Imaging Biomarkers of Lymphatic Dysfunction

淋巴功能障碍的成像生物标志物

基本信息

批准号：
9753366
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
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-14 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9753366
关键词：
Adipose tissue Affect Age Anastomosis - action Anatomy Architecture Axillary Lymph Node Dissection Axillary lymph node group Benign Biochemical Biopsy Body Regions Body mass index Breast Cancer Treatment Breast Cancer survivor Breast Cancer therapy Chronic Clinical Clinical Trials Complex Consensus Cross-Over Studies Cross-Over Trials Data Discrimination Disease Dissection Enrollment Environment Excision Fibrosis Functional disorder Goals Image Imaging Device Impairment Incidence Infection Knowledge Life Limb structure Lymph Lymph Node Dissections Lymph Node Mapping Lymphangiography Lymphatic Lymphatic Diseases Lymphatic System Lymphatic vessel Lymphedema Magnetic Resonance Imaging Malignant Neoplasms Maps Mastectomy Measurement Measures Methodology Methods Neoplasm Metastasis Obstruction Operative Surgical Procedures Outcome Outcome Measure Participant Patient Monitoring Patient Schedules Patient Triage Patient-Focused Outcomes Patients Pharmacology Physiological Prevention Prior Therapy Procedures Proteins Protocols documentation Quality of life Radiation therapy Reporting Resolution Risk Risk Factors Secondary to Sentinel Lymph Node Biopsy Severities Statistical Models Surgeon Symptoms Testing Therapeutic Trials Therapy Evaluation Time Tissues Translating Transplantation Treatment Efficacy Treatment-Related Cancer Triage Water Work aggressive therapy associated symptom base cancer surgery cancer therapy cell motility efficacy evaluation experience hemodynamics high risk imaging approach imaging biomarker imaging modality improved improved outcome in vivo interstitial irritation lymph flow lymph nodes lymphatic circulation malignant breast neoplasm molecular imaging multimodality novel novel marker pressure prevent reduce symptoms standard of care subcutaneous symptomatology theranostics tool

项目摘要

ABSTRACT The goal of this work is to apply novel, noninvasive magnetic resonance imaging (MRI) methods for visualizing lymphatic circulation dysfunction to test fundamental hypotheses about lymphedema risk factors and therapies. Breast cancer treatment-related lymphedema (BCRL) arises secondary to surgical axillary lymph node (LN) dissection and irritation, and is a chronic and lifelong condition affecting a high 21.4% of patients receiving common breast cancer therapies. Reducing condition onset and improving management represent major unmet clinical needs for these 50,000 - 80,000 new patients per year, and emerging efforts focus on improving quality of life through more informed LN dissection and biopsy decisions, optimizing post-surgical complex decongestive therapy (CDT), and exploring novel pharmacological and surgical procedures. However, fundamental gaps in our knowledge persist regarding optimized implementation of these therapies and details of the physiological changes they elicit. The major underlying limitation is that there is a shortage of imaging methods available that can be used to evaluate lymphatic function directly, and there is currently no consensus regarding effective outcome measures for therapeutic efficacy evaluation. Rather, LN removal is frequently based on sentinel LN biopsy and additional subjectivity of the surgeon. Therapy evaluation is frequently based on coarse measurements such as changes in limb volume or patient-reported symptoms, which provide little information on underlying mechanistic changes that could be used to further refine these therapies. As part of our ongoing INFORM clinical trial of BCRL progression and therapy, we have demonstrated potential for new, noninvasive MRI approaches to identify BCRL risk in sub-clinical disease stages, as well as to visualize internal changes in lymphatic functioning as a result of emerging therapies. Here, we propose to extend these studies to improve abilities for BCRL theranostics. (Aim 1) Prevention. We will apply new anatomical and functional LN imaging approaches to identify LN profiles specific to biopsy-confirmed metastatic LNs; findings could be used to better inform LN dissection and reduce the incidence of benign LN removal. (Aim 2) Progression. We will improve our understanding of BCRL risk progression by testing the hypothesis that superficial tissue profiles and subcutaneous adipose accumulation are more prevalent in patients experiencing BCRL progression, and thereby could be used to triage patients for aggressive therapies prior to overt symptoms and irreversible damage. (Aim 3) Therapy. We will perform a repeated-measures cross-over trial to test the hypothesis that mobilization of protein enriched hardened tissue using graded negative pressure therapy in conjunction CDT is superior to standard CDT alone. The overall goal is to develop objective markers of lymphatic dysfunction that can be used in emerging therapeutic trials of cancer and BCRL therapies to reduce both the incidence and severity of symptoms associated with this prevalent and chronic condition.

抽象的这项工作的目标是应用新颖的非侵入性磁共振成像 (MRI) 方法进行可视化淋巴循环功能障碍，以测试有关淋巴水肿危险因素和治疗的基本假设。乳腺癌治疗相关性淋巴水肿 (BCRL) 继发于手术腋窝淋巴结 (LN) 夹层和刺激，是一种慢性终身疾病，影响接受治疗的患者高达 21.4% 常见的乳腺癌治疗方法。减少病情发作和改善管理是主要措施每年有 50,000 - 80,000 名新患者的临床需求未得到满足，新兴努力的重点是改善通过更明智的淋巴结解剖和活检决策来提高生活质量，优化术后复杂性减充血疗法（CDT），并探索新的药理学和外科手术。然而，在这些疗法和细节的优化实施方面，我们的知识仍然存在根本差距它们引起的生理变化。主要的潜在限制是缺乏成像目前尚无可直接评价淋巴功能的方法，但目前尚未达成共识关于治疗效果评估的有效结果措施。相反，LN 去除经常发生基于前哨淋巴结活检和外科医生的额外主观性。治疗评估通常基于粗略的测量结果，例如肢体体积的变化或患者报告的症状，这些数据提供的信息很少有关潜在机制变化的信息可用于进一步完善这些疗法。作为一部分我们正在进行 BCRL 进展和治疗的 INFORM 临床试验，我们已经证明了新的、无创 MRI 方法可识别亚临床疾病阶段的 BCRL 风险，并可视化新兴疗法导致淋巴功能发生内部变化。在此，我们建议延长这些旨在提高 BCRL 治疗诊断能力的研究。（目标 1）预防。我们将应用新的解剖学和功能性淋巴结成像方法，用于识别活检证实的转移性淋巴结特有的淋巴结特征；发现可用于更好地了解淋巴结清扫并减少良性淋巴结切除的发生率。（目标2）进展。我们将通过检验以下假设来加深对 BCRL 风险进展的理解：浅表组织轮廓和皮下脂肪堆积在患有以下疾病的患者中更为普遍 BCRL 进展，因此可用于在公开治疗之前对患者进行积极治疗的分类症状和不可逆转的损害。（目标 3）治疗。我们将进行重复测量交叉试验检验使用分级负压动员富含蛋白质的硬化组织的假设与 CDT 联合治疗优于单独使用标准 CDT。总体目标是开发客观标记淋巴功能障碍的研究可用于新兴的癌症治疗试验和 BCRL 疗法减少与这种流行的慢性疾病相关的症状的发生率和严重程度。