19F MRI to Evaluate Regional Ventilation in Healthy Subjects and Subjects With Cystic Fibrosis

The goal of this study is to evaluate the ability of conventional 'thermally' polarized
perfluorinated gases (19F) mixed with oxygen to detect changes in ventilation using magnetic
resonance imaging (MRI). A secondary goal is to assess the repeatability and the
within-subject variability of these findings in CF lung disease. This is an open label pilot
study expanding on work by other investigators currently using this technique in human
subjects. Projection images using controlled breathing techniques will be obtained using 19F
MRI, correlating spirometric variables with regional distribution of the gases.

Inclusion Criteria for Healthy Participants:

- Non-smokers (<10 pack-year history, and no active smoking in last 1 year);

- No evidence of prior lung disease or lung injury by medical history, physical exam,
and/or spirometry testing;

- Evidence of a personally signed and dated informed consent document indicating that
the subject has been informed of all pertinent aspects of the trial.

- Participants must be willing and able to comply with scheduled visits and other trial
procedures.

Exclusion Criteria for Healthy Participants:

- Active or past smokers with less than 1 years since quitting or >10 pack-year smoking
history

- Unable to undergo a 3.0-Tesla MRI exam of the lungs and chest because of
contraindications including

1. Occupation (past or present) of machiner, welder, grinder;

2. Injury to the eye involving a metallic object

3. Injury to the body by a metallic object (bullet, BB, shrapnel)

4. Presence of a cardiac pacemaker or defibrillator

5. Presence of aneurysm clips

6. Presence of carotid artery vascular clamp

7. Presence of neurostimulator

8. Presence of insulin or infusion pump

9. Presence of implanted drug infusion device that is not known to be MRI compatible
(i.e., was placed outside of UNCH or is older than 10 years)

10. Bone growth or fusion simulator

11. Presence of cochlear, otologic or ear implant

12. Any type of prosthesis (eye, penile, etc.)

13. Artificial limb or joint

14. Non-removable electrodes (on body, head or brain)

15. Intravascular stents, filters or coils

16. Shunt (spinal or intraventricular)

17. Swan-ganz catheter

18. Any implant held in place by a magnet

19. Transdermal delivery system (e.g. Nitro)

20. IUD or diaphragm

21. Tattooed makeup (eyeliner, lips, etc.) or tattoos covering >25% of body surface
area

22. Body piercings (MUST BE REMOVED BEFORE MRI)

23. Any metal fragments

24. Internal pacing wires

25. Metal or wire mesh implants

26. Hearing aid (REMOVE BEFORE MRI) aa. Dentures (REMOVE BEFORE MRI) bb.
Claustrophobia

- Unable to tolerate inhalation of gas mixture

- Participation in a clinical trial with a study drug that may impact lung function in
the past 14 days

- Other severe acute or chronic medical or psychiatric condition or clinical laboratory
abnormality that may increase the risk associated with trial participation or may
interfere with the interpretation of trial results and, in the judgment of the
investigator, would make the participant inappropriate for entry into this trial.

- Pregnancy: women of childbearing potential must have a confirmed negative urine
pregnancy test on the day of the MR scan, prior to the MRI scan.

Inclusion Criteria for CF Participants:

- Non-smokers (<10 pack year history and no active smoking in the past year;

- Diagnosis of cystic fibrosis as via standard sweat chloride/phenotypic
features/genotyping

- Stable lung disease as evidenced by no change in respiratory medications or change in
FEV1 of >15% from baseline over the preceding 4 weeks prior to enrollment

- Baseline FEV1 >30% of predicted. Roughly equivalent numbers of CF subjects with mild
FEV1 >80% of predicted), moderate (FEV1 50-80% of predicted) and severe (FEV1 <50% of
predicted) will be targeted for enrollment.

- No use of supplemental oxygen

- Evidence of a personally signed and dated informed consent document indicating that
the subject has been informed of all pertinent aspects of the trial.

- Participants must be willing and able to comply with scheduled visits and other trial
procedures.

Exclusion Criteria for CF Participants:

- Active or past smokers with less than 1 years since quitting or >10 pack-year smoking
history

- Active asthma flare, as perceived by the study physician or unstable asthma
characterized by advancement of asthma therapy in the last month or two courses of
oral steroids in the past six months.

- Unable to undergo a 3.0-Tesla MRI exam of the lungs and chest because of
contraindications including

1. Occupation (past or present) of machiner, welder, grinder;

2. Injury to the eye involving a metallic object

3. Injury to the body by a metallic object (bullet, BB, shrapnel)

4. Presence of a cardiac pacemaker or defibrillator

5. Presence of aneurysm clips

6. Presence of carotid artery vascular clamp

7. Presence of neurostimulator

8. Presence of insulin or infusion pump

9. Presence of implanted drug infusion device that is not known to be MRI compatible
(i.e., was placed outside of UNCH or is older than 10 years)

10. Bone growth or fusion simulator

11. Presence of cochlear, otologic or ear implant

12. Any type of prosthesis (eye, penile, etc.)

13. Artificial limb or joint

14. Non-removable electrodes (on body, head or brain)

15. Intravascular stents, filters or coils

16. Shunt (spinal or intraventricular)

17. Swan-ganz catheter

18. Any implant held in place by a magnet

19. Transdermal delivery system (e.g. Nitro)

20. IUD or diaphragm

21. Tattooed makeup (eyeliner, lips, etc.) or tattoos covering >25% of body surface
area

22. Body piercings (MUST BE REMOVED BEFORE MRI)

23. Any metal fragments

24. Internal pacing wires

25. Metal or wire mesh implants

26. Hearing aid (REMOVE BEFORE MRI) aa. Dentures (REMOVE BEFORE MRI) bb.
Claustrophobia

- Unable to tolerate inhalation of gas mixture

- Participation in a clinical trial with a study drug that may impact lung function in
the past 14 days

- Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with trial participation or may
interfere with the interpretation of trial results and, in the judgment of the
investigator, would make the participant inappropriate for entry into this trial.

- Pregnancy; women of childbearing potential must have a confirmed negative urine
pregnancy test on the day of the MR scan, prior to the MRI scan.