129Xe MRI Cardiopulmonary

129Xe Gas Exchange MRI to Visualize Cardiopulmonary Function

The goal of this NIH-sponsored study is to characterize three biomarkers derived from 129Xe gas exchange MRI and to understand how they change in response to interventions.

Study Overview

• Status: Recruiting
• Conditions: Polycythemia; Anemia; Interstitial Lung Disease; Dyspnea; Chronic Thromboembolic Pulmonary Hypertension; Acute Pulmonary Embolism
• Intervention / Treatment: Drug: Hyperpolarized Xe129; Other: Oxygen Administration

Detailed Description

This study focuses on the markers that are derived from the interaction of 129Xe with pulmonary capillary red blood cells (RBCs). Specifically, the investigators focus on RBC transfer MRI, cardiogenic oscillations in 129Xe-RBC signal amplitude, and the 129Xe-RBC chemical shift.

In addition to healthy volunteers, the population to be studied will consist of patients scheduled to undergo either transfusion or phlebotomy, those with dyspnea, those with a physician diagnosis of interstitial lung disease (ILD), idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonias (NSIP), chronic hypersensitivity pneumonitis (cHP), and sarcoid, as well as those with either chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism.

• Study Type: Interventional
• Enrollment (Estimated): 125
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bastiaan Driehuys, PhD; Phone Number: 919-684-7786; Email: bastiaan.driehuys@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: Jennifer Korzekwinski; Phone Number: 919-681-7362; Email: jennifer.korzekwinski@duke.edu
      • Contact: Cody Blanton; Phone Number: 919-668-7575; Email: cody.blanton@duke.edu
      • Principal Investigator: Joseph Mammarappallil, MD
      • Sub-Investigator: Bastiaan Driehuys, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for Healthy Volunteers:

(Inclusion Criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial)

1. Outpatients of either gender, age > 18
2. Willing and able to give informed consent and adhere to visit/protocol (Consent must be given before any study procedures are performed.)
3. Subject has no diagnosed pulmonary conditions
4. Subject has not smoked in the previous 5 years
5. Smoking history, if any, is less than or equal to 5 pack-years
6. No history of using other inhaled products more than 1/week for > 1 year

Inclusion Criteria for Transfusion and Phlebotomy Patients:

1. In-patient or outpatients of either sex, age > 18
2. Willing and able to give informed consent and adhere to visit/protocol

And one of the following:

1. Patients who are scheduled to receive a red cell transfusion for anemia.
2. Patients who are scheduled to undergo therapeutic phlebotomy to treat erythrocytosis or polycythemia
3. Healthy volunteers undergoing voluntary whole blood donation (healthy volunteer inclusion criteria noted above)

Inclusion Criteria for Oxygen Administration Patients:

1. In-patient or outpatients of either sex, age > 18
2. Willing and able to give informed consent and adhere to visit/protocol

And one of the following categories (ILD, Dyspnea, CTEPH, or Healthy):

1. Interstitial Lung Disease or Dyspnea

   • Physician diagnosis of Interstitial Lung Disease by a pulmonologist using established criteria or physician referral of patient with dyspnea

   OR

2. Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

   • Patients with a diagnosis of CTEPH, defined as mean PA pressure >20 mmHg with a pulmonary vascular resistance >2 WU and pulmonary capillary wedge pressure ≤15 mmHg at right heart catheterization with evidence of chronic thromboembolic disease on clinical imaging after 3 months of anticoagulation
   • Scheduled for pulmonary thromboendoarterectomy (PTE) surgery and willing to re-turn 3-6 months after for optional follow-up scans

   OR

3. Healthy Volunteer (criteria noted above)

Inclusion Criteria for Acute or Chronic Pulmonary Embolism Patients:

1. In-patient or outpatients of either sex, age > 18
2. Willing and able to give informed consent and adhere to visit/protocol

And one of the following categories (Acute or Chronic)

1. Acute Pulmonary Embolism

   • Patients presenting with acute PE 24-48hrs post-admission
   • Willing to return after 3-6 months of anti-coagulation therapy

   OR

2. Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

   • Patients with a diagnosis of CTEPH, defined as mean PA pressure >20 mmHg with a pulmonary vascular resistance >2 WU and pulmonary capillary wedge pressure ≤15 mmHg at right heart catheterization with evidence of chronic thromboembolic disease on clinical imaging after 3 months of anticoagulation
   • Scheduled for pulmonary thromboendoarterectomy (PTE) surgery and willing to re-turn 3-6 months after for optional follow-up scans

