【作者】 龚静吉；

【导师】 谢明星；

【作者基本信息】 华中科技大学 ， 影像医学与核医学， 2006， 硕士

【摘要】 高强度聚焦超声(high intensity focused ultrasound,HIFU)是一种有效且潜力巨大的非侵入性治疗肿瘤的技术。HIFU的原理是利用超声波具有生物组织内可穿透性及能量可聚集性的特点,将较低强度超声波从体外聚焦于生物体内的靶区内,形成一个高强度超声波汇聚的焦域区,高强度超声产生的生物学效应(主要包括高温热效应、空化效应、机械效应等)致使焦域区组织细胞倾刻变性坏死(此凝固性坏死区域称为生物学焦域),焦域区周围组织无显著损伤。近年来,随着技术的迅速发展,HIFU在肿瘤治疗领域里的应用受到了国内外学者的广泛关注;同时,HIFU治疗设备的性能也在为适应临床需要而不断改进。本研究采用的是自主开发的高强度聚焦超声立体定向治疗并联机器人(3D-guided HIFU Treatment Parallel Connection to Robot,3D-HIFU-TPCR)。与传统治疗仪相比,其具有结构轻巧、制造成本低、响应速度快、运动空间大等优势。此外,传统HIFU治疗仪的声波能量经固定的路径进入目标区聚焦,治疗时超声能量集中分布在声束所通过的组织路径上,易对声波所通过路径上的机体组织产生损伤。自主开发的治疗仪其超声波换能器能够按照控制指令要求,进行圆锥形摆动,可最大程度地将所经路径上的声波能量分布在尽可能大的组织面积上,从而在保证聚焦区治疗效果的情况下,大大降低声波在进出途径上对正常组织的损伤,显著减少了治疗的副作用。这一设计为高强度聚焦超声在肿瘤治疗方面的临床应用提供了更为广阔的应用前景。本课题采用自主开发的3D-HIFU-TPCR对动物离体和活体组织分别进行定点脉冲辐照,旨在探讨该治疗仪所产生损伤效应的精确性、有效性以及影响因素,并初步评价了超声的监控作用,为其随后的临床应用提供实验数据。本研究分三部分展开:第一部分高强度聚焦超声立体定向治疗并联机器人对离体肝脏组织损伤效应的实验研究探讨自主研制的3D-HIFH-TPCR在换能器摆动治疗模式下对离体猪肝组织的定位损伤效应及影响因素。在辐照声强为2000W/cm2时,采用该装置对换能器摆动组和换能器固定组的离体猪肝组织分别进行定点脉冲辐照,辐照深度分别定位于猪肝组织表面下10mm和20mm,辐照时间分别为5s、10s、15s和20s。测量凝固性坏死区体积及其中心距组织表面距离。取靶区组织进行组织病理学检查。比较换能器摆动治疗组和换能器固定治疗组对靶组织的损伤效果,并分析辐照深度及辐照时间对生物学焦域的影响。结果显示:(1)3D-HIFH-TPCR辐照靶区形成凝固性坏死区,与周围组织分界清楚。(2)在相同辐照剂量下,换能器摆动组与换能器固定组所产生的凝固性坏死区体积大小间差异无显著性意义(P>0.05)。(3)凝固性坏死区中心距组织表面的距离与预设辐照深度间差异无显著性意义(P>0.05)。(4)在相同辐照声强及辐照深度下,凝固性坏死区体积的测值随辐照时间增加而增大,体积测值间差异有显著性意义(P<0.05);在相同辐照声强及辐照时间下,凝固性坏死区体积的测值随辐照深度增加而减小,体积测值间差异有显著性意义(P<0.05)。第二部分高强度聚焦超声立体定向治疗并联机器人对活体肝脏组织损伤效应的实验研究本研究采用自主研制的3D-HIFH-TPCR,在辐照声强为2000 W/cm2时对14只实验犬的肝实质进行体外定点脉冲辐照,辐照深度分别为皮下3cm和4cm,辐照时间分别为6min,8min和10min,系列测量辐照后即刻、2min和5min时超声所示靶区强回声区面积,随后解剖观察并测量凝固性坏死区体积及实际最大剖面面积。取凝固性坏死区内及其与周边正常组织交界区组织进行组织学检查。以探讨该装置对活体肝脏组织的定位损伤效应和影响因素,并初步评价了超声在3D-HIFU-TPCR治疗过程中的监控作用。结果显示:(1)3D-HIFH-TPCR辐照活体肝脏组织后超声示靶区回声明显增加,呈强回声改变且其面积随辐照时间的延长而增加。在相同辐照剂量下,辐照后即刻超声所测强回声面积大于实际最大剖面面积,两者间差异有显著性意义(P<0.05),2分钟及5分钟时超声所测强回声面积与实际最大剖面面积间差异无显著性意义(P>0.05)。(2)3D-HIFH-TPCR辐照活体肝脏组织后靶区内形成灰白色凝固性坏死区,周边包绕暗红色充血带,与周围正常组织分界清楚。(3)3D-HIFH-TPCR定点辐照离体组织,在相同辐照声强及辐照深度下,生物学焦域体积的测值随辐照时间的增加而增大,体积测值间差异有显著性意义(P<0.05);在相同辐照声强及辐照时间下,生物学焦域体积的测值随辐照深度的增加而变小,体积测值间差异亦有显著性意义(P<0.05)。第三部分高强度聚焦超声立体定向治疗并联机器人对活体不同组织损伤效应的实验研究采用自主研制的3D-HIFH-TPCR,对活体犬的肾脏和肌肉组织在辐照声强为2000 W/cm2、辐照时间为6min和辐照深度为皮下3cm时分别进行定点脉冲辐照,结合第二部分实验结果,测量和比较辐照后肝脏、肾脏和肌肉3种组织超声声像图中强回声区面积及生物学焦域体积的大小。辐照结束后分别取凝固性坏死区内及其与周边正常组织交界区组织进行组织学检查。比较在相同参数下3D-HIFH-TPCR定位辐照活体不同组织所产生损伤效应。结果显示:在辐照声强为2000 W/cm2、辐照时间为6min和辐照深度为皮下3cm时,活体犬肝脏,肾脏以及肌肉组织超声声像图中强回声区面积分别为(471.40±56.20) mm2、(117.16±16.89) mm2、(881.82±32.54) mm2,生物学焦域体积分别为(3243.49±243.79) mm3、(608.28±73.55) mm3、(7886.82±165.64) mm3;3种组织间强回声面积及生物学焦域大小的差异均有显著性意义(P<0.05),由大到小依次为肌肉、肝脏和肾脏。结论(1)高强度聚焦超声立体定向治疗并联机器人在换能器摆动模式下对组织可产生精确有效的损伤。(2)生物学焦域与辐照剂量及组织生物学特性有关。(3)超声可以准确的反映3D-HIFH-TPCR在生物组织中形成的损伤效应,是一种方便有效的评价方法。更多还原

【Abstract】 BACKGROUND AND PURPOSE HIFU (High Intensity Focused Ultrasound) is one of the most effective and promising non-invasive cancer treatment technologies. Ultrasound power could be concentrated and penetrated into biologic tissues, which make it possible to introduce low power ultrasound into human body and concentrate into the target where the ultrasound power is intensively high. Biologic effects of HIFU would coagulate target tissue in a very shot time while keeping surrounded tissue safe (thermal effects by high temperature, cavitation effects, and mechanical effects, etc.). No notable damage would be caused nearby normal tissues. The application of HIFU in cancer treatment is accepted widely by domestic and international