【作者】 贺雪梅；

【导师】 邹建中；

【作者基本信息】 重庆医科大学 ， 影像医学， 2003， 硕士

【摘要】 【目的】本研究通过超声实时监控HIFU处理离体牛肝组织,实时采集处理过程中不同时间点的声像图，并用热电偶探针监测焦域中心温度，旨在探讨以下问题：①HIFU致凝固性坏死阈辐照剂量的探讨；②生物学焦域面积与HIFU辐照能量间的关系分析；③焦域中心温度与HIFU辐照剂量之间的关系；④靶区声像图特点，灰度值随观察时间变化规律，随辐照辐照剂量变化的关系，与焦域中心温度的关系。⑤声像图上靶区面积与生物学焦域面积之间的关系,找出对声像图的最佳观察时间；⑥ HIFU辐照后即刻声像图上靶区面积与BFR面积回归分析。【材料和方法】新鲜离体牛肝组织，浸泡于0.9%NS中，脱气。JC型高强度聚焦超声肿瘤治疗系统，治疗头频率1.6MHz,辐照深度为20mm。以不同声功率（分别为65.44W、81.8 W、98.16 W、114.52 W、130.88 W、147.24 W、163.6 W、179.96 W、196.32 W），辐照不同时间（每种声功率下分别从1～20秒对牛肝组织进行定点辐照），采集辐照前及HIFU辐照后不同时间（0、5、10、15、30、45、60、90、120、180、240、300秒）靶区二维声像图，然后作图像后处理。热电<WP=6>偶探针测焦域中心温度。辐照结束后，切开组织块，显示最大截面,测量最大损伤径线,数码照相后软件测生物学焦域面积，取正常组织与坏死组织交界区域组织送病理检查。【结果】⑴ 当声功率等于或大于179.96W(9768W/cm2)时,辐照一秒即可产生凝固性坏死;随着声功率每增大16.36W,HIFU致凝固性坏死所需的辐照时间下降1～2秒；而当声功率减小到65.44W时，HIFU致凝固性坏死所需的辐照时间约7秒。⑵ 声功率低于130.88W时，BFR长短径比值均在在3左右，BFR形态变化不明显；声功率等于和高于130.88W时，BFR形态变化在辐照时间1～5秒时变化大，随辐照时间延长渐渐变小，至相对稳定。⑶ 相同输出功率时，BFR的面积随着辐照时间延长而呈增大趋势；相同辐照时间并且辐照时间小于6秒时，BFR随声功率增高无明显的增高，超过6秒后， BFR随着声功率增加呈明显增加趋势。⑷ BFR与HIFU剂量间的曲线拟合方程为：y=0.0164X1.0591 ，（R2=0.9238,P＜0.05）。当HIFU辐照剂量增加到2000J后，BFR面积点值渐渐与曲线分离。⑸ 在一定声功率下，随着辐照时间延长，焦域中心温度升高，但是当辐照时间达到阈值后，即使继续辐照，温度继续升高不明显。声功率小于和等于98.16W时，辐照时间阈值为15～18秒；声功率高于98.16W时，辐照时间阈值为10～12秒；声功率高于196.32W时，时<WP=7>间阈值为8～10秒。随着声功率增加，达到最高温升所需辐照时间阈值缩短。声功率小于等于81.8W时，辐照1～20秒，焦域中心温度值均低于65℃；声功率等于98.16W时，焦域中心温度绝对温升达20℃；声功率大于或等于114.52W后，当辐照时间超过阈值，继续辐照，焦域中心温度随声功率增加变化不明显，而是在80～100℃范围内波动。⑹ 当声功率低于98.16W时，辐照前后灰度差值几乎全为负值，焦域中心温度均低于65℃。当声功率达到98.16W后，灰度值从负值变为正值，致凝固性坏死所需的最小时间和使焦域中心温度值升高到65℃所需时间基本一致，与声像图上出现灰度变化为正值时所对应的时间一致。灰度差值的正负与焦域中心温度有关。以65℃为分界线，低于65℃时，即使发生凝固性坏死，灰度差值为负值；灰度差值为正值时，焦域中心温度高于65℃。⑺ 辐照时间相同，灰度值随HIFU辐照声功率的增高而上升；声功率相同，灰度值随HIFU辐照时间延长而增高。⑻ HIFU辐照后即刻，靶区表现为强回声、稍强回声或回声变化不明显。形态多为爆米花状、喷发状，或团状；中间回声高，周围常见云雾状稍强回声。辐照后随观察时间延长，靶区回声强度渐渐减低，尤其是强回声周边的雾状稍强回声，往往转瞬即逝。此刻的靶区声像图常表现为团块状稍强回声，近似椭圆形或三角形。不论是以不同声功率辐照相同时间还是以相同声功率辐照不同时间，灰度随观察时间变化趋势的走行一致。在HIFU辐照结束后的20秒内，灰度值迅速下降，在40～60秒内呈缓慢下降并且在一分钟左右稳定下来，此刻的灰<WP=8>度值变化主要由凝固性坏死引起。⑼ 二维超声监控HIFU辐照靶区，观察声像图的最佳时间为HIFU辐照后15秒。此刻声像图上靶区面积与生物学焦域面积具有一致性。⑽ 即刻声像图上靶区面积与实测生物学焦域面积回归方程如下：SBFR =12.201+0.379S0 （单位：平方毫米）（R=0.645，P<0.05）。【结论】⑴ 当声功率等于或大于179.96W(9768W/cm2)时,辐照一秒即可产生凝固性坏死;随着声功率增大,HIFU致凝固性坏死所需的辐照时间呈梯度下降；而随着声功率减小，HIFU致凝固性坏死所需的辐照时间呈梯度延长。⑵ 在一定剂量范围内,焦域中心温度与HIFU辐照剂量正相关。以相同声功率辐照不同时间，焦域中心温度随辐照时间延长呈现增高趋势，但辐照时间超过阈值后，温升缓慢，甚至开始下降。随着声功率增加，达到最高温升所需辐照时间阈值缩短。以不同声功率辐照相同时间，焦域中心温度随声功率增高而阶段性升高。⑶ 生物学焦域面积与辐照剂量间呈正相关，在一定剂量范围内，?更多还原

