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.

总结