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(申请人提供)：乳腺癌仍然是女性癌症死亡的第二大原因，也是45岁至55岁女性的主要死亡原因，尽管最近有了各种治疗方法的发展。抗血管生成治疗已成为治疗癌症的重要手段。然而，针对个别患者的抗血管生成治疗的优化仍然没有解决。抗血管生成药物被认为可以暂时使异常血管正常化，并矛盾地增加血流量，从而将药物输送到肿瘤。很大一部分患者对这种抗血管生成治疗没有反应，但尚不清楚失败是由于抗血管生成药物未能使血管系统正常化，还是由于细胞毒素未能杀死细胞。因此，有必要同时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。在这份提案中，我们将调查一次MRI采集和分析，以允许对两者进行评估。动态增强磁共振成像(DCE)已成为评价肿瘤微循环环境的有力工具。在这个方案中，我们介绍了一种新的DCE-MRI分析方法，它结合了组织均质性的绝热近似模型和水交换模型(ATH-WX)。这一分析提供了对血流参数(流量、血管体积分数和血管渗透性表面积乘积)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ATH-WX模型参数与肿瘤生长过程中其他MRI和病理学指标的相关性。在第二阶段，我们将测试所提出的检测早期治疗反应的ATH-WX模型，并将其测量结果与病理进行比较，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模型来衡量节拍化疗(MCT)的抗血管生成效应，在MCT中，一种传统的细胞毒药物同时产生抗血管生成和细胞毒作用。总之，本研究收集的临床前实验数据将被用来检验我们的主要假设，即所提出的新方法(DCE-MRI和ATH-WX)可以同时提供抗血管生成和细胞毒反应的定量测量。该项目的结论将提供一种经过全面测试的非侵入性MRI方法，用于定量测量肿瘤微环境。这一应用中拟议的实验将为利用这种新的DCE-MRI方法通过允许及时改变无效的治疗方案来改善患者管理奠定重要的垫脚石。由于MRI是现代医学中普遍使用的一种无处不在的非侵入性方法，因此在临床前环境下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。