Study On Effect Of Static Pressure And Dissolved Oxygen Content On HIFU-Induced Lesion And Its Possible Mechansim

BackgroundHigh Intensity Focused Ultrasound (HIFU), which is a non-invasive treatment method, has been used in clinical treatment of uterine fibroid, prostate cancer, liver cancer, pancreatic cancer, breast cancer and other benign and malignant tumor, and it demonstrates good efficacy and safety in clinical treatment. The lesion generated by HIFU irradiation is result of together effect of nonlinear acoustic wave propagation, thermal effect, cavitation and boiling bubbles. It is considered that bubble dynamics, bubble dissolution rate, boiling temperature are the function of static pressure, and it is confirmed that overpressure can minimizes bubble activity by dissolving gas bubbles, restricting bubble oscillation and raising the boiling temperature, which means overpressure can inhibit the occurrence and degree of cavitition by increasing cavitation threshold. Thus, overpressure provides a method to study the HIFU treatment mechanism. Different researchers hold different views about the effect of overpressure on lesion generated by HIFU. To further study the effect of different static pressure level on HIFU induced lesion and explore its mechanism, this paper is explored on fresh bovine liver tissue in vitro by applying two HIFU exposure parameters which reflect two different nonlinear propagation condition and the cavitation effects at various hydrostatic ambient pressure. Furthermore we solve the nonlinear Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation numerically as theoretical base of effects of HIFU exposure without cavitation. Therefore, we can compare experimental results of the lesion change without cavitation effect under different pressure with the simulation result. Negative static pressure is applied in HIFU treatment which has not yet been studied, and the level of dissolved oxygen content in degassed water can be further reduced under negative static pressure.PurposeTo explore the effect of different negative static pressure and dissolved oxygen content on lesion generated by HIFU and hope to understand the contribution of nonlinear propagation, cavitation and boiling on lesion generated by HIFU.Method1. Effect of high static pressure (0.1MPa,0.5MPa, 1.0MPa,1.5 MPa, 2.0 MPa,2.5 MPa,3.0 MPa) on lesions in bovine livers generated by HIFU ex vivo.Theoretical study is done by solving different Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation numerically at the spatial peak intensity of ultrasound (US) 3,900W/cm2 and 6,240W/cm2 respectively. Experiment part is performed by use US transducer of 1MHz frequency(diameter=70mm, geometrical focal length=55mm, aperture angle=79 degree) to generate the US exposure at above-mentioned spatial peak intensity (3,900W/cm2 and 6,240W/cm2) in the ex vivo bovine liver tissue under the following ambient static pressure:0.1MPa,0.5MPa, 0.0MPa,1.5MPa,2.0MPa,2.5MPa and 3.0MPa respectively. Passive cavitation detection (PCD) is used to monitor the ultrasonic cavitation signal during exposure under the atmospheric pressure.2. Effect of negative static pressure (-0.09MPa) and different dissolved oxygen content (2.0mg/L,1.5 mg/L,1.0 mg/L) on lesions,and change of hyperechoic and cavitation signal in focal region.Fresh bovine liver tissue in vitro is used as experimental material. Under different environmental conditions, the frequency of transducer is 1.0MHz, power of HIFU is 11,700W/cm2×2s, passive cavitation detection system (PCD) on the bubble and Ultrasound (US) on the echo are used to monitor during the exposure.Result1. Simulation results of KZK equation indicate that the p+/p- of nonlinear propagation and the ratio value of harmonic wave and fundamental wave of 6,240W/cm2 are higher than 3,900W/cm2, but there is little difference between the thermal dose of same exposure dose, 3,900W/cm2x8s and 6,240W/cm2x5s.2. There is broadband noise signal obviously during exposure of higher acoustic intensity 6,240W/cm2x5s, which indicate that cavitation participate in the exposure. But it did not occur in lower acoustic intensity 3,900W/cm2×8s.3. After exposing of 3,900W/cm2x8s, lesion in ex vivo bovine liver has no significant change with static pressure (p>0.05), and corresponds to the calculation result of KZK equation which ignored cavitation. But