Page 34 - Volume 8, Issue 4 - Winter 2012

Fig. 8. (Left) Gross morphology of a histotripsy lesion created in myocardial tissue. The disintegrated liquid has been removed, creating a hole. (Adapted from part of a figure in reference 10) (Right) A microscopic view of intact cells from a section of liver in the lower left, and treated tissue in the upper right. The homogenized tissue is almost completely lacking structure, while less than a cell-length away, the tissue appears normal. The lack of structure in the homogenized region leads to a dark region on an ultrasound image because there are no signif- icant scatterers remaining in this region. The hypoechogenicity is used as an indicator for treatment progression in histotripsy.
in phase—the characteristics of the focused shock—which causes the large tension upon reflection from its surface. Furthermore, the scattered shock constructively interferes with the incident trailing negative pressure to create a region where the tension is greatest. This process is akin to the “spallation” mechanism discussed in lithotripsy. The pattern of cavitation observed after scattering from the single bubble can be predict- ed based on the region where p- is greatest over a cycle (Fig. 7).
Histotripsy lesions
The shock scattering process describes what happens during a single pulse to initiate the cloud for cavitation- based histotripsy. Generally speaking, ~103 - 104 pulses must be applied following this event to mechanically ablate the focal volume of tissue. Provided another pulse is applied quickly enough after the initiation of the cloud, the bubble nuclei which make up the cloud can be repeatedly expand- ed and collapsed. If the pulses are not applied often enough, the cloud nuclei will dissolve back into the medium, and another cloud must be formed through the shock-scattering process. This temporary susceptibility of the medium to be repeatedly cavitated is referred to as “cavitation memory.”29 Cavitation memory is also a prime explanation for why lithotripters operate more efficiently when pulses are applied at slow rates rather than fast rates—this gives the bubbles which would shield acoustic propagation of the shockwave time to dissolve between the pulses.
The outcome of repeatedly expanding and collapsing the cavitation cloud using microsecond-long shock pulses is a complete homogenization of the tissue structure into an acel- lular liquid with a sharp transition zone between completely intact or completely destroyed tissue (Fig. 8). The size of the debris remaining within the region where the cavitation cloud is generated is found to be very small, with about 97%
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result in damage to surrounding tissue through heat diffusion.
Boiling histotripsy
Shock wave heating
Nonlinear waveform distortion of an initially harmonic wave corresponds to generation of higher harmonics that are more readily absorbed and generate more heat. Thermoviscous absorption in water is weak but grows quadratical- ly with frequency. In tissue, additional stronger absorption is caused by mul- tirelaxation processes following a near- ly linear frequency power law. Once shocks that contain very high frequen- cies develop, heating effects increase
31,14
Heat deposition in tis- sue caused by absorption of a plane harmonic wave (Hlin) is proportional to the wave intensity I, i.e., to the pressure amplitude p squared: Hlin = 2aI, where I = p2 / (2c0r0) and a is the absorption coefficient in tissue at the ultrasound fre- quency. On the contrary, absorption at the shocks (Hshock) is
dramatically.
of the volume consisting of fragments subcellular in size. Because the cavitation cloud is spatially confined to the focal volume, this is the only region which is ablated. This feature is a distinct advantage of histotripsy as a therapy—there is no apparent risk of applying too great of a dose to the tissue. In contrast, applying too great of a dose in thermal therapy can
Fig. 9. Comparison of tissue heating using harmonic waves (Hlin) or shock waves (Hshock) of the same intensity I and frequency. (Top) Heat deposition caused by absorption of harmonic waves is proportional to their intensity (red), i.e., pressure amplitude squared, while energy absorption of shock waves is proportional to the shock amplitude cubed (blue). (Bottom) The difference in efficiency of heating increases at larger intensities and can be more than an order of magnitude higher for shock waves as compared to harmonic waves of the same intensity.
30 Acoustics Today, October 2012