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Objective High hydrostatic pressure is mainly used as a mean to study the effect of cavitation on lesions generated by high intensity focused ultrasound (HIFU).However, most of the researchers just suppress the cavitation completely by using a single extremely high hydrostatic pressure which is over the peak acoustic negative pressure,without observing the change of lesions under a lower high hydrostatic pressure.To address this problem,this study investigate the effects of a group of increasing hydrostatic pressure, which are lower than the acoustic peak negative pressure, on lesions generation in ex vivo bovine liver specimens produced by HIFU exposure.Methods Experiment is performed using a US transducer of 1MHz frequency to generate the US of 48,760J/cm2 exposure dose at the different acoustic intensities,6,095W/cm2×8s and 9,752W/cm2×5s,in the ex vivo bovine liver specimens under the following hydrostatic pressure : 0.1MPa, 0.5MPa, 1.0MPa, 1.5MPa, 2.0MPa, 2.5MPa and 3.0MPa respectively.The peak acoustic negative pressure of two groups are 9.58MPa and 10.83MPa respectively, with a difference of 1.24MPa.Passive cavitation detection(PCD) was used to monitor the ultrasonic cavitation signal during exposure under the atmospheric pressure,which indicates that there is a statistically significant increase above noise in broadband emissions when under exposure of 9,752W/cm2×5s, but no under exposure of 6,095W/cm2×8s.Results The results showed that the morphology and size of lesions were similar at 6,095W/cm2×8s exposure under different hydrostatic pressure.But the lesions at 9,752W/cm2 ×5s exposure under 0.1MPa,0.5MPa, 1.0MPa,with cavitation occurring under atmospheric pressure, were larger than those under 1.5MPa, 2.0MPa, 2.5MPa and 3.0MPa.Under hydrostatic pressure of over 1.5MPa,the lesion at 9,752W/cm2×5s exposure was similar to that at 6,095W/cm2×8s exposure.Overpressure could not affect the formation of vapor bubble, but could increase the possibility of dissolving gas bubbles which already existed, resulting in the diminution of bubble quantity and size.Because of the alternative positive pressure and negative pressure, the oscillating bubble formed a bigger scattering range, but overpressure could restrict the bubble oscillation to reduce the lesion size.However, after increasing the hydrostatic pressure to 0.5MPa and 1.0MPa, the lesion in ex vivo bovine liver tissue of higher acoustic intensity group was increased significantly compared with that under the atmospheric pressure (P<0.05).The shape of lesion changed from teardrop into spheroid,and the carbide necrosis appeared in the focal region obviously.The boiling point of the boiling bubble increased with the increase of hydrostatic pressure.The boiling bubble raised the temperature in focus before the cavitation was not completely suppressed, resulting in enlargement of the lesion in focus.Conclusion This study indicated that nonlinear effect caused by the increase of hydrostatic pressure and exposure intensity that had little influence with lesion formation in ex vivo bovine liver when without cavitation and under the same exposure dose.The hydrostatic pressure should increase to that upon the threshold difference of peak acoustic negative pressure to suppress the cavitation when cavitation occurred.But appropriate increase the hydrostatic pressure could increase the energy release when bubble occurred transient cavitation,and could increase the thermal deposition of cavitation bubble through the lesion formation,in turn,increase the lesion.This work provides a theoretical and experimental fundamental for improving the clinical efficiency of HIFU.