Mayer Rulon, Lin Liyong, Fager Marcus, Douglas Dan, McDonough James, Carabe Alejandro
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland 20817, USA.
Department of Radiation Oncology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.
Rev Sci Instrum. 2015 Apr;86(4):044301. doi: 10.1063/1.4917418.
Radiation therapy depends on predictably and reliably delivering dose to tumors and sparing normal tissues. Protons with kinetic energy of a few hundred MeV can selectively deposit dose to deep seated tumors without an exit dose, unlike x-rays. The better dose distribution is attributed to a phenomenon known as the Bragg peak. The Bragg peak is due to relatively high energy deposition within a given distance or high Linear Energy Transfer (LET). In addition, biological response to radiation depends on the dose, dose rate, and localized energy deposition patterns or LET. At present, the LET can only be measured at a given fixed point and the LET spatial distribution can only be inferred from calculations. The goal of this study is to develop and test a method to measure LET over extended areas. Traditionally, radiochromic films are used to measure dose distribution but not for LET distribution. We report the first use of these films for measuring the spatial distribution of the LET deposited by protons. The radiochromic film sensitivity diminishes for large LET. A mathematical model correlating the film sensitivity and LET is presented to justify relating LET and radiochromic film relative sensitivity. Protons were directed parallel to radiochromic film sandwiched between solid water slabs. This study proposes the scaled-normalized difference (SND) between the Treatment Planning system (TPS) and measured dose as the metric describing the LET. The SND is correlated with a Monte Carlo (MC) calculation of the LET spatial distribution for a large range of SNDs. A polynomial fit between the SND and MC LET is generated for protons having a single range of 20 cm with narrow Bragg peak. Coefficients from these fitted polynomial fits were applied to measured proton dose distributions with a variety of ranges. An identical procedure was applied to the protons deposited from Spread Out Bragg Peak and modulated by 5 cm. Gamma analysis is a method for comparing the calculated LET with the LET measured using radiochromic film at the pixel level over extended areas. Failure rates using gamma analysis are calculated for areas in the dose distribution using parameters of 25% of MC LET and 3 mm. The processed dose distributions find 5%-10% failure rates for the narrow 12.5 and 15 cm proton ranges and 10%-15% for proton ranges of 15, 17.5, and 20 cm and modulated by 5 cm. It is found through gamma analysis that the measured proton energy deposition in radiochromic film and TPS can be used to determine LET. This modified film dosimetry provides an experimental areal LET measurement that can verify MC calculations, support LET point measurements, possibly enhance biologically based proton treatment planning, and determine the polymerization process within the radiochromic film.
放射治疗依赖于可预测且可靠地将剂量传递至肿瘤并保护正常组织。与X射线不同，具有几百兆电子伏特动能的质子能够选择性地将剂量沉积至深部肿瘤，且无出射剂量。更好的剂量分布归因于一种被称为布拉格峰的现象。布拉格峰是由于在给定距离内相对较高的能量沉积或高传能线密度（LET）所致。此外，对辐射的生物学反应取决于剂量、剂量率以及局部能量沉积模式或LET。目前，LET只能在给定的固定点进行测量，而LET的空间分布只能通过计算推断。本研究的目标是开发并测试一种在扩展区域测量LET的方法。传统上，放射变色胶片用于测量剂量分布，但不用于测量LET分布。我们报告了首次使用这些胶片来测量质子沉积的LET的空间分布。对于大LET，放射变色胶片的灵敏度会降低。提出了一个将胶片灵敏度与LET相关联的数学模型，以证明LET与放射变色胶片相对灵敏度之间的关联是合理的。质子被引导至与夹在固体水板之间的放射变色胶片平行的方向。本研究提出将治疗计划系统（TPS）与测量剂量之间的缩放归一化差值（SND）作为描述LET的指标。对于大范围的SND，SND与LET空间分布的蒙特卡罗（MC）计算相关。针对具有20 cm单一射程且布拉格峰较窄的质子，生成了SND与MC LET之间的多项式拟合。将这些拟合多项式的系数应用于具有各种射程的测量质子剂量分布。对从扩展布拉格峰沉积并经5 cm调制的质子应用相同的程序。伽马分析是一种在扩展区域的像素级别比较计算得到的LET与使用放射变色胶片测量得到的LET的方法。使用25%的MC LET和3 mm的参数，计算剂量分布区域使用伽马分析的失败率。对于12.5和15 cm窄质子射程，处理后的剂量分布的失败率为5%-10%；对于15、17.5和20 cm且经5 cm调制的质子射程，失败率为10%-15%。通过伽马分析发现，放射变色胶片和TPS中测量的质子能量沉积可用于确定LET。这种改进的胶片剂量测定法提供了一种实验性的面内LET测量，可验证MC计算、支持LET点测量、可能增强基于生物学的质子治疗计划，并确定放射变色胶片内的聚合过程。
