基于形变配准技术及动态四维CT优化的原发性肝癌放射性肝损伤预测指标研究

Precise radiotherapy has become an important approach in the treatment of hepatocellular carcinoma.However,radiation-induced liver disease (RILD) has become an major limitation on the dose escalation for tumor and the clinical outcome improvement. How to predict the probability of RILD effectively has arised lots of research. The common-used currently dosimetric indices to predict probability of RILD was calculated by treatment planning system based on static computed tomography scanning data. The indices contained some uncertainties because the static computed tomography could not reflect the breath motion and the organ deformation accurately, and the uncertainties could affect the accuracy in predicting RILD. Recently four dimensional computed tomography (4D-CT) has been applied in radiotherapy, which could reflect the motion and deformation of the liver and target volume truly through volumetric scan tracking the breath motion, and dynamic CT images which related to time were obtained after reconstruction. In present study, the deformation registration of four dimensional computed tomography images has been proved to be carried out by invesigating the free-form deformation (FFD) approach based on B-splines multiresolution grid, and then the point to point dose accumulation of normal liver tissue could be achieved. The dos-volume indices which were obtained from four dimensional computed tomography applying deformation registration could reduce the effect caused by breath motion, and the prediction could be more accurate and objective, and the anatomic position and the range of RILD could be predicted precisely.

精确放疗是原发肝癌重要的治疗手段之一，而放射性肝损伤限制了肿瘤靶区剂量的提升和临床疗效的提高。如何有效预测放射性肝损伤的发生几率是当前一个研究重点。目前常用的预测放射性肝损伤的剂量-体积指标均基于静态三维CT图像计算而得，由于未考虑肝脏受呼吸影响所致的运动和形变，造成这些指标预测效能较低。近年发展起来的四维CT技术通过追踪呼吸运动结合容积扫描技术，获得与时间相关联的动态CT图像。基于动态CT图像进行肝脏和肿瘤靶区的勾画,可真实反映二者运动和形变情况。本研究通过基于B样条多分辨率网格的自由变形模型FFD四维CT形变配准算法的研究，完成四维CT图像间点对点的形变配准，进而实现正常肝脏组织点对点的剂量累加；以此获得的预测放射性肝损伤发生的剂量-体积指标可克服呼吸运动的影响,提高预测效能；同时基于形变配准技术重建的正常肝脏剂量-体积分布情况可准确预测放射性肝损伤的发生部位。

本课题通过基于形变配准技术及动态四维 CT 优化的原发性肝癌（HCC）放射性肝损伤预测指标的相关研究，为HCC精确放疗时预测放射性肝脏损伤剂量-体积指标计算提供新方法。主要完成的研究包括：①基于形变配准获得强化4D-CT进行HCC个体化内靶区(ITV)制定的可行性研究;②4D-CT与MRI-T2图像经形变配准确定HCC放疗内靶区的应用研究;③.两种形变配准算法在基于4D-CT图像分析呼吸运动对肝脏及靶区形态影响的对照研究;④应用形变配准技术分析呼吸运动对HCC患者正常肝脏及其靶区形态影响的研究;⑤4D-CT和形变配准技术联合在HCC放疗肿瘤靶区和正常肝脏剂量累加评估中的应用研究。.研究结果表明：基于4D-CT和形变配准技术进行HCC肿瘤靶区勾画的两种新方法-应用形变配准技术结合强化3D-CT、平扫4D-CT实现的强化动态4D-CT及MRI-T2 图像与平扫4D-CT实现的动态MRI-T2，在制定HCC的肿瘤靶区时可以大大减少因图像显示不清和未考虑随呼吸运动而造成的勾画误差，提高了靶区勾画精度。改进的Demons算法和自由形变配准模型为4D-CT不同时相图像间的形变配准提供了可行方法，可以用于追踪和量化分析肝脏及肿瘤靶区的运动和形变情况，实现不同时相间图像点对点的形变配准；通过形变配准与4D-CT重新计算得到的新剂量-体积指标与传统基于静态3D-CT图像获得的指标相比，传统的方法高估了肿瘤靶区剂量、剂量分布的适形度与均匀性，正常肝脏不同的剂量-体积指标均有一定幅度的波动。4D-CT与形变配准技术结合可以展现出真实的肿瘤靶区及正常肝脏的剂量分布，进而为弥补肿瘤靶区的剂量不足区域和限制正常肝脏的高剂量区域提供了科学依据。本项目的研究成果为应用动态4D-CT和形变配准方法实现HCC放射治疗中肿瘤靶区及正常肝脏受量的准确累加提供了可行方法，有利于HCC患者的个体化放疗方案的制定。