Developing Hyperpolarized 129Xe MRI Biomarkers for Evaluation of Pulmonary Arterial Hypertension

In this study, hyperpolarized 129Xe MRI will be used to evaluate treatment efficacy in patients with pulmonary arterial hypertension (PAH). Participants will be imaged at 4 timepoints (baseline, 6 weeks post-therapy initiation, 12 weeks, and 18 weeks). Images will be analyzed to develop new biomarkers and to understand treatment effects.

1. Optimize Xe-MRI Oscillation Imaging for PAH. Regional mapping of oscillations in the xenon RBC signal is a new technique that may provide new insights into microvascular function in PH. Recent innovations in Xe-MRI have enabled improvements to this methodology, but these have yet to be explored and optimized.
2. Quantify the short- and long-term repeatability of Xe-MRI oscillation imaging in patients with PAH. Hyperpolarized 129Xe oscillation imaging is a novel technique that may provide regional quantification of pulmonary microvascular function. However, the repeatability of this technique has not been measured, which limits its use as an outcome measure.
3. Determine the minimum time-point at which Xe-MRI shows a clinically meaningful change following treatment. Current standards in the PAH community are to assess treatment efficacy in PAH patients at 3-6 months using 6MWTs, REVEAL Lite scores, echocardiograms, and possibly RHCs. However, Xe-MRI may be more sensitive to functional improvements. We hypothesize that Xe-MRI biomarkers will show a clinically meaningful change within 12 weeks of initiation of pulmonary vasodilators.

Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 18 years of age
* Documented diagnostic right heart catheterization (RHC) at any time prior to screening confirming the diagnosis of WHO PAH Group 1 in any of the following subtypes:

  * Idiopathic PAH
  * Heritable PAH
  * Drug/toxin-induced PAH
  * PAH associated with CTD
* Symptomatic PAH classified as WHO FC I, II, or III.
* Documented Historical RHC with a mPAP ≥ 20 mmHg, PCWP ≤15 mmHg, and PVR ≥ 3 Wood Units (WU)
* Ability to adhere to the study visit schedule, adhere, and comply with all protocol requirements.
* Ability to understand and provide written informed consent.

For patients in the Initiating Therapy Arm:

* Initiation of pulmonary vasodilator therapy within ±3 weeks of baseline imaging timepoint.

For patients in the Stable Arm:

* On stable doses of background PAH therapy and diuretics (i.e., patient-specific dose goal for each therapy already achieved) for at least 90 days prior to screening; for infusion prostacyclins, dose adjustment within 10% of optimal dose is allowed per medical practice

Exclusion Criteria:

* Subject unable to undergo MRI based on MRI safety screening
* Diagnosis of pulmonary hypertension WHO Groups 2, 3, 4, or 5
* Pregnant or breastfeeding female subjects
* Prisoners or incarcerated individuals
* Any major surgical procedure within 90 days prior to study enrollment or planned surgical procedure during the study period.
* Concomitant medical disorder, condition, or history, that in the opinion of the Investigator would impair the subject's ability to participate in or complete the requirements of the study
* Other medical or psychiatric condition which, in the opinion of the Investigator, would place the subject at increased risk or would preclude obtaining voluntary consent or would confound the objectives of the study