4D-CT重建及其在放疗中的应用研究
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摘要
CT图像具有独特的空间分辨和密度分辨优势,是影像技术发展过程中里程碑式的突破。作为一种间接成像技术,与常规X射线透视相比,普通CT图像不能实时反映人体内脏器官随呼吸运动变化的规律,但通过计算机进行三维重建后可以反映其空间结构。近年来,随着影像技术的进步,为了进一步反映人体内脏器官随呼吸运动变化的特征,把时间因素纳入CT图像的扫描和重建过程便出现了四维计算机断层摄影(Four Dimensional Computed Tomography,4D-CT),与普通CT相比,4D-CT大大减少了呼吸运动伪影,不仅能真实地再现肝、肾、肺和膈肌等内脏器官的形态,而且能反映它们的运动范围和运动方式。4D-CT图像与放疗技术相结合,对运动靶区的精确放疗产生了深远的影响:①利用4D-CT图像分析靶区及正常器官在呼吸过程中位置和体积的变化规律,有助于根据患者独特的运动特征进行个体化放疗计划设计,减少靶区照射范围,在提高靶区受照剂量的同时,降低正常组织的毒副作用。②在体部立体定向放疗过程中,用4D-CT图像能方便、准确地研究不同腹压时肿瘤和器官的运动规律,指导放疗过程中腹压技术的使用,达到精确放疗的目的。③用4D-CT图像还可分析靶区与内外标记的相关性,与其它四维影像技术相结合进行精确的四维图像引导放疗,实现肿瘤放疗技术从三维到四维的跨越。
但是,现有的4D-CT图像重建技术仍有这样或那样的缺陷,在放疗中的应用还受到多方面的限制,主要包括:①没有国产的4D-CT系统,进口系统不但昂贵,而且依赖于呼吸监测装置,只能在少数新型CT机上实现4D-CT图像重建。⑦由于4D-CT图像数量众多,通常有1000～2000张,甚至更多,在目前缺乏成熟的四维放疗计划系统的情况下,在4D-CT中勾画靶区和危及器官的工作量约10倍于常规三维适形放疗,使靶区勾画成为制约4D-CT在放疗中广泛应用的瓶颈。③不同相位4D-CT中,运动靶区受照剂量的计算和验证仍然困扰着四维放疗。为了克服4D-CT图像重建对呼吸监测系统的依赖,在普通螺旋CT机上实现4D-CT图像重建,Berlinge等提出了利用杠杆原理的“针影轨迹”重建法,但这种方法在重建过程中能识别的相位数较少,通常只有5个,而且不能识别呼气或吸气的中间状态。为了便于4D-CT在放疗中的应用,McClelland等提出了基于运动模型的连续4D-CT重建法,Zeng等提出了迭代模型重建法。虽然,采用这两种方法重建的4D-CT图像质量较高,但其最大的缺陷是计算时间长达数小时,临床实用价值有限。因此,研究4D-CT图像重建技术及其在放疗中的应用,无论从社会效益还是从经济效益出发,都具有不可估量的价值和意义。
在全面总结进口4D-CT图像重建系统的优缺点及其在放疗应用中存在的问题之后,研究中提出了两种新的4D-CT图像重建法,并编写了相应的软件系统,实现方便、快捷的4D-CT图像重建,打破了没有国产4D-CT图像重建系统的局面,并在此基础上进行了4D-CT图像在放疗中的应用研究,主要内容可概括如下:
(1)呼吸运动对靶区三维重建的影响。用步进马达、驱动器、导轮、有机玻璃球、低密度泡沫等模拟呼吸运动体模。用GE LightSpeed 16排螺旋CT对体模进行扫描,分析不同螺距、层厚和运动周期对靶区扫描后三维重建体积和形态的影响,并计算动态靶区重建体积相对于静态靶区重建体积的偏差。研究中发现:①对于静态靶区,改变扫描层厚与螺距对三维重建体积和外观的影响不明显:②对于动态靶区,不同运动状态下扫描后,重建体积和外观差异显著,其相对偏差的变化范围与靶区大小有关,外形较小的靶区为-39.8%～89.5%,外形较大的靶区为-18.4%～20.5%,说明呼吸运动对靶区三维重建的影响很大,三维适形放疗计划设计所采用的CT图像必须是靶区处于相对静止状态下扫描的图像,否则,放疗计划设计中将存在很大的误差。因此,减少运动伪影并在放疗计划和实施过程中充分考虑靶区的运动规律是实现精确放疗的必要条件。
(2)根据对4D-CT图像重建原理的分析,结合扫描时图像之间的内在联系,本研究创造性地提出了基于“相??像最相似原理”的4D-CT重建法,用VC++程序设计语言和可视化工具软件包(Visual Tools Kits,VTK)开发了相应的软件系统。对自由呼吸状态下的患者进行多床位的“电影”(Cine)扫描,每个床位处Cine扫描的持续时间等于患者的呼吸周期加上1秒。扫描后把相邻图像问的互信息作为相似性的测度,据此对所得扫描图像进行相位排序,实现4D-CT图像重建。实验结果表明,这种方法重建的4D-CT图像质量高、运动伪影显著减少,不仅真实地再现了靶区形态,而且反映了靶区随呼吸运动变化的规律。其不足之处是重建时间稍长,当CT层数在1000～2000时,在Dell Latitude 620笔记本电脑上重建一个相位4D-CT的时间约3-5分钟,另外,该方法不能直接确定呼吸相位。
(3)针对上述不足,为了实现更简便、高效的4D-CT重建,研究中进一步提出了基于呼吸运动过程中胸腹体积/肺体积变化的4D-CT重建法,开发了相应的软件系统,其主要模块包括:数据传输、CT图像读入、阈值分割、体积计算、相位排序、分相4D-CT重建、动态显示、结果输出和打印等。研究中对典型病例进行了4D-CT重建实验,患者在自由呼吸状态下进行多床位的Cine扫描,扫描后根据所得CT图像中胸腹体积/肺体积的变化,确定每一层CT图像在呼吸周期中的相位,按不同相位对所有CT图像进行分组,得到一个完整的呼吸周期中多个相位的CT系列,实现了4D-CT重建。
与昂贵的进口系统相比,本研究开发的4D-CT图像重建系统有如下优势:
①能在所有普通螺旋CT上实现4D-CT重建,其重建过程不依赖于外在的呼吸监测装置,不受CT机本身的软硬件限制,具有普遍适用性。进行4D-CT重建后,可输出任一相位的4D-CT横断位、矢状位、冠状位及三维视图,方便4D-CT在后续临床和科研中的应用。
②能对胸腹部带有热塑体模固定装置的放疗患者进行4D-CT重建,这是对目前进口4D-CT图像重建系统局限性的一次重大突破。当放疗患者采用了热塑体模固定装置时,由于体模的限制,患者体表不再随呼吸而起伏、或者起伏的幅度变得非常微小,在这种情况下,体表监测装置不能准确地确定呼吸相位,从而导致目前进口4D-CT系统不能正常工作。本研究开发的重建系统可根据呼吸运动过程中肺体积的变化和“相邻图像最相似原理”进行4D-CT图像重建,不受热塑体模的影响,将会大大促进4D-CT图像重建技术在体部精确放疗中的应用。
③基于呼吸运动过程中胸腹体积/肺体积变化的4D-CT图像重建系统具有简便??效的优势。例如:在配置为1GB内存的Dell Latitude D620笔记本电脑上,读入1200幅CT图像(512×512),仅需要约40秒,图像分组、排序时间不到10秒,重建任意相位的矢状位、冠状位4D-CT不到2秒。在台式PC上(2GB内存),读入2000幅CT图像(范围覆盖全胸腹)后,也能在10秒内完成4D-CT重建过程,其效率远远高于计算时间长达数小时的基于运动模型的4D-CT重建。
④实现了真正意义上的4D显示。既往4D-CT重建文献中报道了矢状面、冠状面4D-CT图像。本研究不仅完成了矢状面、冠状面4D-CT图像重建,而且完成了4D-CT图像的横断面、矢状面和冠状面3D视图重建,更逼真地反映了内脏器官随呼吸运动变化的规律。
