Visualizing vascular mechanisms of lipedema

这项工作的总体目标是解决临床未满足的需求，脂肪水肿患者使用先进的 磁共振成像（MRI）方法的血管和分子功能障碍，在序列与便携式 肥胖和水肿的临床测量。具体来说，脂肪水肿是一种以皮下脂肪为标志的疾病， 组织（SAT）积聚在下肢，伴有躯体疼痛和水肿，生活质量差 以及严重的心理困扰重要的是，脂肪水肿通常被误诊为肥胖，但 这些症状对肥胖症的干预是难治的，导致延迟诊断，通常在 症状发作。最近呼吁对脂肪水肿采取行动，强调需要进行更多的脂肪水肿研究， 我们在疾病机制和潜在治疗方面的知识仍然存在根本差距。超过 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技术， 为脂肪水肿患者提供一个更完整的，定量的病情特征， 以及改进适当的成像工具。我们已经证明，脂肪水肿是不同的肥胖使用 多模态脂肪水MRI和肢体生物阻抗。我们优化了钠和脂肪的核磁共振成像 下肢组织钠和SAT体积显著升高，但上肢无 与匹配的对照组相比，脂肪水肿的女性。在初步数据中，我们证明皮肤钠可以 通过标准的淋巴治疗，完全缓解充血治疗（CDT）进行动员。最近的调查结果 脂肪水肿中动脉灌注和炎症特征的升高引起了关于血液和 淋巴循环参与疾病的发病机制。在这里，我们首次提出应用分子 和血管（血液和淋巴）成像以及常见的临床工具，以测试以下假设： 假设（1）：超声波可以作为MRI的更容易的替代方法来测量皮下脂肪 假设（2）：CDT后组织钠减少， 下肢，但不是在未经治疗的上肢，脂肪水肿患者符合 假设（3）：下肢血流速度升高，而 与匹配的对照组相比，脂肪水肿患者的淋巴流速降低。影响：成功 本研究的完成将（1）确定适合脂肪水肿筛查的模式，（2）证明 淋巴刺激对脂肪水肿中组织钠的影响，以及（3）促进我们对循环系统的理解 脂肪水肿的机制。

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.