【作者】 敬宗玉；

【导师】 邹建中；

【作者基本信息】 重庆医科大学 ， 影像医学与核医学， 2005， 硕士

【摘要】 【背景和目的】 高强度聚焦超声(High Intensity Focused Ultrasound, HIFU)是近年来兴起的一种无创性、适形热“切除”治疗肿瘤的新技术。HIFU 生物学焦域 (Biological Focal Region, BFR)是 HIFU 热切除肿瘤的刀尖,相比于声学焦域(Acoustical Focal Region, AFR), HIFU 在组织中形成的 BFR,即 HIFU 在组织中的聚焦性能更重要,这直接关系到 HIFU 治疗肿瘤的有效性、安全性和可靠性。而对于一个确定的 HIFU 治疗头来说,HIFU 在组织中形成的 BFR 的形态和大小主要取决于两个方面:一是生物组织本身的生物学特性,包括组织结构(如密度、弹性等)及其功能状态(如血供等),二是 HIFU 的治疗剂量,即输出声功率和辐照时间。研究表明:生物组织本身的生物学特性对 BFR 的影响非常大。因此,至今为止很难有一种标准的生物组织对 HIFU 治疗头的聚焦性能进行评价、对不同 HIFU治疗头的聚焦性能进行比较。所以,建立一种尽可能与生物组织的声、热特性一致的生物组织体模就显得非常重要。本课题的目的和意义是建立一种用于评价HIFU 在组织中的聚焦性能的、与生物组织的声学特性和热学性质一致的组织体模;以该组织体模为载体,搭建一个评价 HIFU 治疗头聚焦性能的实验平台,建立 HIFU在组织中的聚焦性能的评价系统,为 HIFU 治疗头的品质保障提供一个可控的定量工具;有助于推动 HIFU 治疗技术的发展;有助于我们在制定 HIFU 治疗技术的国内、国际行业标准中占据主导地位。本课题旨在探讨以下问题:①建立一种可用于高强度聚焦超声聚焦性能评价的仿组织体模的配方和工艺流程;②测试仿组织体模的声学特性、热学性质,进行 HIFU 生物学效应的研究,并与软组织的相关性质比较;③以自制仿组织体模为载体,初步探讨 HIFU 辐照剂量与生物学效应之间的关系。 【材料和方法】 1 第一部分 按照一定配比将明胶溶液和生物组织匀浆混合,加入甲醛作为交联剂,经充重庆医科大学硕士研究生学位论文 3分搅拌混合均匀后,倒入容器内静置数小时,制得仿组织体模。2 第二部分⑴对制得的仿组织体模进行声学特性(声衰减系数)测试:仪器设备:电子天平(沈阳龙腾电子称量仪器有限公司)JC 型聚焦超声肿瘤治疗系统(重庆海扶(HIFU)技术有限公司生产),两种工作频率 0.7MHz、1.0MHz 的治疗头,输出声功率可调测试方法:辐射压力法⑵ 对自制体模进行热学性质(包括导热系数、比热、熔点)测试:仪器设备:DSC-200 PC Phox 型热流式差式扫描热量仪(德国 NETZSCH 公司)测试方法:热流式差式扫描量热法⑶ 对自制体模进行 HIFU 生物学效应测试:仪器设备:JC 型聚焦超声肿瘤治疗系统。治疗头工作频率 0.7MHz,焦距135mm,焦域 3mm×3mm×25mm,声功率 200W,辐照时间 4 秒,辐照深度 1cm。测试方法:对不同放置时间的真空包装的自制体模进行相同条件的 HIFU辐照实验,观察生物学焦域形态和大小的变化。3 第三部分利用自制体模进行 HIFU 生物学效应的研究,探讨在仿组织体模中,生物学焦域的形态和大小与 HIFU 辐照剂量之间的关系,并与新鲜离体牛肝进行对比。仪器:JC 型聚焦超声肿瘤治疗系统(辐照时间 2-10 秒,辐照深度 1cm,余参数同前)。方法:HIFU 辐照自制体模和牛肝,采集辐照前、辐照后即刻、辐照后 60 秒靶区声像图;辐照结束后,切开体模及牛肝,找到生物学焦域最大切面,数码照相,测量生物学焦域面积及长短径。【结果】1 制得的仿组织体模颜色呈深褐色,外表光滑,结构均匀,具有较好的弹性和韧性。重庆医科大学硕士研究生学位论文 42 经检测,仿组织体模的密度为 1049±2kg/m3; 声衰减系数为 0.532±0.017dB/cm(0.7MHz),0.612±0.021 dB/cm(1.0MHz);导热系数为 0.76±0.08W/m/℃,比热为 3653±143 J/kg-℃,熔点为 154±8℃。3 真空包装的仿组织体模耐储存;但体模颜色随放置时间的延长而逐渐发生变化;对体模进行相同条件的 HIFU 辐照实验得到的生物学焦域形态和大小也因体模放置时间不同而有变化,但生物学焦域的形态在 15 天内是稳定的,面积大小在 2个月内是一致的。4 在仿组织体模中形成的生物学焦域呈水滴形、椭球形,牛肝中形成的生物学焦域呈水滴形、椭球形、球形、锥形;在相同辐照条件下,体模中形成的生物学焦域面积较牛肝中大。5 辐照声功率相同时,仿组织体模上的生物学焦域面积随辐照时间的增加而增大;辐照时间相同时,生物学焦域面积随声功率的增加而增大。6 在仿组织体模内形成的生物学焦域的面积与 HIFU 辐照剂量间的直线回归方程为:Y=-3.496+5.313×10-4X (R=0.970 R2=0.941);在牛肝内形成的生物学焦域面积与 HIFU 辐照剂量间的直线回归方程为:Y=-4.237+5.073×10-4X (R=0.977R2=0.954)。 7 二维超声实时监控 HIFU 辐照自制体模和牛肝时,声像图上均见靶区回声增强,体模上靶区边界较牛肝上靶区边界清晰;体模上靶区灰阶增加值较牛肝靶区灰阶增加值高,HIFU 辐照结束后,体模上灰阶值下降较牛肝靶区灰阶值下降慢。【结论】1 本实验成功研制了一种可以用于 HIFU 生物学效应研究的仿组织体模,该体模具有很好的可塑性、光滑的外观和均匀的结构;与离体更多还原