(4)在完成4D-CT图像重建研究后,基于4D-CT、平均密度投影和最大密度投影CT,研究了运动靶区的表现特征及其进行三维适形和调强放疗时的剂量分布规律:①分析肺尖、右肺和腹部靶区在4D-CT、平均密度投影和最大密度投影CT中的差异。②根据平均密度投影和最大密度投影CT的本质特征,开发了一套软件系统,该系统在生成平均密度投影和最大密度投影CT时不需要进行4D-CT重建、也不用任何呼吸监测装置,可以利用任何能进行Cine模式扫描的CT机生成平均密度投影和最大密度投影CT。③利用自制的运动体模,研究了窗宽/窗位对平均密度投影和最大密度投影CT图像中运动靶区勾画的影响,为运动靶区的精确放疗打下了基础。④在利用4D-CT研究不同相位运动靶区的剂量分布特征时,巧妙地利用了放疗计划系统的图像融合功能,得到不同相位4D-CT系列、平均密度投影和最大密度投影CT中的剂量分布,直观地反映了运动靶区受照剂量分布随呼吸运动变化的特征:(?)靶区随呼吸运动时,根据一个极限相位4D-CT设计的放疗计划可能在另一相对的极限相位中造成靶区遗漏。(?)用平均密度投影和最大密度投影CT勾画靶区后进行三维适形放疗和调强放疗计划设计,其剂量分布能很好地覆盖两个极限呼吸相位4D-CT中的靶区,不会过分扩大照射范围,使运动靶区受到合理的照射。(?)利用平均密度投影和最大密度投影CT还可大大地减轻在多相位4D-CT中进行靶区勾画的劳动强度,是充分利用靶区运动信息的一个切实可行的好方法。⑤根据靶区往返周期运动的特点,木研究提出了简化的运动靶区剂量计算“矩阵叠加”模型??atlab 7.0工具软件,编写了相应的模拟计算程序,通过计算预测运动靶区的受照剂量分布规律。
(5)利用模拟呼吸运动平台和二维空气电离室矩阵MatriXX系统,研究运动靶区实际受照剂量分布的特点。研究中揭示了运动靶区的“边缘剂量模糊效应”和基于多叶准直器的调强放疗子野照射时剂量分布的“随机效应”。正是由于各子野的位置和大小不同,照射运动靶区后产生的剂量分布具有随机性,当子野剂量叠加后,剂量误差有相互抵消的趋向。体模周期运动时,对三维适形放疗照射,在运动方向上所测剂量分布半影较静态时增加6～9 mm,高剂量区域向内收缩约5mm,低剂量区域向外扩张约5mm,但50%等剂量曲线范围及中心区域剂量未见明显改变;调强放疗各子野单独照射且以测量平面最大剂量为归一剂量时,运动和静止状态下所测剂量差异介于-56.4%～56.1%,其平均值约±27%。调强放疗计划所有子野叠加照射时,两种运动状态下在射野中绝大部分区域的剂量分布相对偏差＜±3%,其偏差主要出现在射野边缘,最大约±15%,这与三维适形放疗照射的特点相似。说明无论是三维适形放疗还是调强放疗多次分割照射后,周期运动靶区中心区域受照剂量与静态靶区相近,但高剂量区域向内收缩,低剂量区域向外扩张,实验测量结果与运动靶区剂量计算的“矩阵叠加”模型的预测结果相一致,为利用4D-CT进行运动靶区的剂量评估提供了一种新的方法。
在论文最后总结了研究工作已取得的成果,指出了存在的不足和下一步工作的计划,并列出4D-CT系统中的部分程序流程图和源代码。
Computed Tomography(CT) image owns some unique advantages in spatiality and density resolution,which has become a landmark in the developing history of medical image technique.Compared with the conventional X-ray fluoroscopy,the ordinary CT scan,as an indirect image technique,cannot synchronously characterize the dynamic features of the motion viscera in thorax and abdomen.Nevertheless, ordinary CT can reflect the three-dimensional(3D) spatial structures by applying 3D-CT reconstruction.In recent years,four-dimensional computed tomography (4D-CT) has been developed in order to characterize the dynamic features of motion targets.Compared with traditional CT scan,4D-CT has greatly reduced the motion artifacts,not only representing the shape of organs in thorax and abdomen such as liver,kidney,lung and diaphragm which will move with the respiration,but also reflecting the extents and features of movement.4D-CT and its application in radiation therapy have brought about a profound effect in precise radiotherapy for the thoracic and abdominal organs:①4D-CT can be applied to analyze the characteristics of volume variation and location displacement of targets and organs at risk during the respiratory motion,which is of great help to design the patient-specific treatment plan that can reduce the irradiated area and increase the target dose and at the same time spare the normal tissues.②In the course of stereotactic radiotherapy of lung and liver,4D-CT can be expediently applied to analyze the tumors and organs of motion at varying levels of abdominal compression,which will guide the application of abdominal compression and implement precise radiotherapy for lung and liver tumor.③4D-CT can be used to investigate the correlation between internal fiducial tumor motion and external marker motion and implement 4D image guided radiation therapy(IGRT),which will promote in the advance of radiotherapy from 3D to 4D.
