【作者】 陈超敏；

【导师】 陈光杰；

【作者基本信息】 第一军医大学 ， 生物医学工程， 2007， 博士

【摘要】 放射治疗、手术和化疗是肿瘤治疗的三大主要手段，估计约60％-70％的肿瘤病人需要进行放射治疗。调强放射治疗(IMRT—Intensity ModulationRadiotherapy)是在三维适形放射治疗(3D CRT—three Dimension ConformalRadiotherapy)基础上新近发展起来的更为先进的体外三维立体照射技术，它不仅能使高剂量区的形状在三维方向上与肿瘤的形状一致，而且可对照射野范围内各点输出剂量率按要求的方式调整，优化配置射野内各线束的权重，从而可以较大幅度的增加肿瘤剂量和减少正常组织的受量，极大地提高肿瘤控制率和降低正常组织并发症的发生率。由此具有重要的放射生物学意义，已成为21世纪的放射治疗的主流发展方向。但是，目前在国内临床上应用的IMRT系统仅被国外几家大公司的产品所垄断，无论是Scanditronix MM50回旋加速器的直接调强方式，还是以电动多叶准直器为代表的动态MLC技术(Dynamic MLC，DMLC-IMRT)和静态MLC技术(step-and-shot，SMLC-MLC)的间接调强方式，前者约800万美元的价格令国人望而退步，后者对直线加速器的自动控制和治疗床的高精度要求，使目前我国现有的国产直线加速器和旧型进口加速器都无法满足，此外其电动MLC及计划系统不菲的价格也难以为中小医院所接受。一方面是临床上广泛的迫切需要和必然发展趋势，一方面是难以改变的价格以及硬件条件的瓶颈限制，IMRT技术难以广泛进入我国的临床放射治疗，数以万计的肿瘤患者得不到最佳的治疗。所以IMRT作为一种新的精确放疗技术，无论从硬件还是软件方面目前尚有许多问题需要解决和改进。为此，研究和开发能够为广大医院接受的新型IMRT系统已成为国内外研究的热点。本论文综述了国内外IMRT的研究现状，分析了目前在临床应用的IMRT系统两种主要方式(静态和动态调强)的特点和不足；在已掌握的适形放射治疗技术以及对计算机各类优化算法的深刻理解的基础上，结合我国现有的实际物质条件和技术力量、经济水平，利用已经掌握的靶区(病变)及周围重要器官的三维空间重建和体位精确重复定位技术，研制开发出适合中国国情的、具有自主知识版权、能为广大中小型医院接受并应用、具有较好性能价格比的三维静态调强放射系统，为此，所做的主要工作如下：1、静态调强放射治疗精确定位技术的研究众所周知，待治病灶的精确定位是放射治疗的前提和关键。它包括利用各种影像资料的准确显示、三维重建、勾画、病灶中心的坐标计算和机械定位装置精确定位等多个过程。其中机械定位装置是贯穿整个治疗过程的基准和桥梁，为此我们首先对体部精确定位技术及设备进行了研究，创新地提出分离式精确定位系统(“用于放射治疗的体部精确定位系统”实用新型专利申请号：200620054436.5)改进了原JX-200适形放射治疗系统中的整体式定位系统，进一步提高了系统定位精度，并成功地解决了原定位系统各种不足和缺点。在此基础上我们设计出新型头颈部精确定位系统，并取得很好的临床应用效果。CT模拟定位放射治疗系统是近年来迅速发展的一种定位方法，在本课题中我们着重对其中的激光定位系统开展了研究，掌握了利用步进电机和单片机准确控制激光定位的方法，为今后在精确放射治疗系统中扩展CT模拟定位功能奠定了基础。最后紧跟目前调强放射治疗的最新发展热点，我们开展了基于外部特征的CT／PET异机图像融合精确定位技术和基于图像引导的动态跟踪精确定位技术的初步研究。2、静态调强放射治疗计划系统及优化技术的研究IMRT作为一种新的精确放疗技术，由于技术的复杂性，其优势还远远没有发挥出来，尤其是治疗计划设计目前尚有许多问题需要解决：如选择合适的剂量计算模型和逆向计划优化方法等。随着IMRT研究的深入和逆向治疗计划的发展，放射治疗中如何自动选择射野参数引起了广泛关注，越来越多的科研人员加入到此项课题的研究行列中来。在IMRT治疗计划设计中，需要优化的参数很多，包括射线能量、射束权重、射野方向等。常用优化方法有：线性规划法、均方优化法、梯度方法、有约束模拟退火法和遗传算法等。在本课题的研究中，我们建立了基于笔射束的剂量计算模型，用卷积的方法和快速傅立叶变换(FFT)实现了精确剂量计算；用遗传算对法对IMRT逆向计划的笔射束权重进行了优化；优化过程中采用了基于剂量的目标函数来计算个体适应度的大小，建立了剂量均匀性约束和组织重要程度约束；用等剂量线、三维剂量分布和剂量-体积直方图来评估计划的优劣。最后我们用Visual c#成功开发了“GA-IMRT／200基于遗传算法的调强放射治疗计划系统”并获得国家计算机软件著作登记(2006SR02586)。研究与实验结果表明，遗传算法是一种有效的IMRT笔射束权重优化方法，能够在一个临床可接受的计算时间内得到较高适形度的剂量分布，在IMRT射野参数优化中具有广阔的应用前景。3、静态调强放射治疗实现方法和设备的研究目前在临床上实现调强放射治疗的方法主要有应用Scanditronix MM50回旋加速器法和利用多叶准直器法(静态和动态IMRT)。对于应用回旋加速器实现IMRT，显然与我国各级医院的经济实力不符，而无论是应用NOMOS公司的Peacock系统(MIMiC)，还是应用各种进口动态多叶准直器(step-and-shot，SMLC)，前者其对直线加速器的自动控制和治疗床的高精度要求，使目前我国现有的国产直线加速器和旧型进口加速器都不能满足；后者其价格和使用要求也难以为中小医院所接受。所以研究和开发能够为广大医院接受的新型IMRT系统也已成为我们研究目标和出发点。在本课题中我们首先开展了手动多叶准直器的研究，设计并研制了手动和半自动多叶准直器。然而它们因使用过于费时和繁琐，远不能满足调强放射治疗的临床实际应用。由此根据我国现状和经济水平，我们认为通过采用三维熔铅挡块到达适形照射区域剂量分布变化从而实现静态IMRT的方法，在临床上具有特别重要的意义。为此，我们独创地提出“利用切片法研制三维铅挡块实现调强放射治疗”(发明申请号：021520763)的方法，并对此开展了实验和研究。4、静态调强放射治疗系统实验验证及测试设备的研究三维水箱扫描系统是用于直线加速器定量测量模拟人体模型中射线剂量分布的设备，可全自动连续扫描测量辐射吸收剂量。但三维水箱扫描系统主要依赖进口，价格昂贵。目前国内各大医院根据临床实际应用需要，采用结构简单但能实现主要的功能的成本低廉的剂量测量水箱，又称标准水箱或标准水模。标准水箱设计了一个放水阀门(水龙头)，通过控制水龙头放水至水桶里，实现水深度的减少。如果需要水深度的增加，就采用水杯从水桶舀水至水箱中。在实际测量中，这种工作模式存在测量效率低、劳动强度大、水位控制不精确、对电路及机器有不安全等不足，本项目组为此研制的一种新型立体定向放射治疗系统剂量测量水箱(实用新型专利申请号：200620054436.X)成功地解决了标准水箱上述不足，它具有水泵自动平稳控制水位、快速、安全的特点。最后，我们开展了静态调强放射治疗系统实验验证研究，主要包括系统定位精度的检验、基于人形体模和自制有机玻璃均匀等效方形体模的两种测量相结合的的实验验证与评估。其目的是对静态调强放射治疗系统进行定位精度和剂量验证，前者是机械定位系统、计划系统和直线加速器治疗系统的综合治疗精度的检验；后者主要包括绝对剂量验证和相对剂量验证。更多还原

