High-Resolution Multi-Modality Endoscopic Imaging Probes For Diagnosing Rejection In Lung Transplant Recipients

项目总结 肺移植越来越多地被用于治疗终末期肺部疾病。并发症 常发生慢性排斥反应，导致肺部大部分晚期发病率和死亡率 移植受者。慢性排斥反应的病理表现主要累及小气道或 肺内细支气管炎，通常在未被发现的情况下进展，直到患者出现不可逆转的 肺功能下降。对安全和准确的方法的需求还没有得到满足 对与随后发生慢性排斥反应相关的早期亚临床病变进行分类 无症状患者，以最大限度地保存这些患者的肺功能。 该项目的目标是建立和评估一种能够进行3D成像的临床仪器 对细支气管壁和周围薄壁组织进行移植，以满足这一未得到满足的需求。有了这台仪器，临床医生 将能够以最小的侵入性识别小气道的尺寸和结构变化 肺泡，并检测呼吸道中血管和纤维化的异常。仪器将快速扫描 多支亚段细支气管术对早期诊断可靠、准确 导致慢性排斥的病理学提示更早和更有针对性的治疗干预。 我们提出的仪器是基于一种小型化的柔性支气管腔内成像探头 将多模式光学相干层析成像与自体荧光成像相结合。这么高 最近由我们的学术合作者开发的分辨率和高性能成像已经被 显示出准确和快速地显示小气道和肺泡的精细解剖结构，还 识别肺血管和肺纤维化。 为了开发和评估这样一种临床仪器，我们将首先改进 现有的原型(目标1)旨在增强与相关病理相关的图像特征 肺移植。我们将使用测试夹具和活体动物来验证改进后的性能。目标2是 通过进行适当的安全性评估改进后的仪器用于人体试验的准备情况 以及对该设备的性能测试。在目标3中，我们将评估多通道支气管内膜 临床试验中的成像探针，旨在收集肺移植患者的图像库和 识别图像数据中用于检测与慢性疾病相关的异常的诊断标准 异体肺移植排斥反应。我们将在常规移植后对无症状患者进行成像。 检查和确诊为肺移植功能障碍的患者。我们将关联相关图像 肺功能、组织学和支气管肺泡灌洗结果以及其他临床参数的特征 以及两组患者的临床病史。

PROJECT SUMMARY Lung transplantation is increasingly used to treat patients with end-stage lung diseases. Complications frequently occur with chronic allograft rejection causing most of late morbidity and mortality in lung transplant recipients. Pathological manifestations of chronic rejection mostly affect small airways or bronchioles in the lung, often progressing undetected until the patient presents with an irreversible decline in pulmonary function. There is an unmet need for safe and accurate methods to detect and classify earlier, sub-clinical lesions associated with subsequent development of chronic rejection in asymptomatic patients, to maximize preservation of lung function in these patients. The goal of this project is to build and evaluate a clinical instrument that is capable of 3D imaging of bronchioles and surrounding parenchyma to address this unmet need. With this instrument, clinicians will be able to identify, minimally-invasively, dimensional and structural changes of small airways and alveoli, and to detect vascular and fibrotic abnormalities in the airways. The instrument will rapidly scan many branches of sub-segmental bronchioles for reliable and accurate classification of early pathologies leading to chronic rejection to indicate earlier and more targeted therapeutic interventions. Our proposed instrument is based on a miniaturized flexible endobronchial imaging probe that combines multi-modality optical coherence tomography with autofluorescence imaging. This high resolution and high-capability imaging, recently developed by our academic collaborators, has been shown to accurately and rapidly visualize fine anatomical structures of small airways and alveoli, also identifying pulmonary vasculature and lung fibrosis. Towards the objective of developing and evaluating such a clinical instrument, we will first improve the existing prototypes (Aim 1) to enhance image features associated with relevant pathologies in the lung graft. We will validate the improved performance using test fixtures and live animals. Aim 2 is to evaluate the readiness of the improved instrument for human trials by conducting appropriate safety and performance tests for the device. In Aim 3, we will evaluate the multi-modality endobronchial imaging probe in clinical trials aimed at collecting a library of images of lung transplant patients and identifying diagnostic criteria in the image data for detection of abnormalities associated with chronic rejection of lung allograft. We will image asymptomatic patients during their regular post-transplant exams and patients with established lung transplant dysfunction. We will correlate relevant image features with lung function, histology and bronchoalveolar lavage findings, and other clinical parameters and clinical history in these two groups of patients.