However,there still exist some limitations in the present 4D-CT system. Currently,the main factors that restrict 4D-CT to a wide utilization in precise radiotherapy include the following aspects:①There is not any 4D-CT system developed in native China yet.The imported 4D-CT systems are very expensive, which must depend on external respiration monitor devices while acquiring synchronous respiratory signals and 4D-CT reconstruction can be implemented only by a small number of newer-type CT scanners.②Now there is not perfect commercial 4D treatment planning system(4D-TPS).The 4D-CT data series contain a great number of CT slices,usually 1000～2000 slices or even more.The workload of segmenting targets and organs at risk(OAR) on 4D-CT slices usually needs ten times of that on the conventional CT.As a result,target delineation has become a bottleneck of the application of 4D-CT in radiation therapy.③The dose accumulation and verification of motion targets in 4D treatment planning still are the great problem?? the whole process of 4D radiation therapy.
In order to solve the limitations of the present 4D-CT systems,which must depend on the external respiration monitor systems and implement 4D-CT reconstruction on common helical CT scanners,Berlinge et al proposed a simple 4D-CT reconstruction method,which labels the CT images in the respiratory state by a needle that follows the abdominal respiratory motion by means of leverage.This method can implement 4D-CT reconstruction without external breath monitor and has been greatly accepted in clinics due to its simplicity.But,the positions of the needle in Berlinge's 4D-CT reconstruction were binned into only five respiratory states instead of eight to ten bins used by others and it was impossible to distinguish between the intermediate,inhale and exhale directions of the breathing cycle.Another 4D-CT reconstruction method put forward by McClelland et al was based on continuing 4D motion model.And the iterative sorting method proposed by Zeng et al was based on the internal anatomy motion,which can get a high-quality 4D-CT image.However,all the reconstruction methods have limitations.The disadvantage of those methods is that the calculation will cost several hours.So the application value was very limited.Hence,it is of great necessity to improve the 4D-CT reconstruction and its application in radiation therapy.
On the basis of summarizing the former achievements and limitations of 4D-CT reconstruction and its application in radiotherapy,two novel 4D-CT reconstruction methods have been proposed in our study.The corresponding software systems have been developed,which will result in simple and fast 4D-CT reconstruction.As a result,the condition of no domestic 4D-CT reconstruction system has changed.Thus, the applications of 4D-CT in radiotherapy have been investigated in the study,the main works of which can be recapitulated below:
First,a motion platform that can simulate??an respiration was developed with a step motor,motor driver and low-density foam.Several balls with different sizes made of polyethylene and two potatoes were placed into the low-density foam to simulate tumors with different sizes.The motion phantom was adopted to investigate the respiratory effects on 3D reconstruction of motion targets with different periods and initial phases,which were scanned by a GE LightSpeed16 CT scanner with different pitches and slices.The relative deviations of reconstruction volumes between dynamic targets and the stationary ones were calculated.No obvious differences were observed between the 3D reconstruction volumes of stationary targets scanned with different pitches and slices.But great differences were found between the 3D reconstruction volumes of dynamic targets and stationary ones.The relative deviations of reconstruction volumes of targets,which were scanned with different pitches,slices and periods,were variable among the targets,about -39.8%～89.5%for the smaller targets and -18.4%～20.5%for the larger ones,which indicates that the respiration has great effects on the 3D reconstruction of the tumor targets.The CT images adopted in three-dimensional treatment planning system (3D-TPS) must be acquired while the targets are under static condition.Otherwise, severe errors will be introduced into the treatment plan.In order to implement precise radiotherapy,it is of great necessity to reduce or eliminate the motion artifacts and include motion information of targets in the course of the treatment planning and irradiating processes.
Based on the comprehensive analysis of 4D-CT reconstruction theory, combining with the intrinsic features of CT images for the same target,a novel 4D-CT reconstruction method based on similarity principle of spatial adjacent images has been proposed in our study.The corresponding 4D-CT reconstruction program was developed by Using VC++ program language and Visual Tools Kits(VTK).The CT data of patients with free breathing were acquired??Cine model at several continuing couch positions.The Cine duration time of every couch position was equal to the respiratory period pulsing one second.The mutual information(MI) of spatial adjacent images was taken as the similarity measure,on which the phases resorting were based.The 4D-CT reconstruction has been implemented with conventional multi-slices CT scanners without any external breath monitor device based on the similarity principle.Advantages of this method include the following aspects:high image quality,lower motion artifacts,characterizing not only reality of the periodic motion target,but also extent and disciplinarian of periodic motion.The most apparent disadvantage of the method is that a single phase 4D-CT reconstruction will take several minutes.For instance,the reconstruction process generally costs 3～6 min to complete a single phase 4D-CT on a lap PC(Dell Latitude 620,1GB memory) for 1000～2000 slices CT,which can not distinguish the respiratory phase directly.
