Page 37 - Volume 8, Issue 4 - Winter 2012

shocks develop in a small volume within focal region of a HIFU beam and rapidly heat this volume to boiling tem- peratures. A boiling bubble is initiated in milliseconds and grows to a millimeter size. Shock waves interact with the vapor cavity generating atomization and an acoustic foun- tain from the tissue interface into the cavity. The experi- mental illustration mimicking the histotripsy process in the vapor cavity is presented on the right of the Fig. 12. A frame of high speed photography shows atomization and fountain production at the free tissue/air interface generated by focusing an ultrasound beam at the surface of ex-vivo bovine liver. Atomization and acoustic fountain production were therefore proposed as a mechanism of mechanical tis- sue damage: a large cavity is formed in tissue due to shock heating and boiling in milliseconds, and then interaction of shock waves with the tissue/cavity interface fragments the tissue.
Summary
High intensity focused ultrasound has been previously applied to ablate tissue noninvasively through absorption- induced heating. However, at very high focal pressure amplitudes, strong nonlinear effects manifest such as shock formation, cavitation, and rapid boiling resulting in mechanical effects. At their extreme, these phenomena can be applied to completely disintegrate tissue structures, i.e., to produce histotripsy. Both histotripsy technologies overviewed in this article may hold advantages over thermal therapy. While the dose must be tightly regulated in thermal therapy to control heat diffusion and collateral tissue dam- age, blood vessels can transfer heat away from the treatment site by convection, causing distortion of a thermal lesion. Cavitation clouds and shock-induced boiling are inherently self-limited to the focal volume by the processes described above. Because heat diffusion is not an essential component of histotripsy, the modalities described above may provide a much more compelling argument for the wider clinical acceptance of noninvasive, focused-ultrasound therapy. In addition, bubbles and tissue breakdown can also be visual- ized on ultrasound imaging as targeting feedback for the surgeon, while acoustic detection of heating is very diffi- cult. Finally, the ability to actually disintegrate tissue rather than just causing necrosis may aid reabsorption into the body and allows new clinical applications which cannot be accomplished with thermal HIFU.
It may be surprising that the same effect can be achieved by two completely separate paths, using different acoustic pulsing schemes. However, both of these schemes utilize relatively large cavities (0.1 – 1 mm) created in the tissue to achieve the effect, generated in different ways. It may be stress induced by expansion and collapse of the bub- bles or atomization that fractionate tissue. In reality, it is likely that each mechanism contributes in some degree to both cavitation and boiling histotripsy. Regardless, it is clear that nonlinear acoustic propagation and shock waves play a critical role in both the creation of the cavitation cloud and the vapor cavities of millisecond boiling, as well as provid- ing mechanisms of ultrasound interaction between tissue
and bubbles. These studies reflect the importance of acoustic principles in understanding and predicting the interactions that drive this new medical technology.
Acknowledgments
The authors greatly acknowledge support from the National Institutes of Health (NIH) under grants RO1 EB007643 (V. Khokhlova), R01 EB008998 (Z. Xu), and the T32 Multidisciplinary Training Program in Benign Urology at the University of Washington (A. Maxwell). The authors would like to thank Tzu-Yin Wang, Timothy Hall, William Roberts and many others from the Therapeutic Ultrasound Group at the University of Michigan who have contributed to development of cavitation-based histotripsy. We also thank Michael Canney, Tatiana Khokhlova, Julianna Simon, Wayne Kreider, Joo Ha Hwang, and Yak-Nam Wang who greatly contributed to developing boiling histotripsy tech- nology at the University of Washington over the last several years.AT
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