Modelling Of PAFC Based Scattering Monitoring System for the Characterization of the Therapeutic Micro-Bubbles

Vibhor K. Bhardwaj (Login required)
Department of Electrical and Instrumentation Engineering, Sant Longowal Institute of Engineering & Technology, Punjab, India

Surita Maini
Department of Electrical and Instrumentation Engineering, Sant Longowal Institute of Engineering & Technology, Punjab, India

Paper #3335 received 6 Aug 2019; revised manuscript received 26 Sep 2019; accepted for publication 26 Sep 2019; published online 30 Sep 2019.

DOI: 10.18287/JBPE19.05.030303


In recent years, researchers are eagerly developing the Ultrasound Cavity Agents (UCA) as a therapeutic agent, so that they can deliver the drugs to an intended place in a guided manner with minimal invasiveness and maximum effectiveness. However, control dissolution of the drug is still an issue because the shell of the micro-bubble sometimes collapses instantaneously and start releasing the drug at a faster rate. This sudden rise in the pressure's level can rupture the capillaries and sometimes blood vessels also. Therefore, in such cases, it is a great challenge to examine the dynamics of the micro-bubble as well as the health of the blood vessel. In this essence, this paper presents a study based on the finite element method to examine the potential use of Photo-Acoustic Flow Cyclometery (PAFC) to resolve this issue. The presented model is based on the study of the intensity variations of the optical scatterings engender by the micro-bubbles through PAFC. The results of the study reveal that the proposed model has the potential to be used as a new mechanism to examine the growth of the micro-bubble as well as the health of the blood vessel. Moreover, by analysing the scattering pattern, one can also able to predict the value of the cavitation threshold and the size of the micro-bubble. Hence, the authors envisioned that the modified PAFC system can lead the path of a low-cost and real-time examiner for accurate target drug delivery as well as for the health of the blood vessel. Which in turn potentially increases the localized concentration of the drug to reduce the concerned side-effects of medicine on the other part of the body.


therapeutic agents; microbubble; PAFC; FEM; cavitation threshold

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1. C. A. Sennoga, E. Kanbar, L.Auboire, P.-A. Dujardin, D. Fouan, J.-M. Escoffre, and A. Bouakaz, “Microbubble-mediated ultrasound drug-delivery and therapeutic monitoring,” Expert Opinion on Drug Delivery 14(9), 1031–1043 (2017).

2. J. M Tsutsui, F. Xie, and R. T. Porter, “The use of microbubbles to target drug delivery,” Cardiovascular Ultrasound 2(1), 23 (2004).

3. G. Shapiro, A. W. Wong, M. Bez, F. Yang, S. Tam, L. Even, D. Sheyn, S. Ben-David, W. Tawackoli, G. Pelled, K. W. Ferrara, and D. Gazit, “Multiparameter evaluation of in vivo gene delivery using ultrasound-guided, microbubble-enhanced sonoporation,” Journal of Controlled Release 223, 157–164 (2016).

4. A. A. Doinikov, A. Bouakaz, “Modeling of the dynamics of microbubble contrast agents in ultrasonic medicine: Survey,” Journal of Applied Mechanics and Technical Physics 54(6), 867–876 (2013).

5. J. E. Leeman, J. S. Kim, F. T. H. Yu, X. Chen, K. Kim, J. Wang, X. Chen, F. S. Villanueva, and J. J. Pacella, “Effect of Acoustic Conditions on Microbubble-Mediated Microvascular Sonothrombolysis,” Ultrasound in Medicine & Biology 38(9), 1589–1598 (2012).

6. S. Datta, C.-C. Coussios, A. Y. Ammi, T. D. Mast, G. M. de Courten-Myers, and C. K. Holland, “Ultrasound-Enhanced Thrombolysis Using Definity® as a Cavitation Nucleation Agent,” Ultrasound in Medicine & Biology 34(9), 1424–1433 (2008).

7. S. M. Chowdhury, T. Lee, and J. K. Willmann, “Ultrasound-guided drug delivery in cancer,” Ultrasonography 36(3), 171–184 (2017).

8. F. Li, L. Wang, Y. Fan, and D. Li, “Simulation of noninvasive blood pressure estimation using ultrasound contrast agent microbubbles”, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control 59(4), 715–726 (2012).

