrote the paper. All authors provided active and valuable feedback on the manuscript.

Corresponding author

Correspondence to Sheng Xu.

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The authors declare no competing interests.

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Peer review information Nature Biomedical Engineering thanks John Ho 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 Comparison of existing flexible or stretchable electronic devices for deep-tissue monitoring.

a, Comparison of the detection range (shaded areas underneath each sensing mode) of the stretchable phased array with all other flexible/stretchable biosensors, including optoelectronics, thermal electronics, iontophoresis based electrochemical sensors, terahertz wave-based sensors, a single ultrasonic transducer, and electronic stethoscopes. The phased array has distinct advantages compared to the other sensing modalities in both penetration depth and spatial resolution. With phased array beamforming, the stretchable ultrasonic probe can focus the beam to achieve longer penetration (up to 14 cm in human tissues) and steer the beam to scan over a 40° range with a high signal-to-noise ratio (SNR). The insonation area in 2D can reach ~68.41 cm2, 380 times larger than the insonation area of a single element, ~0.18 cm2, calculated by Field II, MATLAB, MathWorks, Natick, MA. b, Comparison of the penetration depth and detectable object size of representative flexible/stretchable biosensors in the literature. Stretchable optoelectronics illuminates the tissue to analyze changes in blood oxygen saturation, but the depth of penetration is generally limited to ~8 mm8,9,10. Stretchable thermal electronics suffer from similar limitations11,12. Although flexible terahertz devices show high penetration in dielectric materials14, terahertz electromagnetic waves attenuate quickly in water15, leading to a maximum penetration depth of only 0.3 mm in the human tissue16. Flexible electromagnetic devices in the frequency range of ~GHz can penetrate more than 5 cm of human tissue, but their spatial resolution ranges from 5 to 50 cm, which is inadequate for most biomedical applications4. Stretchable stethoscopes based on kinematics can sense vibrations far beneath the skin72; but due to the omnidirectional propagation of vibrations, these devices can receive signals from all organs in their sensing range, and thus lack spatial resolution73,74. Additionally, they can only detect low-frequency pulsations, missing critical information from static objects (for example, their location, dimension, and modulus) or high-frequency pulsations (for example, hemodynamics). The result shows the stretchable phased array has a long penetration depth with sufficient resolving capabilities for deep tissue monitoring.

Extended Data Fig. 2 Performance of the stretchable phased array at all incidence angles in the xz plane on the phantom replicated from the human neck.

a, A schematic setup of the characterization. Ultrasonic field mapping is carried out with the stretchable phased array on a flat (top left) or a curvilinear (top right) surface. The characterization system is composed of a water tank and a 3D motor system with a hydrophone at its tip. b, Mapped ultrasonic fields with the stretchable phased array on a flat (left) or a curvilinear (right) surface with an incidence angle range of 0° - 25°. Scale bars are 2 cm. c, Normalized beam intensity of the stretchable phased array at a typical carotid artery depth (~3 cm) with different incident angles. The inset illustrates the depth at which the intensity measurements are taken. d, Beam directivity of the stretchable phased array at a typical carotid artery depth (~3 cm) with different incident angles. The beam directivity of the stretchable phased array is comparable on the two surfaces at all incident angles in the range tested.

Extended Data Fig. 3 Raw radiofrequency signals of the tissue Doppler in the time domain, and corresponding human anatomy.

a, Raw radiofrequency signals of the tissue Doppler in one cardiac cycle. Note that the y-axis is time. The x-axis is converted to depth by multiplying the ultrasonic speed by the time-of-flight of ultrasonic pulses in the human tissue. As a proof of concept, we neglect the non-uniformity of the ultrasonic speed in the human body. From the pattern, we can clearly observe the reflection peaks from the anterior wall of the right ventricle (RV) in the blue dashed box and the posterior wall of the left ventricle (LV) in the orange dashed box. The positions of the reflection peaks shift during the cardiac cycle. The RV anterior wall peak shifts to the left from 0 to 0.6 s, corresponding to RV diastole, and shifts to the right from 0.6 to 0.8 s, corresponding to RV systole. Meanwhile, the LV posterior wall peak shifts to the right from 0 to 0.6 s, corresponding to LV diastole, and shifts to the left from 0.6 to 0.8 s, corresponding to LV systole. The peak shifting clearly indicates the relaxation and contraction of the cardiac chambers. b, The cross-sectional structure of the parasternal short-axis view corresponding to the signal peaks in a.

Supplementary information

Supplementary Information

Supplementary Discussions 1–10, Figs. 1–38 and captions for Supplementary Videos 1–3.

Reporting Summary

Supplementary Video 1

Phased-array steerability.

Supplementary Video 2

Comparison of wave propagation of the stretchable phased array on planar and curved surfaces.

Supplementary Video 3

Real-time imaging of the conformal probe on a deep-tissue phantom.

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Wang, C., Qi, B., Lin, M. et al. Continuous monitoring of deep-tissue haemodynamics with stretchable ultrasonic phased arrays. Nat Biomed Eng 5, 749–758 (2021). https://doi.org/10.1038/s41551-021-00763-4

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