researchers in recent years. However, with the development of technologies, HIFU treatment equipments should be improved according to clinical requirements.Compared with traditional HIFU cancer treatment machines, our self-developed serial-parallel robot has such merits as lighter structure, lower cost, faster response and larger workspace. Besides, traditional ultrasound transmission profile is static and the ultrasound power would accumulate along transmission trajectory. Inevitable damage would be caused along the trajectory. Whereas,recommended HIFU treatment robot is able to do cone like movement according to driving commands so that the ultrasound power could be distributed in a greater volume and tissue interface where it goes into the patient body. Side effect could be reduced by such treatment scheme without any loss in treatment efficacy, especially for on acoustic interfaces. Such design is supposed to be able to offer much better outcome in clinical HIFU cancer treatment.In vitro and in vivo tissue ablations have been carried out by fixed point HIFU pulse radiation with the help of self-developed cancer treatment robot. The objective of this research is to study the positioning accuracy of HIFU focus in different tissues, HIFU efficacy in tissue ablation and discuss the related factors. Preliminary evaluation has been given for the efficacy of US monitoring and experiment data have been obtained for possible future clinical applications. This research consists of two parts:Part 1. Experimental Study on damage effects in Liver tissue in vitro by 3D-guided HIFU Treatment Parallel Connection to RobotThe objective of this study is to assess in vitro fixed-point ablation efficacy and related affecters in porcine liver with ultrasound transducer doing cone like movement on studied robot. Both transducer movement modes of static position and cone-like rotation have been studied at acoustic focus power of 2000W/cm2. Radiation focus depths have been set to be 10mm and 20mm from the porcine liver surface. Radiation time has been set to be 5s, 10s, 15s and 20s respectively. Variables measured include the volume of coagulated necrosis and the distance between necrosis and tissue surface. Target tissues have been examined pathologically. Comparison has been carried out on the ablation efficacy between data from the group of cone-like rotation transducer and the group of static position transducer. Biological effects of radiation focus depth and radiation time have also been analyzed.Results(1)Radiated HIFU target is a well-delineated gray coagulated necrosis area.(2)With the same radiation dose, there’s no notable difference in coagulated necrosis volume between two groups (P>0.05).(3)There’s no notably difference between preset depth and central coagulated necrosis depth (P>0.05).(4)Coagulated necrosis by static HIFU radiation increases with the radiation time under the same radiation power and depth. Coagulated necrosis by fixed HIFU radiation decreases with radiation focus depth under the same radiation power and time.Part 2. Experimental Study on damage effects in Liver tissue in vivo by 3D-guided HIFU Treatment Parallel Connection to RobotLiver parenchymas of 14 canines have been extracorporeal radiated by static positioned transducer of pulsed 2000W/cm2 HIFU radiation by recommended robot. Radiation targets have been set to be 3cm and 4cm deep