A Prospective, Cohort Study of Hyperpolarized 3He MRI in Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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The purpose of this study is to determine the MRI characteristics of Chronic Obstructive Pulmonary Disease subjects both at baseline and yearly for a period of 5 years, and to correlate these biomarkers with pulmonary function tests, CT scan, 6 Minute-walk tests, and respiratory questionnaires. The central hypothesis is that quantitative assessment of the lung through magnetic resonance imaging of hyperpolarized 3He can detect early alterations in structure and function which are precursors to clinically apparent COPD and that these precursors can be used to predict progression of disease earlier and better than established clinical methods. Novel assessments using 3He MRI will lead to new information about COPD and will be critical for characterizing disease response to therapy. A secondary hypothesis is that a variety of technical improvements in the techniques of hyperpolarized gas MRI will accelerate the translation of this relatively new modality to clinical use.

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: Hyperpolarized Helium-3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent was obtained and documented (after the investigator has given oral and written information about the study to the subject). The subject was conscious, co-operative, and agreed to return for the scheduled visits and tests and any visits required to obtain additional safety information. The subject's medical history, physical examination (including vital signs, pulse oximetry, PFT's, and 12-lead electrocardiogram [ECG]), and clinical laboratory tests (hematology, serum chemistry) obtained at the screening visit were within acceptable limits for entry into the study, as judged by the investigator. Exclusion Criteria: Subject is <40 or >70 years old Subject known to be pregnant Subject with a baseline oxygen requirement > 2 l/min via nasal cannula Any known contraindication to MRI examination Inability to provide informed consent A language, communication, cognitive or behavioral impairment that might interfere with fully informed consent Active drug or alcohol dependence Homelessness or other unstable living situation Active drug or alcohol dependence Significant co-morbidities such as heart disease, kidney disease, liver disease, hematologic or neurological disease that require continuing treatment.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy non-smokers<br>Hyperpolarized Helium-3. Amounts adjusted based on subject's total lung capacity | Drug: Hyperpolarized Helium-3<br> <br> |
| Asymptomatic smokers<br>Hyperpolarized Helium-3. Amounts adjusted based on subject's total lung capacity | Drug: Hyperpolarized Helium-3<br> <br> |
| COPD subjects<br>Hyperpolarized Helium-3. Amounts adjusted based on subject's total lung capacity | Drug: Hyperpolarized Helium-3<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Smoking-Induced Alterations in the Regional Alveolar Oxygen Tension Heterogeneity [Torr] in Smokers Compared to Healthy Controls and COPD Subjects | To measure the specificity and sensitivity of Regional Alveolar Oxygen Tension Heterogeneity in differentiation of healthy smokers from healthy nonsmokers and COPDs | 2 years from baseline (+- 2 months) | 
| Smoking-Induced Alterations in the Apparent Diffusion Coefficient [cm^2/s] in Smokers Compared to Healthy Controls and COPD Subjects | To measure the specificity and sensitivity of Apparent Diffusion Coefficient in differentiation of healthy smokers from healthy nonsmokers and COPDs | 2 years from baseline (+- 2 months) | 
| Smoking-Induced Alterations in the Specific Ventilation [unitless] in Smokers Compared to Healthy Controls and COPD Subjects | To measure the specificity and sensitivity of Specific Ventilation in differentiation of healthy smokers from healthy nonsmokers and COPDs | 2 years from baseline (+- 2 months) |