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Tracking Magnetic Particles Under Ultrasound Imaging Using Contrast-Enhancing Microbubbles

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Electromagnetic Actuation and Sensing in Medical Robotics

Part of the book series: Series in BioEngineering ((SERBIOENG))

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Abstract

In this chapter, motion of magnetic particles were captured using ultrasound imaging with contrast-enhanced microbubbles. Ultrasound videos were captured and analyzed by the created tracking algorithm to determine the efficiency and accuracy of the algorithm. It is necessary to ensure an efficient and accurate tracking method of the particles in order to evaluate future in vitro or in vivo applications of the microbubbles, when implanted into an enclosed system and imaged using ultrasound. First, it was found that the porous structure of the magnetic microbubbles could be successfully fabricated based on a gas foaming technique, using alginate (low viscosity, 2% (w/v)) as the polymer, mixed homogeneously with sodium carbonate (4%) solution. The reaction between sodium bicarbonate and hydrogen peroxide (32 wt %) in the collecting solution allowed the creation of encapsulated microbubbles. The alginate went under crosslinking in the collecting calcium chloride (25% w/v) solution. Second, it was proven that the encapsulated microbubbles enhanced the resultant ultrasound images, with the air bubbles appearing as bright white spots. In contrast, the solid spheres appeared dull and at times could not be seen under ultrasound. The contrast enhancing properties of the microbubbles allowed the microbubbles to be detected by the tracking algorithm, as compared to the solid spheres which could not be detected at all. Third, ground truth of the (x, y) coordinates of the microbubble centroids were determined using manual selection by the user mouse. Based on the accuracy analysis done, the accuracy of the tracking algorithm was 3.33 pixels, or 0.0354 cm, between the algorithm detected and the manually selected (x, y) coordinates of the centroids. Also, the optimal number of particles to be tracked was up to five particles with an accuracy studies.

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References

  1. Cosgrove, D. 2006. Ultrasound contrast agents: an overview. European Journal of Radiology 3: 324–330.

    Article  Google Scholar 

  2. Sirsi, S., and M. Borden. 2009. Microbubble compositions, properties and biomedical applications. Bubble Science Engineering and Technology 1–2: 3–17.

    Article  Google Scholar 

  3. Qin, S., C.F. Caskey, and K.W. Ferrara. 2009. Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering. Physics in Medicine and Biology 6: R27–R57.

    Article  Google Scholar 

  4. Cootney, R.W. 2001. Ultrasound Imaging: Principles and applications in rodent research. Institute for Laboratory Animal Research Journal.

    Google Scholar 

  5. Yang, F., Y. Li, Z. Chen, Y. Zhang, J. Wu, and N. Gu. 2009. Superparamagnetic iron oxide nanoparticle-embedded encapsulated microbubbles as dual contrast agents of magnetic resonance and ultrasound imaging. Biomaterials 23–24: 3882–3890.

    Article  Google Scholar 

  6. Stride, E., K. Pancholi, M.J. Edirisinghe, and S. Samarasinghe. 2008. Increasing the nonlinear character of microbubble oscillations at low acoustic pressures. Journal of the Royal Society, Interface/the Royal Society 24: 807–811.

    Article  Google Scholar 

  7. Harvey, C.J., J.M. Pilcher, R.J. Eckersley, M.J. Blomley, and D.O. Cosgrove. 2002. Advances in ultrasound. Clinical Radiology 3: 157–177.

    Article  Google Scholar 

  8. Heath, K., and P. Dayton. 2013. Current status and prospects for microbubbles in ultrasound theranostics. Nanomedicine and Nanobiotechnology.

    Google Scholar 

  9. Hernot, S., and A.L. Klibanov. 2008. Microbubbles in ultrasound-triggered drug and gene delivery. Advanced Drug Delivery Reviews 60 (10): 1153–1166.

    Article  Google Scholar 

  10. Wei, K., D.M. Skyba, C. Firschke, A.R. Jayaweera, J.R. Lindner, and S. Kaul. 1997. Interactions between microbubbles and ultrasound: in vitro and in vivo observations. Journal of the American College of Cardiology 5: 1081–1088.

    Article  Google Scholar 

  11. Perera, R.H., C. Hernandez, H. Zhou, P. Kota, A. Burke, and A.A. Exner. 2015. Ultrasound imaging beyond the vasculature with new generation contrast agents. Wiley Interdisciplinary reviews: Nanomedicine and Nanobiotechnology.

    Google Scholar 

  12. Keravnou, C., C. Mannaris, and M. Averkiou. 2015. Accurate measurement of microbubble response to ultrasound with a diagnostic ultrasound scanner. IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 1: 176–184.

    Article  Google Scholar 

  13. Unger, E.C., E. Hersh, M. Vannan, and T. McCreery. Gene delivery using ultrasound contrast agents. Echocardiography.

    Google Scholar 

  14. Stride, E., C. Porter, A.G. Prieto, and Q. Pankhurst. 2009. Enhancement of microbubble mediated gene delivery by simultaneous exposure to ultrasonic and magnetic fields. Ultrasound in Medicine and Biology 5: 861–868.

