In aim 1, the study team will compare 129Xe MRI signatures to lung explant pathology, cellular identity from single-cell RNA sequencing, and cellular phenotypes in gas exchange defects to areas that are spared, which the team will hypothesize are exposed to lower levels of hemodynamic shear stress. This will be done by performing 129Xe MRI scans in fifteen subjects (cohort 1) with PAH awaiting a lung transplant, followed by a pathologic assessment (with usual histopathology and single cell RNA sequencing) of the subject's explanted lung after transplant. The study team expect that areas of proliferation and fibrosis will correlate with 129Xe MRI gas exchange and spectroscopic defects~In aim 3, The study team will test whether directly monitoring lung pathology with 129Xe MRI will provide additional prognostic information to standard-of-care clinical monitoring in 45 subjects (cohort 2). At 6-month follow-up appointments, standard-of-care assessments including labs, echocardiography, and six-minute walk distance and 129Xe MRI will be collected. The study team expect that In aim 1, the study team will compare 129Xe MRI signatures to lung explant pathology, cellular identity from single-cell RNA sequencing, and cellular phenotypes in gas exchange defects to areas that are spared, which the study team hypothesizes are exposed to lower levels of hemodynamic shear stress. This will be done by performing 129Xe MRI scans in fifteen subjects (cohort 1) with PAH awaiting a lung transplant, followed by a pathologic assessment (with usual histopathology and single-cell RNA sequencing) of the subject's explanted lung after transplant. The study team expect that areas of proliferation and fibrosis will correlate with 129Xe MRI gas exchange and spectroscopic defects
The overall objective outlined in this study is to determine how pulmonary vascular remodeling in PAH at a cellular and pathological level is associated with changes in gas exchange physiology and hemodynamics (monitored with 129Xe MRI/MRS) and how these signals change with disease progression or treatment.