In order to improve the method mentioned above and implement the 4D-CT reconstruction more conveniently and effectively,another 4D-CT reconstruction method,based on the volume change of the thoracic and abdominal tissues or lung tissue,has been proposed in our study.The corresponding 4D-CT reconstruction program was carried out by using VC++ program language and VTK software tools, including the following modules:image transmission,readin CT image,threshold segmentation,volume calculation,phase resort,dynamic 4D-CT visualization,result output and print.The representative patients,whose CT data under free breathing conditions were acquired in Cine model at several continuing couch positions,were selected to implement the 4D-CT reconstruction.The phase of each CT image within a breathing cycle was determined according to the pixel volume the thoracic and abdominal contours or lung tissues.The CT images of different phases were resorted into different series according to their phases.Several CT series in diffe?? phases of a motion cycle were acquired,which would result in a 4D-CT data that could reflect the characteristics of the periodical motion targets.
Compared with the current imported 4D-CT systems,the advantages of our proposed 4D-CT systems can be summarized as follows:
①The 4D-CT reconstruction of periodical motion targets can be implemented with any general multi-slice CT scanners.The process of the reconstruction does not depend on any external respiratory monitor devices and not restricted to the hardware or software of CT scanner.As a consequence,it can be applied universally.After the 4D-CT reconstruction has been completed,arbitrary single-phase 4D-CT,sagittal or coronal or 3D view CTs can be exported,which will facilitate its application in clinical practice and scientific study.
②It can not be obstructed by thermoplastic immobilization mask(TIM) during the 4D-CT reconstruction and it is a breakthrough with a great value for the current imported 4D-CT reconstruction system.When patient receiving radiotherapy is immobilized with TIM and his/her breathing amplitude is restricted,it will result in a failure determination of respiration phase for the external respiratory monitor system. Therefore,the imported 4D-CT system can not implement 4D-CT reconstruction under this condition.But,the TIM will not affect the 4D-CT reconstruction system developed by our group,which is based on the volume change of thoracic and abdominal tissues or lung volume.Therefore,it will facilitate the popularization of 4D-CT in precise radiotherapy.
③Another advantage of the 4D-CT reconstruction system based on the volume change induced by respiration is very convenient and effective.For example,a lap PC with IGB memory(Dell Latitude 620) will take only 40s to input 1200 slices CT (512×512),less than 10s to resort phases,and less than 2s to reconstruct arbitrary single phase 4D-CT,sagittal or coronal view images.If a powerful PC with 2GB memory is used to input 2000 slices CT,which covers the whole thorax?? abdomen, the 4D-CT reconstruction process will be less than 10s.So it is much more efficient than the hours-consuming conventional iterative computation methodology.
④Real 4D view:The present literatures about 4D-CT reconstructions have only reported sagittal and coronal 4D-CT images.Not only two-dimensional sagittal and coronal 4D-CT images have been reconstructed,but also 3D sagittal and coronal views changing with time have been achieved.Additionally,the living viscera motion induced by respiration can be displayed periodically.
After the 4D-CT system has been developed,the variety characteristics of dose distribution of motion targets receiving three-dimensional conformal radiation therapy(3D-CRT) and intensity modulated radiation therapy(IMRT) have been investigated,based on 4D-CT,averaged intensity projection(AIP) and maximal intensity projection(MIP) CT:①The difference of the target volumes among 4D, AIP and MIP CT of the same patient were analyzed for the tumors located separately at upper lung,middle lung and abdomen.②Based on the intrinsic features of AIP and MIP CT,a software system has been developed to create AIP and MIP CT directly through Cine scan CT data without 4D-CT reconstruction and any external breathing monitoring devices.It can create AIP and MIP CT with any multi-slice CT scanners.③The various characteristics of phantom in AIP and MIP CT images have been investigated with different window widths and levels,which will become the application foundation of AIP and MIP CT image in precise radiotherapy.④The dose distribution on different phases 4D-CT,AIP and MIP CT series were achieved by utilizing the fuse module of conventional 3D-TPS,which can characterize intuitively the dose distributions of motion targets.For the moving target,the dose distributions based on an extreme phase 4D-CT can not cover the whole tumor volume on the other extreme phase of 4D-CT.If the dose calculation is based on the tumor contours on AIP or MIP CT images,it??l cover the entire tumors on two extreme respiratory phase 4D-CT images and the irradiation area will not be enlarged egregiously.Hence,the irradiation to the motion target is reasonable.Furthermore, when the AIP and MIP CT series are used to create the planning for periodic motion targets,it will reduce a lot of work for target delineation on all of 4D-CT images.It is a very effective method to utilize the motion information contained in the 4D-CT data. ⑤According to the features of the clip motion targets,a simplified iterative model of dose calculation matrix was developed in our study,and the corresponding simulation program has been accomplished by using Matlab 7.0 software tools,which can predict the dose distributions of clip motion targets.
On the basis of treatment planning on 4D-CT and AIP/MIP CT images,a 2D air vented ionization chamber array MatriXX system and a platform which can mimic the clip motion of lung tumor were adopted to investigate the influences of respiratory motion on target dose distribution.The edge dose blurring effect was found in the motion phantom experiment and the random effect of the IMRT segment beam based on multileaf collimator(MLC) has been analysed carefully.Because of the random dose deviation for different field sizes,irradiation locations and doses,the accumulated dose deviation can be greatly reduced.Compared with the static phantom in 3D-CRT,the penumbra of dose distribution of the periodic moving phantom along the moving directions has increased by 6～9 mm.The high dose area has shrinked by about 5mm and the low dose area extended by 5mm.But the area of 50%isodose and the dose center area changed little.When a single segment beam of IMRT irradiation was measured and the maximum dose of measuring plane was normalized to 100%,the averaged difference of dose distribution between the static and periodic phantoms was±27%(from -56.4%～56.1%).When all of the segment beams of IMRT were delivered and the integrated dose distribution was measured,the differences were less than±3%?? maximum difference of dose distribution was about±15%,mainly appearing at the field margin,which was similar to 3D-CRT.The results indicate that the dose distributions of most center areas of the periodic moving targets irradiated by multi-fraction 3DCRT/IMRT beams are similar to those of the static targets,while the high dose area of the former has shrinked and the low area extended.The calculated dose distributions match with the measuring results and the iterative model of dose calculation matrix can be served as a new predictor of the dose distributions of the periodic motion targets.