    Article  Google Scholar 

  15. Phillips, P.J. 2001. Contrast pulse sequences (CPS): Imaging nonlinear microbubbles. In 2001 Ultrasonics symposium, Atlanta, GA.

    Google Scholar 

  16. Zhang, F., C. Lanning, L. Mazzaro, A.J. Barker, P.E. Gates, W.D. Strain, J. Fulford, O.E. Gosling, A.C. Shore, N.G. Bellenger, B. Rech, J. Chen, J. Chen, and R. Shandas. 2011. In vitro and preliminary in vivo validation of echo particle image velocimetry in carotid vascular imaging. Ultrasound in Medicine and Biology 3: 450–464.

    Article  Google Scholar 

  17. Westerdale, J., M. Belohlavek, E.M. McMahon, P. Jiamsripong, J.J. Heys, and M. Milano. 2011. Flow velocity vector fields by ultrasound particle imaging velocimetry: in vitro comparison with optical flow velocimetry. Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine 2: 187–195.

    Article  Google Scholar 

  18. Zhang, Y., X. Wang, and B. Qu. 2012. Three-frame difference algorithm research based on mathematical morphology. Procedia Engineering.

    Google Scholar 

  19. Chenouard, N., I. Smal, F. de Chaumont, M. Maška, I.F. Sbalzarini, Y. Gong, J. Cardinale, C. Carthel, S. Coraluppi, M. Winter, A.R. Cohen, W.J. Godinez, K. Rohr, Y. Kalaidzidis, L. Liang, J. Duncan, H. Shen, Y. Xu, K.E. Magnusson, J. Jaldén, H.M. Blau, P. Paul-Gilloteaux, P. Roudot, C. Kervrann, F. Waharte, J.Y. Tinevez, S.L. Shorte, J. Willemse, K. Celler, G.P. van Wezel, H.W. Dan, Y.S. Tsai, C. Ortiz de Solórzano, J.C. Olivo-Marin, and E. Meijering. 2014. Objective comparison of particle tracking methods. Nature methods 3, 281–289.

    Google Scholar 

  20. Stauffer, C., and W.E.L. Grimson. 1999. Adaptive background mixture models for real-time tracking. Computer Vision and Pattern Recognition.

    Google Scholar 

  21. Sun, D., S. Roth, J.P. Lewis, and M.J. Black. 2008. Learning optical flow. Computer vision—ECCV 2008. Lecture Notes in Computer Science 5304: 83–97.

    Article  Google Scholar 

  22. Prabhakar, N., V. Vaithiyanathan, A.P. Sharma, A. Singh, and P. Singha. 2012. Object tracking using frame differencing and template. Research Journal of Applied Sciences, Engineering and Technology.

    Google Scholar 

  23. Cai, X., F. Yang, and N. Gu. 2012. Applications of magnetic microbubbles for theranostics. Theranostics 2 (1): 103–112.

    Article  Google Scholar 

  24. Dharmakumar, R., D.B. Plewes, and G.A. Wright. 2005. A novel microbubble construct for intracardiac or intravascular MR manometry: A theoretical study. Physics in Medicine and Biology 20: 4745–4762.

    Article  Google Scholar 

  25. Soetanto, K., and H. Watarai. 2000. Development of magnetic microbubbles for drug delivery system (DDS). Japanese Journal of Applied Physics 39: 3230–3232.

    Article  Google Scholar 

  26. Park, J.I., D. Jagadeesan, R. Williams, W. Oakden, S. Chung, G.J. Stanisz, and E. Kumacheva. 2010. Microbubbles loaded with nanoparticles: a route to multiple imaging modalities. ACS Nano 11: 6579–6586.

    Article  Google Scholar 

  27. Bae, S.E., J.S. Son, K. Park, and D.K. Han. 2008. Fabrication of covered porous PLGA microspheres using hydrogen peroxide for controlled drug delivery and regenerative medicine. Journal of Controlled Release: Official Journal of the Controlled Release Society 1: 37–43.

    Google Scholar 

  28. Wang, X.L., X. Li, E. Stride, J. Huang, M. Edirisinghe, C. Schroeder, S. Best, R. Cameron, D. Waller, and A. Donald. 2010. Novel preparation and characterization of porous alginate films. Carbohydrate Polymers 79: 989–997.

    Article  Google Scholar 

  29. Chevalier, E., D. Chulia, C. Pouget, and M. Viana. 2008. Fabrication of porous substrates: a review of processes using pore forming agents in the biomaterial field. Journal of Pharmaceutical Sciences 3: 1135–1154.

    Article  Google Scholar 

  30. Cui, W., J. Bei, S. Wang, G. Zhi, Y. Zhao, X. Zhou, H. Zhang, and Y. Xu. 2005. Preparation and evaluation of poly (L-lactide-co-glycolide) (PLGA) microbubbles as a contrast agent for myocardial contrast echocardiography. Journal of biomedical materials research. Part B, Applied biomaterials 1: 171–178.