after exposing of 6,240W/cm2x5s, lesion was bigger than that of 3,900W/cm2x8s under atmospheric pressure and and became distortion obviously. And it was greater than the calculation result of KZK equation which ignored cavitation.4. Lesion was grown when under 0.5MPa and 1.0MPa (p<0.05), and changed into ellipsoidal carbonation necrosis.5. Lesions were similar with each other when pressure increased to 1.5MPa,2.0MPa,2.5MPa and 3.0MPa. They all were smaller than that under atmospheric pressure, and it is correspond to the calculation result of KZK equation and that of 3,900W/cm2x8s.6. Whether it is atmospheric pressure or negative static pressure, acoustic intensity is 11,700W/cm2x2s, dissolved oxygen content is 2.0mg/ L,1.5 mg/L,1.0 mg/L, with the decrease of dissolved oxygen content, lesion is reduced, and the shape is tend to symmetry distribution. Under negative static pressure and the same dissolved oxygen content, the lesion is reduced accordingly and symmetrical distribution comparing with atmospheric pressure. The smaller of dissolved oxygen content, lesion is also smaller. When it is 1.0 mg/L, lesion did not even form.7. Whether it is atmospheric pressure or negative static pressure, acoustic intensity is 11,700W/cm2x2s, dissolved oxygen content is 2.0mg/ L,1.5 mg/L,1.0 mg/L, with the decrease of dissolved oxygen content, hyperechoic were found on B-monitoring, there is slight difference in brightness. Under negative static pressure and the same dissolved oxygen content, the level of hyperechoic is smaller than that when it is under atmospheric pressure, when it is negative static pressure and dissolved oxygen content is 1.0 mg/L, there is no hyperechoic can be seen.8. When it is under atmospheric pressure, acoustic intensity is 11,700W/cm2x2s, dissolved oxygen content is 2.0mg/L,1.5 mg/L,1.0 mg/L respectively, With the decrease of dissolved oxygen content, broadband noise intensity is weakened; when it is under negative static pressure, broadband noise intensity is weakened than that under atmospheric pressure.Conclusions1. With acoustic intensity 6,240W/cm2 × 5s, lesion is greater than that with acoustic intensity 3900W/cm2 × 5s, and also much larger than the simulation result, and the shape of lesion is teardrop-shaped, indicating that the increase of lesion is mainly due to transient cavitation.2. With acoustic intensity 3,900W/cm2×8s, cavitation does not occur under the atmospheric pressure. When it is 0.1MPa,0.5MPa, 1.1MPa, 1.5MPa,2.0MPa,2.5MPa and 3.0MPa, with the ambient pressure rising, the size, shape, extent of HIFU-induced lesion has no significant change, indicating that the variation of tissue acoustic parameters caused by the increase of ambient pressure is small, and the steady-state cavitation contribute to tissue lesion little. The reason is because of the enhanced inertial cavitation.3. Elevated hydrostatic pressure to 0.5MPa, 1.0MPa, lesion volume by same HIFU exposure increased significantly when compared with the normal pressure(p<0.05), the sharp change from teardrop-shaped into spheroid, Focal area appears obviously carbide necrosis.4. Acoustic intensity 6,240W/cm×5s, when the ambient pressure continues to increase to 1.5MPa,2.0MPa,2.5MPa and 3.0MPa, the lesion is in agreement with that with acoustic intensity 3,900W/cm2 × 8s and the theoretical simulation result. Environmental pressure increased to 1.5Mpa, 2.0Mpa,2.5Mpa,3.0MPa, Cavitation bubbles are completely suppressed, and only the effect of nonlinear propagation of ultrasound was left, and cavitation induced by high acoustic intensity make more contribution to the lesion than nonlinear propagation.5. Whether it is under atmospheric pressure or negative static pressure, acoustic intensity is 11,700W/cm2×2s, With the decreases of dissolved oxygen content, lesion is correspondingly smaller and becoming the symmetrical distribution. Negative static pressure and dissolved oxygen content decreases in degassed water can weaken or suppress various degrees cavitation. Meanwhile, B-monitoring system detect hyperechoic, which confirms that the source of hyperechoic is boiling bubbles instead of cavitation bubbles. From the PCD signal from passive cavitation detection and echo from B-mode images,we can found the reason that negative pressure and the level of dissolved oxygen content in water can suppress cavitation at some extent.