Real-time in vivo proton range verification in proton therapy with thallium bromide detectors

摘要 使用质子放射治疗是一个有吸引力的选择，因为它有可能更好地保存健康组织 与带有光子或电子的辐射相比，因为试验结果表明，它可以取代手术 彻底的癌症治疗也是如此。质子疗法利用有限范围的重带电粒子 在其路径末端的强度最大(布拉格峰值)，随后剂量急剧下降。然而， 基于计算机断层扫描(CT)的质子射程预测存在估计的不确定性。为 近端关键器官和可及性有限的治疗(头和颈部)、高异质性(肺)、 或显著的呼吸运动(肝脏)这种不确定性太高，在最好的情况下，治疗是具有挑战性的，如果 也不是不可能。需要新的仪器来监测布拉格峰的位置，以达到1-2毫米的精度 在这些具有挑战性的场景中，在几秒钟内。 我们建议使用新型切伦科夫电荷感应(CCI)溴化铊(TlBr)探测器来探测质子 质子治疗中的射程验证(PRV)。CCI TlBR探测器结合了切伦科夫光的检测，这 利用半导体探测器的传统读数提供亚纳秒级的时间分辨率， 提供出色的能量分辨率和3-D分割。此外，TlBR具有较短的衰减长度 比最常用的瞬发伽马闪烁材料高达6.1 MeV。CCI TlBR探测器提供 独特的性能，因为它们在能量、时间和空间上都提供了出色的性能 分辨率，这符合PRV在质子治疗中的需求。 在这个项目中，我们将测试使用非准直瞬发伽马定时-康普顿相机的可行性 基于像素CCI TlBR探测器的(PGT-CC)相机用于质子治疗中的PRV。我们将制造像素 CCI TlBr型探测器，具有优化的表面处理以耦合光电探测器，并具有高度稳定的长寿命 持久电极；2)在台式设置中表征像素CCI TlBR器件的探测器特征 密封源，包括能量、空间和时间分辨率；3)评估PGT-CC的性能 PRV用像素CCI TlBr探测器制成的照相机，在光束线上，质子加速到67.5 MeV；以及 4)将我们的PGT-CC相机原型与金标技术进行了性能比较 临床光束线上的治疗方案，质子加速到200 MeV。 该项目目标的实现将决定CCI TlBr探测器成为 质子治疗中最具竞争力的PRV设备。建议的检测的成功执行 系统将允许在目前非常严重的治疗区域利用质子治疗的好处 具有挑战性，从而提高了治疗效果，降低了对患者健康器官的毒性。

Summary Radiotherapy using protons is an attractive option as it has the potential to better preserve healthy tissue compared to radiation with photons or electrons, and because trial outcomes indicate it can replace surgery for radical cancer treatments as well. Proton therapy makes use of the finite range of heavy charged particles with an intensity maximum at the end of their path (Bragg peak) followed by a sharp fall-off of the dose. However, predicting the proton range based on computed tomography (CT) scans carries an estimation uncertainty. For treatments with proximal critical organs and limited accessibility (head and neck), high heterogeneities (lung), or significant breath motion (liver) such uncertainty is too high and the therapy is in the best case challenging, if not impossible. New instrumentation is needed to monitor the location of the Bragg peak to 1-2 mm accuracy within several seconds in these challenging scenarios. We propose to use the novel Cerenkov Charge Induction (CCI) thallium bromide (TlBr) detectors for proton range verification (PRV) in proton therapy. CCI TlBr detectors combine the detection of Cerenkov light, which provides sub-nanosecond timing resolution with the conventional readout of semiconductor detectors, which provides excellent energy resolution and 3-D segmentation. Moreover, TlBr has a shorter attenuation length than most commonly used scintillation materials for prompt-gammas up to 6.1 MeV. CCI TlBr detectors provide a unique performance, as they offer simultaneous excellent performance in energy, time, and spatial resolution, that fits the needs of PRV in proton therapy. In this project, we will test the feasibility of using a non-collimated prompt gamma timing – Compton camera (PGT-CC) camera based on pixel CCI TlBr detectors for PRV in proton therapy. We will 1) manufacture pixel CCI TlBr detectors with optimized surface treatment to couple the photodetector and with highly-stable long- lasting electrodes; 2) characterize the detector features of pixel CCI TlBr devices in a benchtop setting using sealed sources, including energy, spatial, and timing resolution; 3) evaluate the performance of a PGT-CC camera for PRV made with pixel CCI TlBr detectors in a beamline with protons accelerated to 67.5 MeV; and 4) compare the performance of our PGT-CC camera prototype with gold standard techniques following realistic treatment protocols at a clinical beamline with protons accelerated to >200 MeV. The accomplishment of the aims of this project will determine the potential of CCI TlBr detectors to become the most competitive devices for PRV in proton therapy. A successful performance of the proposed detection system would allow to exploit the benefits of proton therapy in treatment regions that are currently very challenging, leading to increased treatment efficacy and lower toxicity in the healthy organs of the patients.