Accurate 4D Liver Tumor Localization for Radiotherapy using Contrast-Agent-Free X-ray Imaging and Liver Biomechanical Modeling

摘要 放射治疗已成为治疗原发性和转移性肺癌患者的一种越来越有效的技术。 肝癌，特别是在立体定向放射治疗（SBRT）出现之后。SBRT提供了一个大的， 聚焦放射剂量至肝肿瘤，并实现上级局部控制和存活。然而，对于目前的肝 SBRT，体积通常比实际肿瘤大得多（治疗边缘超出肿瘤15 mm）。 肿瘤边界）进行处理，以说明在计算的锥束下的肿瘤定位不确定性。 断层扫描（CBCT）图像引导。如此大的治疗体积会对正常肝组织产生更多的辐射 和器官的风险，并提出了正常组织毒性的关注，特别是对于肝硬化患者 以及有限的健康肝脏组织储备。它还可以防止进一步的剂量递增，以最大限度地提高疗效 的SBRT。目前，缺乏通过CBCT准确定位肝脏肿瘤的可靠技术，主要是由于 呼吸引起的肝脏运动和肝脏肿瘤与正常肝脏组织的低对比度。在 响应PAR-19-158，我们建议开发一种生物力学建模引导的4DCBCT技术（生物- 4DCBCT），其生成4DCBCT图像以捕获肝脏肿瘤运动，从而进行精确的4D定位。的 Bio-4DCBCT将肝脏生物力学建模纳入4DCBCT生成过程， 显著提高CBCT在低对比度区域的定位精度。本研究的目的是 开发、优化和验证Bio-4DCBCT技术，以实现约2 mm的肿瘤定位精度。在 本研究将追求三个具体目标：SA 1。通过回顾性患者研究优化Bio-4DCBCT。 SA 2.通过开发一个可运动、可变形的物理肝脏体模来评价Bio-4DCBCT。SA 3.评价 通过比较Bio-4DCBCT与当前临床应用的Bio-4DCBCT的前瞻性临床研究 技术.该项目的创新点是Bio-4DCBCT技术及其在精确4D肝脏中的应用 肿瘤定位，从而显著减少治疗体积/切缘， 更有效的肝脏SBRT。Bio-4DCBCT技术是在传统CBCT系统的基础上发展起来的 在标准图像采集协议下，其将容易地应用于全世界的放射治疗诊所 无需硬件升级或图像采集协议改变。成功的临床转化 这项技术有望在目前的肿瘤定位模式中产生有利的转变，不仅适用于肝脏， 也适用于低组织对比度不利地影响放射治疗精度的其它肿瘤部位。

ABSTRACT Radiotherapy has become an increasingly effective technique to treat patients affected by primary and metastatic liver cancers, especially after the advent of stereotactic body radiotherapy (SBRT). SBRT delivers a large and focused radiation dose to liver tumors and achieves superior local control and survival. However, for current liver SBRT, a volume usually much larger than the actual tumor (with treatment margins up to 15 mm beyond the tumor boundary) is treated, to account for tumor localization uncertainties under the cone-beam computed tomography (CBCT) image guidance. Such a large treatment volume incurs more radiation to normal liver tissues and organs-at-risks and raises the concern of normal tissue toxicity, especially for patients with liver cirrhosis and a limited healthy liver tissue reserve. It also prevents further dose escalation to maximize the effectiveness of SBRT. Currently, there lacks a reliable technique to accurately localize liver tumors by CBCT, mostly due to the respiration-induced liver motion and the low contrast of liver tumors against the normal liver tissues. In response to PAR-19-158, we propose to develop a biomechanical modeling-guided 4DCBCT technique (Bio- 4DCBCT), which generates 4DCBCT images to capture the liver tumor motion for accurate 4D localization. The Bio-4DCBCT incorporates liver biomechanical modeling into the 4DCBCT generation process, which can substantially improve the localization accuracy of CBCT at low-contrast regions. The goal of this study is to develop, optimize and validate the Bio-4DCBCT technique to achieve ~ 2 mm tumor localization accuracy. In this study we will pursue three specific aims: SA1. Optimize Bio-4DCBCT through a retrospective patient study. SA2. Evaluate Bio-4DCBCT by developing a motion-enabled, deformable, physical liver phantom. SA3. Evaluate Bio-4DCBCT through a prospective clinical study by comparing Bio-4DCBCT with the current clinically-applied techniques. The innovation of the project is the Bio-4DCBCT technique and its application for accurate 4D liver tumor localization, which leads to substantial treatment volume/margin reduction to achieve safer, more viable and more effective liver SBRT. The Bio-4DCBCT technique is developed on the conventional CBCT system under standard image acquisition protocols, which will be readily applicable in radiotherapy clinics worldwide without hardware upgrade or image acquisition protocol change. The successful clinical translation of this technology is expected to create a favorable shift in current tumor localization paradigms, not only for liver but also for other tumor sites where low tissue contrast adversely affects the radiotherapy treatment accuracy.