DCE MRI Study for Breast Cancer.

DCE 乳腺癌 MRI 研究。

• 批准号: 8435348
• 负责人: Sungheon Gene Kim
• 金额: $ 52.08万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8435348
• 关键词: AT-Hook Motifs; Aftercare; Age; Angiogenesis Inhibitors; Area; Avastin; Benign; Blood Cells; Blood Vessels; Blood flow; Breast Carcinoma; Calculi; Cancer Etiology; Cause of Death; Cell Death; Cells; Cessation of life; Chemotherapy-Oncologic Procedure; Clinical; Combined Modality Therapy; Contracts; Cyclophosphamide; Cytotoxic agent; Data; Detection; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Dose; Drug Delivery Systems; Drug Targeting; Early treatment; Environment; Exhibits; Failure; Individual; Lesion; Life; Magnetic Resonance Imaging; Malignant Neoplasms; Mammary Neoplasms; Measurement; Measures; Methods; Microcirculation; Modeling; Modern Medicine; Monitor; Mus; Pathology; Patients; Perfusion; Physiological; Reporting; Research; Saline; Schedule; Series; Specificity; Spin Labels; Staging; Surface; Testing; Time; Tissues; Translating; Treatment Protocols; Vascular Endothelial Growth Factors; Vascular Permeabilities; Water; Woman; aged; bevacizumab; cell killing; chemotherapy; cytotoxic; density; drug discovery; improved; innovation; interstitial; malignant breast neoplasm; neoplastic cell; novel; novel strategies; pharmacokinetic model; pre-clinical; research study; response; tool; treatment response; treatment strategy; tumor; tumor growth; tumor microenvironment

DESCRIPTION (provided by applicant): Breast cancer remains the second leading cause of cancer death in women and the primary cause of death in women ages 45 to 55, despite recent development of various therapies. Anti-angiogenic treatment approaches have been used as important means of treating cancer. However, optimization of such anti-angiogenic therapies for individual patients remains unresolved. Anti-angiogenics are thought to temporarily normalize abnormal vasculature and paradoxically increase blood flow and hence drug delivery to tumors. A substantial proportion of patients do not respond to this anti-angiogenic therapy but it is unclear whether the failure is due to failure of the anti-angiogenic to normalize the vasculature or failure of the cytotoxic to kill cells. It is therefore necessary to assess both blood flow and cell death to elucidate the mechanism and to monitor the efficacy of combined treatments. In this proposal we will investigate a single MRI acquisition and analysis that will allow assessment of both. Dynamic contrast enhanced (DCE) - MRI has emerged as a powerful tool for assessing tumor microcirculation environment. In this proposal we introduce a novel analysis method for DCE-MRI that combines the adiabatic approximation of tissue homogeneity model with a water exchange model (ATH-WX). This analysis provides estimates of both perfusion parameters (flow, vascular volume fraction, and vascular permeability-surface area product) and cell structural parameters (interstitial volume fraction, and intracellular water life time). The first stage of the study is comprised of a series of experiments to measure the association of the ATH-WX model parameters with other MRI and pathology measures during tumor growth. In the second stage, we will test out the proposed ATH-WX model for detection of early treatment response and compare its measures with pathology, in order to determine the ATH-WX parameters that best correlate with pathological changes induced by the therapy. In the third stage, we plan to apply the ATH-WX model to measure the anti-angiogenic effects of metronomic chemotherapy (MCT) in which a conventional cytotoxic drug is used to induce both anti-angiogenic and cytotoxic effects. In overall, the preclinical experimental data collected in this study will be used to test our main hypothesis that the proposed novel method (DCE-MRI with ATH-WX) can provide quantitative measures of both anti-angiogenic and cytotoxic responses simultaneously. The conclusion of this project will deliver a thoroughly tested noninvasive MRI method for quantitative measurement of tumor microenvironment. The proposed experiments in this application will lay important stepping stones toward utilizing this novel DCE-MRI method to improve patient management by allowing timely changes to ineffective treatment regimens. Since MRI is a ubiquitous and noninvasive method commonly used in modern medicine, the developed method in preclinical environment can be easily translated into a clinical tool for effective management of tumor treatment strategies.

描述（由申请人提供）：尽管最近发生了各种疗法，但乳腺癌仍然是妇女癌症死亡的第二大主要原因和45至55岁的妇女死亡原因。抗血管生成治疗方法已被用作治疗癌症的重要手段。但是，针对个别患者的这种抗血管生成疗法的优化尚未解决。抗血管生成被认为会暂时使异常脉管系统正常化，并矛盾地增加血液流量，从而导致药物递送到肿瘤。很大一部分患者对这种抗血管生成疗法没有反应，但尚不清楚失败是由于抗血管生成使脉管系统归一化或细胞毒性无法杀死细胞的失败。因此，有必要评估血流和细胞死亡，以阐明机制并监测合并治疗的功效。在此提案中，我们将调查单一的MRI获取和分析，以评估两者。动态对比增强（DCE） - MRI已成为评估肿瘤微循环环境的强大工具。在此提案中，我们引入了一种针对DCE-MRI的新分析方法，该方法将组织同质性模型的绝热近似与水交换模型（ATH-WX）结合在一起。该分析提供了灌注参数（流量，血管体积分数和血管通透性 - 表面面积）和细胞结构参数（间质体积分数和细胞内水寿命）的估计。该研究的第一阶段由一系列实验组成，用于测量ATH-WX模型参数与肿瘤生长过程中其他MRI和病理测量的关联。在第二阶段，我们将测试提出的ATH-WX模型，以检测早期治疗反应，并将其措施与病理学进行比较，以确定与治疗诱导的病理变化最有效的ATH-WX参数。在第三阶段，我们计划应用ATH-WX模型来测量分析化疗（MCT）的抗血管生成作用，其中使用常规的细胞毒性药物诱导抗血管生成和细胞毒性作用。总体而言，本研究中收集的临床前实验数据将用于测试我们的主要假设，即提出的新方法（具有ATH-WX的DCE-MRI）可以同时提供抗血管生成和细胞毒性反应的定量测量。该项目的结论将提供彻底测试的无创MRI方法，以定量测量肿瘤微环境。该应用程序中提出的实验将为使用这种新颖的DCE-MRI方法奠定重要的垫脚石，通过允许及时更改无效治疗方案来改善患者管理。由于MRI是现代医学中常用的一种普遍存在且无创的方法，因此在临床前环境中开发的方法可以轻松地转化为有效管理肿瘤治疗策略的临床工具。