Prompt gamma (PG) imaging is widely investigated for spot-by-spot in vivo range verification for proton therapy. Previous studies pointed out that the accuracy of prompt gamma imaging is affected by the statistics (number of protons delivered per pencil beam) of the proton beams and the conformity between prompt gamma and dose distribution (PG-dose correlation). Recently a novel approach to re-optimize conventional treatment plans by boosting a few pencil beams with good PG-dose correlation above the statistics limit for reliable PG detectability was proposed. However, up to now, only PG-dose correlation on the planning computed tomography (CT) was considered, not accounting for the fact that the robustness of the PG-dose correlation is not guaranteed in the cases of interfractional anatomical changes. In this work, this approach is further explored with respect to the robustness of the PG-dose correlation of each pencil beam in the case of interfractional anatomical changes. A research computational platform, combining Monte Carlo pre-calculated pencil beams with the analytical Matlab-based treatment planning system (TPS) CERR, is used for treatment planning. Geant4 is used for realistic simulation of the dose delivery and PG generation for all individual pencil beams in the heterogeneous patient anatomy using multiple CT images for representative patient cases (in this work, CTs of one prostate and one head and neck cancer patient are used). First, a Monte Carlo treatment plan is created using CERR. Thereby the PG emission and dose distribution for each individual spot is obtained. Second, PG-dose correlation is quantified using the originally proposed approach as well as a new indicator, which accounts for the sensitivity of individual spots to heterogeneities in the 3D dose distribution. This is accomplished by using a 2D distal surface (dose surface) derived from the 3D dose distribution for each spot. A few pencil beams are selected for each treatment field, based on their PG-dose correlation and dose surface, and then boosted in the new re-optimized treatment plan. All treatment plans are then fully re-calculated with Monte Carlo on the CT scans of the corresponding patient at three different time points. The result shows that all treatment plans are comparable in terms of dose distribution and dose averaged LET distributions. The spots recommended by our indicators maintain good PG-dose correlation in the cases of interfractional anatomical changes, thus ensuring that the proton range shift due to anatomical changes can be monitored. Compared to another proposed spots aggregation approach, our approach shows advantages in terms of the detectability and reliability of PG, especially in presence of heterogeneities.

中文翻译：

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一种新的治疗计划方法，可应对迅速的伽玛范围验证和分数间解剖变化。

即时伽玛（PG）成像已被广泛研究用于质子治疗的逐点体内范围验证。先前的研究指出，快速伽马成像的准确性受质子束的统计量（每支笔形束传递的质子数）以及即时伽马和剂量分布（PG剂量相关性）之间的一致性的影响。最近，提出了一种新的方法来重新优化常规治疗计划，该方法是通过提高一些具有良好PG剂量相关性的笔形射束，使其高于可靠的PG可检测性的统计极限。但是，到目前为止，仅考虑了计划计算机断层扫描（CT）上的PG剂量相关性，而没有考虑到在骨折间解剖变化的情况下不能保证PG剂量相关性的鲁棒性这一事实。在这项工作中 关于在部分解剖学变化的情况下每个笔形束的PG剂量相关性的鲁棒性，将进一步探讨这种方法。一个研究计算平台将蒙特卡洛预先计算的笔形射束与基于Matlab的分析治疗计划系统（TPS）CERR相结合，用于治疗计划。Geant4用于针对具有代表性的患者病例使用多个CT图像对异构患者解剖结构中所有单个笔形束的剂量输送和PG生成进行逼真的模拟（在这项工作中，使用了一名前列腺癌和一名头颈癌患者的CT） 。首先，使用CERR创建一个蒙特卡洛治疗计划。从而获得每个单独点的PG发射和剂量分布。第二，PG剂量相关性使用最初提出的方法以及新的指标进行量化，该指标考虑了单个斑点对3D剂量分布中异质性的敏感性。这是通过使用从每个点的3D剂量分布派生的2D远端表面（剂量表面）来实现的。根据它们的PG剂量相关性和剂量表面为每个治疗领域选择一些笔形束，然后在新的重新优化的治疗计划中对其进行增强。然后，在三个不同的时间点对相应患者进行CT扫描时，用Monte Carlo完全重新计算所有治疗计划。结果表明，所有治疗方案在剂量分布和平均LET剂量分布方面均具有可比性。我们的指标所推荐的斑点在​​部分间解剖学变化的情况下可保持良好的PG剂量相关性，从而确保可以监测由于解剖学变化引起的质子范围变化。与另一种建议的斑点聚集方法相比，我们的方法在PG的可检测性和可靠性方面表现出优势，尤其是在存在异质性的情况下。