Enhancement Of Tissue Ablation By 430kHz Pusle Wave Combined With 978kHz Continuous Wave In Dual-frequency High Intensity Focused

BackgroundHigh Intensity Focused Ultrasound?HIFU?is a new non-invasive tumor treatment technology in recent years.It can perform conformal ablation of solid tumors under ultrasound or MRI monitoring^[1],and has been used in the clinical treatment of benign and malignant tumors.treatment.As of the end of 2018,more than 250,000 solid tumor patients have been successfully treated worldwide with HIFU technology and achieved satisfactory clinical efficacy?American Focused Ultrasound Foundation Annual Report 2019?.However,the clinical requirements indicate that the limitations of focused ultrasound noninvasive treatment of tumors include ablation of deep or large tumors or ribs in the acoustic channel and other complex acoustic environments.The treatment time is too long,which is likely to increase the risk of surrounding tissue damage.Taking effective synergistic methods to shorten the treatment time and improve the treatment efficiency is the key issue of HIFU treatment.Studies have shown that changing the acoustic environment of the tissue can significantly enhance HIFU ablation.Dual-frequency HIFU helps to increase the rate of temperature rise,short the treatment time,and is one of the hot spots of domestic and foreign research.However,different researchers hold different views on the frequency,excitation waveform,and irradiation parameters in dual-frequency HIFU.This subject uses the interaction of pulse wave and continuous wave with a frequency difference of 548 kHz to control the occurrence of cavitation to enhance damage tissues of using HIFU.ObjectiveIt is clear that the pulse wave joint continuous wave with a frequency difference of 548 kHz enhances the selection of radiation parameters and the mechanism of action of HIFU treatment,and provides new ideas for dual-frequency HIFU to improve the treatment efficiency.Methods1.Study on irradiation parameters of pulse wave and continuous wave for cavitation/Boiling?1?430 kHz transducer is used to excite the pulse wave,the sound power of 150 W,the pulse repetition frequency of 6 Hz,the duty cycle is1%,4%,8%,12%;the corresponding irradiation time is 240 s,60 s,30 s,20 s.By calculating the cumulative cavitation dose at the focal zone,a duty cycle with the strongest cavitation effect is selected for later experiments.?2?Fresh bovine liver tissue was irradiated with pulsed HIFU of the strongest cavitation duty determined by the above experiment,pulse repetition frequency of 6 Hz and frequency of 430 kHz,B-mode probe was used to monitor the target area echo varying,wideband transducer detects cavitation noise signal during the irradiation,studying the sound power and irradiation time of low intensity cavitation and strong cavitation respectively;fresh bovine liver tissue was irradiated with 978 kHz continuous wave HIFU to study the irradiation parameters to achieve no cavitation activity,cavitation activity,cavitation with boiling,respectively.2.Enhancement of liver injury in vitro by dual frequency HIFU under different irradiation parametersTwo transducers with center frequencies of 978 kHz and 430 kHz are confocal placed through a three-dimensional motion device and immersed in degassed water.The continuous wave and the pulse wave are excited at the same time to form a dual-frequency HIFU.The sound power of the continuous wave in the dual-frequency HIFU is 30 W,120 W,and 450 W,and the irradiation time is 60 s,15 s,and 4 s,respectively;the sound power of the pulse wave is 150 W and 400 W,the irradiation time is consistent with the continuous wave,and six groups of dual-frequency HIFU are formed by random combination of continuous wave and pulse wave.The continuous wave acoustic power is 30 W,120 W,and 450 W,and the irradiation time is 60 s,15 s,and 4 s to form three groups of single-frequency HIFU.The damage area,RMS value of broadband noise and B-ultrasonic image of isolated bovine liver tissue irradiated by single frequency HIFU and dual-frequency HIFU were compared.Result1.The pulse HIFU with a frequency of 430 kHz and a pulse repetition frequency of 6 Hz,when the duty ratio is 4%,the cumulative cavitation dose value is the largest,that is,the cavitation effect is the strongest.2.Irradiation of bovine liver tissue with pulse wave HIFU with a frequency of 430 kHz,a pulse repetition frequency of 6 Hz,sound power of150 W and 400 W,and an irradiation time of 60 s can achieve low-intensity cavitation and strong cavitation with no hollow tissue damage was produced;By irradiating the bovine liver tissue with HIFU of 978 kHz,30W-60 s,120 W-15 s and 450 W-4 s respectively,the irradiation mode of no cavitation activity,no cavitation activity damage,cavitation with boiling damage can be realized,and damage area is significant difference among the three groups?P<0.05?.3.When the sound power of continuous wave HIFU is 30 W and the irradiation time is 60 s,there