Imaging Chylo- and Lympho-thorax in Children with Congenital Heart Defects

 描述(由申请人提供)：乳糜胸是一种罕见但严重的并发症，在接受心脏手术的儿童中，是在儿科重症监护病房(PICU)住院时间的重要因素。儿童心脏手术后胸腔积液的发生率估计为1.3-9.2%，并在过去20年中显著增加。乳糜性和淋巴性胸腔积液可导致严重的代谢、免疫和营养并发症，并与高发病率和死亡率有关。其发病机制尚不清楚，但被认为是由于(I)因破裂、撕裂、撕裂或压迫对胸腔导管的直接损害，(Ii)中心静脉(CV)阻塞或高压阻碍胸腔导管引流到静脉系统，或(Iii)较小的淋巴缺陷可能伴随着先天性心脏缺陷。有效的治疗需要基于已知的机制，但没有诊断方法来询问任何个别病例的胸腔积液的原因。目前，胸腔积液的治疗最初是保守的，包括肠道休息和3-4周的饮食调整。虽然75%至85%的患者对保守治疗有反应，但最后的外科治疗，如胸膜固定术和胸管结扎术，在治疗胸腔积液方面的成功有限，可能是因为它们的治疗时间较晚。要改善对这些疗法的不良反应，需要更好地了解具体的淋巴引流机制。然而，在PICU中无法对婴儿淋巴引流进行动态成像，限制了对胸腔积液发病机制的了解，这反过来又阻碍了对这些危重儿童进行适当和及时的治疗。近红外荧光(NIRF)成像已成功地用于调查研究，以评估成人淋巴管系统及其功能，最近在一名患有乳糜胸的婴儿中。在这项应用中，我们建议对出现胸腔积液的幼儿和婴儿进行动态淋巴成像的初步研究。我们这项研究的具体目标将是(I)调整我们目前正在研究的NIRF成像设备，使其能够拒绝环境光，以改进PICU的床边应用；(Ii)使用改进的设备来表征患有胸腔积液的儿童的动态淋巴引流，以评估引流途径；以及(Iii)监测治疗的反应，无论是保守治疗、胸膜固定术还是胸管结扎术，以便更好地了解乳糜胸的治疗。

 DESCRIPTION (provided by applicant): Chylothorax is a rare, but serious complication in children who undergo heart surgery, and is an important factor for the length of stay in pediatric intensive care units (PICU). Incidence of these pleural effusions following cardiac surgery in children is estimated to be 1.3 - 9.2% and has increased significantly in the last two decade. Chylo- and lympho-thorax can lead to serious metabolic, immunologic, and nutritional complications, and is associated with high morbidity and mortality rate. The pathogenesis is poorly understood but is thought to arise from (i) direct damage to the thoracic duct by rupture, laceration, tear, or compression, (ii) central venous (CV) obstruction or high pressure that impedes thoracic duct drainage into the venous system, or (iii) smaller lymphatic defects that may accompany congenital heart defects. Treatments for effective management need to be based upon known mechanism, but there is no diagnostic method to interrogate the causes of pleural effusion in any individual case. Currently, management for pleural effusions is initially conservative, consisting of gut rest as well as dietary modification over a period of 3-4 weeks. Although 75 to 85% of patients respond to conservative treatment, last resort surgical treatments such as pleurodesis and thoracic duct ligation have only limited success in treating pleural effusions, probably due to their lateness of treatment. Improving the poor response to these therapies demands a better understanding of the specific lymphatic drainage mechanisms responsible. Yet the inability to dynamically image lymphatic drainage in infants within the PICU has limited the understanding of pathogenesis of pleural effusions, which in turn has impeded the application of appropriate and timely management for these critically ill children. Near-infrared fluorescence (NIRF) imaging has been successfully used in investigational studies to assess the lymphatic vasculature and its function in adults and more recently in an infant with chylothorax. In this application, we propose to conduct a pilot study of dynamic lymphatic imaging of young children and infants who present with pleural effusion. Our specific aims of the study will be (i) to adapt our current investigational NIRF imaging device to enable ambient light rejection for improved bedside application in the PICU; (ii) to use the modified device to characterize dynamic lymphatic drainage in children with pleural effusion to assess drainage pathways; and (iii) to monitor response to therapy, whether conservative treatment, pleurodesis, or thoracic duct ligation in order to gain a better understanding of the management of chylothorax.