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Stretchable ultrasonic arrays for the three-dimensional mapping of the modulus of deep tissue

Nature Biomedical Engineering volume 7, pages 1321–1334 (2023)Cite this article

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Abstract

Serial assessment of the biomechanical properties of tissues can be used to aid the early detection and management of pathophysiological conditions, to track the evolution of lesions and to evaluate the progress of rehabilitation. However, current methods are invasive, can be used only for short-term measurements, or have insufficient penetration depth or spatial resolution. Here we describe a stretchable ultrasonic array for performing serial non-invasive elastographic measurements of tissues up to 4 cm beneath the skin at a spatial resolution of 0.5 mm. The array conforms to human skin and acoustically couples with it, allowing for accurate elastographic imaging, which we validated via magnetic resonance elastography. We used the device to map three-dimensional distributions of the Young’s modulus of tissues ex vivo, to detect microstructural damage in the muscles of volunteers before the onset of soreness and to monitor the dynamic recovery process of muscle injuries during physiotherapies. The technology may facilitate the diagnosis and treatment of diseases affecting tissue biomechanics.

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Fig. 1: Working principle, design and fabrication of the stretchable ultrasonic array.
Fig. 2: Strategies for elastography.
Fig. 3: Characterizations on phantom models.
Fig. 4: Validation and serial monitoring on biological specimens.
Fig. 5: Multi-site mapping and serial surveillance of delayed-onset muscle soreness in human.

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Data availability

The main data supporting the results of this study are available within the paper and its Supplementary Information. The data generated in this study are available from figshare at https://doi.org/10.6084/m9.figshare.22197139.v1. Source data are provided with this paper.

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Acknowledgements

We thank Z. Wu for the guidance on ultrasonic imaging algorithm and data processing, N. Szeverenyi for the help with MRE testing, S. Sinha for the discussions about eccentric exercise experiments, Y. Wang and R. Kou for the help with Young’s modulus characterizations by a mechanical apparatus, and S. Xiang for the feedback on paper preparation. The material is based on research sponsored by Air Force Research Laboratory (AFRL) under agreement number FA8650-18-2-5402. The US Government is authorized to reproduce and distribute reprints for government purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of Air Force Research Laboratory or the US Government. This work was partially supported by the National Institutes of Health (NIH) grants 1R21EB025521-01, 1R21EB027303-01A1, 3R21EB027303-02S1 and 1R01EB033464-01, and the Center for Wearable Sensors at the University of California, San Diego. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Author information

Author notes

  1. These authors contributed equally: Hongjie Hu, Yuxiang Ma, Xiaoxiang Gao, Dawei Song.

Authors and Affiliations

  1. Materials Science and Engineering Program, University of California San Diego, La Jolla, CA, USA

    Hongjie Hu, Keren Shi, Xiangjun Chen, Baiyan Qi, Sai Zhou, Yue Gu, Xinyu Tian, Xinyi Yang, Jing Mu & Sheng Xu

  2. Department of Nanoengineering, University of California San Diego, La Jolla, CA, USA

    Hongjie Hu, Yuxiang Ma, Xiaoxiang Gao, Mohan Li, Hao Huang, Ray Wu, Hong Ding, Muyang Lin, Yimu Chen, Yusheng Lei, Chonghe Wang, Chunfeng Wang, Yangzhi Zhu, Zhaoxin Chen, Zhiyuan Lou & Sheng Xu

  3. Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA

    Dawei Song

  4. Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA

    Xuejun Qian, Ruimin Chen & Qifa Zhou

  5. Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Wenbo Zhao

  6. Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, USA

    Yitian Tong, Chengchangfeng Lu & Sheng Xu

  7. Department of Computer Science, University of Toronto, Toronto, Ontario, Canada

    Haotian Cui

  8. Department of Mechanical and Aerospace Engineering, University of California San Diego, La Jolla, CA, USA

    Abdulhameed Abdal

  9. Department of Radiology, School of Medicine, University of California San Diego, La Jolla, CA, USA

    Mohammad Eghtedari & Sheng Xu

  10. Department of Aerospace and Mechanical Engineering, University of Southern California, Los Angeles, CA, USA

    Assad Oberai

  11. Department of Bioengineering, University of California San Diego, La Jolla, CA, USA

    Sheng Xu

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  1. Hongjie Hu
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Contributions

