Effects of nonlinear propagation, cavitation, and boiling in lesion formation by high intensity focused ultrasound in a gel phantom

Abstract

The importance of nonlinear acoustic wave propagation and ultrasound-induced cavitation in the acceleration of thermal lesion production by high intensity focused ultrasound was investigated experimentally and theoretically in a transparent protein-containing gel. A numerical model that accounted for nonlinear acoustic propagation was used to simulate experimental conditions. Various exposure regimes with equal total ultrasound energy but variable peak acoustic pressure were studied for single lesions and lesion stripes obtained by moving the transducer. Static overpressure was applied to suppress cavitation. Strong enhancement of lesion production was observed for high amplitude waves and was supported by modeling. Through overpressure experiments it was shown that both nonlinear propagation and cavitation mechanisms participate in accelerating lesion inception and growth. Using B-mode ultrasound, cavitation was observed at normal ambient pressure as weakly enhanced echogenicity in the focal region, but was not detected with overpressure. Formation of tadpole-shaped lesions, shifted toward the transducer, was always observed to be due to boiling. Boiling bubbles were visible in the gel and were evident as strongly echogenic regions in B-mode images. These experiments indicate that nonlinear propagation and cavitation accelerate heating, but no lesion displacement or distortion was observed in the absence of boiling.

Acoustic Emissions During 3.1 MHz Ultrasound Bulk Ablation In Vitro

“…Consistent with a number of other experiments is the sudden onset of increased low-frequency emissions and echo brightness at temperature thresholds suggesting tissue boiling (Khokhlova et al 2006, McLaughlan et al 2006). Both of these effects are likely due to large vapor bubbles, which act as ultrasound reflectors and undergo violent low-frequency oscillation.…”

“…The low-frequency emissions observed here are known to be associated with vaporization and boiling for ultrasound ablation at 3.5 MHz, comparable to the sonication frequency employed here (Anand et al 2004;Khokhlova et al 2006). However, physical mechanisms for the bubble activity causing measurable high-frequency acoustic emissions are not yet fully understood.…”

“…Some HIFU studies have observed a large increase in subharmonic and broadband emissions simultaneous to, or slightly preceding apparent vaporization (Bailey et al 2003;Rabkin et al 2005Rabkin et al , 2006, while others have also observed significant high-frequency acoustic emissions, indicating cavitation, in the absence of tissue boiling (Khokhlova et al 2006;McLaughlan et al 2006). A possible explanation for this apparent inconsistency is the strong dependence of acoustic emissions on the sonication amplitude, as seen here for the subharmonic emissions depicted in Fig.…”

“…This behavior may also depend on the sonication frequency. Another reason for strong dependence of acoustic emissions on sonication characteristics are strongly nonlinear effects that can occur in highintensity focused ultrasound beams (Bailey et al 2003;Khokhlova et al 2006). Thus, although high-frequency, cavitational acoustic emissions may show a consistent relationship with tissue temperature for a particular ultrasound ablation scenario, such relationships may not be applicable if the sonication amplitude or other acoustic conditions are significantly modified.…”

“…Such activity can be exploited to visualize ablation effects (Sanghvi et al 1995;Rabkin et al 2005Rabkin et al , 2006 or to enhance tissue absorption (Melodelima et al 2001;Sokka et al 2003;Umemura et al 2005;Kaneko et al 2005), but can also complicate ultrasound energy deposition and the resulting spatial pattern of tissue coagulation (Watkin et al 1996;Chen et al 2003;Makin et al 2005;. Mechanisms for interactions between cavitation activity and ultrasound-induced heating have been clarified by several detailed numerical modeling studies (Hilgenfeldt et al 2000;Chavrier et al 2000;Yang et al 2004) and phantom experiments (Holt and Roy 2001;Khokhlova et al 2006). Cavitation activity, measured by passive detection of acoustic emissions, has also been found to correlate with cellular-level bioeffects (Edmonds and Ross 1986;Hallow et al 2006) and with ultrasound enhancement of thrombolysis (Datta et al 2006).…”