Advanced Immunoclinical Phenotyping of Rejection in Lung Transplant
Lung transplantation (LT) is the only definitive therapy for many patients with end-stage lung diseases. The supply of donors' lungs is the biggest bottleneck to performing a lung transplant, and many patients die while waiting. Acute Cellular Rejection (ACR) is a significant risk factor for developing chronic allograft failure, a primary reason for death in this patient population. These observations highlight the importance of early diagnosis and management of ACR to prevent chronic graft failure. The preliminary results support the idea that Hyperpolarized Gas Magnetic Resonance Imaging has excellent potential to address this clinical gap. This study hypothesizes that optimized hyperpolarized gas magnetic resonance imaging (HGMRI) signatures can detect early pathophysiologic derangements in lung allografts consistent with ACR. This study also hypothesizes that the optimized HGMRI signatures will correlate with single-cell transcriptomic signatures that reflect dysregulated immune responses associated with ACR.
• All subjects must be willing to participate and undergo the procedure, and be managed as outpatients
• HXe MRI-specific Inclusion
• All patients who successfully underwent a lung transplant at the University of Virginia
• Followed by the medical lung transplant team for the post-lung transplant rejection surveillance program at the University of Virginia
• a clinical diagnosis of lung transplant within the past 12 months
• absence of any significant allograft dysfunction/rejection at the time of the 12-month surveillance bronchoscopy
• the ability to understand a written informed consent form and comply with the requirements of the study.
• have an acceptable pre-bronchoscopy pulmonary function test: FEV1\>45% before use of any bronchodilator
• Must have acceptable pre-procedural screening studies.
• Complete Blood Count: normal WBC, Hgb, and PLT
• PT: Normal \< 1.2
• Basic Metabolic Panel: Normal
‣ Scenario 1 (two visits): Standard bronchoscopy with Normal MRI results and without a diagnosis of acute rejection after bronchoscopy.
⁃ Scenario 2 (two visits): Navigational bronchoscopy with abnormal MRI result but without a diagnosis of acute rejection after bronchoscopy by clinical pathology.
⁃ Scenario 3 (three or four visits): Navigational bronchoscopy with abnormal MRI result and a diagnosis of acute rejection after bronchoscopy by clinical pathology at the first visit, the second visit, or both visits.
⁃ Scenario 4 (one visit): Subjects who previously signed Part 2 Substudy corresponding to the First HXe MRI visit of the Part 3 Substudy (6 or 12 month evaluation). They will be asked to join the Part 3 Substudy to undergo a 24-month follow-up evaluation, including MRI and bronchoscopy, as described for Scenarios 1, 2, or 3.