Laser-enhanced cavitation during high intensity focused ultrasound: An in vivo study

Abstract

Laser-enhanced cavitation during high intensity focused ultrasound (HIFU) was studied in vivo using a small animal model. Laser light was employed to illuminate the sample concurrently with HIFU radiation. The resulting cavitation was detected with a passive cavitation detector. The in vivo measurements were made under different combinations of HIFU treatment depths, laser wavelengths, and HIFU durations. The results demonstrated that concurrent light illumination during HIFU has the potential to enhance cavitation effect by reducing cavitation threshold in vivo. High intensity focused ultrasound (HIFU) is a truly noninvasive thermal-ablation technique. HIFU works through rapidly depositing high intensity ultrasound energy into a small region to induce cell death primarily by hyperthermia after high intensity ultrasound is absorbed by soft tissue. [1][2][3][4][5] While the application of HIFU therapy is expanding, one concern related to HIFU treatment is the prolonged treatment time for large tumors because HIFU lesion is relatively small for each HIFU shot.Cavitation has been shown to yield elevated heating rate above those produced by classical acoustic absorption in tissue and can provide an effective method to improve the efficiency of HIFU treatment.6-12 However, pre-existing nucleation sites for cavitation are not omnipresent in most tissues in vivo. Many research efforts have been made to create nucleation sites for cavitation and reduce cavitation threshold. Both ultrasound contrast agents (UCAs) [13][14][15][16][17][18] and nanoparticles have been studied as methods to deliver cavitation nuclei into the targeted region.19,20 The use of UCA or nanoparticles, however, requires the systematic injection of foreign particles into the blood stream, and would have major concerns regarding toxicity, efficiency, etc. Cavitation bubbles can also be induced in presonication areas by using low frequency, high intensity ultrasound prior to HIFU treatments. 21,22 This technique can enhance cavitation and create larger size lesions in deep tissue without the injection of any contrast agents. However, this technique requires very high acoustic pressure (generally more than 10 MPa) to be delivered into soft tissues in order to induce cavitation in the beginning. In addition, the inception of cavitation is erratic and difficult to predict when induced by ultrasound alone.Laser light has been widely used as a reliable method to induce cavitation through optical breakdown. This procedure is generally performed with high intensity light, and mostly limited to clear media or sample surfaces. 23,24 Hence the application of this technique is limited in the in vivo applications, where treatments in a certain depth in turbid media are often desired.In a previous study, 25 we reported an enhanced heating effect during photoacoustic imaging-guided HIFU therapy. The results suggested that cavitation was enhanced when a diagnostic laser light beam illuminated the sample concurrently with HIFU radiation. Two features were highlighted...

Enhanced laser surface ablation with an integrated photoacoustic imaging and high intensity focused ultrasound system

“…Hu et al demonstrated that combined laser and ultrasound can be used to selectively target micro‐vessels without damaging the surrounding . Similar studies have described how combined laser and ultrasound resulted in increased cavitation , which has been used with optically absorbent nanoparticles for targeted cavitation . These previous ablation studies have looked at internal applications, while this study intends to explore dermatological applications.…”

High-precision, non-invasive anti-microvascular approach via concurrent ultrasound and laser irradiation

“…a blood vessel), the laser-induced photoacoustic wave can converge into the center and achieve a significantly high acoustic pressure and produce cavitation44, which is referred to as “cold bubbles” and has been observed in cells45. Unlike other use of therapeutic ultrasound and laser irradiation4647484950, when ultrasound and laser irradiation are concurrently applied, a portion of the ultrasound waves can modulate the transient thermal-elastic negative stress produced through photospallation, which will increase the cavitation efficiency because of the greater negative pressure31. One of the key features of photoacoustic cavitation is that cavitation may be induced at a laser energy level that is much lower than that needed for laser thermal therapies (such as photothermolysis and photocoagulation) because photoacoustic cavitation is not a strictly thermal effect.…”

“…When a laser pulse is absorbed by hemoglobin, the tissue is excited and the photoacoustic effect occurs. The concurrent application of ultrasound significantly increases the likelihood of micro-cavitation in the blood vessel31. The produced cavitation can then be further enhanced and driven by the subsequent ultrasound pulses.…”

Sonothrombolysis

“…Hydrophobic particulates (Soltani 2013), perfluorocarbon droplets (Pajek et al 2014) and focused laser pulses (Cui et al 2013) have been used to nucleate cavitation effectively during sonothrombolysis. However, ultrasound contrast agents (UCAs), or stabilized microbubbles, are also used to nucleate cavitation.…”