This study will use Magnetic Resonance Imaging (MRI) to study the lungs of 90 volunteers using the inhaled contrast agent, hyperpolarized xenon-129. Once inhaled, this gas can provide information to imagers regarding lung functionality across specific regions of the lungs by assessing the replacement of air during the normal breathing cycle, how much oxygen is in the airspaces, and if the natural spongy tissue structure has been compromised by lung disease. Of the 90 subjects, 70 will be patients who received lung transplantation from the Penn/Temple Lung Transplant Teams and are receiving follow up treatment at HUP or TUH, 10 will be healthy control subjects who participated favorably in our HP 129Xe imaging protocol, and 10 will be patients who have been diagnosed with chronic obstructive pulmonary disease (COPD)-preferentially recruited from the Temple University COPDGene cohort, who have never undergone a lung transplant. 20 of the lung transplant recipient subjects will be patients who have received a recent clinical diagnosis of chronic lung allograft dysfunction (CLAD) prior to enrollment in our study, while the other 50 will have recently undergone their initial transplant surgery at the time of enrollment.
This study assesses the operating characteristics of HP 129Xe MRI in an effort to evaluate its performance in identifying early signs of CLAD or graft acceptance in 70 total lung transplant recipients, 20 of whom have been recently diagnosed with CLAD, 10 non-transplant COPD subjects, and 10 healthy control patients. These subjects will be recruited from the patients of transplant pulmonologists on the Penn and Temple Lung Transplant Team. Subjects will be recruited regardless of race or gender. Study visits will last 1-2 hours for each subject and will occur at various time points following their operation. The baseline visit will occur at the conclusion of their 3 month post-transplant visit, with study follow-up visits occurring at the conclusion of the 6, 9, 12, 18, and 24 month post-transplant visit. For the convenience of the subjects, most study visits will begin at the conclusion of their follow-up visit with their transplant pulmonologist. If this does not work for the subject, an alternative date will be scheduled and the PFT's/Physical exam results from the most recent visit with their transplant pulmonologist will be used for that study visit. There will be a 45-day imaging window for each post-transplant visit, allowing MR imaging to be performed within 45 days before or after the anticipated imaging date, granting more flexibility for both subjects and researchers to ensure that each imaging session is successfully completed. If patients decide to not participate in this study, their decision will not affect their standing with HUP or their physician. Both healthy control subjects and non-transplant COPD subjects will be imaged twice within approximately one week to ensure imaging metric reproducibility in both cohorts. Diagnosed CLAD subjects will undergo a single imaging session each. The images of the diagnosed CLAD subjects will serve as a necessary reference for predicting the early decline of lung function in pre-CLAD transplant recipients.
Study Type
OBSERVATIONAL
Enrollment
45
Hyperpolarized xenon is a contrast imaging agent for lung MR imaging. Inert noble gas xenon is hyperpolarized using Xemed developed technology. The gas is administered to the human subjects as a short seconds-long breath-hold while inside the MRI scanner. Once the gas is inhaled, lung images of HP Xenon distributed within the lung spaces can be acquired. Additionally, xenon follows a similar path to oxygen, dissolving in lung tissue and further in bloodstream.
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Number and extent of functional and microstructural abnormalities observed with hyperpolarized xenon-129 in the lung transplant patients.
The primary endpoint is the number and extent of functional and microstructural abnormalities observed in the lung transplant recipients following inhalation of polarized 129Xe. For the single-breath protocol, images will be obtained immediately after inhalation and during the subsequent breath hold. During the multi-breath protocol, images will be obtained during a \<1 second breath hold at the end of the exhalation. Fractional ventilation will be obtained based on the signal build up for multi-breath breathing of HP 129Xe over the course of the inhalations. Regional alveolar tension of oxygen (PAO2) will be obtained based on the signal decay over time during the breath-hold. ADC will be determined using diffusion sensitizing gradients according to standard imaging protocols. Dissolved phase HP 129Xe will also be obtained by imaging the gas at its different frequencies when bound to hemoglobin and when crossing alveolar walls.
Time frame: up to two years after the lung transplant (imaging at 3, 6, 9, 12, 18, and 24 months post-transplant)
Examine correlations between pulmonary function test scores, questionnaires, and overall scores for the metrics of HP 129Xe MRI ventilation images, ADC, gas exchange, and dissolved phase information.
The relationship between pulmonary function test scores, overall scores of the ventilation images, ADC gas exchange scores, and dissolved phase information generated during HP 129Xe MR imaging will be examined. The statistical plan for the secondary study endpoints will be to use a simple two-sided t-test to see if there are detectable differences between our values within the same patient and their MRI values between the two gases. In this case, the t-test is paired, as we are looking at variables in the same patient.
Time frame: end of the project data analysis
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