from the skin. Treatment time is set to be 6min, 8min, and 10min respectively. In vivo liver parenchyma has been treated and B-scanning image of the target has been examined immediately, 2 min after, and 5 min after respectively. Anatomic coagulated necrosis volume has been examined after HIFU radiation and maximal dissection area has been recorded. Coagulate necrosis and nearby normal tissue has been examined for the histological study of static HIFU ablation in liver in vivo and related affecters. Preliminary evaluation has been given for US imaging in HIFU treatment supervising.Results(1)Target echo would be notably strengthened after HIFU radiation. The area of echo increases with the time of radiation. Under the same radiation dose, immediate strong echo area on B-scanning image after HIFU radiation is notably greater than actual anatomic coagulative dissection area. There’s a significant difference between them (P<0.05). However, there’s no significant difference between maximal actual anatomic dissection area and strong echo area on B-scanning image 2min and 5min after HIFU radiation (P>0.05).(2)Grey coagulated necrosis area has been observed in target area in tissue after HIFU radiation, bounded by a dark red blood congested cone that has a clear border with nearby normal tissue. Biologic focus volume increases with radiation time under the same radiation power and depth. Biologic focus volume decreases with radiation depth under the same radiation time. Part 3: Experimental Study on damage effects in different kinds of tissue in vivo by 3D-guided HIFU Treatment Parallel Connection to RobotKidney and muscle tissue in canine has been processed in vivo by 2000 W/cm2 pulse HIFU by recommended robot. Radiation target has been set to be 3cm away from the skin in kidney and muscle respectively, and radiation time has been set to be 6min. Considering about the experiments in Part II, area of target echo on B-scanning image has been examined in addition to anatomic volume of coagulative necrosis. Histological examination has been carried out after HIFU radiation on coagulative necrosis and surrounding boundary tissue. Static transducer ablation effects on different kinds of tissues have been evaluated under the same treatment parameters on recommended robot.Result Strong echo areas are (471.40±56.20) mm2、(117.16±16.89) mm2、(881.82±32.54) mm2 respectively in canine liver, kidney and muscle tissues in vivo. Acoustic power is 2000W/cm2. Radiation time is 6min. Radiation depth is 3cm beneath the skin. Biological focus volumes have been examined to be (3 243.49±243.79) mm3、(608.28±73.55) mm3、(7 886.82±165.64) mm3 respectively. There’s notably difference in the difference of strong echo area on B-scanning image and actual biological focus area in different kinds of tissues in vivo experiments (P<0.05). From big to small size, the sequence of difference is the tissue of muscle, liver and kidney.CONCLUSIONS:(1) Recommended HIFU treatment robot is able to introduce exact and effective ablation in tissue by swing movement of transducer.(2) Coagulative necrosis takes place in radiation target and has a clear border with nearby normal tissue. The size of biologic focus area is determined by the acoustic and biologic characters of tissues.(3) Ultrasound imaging is an effective method for accurate evaluation of HIFU introduced ablation in biologic tissues.更多还原