# Enhancement of High-Intensity Focused Ultrasound Heating by Short-Pulse Generated Cavitation
## 2 Trigger HIFU Sequence
This was under the consideration that standing wave components tend to decrease the cavitation threshold [47; 48] and may make it difficult to locally generate bubble clouds in a HIFU focal region. The intensity of a heating burst was similar to that in conventional HIFU treatments. The duration time of a heating burst was in the order of 10-500 ms with a consideration of the sustaining duration of cavitation bubbles under the heating burst exposure. The effect of standing wave components on the generation of cavitation by a heating burst was not considered because the acoustic intensity of a heating burst was much less than that of a trigger pulse. As a result, the trigger HIFU sequence was similar to that used for the bubble-enhanced heating with nanoparticles [23]. In the trigger HIFU sequence, the typical acoustic intensity for cavitation generation was higher due to the lack of artificial cavitation nuclei. The duration time of the burst wave for the heat enhancement was shorter because lifetime of cavitation bubbles induced by the trigger pulse is considered to be shorter than that of microbubbles vaporized from nanoparticles with slightly soluble gas [38]. The advantage in the trigger HIFU exposure over the methods using nanoparticles is to have a potentially shorter lead time to be approved as clinical applications. Figure 1 shows three examples of a trigger pulse sequence [35; 36]. Table 1 lists the technics applied to the sequences shown in Figure 1. Figure 1a shows a typical sequence without the focus scanning. Since an ordinary HIFU focal spot has an ellipsoidal shape longer in the HIFU propagation direction, the lateral enlargement of the focal region can reduce the surface-area-to-volume ratio of the region, which decreases the effect of the heat diffusion outward from the region to be treated. In the sequences shown in Figure 1b,c, trigger pulses were rapidly scanned at focal points of 1-6, named \"multi-trigger HIFU sequence\". The focal point was electronically scanned using a 2D array transducer at each corner of a regular hexagon 3 mm each side. The whole hexagonal region was coagulated by thermal conduction between adjacent focal spots. The total acoustic power for the spot scanning of trigger pulse and heating burst were 1400 and 44 W, respectively. The duration and interval time for trigger pulses at each focal point were 25 and 3 us, respectively. The trigger pulses were laterally scanned four times. For heating bursts, the same total acoustic power, duration, and duty cycle were used for both spot scanning in Figure 1b and direct synthesis of focus in Figure 1c. The focal region of the heating bursts in Figure 1c has a ring shape, marked with 1 or 1. A sector vortex method [49; 50] with a vortex mode number of 4 was applied to generate the ring focal region covering six foci of scanned trigger pulses with a spiral wave front. The simulated pressure fields with assuming linear propagation and neglecting attenuation are shown in Figure 2. The duration and interval time were 25 and 4 us, respectively. The focal spot was scanned 834 times in Figure 1b and the spiral direction of the wave front was switched 2502 times in Figure 1c. The subtotal durations of trigger pulses and heating bursts were 0.67 and 145 ms, respectively. Immediately after the end of the heating bursts, a 2 ms interval time was reserved for ultrasonic imaging. The sequence was repeated for 80 or 120 cycles. Since cavitation clouds formed through the shock scattering tend to grow backward from the focal point, the focal points of trigger pulses were intentionally shifted by 7 mm forward from the geometrical focal plane to match the axial position of the generated cavitation clouds to that of the heating focus.