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

摘要：这项提议旨在解决质子射程不确定的长期挑战。 通过开发一种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)。 由于质子束的有限，质子RT有可能实现比光子RT更好的正常组织保存 剂量沉积的射程和布拉格峰(BP)。美国质子中心的数量增加了超过 40%，在过去的4年里。然而，尽管质子放射治疗前景看好，发展迅速，但其治疗效果是 严重受限于质子射程的不确定性(即，BP在患者体内的准确位置) 来自日常患者设置错误、解剖变化和剂量计算的不确定性。为了解释这一点， 实际上，在肿瘤周围增加了比预期更大的治疗余量(可能为1厘米)，以确保 足够的剂量覆盖范围。这些边缘显著增加了对邻近健康组织的剂量，导致 辐射引起的毒性增加。对增加毒性的担忧反过来又限制了可能 被开到肿瘤上，从而限制了我们所能实现的肿瘤控制。因此，有一个重要的和 迫切需要克服束流距离的不确定性，以便充分发挥质子RT的真正潜力 被剥削。PGI已经成为一种很有前途的技术，通过成像来验证和减少距离不确定性 质子RT过程中质子与核的非弹性相互作用产生的瞬发伽马(PG)信号。在我们的 在NIH资助的研究之前，我们开发了一个原型PGI系统，它展示了世界上第一个3D 临床质子束的PG发射图像，距离漂移检测精度~3 mm。尽管 在早期的成功，我们的系统有几个关键的障碍，阻止它被翻译，包括有限的 康普顿相机的计数速率，带有伪影的原始PG图像质量和由于视差而导致的严重失真， 缺乏剂量估算。在这笔赠款中，我们将用硬件和软件来改造整个系统 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 研究方向：(1)开发、集成和同步四摄像头PGI系统到质子RT机中， (2)开发新的图像处理和重建方法，实现高精度的三维剂量验证， 以及(3)进行先导性患者研究，以评估其临床影响。我们已经形成了一流的学术团队 (马里兰州)和行业(瓦里安)的伙伴关系，具有互补的专业知识和合作记录 以确保项目的成功。我们对PGI系统的合作开发和翻译将是 朝着实现我们的长期目标迈出的重要一步，即通过最大限度地缩小质子RT的射程来提高其效率 不确定因素。我们的PGI系统将是第一个在质子过程中提供真正3D在线剂量验证的系统 治疗提供，这可能导致向高精度质子RT的范式转变。这一突破将 充分释放质子放射治疗的潜力，使用最小的治疗余量实现最佳的肿瘤控制 在美国和世界范围内，越来越多的癌症患者接受质子RT治疗，减少了毒性。

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.