Assessing Xenon CT Imaging Biomarkers in Lung Transplant Recipients

描述（申请人提供）：肺移植是晚期肺部疾病患者的重要治疗选择。事实上，大多数患者在移植后可以期待良好的功能恢复和生活质量的提高。尽管早期生存和功能有所改善，但闭塞性细支气管炎（OB），一种普遍进行性小气道功能丧失，严重威胁肺移植受者（lts）的长期前景。OB及其临床相关的闭塞性毛细支气管炎综合征（BOS）是最常见的慢性并发症，影响移植后存活5年的大多数患者。BOS的关键临床特征是通过肺功能测试（PFT）诊断为气道阻塞的发展。然而，PFT是一种全球性的肺功能测量，并不能提供区域性疾病累及或早期BOS的信息。为了预防或延迟BOS的发生，直接评估OB的局部区域发展将是有用的。区域OB地图将使我们能够评估BOS的机制，疾病进展，并为特定肺区域的图像引导活检或治疗提供工具，以提高早期治疗干预的效果。然而，传统的CT或MR成像是有限的，并且不能同时评估与早期BOS变化相关的局部通气和形态学变化。因此，我们开发了一种新的氙气CT区域通气成像技术和肺形态学定量分析方法，并提出这些新工具对于研究移植肺的功能和形态学变化以及ltr异体移植物功能障碍发生和进展的潜在机制至关重要。主要目的是评估我们的氙气CT成像技术，以评估局部通气和形态学变化，并将这些变化与肺功能测试和BOS进展联系起来。本研究的创新之处在于，我们开发了一种新的氙气CT肺部成像技术和一种新的、高效可靠的半自动交互式分割方法。我们的中心假设是，氙气CT可用于量化肺区域通气和形态学的变化，并将这些变化与肺功能和疾病进展联系起来。具体目的是：(1)开发和评估氙CT成像生物标志物，比较肺移植受者BOS分期的横断面差异；(2)确定早期BOS患者氙CT成像生物标志物的纵向变化是否与肺功能指标的纵向变化相关；(3)比较部分患者肺节段性氙CT成像生物标志物异常与节段性气道组织病理学异常。这些目标的完成将量化氙CT成像生物标志物与肺功能之间的横断面（Aim 1）和纵向（Aim 2）关联，为确立其作为移植肺BOS进展的区域成像标志物的实用性提供关键的第一步。

DESCRIPTION (provided by applicant): Lung transplantation is an important treatment option for patients with advanced lung diseases. Indeed, the majority of patients can expect excellent functional recovery and improved quality-of-life after transplant. Despite this improvement in early survival and function, though, obliterative bronchiolitis (OB), a generally progressive loss of small airway function, gravely threatens the long-term outlook for lung transplant recipients (LTRs). OB and its clinical correlate, bronchiolitis obliterans syndrome (BOS), is the most common chronic complication, affecting the majority of patients who survive 5 years after transplantation. The key clinical feature of BOS is the development of airway obstruction diagnosed with pulmonary function testing (PFT). However, PFT is a global lung function measure and does not provide information about regional disease involvement or early BOS. To prevent or delay onset of BOS, it would be useful to directly assess local regional development of OB. The regional OB map would allow us to evaluate mechanisms of BOS, disease progression, and provide a tool for image-guided biopsy or treatment at specific lung regions to improve the efficacy of an early therapeutic intervention. Conventional CT or MR imaging is limited, however, and does not allow a simultaneous evaluation of the regional ventilation and morphologic changes associated with early changes in BOS. Thus, we have developed a novel xenon CT regional ventilation imaging technique and quantitative method for lung morphology analysis, and propose that these new tools are crucial to investigate both functional and morphological changes in transplanted lungs and the underlying mechanisms involved in development and progression of allograft dysfunction in LTRs. The primary objective is to evaluate our xenon CT imaging technique to assess regional ventilation and morphological changes, and to associate these changes with pulmonary function testing and BOS progression. The proposed research is innovative in that we have developed a novel xenon CT lung imaging technique and a new, efficient and reliable semi-automated interactive method for segmentation. Our central hypothesis is that xenon CT can be used to quantify changes in lung regional ventilation and morphology and associate these changes with pulmonary function and disease progression. The Specific Aims are (1) to develop and evaluate xenon CT imaging biomarkers and compare the cross-sectional differences between BOS stages in lung transplant recipients; (2) to determine whether longitudinal changes in xenon CT imaging biomarkers are associated with longitudinal changes in pulmonary function measures in patients with early BOS; and (3) to compare lung segmental abnormalities of xenon CT imaging biomarkers with histopathological abnormalities of segmental airways in selected patients. Completion of these aims will quantify cross-sectional (Aim 1) and longitudinal (Aim 2) associations between the xenon CT imaging biomarkers and pulmonary function, providing a key first step in establishing their utility as regional imaging markers for BOS progression in transplanted lungs.