静压力和溶氧量对HIFU所致损伤的影响及其可能机制的研究

发布时间：2018-04-21 20:40

本文选题：高强度聚焦超声 + 损伤　；参考：《重庆医科大学》2015年硕士论文

【摘要】：背景高强度聚焦超声(HIFU)作为一种无创治疗方法,已用于子宫肌瘤、前列腺癌、肝癌、胰腺癌、乳腺癌等良恶性肿瘤的临床治疗,并展示良好的安全性和有效性。HIFU辐照所致损伤是超声非线性传播、热效应、空化和沸腾泡作用的结果。气泡溶解率、气泡动力学和沸腾温度被认为是压力的函数,已经证实,过压能够通过溶解气泡、限制气泡振荡和提高沸点的方式最小化气泡和气泡的活动,即过压能提高空化阈值从而抑制空化的发生和程度。因而,过压提供了一种研究HIFU治疗机制的手段,不同研究者对过压下HIFU所致损伤的变化持有不同的观点,为进一步研究不同环境压力下HIFU对组织损伤的影响,并探讨其作用机理,本实验采用两个不同的HIFU辐照强度在梯度环境压力下进行离体牛肝组织实验,并通过只考虑非线性作用的KZK方程进行理论仿真,比较了不同环境压力下,空化对牛肝组织损伤的影响。与过压相比,由于负压能进一步降低介质水溶氧量,负压对HIFU治疗的影响尚未有研究报道。目的探讨不同环境压力和溶氧量对HIFU所致损伤的影响,以期认识过压、负压/不同溶氧量下非线性传播、空化和沸腾对HIFU所致损伤的作用。方法1.过压对等剂量下不同HIFU声强所致离体牛肝组织损伤的影响实验分为理论仿真和组织实验两部分。理论部分基于KZK方程计算了常压下空间平均声强3,900W/cm2和6,240W/cm2的非线性波形畸变和谐波滋生,并对相同辐照剂量3,900W/cm2×8s和6,240W/cm2×5s的热剂量(CEM43℃)范围进行了比较,说明非线性传播对损伤的贡献；实验部分采用1MHz的HIFU换能器在常压、0.5MPa、1.0MPa、 1.5MPa、2.0MPa、2.5MPa和3.OMPa七个环境压力两个辐照剂量下对离体牛肝组织分别进行辐照,比较损伤的形态、大小、程度并且PCD检测常压下的空化信号(有空化组和无空化组)。2.负压(-0.09MPa)和不同溶氧量(2. Omg/L、1.5mg/L、1.0mg/L)对HIFU所致损伤的影响及焦域处回声和空化信号的变化用新鲜离体牛肝组织作为实验材料,在上述不同环境条件下,使用频率1.OMHz,辐照强度为11,700W/cm2×2s,辐照过程中分别采用被动空化检测系统(PCD)和超声(US)对辐照焦域处的气泡和回声进行监控。结果1.基于KZK方程仿真计算的6,240W/cm2下的反映非线性传播的P+/P-、谐波与基波的比值均大于3,900W/cm2,但相同辐照剂量3,900W/cm2×8s和6,240W/cm2×5s的热剂量范围差别不大。2.常压下高声强6,240W/cm2×5s辐照过程有明显宽带噪声信号,表明有空化参与,而低声强3,900W/cm2×8s辐照时没有。3.3,900W/cm2×8s辐照后,损伤未随环境压力发生显著改变(p0.05),与未考虑空化的理论计算结果基本一致。而6,240W/cm2×5s辐照后,常压下比低声强辐照的损伤偏大且有明显变形,明显大于未考虑空化的KZK方程仿真结果。4.6,240W/cm2×5s辐照后,0.5MPa, 1.0MPa下损伤较常压下增大(p0.05),出现对称碳化坏死。5.6,240W/cm2×5s辐照后,随着压力增大至1.5MPa、2.0MPa、 2.5MPa和3.OMPa,损伤基本一致(p0.05),但都比常压下损伤偏小(p0.05),这与未考虑空化的KZK方程仿真结果和低声强辐照的损伤基本一致(p0.05)。6.无论是常压还是负压条件下,辐照参数为11,700W/cm2×2s,溶氧量分别为2. Omg/L、1.5 mg/L、1.0 mg/L,随着溶氧量的降低,损伤减小,且趋于椭球形对称分布；相同溶氧量时,负压条件下的损伤明显小于常压下的损伤(p0.05),且负压下、溶氧量1.0 mg/L时甚至未形成损伤。7.无论是常压还是负压条件下,辐照参数为11,700W/cm2×2s,溶氧量分别为2. Omg/L、1.5 mg/L、1.0 mg/L,辐照后B超图像上焦域处强回声水平随溶氧量的降低而减小；相同溶氧量时,负压条件下辐照后B超图像上焦域处强回声水平明显小于常压下的强回声水平,且负压下、溶氧量为1.0 mg/L时未出现肉眼可见的回声增强,甚至未形成损伤。8.常压下,辐照参数为11,700W/cm2×2s,溶氧量分别为2. Omg/L、1.5mg/L、1.0 mg/L,随着溶氧量的降低,HIFU辐照过程中3-7MHz宽带噪声水平减弱。溶氧量为2.Omg/L,与常压相比,负压下HIFU辐照过程中的宽带噪声水平减弱。结论1.常压下,对等剂量的两组辐照参数6,240W/cm2×5s和3900W/cm2×8s,前者有空化发生,后者未发生空化,而基于KZK方程仿真计算的两组热剂量范围差别不大；但辐照参数6,240W/cm2×5s在离体牛肝组织中形成的损伤大于3900W/cm2×8s,也远大于仿真结果,且形态不对称,说明瞬态空化是HIFU所致损伤增大的主要原因。2.对常压下未发生空化的辐照参数3,900W/cm2×8s,环境压力为常压、0.5MPa, 1.0MPa、1.5MPa、2.0MPa、2.5MPa和3.OMPa时,随环境压力升高,HIFU所致损伤大小、形态、程度均未发生显著变化,说明环境压力升高引起的组织声参数的变化对损伤的变化基本没有影响。3.对常压下发生空化的辐照参数6,240W/cm2×5s,当环境压力增加至0.5MPa、1.0MPa时,HIFU辐照后的离体牛肝组织损伤较常压下有显著增加(p0.05),形状由水滴状变为椭球状,并在焦域处出现了边界明显的碳化性坏死。4.对常压下发生空化的辐照参数6,240W/cm2×5s,当环境压力继续增加至1.5MPa、2.0MPa、2.5MPa和3.OMPa时,损伤范围基本一致,且小于常压下的损伤范围；同时损伤范围和理论仿真结果,以及不同环境压力下辐照参数3,900W/cm2×8s的损伤范围基本一致。说明此时空化已被完全抑制,只有超声非线性传播的作用,空化对损伤的作用远大于非线性传播。5.无论是常压还是负压下,辐照参数为11,700W/cm2×2s下的损伤随着溶氧量的降低而减小,且相同溶氧量下,负压下的损伤明显小于常压下的损伤,从被动空化检测和B超图像上回声监控得到其原因与负压和降低介质水中溶氧量能不同程度抑制空化作用有关。
[Abstract]:Background High intensity focused ultrasound ( HIFU ) has been used as a noninvasive method to treat benign and malignant tumors , such as uterine fibroids , prostate cancer , liver cancer , pancreatic cancer and breast cancer .
