Probably, the most important consequence of nonlinear propagation effects is that the boiling temperature of water, 100°C, can be achieved as rapidly as several milliseconds, which leads to the formation of a millimeter-sized boiling bubble at the focus of the transducer (34). This changes the course of treatment dramatically: the incident ultrasound wave is now reflected from the bubble and heat deposition pattern is distorted in unpredictable manner. The lesion shape becomes irregular, generally resembling a tadpole, as illustrated in Figure 3B. Moreover, the motion of the boiling bubble may cause tissue Inhibitors,research,lifescience,medical lysis that can be seen as a vaporized cavity in

the middle of the thermal lesion. Sometimes this effect may be desirable and can be enhanced by using HIFU pulses powerful enough to induce boiling in several milliseconds, and with duration Inhibitors,research,lifescience,medical only check details slightly exceeding

the time to reach boiling temperature (35). In that case the temperature rise is too rapid for protein denaturation to occur, but the interaction of the large boiling bubble with ultrasound field leads to complete tissue lysis, as illustrated in Figure 3C (36). Inhibitors,research,lifescience,medical Radiation force and streaming Radiation force is exerted on an object when a wave is either absorbed or reflected from that object. Complete reflection produces twice the force that complete absorption does. In both cases the force acts in direction of ultrasound propagation and is constant if the amplitude of a wave is steady. If the reflecting or absorbing medium is tissue or other

solid material, the force presses against the medium, producing a pressure termed “radiation Inhibitors,research,lifescience,medical pressure.” For most clinically relevant devices and exposures this effect is not very pronounced: radiation pressure does not exceed a few pascals (14). However, if the medium is liquid (i.e., blood) and can move under pressure, then such pressure can induce streaming with speeds of up to 6 Inhibitors,research,lifescience,medical m/s (37). This effect has important implications in sonotrombolysis, in which a clot-dissolving agent is driven by streaming towards and inside the clot blocking a vessel (38). Image guidance and monitoring of HIFU therapy There are currently two imaging methods employed in commercially available HIFU devices: magnetic resonance imaging (MRI) and diagnostic ultrasound. The role of these methods in treatment is three-fold: Rolziracetam visualization of the target, monitoring tissue changes during treatment and assesment of the treatment outcome. In terms of tumor visualization, both MRI and sonography can provide satisfactory images; MRI is sometimes superior in obese patients (39), but is more expensive and labor-intensive. Unfortunately, to date none of the monitoring methods can provide the image of the thermal lesion directly and in real time as it forms in tissue.