Research On Dynamic Change Of Coagulation Necrosis And Bubble Activities Induced By HIFU

BACKGROUNDHigh intensity focused ultrasound (High Intensity Focused Ultrasound,HIFU) provides a non-invasive and precisely focused treatment method oftumors but no skin incision, and demonstrates good efficacy and safety inclinical treatment. The main physical mechanisms of HIFU are thermaleffect and cavitation effect, from which the role of cavitation in the HIFUtreatment is very complex, and is one of the hot issues in HIFU technologyresearch, besides, reports about the bubble activities of acoustic cavitationand the relationship between them in HIFU irradiation are few. Based onthis, bovine eye lens and tissue mimicking phantom were used asexperimental materials in this paper, and combined high-speed photography,microscope, passive cavitation detection (PCD) and US to investigate thetime-varying regularity of coagulation necrosis, dynamic change of bubblesinduced by HIFU and it’s cavitation mechanism.PURPOSE1. Explore the different regularity of coagulation necrosis in focal region of HIFU and its relationship with acoustic cavitation;2. Study the characteristics of bubble in the process of coagulationnecrosis induced by focused ultrasound.METHODS1. Study on regularity of coagulation necrosis in focal region of HIFUand its relationship with acoustic cavitation.Use bovine eye lens as experimental material, HIFU(frequency=0.94MHz) with same energy and different parameters(100W×6s,200W×3s,300W×2s，600W×1s) to irradiate, and eachrepeated20times. During the experiment use the high-speed camera whileat1000fps frame rate for the formation of coagulation necrosis imaging, anda transducer with center frequency of5MHz for broadband passivecavitation detection. Analyze the volume growth law of coagulationnecrosis and its relationship with the acoustic cavitation.2. Bubble activities in focal region during formation of coagulationnecrosis induced by focused ultrasound in imitation transparent phantomUse fresh homemade tissue mimicking phantom as experimentalmaterial, focused ultrasound with frequency9.10MHz sound power of5W toirradiate, high-speed video camera (1000fps) combined with stereomicroscope (×40) on the irradiation process at the focal region ofcoagulation necrosis and bubble formation process in real-time activity monitoring, with a center frequency of15MHz wideband transducerspassive cavitation detection, real-time monitoring with US imaging. On thisbasis, analyze focused ultrasound-induced coagulation necrosis during thebubble activities and their impact on the target coagulation necrosis.RESULTS1. In groups100W×6s,200W×3s,300W×2s and600W×1s, time forcoagulation necrosis began to appear decreased as an increase in soundpower, respectively:1.90s,0.75s,0.44s,0.36s.2. Coagulation necrosis induced by100W×6s grown linearly duringirradiation, similarly in groups200W×3s and300W×2s when, respectively,irradiated to2.30s and1.50s the linear growth becomes nonlinearly,600W×1s, coagulation necrosis showed non-linear growth trend until theend of irradiation.3. When exposed to100W×6s, no broadband noise occurred, in theremaining three groups broadband noise and harmonics were detected, theamplitude of the fourth harmonic of the sound power of200W×3s and300W×2s group did not significantly increased, while in the group hadsignificantly600W×1s fluctuated, and the amplitude levels above200W×3s and300W×2s group,300W×2s and600W×2s irradiation group,time when RMS amplitude increased were0.30s,0.20s, which earlierbefore coagulation necrosis appeared. 4. Irradiation of focused ultrasound with sound power of5W andfrequency of9.10MHz to phantom tissue transparent, time began to appearcoagulation necrosis was2.70±0.51s, after which, volume of coagulationnecrosis grown, a bubble formed rapidly when8.76±1.64s, the form of thebubble an ellipsoid and its axial is slightly less than the radial axis (1.22±0.30mm,1.27±0.69mm, respectively), the bubbles lasted for a short periodof time(about0.33s) that started to collapse, small bubbles began to appearin front of the focal region after0.10s large bubble appeared, and growntoward the transducer, when exposed to about10.87s coagulation necrosisstarted to change from "cigar-shaped" to "tadpole-shaped".5.14min after the irradiation bubbles in the same position increasedsignificantly (about1~2times increased) than irradiation stoppedimmediately.6. The time when big bubble first appeared and the time when therewas a sudden increase in RMS harmonic frequency curves associated wellwith each other and a hyperecho area can be observed on B-mode image,"cigar-like" shaped and grown stable.CONCLUSIONS1. In groups100W×6s,200W×3s,300W×2s and600W×1s, nocavitation occured when irradiated to100W, increase the sound power,cavitation was detected, and increased as sound power, time for coagulation necrosis to appear shortened, the time required for coagulation necrosisgrown nonlinearly reduced, too. The rate of linear growth portion increasedas sound power. This suggests that the growth trend of coagulation necrosisis well related to the time cavitation happen and its severity, and soundpower plays a more important role when dose is the same.2. Emergence of millimeter bubbles caused by focusedultrasound(frequency=9.10MHz, sound power=5W) was very intense,continued a short time (about0.33s) before collapse, a large number of smallbubbles began to appear in front of the focal region, in the role of bubbles,coagulation necrosis changed from “cigar-shaped” to “tadpole-shaped”.14min after the irradiation bubbles in the same position increasedsignificantly (about1~2times increase) than irradiation stoppedimmediately.3. Millimeter bubbles appear along with the band harmonic noiseamplitude increases suddenly, hyperecho suddenly appeared on B modeimage, this may an evidence of boiling bubble induced by long timehigh-frequency focused ultrasound irradiation, and then the boiling bubblesburst, providing nuclei for cavitation.