Exploring the Utility of Hyperpolarized 129Xe MRI in Healthy Volunteers and Patients With Lung Disease

Study Overview
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Brief Summary
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This is a single centre exploratory study that aims to apply hyperpolarized xenon-129 (129Xe) magnetic resonance imaging (MRI) methods and measurements in individual patients with and without lung disease to better understand lung structure and function and evaluate response to therapy delivered as a part of clinical care.

Detailed Description
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The primary objective of this study is to evaluate the ventilation defect percent (VDP), apparent diffusion coefficient (ADC) and/or the signal-to-noise ratio (SNR) obtained by analysis of hyperpolarized 129Xe MRI at one or more time-points (over time in the absence of therapeutic intervention or following clinically indicated therapy) in healthy volunteers and patients with lung disease including but not limited to: asthma, emphysema, COPD, bronchiectasis, sarcoidosis, pulmonary fibrosis, alpha 1-anti-trypsin deficiency, eosinophilic granulomatosis with polyangiitis and bronchopulmonary dysplasia. This will be a single centre exploratory study in 10 healthy volunteers with normal lung function and no history of lung disease and 50 patients with a clinical diagnosis of lung disease. There is one study visit required for participation. A subset of participants may be asked to return for up to five additional study visits per year for five years. The purpose of additional study visits is to understand how hyperpolarized 129Xe MRI measurements of lung structure and function change over time in the absence of therapeutic intervention or following clinically indicated therapy. All subjects will visit St Joseph's Healthcare Hamilton and undergo: vital signs, pulmonary function testing, questionnaires, proton (1H) MRI, static ventilation and/or diffusion-weighted 129Xe MRI, and sputum induction. Up to four doses of hyperpolarized 129Xe will be inhaled during a single study visit.

Official Title
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Single-centre Study Exploring the Utility of Hyperpolarized 129Xe Magnetic Resonance Imaging in Healthy Volunteers and Patients With Lung Disease

Conditions
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Asthma, Chronic Obstructive Pulmonary Disease, Bronchiectasis, Emphysema, Pulmonary Fibrosis, Bronchopulmonary Dysplasia, Alpha 1-Antitrypsin Deficiency, Sarcoidosis, Pulmonary

Intervention / Treatment
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* Other: Hyperpolarized 129Xe MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for participants with lung disease: Male or female aged 18-85 years with diagnosed lung disease including but not limited to: asthma, emphysema, COPD, bronchiectasis, sarcoidosis, pulmonary fibrosis, alpha 1-anti-trypsin deficiency, eosinophilic granulomatosis with polyangiitis and bronchopulmonary dysplasia. Subject understands the study procedures and is willing to participate in the study as indicated by the signature on the informed consent Subject is judged to be in otherwise stable health on the basis of medical history Able to read and/or understand English Have a diagnosis of lung disease Inclusion Criteria for healthy volunteers: Subjects male or female aged 18-85 years Subject understands the study procedures and is willing to participate in the study as indicated by the signature on the informed consent Subject is judged to be in otherwise stable health on the basis of medical history Able to read and/or understand English No current or previous history of respiratory infection or disease Exclusion Criteria: Age < 18 years or >85 years Pregnancy prior to or during study In the opinion of the investigator, subject is mentally or legally incapacitated, preventing informed consent from being obtained, or cannot read or understand the written material Patient is unable to perform spirometry or plethysmography maneuvers Patient has an implanted mechanically, electrically or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants) (at the discretion of the MRI Technologist/3T Manager) In the investigator's opinion, subject suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI, such as severe claustrophobia Exclusion Criteria for healthy volunteers only: Current or previous history of respiratory infection or disease Current smoker or ex-smoker with ≥10 pack-year history

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with and without lung disease<br>All enrolled patients will undergo pulmonary function testing, questionnaires, 1H MRI, static ventilation and/or diffusion-weighted hyperpolarized 129Xe MRI and sputum induction at one or more timepoints over five years. | Other: Hyperpolarized 129Xe MRI<br>* Magnetic resonance imaging (MRI) using inhaled hyperpolarized 129Xe gas is a research approach for the non-invasive visualization and measurement of lung structure and function.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilation Defect Percent (VDP) | Whole lung and lobe specific ventilation defect percent (VDP) measured from 129Xe static ventilation magnetic resonance images. | 1-5 years | 
| Apparent Diffusion Coefficient (ADC) | Whole lung and lobe specific apparent diffusion coefficient (ADC) measured from 129Xe diffusion-weighted magnetic resonance images. | 1-5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Signal-to-noise ratio (SNR) | Signal-to-noise ratio (SNR) measured from 129Xe static ventilation and diffusion-weighted magnetic resonance images. | 1-5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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magnetic resonance imaging, hyperpolarized xenon-129, lung function, lung structure