| BackgroundAs a non-invasive treatment, high-intensity focused ultrasound (HIFU) ablation has been used in routine clinical practice. According to the transmission way of focused ultrasound beam, HIFU is divided into continuous-wave high intensity focused ultrasound (CHIFU) and pulsed-wave high intensity focused ultrasound (PHIFU). In order to achieve therapeutic results, CHIFU mainly generates high temperature elevation at the focus, resulting in the coagulation necrosis of a targeted tumor. However, long-duration CHIFU irradiation can cause the deposition of heat energy in overlying tissues between the skin and the target, and then lead to undesirable damage on them such as skin burn. In contrast, PHIFU exposures with relatively "duty cycles" (HIFU exposure on/off ratios) generate low levels of heat in the overlying tissues, and produce strong cavitation that enhances heat effect on tumor ablation. This may reduce the side effects of HIFU including the risk of damage on the overlying tissues.By using a HIFU clinical device, high-speed camera system, passive cavitation detection (PCD), thermocouple and B-mode ultrasound imaging, this study was to investigate the role of cavitation in PHIFU ablation for solid tumor. It will provide reliable laboratory data for the clinical application of PHIFU treatment.Purpose1. To investigate the role of cavitation in the PHIFU treatment of the bovine crystalline lens.2. Explore the influence of blood flow on the PHIFU treatment of isolated perfused porcine liver.Methods1. The role of cavitation in the PHIFU ablation of the bovine crystalline lens.Experimental Materials:the crystalline lens was obtained from fresh bovine eyes provided by local slaughterhouse.Experimental methods:(1) The crystalline lenses were randomly divided into PHIFU group (experimental group) and CHIFU group (control group). With the same total irradiation dose and pulse repetition frequency (4Hz), the control group received CHIFU exposure, and the experimental group received PHIFU exposure. Each exposure was repeated 20 times in the study. According to HIFU parameters, this study included following two parts:â‘ At the same total irradiation dose and acoustic power, HIFU ablation was performed with various kinds of duty circle and exposure time. The exposure times were set up according to the duty cycle changes in the PHIFU group, and HIFU parameters (acoustic power/duty cycle/exposure time) used in the study were as follow:control group (500W/100%/1s), experimental group 1 (500W/50%/2s), experimental group 2 (500W/20%/5s) and experimental group 3 (500W/10%/10s). â‘¡At the same total irradiation dose and exposure time, HIFU ablation was performed with various kinds of duty circle and acoustic power. The acoustic powers were set up according to the duty cycle changes in the PHIFU group, and HIFU parameters (acoustic power/duty cycle/exposure time) used in the study were as follow:control group (60W/100%/8s), experimental group 1 (120W/50%/8s), experimental group 2 (240W/25%/8s), experimental group 3 (500W/12%/8s).(2) During HIFU ablation period, a high-speed camera system was used to record the formation process of coagulation necrosis, and passive cavitation detection system was employed to collect cavitation signals in bovine crystalline lens. The experiments were repeated 20 times for each group. Based on high-speed camera recording images, the time required for occurrence of coagulation necrosis was determined. The size and volume of coagulation necrosis was measured and calculated in each group. The relationship between cavitation and the increase of the necrosis volume was also investigated.2. Influence of blood flow on the PHIFU ablation of isolated perfused porcine liver.Experimental Materials:Fresh porcine liver provided by local slaughterhouse was used to establish an in vitro isolated perfused liver model. When successful perfusion was set up in the liver, HIFU ablation was performed in this study.Experimental Methods:(1) The perfused porcine liver was randomly divided into perfusion group (experimental group) and non-perfusion group (control group). With the same total irradiation dose, pulse repetition frequency (100Hz) and focal depth (25mm), both groups received CHIFU and PHIFU single exposure respectively. Each exposure was repeated 10 times in the study. According to HIFU parameters, this study included following two parts:â‘ At the same total irradiation dose and acoustic power, HIFU ablation was performed with various kinds of duty circle and exposure time. The exposure times were set up according to duty cycle changes in the PHIFU group, and HIFU parameters (acoustic power/duty cycle/exposure time) used in the study were as follow:CHIFU exposure (200W/100%/10s), PHIFU exposure 1 (200W/50%/20s), PHIFU exposure 2 (200W/20%/50s) and PHIFU exposure 3 (200W/10%/100s).