9. M. Postema, H. Abraham, O. Krejcar, and D. Assefa, “Size determination of microbubbles in optical microscopy: a best-case scenario,” Optics Express 25(26), 33588 (2017).

10. S. Li, Y. Qin, X. Wang, and X. Yang, “Bubble growth in cylindrically-shaped optical absorbers during photo-mediated ultrasound therapy,” Physics in Medicine & Biology 63(12), 125017.

11. C. Harfield, C. R. Fury, G. Memoli, P. Jones, N. Ovenden, and E. Stride, “Analysis of the Uncertainty in Microbubble Characterization,” Ultrasound in Medicine & Biology 42(6), 1412–1418 (2016).

12. K. Efthymiou, N. Pelekasis, M. B. Butler, D. H. Thomas, and V. Sboros, “The effect of resonance on transient microbubble acoustic response: Experimental observations and numerical simulations,” The Journal of the Acoustical Society of America 143(3), 1392–1406 (2018).

13. J. Sijl, B. Dollet, M. Overvelde, V. Garbin, T. Rozendal, N. de Jong, D. Lohse, and M. Versluis, “Subharmonic behavior of phospholipid-coated ultrasound contrast agent microbubbles,” The Journal of the Acoustical Society of America 128(5), 3239–3252 (2010).

14. S. Paul, A. Katiyar, K. Sarkar, D. Chatterjee, W. T. Shi, and F. Forsberg, “Material characterization of the encapsulation of an ultrasound contrast microbubble and its subharmonic response: Strain-softening interfacial elasticity model,” The Journal of the Acoustical Society of America 127(6), 3864–3857 (2010).

15. V. Garbin, D. Cojoc, E. Ferrari, E. Di Fabrizio, M. L. J. Overvelde, S. M. van der Meer, N. de Jong, D. Lohse, and M. Versluis, “Changes in microbubble dynamics near a boundary revealed by combined optical micromanipulation and high-speed imaging,” Applied Physics Letters 90(11), 114103 (2007).

16. J. E. Chomas, P. A. Dayton, D. May, J. Allen, A. Klibanov, and K. Ferrara, “Optical observation of contrast agent destruction,” Applied Physics Letters 77(7), 1056 (2000).

17. F. Urgiles, J. Perchoux, and T. Bosch, “Characterization of Acoustic Sources by Optical Feedback Interferometry,” Proceedings 1(4), 348 (2017).

18. M. J. Hsu, M. Eghtedari, A. P. Goodwin, D. J. Hall, R. F. Mattrey, and S. C. Esener, “Characterization of individual ultrasound microbubble dynamics with a light-scattering system,” Journal of Biomedical Optics 16(6), 067002 (2011).

19. J. F. Guan, T. J. Matula, “Using light scattering to measure the response of individual ultrasound contrast microbubbles subjected to pulsed ultrasound in vitro,” The Journal of the Acoustical Society of America 116(5), 2832–2842 (2004).

20. E. I. Galanzha, V. P. Zharov, “Photoacoustic flow cytometry,” Methods 55(3), 280–296, (2012).

21. M. A. Juratli, Y. A. Menyaev, M. Sarimollaoglu, A. V. Melerzanov, D. A. Nedosekin, W. C. Culp, J. Y. Suen, E. I. Galanzha, and V. P. Zharov, “Noninvasive label-free detection of circulating white and red blood clots in deep vessels with a focused photoacoustic probe,” Biomedical Optics Express 9(11), 5667–5677 (2018).

22. D. Andrews, “Modelling of Ultrasonic Transducers and Ultrasonic Wave Propagation for Commercial Applications using Finite Elements with Experimental Visualization of Waves for Validation,” Proceedings of the 2014 COMSOL Conference in Cambridge (2014).

23. E. I. Galanzha, M. G. Viegas, T. I. Malinsky, A. V. Melerzanov, M. A. Juratli, M. Sarimollaoglu, D. A. Nedosekin, and V. P. Zharov, “In vivo acoustic and photoacoustic focusing of circulating cells,” Scientific Reports 6(1), 1–15 (2016).

24. M. A. Juratli, Y. A. Menyaev, M. Sarimollaoglu, E. R. Siegel, D. A. Nedosekin, J. Y. Suen, A. V. Melerzanov, T. A. Juratli, E. I. Galanzha, and V. P. Zharov, “Real-Time Label-Free Embolus Detection Using In Vivo Photoacoustic Flow Cytometry,” PLOS One 11(5), e0156269 (2016).

