質子治療是近年於各國方興未艾的癌症治療技術。質子射束具有布拉格峰 (Bragg peak, BP)的物理特性，可提供腫瘤組織較高的劑量且大幅降低周圍的正常組織的傷害。然而，質子射程的不準確性將會造成治療效果不佳。因此應用射程驗證來排除這些不準確性在質子治療過程中扮演非常重要的角色。近年來應用閃爍造影儀設備於質子治療射程驗證的概念已被相繼提出與實現，透過該設備接收治療過程中病人體內放出的瞬發光子 (prompt gamma, PG)訊號可做為質子射程驗證的重要依據。
本研究目標為設計出一套質子治療射程評估用的光子造影儀器，同時結合加馬攝影機 (gamma camera)平面造影驗證腫瘤擺位的幾何精準度與準直儀閃爍偵檢器 (collimator-based camera)進行質子射程驗證，藉由該項驗證工具的開發，將可幫助確保幾何位置並進行質子治療射程驗證。
本研究可分成三大部分，首先針對prompt gamma系統比較兩種collimator-based camera (multi-slit及knife-edge)在質子治療射程驗證的性能表現，分別就能窗選擇、射束能量、射程位移之偵測等參數進行評估，最後選擇適用的collimator-based camera應用在第三部分。在第二部分中，我們先行評估gamma camera於質子治療的可行性，以矩形假體探討不同腫瘤大小、腫瘤移動及腫瘤深度的影響。最後再結合兩種驗證系統共同評估並以單光子斷層掃描 (Single-photon emission computed tomography, SPECT)做為標準影像，此驗證法不但能驗證腫瘤的幾何結構，還可以提供質子治療射程驗證的評估資訊。
實驗結果顯示兩種collimator-based camera系統對於位移的偵測皆有很好的精準度，其中knife-edge系統有較高的偵測效率且具有較低的中子污染問題。而第二部分結果證明對於腫瘤位移的偵測，相較於knife-edge系統gamma camera可提供更高的精準度。最後結合gamma camera與knife-edge射程驗證系統，結果顯示SPECT作為腫瘤定位的標準影像是可行的，不過gamma camera的掃描方式需要被改良，使系統有更精準的腫瘤定位。
整體而言，本實驗所提出的光子造影儀器於質子治療中是可行的，不過中子污染對於collimator-based camera的影響是相當大的，因此中子去除技術的發展在未來是相當重要的，此外，核子醫學影像對於腫瘤的定位是可以信賴的，因此只要能夠克服gamma camera影像品質的問題，該項驗證工具的開發將不是難事，期望此套光子造影儀器於臨床質子治療射程評估中可提供更精準的治療效果。

Proton therapy is gaining popularity in the world. Proton beam possesses the physical property of Bragg peak that can be used to provide higher radiation dose to tumor and spares the normal tissues. However, the inaccuracy in proton range limits the advantages of Bragg peak. The proton range verification plays a very important role in the proton therapy. In recent years, camera equipped with collimators (multi-slit and knife-edge slit collimator) to image prompt gamma (PG) emitted along the proton tracks in the patient have been proposed for range verification.
The aim of the work is to develop a system which combines a gamma camera for tumor localization and collimator-based camera for proton range verification.
This study can be separated into three stages. GATE/GEANT4 will be used as a simulation tool of the proton therapy in all stages. The purpose in the first stage is to compare the performance of multi-slit collimator and knife-edge slit collimator in range verification. Factors including the energy window setting, proton energy, phantom size, and phantom shift that may influence the accuracy of detecting range were studied. In the second stage, we evaluate the feasibility of gamma camera for tumor localization in proton therapy. The tumor size, phantom shift and the depth of tumor localization will be studied in a rectangular PMMA phantom. Finally, in the third stage, we combine gamma camera with the selected range verification system (from stage one) to evaluate this method based on a simulated tumor embedded in a Zubal phantom.
Results in the first stage indicate that both collimator systems have good response to the phantom shift, and knife-edge collimator system achieve higher detection efficiency leading to a smaller deviation in predicting range. In the stage two, gamma camera achieves better accuracy of detecting the phantom shift than knife-edge system. The final stage indicate this method is feasible with SPECT reference image. However, the quality of gamma camera image should be improved by other scanning modes.
We conclude that combining gamma camera and collimator-based camera have potentials for accurately range monitoring in proton therapy. It is noted that neutron contamination has a marked impact on range prediction of the collimator-based camera, especially in multi-slit system. Therefore, a neutron reduction technique for improving the accuracy of range verification of proton therapy is needed.

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