â‘¡At the same total irradiation dose and exposure time, HIFU ablation was performed with various kinds of duty circle and acoustic power. The acoustic powers were set up according to the duty cycle changes in PHIFU exposure, and HIFU parameters (acoustic power/duty cycle/exposure time) used in the study were as follow:CHIFU exposure (60W/100%/10s), PHIFU exposure 1 (120W/50%/10s), PHIFU exposure 2 (240W/25%/10s), PHIFU exposure 3 (500W/12%/10s).(2) During HIFU ablation period, cavitation signals were collected, and temperature at the focus was measured by a thermocouple in each group. Immediately after HIFU exposure, B-mode ultrasound imaging was recorded, and gray-scale values at focal region were compared and measured between pre-and post-HIFU imaging. The liver was then cut into slices for observation of HIFU-induce coagulation necrosis in each exposure, and the biggest longitudinal section of the necrosis was measured for calculating necrosis volume in the liver. A tissue block between the necrotic tissue and normal liver was obtained for pathological examination.Results1. At the same total radiation dose and sound power, coagulation necrosis was observed in the bovine crystalline lens in all groups. The fastest occurrence of the necrosis was detected in the CHIFU group. During PHIFU exposures, duty circle ratio could affect the occurrence time of coagulation necrosis. The smaller the duty cycle was, the necrosis occurred more slowly. When the duty circle was 10% in PHIFU exposure, the occurrence time was significantly longer (P< 0.01), and necrosis volume was significantly smaller (P<0.01). Broadband noise was detected in both CHIFU and PHIFU groups, with the highest RMS level observed in the CHIFU group (100% duty cycle).2. At the same total irradiation dose and exposure time, coagulation necrosis was observed in the crystalline lens during HIFU exposure in all groups. During HIFU exposures, acoustic power level could affect the occurrence time of coagulation necrosis. The higher the acoustic power used, the necrosis occurred more quickly. When acoustic power was 480W in PHIFU exposure, the occurrence time was significantly shorter (P< 0.01), and necrosis volume was significantly larger (P<0.01). Broadband noise was not detected in the CHIFU group, but observed in all PHIFU groups with the highest RMS level observed in the highest acoustic power.3. Under the same CHIFU and PHIFU parameters, the increased gray-scale values, hyperechoic area, temperature rise and coagulation necrosis volume were significantly weaker in the perfusion group than those in the non-perfusion group. There were significant differences between the two groups (P<0.05).4. At the same total radiation dose, PHIFU-induced coagulation necrosis volume was significantly greater than CHIFU irradiation. When the total radiation dose and acoustic power was the same, duty cycle ratio could significantly affect the volume of coagulation necrosis and cavitation intensity in the liver; when the total radiation dose and exposure time were the same, acoustic power levels could significantly affect coagulation necrosis volume and cavitation intensity.Conclusion1. At the same total radiation dose, PHIFU-induced coagulation necrosis volume is significantly greater than CHIFU irradiation.2. Blood flow can significantly influence the effect of CHIFU and PHIFU ablation on perfused porcine liver. Under the same HIFU parameters, coagulation necrosis volume, temperature rise and cavitation intensity are significantly weaker in the perfusion group than those in the non-perfusion group.3. At the same total radiation dose and acoustic power, duty cycle ratios changes can significantly affect coagulation necrosis volume and cavitation intensity; at the same total radiation dose and exposure time, acoustic power level can significantly affect coagulation necrosis volume and cavitation intensity.4. Adjusting duty cycle and acoustic power can significantly change the cavitation intensity at the focus, and then increase the volume of coagulation necrosis during HIFU exposure. |
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