图像引导放射治疗若干关键问题的研究
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摘要
三维适形调强放射治疗已经在国内外的放疗科室和中心中广泛的使用。它可以投放高度适形的辐射剂量到静止的靶区，同时保护周围的危及器官免受过量辐射的伤害，从而减少并发症的发生。但是由于肿瘤和周围危及器官在治疗分次间和分次内的运动，使得调强放疗的好处大打折扣。四维CT和锥形束CT被广泛的用来获取肿瘤和危及器官在分次内和分次间的运动影像。通过开发四维计划和在线自适应放疗等运动管理方法，可以减少肿瘤和危及器官的运动引起的射线投放的偏差，达到精确放疗的目的。
首先，通过四维CT分析了放射治疗过程中肿瘤和周围危及器官在治疗分次内的运动。针对四维CT中仍然存在的呼吸伪影现象，利用正常组织和器官的空间连续性，提出了相邻床位CT图像的空间连续性指数，并用此指数检测和校正四维CT中仍然存在的呼吸伪影，得到更清晰的四维CT图像。
其次，在四维CT图像反映的周期呼吸运动的基础上，提出了子野最优变形的概念，以使变形后的子野在当前呼吸相位的单位加速器跳数产生的剂量分布与在参考相位的子野单位加速器跳数产生的剂量分布尽可能相同。这使得处于参考相位的子野形状可以跟随肿瘤和危及器官的运动而产生相应的变化，并通过共轭梯度法和模拟退火法同时优化各个子野的权重和处于参考相位的形状，得到最优的基于电动多叶准直器的实时跟踪四维放疗计划。实验结果显示，与基于ITV的三维适形放疗计划相比，在确保肿瘤辐射剂量的情况下，四维追踪放疗计划可以进一步的减少周围危及器官所受到的辐射量。
最后，通过锥形束CT获取的在线影像来分析肿瘤和危及器官的分次间运动。针对锥形束CT图像电子密度不准确的问题，开发了基于梯度场的变形配准算法，改善了锥形束CT与扇形束CT间图像配准的精度。并针对在线应用对配准时间要求高的特点，进一步将此变形配准算法在GPU上并行实施，大大缩短了配准时间。根据配准算法产生的变形场，计划CT上的器官轮廓被自动的映射到在线获取的锥形束CT图像上，以用来进行在线的剂量评估。根据配准算法产生的变形场，一种直接射野修正算法被实施，以在线修改放疗计划，使之适应肿瘤和危及器官产生的位置和形状变化，进行更准确的剂量投放。
综上所述，通过四维CT、四维追踪放疗计划和在线修改放疗计划可以更精确的投放辐射剂量到肿瘤，同时进一步减少周围危及器官受到的辐射剂量，从而减少放疗并发症的发生，提高患者的生存质量。
Intensity modulated radiotherapy can deliver highly conformal radiation dose to astationary target, while protecting the surrounding organs at risk from excessiveradiation. However, the inter-fraction and the intra-fraction motion of the tumor andsurrounding organs at risk can greatly compromise the effectiveness of the technique.Four-dimensional CT and cone beam CT is widely used to obtain the intra-fraction andinter-fraction motion of tumor and organs at risk. The development of four-dimensionalradiotherapy planning and on-line adaptive radiotherapy methods can reduce the dosedeviation induced by the tumor motion, to achieve the purpose of precise radiotherapy.
First, the intra-fraction motion of the tumor and surrounding organs at risk wasanalyzed through four-dimensional CT. Making use of the spatial continuity betweenadjacent CT images, the artifacts in four-dimensional CT can be detected and correctedto get a clear four-dimensional CT dataset.
Second, based on the four-dimensional CT, a concept of “optimum deformation”of aperture was proposed. The “optimum deformation” of aperture makes the aperture atthe reference phase can follow the movement of the tumor and organs at risk andproduce a corresponding tracking aperture. Then the shape and weight of all aperturesare separately optimized by the simulated annealing and conjugate gradient method togenerate the optimal multi-leaf collimator based four-dimensional radiation treatmentplanning.
Last, the paper analyzed the inter-fraction motion of tumor and organs at risk byonline cone-beam CT images. For the poor electron density accuracy of cone-beam CTimages, a gradient based deformable registration algorithm was developed to improveregistration accuracy between cone-beam CT and fan-beam CT images. Because of thetime-critical features of online clinical applications, we further implemented thedeformable registration algorithm in parallel on the GPU. It dramatically shortenedregistration time. Based on the deformation field output by registration algorithm, anautomatic mapping algorithm can automatically map contours of tumor and organs from the planning CT to the cone-beam CT. Based on the deformation field output byregistration algorithm, a direct aperture modification algorithm has been used to modifythe radiation treatment plan, so that the new plan can adapt to the position and shapechanges of the tumor and organs at risk.
