重离子对运动肿瘤靶区的适形照射治疗方法研究

发布时间：2018-08-16 13:18

【摘要】：重离子束由于其倒转的深度剂量分布(Bragg峰)特性和高的相对生物学效应,使其在杀死肿瘤细胞的同时正常组织得到有效保护,被誉为二十一世纪最优越的放疗手段。在治疗如头颈部等相对位置比较固定的肿瘤靶区,只要照射前对患者进行有效的固定就能达到精确放疗的目的。然而,临床上一些肿瘤处于运动器官上,靶区运动给治疗计划的实施制造了很多困难。由于靶区处于运动状态,实际照射点和计划照射点位置可能发生偏移,这样导致靶区内照射点相对位置发生改变,致使局部产生剂量热点和冷点,使剂量分布发生严重畸变,甚至对周围的正常组织产生辐射损害,使离子束治疗疗效大幅下降。为了使肿瘤靶区接受高剂量照射,同时使靶区周围的正常组织得到有效保护,进一步发挥离子束放疗的优势,本论文基于HIRFL-CSR深层治疗终端和HIMM治疗装置的被动式和主动式束流配送系统开展了一系列针对运动肿瘤靶区的离子束适形调强放射治疗技术研究,主要研究成果与内容如下:(1)建立了运动靶体的4D-CT扫描方法、开发了一套运动肿瘤靶区的定位装置并建立了CT-WEPL调正曲线。基于西门子Sensation Open CT以及AZ-733V呼吸门控系统实现了运动肿瘤靶区的4D-CT扫描。发明设计了一种放射治疗中胸腹部随患者呼吸运动肿瘤靶区的定位装置及方法。由于该装置使患者在CT扫描,制定治疗计划以及计划实施均在相同的坐标系内进行,因此能够确保靶区定位和放疗计划的精确实施。为了获得肿瘤靶区的ITV(内靶),本工作通过实验依托HIRFL-CSR建立了近物所自己的CT-WEPL调正曲线。(2)提出了可调控慢引出时间点扫描应用于运动肿瘤靶区的适形照射治疗方法,并通过计算机模拟验证了该方法的有效性。结果显示,随着束流慢引出时间的增加靶区内剂量分布均匀性逐渐变好。对于可调控慢引出时间结合体多次扫描的情况,需要合理的选择慢引出时间才能得到理想的均匀剂量分布。对于可调控慢引出时间结合层多次扫描的情况,尽管施加了10次的层多次扫描,但剂量均匀性没有得到有效改善。对于可调控慢引出时间结合增大相邻扫描点束斑重叠度的情况,采用增大束斑半高宽的方法可以有效提高靶区内的剂量分布均匀性,而采用减小相邻扫描点间距的方法并没有起到提高靶区剂量分布均匀性的效果。(3)设计加工了一套人体呼吸模拟系统并基于该系统开展了一系列靶区运动补偿实验。人体呼吸模拟系统由四部分组成:二维运动平台,双楔系统,多楔系统和系统台架。除系统台架外其它子系统的运动模式包括:函数模式、数列模式、传感器模式、加速器外控模式以及补偿模式。基于该系统我们开展了运动靶区的多次扫描实验,增大束斑半高宽对靶区运动的补偿实验,手动多叶光栅主动跟踪实验以及纵向运动补偿实验。多次扫描和增大束斑半高宽有效的提高了运动靶区的剂量分布均匀性,但这两种方法都会导致剂量半影的增大,若应用于临床上对周围正常组织的辐射损害相应也会变大。(4)在HIRFL-CSR深层治疗终端建立了呼吸门控系统。该系统通过opto NCDT1700-750激光位移传感器间接获取靶区运动信息。由于从探测到靶区位置到束流照射有一个时间延迟,我们发展了一种交互式多模型的机动目标跟踪算法,并将其应用于呼吸运动预测。结果显示,呼吸预测算法的引入使剂量分布均匀性得到大幅提高。对HIRFL-CSR深层治疗终端建立的呼吸门控系统进行实验测试表明,在被动式束流配送系统下采用呼吸门控照射方法,剂量半影明显减小,基本恢复到与静态情况下相类似的剂量分布。然而,采用呼吸门控照射方式使照射时间大幅提高,有效剂量率明显下降。(5)提出了生物视听反馈呼吸引导技术并通过实验测试验证了该方法的有效性。鉴于现有技术在基于同步加速器脉冲式束流配送治疗运动靶区时过程繁琐,效率低和系统误差较大的问题,我们提出了一种呼吸引导方法,该方法有效地将个体化视听反馈系统、呼吸屏气技术和基于同步加速器的呼吸门控技术结合起来,帮助患者将自己的呼吸周期与加速器磁激励周期同步。通过志愿者测试发现,在被动式束流配送系统下,采用呼吸引导技术使照射效率提高了1.73~4.65倍,照射精度提高了10倍左右,并且该方法在分次治疗间具有重复性。在主动式束流配送系统下,我们对呼吸引导技术进行了剂量模拟验证。结果显示,采用呼吸引导的照射模式使剂量分布基本恢复到了与静态情况下相类似的均匀分布。与常规自由呼吸模式下呼吸门控治疗效果相比,呼吸引导不但提高了治疗效率而且降低了门控窗内靶区的残余运动,因此大幅提高了治疗的疗效。
[Abstract]:Heavy ion beams, due to their inverted depth dose distribution (Bragg peak) characteristics and high relative biological effects, can effectively protect normal tissues while killing tumor cells. They are considered as the best radiotherapy in the 21st century. However, in clinic, some tumors are located in moving organs. Target movement makes it difficult to implement the treatment plan. As the target is in motion, the actual and planned positions of the irradiation points may be offset, resulting in the relative position of the irradiation points in the target area. In order to protect the normal tissues around the target area and protect the normal tissues effectively, ion beam radiation therapy can be further developed. Based on the passive and active beam delivery systems of HIRFL-CSR and HIMM, a series of ion beam conformal intensity modulated radiation therapy (IMRT) techniques for moving tumor targets have been developed in this paper. The main research results and contents are as follows: (1) A 4D-CT scanning method for moving target has been developed. Based on Siemens Sensation Open CT and AZ-733V respiratory gating system, the 4D-CT scanning of the moving tumor target area was realized. A device and method for locating the moving tumor target area in the chest and abdomen with patients breathing in radiotherapy were invented and designed. In order to obtain the ITV (internal target) of tumor target area, we established the CT-WEPL correction curve of the near object through the HIRFL-CSR experiment. The results show that the uniformity of dose distribution in the target area gradually improves with the increase of the slow extraction time of the beam. For