【Abstract】 Radiotherapy, surgery and chemotherapy are three main techniques of tumor treatment. It is estimated that about 60%-70% of cancer patients require radiotherapy. Intensity Modulated Radiotherapy (IMRT) is a three-dimensional conformal radiotherapy (3D CRT) based on the recent development of the more advanced physical basis of radiotherapy, which enable high-dose in the three-dimensional shape of the tumor shape with the same direction, and it can adjust output of dosage in every point according to the manner required within the scope of the radiotherapy field, optimizing the allocation of beam weights, which can greatly increase the tumor dose and reduce the volume of normal tissue by greatly improve tumor control and reduce the incidence of normal tissue complications. This is of important significance in radiobiology, radiotherapy has become the mainstream of the 21st century.However, as a new precise radiotherapy techniques, the actual complexity of the issue, the advantage of IMRT is far from being played out, in terms of hardware and software are still many issues that need to be addressed and improved. Therefore, research and development for new IMRT system in the majority of hospitals at home and abroad has become a hot topic. This paper summarizes the status of IMRT. Clinical application of the 1MRT system in two main ways (static and dynamic modulation) the characteristics and shortcomings; Based on a deep understanding of conformal radiotherapy and various optimization algorithm of computer technology, considering the actual conditions of China’s material and technical resources and economic level, We already know that the use of target (disease) and the three-dimensional reconstruction of around vital organs and technology of repeatable precise positioning, developed suited to China’s national conditions, with independent intellectual property, for the majority of small and medium-sized hospitals and application better functional 3D static intensity modulated radiotherapy system, which was done mainly as follows:1. Study on precise positioning technology of Static Intensity Modulated RadiotherapyAs we all know, the question of the precise location of tumor focus is the premise and key in radiotherapy. It includes information on the use of various accurate imaging method, three-dimensional reconstruction, sketches, calculation of the tumor focus and mechanical positioning system coordinates accurate positioning and other processes. Mechanical positioning device which is the benchmark and bridges throughout the entire course of treatment. We turn first to this body precise positioning technology and equipment, Innovational proposed separate and accurate positioning system ("body accurate positioning system for radiotherapy," utility model patent applications No: 200620054436.5), improve the original JX-200 positioning system in conformal radiotherapy as a whole system, and further improve the positioning accuracy of the system, and successfully resolved the deficiencies and shortcomings of the original positioning system. On this basis we are designing a new head and neck precise positioning system, and achieved good clinical results. CT simulation system in radiotherapy is a method of positioning has grown rapidly in recent