Reducing Range Uncertainties in Proton Radiation Therapy

质子放射治疗的主要生理优势是患者体内的质子范围有限。 然而，今天实行的质子处理计划和交付受到相当大的影响 不确定的范围，因此在远距离剂量下降区域的位置。我们的总体目标是 在临床上最大限度地利用物理质子优势，即射程。我们假设， 主要通过使用先进的成像技术，我们可以大幅降低距离不确定度， 并在准静态情况下将递送给患者的剂量的深度位置控制在1 mm以内 在存在分数运动的情况下，在3 mm内。我们进一步假设，这将导致 大大提高了目标覆盖率和/或减少了对附近关键结构的剂量。为了满足 总体目标和检验假设，我们将努力实现3个具体目标。目标1是缩小射程 静态情景中的不确定性。它包括通过过滤方法减少CT金属伪影 以及更高能量的使用。它还解决了将CT数转换为停止幂的问题，这 是精确的剂量计算所必需的。将开发蒙特卡罗剂量计算方法。我们会 不仅旨在高精度地计算质子射程，而且还研究了由于 组织不均一性，这导致远端剂量下降的陡度降低。目标2是射程 在存在器官运动的情况下进行控制。在这里，我们将介绍时空(4D)成像技术 分析运动特性，并在数字体模中模拟器官运动。我们将专注于门禁 减轻动议影响的策略。我们还将致力于改善定位和固定 精确度，例如光学成像技术。第三个目标是验证可实现的水平 精确度。这将通过三种方式实现。首先，我们将研究体内试验的可行性和实用性 使用PET/CT扫描的测量是在质子处理部分之后立即进行的。我们也会做幻影 在静态体模和生物运动体模(猪肺)中进行测量。最后，我们会 测量高能质子束穿过患者后的剩余射程，并将其与 期望值。所有AIMS普遍适用于被动散射质子治疗和IMPT。 总体而言，这个项目将展示质子的主要物理优势在多大程度上(即，有限范围) 可以转化为患者的剂量学优势。这项研究的临床相关性将在#年进行。 项目1和项目2。

The main physical advantage of proton radiation therapy is the finite range of protons in the patient. However, proton treatment planning and delivery, as practiced today, is affected by considerable uncertainties in the range and therefore in the position of the distal dose fall-off region. Our overall goal is to utilize the physical proton advantage, i.e., the range, to its full extent in the clinic. We hypothesize that, mainly through the use of advanced imaging technology, we can reduce range uncertainties substantially, and control the depth position of the dose delivered to the patient to within 1 mm in the quasi-static case and within 3 mm in the presence of intra-fractional motion. We further hypothesize that this will lead to substantially improved target coverage and/or reduced dose to nearby critical structures. To meet the overall goal and test the hypotheses we will strive to achieve 3 Specific Aims. Aim 1 is the reduction of range uncertainties in the static scenario. It involves the reduction of CT metal artifacts through a filtering approach and the use of higher energies. It also addresses the conversion of CT numbers to stopping powers, which are needed for accurate dose calculation. Monte Carlo dose calculation methods will be developed. We will not only aim to calculate the proton range with great precision, but also to investigate range degradation due to tissue heterogeneities, which leads to a reduced steepness of the distal dose fall-off. Aim 2 is range control in the presence of organ motion. Here we will introduce spatio-temporal (4D) imaging techniques to analyze motion characteristics, and simulate organ motion in a numerical phantom. We will focus on gating strategies to mitigate the effects of the motion. We will also aim to improve positioning and immobilization accuracies, for example with optical imaging techniques. The third aim is to validate the achievable level of accuracy. This will be done in three ways. First we will investigate the feasibility and utility of in-vivo measurements using PET/CT scans taken directly after a proton treatment fraction. We will also do phantom measurements, both in a static phantom and in a biological motion phantom (swine lung). Finally, we will measure the residual range of an energetic proton beam after traversing the patient, and compare it with the expected value. All Aims are generally applicable to both passively scattered proton therapy and IMPT. Overall this project will show to what degree the primary physical advantage of protons (i.e., the finite range) can be translated into a dosimetric advantage in patients. The clinical relevance of this will be studied in Project 1 and Project 2.