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

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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.