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

• 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
• 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

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.

摘要 存活5年以上的肺移植受者中，高达80%的人会发展成慢性同种异体肺移植 功能障碍(CLAD)，一种异质性的进行性疾病，特征是渐进性和不可逆转性 功能衰退最终导致死亡。一旦开发出来，大多数包衣类型都没有反应 以及目前可用的治疗干预措施。因此，早期诊断疑似包衣对 旨在延缓疾病发病和/或进展的努力，通常是通过侵略性的 相关免疫危险因素的治疗。 尽管最近修订了标准，但目前的临床依赖于肺活量测定来诊断可疑的包裹体 有几个缺点：即，由肺组织提供的测量的全球性 功能测试(PFT)，它们未能区分排斥反应和感染是功能性的原因 下降，观察员之间在解释其结果时经常出现分歧，最后，他们无法改进 经纤维支气管镜活检的靶向性。一种能够灵敏和准确地检测到 包膜起病更早，空间特异性更强，具有重要的临床价值。 为满足这一需要，拟议的项目将使用敏感的区域性肺功能测量。 各种超极化氙气-129磁共振成像技术唯一能够提供的 能够在肺活量测量显示临床症状之前诊断疑似包裹体的成像标记物 显著的功能衰退；理想情况下，这些标记还将能够区分 在任何一种症状出现之前，包裹体的阻塞性和限制性形式。 该项目的第一个任务将是使用多呼吸HP Xe-129磁共振成像来建立区域特异性 肺活量(SV)和肺泡氧分压(PAO2)作为早期诊断梗阻的影像指标 包层：在这些敏感的气体置换动态指标中增加了异质性 与肺活量测定仪相比，移植肺可以更早地提供包膜相关功能衰退的迹象。下一首, 我们将使用溶解相HP Xe-129成像来量化肺泡气体交换效率和 运输，以检测与肺功能相关的纤维化和血流障碍 穿着有限制性的衣服。最后，我们将尝试从放射学的角度定义几种新的包裹体分类。 与已知的相关危险因素，如缺血再灌注损伤，呼吸道感染，抗体- 介导性损伤和胃食道反流。