Page 30 - Volume 8, Issue 4 - Winter 2012

Michigan,10-12 while the boiling-based method was discovered
13-15
The mechanisms of generating bubbles through each mode are quite different, but surprisingly, both techniques produce
a few years ago at the University of Washington.
similar lesions through tissue disintegration.
Histotripsy could be employed as a noninvasive treat-
ment for many diseases, such as malignant tumors, benign prostatic hyperplasia (BPH), deep vein thrombosis, and congenital heart defects. The unique ability of histotripsy to actually liquefy the tissue (rather than just thermally destroying it) means that the lesion content can be passed out of natural body orifices or easily reabsorbed by sur- rounding tissue. For instance, excess prostate tissue for BPH can be passed through the urinary system, offering imme- diate decompression and relief of symptoms. Thus far, both cavitation and boiling techniques have been demonstrated
16-18
tissue disintegration.
Background
The majority of HIFU sources (including those for his- totripsy) are piezoelectric, made from ceramics such as lead- zirconate-titanate (PZT) or composites of PZT with passive materials. High-voltage periodic signals are applied to the piezoelectric element by a radiofrequency amplifier to gener- ate ultrasound vibration of the transducer surface. Focusing is accomplished by several techniques. One method is to sim- ply form the piezoelectric material to the shape of a spherical bowl with a natural focal point at its radius of curvature (Fig. 3). An alternative to this approach is to couple an acoustic lens to a flat source, which creates similar focusing without the need to precisely form the piezoelectric material. Finally, focusing can be achieved electronically using array transduc-
This article discusses the acoustics of both types of histotripsy – including the processes of gener- ation and focusing of intense ultrasound, the formation of cavitation clouds and rapid boiling in tissue, and the inter- actions of ultrasound shock waves with bubbles leading to
in animal studies.
ers with multiple distinct elements. The phase of the output between different elements is controlled to create construc- tive interference at a desired focal point. The advantage of this last technique is that the focus can be electronically steered to different locations without physically changing the position of the device. Ultrasound imaging probes that typi- cally comprise lensing and array focusing are often combined with HIFU transducers to create high-resolution images of the treatment site and provide treatment feedback to the operator.
Sources used for histotripsy studies are highly focused
having similar apertures and radii of curvature ranging
from about 5 to 15 cm. The sources operate at high power
outputs to provide intensity levels at the focus from 10 to
2
>30 kW/cm . Although initially sinusoidal waves are irradi-
ated from the transducer, they become distorted while propagating to the focus due to combined nonlinear and diffraction effects.
The sound speed of high amplitude acoustic waves depends on the local pressure causing nonlinear propagation effects. The speed of sound is increased under compressive pressure and decreased for rarefactive pressure in compari- son with the ambient sound speed, c0, which leads to distor- tions of acoustic waveform. These nonlinear distortions accumulate over the propagation distance as a gradual steep- ing of the wave front and finally result in formation of shocks. For an initially harmonic wave, the shock formation distance xsh is xsh = c30r0/(2pp0f0b), where r0 is the density, p0 is acoustic pressure amplitude, f0 is the ultrasound frequency, and b is the nonlinear parameter of the propagation medium. For example, the shock formation distance in water for an ultrasound wave of 2 MHz frequency and 15 MPa pressure amplitude (8 kW/cm2) is 5 mm. High amplitude focal regions of HIFU transducers are typically longer than this distance and focal intensities even higher than 30 kW/cm2 have been reported, therefore formation of shocks is typical for his- totripsy and very probable in some other clinical HIFU situ- ations. In addition, the waveform achieves a strong posi- tive/negative pressure asymmetry caused by a different dif- fraction phase shift between harmonics of the fundamental frequency generated in the beam, leading to high shock
10,19
periodic schemes of irradiation (Fig. 4). However, in cavita-
tion-based histotripsy, the operational frequency is relative-
ly low (typically from 0.75 MHz to 1 MHz), the pulses are
short (3-20 cycles) and delivered often (10 Hz – 1 kHz). In
this regime, each pulse excites a cloud of cavitation
microbubbles to expand and collapse in response to the
acoustic pressure. Usually, a focal volume is treated with 103
4 10
- 10 pulses for complete ablation. Focal peak pressures are
approximately p = 15 – 25 MPa, and p > 80 MPa. In boil- -+
ing histotripsy, the frequency is higher (1 - 3 MHz), the
pulses are much longer (3000-10000 cycles) and delivered
less often (0.5 – 1 Hz) (Fig. 4b). The peak pressures are
lower,aboutp =10–15MPaandp >40MPa.Inthis -+
regime, boiling is initiated within each millisecond-long pulse due to effective tissue heating by shocks. Interaction
amplitudes (Fig. 4).
Both cavitation and boiling histotripsy employ pulse-
Fig. 3. A spherically-focused piezocomposite HIFU transducer of 0.75 MHz fre- quency, with a 15-cm diameter and 12-cm radius of curvature used for cavitation- cloud histotripsy. An imaging probe is positioned in its central hole to visualize the focal region, providing valuable feedback for targeting and monitoring the treat- ment progress. Visualization is based on high echogenicity of cavitation bubbles that are strong scatters of ultrasound.
26 Acoustics Today, October 2012