At the end of the study,the achieved results and deficiencies were summarized, and part of the 4D-CT program frames and codes were listed for further study.
但是,现有的4D-CT图像重建技术仍有这样或那样的缺陷,在放疗中的应用还受到多方面的限制,主要包括:①没有国产的4D-CT系统,进口系统不但昂贵,而且依赖于呼吸监测装置,只能在少数新型CT机上实现4D-CT图像重建。⑦由于4D-CT图像数量众多,通常有1000～2000张,甚至更多,在目前缺乏成熟的四维放疗计划系统的情况下,在4D-CT中勾画靶区和危及器官的工作量约10倍于常规三维适形放疗,使靶区勾画成为制约4D-CT在放疗中广泛应用的瓶颈。③不同相位4D-CT中,运动靶区受照剂量的计算和验证仍然困扰着四维放疗。为了克服4D-CT图像重建对呼吸监测系统的依赖,在普通螺旋CT机上实现4D-CT图像重建,Berlinge等提出了利用杠杆原理的“针影轨迹”重建法,但这种方法在重建过程中能识别的相位数较少,通常只有5个,而且不能识别呼气或吸气的中间状态。为了便于4D-CT在放疗中的应用,McClelland等提出了基于运动模型的连续4D-CT重建法,Zeng等提出了迭代模型重建法。虽然,采用这两种方法重建的4D-CT图像质量较高,但其最大的缺陷是计算时间长达数小时,临床实用价值有限。因此,研究4D-CT图像重建技术及其在放疗中的应用,无论从社会效益还是从经济效益出发,都具有不可估量的价值和意义。
在全面总结进口4D-CT图像重建系统的优缺点及其在放疗应用中存在的问题之后,研究中提出了两种新的4D-CT图像重建法,并编写了相应的软件系统,实现方便、快捷的4D-CT图像重建,打破了没有国产4D-CT图像重建系统的局面,并在此基础上进行了4D-CT图像在放疗中的应用研究,主要内容可概括如下:
(1)呼吸运动对靶区三维重建的影响。用步进马达、驱动器、导轮、有机玻璃球、低密度泡沫等模拟呼吸运动体模。用GE LightSpeed 16排螺旋CT对体模进行扫描,分析不同螺距、层厚和运动周期对靶区扫描后三维重建体积和形态的影响,并计算动态靶区重建体积相对于静态靶区重建体积的偏差。研究中发现:①对于静态靶区,改变扫描层厚与螺距对三维重建体积和外观的影响不明显:②对于动态靶区,不同运动状态下扫描后,重建体积和外观差异显著,其相对偏差的变化范围与靶区大小有关,外形较小的靶区为-39.8%～89.5%,外形较大的靶区为-18.4%～20.5%,说明呼吸运动对靶区三维重建的影响很大,三维适形放疗计划设计所采用的CT图像必须是靶区处于相对静止状态下扫描的图像,否则,放疗计划设计中将存在很大的误差。因此,减少运动伪影并在放疗计划和实施过程中充分考虑靶区的运动规律是实现精确放疗的必要条件。
(2)根据对4D-CT图像重建原理的分析,结合扫描时图像之间的内在联系,本研究创造性地提出了基于“相??像最相似原理”的4D-CT重建法,用VC++程序设计语言和可视化工具软件包(Visual Tools Kits,VTK)开发了相应的软件系统。对自由呼吸状态下的患者进行多床位的“电影”(Cine)扫描,每个床位处Cine扫描的持续时间等于患者的呼吸周期加上1秒。扫描后把相邻图像问的互信息作为相似性的测度,据此对所得扫描图像进行相位排序,实现4D-CT图像重建。实验结果表明,这种方法重建的4D-CT图像质量高、运动伪影显著减少,不仅真实地再现了靶区形态,而且反映了靶区随呼吸运动变化的规律。其不足之处是重建时间稍长,当CT层数在1000～2000时,在Dell Latitude 620笔记本电脑上重建一个相位4D-CT的时间约3-5分钟,另外,该方法不能直接确定呼吸相位。
(3)针对上述不足,为了实现更简便、高效的4D-CT重建,研究中进一步提出了基于呼吸运动过程中胸腹体积/肺体积变化的4D-CT重建法,开发了相应的软件系统,其主要模块包括:数据传输、CT图像读入、阈值分割、体积计算、相位排序、分相4D-CT重建、动态显示、结果输出和打印等。研究中对典型病例进行了4D-CT重建实验,患者在自由呼吸状态下进行多床位的Cine扫描,扫描后根据所得CT图像中胸腹体积/肺体积的变化,确定每一层CT图像在呼吸周期中的相位,按不同相位对所有CT图像进行分组,得到一个完整的呼吸周期中多个相位的CT系列,实现了4D-CT重建。
与昂贵的进口系统相比,本研究开发的4D-CT图像重建系统有如下优势:
①能在所有普通螺旋CT上实现4D-CT重建,其重建过程不依赖于外在的呼吸监测装置,不受CT机本身的软硬件限制,具有普遍适用性。进行4D-CT重建后,可输出任一相位的4D-CT横断位、矢状位、冠状位及三维视图,方便4D-CT在后续临床和科研中的应用。
②能对胸腹部带有热塑体模固定装置的放疗患者进行4D-CT重建,这是对目前进口4D-CT图像重建系统局限性的一次重大突破。当放疗患者采用了热塑体模固定装置时,由于体模的限制,患者体表不再随呼吸而起伏、或者起伏的幅度变得非常微小,在这种情况下,体表监测装置不能准确地确定呼吸相位,从而导致目前进口4D-CT系统不能正常工作。本研究开发的重建系统可根据呼吸运动过程中肺体积的变化和“相邻图像最相似原理”进行4D-CT图像重建,不受热塑体模的影响,将会大大促进4D-CT图像重建技术在体部精确放疗中的应用。
③基于呼吸运动过程中胸腹体积/肺体积变化的4D-CT图像重建系统具有简便??效的优势。例如:在配置为1GB内存的Dell Latitude D620笔记本电脑上,读入1200幅CT图像(512×512),仅需要约40秒,图像分组、排序时间不到10秒,重建任意相位的矢状位、冠状位4D-CT不到2秒。在台式PC上(2GB内存),读入2000幅CT图像(范围覆盖全胸腹)后,也能在10秒内完成4D-CT重建过程,其效率远远高于计算时间长达数小时的基于运动模型的4D-CT重建。
④实现了真正意义上的4D显示。既往4D-CT重建文献中报道了矢状面、冠状面4D-CT图像。本研究不仅完成了矢状面、冠状面4D-CT图像重建,而且完成了4D-CT图像的横断面、矢状面和冠状面3D视图重建,更逼真地反映了内脏器官随呼吸运动变化的规律。