is no white coagulative necrosis in the irradiation area,no broadband noise enhancement during the irradiation,and no echo enhancement in the target area after the irradiation.However,when joint the pulse wave HIFU of 150 W and exposure time for 60 s,white elliptical coagulation necrosis appeared in the confocal irradiation area of dual-frequency HIFU,and the broadband noise increased during the irradiation process;when joint a pulse wave HIFU with a sound power of400 W and exposure time for 60 s,the confocal irradiation area of dual-frequency HIFU is white spherical coagulation necrosis and hollow tissue damage,broadband noise is enhanced during the irradiation process,and the target area echo is enhanced after the irradiation;the damage area of dual-frequency HIFU in the two groups was larger than that of single frequency HIFU,and there was significant difference between the three groups?P<0.05?.4.When the sound power of continuous wave HIFU is 120 W and the irradiation time is 15 s,white elliptical coagulation necrosis can be seen in the irradiation area,broadband noise appears during the irradiation,and the echo in the target area increases after the irradiation.However,when joint a pulse wave HIFU with a sound power of 150 W and exposure time for 15 s,white elliptical coagulation necrosis appeared in the confocal irradiation area of dual-frequency HIFU,the broadband noise increased during the irradiation,and the echo in the target area increased after the irradiation;when joint a pulse wave HIFU with a sound power of 400 W and exposure time for 15 s,the confocal irradiation area of dual-frequency HIFU is white spherical coagulation necrosis and hollow tissue damage,broadband noise is enhanced during the irradiation process,and the target area echo is enhanced after the irradiation;the damage area and B-mode grayscale difference between the two groups of dual-frequency HIFU are greater than the single-frequency HIFU,and there are significant differences between the three groups?P<0.05?.5.When the sound power of continuous wave HIFU is 450 W and the irradiation time is 4 s,the damage shape in the irradiation area is"tadpole-shaped",the broadband noise increases during the irradiation,and the echo in the target area increases after the irradiation.However,when the pulse wave HIFU with sound power of 150 W and exposure time for 4 s is combined,the damage shape of the dual-frequency HIFU confocal irradiation area is"tadpole-shaped",the broadband noise is increased during the irradiation process,and the target area echo is enhanced after the irradiation;when joint a pulse wave HIFU with a sound power of 400 W and exposure time for 4 s,the damage shape with confocal irradiation area of dual frequency is elliptical and the damage length becomes shorter,the broadband noise increases during the irradiation process,and the echo in the target area increases after the irradiation.The results show that when the continuous wave HIFU with a sound power of 450 W with an irradiation time of 4 s and the combined pulse wave with a sound power of400 W with an irradiation time of 4 s,the damage area of bovine liver tissue caused by dual-frequency HIFU is less than the continuous wave HIFU with a sound power of 450 W with irradiation time of 4 s,and the dual-frequency HIFU with pulse wave combined with 150 W and irradiation time of 4 s,and there are significant differences?P<0.05?;there was no significant difference in the damage area between the continuous wave HIFU joint a sound power of 450 W with irradiation time of 4 s and the dual-frequency HIFU with a combined sound power of 150 W and an irradiation time of 4 s?P>0.05?;there is no significant difference in B-grayscale difference between the three groups?P>0.05?.Conclusion1.For the determined ultrasonic frequency,pulse repetition frequency and sound power,adjusting the duty cycle of the pulse wave can control the intensity of cavitation;adjusting the sound power-irradiation time parameter can control the cavitation/boiling of the continuous wave HIFU.2.Continuous wave HIFU without cavitation activity and damage,continuous wave HIFU with cavitation activity and damage combined with pulse wave HIFU with cavitation activity to form dual-frequency HIFU enhances tissue ablation,and it increases as the sound power of the pulse wave HIFU increases,the mechanism is to further enhance the cavitation effect.This provides new ideas for improving the efficiency of HIFU treatment.3.When the continuous wave HIFU with cavitation and boiling activity is combined with the pulse wave HIFU with cavitation activity to form a dual-frequency HIFU,the cavitation activity is suppressed,and it shows a decreasing trend as the sound power of the pulse wave HIFU increases,which prompts When dual-frequency HIFU is used to ablate the lesion tissue,it is meaningful to reduce the sound power of continuous wave HIFU and select appropriate continuous wave irradiation parameters to improve the treatment efficiency of HIFU.