years, In this issue we focus on the laser positioning system and mastered the use of laser walking motor and the way of SCM controlling accuracy positioning, to lay the foundation for future expansion in CT simulation function in precise radiotherapy system. Finally keep up with the latest developments in the current hot Intensity Modulated Radiation Therapy. We went on a different plane on the research of the external characteristics of CT/PET image fusion and based on image guided dynamic tracking precise positioning technology. 2. Study on Intensity Modulated Radiotherapy planning system and static optimization technologyIMRT, as a new accurate radiotherapy technology, is so complicated that the advantages of it have not yet been fully utilized until recently. There are many difficult problems, including how to select models of dose calculation and how to select the optimization methods of inverse planning to produce highly accurate dose, need to be dealt with. With the development of IMRT and inverse planning, the automatic selection of suitable beam parameters in external beam radiotherapy has gained wide interests, and is being studied by more and more researchers. There are many beam parameters need to be optimized, including beam energy, beam weights, and beam directions. Linear programming, quadratic programming, gradient programming, constrained simulated annealing and genetic algorithms are the typical optimization methods. In this thesis, the dose calculation model based on pencil beams was constructed, two-dimensional convolution and Fast Fourier Transform (FFT) methods were used to do dose calculation. GA was used to optimize beam weights in IMRT inverse planning, during the evolution of GA, objective function based on dose constrain was used to calculate the fitness of individuals. Dose homogeneous constrain and important factors constrain in different tissues are constructed. Iso-dose curve and dose-volume histogram were used to evaluate the treatment plan. At the end of this work, the treatment planning system of IMRT has been successfully developed with Visual c#.net 2005. Finally, we used Visual c# successfully developed a "GA-IMRT/200 intensity modulated radiotherapy planning system based on genetic algorithm ", it received the national computer software registration (2006SR02586). Research and experimental results show that the genetic algorithm is an effective IMRT beam weight optimization method, can calculate on the higher conformal dose distribution in a clinically acceptable time, have broad application prospects in IMRT parameter optimization. 3. Study on implementation and equipment of static IMRTCurrently Scanditronix MM50 roundabout accelerator and multi-leaf collimator (static and dynamic IMRT) are the two main methods in clinic to achieve IMRT. To use cyclotron for the realization of IMRT is obviously inconsistent with the economic strength of our various hospitals. The NOMOS Company’s Peacock (MIMIC) system requires so high-precision of the control and treatment bed that domestic current linear accelerator and import old accelerator cannot reach the requirement. And the application of various imports dynamic multi-leaf collimator (step-and-shot, SMLC) will be difficult for prices and the use of small hospitals to accept. There is an urgent need and inevitable trend for the use of IMRT in clinic. However, as the expensive price and hardware limitations it is difficult for the IMRT to enter China’s clinical radiation therapy widely and thus tens of thousands of cancer patients cannot get the best treatment. Therefore, research and development for new IMRT system acceptable to the majority of hospitals have become the target and starting point of our study. In this paper, we first launched a research of manual multi-leaf collimator, then designed and developed a manual and semi-automatic multi-leaf collimator. However, they cannot use too cumbersome to meet the clinical application of IMRT. So we devise a new method to achieve static IMRT through using dose distribution of the three-dimensional conformal melting blocks. Under the China’s current economic level, we believe that this method has an especially meaning in clinical application. Therefore, we propose innovative "use of 3D blocks biopsy method developed to achieve Intensity Modulated Radiation Therapy" (for its invention: 021520763), and also conduct experiments and research.4. Study on Static Intensity Modulated Radiotherapy System research experiments and test equipment3D water tank scanning system is a equipment that use linear accelerator quantitative measuring the dose distribution by simulating the distribution of rays in the model of the human body, it can measure radiation absorbed dose by automatic scanning. However, the 3D water tank scanning system mainly relied on imports and with expensive price. Currently a simple structured dose measuring water tank with low-cost are used to achieve the main function in major hospitals at home according to practical application needs in clinic, its name is standard water tank or water model. The standard water tank designed a penstock (tap), and buckets placed by controlling the taps, reduce the depth of the water. If the depth of water needs to increase, use a cup scoop a portion of water from buckets to water tank. In actual measurement, this working mode are of low efficiency measurement, large labor-intensive, water controlling inaccurate, insecurity to circuits and machinery. For this reason the project team developed a new type of stereotactic radiosurgery treatment system dose measuring water tank (utility model patent application number: 200620054436.X), it successfully resolved the above shortage of standard water tank, It has smooth automatic control of water pumps, rapid and secure features. Finally, we conducted an experiment in Static Intensity Modulated Radiotherapy system, including the system’s accuracy test, experimental verification and evaluation based on combination of two measurements: physical modeling and self-made plexiglass equivalent quadrate physical modeling. The purpose are positioning accuracy and dose verification in Static Intensity Modulated Radiotherapy, the former are integrated test of treatment accuracy in mechanical positioning, planning systems and linear accelerator treatment systems; the latter include absolute and relative dose verification.更多还原