(4)在完成4D-CT图像重建研究后,基于4D-CT、平均密度投影和最大密度投影CT,研究了运动靶区的表现特征及其进行三维适形和调强放疗时的剂量分布规律:①分析肺尖、右肺和腹部靶区在4D-CT、平均密度投影和最大密度投影CT中的差异。②根据平均密度投影和最大密度投影CT的本质特征,开发了一套软件系统,该系统在生成平均密度投影和最大密度投影CT时不需要进行4D-CT重建、也不用任何呼吸监测装置,可以利用任何能进行Cine模式扫描的CT机生成平均密度投影和最大密度投影CT。③利用自制的运动体模,研究了窗宽/窗位对平均密度投影和最大密度投影CT图像中运动靶区勾画的影响,为运动靶区的精确放疗打下了基础。④在利用4D-CT研究不同相位运动靶区的剂量分布特征时,巧妙地利用了放疗计划系统的图像融合功能,得到不同相位4D-CT系列、平均密度投影和最大密度投影CT中的剂量分布,直观地反映了运动靶区受照剂量分布随呼吸运动变化的特征:(?)靶区随呼吸运动时,根据一个极限相位4D-CT设计的放疗计划可能在另一相对的极限相位中造成靶区遗漏。(?)用平均密度投影和最大密度投影CT勾画靶区后进行三维适形放疗和调强放疗计划设计,其剂量分布能很好地覆盖两个极限呼吸相位4D-CT中的靶区,不会过分扩大照射范围,使运动靶区受到合理的照射。(?)利用平均密度投影和最大密度投影CT还可大大地减轻在多相位4D-CT中进行靶区勾画的劳动强度,是充分利用靶区运动信息的一个切实可行的好方法。⑤根据靶区往返周期运动的特点,木研究提出了简化的运动靶区剂量计算“矩阵叠加”模型??atlab 7.0工具软件,编写了相应的模拟计算程序,通过计算预测运动靶区的受照剂量分布规律。
(5)利用模拟呼吸运动平台和二维空气电离室矩阵MatriXX系统,研究运动靶区实际受照剂量分布的特点。研究中揭示了运动靶区的“边缘剂量模糊效应”和基于多叶准直器的调强放疗子野照射时剂量分布的“随机效应”。正是由于各子野的位置和大小不同,照射运动靶区后产生的剂量分布具有随机性,当子野剂量叠加后,剂量误差有相互抵消的趋向。体模周期运动时,对三维适形放疗照射,在运动方向上所测剂量分布半影较静态时增加6～9 mm,高剂量区域向内收缩约5mm,低剂量区域向外扩张约5mm,但50%等剂量曲线范围及中心区域剂量未见明显改变;调强放疗各子野单独照射且以测量平面最大剂量为归一剂量时,运动和静止状态下所测剂量差异介于-56.4%～56.1%,其平均值约±27%。调强放疗计划所有子野叠加照射时,两种运动状态下在射野中绝大部分区域的剂量分布相对偏差＜±3%,其偏差主要出现在射野边缘,最大约±15%,这与三维适形放疗照射的特点相似。说明无论是三维适形放疗还是调强放疗多次分割照射后,周期运动靶区中心区域受照剂量与静态靶区相近,但高剂量区域向内收缩,低剂量区域向外扩张,实验测量结果与运动靶区剂量计算的“矩阵叠加”模型的预测结果相一致,为利用4D-CT进行运动靶区的剂量评估提供了一种新的方法。
在论文最后总结了研究工作已取得的成果,指出了存在的不足和下一步工作的计划,并列出4D-CT系统中的部分程序流程图和源代码。
Computed Tomography(CT) image owns some unique advantages in spatiality and density resolution,which has become a landmark in the developing history of medical image technique.Compared with the conventional X-ray fluoroscopy,the ordinary CT scan,as an indirect image technique,cannot synchronously characterize the dynamic features of the motion viscera in thorax and abdomen.Nevertheless, ordinary CT can reflect the three-dimensional(3D) spatial structures by applying 3D-CT reconstruction.In recent years,four-dimensional computed tomography (4D-CT) has been developed in order to characterize the dynamic features of motion targets.Compared with traditional CT scan,4D-CT has greatly reduced the motion artifacts,not only representing the shape of organs in thorax and abdomen such as liver,kidney,lung and diaphragm which will move with the respiration,but also reflecting the extents and features of movement.4D-CT and its application in radiation therapy have brought about a profound effect in precise radiotherapy for the thoracic and abdominal organs:①4D-CT can be applied to analyze the characteristics of volume variation and location displacement of targets and organs at risk during the respiratory motion,which is of great help to design the patient-specific treatment plan that can reduce the irradiated area and increase the target dose and at the same time spare the normal tissues.②In the course of stereotactic radiotherapy of lung and liver,4D-CT can be expediently applied to analyze the tumors and organs of motion at varying levels of abdominal compression,which will guide the application of abdominal compression and implement precise radiotherapy for lung and liver tumor.③4D-CT can be used to investigate the correlation between internal fiducial tumor motion and external marker motion and implement 4D image guided radiation therapy(IGRT),which will promote in the advance of radiotherapy from 3D to 4D.
