肺部肿瘤运动的数值模拟

目的模拟肺部肿瘤在呼吸作用下的运动,探索有限元分析方法模拟肺的变形和肺部肿瘤运动的可行性。方法利用四维CT影像获得病人从吸气开始到结束各相位的图像,以计算机辅助设计表面重建方法提取吸气过程中的肺表面形态。根据吸气开始时刻表面建立有限元模型。根据各相位表面与吸气开始时刻表面的差异,提取位移载荷。将位移载荷施加到模型表面,通过有限元计算,模拟肿瘤在呼吸过程中的运动和变形。结果数值模拟表明,肺变形的误差在2 mm以内,肿瘤位移和变形的误差在1 mm以内。肿瘤在弹性模量为50 kPa时,模拟的位移和变形精度更高。结论采用有限元法可实现肺部和肺内肿瘤运动模拟,本研究为基于数值模拟的肺部肿瘤非射线追踪方法提供了依据。     

基于4D-CT最大呼吸气相位图像获取三维肺通气的信息

背景：传统的肺功能成像技术存在诸多不便,利用4D-CT中蕴含的通气信息进行功能图像的快速提取对肺部疾病的诊断和治疗有非常重要的意义。 目的：探讨基于三维变形图像配准算法从4D-CT最大吸气相位和最大呼气相位图像中获取肺通气的三维分布的可行性。 方法：利用电影模式采集自由呼吸状态下的胸部CT图像并利用已开发的4D-CT软件进行四维重建,得到吸气末和呼气末双相位CT图像,依次进行肺组织分割、利用基于体积的变形图像配准算法进行三维图像配准、量化分析三维空间象素的位移矢量,最后得到通气度量图即肺功能区的三维分布图。 结果与结论：利用三维变形图像配准算法,实现了从4D-CT最大吸气相位和最大呼气相位图像中获取在任意横断位、冠状位和矢状位的肺通气分布。     

基于4D-CT和Mimics软件模拟分析肺癌肿瘤的呼吸运动规律

目的：利用Mimics10.01软件和4D-CT10个呼吸时相的肺部三维模型,研究肺部肿瘤的呼吸运动规律。方法：选择1例左上肺癌患者,在肿瘤上、中、下部植入3个金标,间隔为6 mm,4D-CT扫描相位排序后重建10个呼吸时相的CT图像。将10个时相的CT图像依次导入Mimics10.01软件中,采用阈值分割、区域生长的方法提取肺部区域,重建左右肺的三维模型。测量10个呼吸时相的左右肺体积和表面积;吸气末与呼气末时相之间左肺三维模型之间的偏差也进行了分析。在每个时相的CT图像上读取植入3个金标的位置坐标,求出金标在X、Y、Z方向上质心的坐标。结果：从吸气末到呼气末左、右肺体积的变化范围分别为12.8%和12.4%,左、右肺表面积的变化范围为6.6%和6.7%。3个金标的质心变化幅度在左右、头脚、前后方向分别为2 mm,1mm和2.7 mm。结论：利用4D-CT的图像和Mimics软件重建得出的肺模型可以方便地计算肺体积以及靶区的运动范围,有利于根据患者的靶区运动特征实现个体化治疗。     

基于临床CT数字体相关和有限元分析的股骨内部变形场研究

目的 验证基于临床CT的数字体相关(digital volume correlation, DVC)方法在测量股骨内部变形场时的准确性,并通过DVC进一步测量股骨在跌倒情况下的内部变形,验证基于临床CT的有限元分析方法(finite element analysis, FEA)在计算股骨内部变形场的准确性。方法 使用猪股骨,模拟侧向跌倒姿态,进行分步力学加载实验,同步进行多次CT成像。通过重复扫描和虚拟位移验证DVC方法的准确性。DVC以子体积作为配准两组图像的研究对象,分别设置8、12、16和20 mm的子体积进行测试。量化误差指标包括位移系统误差-平均值(mean)、位移随机误差-标准差(standard deviation, SD)、应变准确度-平均绝对误差(mean absolute error, MAER)和应变精确度-标准差误差(standard deviation of the error, SDER)。基于CT图像建立股骨有限元模型,模拟实验条件,计算股骨内部位移,与DVC测量的内部变形场对比验证。结果 基于临床CT的DVC方法重复扫描位移偏差小于0.013 mm, M...     

