Novel four dimensional magnetic resonance imaging to monitor pancreatic tumor infiltrating blood vessels and tumor response to chemoradiation therapy

背景：胰腺癌患者的预后很差，累积5年 生存率7%。大多数患者表现为局部晚期（LAPC）或边缘性可切除 （BRC）胰腺癌。边缘阴性患者的总生存率 放化疗后切除者是未切除者的2-3倍。上级 手术的结果要求针对降级患者的新的局部治疗策略， 提高切除率。靶向治疗，如立体定向放射治疗（SBRT） 同时对肿瘤浸润血管进行整合加强（SIB）， 消毒血管周围的癌组织，限制手术。然而，SIB治疗不是 由于在管理内部器官运动、可视化和 分割增强体积，并跟踪肿瘤对当前CT治疗的反应 基于规划和响应评估。磁共振成像（MRI）本质上是 软组织对比度上级于CT，但直到最近，很少有序列可用于解决 胰腺放射治疗的特定需求，包括需要解决运动和区分 肿瘤浸润血管。我们开创了一种基于三维k空间重排序的四维MRI（4D- MRI）技术用于腹部。尽管分辨率很高，但目前的4D-MRI图像 血管对比度不足以进行分割和定位。 目标：本研究的第一个目标是优化4D-MRI技术， 用于SBRT-SIB靶定位的足够高的血管对比度。第二个目标是使用 这种新型的4D-MRI与血管突出显示，以确定预测肿瘤的成像标记物， 放化疗干预后的可切除性。 方法：我们将通过引入一个新的板选择性函数来优化新的序列 其突出肿瘤包裹血管并量化对比噪声的增强 (CNR)比率以及胰腺肿瘤内血管的形态学变化。的流程 体模和健康志愿者将用于优化4D-MRI参数，例如 径向线，分辨率和平板选择性体积。CNR将与流速相关， 幻影为了验证该方法，我们还将招募30名诊断为LAPC或 BRPC并进行放化疗前后4D-MRI研究。血管的变化 CNR、几何结构和形态将与标准临床结局相关。 影响：本研究的成功将提供一种能够定位 涉及血管的肿瘤，同时克服呼吸运动模糊。这些信息将被 可用于指导靶向辐射剂量递增到由参与者定义的增强体积 血管，最初排除切除。因此，该项目满足了以下未满足的需求： 目前的胰腺癌管理，因为超过85%的患者具有不可切除的 由于血管受累而导致的癌症。

Background: Pancreas cancer patients have a dismal prognosis, with the cumulative 5-year survival of 7%. Most patients present with locally advanced (LAPC) or borderline resectable (BRPC) pancreatic cancer. The overall survival rates in the patients undergoing margin-negative resection after chemoradiation therapies are 2-3 times of the unresected group. The superior outcome of surgery calls for novel local treatment strategies aiming at downstaging patients and improving resection rate. Targeted therapy such as stereotactic body radiation therapy (SBRT) with simultaneous integrated boost (SIB) to tumor infiltrating blood vessels has the potential to sterilize cancerous tissue around the vessels that limit surgery. However, the SIB treatment is not commonly applied due to challenges in managing internal organ motion, visualization and segmentation of boost volumes, and tracking the tumor response to the therapy with current CT based planning and response assessment. Magnetic resonance imaging (MRI) is intrinsically superior to CT in soft tissue contrast, but until recently, few sequences were available to address the specific needs in pancreas radiotherapy including the need to resolve motion and differentiate tumor infiltrated vessels. We pioneered a 3D k-space resorting based four-dimensional MRI (4D- MRI) technique for the abdomen. Despite its high resolution, the current 4D-MRI images have insufficient vessel contrast for segmenting and targeting. Goals: The first goal of this study is to optimize the 4D-MRI technique so it generates a sufficiently high blood vessel contrast for SBRT-SIB target localization. The second goal is to use this novel 4D-MRI with vessel highlight to identify imaging makers that predict tumor resectability after chemoradiation therapy intervention. Methods: We will optimize the novel sequence by incorporating a new slab-selective function which highlights tumor encasing blood vessels and quantify the enhancement of contrast-to-noise (CNR) ratio as well as morphological changes for the vessels within the pancreatic tumor. A flow phantom and healthy volunteers will be used to optimize 4D-MRI parameters such as the number of radial lines, resolution and slab-selective volume. The CNR will be correlated to flow rates in the phantom. To validate the method, we will also recruit 30 patients diagnosed with LAPC or BRPC and perform pre- and post- chemoradiation 4D-MRI studies. The changes of the vessel CNR, geometry and morphology will be correlated to standard clinical outcomes. Impact: Success of this study will provide a non-invasive imaging method capable of localizing tumor involving blood vessels while overcoming respiratory motion blur. The information will be available to guide targeted radiation dose escalation to the boost volume defined by the involved vessels, which initially preclude resection. Therefore, the project answers an unmet need in current pancreatic cancer management since more than 85% of the patients have non-resectable cancer due to vessel involvement.