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

• 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
• 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

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.

项目摘要 了解癌症生物学的最新进展导致癌症数量增加 疗法。在人类临床试验中对这些新疗法的评估与高成本和 潜在风险。成像方法可以通过识别患者来在此评估中发挥重要作用 回应治疗。当前对治疗结果的放射学评估主要依赖 肿瘤大小的变化。这是一个主要的限制因素，因为许多治疗剂对 微观水平先于肿瘤大小的变化。一种已广泛针对的肿瘤特性 对于新的癌症疗法是肿瘤血管生成（或灌注），已证明支持肿瘤 增殖和浸润。我们最近开发了定量磁共振成像（MRI） 技术称为动脉自旋标记（ASL），可以非侵入性地测量肿瘤灌注 给药外源对比剂。 ASL MRI使用高渗透性水作为示踪剂，磁性 在动脉血液中标记水质子并测量其在感兴趣的组织中的积累。我们 已经在多个临床试验中使用ASL监测治疗反应，并表明ASL测量了 肾脏患者开始抗血管生成治疗后8天，肿瘤灌注降低 细胞癌（RCC），比肿瘤大小的变化要早得多。但是，ASL没有经历强大的 和严格的验证过程将作为定量成像方法确定。在这个项目中，我们将 验证ASL测量灌注作为定量成像标记，以评估患者的治疗反应 脑肿瘤（多形胶质母细胞瘤，GBM）和转移性RCC，两个已知的高度血管化肿瘤。 该项目的具体目的是：1）证明ASL测量的灌注的可靠性和精度 在大脑和肾脏中，有30位正常志愿者； 2）根据基线预测临床结果（前 治疗）40例新诊断的GBM患者的灌注和治疗后灌注的早期变化 接受化学放疗疗法； 3）根据基线预测长期结果（预处理） 40例转移性RCC患者的灌注和治疗后灌注的早期变化 抗血管生成疗法。在第一个目标中，我们还将使用新颖的3D印刷开发质量控制协议 灌注幻影，目前在UT西南（UTSW）医疗中心可用来衡量可靠性 和ASL测量流量的精度。在第二和第三目标中，我们将合并自动化和半 肿瘤分割和分析的自动化方法，以便可以在其他地方复制这些结果。 AIM 2和3的患者将从UTSW正在进行的临床试验中招募。在这两个目标中，我们都会 检验我们的假设，即治疗后立即肿瘤灌注的降低，与基线相比 与提高的无进展生存率和总体存活率相关。 ASL测量的此类早期变化 灌注可能比解剖学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可能有毒的治疗方法来及时管理。