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

项目摘要 肺移植越来越多地用于治疗终末期肺病患者。并发症 常发生慢性排斥反应，导致肺内大部分的晚期发病和死亡 移植接受者慢性排斥反应的病理表现主要影响小气道或 肺中的细支气管，通常进展未被发现，直到患者出现不可逆的 肺功能下降。存在对安全和准确的方法的未满足的需求，以检测和 分类早期，亚临床病变与随后的慢性排斥反应的发展， 无症状患者，以最大限度地保护这些患者的肺功能。 该项目的目标是构建和评估能够进行3D成像的临床仪器 细支气管和周围的实质，以解决这一未满足的需求。有了这个工具，临床医生 将能够以最小侵入性的方式识别小气道的尺寸和结构变化， 肺泡，并检测气道中的血管和纤维化异常。仪器会快速扫描 亚段细支气管的多个分支用于可靠和准确的早期分类 导致慢性排斥反应的病理指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个小型化的柔性支气管内成像探头， 将多模态光学相干断层扫描与自体荧光成像相结合。这种高 我们的学术合作者最近开发的高分辨率和高性能成像技术， 显示出精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。 为了开发和评估这种临床仪器的目标，我们将首先改进 现有的原型（目标1），以增强与相关病理学相关的图像特征， 肺移植我们将使用测试夹具和活体动物验证改进的性能。目标二是 通过进行适当的安全性评估， 和性能测试。在目标3中，我们将评价多模态支气管内 临床试验中的成像探头，旨在收集肺移植患者的图像库， 识别所述图像数据中的诊断标准，以用于检测与慢性炎症相关的异常。 肺移植排斥反应。我们将在移植后定期对无症状患者进行成像 检查和确定肺移植功能障碍的患者。我们将相关图像 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 以及这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.