Hyperpolarized 129Xe MRI for Imaging Pulmonary Function

Non-invasive imaging of pulmonary function is expected to provide critical insights that are
needed to spur progress in characterizing and treating chronic pulmonary diseases. The
current primary diagnostic measure is pulmonary function testing (PFT), which was introduced
in the mid-19th century, yet remains the standard of care today. PFTs have the advantage of
being non-invasive and widely available, but suffer from poor sensitivity and high
variability. Thus, PFTs are ineffective in assessing therapeutic response or disease
progression on reasonable time scales, given the frequent heterogeneity of disease and the
lung's compensatory mechanisms.

It has long been appreciated that improving sensitivity requires assessing the lungs
regionally. To this end, methods, such as computed tomography (CT), provide insights into
lung structure, but lung function must be inferred. However, of greater concern is the high
radiation dose associated with CT, which precludes frequent longitudinal follow-up imaging.
Alternatively, regional imaging of both ventilation and perfusion is possible using nuclear
medicine techniques such as planar scintigraphy, single photon computed tomography (SPECT),
or positron emission tomography (PET). However, as with CT imaging, all these modalities
expose the subject to ionizing radiation and cannot be applied serially without a compelling
clinical need. Moreover, these nuclear imaging modalities suffer from poor spatial and
temporal resolution.

The key role for HP 129Xe MRI is that it can enable non-invasive high-resolution imaging of
all aspects of pulmonary structure and function. We have recently shown HP 129Xe MRI to
visualize pulmonary ventilation with high resolution, as well as the ability to show
abnormalities of the alveolar microstructure that are associated with the emphysema phenotype
of COPD. We have also demonstrated the fundamentally new capability to directly visualize the
uptake of 129Xe into the pulmonary capillary blood and tissues, which can provide an even
more complete picture of pulmonary function by supplying regional gas exchange information.

Xenon is a noble gas that is not chemically altered by the body. A small fraction of the
inhaled Xe is absorbed into the blood stream and has documented anesthetic effects at
moderate concentrations. The levels of gas used in this protocol are within the previously
derived safe limits for both animals and humans. The stable isotope 129Xe can be
hyperpolarized, which is a means to enhance its gross MRI signal by a factor of ∼100,000.
Such signal enhancement makes it possible to image the inhaled gas with high spatial and
temporal resolution. Moreover, the properties of 129Xe enable images to be acquired with
multiple forms of contrast including ventilation, lung microstructure, and regional gas
exchange. Because 129Xe MRI uses no ionizing radiation, and only an inhaled gas contrast
agent, it has the potential to be used in longitudinal studies to test the effects of therapy
or monitor progression of disease noninvasively.

Inclusion Criteria:

Inclusion Criteria for Healthy Control Subjects

1. Subject has no diagnosed pulmonary conditions

2. Subject has not smoked in the previous 5 years.

3. Smoking history, if any, is less than or equal to 5 pack-years.

Inclusion Criteria for Subjects with lung disease

1. Subject has a diagnosis of pulmonary dysfunction made by a physician

2. No acute worsening of pulmonary function in the past 30 days

Exclusion Criteria:

1. Subject is less than 18 years old

2. MRI is contraindicated based on responses to MRI screening questionaire

3. Subject is pregnant or lactating

4. Respiratory illness of a bacterial or viral etiology within 30 days of MRI

5. Subject has received an investigational medicinal product (not including 129Xe) within
30 days of MRI

6. Subject has any form of known cardiac arrhythmia

7. Subject does not fit into 129Xe vest coil used for MRI

8. Subject cannot hold his/her breath for 15 seconds

9. Subject deemed unlikely to be able to comply with instructions during imaging