Visualizing vascular mechanisms of lipedema

脂肪水肿的血管机制可视化

• 批准号: 10590660
• 负责人: Rachelle L Crescenzi
• 金额: $ 50.84万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-20 至 2026-03-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10590660
• 关键词: Address; Adipose tissue; Affect; Angiography; Awareness; Blood; Blood Circulation; Blood Flow Velocity; Blood Vessels; Blood flow; Body fat; Body mass index; Characteristics; Clinical; Clinical Trials; Data; Deposition; Diagnosis; Diet; Disease; Edema; Exercise; Fatty acid glycerol esters; Female; Foundations; Functional disorder; Future; Goals; Image; Imaging Device; Inflammatory; Investigation; Knowledge; Leg; Limb structure; Lipedema; Lower Extremity; Lymphangiography; Lymphatic; Lymphedema; Magnetic Resonance Imaging; Manuals; Measures; Medicine; Modality; Molecular; Morbidity - disease rate; Obesity; Pain; Pain Measurement; Pathogenesis; Pathologic; Patients; Perfusion; Pharmacologic Substance; Phenotype; Physical therapy; Physiology; Quality of life; Radiology Specialty; Refractory; Reporting; Research; Research Personnel; Sensitivity and Specificity; Skin; Sodium; Symptoms; System; Techniques; Technology; Testing; Time; Tissues; Upper Extremity; Vascular Diseases; Visualization; Water; Woman; Work; arm; case control; comparison control; design; diagnostic screening; evidence base; imaging biomarker; imaging modality; improved; inflammatory marker; lymph flow; lymphatic circulation; lymphatic imaging; lymphatic insufficiency; lymphatic vessel; multimodality; novel; obesity treatment; portability; psychological distress; screening; secondary lymphedema; subcutaneous; symptomatology; tool; ultrasound; volunteer; whole body imaging

The overall goal of this work is to address clinical unmet needs for patients with lipedema using advanced magnetic resonance imaging (MRI) methods of vascular and molecular dysfunction, in sequence with portable clinical measures of adiposity and edema. Specifically, lipedema is a disease marked by subcutaneous adipose tissue (SAT) accumulation in the lower extremities accompanied by somatic pain and edema, poor quality of life and significant psychological distress. Importantly, lipedema is commonly misdiagnosed as obesity, yet symptoms are refractory to interventions for obesity leading to delayed diagnosis typically 22 years after symptom onset. A recent call to action for lipedema highlights the need for additional lipedema research, as fundamental gaps persist in our knowledge regarding both disease mechanisms and potential treatments. Over the past five years and with support from the Lipedema Foundation, we have developed a whole-body imaging strategy for patients with lipedema to provide a more complete, quantitative perspective on condition features, as well as to refine appropriate imaging tools. We have demonstrated that lipedema is distinct from obesity using multi-modal fat-water MRI and limb bioimpedance. We optimized sodium and fat-fraction MRI to demonstrate significantly elevated tissue sodium and SAT volume in the lower extremities, but not upper extremities, of females with lipedema compared to matched controls. In preliminary data we demonstrate that skin sodium can be mobilized by a standard lymphatic therapy, complete decongestive therapy (CDT). Recent findings of elevated arterial perfusion and inflammatory profiles in lipedema raise significant questions about how blood and lymphatic circulation are involved in disease pathogenesis. Here we propose for the first time to apply molecular and vascular (blood and lymphatic) imaging together with common clinical tools to test the following hypotheses: Hypothesis (1): ultrasound can be used as a more accessible alternative to MRI for measuring subcutaneous fat deposition and distinguishing lipedema from obesity; Hypothesis (2): tissue sodium reduces following CDT in the lower extremities, but not in the untreated upper extremities, of patients with lipedema consistent with improvements in symptomatology; Hypothesis (3): lower-extremity blood flow velocity is elevated, while lymphatic flow velocity reduced, in patients with lipedema compared to matched controls. Impact: Successful completion of this study will (1) determine modalities appropriate for lipedema screening, (2) demonstrate effects of lymphatic stimulation on tissue sodium in lipedema, and (3) advance our understanding of the circulatory mechanisms involved in lipedema.

这项工作的总体目的是使用高级患者满足脂肪充血患者的临床未满足需求 血管和分子功能障碍的磁共振成像（MRI）方法，序列 肥胖和水肿的临床指标。具体而言，脂肪充血是皮下脂肪标记的疾病 组织（SAT）在下肢积累，伴有躯体疼痛和水肿，生活质量差 和严重的心理困扰。重要的是，脂质肿通常被误诊为肥胖症 症状对肥胖的干预措施难治性，导致诊断延迟，通常是22年后 症状发作。最近的脂肪充血行动呼吁强调了需要进行其他脂肪水肿的需求， 我们对疾病机制和潜在治疗的知识持续存在基本差距。超过 过去五年，在Lipedema基金会的支持下，我们开发了全身成像 脂肪水肿患者的策略，以提供有关状况特征的更完整，定量的观点， 以及完善适当的成像工具。我们已经证明，脂肪充血与使用的肥胖不同 多模式的脂肪 - 水MRI和肢体阻抗。我们优化了钠和脂肪分数MRI以证明 在下肢而不是上肢，但没有明显地升高组织钠和SAT体积 与匹配的对照相比，具有脂肪充血的女性。在初步数据中，我们证明了皮肤钠可以 通过标准的淋巴疗法动员，完全充气疗法（CDT）。最新发现 脂肪充血中的动脉灌注和炎症特征升高，就血液和如何血液和 淋巴循环涉及疾病发病机理。在这里，我们首次提出应用分子 以及血管（血液和淋巴）成像以及常见的临床工具来检验以下假设： 假设（1）：超声可以用作测量皮下脂肪的更容易获得的MRI替代品 沉积和区分脂肪与肥胖；假设（2）：组织钠在CDT中降低 下肢，但在未经治疗的上肢中，脂质肿的患者与 症状的改善；假设（3）：下肢血流速度升高，而 与匹配对照相比，脂肪水肿患者的淋巴流速度降低。影响：成功 这项研究的完成将（1）确定适合脂肪性筛查的方式，（2）证明了影响 脂肪水肿的组织钠的淋巴刺激，（3）提高我们对循环系统的理解 涉及脂质的机制。