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Noninvasive Estimation of Tumor Interstitial Fluid Pressure from Subharmonic Scattering of Ultrasound Contrast Microbubbles

Wang, Yun, Lu, Huimin, Huang, Laixin, Li, Deyu, Qiu, Weibao, Li, Lingling, Xu, Gang, Su, Min, Zhou, Jianhua, Li, Fei·2023·Biosensors
DOI 10.3390/bios13050528PMC PMC10216054
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Abstract

The noninvasive estimation of interstitial fluid pressure (IFP) using ultrasound contrast agent (UCA) microbubbles as pressure sensors will provide tumor treatments and efficacy assessments with a promising tool. This study aimed to verify the efficacy of the optimal acoustic pressure in vitro in the prediction of tumor IFPs based on UCA microbubbles’ subharmonic scattering. A customized ultrasound scanner was used to generate subharmonic signals from microbubbles’ nonlinear oscillations, and the optimal acoustic pressure was determined in vitro when the subharmonic amplitude reached the most sensitive to hydrostatic pressure changes. This optimal acoustic pressure was then applied to predict IFPs in tumor-bearing mouse models, which were further compared with the reference IFPs measured using a standard tissue fluid pressure monitor. An inverse linear relationship and good correlation (r = −0.853, p < 0.001) existed between the subharmonic amplitude and tumor IFPs at the optimal acoustic pressure of 555 kPa, and pressure sensitivity was 1.019 dB/mmHg. No statistical differences were found between the pressures measured by the standard device and those estimated via the subharmonic amplitude, as confirmed by cross-validation (mean absolute errors from 2.00 to 3.09 mmHg, p > 0.05). Our findings demonstrated that in vitro optimized acoustic parameters for UCA microbubbles’ subharmonic scattering can be applied for the noninvasive estimation of tumor IFPs.

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Figure 1 In vitro acoustic attenuation experiment setup.
Figure 1 In vitro acoustic attenuation experiment setup.CC BY · PubMed Central
Figure 2 In vitro flow circulation system for acoustic scattering measurement.
Figure 2 In vitro flow circulation system for acoustic scattering measurement.CC BY · PubMed Central
Figure 3 The schematic of in vivo experiment. (a) Ultrasonic RF data acquisition and IFP measurement. (b–d) ROI selected from reconstructed B-mode image of tumors and subharmonic wave extraction (red box, ROI selected).
Figure 3 The schematic of in vivo experiment. (a) Ultrasonic RF data acquisition and IFP measurement. (b–d) ROI selected from reconstructed B-mode image of tumors and subharmonic wave extraction (red box, ROI selected).CC BY · PubMed Central
Figure 4 The RF data processing flow (red box, ROI selected).
Figure 4 The RF data processing flow (red box, ROI selected).CC BY · PubMed Central
Figure 5 Acoustic attenuation spectra of Sonazoid microbubbles’ suspensions at different injection times. (a) 1 min, (b) 3 min, (c) 5 min, (d) 9 min after injection.
Figure 5 Acoustic attenuation spectra of Sonazoid microbubbles’ suspensions at different injection times. (a) 1 min, (b) 3 min, (c) 5 min, (d) 9 min after injection.CC BY · PubMed Central
Figure 6 The results of in vitro experiments. (a) The amplitude of subharmonic increases with the increased acoustic pressure at ambient pressures of 10 mmHg and 40 mmHg. (b) Subharmonic amplitudes vary with ambient pressure at acoustic pressures of 407 kPa (r = −0.883, p = 0.117), 555 kPa (r = −0.966, p = 0.034), and 663 kPa (r = −0.924, p = 0.076).
Figure 6 The results of in vitro experiments. (a) The amplitude of subharmonic increases with the increased acoustic pressure at ambient pressures of 10 mmHg and 40 mmHg. (b) Subharmonic amplitudes vary with ambient pressure at acoustic pressures of 407 kPa (r = −0.883, p = 0.117), 555 kPa (r = −0.966, p = 0.034), and 663 kPa (r = −0.924, p = 0.076).CC BY · PubMed Central
Figure 7 Correlation analysis between tumor IFP and subharmonic amplitudes. The dotted curves on either side of the fitted lines are limits of 95% confidence intervals.
Figure 7 Correlation analysis between tumor IFP and subharmonic amplitudes. The dotted curves on either side of the fitted lines are limits of 95% confidence intervals.CC BY · PubMed Central

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Metadata

Authors
Wang, Y., Lu, H., Huang, L., Li, D., Qiu, W., Li, L., Xu, G., Su, M., Zhou, J., & Li, F.
Venue
Biosensors
Publisher
MDPI AG
Published
2023-05-08
Volume
13
Issue
5
Pages
528
ISSN
2079-6374
DOI
10.3390/bios13050528
PMC
PMC10216054
Cited by
13
References
0
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • National Natural Science Foundation of China (81671698, 81927808, 12074402, 12004411, JCYJ20200109114825064, ZDSYS201802061806314, GJHZ20210705141404012, 2022M712262)
  • Shenzhen Basic Research Program (81671698, 81927808, 12074402, 12004411, JCYJ20200109114825064, ZDSYS201802061806314, GJHZ20210705141404012, 2022M712262)
  • Shenzhen Key Laboratory of Ultrasound Imaging and Therapy (81671698, 81927808, 12074402, 12004411, JCYJ20200109114825064, ZDSYS201802061806314, GJHZ20210705141404012, 2022M712262)
  • Shenzhen Science and Technology Program (81671698, 81927808, 12074402, 12004411, JCYJ20200109114825064, ZDSYS201802061806314, GJHZ20210705141404012, 2022M712262)
  • China Postdoctoral Science Foundation (81671698, 81927808, 12074402, 12004411, JCYJ20200109114825064, ZDSYS201802061806314, GJHZ20210705141404012, 2022M712262)

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CoChat. (2026). Citation check: Noninvasive Estimation of Tumor Interstitial Fluid Pressure from Subharmonic Scattering of Ultrasound Contrast Microbubbles. https://app.cochat.ai/papers/10.3390/bios13050528
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Wang, Y., Lu, H., Huang, L., Li, D., Qiu, W., Li, L., Xu, G., Su, M., Zhou, J., & Li, F. (2023). Noninvasive Estimation of Tumor Interstitial Fluid Pressure from Subharmonic Scattering of Ultrasound Contrast Microbubbles. Biosensors. https://doi.org/10.3390/bios13050528