3-dimensional prompt gamma imaging for online proton beam dose verification

摘要：该提案旨在解决质子探测器射程不确定性的长期挑战 通过开发用于体内剂量验证的新型3D即时伽马成像（PGI）系统，来实现放射治疗（RT）。 由于质子射束的有限性，质子RT可以潜在地实现比光子RT更好的正常组织保留。 范围和布拉格峰（BP）的剂量沉积。美国质子中心的数量增加了超过 在过去的四年里，40%。然而，尽管质子RT的前景和快速增长，其治疗效果是 受到质子束范围内的不确定性的严重限制（即，BP在患者体内的精确位置）出现 来自日常患者设置错误、解剖变化和剂量计算不确定性。为了解释这一点， 在实践中，在肿瘤周围增加大于期望的治疗边缘（可能>1cm），以确保 足够的剂量覆盖。这些边缘显著增加了邻近健康组织的剂量，导致 辐射引起的毒性增加。对毒性增加的担忧反过来又限制了可以 因此限制了我们对肿瘤的控制。因此，有一个重要的和 迫切需要克服射束范围的不确定性，以便能够充分发挥质子RT的真正潜力。 被剥削PGI已经成为一种很有前途的技术，通过成像来验证和最小化距离不确定性。 在质子RT期间，从非弹性质子-核相互作用发出的瞬发γ（PG）信号。 在NIH资助的研究之前，我们开发了一个原型PGI系统，展示了世界上第一个3D 临床质子束的PG发射图像，范围偏移检测精度为~3 mm。 早期的成功，我们的系统有几个关键的障碍，阻止它被翻译，包括有限的 康普顿照相机的计数率，粗糙的PG图像质量，由于视差造成的伪影和严重失真， 缺乏剂量估算。在这项拨款中，我们会从硬件和软件两方面， 创新，以克服目前的障碍，实现高精度的3D剂量验证。以下目标将 追求：（1）开发，集成和同步四摄像头PGI系统到质子RT机， (2)开发新的图像处理和重建方法，以实现高精度3D剂量验证， 以及（3）进行试点患者研究以评估其临床影响。我们已经形成了一个一流的学术 （马里兰州）和行业（瓦里安）的合作伙伴关系，具有互补的专业知识和合作的良好记录 以确保项目的成功。我们合作开发和翻译的PGI系统将是一个 这是实现我们通过最小化质子RT范围来提高其疗效的长期目标的重要一步 不确定性我们的PGI系统将是第一个提供真正的3D在线剂量验证在质子 治疗交付，这可能导致向高精度质子RT的范式转变。这一突破将 释放质子RT的全部潜力，使用最小的治疗余量来实现最佳的肿瘤控制， 在美国和全球范围内，质子RT治疗的癌症患者数量不断增加，从而降低了毒性。

ABSTRACT: This proposal aims to address the long-term challenge of range uncertainties in proton radiotherapy (RT) by developing a novel 3D prompt gamma imaging (PGI) system for in vivo dose verification. Proton RT can potentially achieve better normal tissue sparing than photon RT due to proton beams’ finite range and Bragg peak (BP) in dose deposition. The number of proton centers in the US has increased by over 40% in the past 4 years. However, despite the promise and rapid growth of proton RT, its treatment efficacy is severely limited by uncertainties in the proton beam range (i.e., the precise location of BP in the patient) arising from daily patient setup errors, anatomic change, and dose calculation uncertainties. To account for this, larger-than-desirable treatment margins (potentially>1cm) are added around the tumor in practice to ensure adequate dose coverage. These margins significantly increase the dose to adjacent healthy tissues, leading to an increase in radiation-induced toxicities. Concerns of increased toxicities, in turn, constrain the dose that can be prescribed to the tumor and thus limit the tumor control we can achieve. Therefore, there is a significant and critical need to overcome beam range uncertainties so that the true potential of proton RT can be fully exploited. PGI has become a promising technique to verify and minimize range uncertainties by imaging the prompt gamma (PG) signals emitted from the non-elastic proton-nucleus interactions during proton RT. In our prior NIH-funded research, we developed a prototype PGI system that demonstrated the world's first 3D images of PG emission from clinical proton beams with a range shift detection accuracy of ~3 mm. Despite the early success, our system had several critical barriers that prevented it from being translated, including limited count rate of the Compton camera, crude PG image quality with artifacts and severe distortion due to parallax, and lack of dose estimation. In this grant, we will revamp the entire system with both hardware and software innovations to overcome current barriers to achieve high precision 3D dose verification. The following aims will be pursued: (1) develop, integrate and synchronize a quad-camera PGI system into the proton RT machine, (2) develop novel image processing and reconstruction methods to achieve high-precision 3D dose verification, and (3) perform a pilot patient study to evaluate its clinical impact. We have formed a top-tier academic (Maryland) and industry (Varian) partnership with complementary expertise and a track record of collaboration to ensure the success of the project. Our collaborative development and translation of the PGI system will be a major step toward fulfilling our long-term goal of improving the efficacy of proton RT by minimizing its range uncertainties. Our PGI system will be the first to provide truly 3D online dose verification during proton treatment delivery, which can lead to a paradigm shift toward high-precision proton RT. This breakthrough will unleash the full potential of proton RT to use minimal treatment margin to achieve optimal tumor control with reduced toxicities for the growing number of cancer patients treated by proton RT in the US and worldwide.