    Article  Google Scholar 

  31. Zhang, H., X.J. Ju, R. Xie, C.J. Cheng, P.W. Ren, and L.Y. Chu. 2009. A microfluidic approach to fabricate monodisperse hollow or porous poly (HEMA-MMA) microspheres using single emulsions as templates. Journal of Colloid and Interface Science 1: 235–243.

    Article  Google Scholar 

  32. Butler, R., C.M. Davies, and A.I. Cooper. 2001. Emulsion templating using high internal phase supercritical fluid emulsions. Advanced Materials 13: 1459–1463.

    Article  Google Scholar 

  33. Yang, S., K.F. Leong, Z. Du, and C.K. Chua. 2002. The design of scaffolds for use in tissue engineering. Tissue Engineering Part II: Rapid Prototyping Techniques 1: 1–11.

    Google Scholar 

  34. Tsang, V.L., and S.N. Bhatia. 2004. Three-dimensional tissue fabrication. Advanced Drug Delivery Reviews 11: 1635–1647.

    Article  Google Scholar 

  35. Stride, E., and M. Edirisinghe. 2009. Novel preparation techniques for controlling microbubble uniformity: a comparison. Medical and Biological Engineering and Computing 8: 883–892.

    Article  Google Scholar 

  36. Liu, Z., T. Lammers, J. Ehling, S. Fokong, J. Bornemann, F. Kiessling, and J. Gätjens. 2011. Iron oxide nanoparticle-containing microbubble composites as contrast agents for MR and ultrasound dual-modality imaging. Biomaterials 26: 6155–6163.

    Article  Google Scholar 

  37. Gurruchaga, H., L. Saenz Del Burgo, J. Ciriza, G. Orive, R.M. Hernández, and J.L. Pedraz. 2015. Advances in cell encapsulation technology and its application in drug delivery. Expert Opinion on Drug Delivery 1–17.

    Google Scholar 

  38. Pareta, R., and M.J. Edirisinghe. 2006. A novel method for the preparation of biodegradable microspheres for protein drug delivery. Journal of the Royal Society, Interface 3 (9): 573–582.

    Article  Google Scholar 

  39. Huang, K.S., Y.S. Lin, W.R. Chang, Y.L. Wang, and C.H. Yang. 2013. A facile fabrication of alginate microbubbles using a gas foaming reaction. Molecules 18 (8): 9594–9602.

    Article  Google Scholar 

  40. Ultrasonix Transducer Guide. 2015.

    Google Scholar 

  41. Ihnatsenka, B., and A.P. Boezaar. 2010. Ultrasound: Basic understanding and learning the language. International Journal of Shoulder Surgery.

    Google Scholar 

  42. Kwon, J.O., S.Y. Ji, B.C. Jeong, and K.C. Sang. 2013. A novel drug delivery method by using a microrobot incorporated with an acoustically oscillating bubble. In 2013 IEEE 26th International Conference Micro Electro Mechanical Systems (MEMS), Taipei.

    Google Scholar 

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Acknowledgements

The authors would like to thank the support from NUS teams in Dr H. Ren’s, Dr J. Li’s and Dr C. Yap’s lab.

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Appendices

Appendices

Appendix 1: Algorithm Results

Appendix 2: Comparison of Various Ultrasound Imaging Setups

Tested ultrasound imaging setups

1. Flow of microbubbles through rubber tubes

Movement of microbubbles induced through flow

Advantages

Disadvantages

(+) Setup mimics flow of microbubbles in vessel-like conditions

(–) Magnetic particles do not appear spherical

(–) Ultrasound intensity attenuated by rubber tube

2. Floating particles

Advantages

Disadvantages

(+) Particles appear spherical

(+) Movement is in both x and z direction

(–) Ultrasound attenuation at plastic-water interface

3. Magnetic Particles in Dish

Advantages

Disadvantages

(+) Movement of multiple magnetic spheres can be recorded

(–) Magnetic spheres do not appear as distinct particles with clustering of spheres

4. Small magnet used to control movement of magnetic spheres

Advantages

Disadvantages

(+) Easy control

(+) No attenuation from interface, direct observation

(–) Magnet interferes with ultrasound imaging

5. Large magnet planar magnet

Advantages

Disadvantages

(+) Direct observation of microbubbles without attenuation from interface

(+) Movement along x axis captured

(–) Magnetic field from magnet interferes with ultrasound probe

(–) Movement of particle in z direction is not captured

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Loh, K., Ren, H. (2018). Tracking Magnetic Particles Under Ultrasound Imaging Using Contrast-Enhancing Microbubbles. In: Ren, H., Sun, J. (eds) Electromagnetic Actuation and Sensing in Medical Robotics. Series in BioEngineering. Springer, Singapore. https://doi.org/10.1007/978-981-10-6035-9_8

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  • DOI: https://doi.org/10.1007/978-981-10-6035-9_8

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  • Online ISBN: 978-981-10-6035-9

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