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; 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.

概括 多达80％的肺移植接受者生存超过五年，将发展慢性同种异体移植 功能障碍（clad），一种以渐进和不可逆为特征的异源，进行性疾病 功能下降最终导致死亡。一旦开发，大多数外壳类型都不会响应 很好，目前可用的治疗干预措施。因此，早期诊断可疑的外壳对 旨在延迟疾病发作和/或进展的努力，通常通过侵略性进行 治疗相关的免疫风险因素。 尽管最近修改了标准，但目前对肺活量测定法的临床依赖诊断可疑壳 遭受了几个缺点：即，肺部提供的测量的全球性质 功能测试（PFT），它们无法区分排斥和感染作为功能的原因 衰落，经常出现在解释其结果时的观察者间分歧，最后他们无法改善 靶向经支气管活检的靶向。能够敏感，准确检测的成像方式 较早的外壳发作，并且具有更大的空间特异性将提供显着的临床价值。 为了应对这种需求，拟议的项目将使用肺功能的敏感，区域测量值 各种超极化XENON-129 MRI技术具有独特的能力，能够提供一组 在肺活量测量之前，能够诊断出可疑外壳的成像标记显示出临床上的 功能下降的显着下降；理想情况下，这些标记还将使得能够区分 在有症状之前，施法的阻塞性和限制性形式。 该项目的第一个任务是使用多呼吸hp Xenon-129 MR成像来建立特定区域 通风（SV）和肺泡氧张力（PAO2）作为成像标记，用于早期诊断阻塞性 外壳：这些在这些敏感的气体替代动力学测量中的异质性增加 移植的肺部将提供与肺活量测定法相关的功能下降的早期指示。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的纤维化和血流障碍 限制性的外壳。最后，我们将尝试从放射学上定义几个新型的clad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。