Hyperpolarized 129Xe MRI for Imaging Pulmonary Function

Sponsor

Bastiaan Driehuys (Other)

Overall Status

Recruiting

CT.gov ID

NCT01280994

Collaborator

(none)

445

Enrollment

Location

143

Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to develop and evaluate the usefulness of MRI using 129Xe gas for regional assessment of pulmonary function. Specifically, three forms of 129Xe MRI contrast will be the investigators focus - 1) imaging of the 129Xe ventilation distribution, 2) imaging the alveolar microstructure via the 129Xe apparent diffusion coefficient (ADC), and 3) imaging 129Xe that dissolves in the pulmonary blood and tissues upon inhalation. Such imaging of 129Xe gas transfer is expected to be uniquely sensitive to pathologies affecting gas exchange (fibrosis, emphysema, pulmonary hypertension) and provide new insights regarding the normal resting heterogeneity of pulmonary gas exchange.

Condition or Disease	Intervention/Treatment	Phase
Interstitial Lung Disease	Drug: Hyperpolarized 129Xenon Gas	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

445 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Hyperpolarized 129Xe MR Imaging of the Lung Function in Healthy Volunteers and Subjects With Pulmonary Disease

Study Start Date :

Jan 1, 2011

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Outcome Measures

Primary Outcome Measures

Number of Participants with Adverse Events as a Measure of Safety and Tolerability [5 years]
The purpose of this trial is to examine the ability of HP 129Xe imaging to characterize the lung in healthy and diseased states. The safety endpoint for each subject is to record any adverse events as a measure of safety and tolerability. The technical endpoint for each subject is the acquisition of technically adequate HP 129Xe MR images.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Inclusion Criteria for Healthy Control Subjects

Subject has no diagnosed pulmonary conditions
Subject has not smoked in the previous 5 years.
Smoking history, if any, is less than or equal to 5 pack-years.

Inclusion Criteria for Subjects with lung disease

Subject has a diagnosis of pulmonary dysfunction made by a physician
No acute worsening of pulmonary function in the past 30 days

Exclusion Criteria:

Subject is less than 18 years old
MRI is contraindicated based on responses to MRI screening questionaire
Subject is pregnant or lactating
Respiratory illness of a bacterial or viral etiology within 30 days of MRI
Subject has received an investigational medicinal product (not including 129Xe) within 30 days of MRI
Subject has any form of known cardiac arrhythmia
Subject does not fit into 129Xe vest coil used for MRI
Subject cannot hold his/her breath for 15 seconds
Subject deemed unlikely to be able to comply with instructions during imaging