Monitoring Of Cavitation Activity Research Articles

Focused Ultrasound and Lithotripsy.

Shock wave lithotripsy has generally been a first choice for kidney stone removal. The shock wave lithotripter uses an order of microsecond pulse durations and up to a 100 MPa pressure spike triggered at approximately 0.5-2 Hz to fragment kidney stones through mechanical mechanisms. One important mechanism is cavitation. We proposed an alternative type of lithotripsy method that maximizes cavitation activity to disintegrate kidney stones using high-intensity focused ultrasound (HIFU). Here we outline the method according to the previously published literature (Matsumoto et al., Dynamics of bubble cloud in focused ultrasound. Proceedings of the second international symposium on therapeutic ultrasound, pp 290-299, 2002; Ikeda et al., Ultrasound Med Biol 32:1383-1397, 2006; Yoshizawa et al., Med Biol Eng Comput 47:851-860, 2009; Koizumi et al., A control framework for the non-invasive ultrasound the ragnostic system. Proceedings of 2009 IEEE/RSJ International Conference on Intelligent Robotics and Systems (IROS), pp 4511-4516, 2009; Koizumi et al., IEEE Trans Robot 25:522-538, 2009). Cavitation activity is highly unpredictable; thus, a precise control system is needed. The proposed method comprises three steps of control in kidney stone treatment. The first step is control of localized high pressure fluctuation on the stone. The second step is monitoring of cavitation activity and giving feedback on the optimized ultrasound conditions. The third step is stone tracking and precise ultrasound focusing on the stone. For the high pressure control we designed a two-frequency wave (cavitation control (C-C) waveform); a high frequency ultrasound pulse (1-4 MHz) to create a cavitation cloud, and a low frequency trailing pulse (0.5 MHz) following the high frequency pulse to force the cloud into collapse. High speed photography showed cavitation collapse on a kidney stone and shock wave emission from the cloud. We also conducted in-vitro erosion tests of model and natural kidney stones. For the model stones, the erosion rate of the C-C waveform showed a distinct advantage with the combined high and low frequency waves over either wave alone. For optimization of the high frequency ultrasound intensity, we investigated the relationship between subharmonic emission from cavitation bubbles and stone erosion volume. For stone tracking we have also developed a non-invasive ultrasound theragnostic system (NIUTS) that compensates for kidney motion. Natural stones were eroded and most of the resulting fragments were less than 1 mm in diameter. The small fragments were small enough to pass through the urethra. The results demonstrate that, with the precise control of cavitation activity, focused ultrasound has the potential to be used to develop a less invasive and more controllable lithotripsy system.

Passive Cavitation Detection during Pulsed HIFU Exposures of Ex Vivo Tissues and In Vivo Mouse Pancreatic Tumors

Pulsed high-intensity focused ultrasound (pHIFU) has been shown to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rare factional focal pressures (1–12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms and pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KrasLSL.G12 D/+; p53 R172 H/+; PdxCretg/+ (KPC) mice and closely re-capitulate human disease in their morphology. The cavitation threshold, defined at 50% cavitation probability, was found to vary broadly among the investigated tissues (within 2.5–10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but it decreased rapidly and stopped over the first few pulses ex vivo. Cavitation activity depended on the interplay between the destruction and circulation of cavitation nuclei, which are not only used up by HIFU treatment but also replenished or carried away by circulation in vivo. These findings are important for treatment planning and optimization in pHIFU-induced drug delivery, in particular for pancreatic tumors.