Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jpNishida et al demonstrated the potential of SWT as a treatment for IHD; in a porcine model of chronic IHD, SWT improved ejection fraction, wall thickening, myocardial blood flow and capillary density compared with sham therapy. 5 Similar results were demonstrated in porcine models of acute myocardial infarction 6 and ischemia-reperfusion injury. 7 Human studies soon followed, with Fukumoto et al first describing decreased angina and nitroglycerine use, and improved nuclear myocardial perfusion among patients with IHD who underwent SWT 3 times a week for 3 weeks. 8 Following small randomized, double-blinded trials, 9-11 clinical use of SWT for IHD has spread through Japan, Israel, and parts of Europe, where it received CE Mark approval in 2010. 12 However, clinical use has yet to spread globally, potentially due to the small subject size and efficacy of clinical trials.Unlike SWT, therapeutic ultrasound (TUS) is an acoustic technique in which multiple cycles of a single-frequency (usually 1-10 MHz) sinusoidal ultrasound wave are transmitted from an extracorporeal-focused source into the tissue of interest ( Figure 1B). The frequency, amplitude and duration of the lobal burdens of ischemic heart disease (IHD) and peripheral arterial disease (PAD) have been increasing. 1 IHD leads to approximately 7.2 million deaths per year, 2 and PAD affects over 200 million patients globally. 3 While modern revascularization methods such as bypass graft surgery and percutaneous interventions have decreased morbidity and mortality associated with these diseases, these treatments remain limited by small vessel disease and the risks of reoperation. 4 Thus, there is a strong need for novel, noninvasive and effective therapies for the promotion of angiogenesis for the treatment of these diseases. Editorial p 1906Extracorporeal shock wave therapy (SWT) is an acoustic treatment modality that sends individual acoustic shock waves in a beam focused onto the area of interest. Each shock wave consists of an approximately 1 μs-long, positive (compressional) pulse followed by a longer (~5 μs), lower amplitude negative (rarefactional) pressure pulse ( Figure 1A). In a landmark study, Therapeutic Ultrasound Promotes Reperfusion and Angiogenesis in a Rat Model of Peripheral Arterial DiseaseBabak Nazer, MD; Farzin Ghahghaie, MD; Risa Kashima, PhD; Tatiana Khokhlova, PhD; Camilo Perez, BSc; Lawrence Crum, PhD; Tom Matula, PhD; Akiko Hata, PhDBackground: Shock wave therapy (SWT) is an acoustic technology clinically used for the non-invasive treatment of ischemic heart disease (IHD). Therapeutic ultrasound (TUS) has more recently been developed for the same indication, although its effects on reperfusion and angiogenesis have yet to be directly compared to those of SWT.

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Characterizing ultrasound contrast agents (UCAs) involve measuring the size and population distribution. However, these instruments do not allow for characterization of shell properties, which are important for (1) stability to administration and circulation throughout the vasculature; (2) UCA response to ultrasound; and (3) conjugating ligands for molecular imaging. Thus it is critical to understand the physical and rheological properties of shells. We previously developed a light scattering technique to characterize the shell properties of UCAs [Guan and Matula, JASA, Vol 116(5), 2004; Tu, et al., IEEE Trans. Ultrason., Ferroelec., and Freq. Control, vol. 58(5), 2011]. The most recent manifestation involves a flow cytometer modified with a custom square quartz flow cell in place of the standard nozzle and fluid jet. Acoustic coupling to the carrier sheath fluid and UCA samples occurred through a PZT bonded to one side of the flow cell. The PZT-driven UCA oscillations were processed and fitted to the Marmottant UCA model. Shell properties for UCAs (including Definity, Optison, SonoVue, and even homemade bubbles) were determined. The focus of this talk will be on pressure calibration and additional measurements of unpublished data from Optison and homemade bubbles. (Funded in part by the Life Sciences Discovery Fund #3292512)

Abscesses are infected walled-off collections of pus and bacteria. They can affect any part of the body. Current treatment is typically limited to antibiotics, catheter drainage and hospitalization, or surgical wash-out when inaccessible, loculated or unresponsive to initial care efforts. Although bacteria can develop drug resistance, they remain susceptible to thermal and mechanical damage. High Intensity Focused Ultrasound (HIFU) generates localized heating and cavitation, and represents a potential new noninvasive treatment modality. This talk describes initial experiments in which non-thermal HIFU treatment was used to inactivate small volumes (100 μL—10 mL) of Escherichia colisuspensions (~1 × 109 cells/mL) with 1 or 2-MHz transducers. Free-field focal acoustic pressures were as high as 16 (9.9) MPa peak positive (negative). Survival was assessed by coliform counting, and by alamarBlue® vital staining. At duty factors of 0.01 or 0.2, and the highest acoustic pressures, there was no biologically significant heating of the exposed samples. Inactivation was treatment time-dependent, and was well described by a half-life model. There was a well-defined (free field-equivalent) acoustic pressure threshold, with significant cell inactivation above ~7 MPa peak negative pressure.

In the 1980s shockwave lithotripsy emerged as a revolutionary advancement for the treatment of kidney stones. Initial studies with patients showed SWL to be highly effective. The technology was elegant, outcomes exceptionally positive and early tests suggested treatment was safe. As experience with SWL grew, limitations surfaced. A key finding was that SWs have the potential to induce significant trauma to the kidney. Our group convinced the NIH it was time to conduct a rigorous assessment to characterize the adverse effects of SWL and determine the mechanisms of SW action in stone breakage and tissue injury. The NIH Program Project Grant mechanism mandated we establish a panel of external advisors to help guide our work. We needed expertise in physical acoustics, cavitation and animal models of ultrasound exposure. We wanted a leading expert. We were extremely fortunate to land Ed Carstensen. Ed worked with us for nearly 15 years, well into our third renewal cycle. He was a brilliant scientist, a man dedicated to the highest standards of conduct in research. Ed taught us a great deal, he inspired by example and had an exceptional influence on our work and on the greater field of lithotripsy research. [Work supported by NIH-DK43881.]