【Abstract】 【Background and objectives】: It is well known that High Intensity Focused Ultrasound ( HIFU ) has become a new technology for hyperthermal ablation the solid malignancies. And the single coagulation necrosis region induced by HIFU was defined by Wang as Biological Focal Region (BFR). The BFR is the knife point of HIFU to hyperthermal ablating the tumor. So the investigation of the BFR is the guarantee of the effectivity and security of HIFU therapy, and it embodied the focusing performance of the HIFU energy transducer whether the BFR can be controlled. Studies showed that the appearance and area of the BFR were influenced by bionomics of the biological tissue itself and output energy of the HIFU as to one definite transducer. So, if the carrier used to investigate the BFR has the same bionomics, and under the same output energy, the appearance and area of the BFR can reflect the focusing performance of the HIFU energy transducer. The purpose and significance of our study is to develop one tissue mimicking phantom which can be used evaluating the focusing performance of the HIFU energy transducer, and the phantom should has the same acoustic characteristic and thermotic characteristic as the biological tissue; to establish one system to evaluating the focusing performance of the HIFU energy transducer; to advancing the development of the technology of hyperthermal ablation tumors. The objectives of our study is: ① to develop a HIFU phantom which mimicking the soft tissue; ② to measure the acoustic characteristic and thermotics property of the phantom; ③ to explore the variation of the BFR while exposed to the ultrasound with different exposure powers and exposure time. 【Materials and methods】: part 1 The tissue mimicking phantom was made from water、gelatin、some fresh biologic tissue. part 2 1 To measure the ultrasonic parameters of this kind of phantom, including attenuation coefficient by the method of radiation pressure. 2 To measure the thermotics parameters of the phantom, including thermal conductivity, specific heat , fusion point et al under the Measurement meter. 3 To detect the HIFU biological effect of the phantom under the Model JC focused ultrasound tumor therapeutic system, abbreviated as Haife Knife, developed and produced by Chongqing HIFU Technology Co. Ltd (working frequency: 0.7MHz; acoustic power: 200W; focal distance: 135mm; Acoustic focal region: 3×3×25mm3). part 3 1 Experimental device: model JC focused ultrasound tumor therapeutic system. 2 Material: self-made tissue mimicking phantom; fresh bovine liver tissue samples in-vitro, were immersed in 0.9%NS, and then degassed 30 minutes for application. 3 Parameters: the phantom and bovine liver was irradiated by different acoustic powers (180W、200W、 220W); under each power, the exposure time duration was from 2-10 seconds; and the exposure depth was kept at 10mm. 4 Method: ①To monitor the whole irradiation process by ultrasonogram, and to gather the images of targeted region on utrasonogram before and at varioustimes (0、60s) after HIFU irradiation; measured and analyzed the grayscale on ultrasonogram through a software—Grayval (V1.0). ② To anatomise the self-made phantom and bovine liver, then find the largest area of the BFR, to measure the area of the BFR, take photos using digital camera. 【Results】 1 The self-made phantom is sable, has smooth and glossy appearance, well-distributed construction, and good elasticity. 2 We measured the followed values for acoustic and thermal properties: density 1049±2kg/m3; attenuation 0.532±0.017dB/cm(0.8MHz) ,0.612±0.021 dB/cm(1.0MHz); thermal conductivity 0.76±0.08W/m/℃; specific heat 3653±143 J/kg-℃; fusion point154±8℃. 3 The tissue mimicking phantom in vacuum-packed can reserve more longer, but the color of the phantom was changed gradually. The appearance and area of the BFR also changed but the appearance of the BFR is stable in 15 days and the area of the BFR is stable in 60 days after HIFU exposure in the self-made phantom. 4 The appearance更多还原