Abstract：
Objective.In this paper, we present MONAS (MicrOdosimetry-based modelliNg for relative biological effectiveness (RBE) ASsessment) toolkit. MONAS is a TOPAS Monte Carlo extension, that combines simulations of microdosimetric distributions with radiobiological microdosimetry-based models for predicting cell survival curves and dose-dependent RBE.Approach.MONAS expands TOPAS microdosimetric extension, by including novel specific energy scorers to calculate the single- and multi-event specific energy microdosimetric distributions at different micrometer scales. These spectra are used as physical input to three different formulations of themicrodosimetric kinetic model, and to thegeneralized stochastic microdosimetric model(GSM2), to predict dose-dependent cell survival fraction and RBE. MONAS predictions are then validated against experimental microdosimetric spectra andin vitrosurvival fraction data. To show the MONAS features, we present two different applications of the code: (i) the depth-RBE curve calculation from a passively scattered proton SOBP and monoenergetic12C-ion beam by using experimentally validated spectra as physical input, and (ii) the calculation of the 3D RBE distribution on a real head and neck patient geometry treated with protons.Main results.MONAS can estimate dose-dependent RBE and cell survival curves from experimentally validated microdosimetric spectra with four clinically relevant radiobiological models. From the radiobiological characterization of a proton SOBP and12C fields, we observe the well-known trend of increasing RBE values at the distal edge of the radiation field. The 3D RBE map calculated confirmed the trend observed in the analysis of the SOBP, with the highest RBE values found in the distal edge of the target.Significance.MONAS extension offers a comprehensive microdosimetry-based framework for assessing the biological effects of particle radiation in both research and clinical environments, pushing closer the experimental physics-based description to the biological damage assessment, contributing to bridging the gap between a microdosimetric description of the radiation field and its application in proton therapy treatment with variable RBE.
摘要：
目的:在本文中,我们提出MONAS（基于显微术的modelliNg用于相对生物学有效性（RBE）评估）工具包。MONAS是TOPAS蒙特卡洛的延伸，将微剂量测定分布的模拟与基于放射生物学微剂量测定的模型相结合，用于预测细胞存活曲线和剂量依赖性RBE。
方法:MONAS扩展TOPAS微剂量扩展,通过包括新颖的特定能量记分器来计算不同微米尺度下的单事件和多事件特定能量微剂量分布。这些光谱用作微剂量动力学模型（MKM）的三种不同公式的物理输入，和广义随机微剂量模型(GSM2)，预测剂量依赖性细胞存活分数和RBE。然后根据实验微剂量光谱和体外存活分数数据验证MONAS预测。要显示MONAS功能，我们介绍了该代码的两种不同应用：i）通过使用实验验证的光谱作为物理输入，从被动散射质子SOBP计算深度RBE曲线，和ii)在用质子治疗的真实头颈部患者几何结构上的3DRBE分布的计算。＆＃xD;主要结果：MONAS可以通过四种临床相关的放射生物学模型从实验验证的微剂量光谱中估算剂量依赖性RBE和细胞存活曲线。从质子SOBP场的放射生物学特征来看，我们观察到众所周知的辐射场远端边缘RBE值增加的趋势。计算的3DRBE图证实了SOBP分析中观察到的趋势，在目标的远端边缘发现最高的RBE值。＆＃xD;意义：MONAS扩展提供了一个全面的基于微剂量学的框架，用于评估粒子辐射在研究和临床环境中的生物效应，将基于实验物理的描述推向生物损伤评估，有助于弥合辐射场的微剂量学描述与其在可变RBE的质子治疗中的应用之间的差距。
