Reducing Range Uncertainties in Proton Radiation Therapy

质子放射治疗的主要物理优势是患者体内质子的有限范围。 然而，质子治疗计划和交付，如今天所实践的，受到相当大的影响。 范围的不确定性以及因此远端剂量下降区域的位置的不确定性。我们的总体目标是 利用物理质子优势，即，范围，在诊所的最大范围内。我们假设， 主要是通过使用先进的成像技术，我们可以大大减少距离的不确定性， 并在准静态情况下将输送给患者的剂量的深度位置控制在1 mm以内， 在存在分次内运动的情况下在3 mm内。我们进一步假设，这将导致 基本上提高了目标覆盖率和/或减少了对附近关键结构的剂量。满足 总体目标和测试的假设，我们将努力实现3个具体目标。目标1是缩小射程 静态场景中的不确定性。它涉及通过滤波方法减少CT金属伪影 以及更高能量的使用。它还涉及CT数到阻止能力的转换， 需要精确的剂量计算。将开发蒙特卡罗剂量计算方法。我们将 不仅要高精度地计算质子射程，而且要研究由于 组织异质性，这导致远端剂量下降的陡度降低。目标2是射程 在器官运动的存在下进行控制。在这里，我们将介绍时空（4D）成像技术， 分析运动特征，并在数字体模中模拟器官运动。我们将专注于门控 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达到的 精度这将通过三种方式实现。首先，我们将调查的可行性和效用，在体内 使用质子治疗部分后直接进行的PET/CT扫描进行测量。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。最后我们将 测量高能质子束穿过患者后的剩余范围，并将其与 期望值。所有目标通常适用于被动散射质子治疗和IMPT。 总的来说，这个项目将显示质子的主要物理优势（即，有限范围） 可以转化为患者的剂量优势。这一点的临床相关性将在 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.