Exclusion Criteria for All subjects:

Subjects presenting with any of the following will not be included in the trial:

1. MRI is contraindicated based on responses to MRI screening questionnaire
2. Subject is pregnant or lactating
3. Resting O2 saturation <90% with maximum supplemental O2 delivered by nasal canula
4. Respiratory illness of a bacterial or viral etiology within 30 days of MRI
5. Subject has history of any known ventricular cardiac arrhythmia
6. Subject has history of cardiac arrest within the last year
7. Subject does not fit into 129Xe vest coil used for MRI
8. Subject cannot hold his/her breath for 10 seconds
9. Subject deemed unlikely to be able to comply with instructions during imaging
10. Medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Transfusion and Phlebotomy Patients; Individuals receiving treatment for their blood hemoglobin levels or are a healthy volunteer who is planning to donate blood.	Drug: Hyperpolarized Xe129; Hyperpolarized xenon will be administered in multiple doses in volumes up to 25% of subject TLC followed by a breath hold of up to 15 seconds.
Active Comparator: Acute or Chronic Pulmonary Embolism Patients; Individuals recently diagnosed with a blood clot in their lungs.	Drug: Hyperpolarized Xe129; Hyperpolarized xenon will be administered in multiple doses in volumes up to 25% of subject TLC followed by a breath hold of up to 15 seconds.
Active Comparator: Oxygen Administration Patients; Individuals diagnosed with a chronic blood clot in their lungs and are planning on having surgery to remove it (CTEPH), or have an interstitial lung disease (ILD), or have dyspnea, or are a healthy volunteer.	Drug: Hyperpolarized Xe129; Hyperpolarized xenon will be administered in multiple doses in volumes up to 25% of subject TLC followed by a breath hold of up to 15 seconds.; Other: Oxygen Administration; Oxygen administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in RBC to Membrane Ratio Pre and Post Transfusion or Apheresis	The investigators will validate the Hb (hemoglobin) correction model in anemia patients pre/post transfusion and blood donors pre/post apheresis.	Up to 5 days pre/post transfusion or apheresis
Change in RBC Oscillation Amplitude Post Therapy	Patients with chronic PE are treated surgically and those with acute PE are treated with anticoagulation therapy.	Baseline, 3-6 months post-treatment
Change in RBC (red blood cell) Chemical Shift After Oxygen Administration	To test the effects of oxygen on 129Xe MRI/MRS in healthy subjects, those with ILD, those with dyspnea, and patients with chronic thromboembolic pulmonary hypertension (CTEPH).	Baseline, 1 day

Collaborators and Investigators

• Sponsor: Bastiaan Driehuys
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Joseph Mammarappallil, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2024
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: September 8, 2023
• First Submitted That Met QC Criteria: September 8, 2023
• First Posted (Actual): September 15, 2023

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Hematologic Diseases; Signs and Symptoms, Respiratory; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Lung Diseases, Interstitial; Anemia; Polycythemia; Dyspnea; Inorganic Chemicals; Elements; Chalcogens; Gases; Oxygen
• Other Study ID Numbers: Pro00113114

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: A major focus of this work is sharing and dissemination of the image acquisition and analysis methods we develop as well as standard operating procedures for 129Xe MRI.
• IPD Sharing Time Frame: In all instances we will adhere to the NIH Sharing Policies and Related Guidance on NIH-Funded Research Resources for Recipients of NIH Grants and Contracts on Obtaining (https://grants.nih.gov/policy/sharing.htm) and Disseminating Biomedical Research Re-sources (issued December 1999). However, we intend to greatly exceed these requirements, making as much of our work freely available to the broader research community either before, or immediately after publication of manuscripts, as well as through PubMedCentral. While we will provide relevant protocols upon request at any time, we further intend to pursue several proactive data sharing mechanisms.
• IPD Sharing Access Criteria: We are committed to making de-identified datasets and image analysis available to qualified investigators. When required scientifically, data including identifiers will be shared under an agreement that provides for: (1) a commitment to using data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data appropriately; and (3) a commitment to destroying or returning the data after analyses are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No