Predicting the onset of chronic rejection in lung transplant recipients using hyperpolarized 129Xe imaging

使用超极化 129Xe 成像预测肺移植受者慢性排斥反应的发生

基本信息

批准号：
10192820
负责人：
RAHIM R RIZI
金额：
$ 79.38万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-15 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10192820
关键词：
Acids Air Allografting Alveolar Antibodies Bilateral Biopsy Bronchiolitis Obliterans Cause of Death Cessation of life Characteristics Chronic Chronic Obstructive Airway Disease Classification Clinical Clinical Trials Diagnosis Diagnostic Imaging Diagnostic Procedure Diagnostic Sensitivity Diffuse Disadvantaged Disease Drops Early Diagnosis Early Intervention Failure Fibrosis Frequencies Functional disorder Future Gases Gastroesophageal reflux disease Hemoglobin Heterogeneity Human Image Immunologics Impairment Infection Injury Institution Localized Disease Lung Lung Transplantation Magnetic Resonance Imaging Measurement Measures Mediating Nature Obstruction Onset of illness Operative Surgical Procedures Oxygen Patients Peripheral Phase Phenotype Prognostic Marker Prophylactic treatment Protocols documentation Pulmonary Function Test/Forced Expiratory Volume 1 Pulmonary Gas Exchange Pulmonary function tests Radiology Specialty Reflux Reperfusion Injury Research Personnel Respiratory Tract Infections Risk Factors Sensitivity and Specificity Specificity Spirometry Staging Structure Structure of parenchyma of lung Survival Rate Syndrome Techniques Therapeutic Intervention Tidal Volume Tissues Transplant Recipients Transplantation Visit Work X-Ray Computed Tomography Xenon aggressive therapy airway obstruction base clinical Diagnosis clinical phenotype clinically significant early onset follow-up functional decline imaging biomarker imaging modality improved lung allograft mortality neutrophil novel post-transplant predictive marker pulmonary function recruit response routine imaging therapeutically effective ventilation

项目摘要

Summary Up to 80% of lung transplant recipients who survive beyond five years will develop chronic lung allograft dysfunction (CLAD), a heterogenous, progressive condition characterized by the gradual and irreversible functional decline eventually leading to death. Once developed, the majority of CLAD types do not respond well to currently available therapeutic interventions. Early diagnosis of suspected CLAD is therefore crucial to efforts aimed at the delaying disease onset and/or progression, which usually proceed via the aggressive treatment of associated immunological risk factors. Despite recently revised criteria, the current clinical reliance on spirometry to diagnose suspected CLAD suffers from several disadvantages: namely, the global nature of the measurements provided by pulmonary function tests (PFTs), their failure to differentiate between rejection and infection as the cause of functional decline, frequent inter-observer disagreement in interpreting their results and, finally, their inability to improve the targeting of transbronchial biopsy. An imaging modality capable of sensitively and accurately detecting CLAD-onset earlier and with more spatial specificity would provide significant clinical value. In response to this need, the proposed project will use the sensitive, regional measurements of lung function which various hyperpolarized xenon-129 MRI techniques are uniquely capable of providing to develop a set of imaging markers capable of diagnosing suspected CLAD before spirometric measurements reveal a clinically significant functional decline; ideally, these markers will also enable a distinction to be made between obstructive and restrictive forms of CLAD before either becomes symptomatic. The first task of this project will be to use multi-breath HP xenon-129 MR imaging to establish regional specific ventilation (SV) and alveolar oxygen tension (PAO2) as imaging markers for the early diagnosis of obstructive CLAD: increased heterogeneity in these sensitive measures of gas replacement dynamics within the transplanted lung will offer an earlier indication of CLAD-associated functional decline than spirometry. Next, we will use dissolved-phase HP xenon-129 imaging to quantify the efficiency of alveolar gas exchange and transport in order to detect the fibrotic and bloodflow impediments to pulmonary function associated with restrictive CLAD. Finally, we will attempt to radiologically define several novel sub-classifications of CLAD related to known associated risk factors such as ischemia reperfusion injury, respiratory infection, antibody- mediated injury and gastroesophageal reflux.

概括存活超过五年的肺移植受者中，高达 80% 会出现慢性同种异体肺移植功能障碍（CLAD），一种异质的、进行性的病症，其特征是逐渐且不可逆转的功能衰退最终导致死亡。一旦开发出来，大多数 CLAD 类型都不会做出反应以及目前可用的治疗干预措施。因此，疑似 CLAD 的早期诊断对于旨在延缓疾病发作和/或进展的努力，通常通过积极的方式进行治疗相关的免疫危险因素。尽管最近修订了标准，但目前临床仍依赖肺活量测定法来诊断疑似 CLAD 具有几个缺点：即，由肺提供的测量的全局性质功能测试（PFT），无法区分排斥和感染是功能障碍的原因下降，观察者之间在解释结果时经常出现分歧，最后，他们无法改进经支气管活检的靶向性。一种能够灵敏、准确地检测的成像方式 CLAD 发病较早且具有更高的空间特异性将提供重要的临床价值。为了满足这一需求，拟议的项目将使用肺功能的敏感区域测量各种超极化氙 129 MRI 技术能够独特地开发出一套能够在肺活量测量揭示临床症状之前诊断疑似 CLAD 的成像标记物功能显着下降；理想情况下，这些标记还可以区分在出现症状之前，先进行阻塞性和限制性形式的 CLAD。该项目的首要任务是使用多呼吸 HP xenon-129 MR 成像来建立区域特定通气量 (SV) 和肺泡氧分压 (PAO2) 作为早期诊断梗阻的影像学标志物 CLAD：这些气体置换动力学敏感指标的异质性增加与肺活量测定相比，移植肺将提供 CLAD 相关功能下降的更早指示。下一个，我们将使用溶解相 HP xenon-129 成像来量化肺泡气体交换的效率和运输以检测与肺功能相关的纤维化和血流障碍限制性 CLAD。最后，我们将尝试从放射学角度定义 CLAD 的几个新子分类与已知的相关危险因素有关，例如缺血再灌注损伤、呼吸道感染、抗体- 介导的损伤和胃食管反流。