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.

项目总结/摘要 本研究的总体目标是验证UAB发明的名为P4的灌注体模（床旁 便携式灌注体模），用于胰腺肿瘤对 新辅助治疗DCE-MRI已用于非侵入性评估实体瘤的早期治疗反应， 通过在解剖学肿瘤收缩之前检测组织灌注的变化来检测肿瘤。然而，测量 在DCE-MRI的多中心试验中，不同扫描仪之间的变异性仍然是一个主要问题。为了解决这个 为了解决这个问题，我们发明了P4，它足够小，可以在标准MRI的孔中同时成像 扫描仪与病人，因此可以作为一个内部参考，以检测和纠正扫描仪相关的 定量DCE-MRI参数的变化。我们已经证实，该器械的使用减少了 DCE-MRI测量的变异性降低到约4%，尽管校正前约为20%。我们现在 假设P4可以帮助确定胰腺肿瘤在新辅助治疗中的早期治疗反应， 设置.胰腺肿瘤是典型的低灌注，但我们最近证明，肿瘤 在有效的化疗后灌注可以显著增加。选择更有效的治疗方法 对于边缘性可切除的胰腺癌患者来说，早期治疗尤为重要， 可以降低肿瘤的分期从而进行可治愈的手术提出了以下三个具体目标。目标1（UG 3- 1）：开发一次性P4，其与患者同时成像以提高准确性，以及 定量DCE-MRI测量的重现性。对于常规和广泛的临床应用，体模 应该是即用型、廉价型和一次性的。将采用注塑成型方法， 制造一次性P4。目标2（UG 3 -2）：开发分析腹部DCE-MRI的软件包 用P4拍摄的照片。图像处理将按八个步骤顺序进行。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 联合收割机将所有八个模块结合起来，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见，但为了提高操作速度。软件前面板将更新， 使用来自多个用户的反馈的高效操作。目的3（UH 3 -1）：评价DCE-MRI的变化 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的参数 在使用P4进行错误校正之后。共有50例边缘性可切除胰腺癌患者进入 新辅助疗法将在两个研究机构招募（每个机构n=25）。DCE-MRI的变化 治疗开始后4周的肿瘤参数将与治疗反应相关 通过完成新辅助治疗后的切缘阴性切除率进行评估，并评价为 基于P4的误差校正后的替代生物标志物。