Translating Proton CT from the Physics Laboratory to Clinical Application

描述（由申请人提供）：近年来，用于癌症治疗的质子疗法已经获得了广泛的认可并引起了极大的兴趣，这一点可以从美国和世界各地越来越多的质子放射治疗设施中得到证明。这种兴趣的原因是质子治疗可以通过应用非常适形的剂量分布来进一步改善癌症治疗的结果，其中传递到健康组织的剂量甚至比最先进的光子治疗技术更少。另一个原因是工业界承诺开发更紧凑、更便宜的质子技术。质子治疗中的一个未解决的问题是目前无法预测组织中质子的确切范围，这是由于将CT Hounsfield单位转换为质子阻止能力的不准确性以及在治疗室中缺乏每天预测质子范围的低剂量成像模态。这是不幸的，因为质子的主要承诺是能够在位于肿瘤后面的关键正常组织结构之前阻止辐射。造成这种不确定性的主要技术限制是使用基于X射线的计算机断层扫描（xCT）进行质子治疗计划，以及缺乏用于日常治疗室图像引导的低剂量模式。使用xCT的原因是其广泛的可用性和在放射治疗计划和图像引导中的既定作用。在这里，我们建议通过在治疗室中使用质子计算机断层扫描（pCT）进行质子治疗计划和图像引导来克服xCT当前的局限性。通过在物理学和医学接口方面的努力，我们将利用近年来在开发原型pCT扫描仪和先进图像重建方法方面的经验。我们将从目前的原型扫描仪过渡到临床pCT扫描仪。原型将用于证明pCT与X射线CT相比的价值（特定目标1）。我们还将研究原型的技术局限性，并在高能物理学和计算机科学与工程领域合作者的帮助下，开发适合临床应用的头部pCT扫描仪（具体目标2）。最后，我们将与商业质子治疗合作伙伴一起开发工程概念，并为受控技术转让做好准备（具体目标3）。本提案的交付物将是一种临床pCT头部扫描仪，用于全面评估pCT在质子治疗临床应用中的价值，并作为低剂量CT成像模式。如果成功，这项研究和开发将改变目前质子治疗计划只能基于X射线CT的模式，转向使用更准确的基于pCT的计划和pCT图像引导的质子治疗。这将为在临床试验中测试全新的临床质子治疗方案打开大门。 公共卫生相关性：质子治疗是一种有吸引力的癌症治疗形式，它可以通过应用非常适形的剂量分布来进一步改善局部控制和生存，其中传递到健康组织的剂量甚至比最先进的光子治疗技术更少。质子治疗中的一个未解决的问题是目前无法预测组织中质子的确切范围，这是由于将CT Hounsfield单位转换为质子阻止能力的不准确性以及在治疗室中缺乏每天预测质子范围的低剂量成像模态。该提案旨在开发、测试和转换从高能物理学借来的质子三维断层成像（质子CT）技术，以最大限度地减少这些不确定性，并在治疗室提供低剂量成像模式，从而改善质子治疗。

DESCRIPTION (provided by applicant): Proton therapy for cancer treatment has gained much recognition and attracted great interest in recent years as evidenced by the increasing number of proton radiation therapy facilities in the United States and around the world. The reason for this interest is that proton therapy could further improve the results of cancer treatments by applying very conformal dose distributions with less dose delivered to healthy tissues than with even the most advanced photon therapy techniques. Another reason is the promise from industry to develop more compact and less expensive proton technology. One unsolved problem in proton therapy is the current inability to predict the exact range of protons in tissue due to inaccuracy of converting CT Hounsfield units to proton stopping power and the lack of a low-dose imaging modality in the treatment room predicting the range of protons on a day-to-day basis. This is unfortunate, because the major promise of protons is the ability to stop the radiation in front of a critical normal tissue structure positioned behind a tumor. The technological limitation mostly responsible for this uncertainty is the use of x-ray based computed tomography (xCT) for proton treatment planning and the lack of a low-dose modality for daily treatment-room image guidance. The reason for using xCT is its wide availability and established role in radiation therapy treatment planning and image guidance. Here, we are proposing to overcome the current limitations of xCT by using proton computed tomography (pCT) for proton treatment planning and image guidance in the treatment room. With this effort at the interface of physics and medicine, we will leverage our experience of recent years in developing a prototype pCT scanner and advanced image reconstruction methods. We will make the transition from the current prototype scanner to a clinical pCT scanner. The prototype will be used to demonstrate the value of pCT in comparison to x-ray CT (specific aim 1). We will also study the technological limitations of the prototype and, with the help of our collaborators in high energy physics and computer science and engineering, develop a head pCT scanner that is suitable for clinical applications (specific aim 2). Lastly, we will develop engineering concepts with a commercial proton therapy partner and prepare the stage for a controlled technology transfer (specific aim 3). The deliverable of this proposal will be a clinical pCT head scanner for thorough evaluation of the value of pCT for clinical applications in proton therapy and as a low-dose CT imaging modality. If successful, this research and development will shift the current paradigm that proton treatment planning can only be based on x-ray CT, toward the use of more accurate pCT-based planning and pCT-image guided proton therapy. This will open the door for entirely new clinical proton treatment protocols to be tested in clinical trials. PUBLIC HEALTH RELEVANCE: Proton therapy is an attractive form of cancer treatment that could further improve local control and survival by applying very conformal dose distributions with fewer doses delivered to healthy tissues than with even the most advanced photon therapy techniques. One unsolved problem in proton therapy is the current inability to predict the exact range of protons in tissue due to inaccuracy of converting CT Hounsfield units to proton stopping power and the lack of a low-dose imaging modality in the treatment room predicting the range of protons on a day-to-day basis. This proposal aims to develop, test and translate technology borrowed from high energy physics for 3D tomographic imaging with protons (proton CT) to minimize these uncertainties and to provide a low-dose imaging modality in the treatment room, and thereby improve proton therapy.