In summary,4D-CT,4D tracking treatment plan and on-line modified treatmentplan can more accurately deliver dose to the tumor while further reducing the dosereceived by the surrounding organs at risk. It can reduce the incidence of radiationcomplications, improve patient quality of life.
首先，通过四维CT分析了放射治疗过程中肿瘤和周围危及器官在治疗分次内的运动。针对四维CT中仍然存在的呼吸伪影现象，利用正常组织和器官的空间连续性，提出了相邻床位CT图像的空间连续性指数，并用此指数检测和校正四维CT中仍然存在的呼吸伪影，得到更清晰的四维CT图像。
其次，在四维CT图像反映的周期呼吸运动的基础上，提出了子野最优变形的概念，以使变形后的子野在当前呼吸相位的单位加速器跳数产生的剂量分布与在参考相位的子野单位加速器跳数产生的剂量分布尽可能相同。这使得处于参考相位的子野形状可以跟随肿瘤和危及器官的运动而产生相应的变化，并通过共轭梯度法和模拟退火法同时优化各个子野的权重和处于参考相位的形状，得到最优的基于电动多叶准直器的实时跟踪四维放疗计划。实验结果显示，与基于ITV的三维适形放疗计划相比，在确保肿瘤辐射剂量的情况下，四维追踪放疗计划可以进一步的减少周围危及器官所受到的辐射量。
最后，通过锥形束CT获取的在线影像来分析肿瘤和危及器官的分次间运动。针对锥形束CT图像电子密度不准确的问题，开发了基于梯度场的变形配准算法，改善了锥形束CT与扇形束CT间图像配准的精度。并针对在线应用对配准时间要求高的特点，进一步将此变形配准算法在GPU上并行实施，大大缩短了配准时间。根据配准算法产生的变形场，计划CT上的器官轮廓被自动的映射到在线获取的锥形束CT图像上，以用来进行在线的剂量评估。根据配准算法产生的变形场，一种直接射野修正算法被实施，以在线修改放疗计划，使之适应肿瘤和危及器官产生的位置和形状变化，进行更准确的剂量投放。
综上所述，通过四维CT、四维追踪放疗计划和在线修改放疗计划可以更精确的投放辐射剂量到肿瘤，同时进一步减少周围危及器官受到的辐射剂量，从而减少放疗并发症的发生，提高患者的生存质量。
Intensity modulated radiotherapy can deliver highly conformal radiation dose to astationary target, while protecting the surrounding organs at risk from excessiveradiation. However, the inter-fraction and the intra-fraction motion of the tumor andsurrounding organs at risk can greatly compromise the effectiveness of the technique.Four-dimensional CT and cone beam CT is widely used to obtain the intra-fraction andinter-fraction motion of tumor and organs at risk. The development of four-dimensionalradiotherapy planning and on-line adaptive radiotherapy methods can reduce the dosedeviation induced by the tumor motion, to achieve the purpose of precise radiotherapy.
First, the intra-fraction motion of the tumor and surrounding organs at risk wasanalyzed through four-dimensional CT. Making use of the spatial continuity betweenadjacent CT images, the artifacts in four-dimensional CT can be detected and correctedto get a clear four-dimensional CT dataset.
Second, based on the four-dimensional CT, a concept of “optimum deformation”of aperture was proposed. The “optimum deformation” of aperture makes the aperture atthe reference phase can follow the movement of the tumor and organs at risk andproduce a corresponding tracking aperture. Then the shape and weight of all aperturesare separately optimized by the simulated annealing and conjugate gradient method togenerate the optimal multi-leaf collimator based four-dimensional radiation treatmentplanning.
Last, the paper analyzed the inter-fraction motion of tumor and organs at risk byonline cone-beam CT images. For the poor electron density accuracy of cone-beam CTimages, a gradient based deformable registration algorithm was developed to improveregistration accuracy between cone-beam CT and fan-beam CT images. Because of thetime-critical features of online clinical applications, we further implemented thedeformable registration algorithm in parallel on the GPU. It dramatically shortenedregistration time. Based on the deformation field output by registration algorithm, anautomatic mapping algorithm can automatically map contours of tumor and organs from the planning CT to the cone-beam CT. Based on the deformation field output byregistration algorithm, a direct aperture modification algorithm has been used to modifythe radiation treatment plan, so that the new plan can adapt to the position and shapechanges of the tumor and organs at risk.
In summary,4D-CT,4D tracking treatment plan and on-line modified treatmentplan can more accurately deliver dose to the tumor while further reducing the dosereceived by the surrounding organs at risk. It can reduce the incidence of radiationcomplications, improve patient quality of life.
引文
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