DCE MRI Study for Breast Cancer.

DCE 乳腺癌 MRI 研究。

基本信息

批准号：
8244309
负责人：
Sungheon Gene Kim
金额：
$ 55.87万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
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/8244309
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 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

项目摘要

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. PUBLIC HEALTH RELEVANCE: Assessment of anti-angiogenic therapy, using either an anti-angiogenic targeted drug or a cytotoxic drug with metronomic schedule, requires an effective non-invasive method of measuring both the anti-angiogenic and cytotoxic effects of the therapies. Our underlying hypothesis is that a single dynamic contract enhanced MRI measurement using the adiabatic approximation of tissue homogeneity with water exchange (ATH-WX) model provides a means of assessing both anti-angiogenic and cytotoxic responses to anti-angiogenic therapies. The research in this proposal will establish an innovative method of assessing chemotherapy that will significantly improve drug discovery and patient management in a variety of cancers including breast cancer.

描述（由申请人提供）：尽管最近开发了各种治疗方法，但乳腺癌仍然是女性癌症死亡的第二大原因，也是 45 至 55 岁女性死亡的主要原因。抗血管生成治疗方法已被用作治疗癌症的重要手段。然而，针对个体患者的此类抗血管生成疗法的优化仍未解决。抗血管生成药物被认为可以暂时使异常脉管系统正常化，并相反地增加血流量，从而增加向肿瘤的药物输送。相当一部分患者对这种抗血管生成治疗没有反应，但尚不清楚这种失败是否是由于抗血管生成药物未能使脉管系统正常化或细胞毒素未能杀死细胞所致。因此，有必要评估血流和细胞死亡，以阐明其机制并监测联合治疗的疗效。在本提案中，我们将研究单个 MRI 采集和分析，以便对两者进行评估。动态对比增强 (DCE) - MRI 已成为评估肿瘤微循环环境的有力工具。在本提案中，我们介绍了一种新颖的 DCE-MRI 分析方法，该方法将组织均匀性模型的绝热近似与水交换模型 (ATH-WX) 相结合。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积乘积）和细胞结构参数（间质体积分数和细胞内水寿命）的估计。研究的第一阶段包括一系列实验，以测量肿瘤生长过程中 ATH-WX 模型参数与其他 MRI 和病理学测量之间的关联。在第二阶段，我们将测试所提出的用于检测早期治疗反应的ATH-WX模型，并将其测量值与病理学进行比较，以确定与治疗引起的病理变化最相关的ATH-WX参数。在第三阶段，我们计划应用ATH-WX模型来测量节拍化疗（MCT）的抗血管生成作用，其中使用常规细胞毒性药物诱导抗血管生成和细胞毒性作用。总的来说，本研究中收集的临床前实验数据将用于检验我们的主要假设，即所提出的新方法（DCE-MRI 与 ATH-WX）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一种经过彻底测试的无创 MRI 方法，用于定量测量肿瘤微环境。本申请中提出的实验将为利用这种新型 DCE-MRI 方法通过及时改变无效的治疗方案来改善患者管理奠定重要的基础。由于MRI是现代医学中普遍使用的一种普遍存在的无创方法，因此在临床前环境中开发的方法可以很容易地转化为有效管理肿瘤治疗策略的临床工具。公共卫生相关性：使用抗血管生成靶向药物或具有节拍时间表的细胞毒性药物来评估抗血管生成治疗，需要一种有效的非侵入性方法来测量治疗的抗血管生成和细胞毒性作用。我们的基本假设是，使用水交换组织均匀性绝热近似 (ATH-WX) 模型的单一动态收缩增强 MRI 测量提供了一种评估抗血管生成治疗的抗血管生成和细胞毒性反应的方法。该提案中的研究将建立一种评估化疗的创新方法，该方法将显着改善包括乳腺癌在内的多种癌症的药物发现和患者管理。