Diagnosis of Subglottic Stenosis and Edema in Neonates Using OCT

描述（由申请人提供）：我们寻求开发关键技术，以帮助早产儿和出生头几天的新生儿生存，并避免由声门下狭窄（SGS）引起的严重气道并发症，声门下狭窄是儿童中最常见的获得性喉部异常，也是婴儿中最常见的需要气管切开术的异常。SGS是可以预防的，是由气管内插管在生命的关键的头几天引起的。在早产儿和新生儿中，这种情况可能未被发现或作为威胁生命的事件出现。随着新生儿重症监护技术的进步，更好地治疗甚至预防声门下狭窄的能力得到了提高，但诊断仍然是一个持续争议和辩论的来源。声门下组织本质上是脆弱的，容易受损，并迅速发展为水肿变化，易发生炎症、瘢痕形成和狭窄。手术内窥镜检查仍然是诊断SGS的金标准。不幸的是，手术需要全身麻醉，并且仅限于表面解剖特征，不能提供亚上皮组织的详细分析。由于新生儿对生理应激的耐受性有限，肺、心脏和缺氧阈值可能会推迟对气道的评估，因此这种临床情况往往很复杂。从本质上讲，评估新生儿气道的最终挑战是在准确表征喉组织的同时，最大限度地减少诊断性创伤和生理应激。光学相干断层扫描（OCT）是一种利用光产生分辨率超过10米的活体组织高分辨率图像的成像方式。OCT允许人们根据实时帧率的组织光学特性区分上皮和底层组织微结构。使用OCT可以非侵入性地表征活体组织，远远超出了目前MRI， CT和超声波的成像能力。我们建议设计和构建高速、高分辨率的OCT技术，结合基于3d MEMs的探针，对新生儿重症监护室的新生儿和婴儿气道进行成像，并确定OCT在诊断这些危重患者声门下气道疾病的发生和进展中的潜在作用。首先，我们将在新西兰白兔SGS模型上优化技术，并将OCT与常规显微镜进行比较。然后，我们将在加州大学欧文分校儿童医院橙县icu对200名插管新生儿进行声门下气道成像，并将OCT获得的形态学和结构特征与生理和功能变量（如胎龄、体重和拔管失败次数）相关联，以确定可用于更好地预测气管拔管成功的变量，监测插管过程中病理生理变化的进展。了解新生儿气道的体内生长发育情况。我们相信我们将能够建立OCT作为一种可行的诊断成像方式，用于监测新生儿气道，诊断早期起病的SGS和其他ICU获得性喉部和上呼吸道疾病，这些疾病导致拔管失败，最终气管切开术。

DESCRIPTION (provided by applicant): We seek to develop critical technology to help pre-mature infants and newborns in the first days of life survive and avoid serious airway complications that arise from subglottic stenosis (SGS), the most common acquired anomaly of the larynx in children and the most common abnormality requiring tracheotomy in infants. SGS is preventable and is caused by endotracheal intubation during the critical first days of life. In the premature infant and newborn, this condition may pass undetected or present as a life-threatening event. The ability to better treat and even prevent subglottic stenosis has improved with technical advances in neonatal intensive care, but diagnosis remains a source of continued controversy and debate. The tissues of the subglottis are delicate in nature, easily damaged, and rapidly develop edematous changes, and are predisposed to inflammation, scar formation, and stenosis. Surgical endoscopy has remained the gold standard in the diagnosis of SGS. Unfortunately, surgery requires general anesthesia and is limited to the characterization of the surface anatomy and does not provide detailed analysis of the sub-epithelial tissues. This clinical circumstance is often complicated as the pulmonary, cardiac, and hypoxic thresholds in the newborn population may postpone the evaluation of the airway due to limited tolerances to physiologic stress. In essence, the ultimate challenge in the evaluation of the newborn airway is to minimize diagnostic trauma and physiologic stress while accurately characterizing the laryngeal tissues. Optical Coherence Tomography (OCT) is an imaging modality that utilizes light to produce high-resolution images of living tissues with a resolution in excess of 10 5m. OCT allows for one to distinguish the epithelium from the underlying tissue microstructures based on tissue optical properties with real-time frame rates. Using OCT one can non-invasively characterize living tissues well beyond the current imaging capacities of MRI, CT and ultrasound. We propose to design and construct high speed, high resolution OCT technology combined with 3-D MEMs based probes to image the newborn and infant airways in the neonatal intensive care unit, and define the potential role of OCT in diagnosing the onset and progression of subglottic airway disease in these critically ill patients. First we will optimize the technology in a New Zealand white rabbit model of SGS and compare OCT with conventional microscopy. Then, we will image the subglottic airway in 200 intubated neonates at the UC Irvine-Children's of Hospital of Orange County ICUs and correlate morphologic and structural features obtained with OCT with physiologic and functional variables such as gestational age, weight, and number of failed extubations in order to identify variables that can be used to better predict successful airway extubation, monitor progression of pathophysiologic changes during intubation, and understand the in vivo growth and development of the neonatal airway. We believe we will be able to establish OCT as a viable diagnostic imaging modality that can be used to monitor the neonatal airway and diagnose the early the onset SGS and other ICU acquired laryngeal and upper airway diseases that lead to failed extubation and ultimately tracheostomy. PUBLIC HEALTH RELEVANCE: Subglottic stenosis is the most common indication for tracheostomy in critically ill neonates. Early diagnosis of disease onset may lead to reduction in the incidence of tracheostomy and other airway complications. Development of an office-based treatment technology to diagnosis subglottic stenosis or monitor its development would reduce the need for morbidity and decrease health care costs.