Visualizing vascular mechanisms of lipedema

这项工作的总体目标是解决临床上未满足的需求，为脂肪肿患者使用先进的 磁共振成像(MRI)血管和分子功能障碍的方法，顺序与便携式 肥胖和水肿症的临床测量。具体地说，脂肿是一种以皮下脂肪为特征的疾病。 肢体组织(SAT)积聚伴有躯体疼痛和浮肿，生活质量差 以及严重的心理痛苦。重要的是，脂肿通常被误诊为肥胖，但 对肥胖的干预导致延迟诊断的症状很难出现，通常是在22年后 症状出现。最近对脂肿采取行动的呼吁强调了对脂肿进行更多研究的必要性，因为 关于疾病机制和可能的治疗方法，我们的知识中仍然存在根本性的差距。完毕 在过去的五年里，在Lipedema基金会的支持下，我们开发了一种全身成像 为脂肪浮肿患者提供更完整、更定量的状况特征透视的策略， 以及改进适当的成像工具。我们已经证明了脂肿与肥胖是不同的 多模式脂肪水磁共振成像和肢体生物阻抗。我们优化了钠和脂肪含量的磁共振成像来证明 四肢组织钠和SAT显著升高，但上肢无明显变化 患有脂肿的女性与匹配的对照组进行比较。在初步数据中，我们证明了皮肤钠可以 可通过标准淋巴疗法、完全去充血疗法(CDT)动员起来。最近发现的 脂肿患者动脉血流灌注量和炎症特征的升高引发了关于血液和血液成分如何变化的重大问题。 淋巴循环参与了疾病的发病机制。在这里，我们首次提出将分子 和血管(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)：超声波可以作为测量皮下脂肪的一种比MRI更容易接受的替代方法 脂肪沉积与肥胖的鉴别；假说(2)：CDT后组织钠减少 脂肪浮肿患者的下肢，但不是未经治疗的上肢，符合 症状学改善；假设(3)：下肢血流速度加快，而 与匹配的对照组相比，脂肿患者的淋巴流速降低。影响：成功 这项研究的完成将(1)确定适合于脂肪肿筛查的方式，(2)展示效果 淋巴刺激对脂肿组织钠的影响，以及(3)促进我们对循环的理解 脂溢症的发生机制。

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.