Disposable Perfusion Phantom for Accurate DCE-MRI Measurement of Pancreatic Cancer Therapy Response

用于准确测量胰腺癌治疗反应的一次性灌注模型

• 批准号: 10464911
• 负责人: Harrison Kim
• 金额: $ 47.98万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10464911
• 关键词: Abdomen; Address; Adoption; Anatomy; Cancer Patient; Clinic; Clinical; Clinical Trials; Collaborations; Computer software; Contrast Media; Data; Data Analyses; Devices; Early treatment; Error Sources; Excision; Feedback; Goals; Human Resources; Image; Individual; Injections; Institutes; Interobserver Variability; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of pancreas; Measurement; Measures; Methodology; Molds; Multi-Institutional Clinical Trial; Names; Neoadjuvant Therapy; Operative Surgical Procedures; Outcome; Participant; Patients; Perfusion; Phase; Production; Reproducibility; Research Institute; Resectable; Site; Solid Neoplasm; Speed; Surrogate Markers; Technology; Testing; Time; Tissues; Treatment Protocols; Update; Variant; base; cancer care; chemotherapy; clinical research site; contrast enhanced; cost; effective therapy; gastrointestinal; image processing; imaging biomarker; imaging platform; imaging system; improved; multi-site trial; operation; pancreatic neoplasm; patient stratification; point of care; portability; precision medicine; predictive marker; programs; prototype; quality assurance; radiologist; recruit; response; tool; treatment optimization; treatment response; tumor

PROJECT SUMMARY / ABSTRACT The overall goal of this study is to validate a UAB-invented perfusion phantom named P4 (Point-of-care Portable Perfusion Phantom) for accurate DCE-MRI measurement of pancreatic tumor response to neoadjuvant therapy. DCE-MRI has been utilized to noninvasively assess early therapeutic response in solid tumors by detecting changes in tissue perfusion prior to anatomic tumor shrinkage. However, measurement variability across different scanners remains a major concern in multi-site trials of DCE-MRI. To address this concern, we invented the P4 that is small enough to be imaged concurrently in the bore of a standard MRI scanner with a patient, thus can serve as an internal reference to detect and correct the scanner-dependent variation in quantitating DCE-MRI parameters. We have confirmed that the use of this device decreased variability in DCE-MRI measurement to about 4%, although it was about 20% before correction. We now hypothesize that the P4 can help identify early therapeutic response of pancreatic tumors in the neoadjuvant setting. Pancreatic tumors are typically hypo-perfused, but we have recently demonstrated that the tumor perfusion can be significantly increased after an effective chemotherapy. Choosing the more effective therapy early is particularly important for patients with borderline-resectable pancreatic cancer, as an effective therapy can downstage a tumor to allow curable surgery. Three specific aims are proposed as follows. Aim 1 (UG3- 1): Develop a disposable P4 that is concurrently imaged with a patient for improved accuracy and reproducibility in quantitative DCE-MRI measurement. For routine and widespread clinical use, the phantom should be ready-to-use, inexpensive and disposable. Injection molding methodology will be employed to manufacture the disposable P4. Aim 2 (UG3-2): Develop a software package analyzing abdominal DCE-MRI images obtained with the P4. Image processing will be conducted sequentially in eight steps. To date, we have developed eight prototype software program modules (one for each step). In this study, we aim to combine all eight modules for seamless data flow, while making each module automated/semi-automated not only to reduce user bias but to improve speed of operation. The software front panel will be updated for more efficient operation using feedback from multiple users. Aim 3 (UH3-1): Evaluate the changes of DCE-MRI parameters as surrogate imaging biomarkers for pancreatic cancer therapy response in a multi-site setting after error correction using the P4. A total of 50 patients with borderline resectable pancreatic cancer entering neoadjuvant therapy will be recruited in two research institutes (n=25 per institute). The changes of DCE-MRI parameters in tumors for 4 weeks after therapy initiation will be correlated with the therapeutic response assessed by margin-negative resection rate after completion of neoadjuvant therapy, and evaluated as surrogate biomarkers after P4-based error correction.

项目概要/摘要 本研究的总体目标是验证 UAB 发明的名为 P4（Point-of-care）的灌注模型 便携式灌注体模）用于准确测量胰腺肿瘤对 DCE-MRI 的反应 新辅助治疗。 DCE-MRI 已用于无创评估实体瘤的早期治疗反应 通过在肿瘤解剖缩小之前检测组织灌注的变化来检测肿瘤。然而，测量 不同扫描仪之间的差异仍然是 DCE-MRI 多站点试验中的一个主要问题。为了解决这个问题 担心，我们发明了 P4，它足够小，可以在标准 MRI 的孔中同时成像 扫描仪与患者一起使用，因此可以作为内部参考来检测和纠正扫描仪依赖性 DCE-MRI 参数定量的变化。我们已确认该设备的使用量有所减少 DCE-MRI 测量的变异性约为 4%，尽管校正前约为 20%。我们现在 假设 P4 可以帮助识别胰腺肿瘤新辅助治疗的早期治疗反应 环境。胰腺肿瘤通常是低灌注的，但我们最近证明肿瘤 有效化疗后灌注可显着增加。选择更有效的治疗方法 作为一种有效的治疗方法，早期治疗对于临界可切除胰腺癌患者尤为重要 can downstage a tumor to allow curable surgery.提出以下三个具体目标。目标 1（UG3- 1)：开发一次性 P4，与患者同时成像，以提高准确性和 定量 DCE-MRI 测量的再现性。对于常规和广泛的临床使用，模型 应该是即用型、廉价且一次性的。将采用注塑方法 制造一次性P4。目标 2 (UG3-2)：开发分析腹部 DCE-MRI 的软件包 使用 P4 获得的图像。图像处理将分八步顺序进行。迄今为止，我们 开发了八个原型软件程序模块（每个步骤一个）。在这项研究中，我们的目标是 结合所有八个模块以实现无缝数据流，同时使每个模块自动化/半自动化 只是为了减少用户偏差而是为了提高操作速度。软件前面板将更新更多 利用多个用户的反馈进行有效的操作。目标 3 (UH3-1)：评估 DCE-MRI 的变化 参数作为多部位环境中胰腺癌治疗反应的替代成像生物标志物 使用 P4 进行纠错后。共有50名边缘性可切除胰腺癌患者进入 新辅助治疗将在两个研究机构中招募（每个机构 25 名）。 DCE-MRI变化 治疗开始后 4 周内肿瘤参数将与治疗反应相关 通过新辅助治疗完成后的切缘阴性切除率进行评估，并评估为 基于 P4 的纠错后的替代生物标志物。