Translating Proton CT from the Physics Laboratory to Clinical Application

描述（由申请人提供）：近年来，质子放射治疗在美国和世界各地越来越多的质子放射治疗设施证明，质子治疗癌症得到了广泛的认可和引起了极大的兴趣。这种兴趣的原因是质子治疗可以进一步改善癌症治疗的结果，通过应用非常适形的剂量分布，甚至比最先进的光子治疗技术提供更少的剂量给健康组织。另一个原因是工业界承诺开发更紧凑、更便宜的质子技术。质子治疗的一个未解决的问题是目前无法准确预测组织中质子的范围，这是由于将CT霍斯菲尔德单位转换为质子停止功率的准确性不高，以及治疗室中缺乏预测质子范围的低剂量成像模式。这是不幸的，因为质子的主要前景是能够在肿瘤后面的关键正常组织结构前阻止辐射。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治疗计划和图像指导中的既定作用。在这里，我们建议利用质子计算机断层扫描（pCT）在治疗室进行质子治疗计划和图像指导，以克服目前xCT的局限性。通过这项物理和医学结合的努力，我们将利用近年来的经验开发pCT扫描仪原型和先进的图像重建方法。我们将从目前的原型扫描仪过渡到临床pCT扫描仪。该原型将用于演示pCT与x射线CT相比的价值（具体目的1）。我们还将研究原型的技术局限性，并在高能物理和计算机科学与工程合作者的帮助下，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）。该提案的交付成果将是临床pCT头部扫描仪，用于全面评估pCT在质子治疗中的临床应用价值，以及作为低剂量CT成像方式。如果成功，这项研究和发展将改变目前质子治疗计划只能基于x射线CT的范式，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。

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.