ABSTRACT
Assessing small airway functional impairment, therapeutic response and disease progression in patients with pulmonary vascular and/or interstitial lung disease (ILD) continues to be challenging. Hyperpolarized Xenon (Xe) MRI enables noninvasive evaluation and regional quantification of alveolar gas exchange via three-dimensional mapping of ventilation, interstitial membrane uptake and red blood cell transfer. This global, open-label, multicenter study will implement harmonized methodology to evaluate safety and tolerability of hyperpolarized Xe gas in patients with pulmonary hypertension and ILD. Adult patients (n=200) with pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, idiopathic pulmonary fibrosis or ILD-associated systemic sclerosis (SSc-ILD) will be enrolled and undergo Xe MRI for evaluation of treatment response and comparison with standard-of-care diagnostic measurements. Eligible patients will be initiating/changing therapy or undergoing a disease-specific procedure. An exploratory cohort (n=50) will allow Xe MRI in patients with long-COVID, unexplained dyspnea, possible transplant (lung or stem cell) rejection, World Health Organization group 3 pulmonary hypertension or other ILDs. Healthy volunteers (n=50) will be enrolled to evaluate Xe MRI reproducibility. Changes in Xe MRI (within patient groups) at 1, 3, 6 and 12 months;Cross-sectional and longitudinal relationships of Xe MRI with spirometry, including diffusing capacity of carbon monoxide (DLCO);Xe MRI measurements compared with right heart catheterization (RHC) and echocardiogram [PH patients] and computed tomography (CT) [ILD patients]. Relationship of Xe MRI quantitative measures across compartments (air/tissue/blood) to treatment response;Changes in Xe MRI parameters to assess temporal relationship to changes in standard diagnostics, healthcare utilization, quality-of-life andmorbidity/mortality;Relationship of Xe MRI cardiogenic oscillation signals of pulmonary-vascular hemodynamics with RHC and clinical outcomes. Patients will begin enrollment within the USA in mid-2022. All patients will participate for at least 1 year (and up to 3 years). Interim analyses will be conducted yearly, with additional snapshots periodically.