基于显微CT的骨微观三维变形场测量系统的研究

目的初步构建一套集成显微CT与力学加载装置的测试系统,结合数字体相关技术(digital volume correla-tion,DVC)实现骨组织内部微观三维变形场的测量。方法选用微型力学加载装置进行单轴压缩试验,维持载荷不变的同时对试样进行CT扫描;采用DVC方法对连续CT图像序列进行相关匹配和搜索计算,测量载荷变化前后试样内部结构沿三维方向的微观位移值;通过零位移重复扫描和刚体平移评价该系统的测量精度及准确度;利用该系统测试牛松质骨块的三维位移场分布。结果零位移重复扫描结果显示该系统测量加载方向的位移准确度最高,测量精度低于CT扫描分辨率的1/10;刚体平移结果显示计算位移标准差为0.001～0.002μm;松质骨块测试区域在600 N载荷作用下沿加载方向的微观位移范围为100.35～110.25μm,位移场呈现多层逐级分布。结论该系统能够满足数字体相关法测量位移的准确度及精度要求,能够实现骨组织内部微观结构的三维变形场测量,可以作为进一步研究骨组织内部变形分布与结构成分响应关系的测量平台。     

基于双目视觉的呼吸运动实时跟踪方法研究

探讨一种基于双目视觉实时监测和跟踪人体的呼吸运动情况,减少肿瘤靶区组织因呼吸等运动产生位移而引起的治疗误差,以实现在放疗过程中减少呼吸运动对精确放疗产生的影响。采用放置治疗床上方的双摄像机,实时采集带有标记物的图片传送给计算机,使用余弦算法对放置胸腹体表的标记物进行特征识别,对视差信息进行图片匹配,采用双目视觉和小孔成像原理计算标记物三维坐标,通过监测标记物随时间变化的具体坐标可获取标记物是否因呼吸等运动产生位移。实验中,实时测量9个标记物的三维坐标。实验结果表明,9个体表标记物的测量值与实际值之间的平均误差小于±1 mm,其标准误差值小于0.12 mm,且计算一次9个标记物三维坐标需要35 ms。基于双目视觉的呼吸运动跟踪是一种高精度、良好实时性与稳定性的跟踪方法,可以减少呼吸运动对精确放疗产生的影响。     

应用4D-CT进行肺通气功能三维分布的研究

目的探讨利用4D-CT获取肺通气功能三维分布的可行性。方法患者在自由呼吸状态下进行电影模式扫描,采集一个完整呼吸周期下的胸部CT图像,利用本研究开发的4D-CT重建软件系统获取4D-CT图像;再用三维变形图像配准算法,对4D-CT系列中相邻相位CT进行图像配准、获得从一个呼吸状态到另一个状态变化时肺部CT像素的三维位移矢量,量化分析此三维矢量,从而得到反映呼吸过程中肺部CT像素变化程度的灰度示意图,即通气功能强弱分布;最后,将此灰度图伪彩化并与参考CT图像进行融合,再行冠状位、矢状重建。结果利用三维变形图像配准算法,从4D-CT中获取了任意横断位、冠状位和矢状位的肺通气分布,即肺通气功能的三维分布。结论用4D-CT获取肺通气功能三维分布完全可行。     

三维肿瘤运动和体表标记物运动的研究

目的：研究呼吸导致的肺部肿瘤运动和体表标记物运动轨迹之间的火系。材料与方法：我们利用模拟定位机对肺癌病人呼吸运动中肿瘤三维运动和体表标记物的运动进行了监测并处理，再对这些数据进行频域分析和秩相关分析。结果：我们得到了患者肺部肿瘤运动与体表标记物运动的波形，分析出了呼吸的频率和运动之间的相关性。结论：不同患者间随呼吸的肿瘤运动差异较大，且肺部肿瘤运动与体表标记物运动小都具有相关性。     

磁探测电阻抗成像呼吸监测仿真研究

为了探索磁探测电阻抗成像应用于肺部呼吸监测中的可行性,针对新型磁探测电阻抗成像技术的正问题,以真实人体肺部数据构建成像体物理模型,采用了有限元方法得到成像体内部的电势和电流密度分布,然后根据毕奥-萨伐尔定律分别获得呼气末与吸气末成像体外部的磁感应强度仿真数据。结果表明,吸气末时成像体周围的磁感应强度值比呼气末小8.875%。研究结果显示了呼吸时由于肺容积、电导率的不同而导致周围磁感应强度的差异等信息,为后续磁探测电阻抗成像的图像重建以及临床疾病检测奠定了基础。     

生物力学影响的靶区位姿精度保持方法研究

目的:分析二次摆位中靶区位姿在生物力学影响下的器官肿瘤变形规律,控制机械臂位置来补偿此误差。方法:利用解剖学和生物力学相关知识,通过Mimics v17.0软件建立包含肿瘤的肺组织有限元模型,将建立的有限元模型导入ANSYS15.0,利用前人总结的生物力学特性参数仿真分析肺和肿瘤的变形误差。结果:得到在二次摆位中肺组织最大变形为21.24 mm,肿瘤最大变形为3.17 mm,并利用二次多项式拟合给出了误差模型,摆位验证后其误差变形均在此范围内,其中头脚方向变形最大。结论:基于自主设计的六自由度摆位医用机械臂提出一种通过前馈修正的位置控制方法,该方法在二次摆位过程中可以预先补偿肿瘤的位移误差,提高放疗精度和效率,减少对治疗靶区周围正常组织的损伤。 【关键词】靶区位姿;生物力学;变形误差;前馈修正     

