Quantitative Non-Contrast Perfusion using Arterial Spin Labeling for Assessment of Cancer Therapy Response

使用动脉旋转标记进行定量非对比灌注评估癌症治疗反应

基本信息

批准号：
9765190
负责人：
Ananth Jayaseelan Madhuranthakam
金额：
$ 22.96万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9765190
关键词：
3D Print Affect Aftercare Angiogenesis Inhibitors Award Blood Blood Vessels Brain Brain Neoplasms Cancer Biology Clinical Clinical Trials Collaborations Contrast Media Custom Data Databases Evaluation Exhibits Glioblastoma Glioma Grant Healthcare Human Image Imaging Techniques Infiltration Informatics Kidney Label Letters Magnetic Resonance Imaging Magnetism Measurement Measures Medical center Metastatic Renal Cell Cancer Methods Microscopic Monitor Morphology Neoplasm Metastasis Neoplasms in Vascular Tissue Newly Diagnosed Nutrient Oncologist Outcome Oxygen Participant Patients Perfusion Perfusion Weighted MRI Permeability Phase Physiological Play Predisposition Process Progression-Free Survivals Property Protocols documentation Protons Quality Control Radiation Therapy Oncology Group Radiology Specialty Renal Cell Carcinoma Renal carcinoma Research Risk Role Solid Neoplasm Specialist Specialized Program of Research Excellence Spin Labels Standardization Techniques Testing Therapeutic Agents Time Tissues Tracer Translations Treatment outcome Tumor Angiogenesis Validation Vascular blood supply Water anatomic imaging angiogenesis base cancer imaging cancer therapy chemoradiation clinical practice clinical translation contrast enhanced cost cytotoxic experience image archival system imaging approach imaging biomarker imaging modality imaging scientist improved interest member multidisciplinary novel novel therapeutics predict clinical outcome prospective quantitative imaging radiologist recruit response targeted cancer therapy treatment response tumor tumor vascular supply volunteer

项目摘要

Project Summary Recent advances in the understanding of cancer biology have led to an increased number of cancer therapies. The evaluation of these new therapies in human clinical trials is associated with high cost and potential risks. Imaging approaches can play an important role in this evaluation by identifying patients who respond to treatments. The current radiological assessment of treatment outcomes predominantly relies on changes in tumor size. This is a major limiting factor as the effects of many therapeutic agents at the microscopic level precede changes in tumor size. One such tumor property that has been extensively targeted for new cancer therapies is tumor angiogenesis (or perfusion), which has been shown to support tumor proliferation and infiltration. We have recently developed a quantitative magnetic resonance imaging (MRI) technique, called Arterial Spin Labeling (ASL) that can measure tumor perfusion non-invasively and without the administration of exogenous contrast agent. ASL MRI uses highly permeable water as a tracer, by magnetically labeling the water proton in the arterial blood and measuring their accumulation in the tissue of interest. We have used ASL to monitor therapy response in multiple clinical trials and have shown that ASL measured tumor perfusion decreased as early as 8 days after the initiation of antiangiogenic therapy in patients with renal cell carcinoma (RCC), much earlier than the tumor size changes. However, ASL has not undergone a robust and rigorous validation process to be established as a quantitative imaging method. In this project, we will validate ASL measured perfusion as a quantitative imaging marker to evaluate treatment response in patients with brain tumors (glioblastoma multiforme, GBM) and metastatic RCC, two known highly vascularized tumors. The specific aims of the project are: 1) To demonstrate the reliability and precision of ASL measured perfusion in the brain and kidneys of 30 normal volunteers; 2) To predict clinical outcomes based on baseline (pre- treatment) perfusion and early changes in post-treatment perfusion in 40 patients with newly diagnosed GBM undergoing chemoradiation therapy; and 3) To predict long-term outcomes based on baseline (pre-treatment) perfusion and early changes in post-treatment perfusion in 40 patients with metastatic RCC undergoing antiangiogenic therapies. In the first aim, we will also develop quality-control protocols using a novel 3D printed perfusion phantom, currently available at UT Southwestern (UTSW) Medical Center to measure the reliability and precision of ASL measured flow. In the second and third aims, we will incorporate automated and semi- automated methods for tumor segmentation and analysis, such that these results can be replicated elsewhere. The patients for aims 2 and 3 will be recruited from ongoing clinical trials at UTSW. In both these aims, we will test our hypothesis that greater reduction in tumor perfusion immediately after treatment, compared to baseline correlates with improved progression free survival and overall survival. Such early changes in ASL measured perfusion may predict tumor responsiveness better than anatomical imaging, thereby affecting patient management in a timely manner by changing treatments that may be ineffective and potentially toxic.

项目概要对癌症生物学理解的最新进展导致癌症数量增加疗法。在人体临床试验中对这些新疗法进行评估需要高昂的成本和潜在风险。影像学方法可以通过识别患者来在评估中发挥重要作用对治疗有反应。目前治疗结果的放射学评估主要依赖于肿瘤大小的变化。这是一个主要的限制因素，因为许多治疗药物的作用在微观水平先于肿瘤大小的变化。一种已被广泛靶向的肿瘤特性新的癌症疗法是肿瘤血管生成（或灌注），已被证明可以支持肿瘤扩散和渗透。我们最近开发了定量磁共振成像（MRI）称为动脉旋转标记 (ASL) 的技术，可以非侵入性地测量肿瘤灌注，且无需外源性造影剂的施用。 ASL MRI 使用高渗透性水作为示踪剂，通过磁力标记动脉血中的水质子并测量它们在感兴趣组织中的积累。我们在多项临床试验中使用 ASL 来监测治疗反应，并表明 ASL 测量肾病患者开始抗血管生成治疗后 8 天，肿瘤灌注就下降细胞癌（RCC）的发生，比肿瘤大小的变化要早得多。然而，ASL 尚未经历强劲的发展并建立严格的验证过程作为定量成像方法。在这个项目中，我们将验证 ASL 测量的灌注作为定量成像标志物以评估患者的治疗反应脑肿瘤（多形性胶质母细胞瘤，GBM）和转移性肾细胞癌，这两种已知的高度血管化肿瘤。该项目的具体目标是： 1) 证明 ASL 测量灌注的可靠性和精确度 30 名正常志愿者的大脑和肾脏； 2）根据基线预测临床结果（预 40 例新诊断 GBM 患者的治疗）灌注及治疗后灌注的早期变化正在接受放化疗； 3) 根据基线（治疗前）预测长期结果 40例转移性肾细胞癌患者的灌注及治疗后早期灌注变化抗血管生成疗法。在第一个目标中，我们还将使用新型 3D 打印技术开发质量控制协议灌注模型，目前可在 UT Southwestern (UTSW) 医疗中心用于测量可靠性和 ASL 测量流量的精度。在第二个和第三个目标中，我们将结合自动化和半自动化肿瘤分割和分析的自动化方法，以便这些结果可以在其他地方复制。目标 2 和 3 的患者将从 UTSW 正在进行的临床试验中招募。为了这两个目标，我们将检验我们的假设，即与基线相比，治疗后肿瘤灌注立即大幅减少与改善的无进展生存期和总生存期相关。测量到的 ASL 的早期变化灌注可以比解剖成像更好地预测肿瘤反应性，从而影响患者通过改变可能无效且具有潜在毒性的治疗方法来及时进行管理。