【Abstract】 AimsThe study aims at exploring issuses during the application of high intensity of focused ultrasound (HIFU)as follows:1. Threshold dosage of HIFU to produce coagulated necrosis;2. Relationship between the area of the biologic focal region(BFR) and HIFU dosage;3. Relationship between the temperature of the focus and HIFU dosage;4. Charater of targeted region on ultrasonogram, and its change along with the observing time. relationship among the grayscale changes of targeted region , HIFU dosage and the temperature of the focus;5. To get the best time to examine the ultrasonogram;6. Relationship between the area of BFR and the targeted region in ultrasonogram. Materials and methods:1.Exprimental devices: Model JC focused ultrasound tumor therapeutic system,abbreviated<WP=11>as Haifu Knife, developed and produced by Chongqing HIFU Technology Co,Ltd, was applied in the expriment.The equipment integrates two transducers, one is imaging probe for localization and monitoring. The other is treatment head operating at a frequency of 1.6MHz with a focusing inclination of 68.60,and having a fixed acoustic focal region of 0.62mm×0.62mm×4.1mm. At the focus, ISATA ranged from 0 to 27000 W/cm2.The temperature measurement system comprises a needle thermocouple with a diameter of 0.7mm, a ZXJ-8 intelligentized auto digital examing instrument and a computer with data acquisition software for automatically acquiring and displaying temperature vs time.2.Parameters: The bovine liver was irradiated by different acoustic powers(65.44W、81.8 W、98.16 W、114.52 W、130.88 W、147.24 W、163.6 W、179.96 W、196.32 W),and under each acoustic power,the exposure time duration was from 1～20 seconds; keeping the depth at 20mm. 3.The air containing level of circulating degassed water was less than 3 ppm in the container.4.Material: Fresh bovine liver tissue samples in-vitro,were immersed in 0.9%NS,and then degassed 25 minutes for application.5.Methods:<WP=12>⑴ Put the thermal probe into the center of focal area under the monitor of ultrasonography.⑵ The process of irradiation to monitor the whole irradiation process by ultrasonogram, and to gather the images of targeted region on ultrasonogram before and at various times(0、5、10、15、30、45、60、90、120、180、240、300 S) after HIFU irradiation; at the same time,to measure the temprature at the focus.⑶ To anatomise the bovine liver after HIFU irradiation ,to measure the diameter of the coagulative area , take photos using digital camera.⑷ We measured and analyzed the grayscale and the area of target region on ultrasonogram through a software —GrayVal(V1.0) . Results:1.When the acoustic power was equal to or higher than 179.96W, the threshold time to induce coagulative necrosis is 1 second; but when the acoustic power was lower than 65.44W, the threshold time to produce coagulative necrosis was about 7 seconds. In the range of 65.44～179.96W, the acoustic power increased 16.36W, the time to produce coagulative necrosis was 1～2 seconds prolonged.2.When the acoustic power was lower than 130.88W, the diameter ratio of longitudinal to horizontal was less than 3; the change of BFR form was minimal, when the acoustic power was higher than 130.88W, the<WP=13>diameter ratio of longitudinal to horizontal changed fast in first 5 seconds, and then lower along with the time prolonged, finally kept relatively stable.3.The BFR increased as the exposure time prolonged; the BFR didn’t change obviously within 6 seconds when the acoustic power increased, but when the exposure time was over 6 seconds, it increased along with acoustic power increase.4.The equation of BFR and HIFU dosage we concluded from the study was : y=0.0164X1.0591 ,(R2=0.9238,P<0.05).5.When the acoustic power was lower than 98.16W,the threshold time to get the peak temperature were 15～18s; When the acoustic power was higher than 98.16W and 196.32W, the threshold time were 10～12S, 8～10S respectively. When the acoustic power was equa更多还原