Gas Exchange MRI to Visualize Regional Therapy Response in Interstitial Lung Disease (Xe MRI in ILD)

Optimizing and Standardizing 129Xe Gas Exchange MRI to Visualize Regional Therapy Response in Interstitial Lung Disease

The purpose of this multi-centered, NIH-sponsored study is to to develop an optimal protocol for using non-invasive 129Xe gas exchange MRI to detect changing disease activity in interstitial lung diseases (ILDs). We base this study on the demonstrated promise of 129Xe as a biomarker for both prognosis and therapy response, overwhelming interest from both industry and academic partners, and impending FDA approval for 129Xe ventilation MRI. This requires disseminating standardized and repeatable methods for 3D 129Xe functional MRI in order to facilitate innovative multi-center observational and interventional trials that can advance our understanding of fibrotic lung disease, while accelerating the development of novel therapies.

Study Overview

• Status: Active, not recruiting
• Conditions: ILD
• Intervention / Treatment: Drug: Xenon-129

Detailed Description

There remains an urgent need to better phenotype interstitial lung diseases, predict trajectories, monitor progression, and measure treatment response. Because ILD pathology is spatially and temporarly heterogeneous, the problem demands a 3-dimensional (3D) lung assessment. To this end, CT imaging patterns are critical in IPF diagnosis, but such structural imaging is insensitive to changing functional status. Thus, we have developed hyperpolarized (HP) 129Xe MRI, whose unique properties enable rapid, non-invasive, 3D functional assessment of inhaled gas distribu-tion in the airspaces, as well as its uptake in the pulmonary interstitium (barrier tissues) and trans-fer to the pulmonary capillary red blood cells (RBCs). This way of probing regional gas exchange confers sensitivity to micron-scale interstitial barrier thickening and locally diminished RBC trans-fer. We have used 129Xe MRI to predict outcomes such as death or the need for transplant and have provided preliminary evidence showing that barrier uptake is a sensitive and early marker of therapy response. These advancements have led to demands for wider dissemination, which drives an urgent need to harmonize acquisition protocols and quantification methods.

This work will be conducted by 4 collaborating centers - Duke University, the University of Cincinnati, Cincinnati Children's Hospital Medical Center, and the University of Iowa. Cincinnati Children's will operate under its own IRB protocol and IND, but each site will share data and imaging techniques in order to establish best practices under an approved data sharing agreement. The specific aims of the work conducted at Cincinnati Children's:

Aim 1 - Establish Harmonized Quantitative Analysis of Gas Exchange MRI/MRS. We will deploy a reconstruction and analysis package enabling users of any of three major MRI vendor platforms to obtain robust, real-time quantitative analysis of images and spectra. We will demonstrate that healthy reference cohorts are equivalent to ±10% across 4 centers and use this to build the de-finitive multi-site healthy reference distributions.

Aim 2 - Deploy a Clinical Framework to Identify Active Fibrosis and Normal Aging. To position the technology for clinical deployment and interpretation, we will develop a physiologic model incor-porating ventilation, barrier and RBC metrics to explain the underlying factors responsible for a given patient's diffusing capacity (DLCO) and transfer coefficient (KCO). This framework will be deployed to readers who will differentiate ILD from normal aging.

Aim 3 - Maximize and Measure Repeatability of 129Xe MRI/MRS Metrics across MRI Platforms. We will improve upon published repeatability of ±15-20% by harmonizing MRI/MRS protocols by improved coaching, optimized dose delivery, and tailoring the inhaled dose volume to the individ-ual patient. Using these approaches, each center will demonstrate coefficients of repeatability of ±6% or better in patients with ILD.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

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

Study Population

- Patients with ILD and healthy controls

Description

Inclusion Criteria:

1. Outpatients age 18 - 90 years old.
2. Subject has no diagnosed pulmonary conditions
3. Subject has not smoked in the previous 5 years
4. Smoking history, if any, is less than or equal to 5 pack-years

Additional inclusion criteria for menstruation sub-study in healthy volunteers

1. Subject has a regular 26-30-day menstrual cycle
2. Subject is taking prescribed hormonal contraceptives that preserve a regular menstrual cycle.

Exclusion Criteria:

1. MRI is contraindicated based on responses to MRI screening questionnaire
2. Subject is pregnant or lactating
3. Resting oxygen saturation on room air <90%
4. Respiratory illness of a bacterial or viral etiology within 30 days of MRI
5. Subject has history of any known severe ventricular cardiac arrhythmia, as determined by the study physician.
6. Subject has history of cardiac arrest within the last year
7. Subject cannot hold their breath for 16 seconds

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hyperpolarized 129 Xenon; Hyperpolarized xenon gas will be administered in 20% of each subject's forced vital capacity (FVC) with up to 1000 milliliters of xenon being given to a participant followed by a breath hold of up to 16 seconds	Drug: Xenon-129; Inhaled contrast for MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximize and Measure Repeatability of 129Xe MRI/MRS Metrics across MRI Platforms	Harmonize MRI/MRS protocols by improved coaching, optimized dose delivery, and tailoring the inhaled dose volume to the individual patient. Using these approaches, each center will demonstrate coefficients of repeatability of ±6% or better in patients with ILD.	1 day
Establish Harmonized Quantitative Analysis of Gas Exchange MRI/MRS	Deploy a reconstruction and analysis package enabling users of any of three major MRI vendor platforms to obtain robust, real-time quantitative analysis of images and spectra.	1 day
Deploy a Clinical Framework to Identify Active Fibrosis and Normal Aging	To position the technology for clinical deployment and interpretation, we will develop a physiologic model incorporating ventilation, barrier and RBC metrics to explain the underlying factors responsible for a given patient's diffusing capacity (DLCO) and transfer coefficient (KCO)	1 Day

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: Zack Cleveland, PhD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: September 3, 2021
• First Submitted That Met QC Criteria: August 23, 2023
• First Posted (Actual): August 25, 2023

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Xenon-129
• Other Study ID Numbers: 2021-0031 (Other Identifier: M D Anderson Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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