Therapeutic ultrasound: Recent trends and future perspectives

AbstractBefore ultrasound-imaging systems became widely available, ultrasound therapy devices showed great promise for general use in medicine. However, it is only in the last decade that ultrasound therapy has begun to obtain clinical acceptance. Recently, a variety of novel applications of therapeutic ultrasound have been developed that include sonothrombolysis, site-specific and ultrasound-mediated drug delivery, shock wave therapy, lithotripsy, tumor ablation, acoustic hemostasis and several others. This paper reviews a few selected applications of therapeutic ultrasound. It will address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. As a plenary presentation, its audience is intended for the ultrasound scientist or engineer, and thus is not presented at the level of the experienced medical ultrasound professional

The role of trapped bubbles in kidney stone detection with the color Doppler ultrasound twinkling artifact

The color Doppler ultrasound twinkling artifact, which highlights kidney stones with rapidly changing color, has the potential to improve stone detection; however, its inconsistent appearance has limited its clinical utility. Recently, it was proposed stable crevice bubbles on the kidney stone surface cause twinkling; however, the hypothesis is not fully accepted because the bubbles have not been directly observed. In this paper, the micron or submicron-sized bubbles predicted by the crevice bubble hypothesis are enlarged in kidney stones of five primary compositions by exposure to acoustic rarefaction pulses or hypobaric static pressures in order to simultaneously capture their appearance by high-speed photography and ultrasound imaging. On filming stones that twinkle, consecutive rarefaction pulses from a lithotripter caused some bubbles to reproducibly grow from specific locations on the stone surface, suggesting the presence of pre-existing crevice bubbles. Hyperbaric and hypobaric static pressures were found to modify the twinkling artifact; however, the simple expectation that hyperbaric exposures reduce and hypobaric pressures increase twinkling by shrinking and enlarging bubbles, respectively, largely held for rough-surfaced stones but was inadequate for smoother stones. Twinkling was found to increase or decrease in response to elevated static pressure on smooth stones, perhaps because of the compression of internal voids. These results support the crevice bubble hypothesis of twinkling and suggest the kidney stone crevices that give rise to the twinkling phenomenon may be internal as well as external

Cavitation clouds created by shock scattering from bubbles during histotripsy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98656/1/JAS001888.pd

Ultrasound Based Method and Apparatus for Stone Detection and to Facilitate Clearance Thereof

Described herein are methods and apparatus for detecting stones by ultrasound, in which the ultrasound reflections from a stone are preferentially selected and accentuated relative to the ultrasound reflections from blood or tissue. Also described herein are methods and apparatus for applying pushing ultrasound to in vivo stones or other objects, to facilitate the removal of such in vivo objects

Cavitation in shock wave lithotripsy: the critical role of bubble activity in stone breakage and kidney trauma

Objective: Shock Wave Lithotripsy (SWL) is the use of shock waves to fragment kidney stones. We have undertaken a study of the physical mechanisms responsible for stone comminution and tissue injury in SWL. SWL was originally developed on the premise that stone fragmentation could be induced by a short duration, high amplitude positive pressure pulse. Even though the SWL waveform carries a prominent tensile component, it has long been thought that SW damage to stones could be explained entirely on the basis of mechanisms such as spallation, pressure gradients, and compressive fracture. We contend that not only is cavitation also involved in SWL, bubble activity plays a critical role in stone breakage and is a key mechanism in tissue damage. Methods: Our evidence is based upon a series of experiments in which we have suppressed or minimized cavitation, and discovered that both stone comminution and tissue injury is similarly suppressed or minimized. Some examples of these experiments are (1) application of overpressure, (2) time reversal of acoustic waveform, (3) acoustically-transparent, cavitation-absorbing films, and (4) dual pulses. In addition, using passive and active ultrasound, we have observed the existence of cavitation, in vivo, and at the site of tissue injury. Results: Numerical and experimental results showed mitigation of bubble collapse intensity by time-reversing the lithotripsy pulse and in vivo treatment showed a corresponding drop from 6.1% ± 1.7% to 0.0% in the hemorrhagic lesion. The time-reversed wave did not break stones. Stone comminution and hemolysis were reduced to levels very near sham levels with the application of hydrostatic pressure greater than the near 10-MPa amplitude of the negative pressure of the lithotripter shock wave. A Mylar sheet 3-mm from the stone surface did not inhibit erosion and internal cracking, but a sheet in contact with the stone did. In water, mass lost from stones in a dual pulse lithotripter is 8 times greater than with a single lithotripter, but in glycerol, which reduces the pressures generated in bubble implosion, the enhancement is lost. Conclusion: This cavitation-inclusive mechanistic understanding of SWL is gaining acceptance and has had clinical impact. Treatment at slower SW rate gives cavitation bubble clusters time to dissolve between pulses and increases comminution. Some SWL centers now treat patients at slower SW rate to take advantage of this effect. An elegant cavitation-aware strategy to reduce renal trauma in SWL is being tested in experimental animals. Starting treatment at low amplitude causes vessels to constrict and this interferes with cavitation-mediated vascular injury. Acceptance of the role of cavitation in SWL is beginning to be embraced by the lithotripter industry, as new dual-pulse lithotripters—based on the concept of cavitation control— have now been introduced

