Hyperpolarized 129Xe MRI to Identify Structural Determinants of Low Lung Function and Respiratory Symptoms in Young Adults From the Lung Health Cohort - November 30th 2023

  • A subset of young adults participating in the American Lung Association (ALA) Lung Health Cohort (LHC) will be imaged using Hyperpolarized 129Xe MRI to assess lung structure and function. Images will be used to improve the understanding of lung health and early lung abnormalities that may lead to chronic lung disease.

  • Part A will include participants with FEV1 > 85% predicted and no respiratory symptoms as determined at the baseline visit for the Lung Health Cohort.

  • Part B will include participants with FEV1 < 85% predicted as determined at the baseline visit for the Lung Health Cohort.

  • Part C will include participants with respiratory symptoms as determined at the baseline visit for the Lung Health Cohort.

  • Primary Outcome Measures

    • Xe-MRI Apparent Diffusion Coefficient. Correlation of Xe-MRI with FEV1/FVC and other measures of lung function.

Contact for project information: Peter J. Niedbalski, PhD

Sites involved: University of Kansas Medical Center, John Hopkins University, University of Iowa, Duke University, University of Illinois at Chicago, Baylor College of Medicine, M.D. Anderson Cancer Center

HyPOINT Study - January 13th 2020

  • Hyperpolarized Imaging for New Treatments (HyPOINT), trial is a multicenter prospective, two phase study involving four sites with proven expertise 129Xe MRI and CF clinical care

  • Phase 1 will include implementation of a centralized analysis program of repeated 129Xe MRI scanning in CF patients with mild lung disease to define the intra-subject variability of the primary outcome ventilation defect percentage (VDP)

  • Phase 2 will be an observational study of patients assessed before and after the clinical initiation of triple-combination modulator therapy

  • The primary endpoint for Phase 2 is the change of VDP after 28 days of triple-combination modulator therapy

  • Phase 2 will also address how highly-effective modulator therapies affect lung function trajectories by measuring 129Xe MRI at 28 days (± 7 days), 6 months (± 28 days), and 12 months (± 28 days) after start of therapy

  • Finally, to understand how 129Xe MRI can be used in combination with existing measures of lung function (e.g. spirometry, multiple breath washout), we will directly compare the repeated data collected in both Phase 1 and Phase 2 to these established measures of lung function that are currently used in observational and interventional studies

    Contact for project information: Jason C Woods, PhD

    Sites involved: Children's Hospital Medical Center, Cincinnati, University of Virginia, University of Wisconsin, Madison, The Hospital for Sick Children

BEGINNING Study - May 1st 2022

  • BEGIN Novel ImagiNG Biomarkers (BEGINNING), is a prospective two-part study involving four BEGIN sites who also have expertise in 129Xe MRI, abdominal MRI, and CF clinical care

  • Part A will include yearly pulmonary MRI and abdominal MRI in young CF patients (3-5 y.o.) to define the inter-subject variability and longitudinal changes in disease in the lung, liver, and pancreas, compared to control patients without CF and compared to clinical data obtained in the larger BEGIN study

  • Part B will be an observational study of patients assessed before and after the clinical initiation of triple-combination modulator therapy

  • The primary endpoints for Part B will be changes in structural and/or functional imaging measures within each organ, supported by preliminary data

  • To directly compare the repeated data collected in both Part A and Part B to multiple objective measures obtained via BEGIN—namely, lung clearance index (LCI) measured by multiple-breath washout testing, liver and pancreatic function testing, gastrointestinal questionnaires and stool scale, and physical characteristics

    Contact for project information: Jason C Woods, PhD

    Sites involved: Children's Hospital Medical Center, Cincinnati, University of Kansas, University of Iowa, University of Virginia

Imaging Measures of Respiratory Health Registry (iMRH) - October 29th 2021

  • Imaging Measures of Respiratory Health Registry (iMRH), is a prospective, observational cohort registry that aims to collect data on pulmonary structure and function in healthy people and those with respiratory disease, using structural and functional pulmonary 1H-MRI and hyperpolarized 129Xe-MRI.

