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

新型四维磁共振成像监测胰腺肿瘤浸润血管和肿瘤对放化疗的反应

• 批准号: 9804795
• 负责人: Zhaoyang Fan
• 金额: $ 19.66万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-17 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9804795
• 关键词: 3-Dimensional; 4D MRI; Abdomen; Address; Aftercare; Blood Vessels; CA-19-9 Antigen; Cancerous; Clinical; Collaborations; Data; Development; Diagnosis; Disease; Evaluation; Excision; Four-dimensional; Geometry; Goals; Image; Imagery; Imaging Techniques; Invaded; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of pancreas; Methods; Monitor; Morphologic artifacts; Morphology; Motion; Neoadjuvant Therapy; Neoplasms in Vascular Tissue; Noise; Operative Surgical Procedures; Organ; Outcome; Pancreas; Pancreatic Ductal Adenocarcinoma; Patient-Focused Outcomes; Patients; Phase; Prediction of Response to Therapy; Primary Neoplasm; Quantitative Evaluations; Radial; Radiation; Radiation Dose Unit; Radiation therapy; Reproducibility; Research Personnel; Resectable; Resolution; Resort; Scanning; Solid Neoplasm; Specificity; Surgeon; Survival Rate; Techniques; Testing; Therapeutic Intervention; Three-Dimensional Image; Time; Tissues; Treatment outcome; Unresectable; base; chemoradiation; contrast enhanced; contrast imaging; effective therapy; healthy volunteer; imaging biomarker; imaging modality; imaging study; improved; non-invasive imaging; novel; outcome forecast; pancreatic cancer patients; pancreatic neoplasm; recruit; respiratory; response; response biomarker; soft tissue; success; surgery outcome; targeted treatment; treatment planning; treatment response; treatment strategy; tumor

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.

背景：胰腺癌患者预后不佳，累计 5 年预后较差。 存活率7%。大多数患者表现为局部晚期 (LAPC) 或临界可切除 (BRPC) 胰腺癌。切缘阴性患者的总生存率 放化疗后的切除量是未切除组的2-3倍。上级 手术的结果需要新的局部治疗策略来降低患者的分期 提高切除率。靶向治疗，例如立体定向放射治疗 (SBRT) 对肿瘤浸润血管进行同步整合增强（SIB）有可能 对限制手术的血管周围的癌组织进行消毒。然而，SIB 治疗并不 由于管理内部器官运动、可视化和 分割增压量，并使用当前 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 在软组织对比度方面优于 CT，但直到最近，很少有序列可用于解决 胰腺放射治疗的具体需求，包括解决运动和区分的需求 肿瘤浸润血管。我们首创了基于 3D k 空间的四维 MRI（4D- MRI）腹部技术。尽管分辨率很高，但当前的 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，使其生成 足够高的血管对比度用于 SBRT-SIB 目标定位。第二个目标是使用 这种新颖的 4D-MRI 具有血管突出显示功能，可识别预测肿瘤的成像标记 放化疗干预后的可切除性。 方法：我们将通过结合新的板选择函数来优化新颖的序列 突出显示肿瘤包裹的血管并量化噪声对比度的增强 (CNR) 比率以及胰腺肿瘤内血管的形态变化。一股流 模型和健康志愿者将用于优化 4D-MRI 参数，例如数量 径向线、分辨率和板选择性体积。 CNR 将与流量相关 幻影。为了验证该方法，我们还将招募 30 名诊断为 LAPC 或 BRPC 并进行放化疗前和放化疗后 4D-MRI 研究。船舶的变化 CNR、几何形状和形态将与标准临床结果相关。 影响：这项研究的成功将提供一种能够定位的非侵入性成像方法 涉及血管的肿瘤，同时克服呼吸运动模糊。该信息将是 可用于指导有针对性的辐射剂量升级至由相关人员定义的增压量 血管，最初妨碍切除。因此，该项目满足了未满足的需求 目前的胰腺癌治疗方法是因为超过 85% 的患者患有不可切除的癌症 由于血管受累而发生癌症。