The experimental parts were irradiated with a 1MHz HIFU transducer at normal pressure , 0.5MPa , 1.0MPa , 1.5MPa , 2.0MPa , 2.5MPa and 3.OMPa at two irradiation doses . The morphology , size and degree of damage were compared , and the cavitation signal at normal pressure was detected by PCD ( cavitation group and cavitation group ) . 2 . Negative pressure ( - 0.09MPa ) and different dissolved oxygen ( 2 ) . The effects of Omg / L , 1.5mg / L , 1.0 mg / L on HIFU - induced damage and the change of echo and cavitation signals in focal area were monitored . Results 1 . The results showed that the ratio of harmonic to fundamental wave was more than 3 , 900 W / cm ~ 2 at normal pressure . Omg / L , 1.5 mg / L , 1.0 mg / L , decreased with the decrease of dissolved oxygen , and tended to be ellipsoidal symmetric distribution ;
Under the condition of atmospheric pressure or negative pressure , the irradiation parameters were 11,700 W / cm2 脳 2s and the dissolved oxygen content was 2 . Omg / L , 1.5 mg / L , 1.0 mg / L , the strong echo level at the focal region of B - ultrasonic image after irradiation decreased with the decrease of dissolved oxygen ;
At the same dissolved oxygen level , the strong echo level at the upper focal region of B - ultrasonic image after irradiation under negative pressure was significantly lower than that at atmospheric pressure , and no visible echo enhancement occurred at 1.0 mg / L under negative pressure , even without damage . 8 . Under normal pressure , the irradiation parameters were 11,700 W / cm2 脳 2s and the dissolved oxygen content was 2 . Conclusion 1 . Under normal pressure , two groups of irradiation parameters 6 , 240 W / cm 2 脳 5 s and 3900W / cm 2 脳 8 s , the former has cavitation , and the difference between the two groups is not large .
The damage size , shape and extent of HIFU induced by HIFU were more than 3900W / cm ~ 2 脳 8 s , which was more than 3900W / cm ~ 2 脳 8 s .
At the same time , the damage range and the theoretical simulation result , and the irradiation parameters 3 , 900 W / cm 2 脳 8 s in different ambient pressure are basically consistent . The results show that the cavitation has been completely suppressed , and only the effect of ultrasonic nonlinear propagation is more than that of non - linear propagation . 5 . Under normal pressure or negative pressure , the damage of cavitation damage is much larger than that of non - linear propagation . Under the same oxygen dissolved oxygen , the damage under negative pressure is obviously lower than that under normal pressure . The reason is related to the negative pressure and the decrease of dissolved oxygen content in the medium water .

【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R454.3

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