Imaging lymphatic function in patients with breast cancer related lymphedema

乳腺癌相关淋巴水肿患者的淋巴功能成像

• 批准号: 9042875
• 负责人: Manus J Donahue
• 金额: $ 39.5万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-14 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9042875
• 关键词: Acute; Affect; Age; Analysis of Variance; Axillary lymph node group; Behavioral; Biochemical; Blood flow; Brain; Breast; Breast Cancer Treatment; Breast Cancer survivor; Chemicals; Chronic; Clinical; Clinical Trials; Contrast Media; Data; Dependence; Disease; Disease Progression; Dissection; Environment; Equipment; Female; Functional Magnetic Resonance Imaging; Functional disorder; Health; Hospitals; Human; Image; Impairment; Incidence; Individual; Knowledge; Leg; Limb structure; Liver; Logistic Regressions; Lymph; Lymphatic; Lymphatic System; Lymphedema; Magnetic Resonance Imaging; Manual Lymphatic Drainage; Mastectomy; Measurement; Measures; Methodology; Methods; Modeling; Monitor; Motivation; Neurosciences; Obstruction; Operative Surgical Procedures; Patients; Physiological; Physiology; Population; Procedures; Property; Proteins; Protocols documentation; Quality of life; Radiation therapy; Radioactive Tracers; Reporting; Reproducibility; Research; Risk; Secondary to; Severity of illness; Shoulder; Signal Transduction; Specialized Center; Spin Labels; Staging; Structure; Techniques; Testing; Therapeutic; Time; Translating; Weight; Woman; Work; arm; disability; fluid flow; follow-up; high risk; imaging biomarker; imaging modality; in vivo; interstitial; lymph flow; malignant breast neoplasm; novel; pre-clinical; prevent; response; volunteer

DESCRIPTION (provided by applicant): This work will apply novel, noninvasive structural and functional magnetic resonance imaging (MRI) methods to patients with mild and moderate breast cancer-related lymphedema (BCRL) for the first time to test fundamental hypotheses about relationships between lymphatic compromise and imaging biomarkers that may portend disease progression and individualized therapy response. BCRL is a chronic, debilitating disease caused by lymphatic flow obstruction in the legs, arms, and shoulder regions. Lymphedema secondary to mastectomy and radiation therapy is a growing health concern and has been reported to occur, on average, in 20% of women within three years after breast cancer treatment and in as many as 94% of women five years after breast cancer treatment. While there is no cure for lymphedema, it has been shown that behavioral adjustments and aggressive therapeutic management of patients in early or subclinical disease stages can prevent or reduce long-term impairment. However, very limited information is available for identifying patients at highest risk for lymphedema. Several specialized imaging methods have demonstrated that reduced lymphatic flow velocity and related lymphatic contractility impairment may portend lymphedema risk, however these approaches require radioactive tracers and/or exogenous contrast agents, are generally only available in specialized centers, and are not performed in routine patient management. We have very recently demonstrated that arterial spin labeling (ASL), a popular and noninvasive MRI method for measuring blood flow, can be adapted to measure flow of lymphatic fluid to axillary lymph nodes, and furthermore that lymphatic velocities reported using this technique are consistent with similar measures using exogenous contrast agents. Additionally, we have shown that chemical exchange saturation transfer (CEST) MRI can be used to characterize interstitial protein accumulation in patients in preclinical BCRL stages prior to limb volume changes. Importantly, both spin labeling and CEST utilize standard MRI equipment available at most hospitals and therefore can easily be disseminated to clinical or research centers seeking to expand their abilities to characterize lymphatic compromise. Here, we propose to assess the ranges of lymphatic flow velocities and interstitial protein accumulation in healthy individuals (Aim 1) and BCRL patients in preclinical, mild, and moderate stages of impairment (Aim 2), and finally to assess how lymphatic system compromise changes in response to manual lymphatic drainage therapy and to what extent lymphatic flow velocity and interstitial protein accumulation may predict lymphedema progression (Aim 3). This work will for the first time apply a noninvasive, multi-modal MRI protocol, which has demonstrated clinical potential in neuroscience, liver, and breast applications, to the human lymphatic system to better characterize lymphatic dysfunction and lymphedema risk in the growing breast cancer survivor population.

描述（由申请人提供）：这项工作将首次对轻度和中度乳腺癌相关性水肿（BCRL）患者应用新型、非侵入性结构和功能磁共振成像（MRI）方法，以检验有关淋巴损害与可能预示疾病进展和个体化治疗反应的成像生物标志物之间关系的基本假设。BCRL是一种慢性、使人衰弱的疾病，由腿部、手臂和肩部区域的淋巴流动阻塞引起。乳房切除术和放射治疗继发的淋巴水肿是一个日益严重的健康问题，据报道，平均20%的女性在乳腺癌治疗后三年内发生，多达94%的女性在乳腺癌治疗后五年内发生。虽然没有治愈水肿的方法，但已经表明，在早期或亚临床疾病阶段对患者进行行为调整和积极的治疗管理可以预防或减少长期损害。然而，可用于识别水肿最高风险患者的信息非常有限。几种专门的成像方法已经证明，淋巴流速降低和相关的淋巴收缩性损害可能预示着水肿风险，但是这些方法需要放射性示踪剂和/或外源性造影剂，通常仅在专门的中心可用，并且不在常规患者管理中进行。我们最近已经证明，动脉自旋标记（ASL），一种流行的和非侵入性的MRI血流测量方法，可以适用于测量淋巴液流量腋窝淋巴结，此外，使用这种技术报告的淋巴速度与使用外源性造影剂的类似措施是一致的。此外，我们已经证明，化学交换饱和转移（CEST）MRI可用于表征肢体体积变化前临床前BCRL阶段患者的间质蛋白积聚。重要的是，自旋标记和CEST都利用大多数医院可用的标准MRI设备，因此可以很容易地传播到临床或研究中心，以扩大其表征淋巴损害的能力。在这里，我们建议评估健康个体（目标1）和处于临床前、轻度和中度损伤阶段（目标2）的BCRL患者的淋巴流速和间质蛋白积聚的范围，最后评估淋巴系统如何响应手动淋巴引流治疗而损害变化，以及淋巴流速和间质蛋白积累在多大程度上可以预测水肿进展（目标3）。这项工作将首次将一种非侵入性的多模式MRI方案应用于人类淋巴系统，该方案已在神经科学，肝脏和乳腺应用中表现出临床潜力，以更好地表征淋巴功能障碍和不断增长的乳腺癌幸存者人群中的水肿风险。