Abolfath Ramin, Helo Yusuf, Carlson David J, Stewart Robert, Grosshans David, Mohan Radhe
Department of Radiation Physics and Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 75031, USA.
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Med Phys. 2020 Jul;47(7):3184-3190. doi: 10.1002/mp.14165. Epub 2020 Apr 30.
To revisit the formulation of the mean chord length in microdosimetry and replace it by the particle mean free path appropriate for modelings in radiobiology.
We perform a collision-by-collision followed by event-by-event Geant4 Monte Carlo simulation and calculate double-averaged stepping length, 〈〈l〉〉, for a range of target sizes from mm down to μm and depth in water. We consider 〈〈l〉〉 to represent the particle mean free path.
We show that 〈〈l〉〉 continuously drops as a function of depth and asymptotically saturates to a minimum value in low energies, where it exhibits a universal scaling behavior, independent of particle nominal beam energy. We correlate 〈〈l〉〉 to linear density of DNA damage, complexities of initial lethal lesions and illustrate a relative difference between predictive RBEs in model calculations using mean chord length vs the proposed mean free path. We demonstrate consistency between rapid increase in RBE within and beyond the Bragg peak and 〈〈l〉〉, a decreasing function of depth.
An interplay between localities in imparted energy at nanometer scale and subsequent physio-chemical processes, causalities and pathways in DNA damage requires substitution of geometrical chord length of cell nuclei by mean-free path of proton and charged particles to account for a mean distance among sequential collisions in DNA materials. To this end, the event averaging over cell volume in the current microdosimetry formalism must be superseded by the collision averaging scored within the volume. The former, is fundamentally a global attribute of the cell nuclei surfaces and boundaries and is characterized by their membrane diameters, hence such global indices are not appropriate to quantitatively represent the radiobiological strength of the particles and their RBE variabilities that is associated with the sensitivities to local structure of the collisions and their spatio-temporal collective patterns in DNA materials.
重新审视微剂量学中平均弦长的公式，并将其替换为适用于放射生物学建模的粒子平均自由程。
我们进行逐个碰撞然后逐个事件的Geant4蒙特卡罗模拟，并计算从毫米到微米范围内一系列靶尺寸以及水中深度的双平均步长〈〈l〉〉。我们认为〈〈l〉〉代表粒子平均自由程。
我们表明〈〈l〉〉作为深度的函数持续下降，并在低能量下渐近饱和到最小值，在该能量下它呈现出通用的标度行为，与粒子标称束能量无关。我们将〈〈l〉〉与DNA损伤的线密度、初始致死损伤的复杂性相关联，并说明了在使用平均弦长与提议的平均自由程的模型计算中预测相对生物效应（RBE）之间的相对差异。我们证明了布拉格峰内外RBE的快速增加与〈〈l〉〉（深度的递减函数）之间的一致性。
在纳米尺度上传递能量的局部性与随后的物理化学过程、DNA损伤中的因果关系和途径之间的相互作用，要求用质子和带电粒子的平均自由程代替细胞核的几何弦长，以考虑DNA材料中连续碰撞之间的平均距离。为此，当前微剂量学形式中对细胞体积的事件平均必须被体积内得分的碰撞平均所取代。前者从根本上说是细胞核表面和边界的全局属性，并由它们的膜直径表征，因此这种全局指标不适用于定量表示粒子的放射生物学强度及其与DNA材料中碰撞局部结构的敏感性及其时空集体模式相关的RBE变异性。