However,there still exist some limitations in the present 4D-CT system. Currently,the main factors that restrict 4D-CT to a wide utilization in precise radiotherapy include the following aspects:①There is not any 4D-CT system developed in native China yet.The imported 4D-CT systems are very expensive, which must depend on external respiration monitor devices while acquiring synchronous respiratory signals and 4D-CT reconstruction can be implemented only by a small number of newer-type CT scanners.②Now there is not perfect commercial 4D treatment planning system(4D-TPS).The 4D-CT data series contain a great number of CT slices,usually 1000～2000 slices or even more.The workload of segmenting targets and organs at risk(OAR) on 4D-CT slices usually needs ten times of that on the conventional CT.As a result,target delineation has become a bottleneck of the application of 4D-CT in radiation therapy.③The dose accumulation and verification of motion targets in 4D treatment planning still are the great problem?? the whole process of 4D radiation therapy.
In order to solve the limitations of the present 4D-CT systems,which must depend on the external respiration monitor systems and implement 4D-CT reconstruction on common helical CT scanners,Berlinge et al proposed a simple 4D-CT reconstruction method,which labels the CT images in the respiratory state by a needle that follows the abdominal respiratory motion by means of leverage.This method can implement 4D-CT reconstruction without external breath monitor and has been greatly accepted in clinics due to its simplicity.But,the positions of the needle in Berlinge's 4D-CT reconstruction were binned into only five respiratory states instead of eight to ten bins used by others and it was impossible to distinguish between the intermediate,inhale and exhale directions of the breathing cycle.Another 4D-CT reconstruction method put forward by McClelland et al was based on continuing 4D motion model.And the iterative sorting method proposed by Zeng et al was based on the internal anatomy motion,which can get a high-quality 4D-CT image.However,all the reconstruction methods have limitations.The disadvantage of those methods is that the calculation will cost several hours.So the application value was very limited.Hence,it is of great necessity to improve the 4D-CT reconstruction and its application in radiation therapy.
On the basis of summarizing the former achievements and limitations of 4D-CT reconstruction and its application in radiotherapy,two novel 4D-CT reconstruction methods have been proposed in our study.The corresponding software systems have been developed,which will result in simple and fast 4D-CT reconstruction.As a result,the condition of no domestic 4D-CT reconstruction system has changed.Thus, the applications of 4D-CT in radiotherapy have been investigated in the study,the main works of which can be recapitulated below:
First,a motion platform that can simulate??an respiration was developed with a step motor,motor driver and low-density foam.Several balls with different sizes made of polyethylene and two potatoes were placed into the low-density foam to simulate tumors with different sizes.The motion phantom was adopted to investigate the respiratory effects on 3D reconstruction of motion targets with different periods and initial phases,which were scanned by a GE LightSpeed16 CT scanner with different pitches and slices.The relative deviations of reconstruction volumes between dynamic targets and the stationary ones were calculated.No obvious differences were observed between the 3D reconstruction volumes of stationary targets scanned with different pitches and slices.But great differences were found between the 3D reconstruction volumes of dynamic targets and stationary ones.The relative deviations of reconstruction volumes of targets,which were scanned with different pitches,slices and periods,were variable among the targets,about -39.8%～89.5%for the smaller targets and -18.4%～20.5%for the larger ones,which indicates that the respiration has great effects on the 3D reconstruction of the tumor targets.The CT images adopted in three-dimensional treatment planning system (3D-TPS) must be acquired while the targets are under static condition.Otherwise, severe errors will be introduced into the treatment plan.In order to implement precise radiotherapy,it is of great necessity to reduce or eliminate the motion artifacts and include motion information of targets in the course of the treatment planning and irradiating processes.
Based on the comprehensive analysis of 4D-CT reconstruction theory, combining with the intrinsic features of CT images for the same target,a novel 4D-CT reconstruction method based on similarity principle of spatial adjacent images has been proposed in our study.The corresponding 4D-CT reconstruction program was developed by Using VC++ program language and Visual Tools Kits(VTK).The CT data of patients with free breathing were acquired??Cine model at several continuing couch positions.The Cine duration time of every couch position was equal to the respiratory period pulsing one second.The mutual information(MI) of spatial adjacent images was taken as the similarity measure,on which the phases resorting were based.The 4D-CT reconstruction has been implemented with conventional multi-slices CT scanners without any external breath monitor device based on the similarity principle.Advantages of this method include the following aspects:high image quality,lower motion artifacts,characterizing not only reality of the periodic motion target,but also extent and disciplinarian of periodic motion.The most apparent disadvantage of the method is that a single phase 4D-CT reconstruction will take several minutes.For instance,the reconstruction process generally costs 3～6 min to complete a single phase 4D-CT on a lap PC(Dell Latitude 620,1GB memory) for 1000～2000 slices CT,which can not distinguish the respiratory phase directly.
In order to improve the method mentioned above and implement the 4D-CT reconstruction more conveniently and effectively,another 4D-CT reconstruction method,based on the volume change of the thoracic and abdominal tissues or lung tissue,has been proposed in our study.The corresponding 4D-CT reconstruction program was carried out by using VC++ program language and VTK software tools, including the following modules:image transmission,readin CT image,threshold segmentation,volume calculation,phase resort,dynamic 4D-CT visualization,result output and print.The representative patients,whose CT data under free breathing conditions were acquired in Cine model at several continuing couch positions,were selected to implement the 4D-CT reconstruction.The phase of each CT image within a breathing cycle was determined according to the pixel volume the thoracic and abdominal contours or lung tissues.The CT images of different phases were resorted into different series according to their phases.Several CT series in diffe?? phases of a motion cycle were acquired,which would result in a 4D-CT data that could reflect the characteristics of the periodical motion targets.
