Hybrid virtual-MRI/CBCT: A new paradigm for image guidance in liver SBRT

摘要 该方案旨在建立一种用于辐射精确图像制导的混合虚拟MRI/CBCT系统 肝癌的治疗。立体定向全身放射治疗(SBRT)改善了治疗结果 常规分割放射治疗通过在几个分割中提供高分割剂量来实现。然而，SBRT的 肝癌的局部失败率仍然很高，2-3年高达20%-30%，总体级别高；毒性发生率上升 到30%的患者因治疗而死亡。以前的研究表明， 治疗结果和所使用的图像引导技术的肿瘤定位精度。目前，锥体 BEAM CT(CBCT)是目前应用最广泛的肝脏SBRT成像技术。然而，CBCT具有极大的 软组织对比度有限，大多数肝脏肿瘤无法显示。因此，它的定位误差是 经常超过6 mm，肿瘤体积的剂量覆盖率可降至90%以下，这远远不足以 肿瘤控制。大幅减少定位误差是提高肝脏SBRT治疗效果的关键。 MRI-放射治疗联合机可为肝脏肿瘤定位提供MRI对比度。然而，这样的 对于大多数诊所来说，机器既稀有又昂贵。因此，迫切需要一个替代解决方案来满足 所有放射肿瘤科无处不在的需求：一种新的低成本成像形式的解决方案 具有MRI等效对比度的系统。由于CBCT在大多数放射治疗机器上都很容易获得，因此 基于CBCT的成像系统将是最有效的策略。我们最近的出版物展示了 这一战略的可行性。(Harris，Med Phys 2018)我们的长期目标是建立下一代 具有虚拟多模式成像能力的CBCT系统，用于高精度肿瘤定位和自适应 放射治疗中的治疗。在这个应用程序中，我们的总体目标是建立一个新的系统来生成 来自CBCT的混合虚拟-MRI/CBCT，在肝脏内使用虚拟-MRI进行靶点定位和增强 肝脏外CBCT用于健康组织验证。具体目标是：(1)。建立3D混合虚拟- MRI/CBCT系统用于屏气肝SBRT无呼吸运动的影像引导。(2)。建立4D 混合虚拟MRI/CBCT系统用于呼吸运动自由呼吸肝脏SBRT的图像引导。(3)。 通过模拟研究和前瞻性临床试验对系统进行优化和临床评估。我们的 通过学术-产业合作伙伴关系预期的成果是新型混合虚拟磁共振成像/CBCT系统 准备集成到所有只有CBCT系统的放射治疗机器上。这一新的成像功能将 具有重大的临床影响，因为它将通过以下方式创造图像引导放射治疗的范式转变 使广泛使用的CBCT系统发生革命性变化，以实现低成本、高精度虚拟多通道的新时代 形态引导放射治疗。这种精确的制导可以在升级肿瘤控制方面取得突破 以及将肝脏SBRT的毒性降至最低，以及治疗软组织中肿瘤的其他部位。

ABSTRACT This proposal aims to establish a hybrid virtual-MRI/CBCT system for precision image guidance in radiation therapy of liver cancer. Stereotactic body radiation therapy (SBRT) improves the treatment outcome over conventional fractionated radiotherapy by delivering high fractional dose in few fractions. However, SBRT of liver cancer still has high local failure rate up to 20-30% at 2-3 years and high overall grade>=3 toxicity rate up to 30% with patient deaths from the treatment. Previous studies demonstrated a strong correlation between the treatment outcome and the tumor localization accuracy of the image guidance technique used. Currently, cone beam CT (CBCT) is the most widely used imaging technique for liver SBRT. However, CBCT has extremely limited soft tissue contrast with no visualization of most liver tumors. As a result, its localization error is frequently over 6mm, and the dose coverage of tumor volume can fall below 90%, which is far from enough for tumor control. Drastically reducing localization errors is imperative to improve the outcome of liver SBRT. Combined MRI-Radiotherapy machines could provide MRI contrast for liver tumor localization. However, such machines are rare and expensive for most clinics. As such, an alternative solution is urgently required to meet the ubiquitous need of all radiation oncology departments: a solution in the form of a novel low-cost imaging system with MRI equivalent contrast. Since CBCT is readily available on most radiotherapy machines, creating CBCT-based imaging systems would be the most effective strategy. Our recent publication demonstrated the feasibility of such strategy. (Harris, Med Phys 2018) Our long-term goal is to establish the next generation of CBCT systems with virtual multi-modality imaging capabilities for high precision tumor localization and adaptive therapy in radiation therapy. In this application, our overall objective is to establish a novel system to generate hybrid virtual-MRI/CBCT from CBCT, with virtual-MRI inside the liver for target localization and augmented CBCT outside the liver for healthy tissue verification. The specific aims are: (1). Establish a 3D hybrid virtual- MRI/CBCT system for image guidance in breath-hold liver SBRT without respiratory motion. (2). Establish a 4D hybrid virtual-MRI/CBCT system for image guidance in free-breathing liver SBRT with respiratory motion. (3). Optimize and clinically evaluate the systems through simulation studies and a prospective clinical trial. Our expected deliverables through the academic-industrial partnership are novel hybrid virtual-MRI/CBCT systems ready to be integrated to all radiotherapy machines with only CBCT systems. This new imaging capability will have significant clinical impact because it will create a paradigm shift in image-guided radiation therapy by revolutionizing the widely used CBCT systems to enable a new era of low-cost high-precision virtual multi- modality guided radiotherapy. This precision guidance can lead to breakthrough in escalating the tumor control and minimizing the toxicities of liver SBRT as well as treatments of other sites with tumors in the soft tissue.