组织蛋白酶D新的糖基化异构体在肺癌中表达的临床意义及其与预后的相关性

目的 探讨组织蛋白酶D（CTSD）新的糖基化异构体与肺癌临床病理特征及预后的相关性。 方法 应用免疫组织化学和半定量RT PCR方法检测119例肺癌组织和39例癌旁组织中CTSD的表达;Western blotting分析CTSD各异构体表达特点;去糖基化实验检测CTSD 蛋白的糖基化修饰;Kaplan-Meier分析66kD异构体、临床病理资料与肺癌术后整体生存期的相关性。 结果 CTSD在肺鳞癌、腺癌和小细胞肺癌组织中高表达;66kD蛋白为CTSD新的糖基化异构体,该异构体表达与肺癌组织类型、临床分期、淋巴结转移和患者的吸烟史密切相关（P<0.05）,阳性表达和阴性表达患者术后中位生存时间分别为20.0和30.0个月（P<0.05）;肺癌组织类型、临床分期、淋巴结转移、肿瘤大小和66kD异构体表达是影响肺癌预后的独立因素。 结论 CTSD 66kD异构体阳性表达可能是肺癌预后不良的分子标志物之一。     

A deformable phantom for 4D radiotherapy verification: design and image registration evaluation

Motion of thoracic tumors with respiration presents a challenge for three-dimensional (3D) conformal radiation therapy treatment. Validation of techniques aimed at measuring and minimizing the effects of respiratory motion requires a realistic deformable phantom for use as a gold standard. The purpose of this study was to develop and study the characteristics of a reproducible, tissue equivalent, deformable lung phantom. The phantom consists of a Lucite cylinder filled with water containing a latex balloon stuffed with dampened natural sponges. The balloon is attached to a piston that mimics the human diaphragm. Nylon wires and Lucite beads, emulating vascular and bronchial bifurcations, were uniformly glued at various locations throughout the sponges. The phantom is capable of simulating programmed irregular breathing patterns with varying periods and amplitudes. A tissue equivalent tumor, suitable for holding radiochromic film for dose measurements was embedded in the sponge. To assess phantom motion, eight 3D computed tomography data sets of the static phantom were acquired for eight equally spaced positions of the piston. The 3D trajectories of 12 manually chosen point landmarks and the tumor center-of-mass were studied. Motion reproducibility tests of the deformed phantom were established on seven repeat scans of three different states of compression. Deformable image registration (DIR) of the extreme breathing phases was performed. The accuracy of the DIR was evaluated by visual inspection of image overlays and quantified by the distance-to-agreement (DTA) of manually chosen point landmarks and triangulated surfaces obtained from 3D contoured structures. In initial tests of the phantom, a 20-mm excursion of the piston resulted in deformations of the balloon of 20 mm superior-inferior, 4 mm anterior-posterior, and 5 mm left-right. The change in the phantom mean lung density ranged from 0.24 (0.12 SD) g/cm3 at peak exhale to 0.19 (0.12 SD) g/cm3 at peak inhale. The SI displacement of the landmarks varied between 94% and 3% of the piston excursion for positions closer and farther away from the piston, respectively. The reproducibility of the phantom deformation was within the image resolution (0.7 x 0.7 x 1.25 mm3). Vector average registration accuracy based on point landmarks was found to be 0.5 (0.4 SD) mm. The tumor and lung mean 3D DTA obtained from triangulated surfaces were 0.4 (0.1 SD) mm and 1.0 (0.8 SD) mm, respectively. This phantom is capable of reproducibly emulating the physically realistic lung features and deformations and has a wide range of potential applications, including four-dimensional (4D) imaging, evaluation of deformable registration accuracy, 4D planning and dose delivery.     