  • Outcome measures generated from MRI may include but are not limited to measures of regional ventilation, pulmonary microarchitecture, and regional gas exchange. Additionally, one of the goals of the registry is to facilitate the development of novel image analysis techniques that have not yet been invented.

  • Primary Outcome Measures:

    • Structural proton (1H) MRI data. Includes all proton MRI images collected to assess pulmonary structure

    • Functional proton (1H) MRI data. Includes all proton MRI images collected to assess pulmonary function

    • Functional hyperpolarized 129-xenon (129Xe) MRI data. Includes all proton images collected to assess pulmonary function. Data may be analyzed qualitatively and quantitatively

  • Secondary Outcome Measures:

    • Resting oxygen saturation

    • CFQ-R Respiratory domain. Only for participants with cystic fibrosis

    • St. George Respiratory Questionnaire. Only for participants with respiratory disease

    Contact for project information: Jonathan Rayment MDCM, MSc

    Sites involved:  British Columbia Children's Hospital, St. Paul's Hospital

¹²⁹Xe MRI To Assess Disease Progression in Patients With COPD Treated With Or Without Azithromycin And Standard-of-Care Medications - November 16th 2021

  • This study will test whether daily use of azithromycin will reduce the rate of exacerbations and improve lung ventilation and perfusion assessed by XE-MRI. The sensitivity of XE-MRI to detect COPD progression will be compared with standard clinical assessment measures including standard lung function tests, 6-minute walk test, and patient reported quality of life.

  • Primary Outcome Measures:

    • Change in ¹²⁹XE MRI VDP from Baseline to 24 weeks [ Time Frame: Baseline up to Week 24]

    • Rate of Moderate/Severe AEs [ Time Frame: Baseline up to Week 48]

    • Rate of Moderate/Severe Exacerbation [ Time Frame: Baseline up to Week 48]

    • A moderate COPD exacerbation is defined as new or increased COPD symptoms (e.g., dyspnea, sputum volume, and sputum purulence) for at least 2 consecutive days that lead to treatment with systemic corticosteroids and/or antibiotics. A severe COPD exacerbation is defined as new or increased COPD symptoms (e.g., dyspnea, sputum volume, and sputum purulence) for at least 2 consecutive days that lead to hospitalization or death.

  • Secondary Outcome Measures:

    • Absolute Change in Pre-bronchodilator FEV-1 (Liters) [ Time Frame: Baseline up to Week 24]

    • Absolute Change in Pre-bronchodilator FEV-1 (Liters) [ Time Frame: Baseline up to Week 48]

    • Number of Participant with Adverse Events with Severity Determined According to The World Health Organization (WHO) Toxicity Scale [ Time Frame: Baseline up to 24 months

    Contact for project information:  Bastiaan Driehuys, PhD, Loretta Que, MD, Robert Tighe MD, Tony Huang, MD

    Sites involved:  University of Iowa, University of Kansas Medical Center, Duke Asthma Allergy and Airway Center, University of Virginia Health System, St. Joseph's Healthcare Hamilton, Genentech, inc.

¹²⁹Xe and Free-Breathing ¹H Ventilation MRI in Patients with Cystic Fibrosis: A Dual-Center Study - October 11th 2022

  • Free-breathing 1H ventilation MRI shows promise but only single-center validation has yet been performed against methods which directly image lung ventilation in patients with cystic fibrosis (CF).

  • Purpose: To investigate the relationship between 129Xe and 1H ventilation images using data acquired at two centers (University of Sheffield, UK & Hannover Medical School, Germany)

  • Population: Center 1; 24 patients with CF (12 female) aged 9–47 years. Center 2; 7 patients with CF (6 female) aged 13–18 years, and 6 healthy controls (6 female) aged 21–31 years. Data were acquired in different patients at each center.

  • 1H ventilation MRI shows large-scale agreement with 129Xe ventilation MRI in CF patients with established lung disease but may be less sensitive to subtle ventilation changes in patients with early-stage lung disease.

    Contact for project information:  Jim Wild, PhD

    Sites involved:  University of Sheffield, Hannover Medical School