Developing Optimal Parameters for Hyperpolarized Noble Gas and Inert Fluorinated Gas MRI of Lung Disorders

Study Overview
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Brief Summary
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The goal of this research is to optimize the MRI system to obtain ideal lung images using Hyperpolarized (HP) Noble and Inert Fluorinated Gases as contrast agents. Lung coils tuned to the frequencies of these gases will be used. This study will take place at TBRHSC in the Cardiorespiratory Department and in the Research MRI facility.

Detailed Description
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MR images of the lung obtained using HP 3He, HP 129Xe, and inert fluorinated gases essentially show the distribution of the inhaled gas inside the lungs. Measurements can be performed on these images to provide additional information that can be related to pulmonary function. Participation will involve at least two study visits. During the first visit, participants will provide written, informed consent, and undergo eligibility screening. Study drug administration, use of the investigational devices, and MR imaging for this study will be performed at the 3T Research MRI at the Thunder Bay Regional Health Sciences Centre (TBRHSC). Pulmonary Function Tests (PFTs) will be performed at TBRHSC by a Registered Respiratory Therapist (RRT) and an MR Tech will be present for the duration of participant scans. Participants will be placed in the MRI with the appropriate chest coil wrapped around them like a vest. Several inhalation procedures will be carried out during scanning. Participants safety will be closely monitored throughout the entire study.

Official Title
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Developing Optimal Parameters for Hyperpolarized Noble Gas (3He and 129Xe) and Inert Fluorinated Gas Magnetic Resonance Imaging of Lung Disorders

Conditions
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Bronchiectasis, Lung Transplant, Lung Resection, Lung Cancer, Asthma, Cystic Fibrosis, Chronic Obstructive Pulmonary Disease, Emphysema, Mesothelioma, Asbestosis, Pulmonary Embolism, Interstitial Lung Disease, Pulmonary Fibrosis, Seasonal Allergies, Cold Virus, Lung Infection, Pulmonary Hypertension, Pulmonary Dysplasia, Obstructive Sleep Apnea

Intervention / Treatment
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* Drug: HP 3He
* Drug: HP 129Xe
* Drug: PFP
* Drug: SF6
* Device: 129Xe Small and Large Human Lung Coil
* Device: 3He Human Lung Coil
* Device: PFP and SF6 Human Lung Coil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is either: A healthy volunteer (i.e.: someone not diagnosed with a lung disorder written below; this may include smokers who have not been diagnosed with a lung disorder) or Has been diagnosed with one of the following respiratory disorders: lung transplants, lung resection, lung cancer, asthma, cystic fibrosis, chronic obstructive pulmonary disease, emphysema, mesothelioma, asbestosis, pulmonary embolism, interstitial lung disease, pulmonary fibrosis, bronchiectasis, seasonal allergies, pneumonia, cold virus, lung infection, pulmonary hypertension, pulmonary dysplasia, obstructive sleep apnea Able to provide informed consent Able to hold their breath for imaging: Healthy volunteers enrolled in this study must be able to hold their breath for 25 seconds Lung disorder participants must be able to hold their breath for 15 seconds Exclusion Criteria: Have contraindication to MR imaging (i.e. ferrous implants, cardiac pacemakers) - determined by MR screening prior to scans. Have a history of claustrophobia. Female exclusion only: are or may be pregnant. Requires an oxygen mask and cannot use a nasal cannula. Blood oxygen saturation is below 92% (measured at rest in a sitting position, and with an O2 nasal cannula if the participant normally uses one). Has had an acute respiratory infection in the past 10 days. Is a student currently enrolled in a course at Lakehead University where the Principal Investigator (PI) is the instructor. Is a student currently enrolled in a degree program at Lakehead University where the PI is their direct thesis supervisor. Is currently an employee of the PI at the Thunder Bay Regional Research Institute (TBRRI) and/or Lakehead University.