25. L. C. Cabrelli, P. I. B. G. B. Pelissari, A. M. Deana, A. A. O. Carneiro, and T. Z. Pavan, “Stable phantom materials for ultrasound and optical imaging,” Physics in Medicine and Biology 62(2), 432–447 (2017).

26. M. Kerker, The scattering of light and other electromagnetic radiation, Academic press, New York (1969).

27. F. M. Kahnert, “Numerical methods in electromagnetic scattering theory,” Journal of Quantitative Spectroscopy and Radiative Transfer 79–80, 775–824 (2003).

28. T. Wriedt, “A Review of Elastic Light Scattering Theories,” Particle & Particle Systems Characterization 15(2), 67–74 (1998).

29. V. Myroshnychenko, J. Rodríguez-Fernández, I. Pastoriza-Santos, A. M. Funston, C. Novo, P. Mulvaney, L. M. Liz-Marzán, and F. J. G. de Abajo, “Modelling the optical response of gold nanoparticles,” Chemical Society Reviews 37(9), 1792–1805 (2008).

30. M. R. Rashidian Vaziri, A. Omidvar, B. Jaleh, and N. Partovi Shabestari, “Investigating the extrinsic size effect of palladium and gold spherical nanoparticles,” Optical Materials 64, 413–420 (2017).

31. D. L. Kingsbury, P. L. Marston, “Mie scattering near the critical angle of bubbles in water,” Journal of the Optical Society of America 71(3), 358 (1981).

32. M. A. Blizard, “Scattering Of Light By A Coated Bubble In Water Near The Critical And Brewster Scattering Angles,” Proceeding of SPIE 925, 308 (1988).

33. L. Shi, L. A. Sordillo, A. Rodríguez-Contreras, and R. Alfano, “Transmission in near-infrared optical windows for deep brain imaging,” Journal of Biophotonics 9(1–2), 38–43 (2016).

34. L. Hoff, P. C. Sontum, and J. M. Hovem, “Oscillations of polymeric microbubbles: Effect of the encapsulating shell,” The Journal of the Acoustical Society of America 107(4), 2272–2280 (2000).

35. D. Chatterjee, K. Sarkar, “A Newtonian rheological model for the interface of microbubble contrast agents,” Ultrasound in Medicine & Biology 29(12), 1749–1757 (2003).

36. H. Assadi, R. Karshafian, and A. Douplik, “Optical scattering properties of intralipid phantom in presence of encapsulated microbubbles,” International Journal of Photoenergy 2014, 1–9 (2014).

37. J. Herbert, K. Bertling, T. Taimre, A. D. Rakić, and S. Wilson, “Microparticle discrimination using laser feedback interferometry,” Optics Express 26(20), 25778 (2018).

38. J. Chen, K. S. Hunter, and R. Shandas, “Wave scattering from encapsulated microbubbles subject to high-frequency ultrasound: Contribution of higher-order scattering modes,” The Journal of the Acoustical Society of America 126(4), 1766 (2009).

39. P. Marmottant, S. van der Meer, M. Emmer, M. Versluis, N. de Jong, and S. Hilgenfeldt, D. Lohse, “A model for large amplitude oscillations of coated bubbles accounting for buckling and rupture,” The Journal of the Acoustical Society of America 118(6), 3499–3505 (2005).

40. G. L. Chahine, C.-T. Hsiao, “Modeling Microbubble Dynamics In Biomedical Applications,” Journal of Hydrodynamics 24(2), 169–183 (2012).

41. J. M. Hyvelin, E. Gaud, M. Costa, A. Helbert, P. Bussat, T. Bettinger, and P. Frinking, “Characteristics and Echogenicity of Clinical Ultrasound Contrast Agents: An in Vitro and in Vivo Comparison Study,” Journal of Ultrasound in Medicine 36(5), 941–953 (2017).

42. G. L. Chahine, “Interaction Between an Oscillating Bubble and a Free Surface,” Journal of Fluids Engineering 99(4), 709–716 (1977).

43. A. N. Bashkatov, E. A. Genina, V. I. Kochubey, and V. V. Tuchin, “Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm,” Journal of Physics D: Applied Physics 38(15), 2543–2555 (2005).

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