Cavitation in shock wave lithotripsy: the critical role of bubble activity in stone breakage and kidney trauma

Objective: Shock Wave Lithotripsy (SWL) is the use of shock waves to fragment kidney stones. We have undertaken a study of the physical mechanisms responsible for stone comminution and tissue injury in SWL. SWL was originally developed on the premise that stone fragmentation could be induced by a short duration, high amplitude positive pressure pulse. Even though the SWL waveform carries a prominent tensile component, it has long been thought that SW damage to stones could be explained entirely on the basis of mechanisms such as spallation, pressure gradients, and compressive fracture. We contend that not only is cavitation also involved in SWL, bubble activity plays a critical role in stone breakage and is a key mechanism in tissue damage. Methods: Our evidence is based upon a series of experiments in which we have suppressed or minimized cavitation, and discovered that both stone comminution and tissue injury is similarly suppressed or minimized. Some examples of these experiments are (1) application of overpressure, (2) time reversal of acoustic waveform, (3) acoustically-transparent, cavitation-absorbing films, and (4) dual pulses. In addition, using passive and active ultrasound, we have observed the existence of cavitation, in vivo, and at the site of tissue injury. Results: Numerical and experimental results showed mitigation of bubble collapse intensity by time-reversing the lithotripsy pulse and in vivo treatment showed a corresponding drop from 6.1% ± 1.7% to 0.0% in the hemorrhagic lesion. The time-reversed wave did not break stones. Stone comminution and hemolysis were reduced to levels very near sham levels with the application of hydrostatic pressure greater than the near 10-MPa amplitude of the negative pressure of the lithotripter shock wave. A Mylar sheet 3-mm from the stone surface did not inhibit erosion and internal cracking, but a sheet in contact with the stone did. In water, mass lost from stones in a dual pulse lithotripter is 8 times greater than with a single lithotripter, but in glycerol, which reduces the pressures generated in bubble implosion, the enhancement is lost. Conclusion: This cavitation-inclusive mechanistic understanding of SWL is gaining acceptance and has had clinical impact. Treatment at slower SW rate gives cavitation bubble clusters time to dissolve between pulses and increases comminution. Some SWL centers now treat patients at slower SW rate to take advantage of this effect. An elegant cavitation-aware strategy to reduce renal trauma in SWL is being tested in experimental animals. Starting treatment at low amplitude causes vessels to constrict and this interferes with cavitation-mediated vascular injury. Acceptance of the role of cavitation in SWL is beginning to be embraced by the lithotripter industry, as new dual-pulse lithotripters—based on the concept of cavitation control— have now been introduced

Improving burst wave lithotripsy effectiveness for small stones and fragments by increasing frequency: theoretical modeling and ex vivo study

Introduction and Objective: In clinical trial NCT03873259, a 2.6-mm lower pole stone was treated transcutaneously and ex vivo with 390-kHz burst wave lithotripsy (BWL) for 40 minutes and failed to break. The stone was subsequently fragmented with 650-kHz BWL after a 4-minute exposure. This study investigated how to fragment small stones and why varying BWL frequency may more effectively fragment stones to dust. Methods: A linear elastic model was used to calculate the stress created inside stones from shock wave lithotripsy (SWL) and different BWL frequencies mimicking the stone’s size, shape, lamellar structure, and composition. To test model predictions about the impact of BWL frequency, matched pairs of stones (1-5 mm) were treated at 1) 390 kHz, 2) 830 kHz, and 3) 390 kHz followed by 830 kHz. The mass of fragments greater than 1 and 2 mm was measured over 10 minutes of exposure. Results: The linear elastic model predicts that the maximum principal stress inside a stone increases to more than 5.5 times the pressure applied by the ultrasound wave as frequency is increased, regardless of composition tested. The threshold frequency for stress amplification is proportionate to the wave speed divided by the stone diameter. Thus, smaller stones may be likely to fragment at higher frequency, but not lower frequency below a limit. Unlike with SWL, this amplification in BWL occurs consistently with spherical and irregularly shaped stones. In water tank experiments, stones smaller than the threshold size broke fastest at high frequency (p=0.0003), whereas larger stones broke equally well to sub-millimeter dust at high, low, or mixed frequency. Conclusions: For small stones and fragments, increasing frequency of BWL may produce amplified stress in the stone causing the stone to break. Using the strategies outlined here, stones of all sizes may be turned to dust efficiently with BWL

Standing waves for acoustic levitation

Standing waves are the most popular method to achieve acoustic trapping. Particles with greater acoustic impedance than the propagation medium will be trapped at the pressure nodes of a standing wave. Acoustic trapping can be used to hold particles of various materials and sizes, without the need of a close-loop controlling system. Acoustic levitation is a helpful and versatile tool for biomaterials and chemistry, with applications in spectroscopy and lab-on-a-droplet procedures. In this chapter, multiple methods are presented to simulate the acoustic field generated by one or multiple emitters. From the acoustic field, models such as the Gor'kov potential or the Flux Integral are applied to calculate the force exerted on the levitated particles. The position and angle of the acoustic emitters play a fundamental role, thus we analyse commonly used configurations such as emitter and reflector, two opposed emitters, or arrangements using phased arrays