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

背景：胰腺癌患者预后较差，累积为5年 存活率为7%。大多数患者存在局部晚期(LAPC)或交界性可切除 (BRPC)胰腺癌。切缘阴性患者的总体存活率 放化疗后切除是未切除组的2~3倍。《上级》 手术的结果需要新的局部治疗策略，旨在降低患者和 提高切除率。立体定向全身放射治疗(SBRT)等靶向治疗 同时积分增强(SIB)对肿瘤浸润性血管具有潜在的作用 对限制手术的血管周围的癌细胞组织进行消毒。然而，SIB的待遇并不是 由于在管理内部器官运动、可视化和 增强体积的分割，并用当前CT跟踪肿瘤对治疗的反应 基于规划和响应评估。磁共振成像(MRI)本质上是 在软组织对比方面优于CT，但直到最近，还很少有序列可供处理 胰腺放射治疗中的特殊需要，包括解决运动和鉴别的需要 肿瘤浸润性血管。我们首创了一种基于3D k空间重现的四维MRI(4D- 腹部的核磁共振成像技术。尽管分辨率很高，但目前的4D-MRI图像 血管对比度不足，无法进行分割和定位。 目标：这项研究的第一个目标是优化4D-MRI技术，使其产生 足够高的血管对比度可用于SBRT-SIB靶点定位。第二个目标是使用 这种新型的4D-MRI具有血管突出显示功能，可以识别预测肿瘤的成像标志物 放化疗干预后的可切除性。 方法：我们将通过加入新的平板选择功能来优化新的序列 它突出了肿瘤包裹血管并量化了对比噪声的增强 (CNR)比率以及胰腺肿瘤内血管的形态变化。一种流动 将使用幻影和健康志愿者来优化4D-MRI参数，如数量 放射线、分辨率和板材选择体积。CNR将与流入的流量相关 幽灵。为了验证该方法，我们还招募了30名被诊断为LAPC或 并进行放化疗前后的4D-MRI检查。血管的变化 CNR、几何形状和形态将与标准的临床结果相关。 影响：该研究的成功将提供一种能够定位的非侵入性成像方法 肿瘤累及血管，同时克服呼吸运动模糊。这些信息将是 可用于引导定向辐射剂量升级到相关人员定义的增强体积 血管，这最初排除了切除。因此，该项目满足了未得到满足的需求 目前胰腺癌的治疗方法是85%以上的患者不能切除 因血管受累而致癌。

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.