Prevention of post-focal thermal damage by formation of bubbles at the focus during high intensity focused ultrasound therapy

Abstract

Safety concerns exist for potential thermal damage at tissue-air or tissue-bone interfaces located in the post-focal region during high intensity focused ultrasound (HIFU) treatments. We tested the feasibility of reducing thermal energy deposited at the post-focal tissue-air interfaces by producing bubbles (due to acoustic cavitation and/or boiling) at the HIFU focus. HIFU (in-situ intensities of 460-3500 W/cm2, frequencies of 3.2-5.5 MHz) was applied for 30 s to produce lesions (in turkey breast in-vitro (n = 37), and rabbit liver (n = 4) and thigh muscle in-vivo (n = 11)). Tissue temperature was measured at the tissue-air interface using a thermal (infrared) camera. Ultrasound imaging was used to detect bubbles at the HIFU focus, appearing as a hyperechoic region. In-vitro results showed that when no bubbles were present at the focus (at lower intensities of 460-850 W/cm2), the temperature at the interface increased continuously, up to 7.3 +/- 4.0 degrees C above the baseline by the end of treatment. When bubbles formed immediately after the start of HIFU treatment (at the high intensity of 3360 W/cm2), the temperature increased briefly for 3.5 s to 7.4 +/- 3.6 degrees C above the baseline temperature and then decreased to 4.0 +/- 1.4 degrees C above the baseline by the end of treatment. Similar results were obtained in in-vivo experiments with the temperature increases (above the baseline temperature) at the muscle-air and liver-air interfaces at the end of the high intensity treatment lower by 7.1 degrees C and 6.0 degrees C, respectively, as compared to the low intensity treatment. Thermal effects of HIFU at post-focal tissue-air interfaces, such as in bowels, could result in clinically significant increases in temperature. Bubble formation at the HIFU focus may provide a method for shielding the post-focal region from potential thermal damage.

Figure 1

Soft tissue-air interface in the HIFU post-focal region. (a) Schematic of the HIFU treatment with no bubbles present at the focus. Reflection at the soft tissue-air interface may result in the thermal damage in healthy tissues. (b) Schematic of the HIFU treatment in which bubbles were produced at the focus, impeding the propagation of the HIFU beam beyond focus. No thermal damage is expected at the post-focal soft tissue-air interface in this case.

Figure 2

In-vitro and in-vivo experimental setups. The temperature at the tissue-air interface in the post-focal region was measured using a thermal camera. (a) Treatment of the turkey breast in-vitro was performed using a 3.2 MHz HIFU device (focus at 3.5 cm). HIFU focus was observed using B-mode ultrasound imaging. (b) In-vivo treatment was performed using an intraoperative 5.5 MHz HIFU solid cone applicator (with the focus located at ∼1 cm from the tip of the applicator).

Figure 3

A representative ultrasound (a) and thermal image (b) obtained during the in-vitro HIFU treatment at the high in-situ intensity of 3360 W∕cm². Hyperecho formation at the HIFU focus (arrowhead). Cursor of the thermal camera was able to track the highest temperature in real time (arrow).

Figure 4

Temperature at the tissue-air interface in the post-focal region as a function of HIFU exposure time for in-vitro treatments at: (a) 460 W∕cm² (n=11), (b) 650 W∕cm² (n=8), (c) 850 W∕cm² (n=9), and (d) 3360 W∕cm² (n=9). Data are represented as mean±standard error of the mean.

Figure 5

Comparison of temperature increases at the in-vitro tissue-air interface at different HIFU intensities.

Figure 6

Gross appearance of the lesions produced in the turkey breast in-vitro at HIFU intensities of: (a) 460 W∕cm², (b) 650 W∕cm², (c) 850 W∕cm², and (d) 3360 W∕cm². At the highest intensity, the lesions grew to the front surface from which HIFU energy was applied. The HIFU transducer was located on the right-hand side of the images in all cases.

Figure 7

Temperature at the in-vivo tissue-air interface in the post-focal region at the low and high HIFU intensity. (a) Treatment of thigh muscle (n=6 at 1200 W∕cm²; n=5 at 3500 W∕cm²). Interface was located at 2 cm from the HIFU focus. (b) Liver treatment (n=2 for each intensity). Interface was located at approximately 1 cm from the HIFU focus. Data are represented as mean±standard error of the mean.

Figure 8

Gross appearance of HIFU lesions (arrows) produced in the liver in-vivo at (a) 800 W∕cm² and (b) 3500 W∕cm². Dotted lines are used to outline the HIFU lesions at tissue depth. Solid lines are used to show the border between the liver cross section and the front surface of the liver (that was in contact with the HIFU transducer). Drawings show position of the HIFU transducer relative to the lesion location.