Precise image guidance for liver cancer stereotactic body radiotherapy using element-resolved motion-compensated cone beam CT

项目摘要 肝癌，无论是原发的还是转移性的，发病率都在增加，并且与显著的 死亡率。立体定向全身放射治疗(SBRT)是一种有效、安全、可行的首创治疗方法。 不能切除的肝脏恶性肿瘤局部控制线的选择。尽管如此，很大的差距(通常 ~1 cm)，以适应锥形射束下肿瘤定位的不确定性 CT(CBCT)影像引导。由于呼吸运动和肿瘤对比度的消失，肿瘤靶点 无法在CBCT中可视化。基于解剖或植入的下位肿瘤定位入路 代用品是临床标准，导致大量肿瘤位置的不确定性和典型的切缘大小为 ~1厘米。因此，向大量正常组织输送高剂量，引起毒性问题， 尤其是对因癌症和/或肝功能障碍引起的患者的治疗更为实质性。此外, 正常的组织毒性限制了进一步的剂量递增，以提高临床效益。这一期预计将 当将SBRT扩展到更广泛的患者群体时，例如那些肿瘤体积较大的患者，情况会变得更加严重。 几种新兴的成像方法已经显示出提高图像制导精度的潜力，但也 遇到了挑战。到目前为止，还没有一种方法可以在临床上提供准确、可靠的 肝脏SBRT的可译性影像引导。最近，我们小组取得了突破性进展， 使用标准的CBCT平台重建元素组成图像。采用KVP-交换 技术，一种新的空间和光谱图像正则化的图像重建方法，以及一种新的 基于稀疏字典的元素分解方法，元素组成的准确率达到~3% 这是在幻影研究中测试的。我们还积累了重建高质量的 呼吸运动条件下的CBCT图像。有了这些成功的武装，这项研究的总体目标是 一种新型元素分辨运动补偿(ERMC-)CBCT碘造影剂的研制 在标准治疗计划CT扫描中仅使用20%对比剂进行精确扫描(不确定度2 mm) 影像引导在肝脏SBRT中的应用。我们将追求三个具体目标(SA)：SA1。发展全面的ERMC- CBCT系统。SA2.通过体模研究优化扫描参数。SA3.对10例患者进行研究 目的：测试ERMC-CBCT图像引导的安全性、可行性和肿瘤定位的准确性。这个 本项目的创新之处在于一种新颖的ERMC-CBCT系统及其在临床重大问题中的应用 肿瘤在肝脏SBRT中的定位。除了显著提高定位精度和 因此临床上保留正常组织的潜力和剂量递增，我们的项目也具有一定的意义 利用CBCT最大限度地发挥其在许多其他高级图像制导任务中的潜力 申请。ERMC-CBCT系统是在传统的CBCT平台上开发的，该平台是应用最广泛的 在放射治疗中提供图像引导平台，确保其可翻译性。

Project Summary Liver cancers, both primary and metastatic, are increasing in incidence and are associated with significant mortality. Stereotactic Body Radiotherapy (SBRT) has been established as an effective, safe, and feasible first- line option in the local control of unresectable hepatic malignancies. Nonetheless, a large margin (typically ~1cm) has to be used in current liver SBRT to accommodate tumor positioning uncertainty under cone-beam CT (CBCT) image guidance. Because of respiratory motion and vanishing tumor contrast, the tumor target cannot be visualized in CBCT. Inferior tumor positioning approach based on anatomical or implanted surrogates are clinical standard, leading to substantial tumor position uncertainty and a typical margin size of ~1cm. Consequently, high dose to a large volume of normal tissue is delivered, causing a toxicity concern, especially in patients with liver dysfunction caused by cancer and/or treatments is more substantial. In addition, normal tissue toxicity limits further dose escalation to improve clinical benefits. This issue is expected to become more severe, when extending SBRT to a wider patient population, e.g. those with a large tumor size. Several emerging imaging approaches have showed potential to improve image guidance accuracy but also encountered challenges. To date, there is no approach that can provide accurate, reliable, and clinically translatable image guidance for liver SBRT. Recently, our group has made a breakthrough towards reconstructing elemental composition image using a standard CBCT platform. Employing a kVp-switching technique, a novel image reconstruction method with spatial and spectral image regularization, as well as a sparse-dictionary based element decomposition method, we achieved ~3% accuracy in elemental composition as tested in phantom studies. We have also accumulated extensive experience in reconstructing high-quality CBCT images under respiratory motion. Armed with these successes, the overall goal of this study is to develop a novel element-resolved and motion-compensated (ERMC-) CBCT to image iodine contrast agent using only 20% contrast injection in a standard treatment planning CT scan for precise (uncertainty <2mm) image guidance in liver SBRT. We will pursue three specific aims (SAs): SA1. Develop the overall ERMC- CBCT system. SA2. Optimize scan parameters via phantom studies. SA3. Perform studies in 10 patient cases to test safety, feasibility, and tumor positioning accuracy of ERMC-CBCT based image guidance. The innovation of this project is a novel ERMC-CBCT system and its application for a clinically significant problem of tumor localization in liver SBRT. Besides the significance of substantially improved localization accuracy and therefore clinical potential of normal tissue sparing and dose escalation, our project also holds the significance of utilizing CBCT to its maximal potential for many other advanced image guidance tasks and quantitative applications. The ERMC-CBCT system is developed on a conventional CBCT platform, the most widely available image-guidance platform in radiotherapy, ensuring its translatability.