Ho.H., Y.M., X.G., D.S. and S.X. designed the research. Ho.H., Y.M., M.L. and Ha.H. performed the experiments. Y.M., X.G. and D.S. performed the data processing and simulations. Ho.H., Y.M. and X.G. analysed the data. Ho.H., D.S., X.G. and S.X. wrote the paper. All authors provided constructive and valuable feedback on the manuscript.

Corresponding author

Correspondence to Sheng Xu.

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Competing interests

The authors declare no competing interests.

Peer review

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Nature Biomedical Engineering thanks Antoine Nordez, Xiaoning Jiang 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 Simulation results of uniform and nonuniform compressions.

(a) A synthetic specimen with an inclusion that has a shear modulus 10 times higher than that of the surrounding matrix. The synthetic “measured” displacement fields based on (b) uniform compression and (c) non-uniform compression on the specimen. (d) and (e) show the strain distributions from uniform and non-uniform compression, respectively. The strain distributions vary upon different applied loads, which indicates that the strain-based elastography is qualitative only reflecting a relative stiffness of each component. The reconstructed modulus distributions obtained from solving inverse elasticity problems based on (f) uniform compression and (g) non-uniform compression. (h) Quantitative analysis of modulus contrasts and their deviations from the ground truth in (a).

Extended Data Fig. 2 Validating the device’s reliability on six subjects.

(a) Strain mapping results of upper arms of six subjects for the evaluation of the intra-session reliability. (b) Strain mapping results of upper arms of six subjects for the evaluation of the inter-day reliability.

Extended Data Fig. 3 Serial surveillance of delayed-onset muscle soreness in multiple subjects.

Serial monitoring results of normalized modulus contrast of the biceps brachii muscle before and after the eccentric exercise. All six subjects did two rounds of experiments. In the first round, all subjects took the natural recovery after doing the exercise. In the second round, subjects in (a), (b) took natural recovery, subjects in (c), (d) took massotherapy, and subjects in (e), (f) took hyperthermia. For each test, we mapped the modulus distribution of the muscle. Then, we calculated the mean and standard deviations of the biceps brachii area. In each physiotherapy session, data are normalized by the modulus contrast of the biceps brachii muscle before exercise.

Extended Data Fig. 4 Validation by a clinical standard method on a larger sample size.

(a) Changes in the maximal voluntary contraction torque (black) and normalized modulus contrast (blue) of the biceps brachii muscle measured by the stretchable ultrasonic array before and after the eccentric exercise of 16 subjects. The points and error bars of the blue curves indicate the mean and standard deviation of modulus contrast of the biceps brachii muscle of every test. For each test, we mapped the modulus distribution of the muscle. Then, we calculated the mean and standard deviations of the biceps brachii area. In each physiotherapy session, data were normalized by the modulus contrast of the biceps brachii muscle before exercise. As a clinical standard approach, the maximal voluntary contraction can validate the muscle strength and muscle damage. (b) P-values of the clinical standard method and the stretchable ultrasonic array, which were calculated by single-sided paired t-test. Error bars are standard deviations of the data of 16 subjects (n = 16).

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Simulation illustrating the principle of ultrasound elastography.

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Hu, H., Ma, Y., Gao, X. et al. Stretchable ultrasonic arrays for the three-dimensional mapping of the modulus of deep tissue. Nat. Biomed. Eng 7, 1321–1334 (2023). https://doi.org/10.1038/s41551-023-01038-w

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