Université Grenoble-Alpes, UGA/INSERM UA7 STROBE, 2280 rue de la Piscine, Saint-Martin d'Hères, 38400, France.
Centre Hospitalier Universitaire Grenoble-Alpes, CS10217, Grenoble, 38043, France.
Med Phys. 2022 Jun;49(6):3999-4017. doi: 10.1002/mp.15637. Epub 2022 Apr 12.
Microbeam radiation therapy (MRT) is a treatment modality based on spatial fractionation of synchrotron generated X-rays into parallel, high dose, microbeams of a few microns width. MRT is still an underdevelopment radiosurgery technique for which, promising preclinical results on brain tumors and epilepsy encourages its clinical transfer.
A safe clinical transfer of MRT needs a specific treatment planning system (TPS) that provides accurate dose calculations in human patients, taking into account the MRT beam's properties (high-dose gradients, spatial fractionation, polarization effects). So far, the most advanced MRT TPS, based on a hybrid dose calculation algorithm, is limited to a macroscopic rendering of the dose and does not account for the complex dose distribution inherent to MRT if delivered as conformal irradiations with multiple incidences. For overcoming these limitations, a multi-scale full Monte-Carlo calculation engine called penMRT has been developed and benchmarked against two general-purpose Monte Carlo (MC) codes: penmain based on PENELOPE and Gate based on Geant4.
PenMRT, is based on the PENELOPE (2018) MC code, modified to take into account the voxelized geometry of the patients (computed tomography [CT]-scans) and is offering an adaptive micrometric dose calculation grid independent of the CT size, location, and orientation. The implementation of the dynamic memory allocation in penMRT, makes the simulations feasible within a huge number of dose scoring bins. The possibility of using a source replication approach to simulate arrays of microbeams, and the parallelization using OpenMPI have been added to penMRT in order to increase the calculation speed for clinical usages. This engine can be implemented in a TPS as a dose calculation core.
The performance tests highlight the reliability of penMRT to be used for complex irradiation conditions in MRT. The benchmarking against a standard PENELOPE code did not show any significant difference for calculations in centimetric beams, for a single microbeam and for a microbeam array. The comparisons between penMRT and Gate as an independent MC code did not show any difference in the beam paths, whereas, in valley regions, relative differences between the two codes rank from 1% to 7.5% which are probably due to the differences in physics lists that are used in these two codes. The reliability of the source replication approach has also been tested and validated with an underestimation of no more than 0.6% in low-dose areas.
Good agreements (a relative difference between 0% and 8%) were found when comparing calculated peak to valley dose ratio values using penMRT, for irradiations with a full microbeam array, with calculated values in the literature. The high-resolution calculated dose maps obtained with penMRT are used to extract differential and cumulative dose-volume histograms (DVHs) and analyze treatment plans with much finer metrics regarding the irradiation complexity. To our knowledge, these are the first high-resolution dose maps and associated DVHs ever obtained for cross-fired microbeams irradiation, which is bringing a significant added value to the field of treatment planning in spatially fractionated radiation therapy.
微束放射治疗（MRT）是一种基于同步加速器产生的 X 射线的空间分割成平行的高剂量、几微米宽的微束的治疗方式。MRT 仍然是一种发展中的放射外科技术，其在脑肿瘤和癫痫方面的有前景的临床前结果鼓励了其临床转化。
MRT 的安全临床转化需要一个特定的治疗计划系统（TPS），该系统能够在考虑到 MRT 光束特性（高剂量梯度、空间分割、极化效应）的情况下，为人类患者提供准确的剂量计算。迄今为止，最先进的基于混合剂量计算算法的 MRT TPS 仅限于宏观剂量渲染，并且如果采用多入射角的适形照射，则不考虑固有的复杂剂量分布。为了克服这些限制，开发了一种称为 penMRT 的多尺度全蒙特卡罗计算引擎，并与两种通用蒙特卡罗（MC）代码进行了基准测试：基于 PENELOPE 的 penmain 和基于 Geant4 的 Gate。
penMRT 基于 PENELOPE（2018）MC 代码，经过修改可以考虑患者的体素化几何形状（计算机断层扫描 [CT]-扫描），并提供了一个自适应的微剂量计算网格，与 CT 的大小、位置和方向无关。penMRT 中动态内存分配的实现使得在大量剂量评分箱中进行模拟成为可能。为了增加临床应用的计算速度，penMRT 中添加了使用源复制方法模拟微束阵列的可能性，以及使用 OpenMPI 进行并行化。该引擎可以作为剂量计算核心在 TPS 中实现。
性能测试突出了 penMRT 在 MRT 中复杂照射条件下使用的可靠性。与标准 PENELOPE 代码的基准测试显示，在厘米束、单个微束和微束阵列的计算中，没有任何显著差异。penMRT 与 Gate 作为独立的 MC 代码的比较没有显示出在束路径上的任何差异，而在谷地区域，两个代码之间的相对差异从 1%到 7.5%不等，这可能是由于这两个代码中使用的物理列表不同所致。源复制方法的可靠性也已经过测试和验证，在低剂量区域的估计值不超过 0.6%。
当使用 penMRT 比较使用全微束阵列进行的照射的计算峰值到谷值剂量比时，与文献中的计算值相比，发现（0%到 8%之间的）相对差异很好。penMRT 获得的高分辨率计算剂量图可用于提取微分和累积剂量体积直方图（DVHs），并使用与照射复杂性相关的更精细指标分析治疗计划。据我们所知，这些是首次为交叉射击微束照射获得的高分辨率剂量图和相关的 DVHs，为空间分割放射治疗的治疗计划领域带来了显著的附加价值。