Compared with the current imported 4D-CT systems,the advantages of our proposed 4D-CT systems can be summarized as follows:
①The 4D-CT reconstruction of periodical motion targets can be implemented with any general multi-slice CT scanners.The process of the reconstruction does not depend on any external respiratory monitor devices and not restricted to the hardware or software of CT scanner.As a consequence,it can be applied universally.After the 4D-CT reconstruction has been completed,arbitrary single-phase 4D-CT,sagittal or coronal or 3D view CTs can be exported,which will facilitate its application in clinical practice and scientific study.
②It can not be obstructed by thermoplastic immobilization mask(TIM) during the 4D-CT reconstruction and it is a breakthrough with a great value for the current imported 4D-CT reconstruction system.When patient receiving radiotherapy is immobilized with TIM and his/her breathing amplitude is restricted,it will result in a failure determination of respiration phase for the external respiratory monitor system. Therefore,the imported 4D-CT system can not implement 4D-CT reconstruction under this condition.But,the TIM will not affect the 4D-CT reconstruction system developed by our group,which is based on the volume change of thoracic and abdominal tissues or lung volume.Therefore,it will facilitate the popularization of 4D-CT in precise radiotherapy.
③Another advantage of the 4D-CT reconstruction system based on the volume change induced by respiration is very convenient and effective.For example,a lap PC with IGB memory(Dell Latitude 620) will take only 40s to input 1200 slices CT (512×512),less than 10s to resort phases,and less than 2s to reconstruct arbitrary single phase 4D-CT,sagittal or coronal view images.If a powerful PC with 2GB memory is used to input 2000 slices CT,which covers the whole thorax?? abdomen, the 4D-CT reconstruction process will be less than 10s.So it is much more efficient than the hours-consuming conventional iterative computation methodology.
④Real 4D view:The present literatures about 4D-CT reconstructions have only reported sagittal and coronal 4D-CT images.Not only two-dimensional sagittal and coronal 4D-CT images have been reconstructed,but also 3D sagittal and coronal views changing with time have been achieved.Additionally,the living viscera motion induced by respiration can be displayed periodically.
After the 4D-CT system has been developed,the variety characteristics of dose distribution of motion targets receiving three-dimensional conformal radiation therapy(3D-CRT) and intensity modulated radiation therapy(IMRT) have been investigated,based on 4D-CT,averaged intensity projection(AIP) and maximal intensity projection(MIP) CT:①The difference of the target volumes among 4D, AIP and MIP CT of the same patient were analyzed for the tumors located separately at upper lung,middle lung and abdomen.②Based on the intrinsic features of AIP and MIP CT,a software system has been developed to create AIP and MIP CT directly through Cine scan CT data without 4D-CT reconstruction and any external breathing monitoring devices.It can create AIP and MIP CT with any multi-slice CT scanners.③The various characteristics of phantom in AIP and MIP CT images have been investigated with different window widths and levels,which will become the application foundation of AIP and MIP CT image in precise radiotherapy.④The dose distribution on different phases 4D-CT,AIP and MIP CT series were achieved by utilizing the fuse module of conventional 3D-TPS,which can characterize intuitively the dose distributions of motion targets.For the moving target,the dose distributions based on an extreme phase 4D-CT can not cover the whole tumor volume on the other extreme phase of 4D-CT.If the dose calculation is based on the tumor contours on AIP or MIP CT images,it??l cover the entire tumors on two extreme respiratory phase 4D-CT images and the irradiation area will not be enlarged egregiously.Hence,the irradiation to the motion target is reasonable.Furthermore, when the AIP and MIP CT series are used to create the planning for periodic motion targets,it will reduce a lot of work for target delineation on all of 4D-CT images.It is a very effective method to utilize the motion information contained in the 4D-CT data. ⑤According to the features of the clip motion targets,a simplified iterative model of dose calculation matrix was developed in our study,and the corresponding simulation program has been accomplished by using Matlab 7.0 software tools,which can predict the dose distributions of clip motion targets.
On the basis of treatment planning on 4D-CT and AIP/MIP CT images,a 2D air vented ionization chamber array MatriXX system and a platform which can mimic the clip motion of lung tumor were adopted to investigate the influences of respiratory motion on target dose distribution.The edge dose blurring effect was found in the motion phantom experiment and the random effect of the IMRT segment beam based on multileaf collimator(MLC) has been analysed carefully.Because of the random dose deviation for different field sizes,irradiation locations and doses,the accumulated dose deviation can be greatly reduced.Compared with the static phantom in 3D-CRT,the penumbra of dose distribution of the periodic moving phantom along the moving directions has increased by 6～9 mm.The high dose area has shrinked by about 5mm and the low dose area extended by 5mm.But the area of 50%isodose and the dose center area changed little.When a single segment beam of IMRT irradiation was measured and the maximum dose of measuring plane was normalized to 100%,the averaged difference of dose distribution between the static and periodic phantoms was±27%(from -56.4%～56.1%).When all of the segment beams of IMRT were delivered and the integrated dose distribution was measured,the differences were less than±3%?? maximum difference of dose distribution was about±15%,mainly appearing at the field margin,which was similar to 3D-CRT.The results indicate that the dose distributions of most center areas of the periodic moving targets irradiated by multi-fraction 3DCRT/IMRT beams are similar to those of the static targets,while the high dose area of the former has shrinked and the low area extended.The calculated dose distributions match with the measuring results and the iterative model of dose calculation matrix can be served as a new predictor of the dose distributions of the periodic motion targets.
At the end of the study,the achieved results and deficiencies were summarized, and part of the 4D-CT program frames and codes were listed for further study.
引文
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