Imaging sodium and lymphatics in lymphedema

淋巴水肿中钠和淋巴管的成像

基本信息

批准号：
10546461
负责人：
Rachelle L Crescenzi
金额：
$ 48.94万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-25 至 2025-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10546461
关键词：
Address Adipose tissue Affect Age Area Assisted Circulation Biological Markers Blood Vessels Body mass index Cells Chronic Disease Clinical Clinical Trials Cross-Sectional Studies Data Deposition Disease Disease model Early Intervention Endometrial Carcinoma Excision Fibrosis Functional Imaging Functional disorder Future Goals High Prevalence Human Image Imaging Device Immune Impairment Inflammation Intervention Knowledge Leg Limb structure Longitudinal Studies Lower Extremity Lymphangiogenesis Lymphangiography Lymphatic Lymphatic Diseases Lymphatic clearance Lymphatic function Lymphedema Lymphoid Tissue Magnetic Resonance Imaging Malignant Neoplasms Manual Lymphatic Drainage Manuals Maps Measurement Measures Mediating Methods Molecular National Heart, Lung, and Blood Institute Operative Surgical Procedures Patient Triage Patients Pharmacologic Substance Physiology Procedures Progressive Disease Race Radiology Specialty Regulation Reporting Reproducibility Risk Risk Assessment Rodent Rodent Model Role Severities Severity of illness Skin Skin Tissue Sodium Source Standardization Subcutaneous Tissue Suction Lipectomy Swelling Technology Testing Therapeutic Intervention Time Tissues Tumor Debulking Upper Extremity Work aggressive therapy blood pressure control cancer therapy comparison control healthy volunteer human disease imaging biomarker imaging modality in vivo innovation interstitial lymph flow lymph nodes lymph stasis lymphatic circulation lymphatic dysfunction lymphatic insufficiency lymphatic vasculature lymphatic vessel non-invasive imaging novel novel marker potential biomarker response secondary lymphedema subcutaneous subcutaneous fibrosis tissue biomarkers tool treatment response working group

项目摘要

The overall goal of this work is to investigate lymphatic vascular mechanisms of tissue sodium handling using novel, noninvasive imaging tools sensitive to sodium and lymphatics in patients with well-characterized lymphatic disease. Findings are intended to inform mechanisms of lymphatic clearance of tissue sodium, and provide novel imaging biomarkers of lymphedema progression and treatment response. Recent evidence supports that lymphatics regulate interstitial sodium levels. When lymphatic clearance is impaired, hypertonic interstitial sodium results in tissue swelling, skin sodium storage, and poor blood pressure control. When lymphatic clearance is impaired in rodent models of lymphedema, lymph stasis and inflammation ensues, leading to tissue remodeling and fibrosis. These data suggest, but do not confirm, that impaired lymphatic clearance contributes to tissue sodium storage and fibrosis. However, this possibility has not been investigated rigorously owing to a lack of clinically-feasible measurement tools sensitive to sodium and lymphatics in humans. To address this need, we have developed noninvasive, in vivo MRI approaches to quantify lymphatic vasculature and dynamics, and interstitial measures of tissue sodium content. We have applied a subset of these methods (i) in patients with unilateral upper-extremity lymphedema and we confirmed lateralized lymph stasis and enlarged lymphatic collector cross-sectional area that reduced following manual lymphatic drainage therapy, and (ii) in patients with lower-extremity lymphatic impairment in whom we reported significantly elevated sodium in the skin and subcutaneous tissue, compared to age-, BMI-, and race-matched controls. In preliminary data presented here, we show that in patients with advanced lower-extremity lymphedema and fibrosis, sodium-rich tissue co-localizes with subcutaneous fibrosis, and tissue sodium reduces following complete decongestive therapy (CDT). Here, we will extend this work to test fundamental hypotheses regarding sodium storage, lymphatic dysfunction, and lymphatic mobilization therapy. Hypothesis (1): In patients at-risk for secondary lymphedema, tissue sodium content (TSC) is elevated and inversely correlates with lymphatic flow velocity. Hypothesis (2): Skin TSC positively correlates with lymphedema stage; deep subcutaneous sodium co-localizes with fibrotic tissue in patients with lymphedema and fibrosis. Hypothesis (3): TSC decreases and lymphatic flow velocity increases after a course of CDT in affected limbs with lymphedema; imaging metrics do not change in a similar time-period in healthy volunteers. Impact: Results will confirm how TSC relates to lymphatic dysfunction, and specifically whether TSC can be reduced by manual stimulation of lymphatic channels. This will motivate early intervention as a candidate treatment for reducing fibrosis onset, but more broadly will outline clinically-feasible biomarkers of intervention response which could have significance for future clinical trials that seek to evaluate the impact of emerging lymphatic therapies on tissue sodium storage.

这项工作的总体目的是研究使用组织钠处理的淋巴血管机制特征良好的淋巴样患者对钠和淋巴管敏感的新型无创成像工具疾病。发现旨在为组织钠的淋巴清除机制提供信息，并提供新颖成像淋巴水肿进展和治疗反应的生物标志物。最近的证据支持淋巴管调节间质钠水平。当淋巴清除受损时，高渗性间隙钠导致组织肿胀，皮肤储存和血压控制不良。淋巴时随之而来的淋巴水肿，淋巴结和炎症的啮齿动物模型会损害清除重塑和纤维化。这些数据表明，但没有确认淋巴清除受损有助于进行钠储存和纤维化。但是，由于缺乏对人类中钠和淋巴管敏感的临床上可行的测量工具。解决这个问题需要，我们开发了无创的体内MRI方法来量化淋巴管和动力学，和组织钠含量的间隙度量。我们已经在患者中应用了这些方法的子集（i）单侧上胎淋巴水肿，我们证实了侧向淋巴结和淋巴肿大在手动淋巴引流疗法后减少的收集器横截面区域，以及（ii）患者下淋巴性损伤，我们报告的皮肤中钠的升高显着升高与年龄，BMI和种族匹配的对照相比，皮下组织。在此处提供的初步数据中我们表明，在患有晚期淋巴水肿和纤维化的患者中，富含钠的组织会共定位。在完全充气治疗（CDT）后，皮下纤维化和组织钠会减少。这里，我们将把这项工作扩展到测试有关钠储存，淋巴功能障碍和的基本假设淋巴动员疗法。假设（1）：在次级淋巴水肿的患者中，组织钠含量（TSC）升高，并与淋巴流速度成反比。假设（2）：皮肤TSC 与淋巴水肿的正相关；深层皮下钠与纤维化组织共定位淋巴水肿和纤维化患者。假设（3）：TSC降低，淋巴流速度增加在患有淋巴水肿的受影响的肢体中CDT疗程后；成像指标在类似的时间周期内不会改变在健康的志愿者中。影响：结果将证实TSC与淋巴功能障碍的关系，特别是是否可以通过手动刺激淋巴通道来减少TSC。这将激发早期干预作为减少纤维化发作的候选治疗方法，但更广泛地概述了临床上可行的生物标志物干预反应可能对未来的临床试验具有重要意义，该试验试图评估影响在组织钠储存方面的新兴淋巴疗法。