MagniXene MRI Use in Patients With Asthma and COPD to Assess Regional Lung Function by Delineating Ventilation Defects

HXe MRI provides a diversity of imaging techniques for interrogating pulmonary function and
lung microstructure. The most mature of these techniques utilizes HXe spin-density MRI to
depict regional lung ventilation. Prior work suggests that ventilation imaging has utility
in all obstructive lung diseases. This is a Phase II clinical trial to assess HXe MRI
capability of providing qualitative and quantitative clinical information regarding lung
ventilation. Proton and xenon images will be acquired within single breath holds on 28
subjects per year, including healthy volunteers and patients with COPD and asthma. All
studies will include repeat scans and Pulmonary Function Tests (PFT). Ventilation scans with
Technetium-99m (Tc-99m) diethylene-triamine-pentaacetate (DTPA) aerosol scintigraphy will be
acquired on lung patients.

The primary goal of this aim is to validate the effectiveness of HXe ventilation MRI for
delineating regions of normal and abnormal lung ventilation. To validate the regional
depiction of ventilation, HXe MRI ventilation will be compared with nuclear medicine Tc-99m
DTPA ventilation scintigraphy. The comparatively low spatial and temporal resolution of
ventilation scintigraphy will limit this study to demonstrating only that HXe MRI
ventilation is not inferior to the current clinical standard. Additionally, the concordance
between measurements of the whole lung volume from both proton MRI and HXe MRI with PFT, the
current clinical standard for lung volume measurement, will be assessed as a secondary
outcome of the study.

Inclusion Criteria (healthy subjects):

- Currently feeling well without respiratory symptoms.

- No history of lung disease.

- Never personally smoked (defined as less 100 cigarettes in their lifetime).

Inclusion Criteria (COPD subjects):

- Forced Expiratory Volume in 1 second (FEV1)<80% predicted OR FEV1 to Forced Vital
Capacity (FVC) ratio <70%

- Smoking history >10 pack years

- Subjects should be at their clinical baseline on the day of imaging

- Subjects must be clinically stable in order to participate in the study

Inclusion Criteria (asthma subjects):

- Greater than 10% increase in FEV1 30-50 minutes after administration of albuterol;

- Subjects should be at their clinical baseline on the day of imaging;

- Subjects must be clinically stable in order to participate in the study.

Exclusion Criteria:

- Baseline oxygen requirement.

- Blood oxygen saturation of 92% less than as measured by pulse oximetry on the day of
imaging.

- FEV1 percent predicted less than 25%.

- Pregnancy or lactation.

- Claustrophobia, inner ear implants, aneurysm or other surgical clips, metal foreign
bodies in eye, pacemaker or other contraindication to MR scanning. Subjects with any
implanted device that cannot be verified as MRI compliant will be excluded.

- Chest circumference greater than that of the xenon MR coil.

- History of congenital cardiac disease, chronic renal failure, or cirrhosis.

- Inability to understand simple instructions or to hold still for approximately 10
seconds.

- History of respiratory infection within 2 weeks prior to the MR scan.

- History of heart attack, stroke and/or poorly controlled hypertension.

- Known hypersensitivity to albuterol or any of its components, or levalbuterol.