非小细胞肺癌中Frat1与Axin表达的相关性及意义

目的近年来肺癌的发病率及死亡率逐年升高,寻找新的靶向治疗方向的要求日益迫切。作为Wnt通路中的一个新成员,Frat1在肺癌组织中的表达情况以及Frat1与Axin在肺癌组织中表达相关性的研究甚少。方法用免疫组化SP法对120例原发性非小细胞肺癌(NSCLC)患者手术标本中Frat1和Axin的表达进行检测,使用SPSS 16.0统计数据。结果在NSCLC中Frat1的阳性表达与肺癌组织的低分化(P=0.004)、淋巴结转移(P=0.033)、TNM分期相关(P=0.039);Axin的异常表达与肺癌组织的低分化(P=0.001)、淋巴结转移(P=0.036)、TNM分期相关(P=0.043);Frat1的阳性表达与Axin的异常表达有相关性(P=0.025)。结论 Frat1和Axin在NSCLC中与肺癌的低分化、转移、高级别TNM分期等恶性表型有关,Frat1和Axin在癌组织中的表达有相关性,Frat1可能成为非小细胞肺癌患者靶向治疗的新靶点。     

Quantifying the accuracy of automated structure segmentation in 4D CT images using a deformable image registration algorithm

Four-dimensional (4D) radiotherapy is the explicit inclusion of the temporal changes in anatomy during the imaging, planning, and delivery of radiotherapy. One key component of 4D radiotherapy planning is the ability to automatically ("auto") create contours on all of the respiratory phase computed tomography (CT) datasets comprising a 4D CT scan, based on contours manually drawn on one CT image set from one phase. A tool that can be used to automatically propagate manually drawn contours to CT scans of other respiratory phases is deformable image registration. The purpose of the current study was to geometrically quantify the difference between automatically generated contours with manually drawn contours. Four-DCT data sets of 13 patients consisting of ten three-dimensional CT image sets acquired at different respiratory phases were used for this study. Tumor and normal tissue structures [gross tumor volume (GTV), esophagus, right lung, left lung, heart and cord] were manually drawn on each respiratory phase of each patient. Large deformable diffeomorphic image registration was performed to map each CT set from the peak-inhale respiration phase to the CT image sets corresponding with subsequent respiration phases. The calculated displacement vector fields were used to deform contours automatically drawn on the inhale phase to the other respiratory phase CT image sets. The code was interfaced to a treatment planning system to view the resulting images and to obtain the volumetric, displacement, and surface congruence information; 692 automatically generated structures were compared with 692 manually drawn structures. The auto- and manual methods showed similar trends, with a smaller difference observed between the GTVs than other structures. The auto-contoured structures agree with the manually drawn structures, especially in the case of the GTV, to within published interobserver variations. For the GTV, fractional volumes agree to within 0.2+/-0.1, center of mass displacements agree to within 0.5+/-1.5 mm, and agreement of surface congruence is 0.0+/-1.1 mm. The surface congruence between automatic and manual contours for the GTV, heart, left lung, right lung and esophagus was less than 5 mm in 99%, 94%, 94%, 91% and 89%, respectively. Careful assessment of the performance of automatic algorithms is needed in the presence of 4D CT artifacts.     

Dosimetric investigation of lung tumor motion compensation with a robotic respiratory tracking system: an experimental study

The benefits of using Synchrony Respiratory Tracking System (RTS) in conjunction with the CyberKnife robotic treatment device to treat a "breathing tumor" in an anthropomorphic, tissue-equivalent, thoracic phantom have been investigated. The following have been studied: (a) Synchrony's ability to allow the CyberKnife to deliver accurately a planned dose distribution to the free-breathing phantom and (b) the dosimetric implications when irregularities in the breathing cycle and phase differences between internal (tumor) and external (chest) motion exist in the course of one treatment fraction. The breathing phantom PULMONE (phantom used in lung motion experiments) has been used, which can imitate regular or irregular breathing patterns. The breathing traces from two patients with lung cancer have been selected as input. Both traces were irregular in amplitude, frequency, and base line. Patient B demonstrated a phase difference between internal and external motion, whereas patient A did not. The experiment was divided into three stages: In stage I-static, the treatment was delivered to the static phantom. In stage II-motion, the phantom was set to breathe, following the breathing trace of each of the two patients. Synchrony was switched off, so no motion compensation was made. In stage III-compensation, the phantom was set to breathe and Synchrony was switched on. A linear correspondence model was chosen to allow for phase differences between internal and external motion. Gafchromic EBT film was inserted in the phantom tumor to measure dose. To eradicate small errors in film alignment during readout, a gamma comparison with pass criteria of 3%/3 mm was selected. For a more quantitative approach, the percentage of pixels in each gamma map that exceeded the value of 1 (P1) was also used. For both breathing signals, the dose blurring caused by the respiratory motion of the tumor in stage II was degraded considerably compared with stage I (P1 = 15% for patient A and 8% for patient B). The motion compensation via the linear correspondence model was sufficient to provide a dose distribution that satisfied the set gamma criteria (P1=3% for patient A and 2% for patient B). Synchrony RTS has been found satisfactory in recovering the initial detail in dose distribution, for realistic breathing signals, even in the case where a phase delay between internal tumor motion and external chest displacement exists. For the signals applied here, a linear correspondence model provided an acceptable degree of motion compensation.