The overall study objectives outlined in this study are to derive 129Xe MRI pulmonary vascular biomarker signatures that differentiate common subtypes of PAH and to determine the ability of 129Xe MRI to longitudinally monitor disease progression and response to therapy in PAH, with the aid of additional assessments, such as labs, echocardiography, and six-minute walk distance (6MWD).

Subject Enrollment This study will consent and enroll 20 subjects total.

• For Arm 1, 10 subjects with Idiopathic Pulmonary Arterial Hypertension (IPAH) will be consented and enrolled. For Arm 2, 10 subjects with Connective Tissue Disease Associated Pulmonary Arterial Hypertension (PAH-CTD) will be consented and enrolled.

Study Design This study will be observational. Subjects in both arms of the trial will undergo a 129Xe MRI/MRS at timepoints of baseline, 3 months, 6 months, and 12 months. In addition to the this, data from standard of care assessments, such as labs, echocardiography, and six-minute walk distance (6MWD), will also collected at these timepoints.

Primary Study Endpoints The primary endpoint for this trial will be the change in defect + low percentage of RBC signal on hyperpolarized 129Xe MRI from baseline to 12 months

Secondary Study Endpoints

There will be several secondary endpoints for this trial:

• Change in regional and global RBC Oscillation Amplitudes on hyperpolarized 129Xe MR spectroscopy from baseline to 12 months
• Change in 6MWD from baseline to 12 months
• Change in NTproBNP from baseline to 12 months
• Change in WHO FC from baseline to 12 months

Primary Safety Endpoints

There will be several primary safety endpoints for this trial:

• Frequency of Adverse Events (AE) and/or Serious Adverse Events (SAE)
• Withdrawals due to adverse event or death
• Incidence of Adverse Events of Significant Interest (AESI):
• Electrocardiogram and any findings
• Physical examination and vital signs

Inclusion Criteria:

Arm 1 -IPAH

• Age: 18-75 years
• WHO functional class 2 or 3
• Mean pulmonary artery pressures > 20 mmHg
• Pulmonary capillary wedge pressure ≤15 mmHg
• Pulmonary vascular resistance > 2 Wood Units (WU)
• No other cause identified for PAH

Arm 2 -PAH-CTD

• Age: 18-75 years
• WHO functional class (FC) 2 or 3
• Mean pulmonary artery pressures > 20 mmHg
• Pulmonary capillary wedge pressure ≤15 mmHg
• Pulmonary vascular resistance > 2 WU
• Diagnosis of connective tissue disease

Exclusion Criteria:

• PH other than Idiopathic PAH or PAH associated with CTD; any conditions that prevent the performance of 129Xe MRI scans will be excluded from the study.