Imaging Biomarkers of Lymphatic Dysfunction

淋巴功能障碍的成像生物标志物

• 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
• 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

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 这项工作的目的是应用新颖的无创磁共振成像（MRI）方法来可视化 淋巴循环功能障碍，以测试有关淋巴水肿风险因素和疗法的基本假设。 乳腺癌治疗相关淋巴水肿（BCRL）是继发于手术腋窝淋巴结（LN）的继发的 解剖和刺激，是一种慢性和终身疾病，影响21.4％的患者 常见的乳腺癌疗法。减少条件发作和改善管理代表了主要 每年这50,000至80,000名新患者的临床需求未满足，新兴的工作重点是改善 通过更明智的LN解剖和活检决策，生活质量，优化手术后综合体 充气疗法（CDT），并探索新型的药理和外科手术。然而， 关于优化这些疗法和细节的优化实施，我们的知识中的基本差距持续存在 他们引起的生理变化。主要的基本限制是成像短缺 可用于直接评估淋巴功能的方法，目前尚无共识 关于治疗功效评估的有效结果指标。相反，LN去除经常 基于LN活检和外科医生的其他主观性。治疗评估经常基于 关于粗略测量的，例如肢体体积的变化或患者报告的症状，这些症状几乎没有 有关潜在机械变化的信息，可用于进一步完善这些疗法。作为 我们正在进行的有关BCRL进展和治疗的信息临床试验，我们证明了新的，新的潜力 无创的MRI方法以识别亚临床疾病阶段的BCRL风险，并可视化 淋巴功能的内部变化是由于新兴疗法而导致的。在这里，我们建议扩展这些 提高BCRL治疗学能力的研究。 （目标1）预防。我们将应用新的解剖学和 功能性LN成像方法，以识别针对活检证实的转移性LN特异性的LN曲线；发现 可以用来更好地告知LN解剖并减少良性LN去除的发生率。 （目标2） 进展。我们将通过检验以下假设来提高对BCRL风险发展的理解。 在患者中，表面组织谱和皮下脂肪的积累更为普遍 BCRL进展，因此可以在公开之前将患者用于分类患者进行侵略性疗法 症状和不可逆转的损害。 （目标3）治疗。我们将进行重复测量的交叉试验 检验以下假设，即使用分级负压动员蛋白质富集硬化组织 CDT结合中的治疗仅优于标准CDT。总体目标是制定客观标记 可用于癌症和BCRL疗法的新兴治疗试验的淋巴功能障碍 减少与这种普遍和慢性病有关的症状的发病率和严重程度。