Ages Eligible for Study
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Minimum Age: 18 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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Participants<br>Participants will inhale investigational gases (HP 3He, HP 129Xe, PFP and SF6) according to the procedure for that intervention. All participants can potentially inhale all the gases. Magnetic resonance imaging will be performed during breath-holds or continuous breathing (gas-dependent) with the appropriate investigational human lung coil (3He Human Lung Coil, 129Xe Small and Large Human Lung Coil, or PFP and SF6 Human Lung Coil), using the 3T Research MRI at the Thunder Bay Regional Health Sciences Centre. | Drug: HP 3He<br>* 3He will be hyperpolarized using a custom-built polarizer to enhance its MRI signal. Hyperpolarization does not change the chemical or physical properties of helium gas.<br>* Other names: Hyperpolarized helium 3;Drug: HP 129Xe<br>* 129Xe will be hyperpolarized using a Xemed polarizer to enhance its MRI signal. Hyperpolarization does not change the chemical or physical properties of xenon gas.<br>* Other names: Hyperpolarized xenon 129;Drug: PFP<br>* Perfluoropropane (PFP) will be premixed and delivered to the participants with no further processing.<br>* Other names: Perfluoropropane;Drug: SF6<br>* Sulfur hexafluoride (SF6) will be premixed and delivered to the participant with no further processing.<br>* Other names: Sulfur hexafluoride;Device: 129Xe Small and Large Human Lung Coil<br>* The investigational 129Xe small and large quadrature lung coils are sensitive to 129Xe resonant frequencies and therefore will be paired with the investigational drug 129Xe. The size of the coil used will depend on the participants' body size.<br>Device: 3He Human Lung Coil<br>* The investigational 3He quadrature lung coil is sensitive to 3He resonant frequencies and therefore will be paired with the investigational drug 3He.<br>Device: PFP and SF6 Human Lung Coil<br>* The investigational PFP and SF6 quadrature lung coil is sensitive to inert fluorinated gas resonant frequencies and therefore will be paired with both PFP and SF6.<br>|
| Experimental: Lung Disorder Participants<br>Participants will inhale investigational gases (HP 3He, HP 129Xe, PFP and SF6) according to the procedure for that intervention. All participants can potentially inhale all the gases. Magnetic resonance imaging will be performed during breath-holds or continuous breathing (gas-dependent) with the appropriate investigational human lung coil (3He Human Lung Coil, 129Xe Small and Large Human Lung Coil, or PFP and SF6 Human Lung Coil), using the 3T Research MRI at the Thunder Bay Regional Health Sciences Centre. | Drug: HP 3He<br>* 3He will be hyperpolarized using a custom-built polarizer to enhance its MRI signal. Hyperpolarization does not change the chemical or physical properties of helium gas.<br>* Other names: Hyperpolarized helium 3;Drug: HP 129Xe<br>* 129Xe will be hyperpolarized using a Xemed polarizer to enhance its MRI signal. Hyperpolarization does not change the chemical or physical properties of xenon gas.<br>* Other names: Hyperpolarized xenon 129;Drug: PFP<br>* Perfluoropropane (PFP) will be premixed and delivered to the participants with no further processing.<br>* Other names: Perfluoropropane;Drug: SF6<br>* Sulfur hexafluoride (SF6) will be premixed and delivered to the participant with no further processing.<br>* Other names: Sulfur hexafluoride;Device: 129Xe Small and Large Human Lung Coil<br>* The investigational 129Xe small and large quadrature lung coils are sensitive to 129Xe resonant frequencies and therefore will be paired with the investigational drug 129Xe. The size of the coil used will depend on the participants' body size.<br>Device: 3He Human Lung Coil<br>* The investigational 3He quadrature lung coil is sensitive to 3He resonant frequencies and therefore will be paired with the investigational drug 3He.<br>Device: PFP and SF6 Human Lung Coil<br>* The investigational PFP and SF6 quadrature lung coil is sensitive to inert fluorinated gas resonant frequencies and therefore will be paired with both PFP and SF6.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Signal to Noise Ratio | The primary objective of this study is to determine an optimized set of scan parameters that will produce clear, anatomically and clinically relevant images of the lungs for healthy participants and various types of lung disorder participants, and using one or more gas type (3He, 129Xe, PFP, SF6). | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation with PFTs | The secondary objective of this study is to correlate the results with PFTs, including spirometry and plethysmography. | 2 years |