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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Hyperpolarized Xe129

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants to be enrolled will include individuals with diagnosed pulmonary arterial hypertension.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Initiating Therapy; PAH patients who are newly initiating background therapy to treat pulmonary arterial hypertension.	Drug: Hyperpolarized Xe129; Lung MRI using gaseous contrast agent hyperpolarized 129Xe.; Other Names: 129Xe; HP Xenon; Xenon MRI
Stable; PAH patients who are stable on therapy (On stable doses of background PAH therapy and diuretics for at least 90 days prior to screening).	Drug: Hyperpolarized Xe129; Lung MRI using gaseous contrast agent hyperpolarized 129Xe.; Other Names: 129Xe; HP Xenon; Xenon MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in RBC/Membrane Ratio	Absolute change over 4 imaging timepoints of RBC/Membrane Ratio from xenon MRI.	18 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Xenon RBC uptake	Absolute change over 4 imaging timepoints of RBC/Gas ratio from xenon MRI.	18 weeks
Change in Xenon RBC oscillation amplitude	Absolute change over 4 imaging timepoints of RBC oscillation amplitude from xenon MRI.	18 weeks

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Peter Niedbalski, PHD, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2022
• Primary Completion (Actual): March 31, 2025
• Study Completion (Actual): July 31, 2025

Study Registration Dates

• First Submitted: April 13, 2022
• First Submitted That Met QC Criteria: April 13, 2022
• First Posted (Actual): April 21, 2022

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Physiological Effects of Drugs; Anesthetics; Central Nervous System Depressants; Anesthetics, General; Anesthetics, Inhalation; Xenon
• Other Study ID Numbers: 00148587

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Upon reasonable request, deidentified subject data, including xenon MRI images may be shared with other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No