the case of multiple scans of the adjustable slow extraction time combination, a reasonable selection of slow extraction time is needed. The uniformity of dose distribution can be obtained only when the extraction time is controlled. For the case of multiple scan of the slow extraction time binding layer, the uniformity of dose is not improved effectively although 10 times of multiple scan are applied. The method of height and width can effectively improve the uniformity of dose distribution in the target area, but the method of reducing the distance between adjacent scanning points can not improve the uniformity of dose distribution in the target area. (3) A human respiratory simulation system was designed and manufactured and a series of motion compensation experiments were carried out based on the system. The system consists of four parts: two-dimensional motion platform, double-wedge system, multi-wedge system and system bench. The motion modes of other subsystems besides the system bench include: function mode, sequence mode, sensor mode, accelerator external control mode and compensation mode. Experiments of half-width compensation for target motion, manual multi-leaf grating active tracking and longitudinal motion compensation. Multiple scanning and increasing the half-width of the beam spot effectively improve the uniformity of dose distribution in the moving target area, but both methods will lead to the increase of dose penumbra. (4) A respiratory gating system was established at the HIRFL-CSR terminal. The system obtains target motion information indirectly by opto NCDT1700-750 laser displacement sensor. Since there is a time delay from the detection of target location to the beam irradiation, an interactive multi-model maneuvering target tracking system was developed. The results show that the uniformity of dose distribution is greatly improved by introducing the respiratory prediction algorithm. The experimental results of the respiratory gating control system of HIRFL-CSR deep-seated treatment terminal show that the dose penumbra is significantly reduced by using the respiratory gating irradiation method in passive beam delivery system. However, breath-gated irradiation greatly increases the irradiation time and significantly reduces the effective dose rate. (5) A bio-audiovisual feedback breath guidance technique is proposed and its effectiveness is verified by experimental tests. Pulsed beam delivery is a complex, inefficient and error-prone method for the treatment of moving targets. We propose a breathing guidance method which effectively combines the individualized audio-visual feedback system, breath holding technology and breathing gating technology based on synchrotron to help patients to adjust their breathing cycles with their own. The results of volunteer test show that the irradiation efficiency and the irradiation accuracy are increased by 1.73-4.65 times and 10 times respectively in passive beam delivery system, and the method is repeatable in the course of fractional treatment. Respiratory-guided irradiation was used to restore the dose distribution to a uniform distribution similar to that of static irradiation. Compared with conventional free-breathing ventilation, respiratory-guided irradiation not only improved the treatment efficiency, but also reduced the residual movement of target area in the door-controlled window. Therefore, the therapeutic effect has been greatly improved.
【学位授予单位】：中国科学院研究生院（近代物理研究所）
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R73-36

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