Chronic obstructive pulmonary disease (COPD) is an increasingly urgent public health concern on both the national and global levels. Not only is the disorder a major cause of mortality, but the dyspnea, reduced capacity for physical exertion, and periodic exacerbations that it causes result in tremendous disability and cost. Treatment options for established COPD remain limited in number, diversity, and effectiveness. However, in recent years, significant innovation has been accomplished in the field of lung volume reduction (LVR), which seeks to enhance global lung function through the removal, occlusion, or obliteration of hyperinflated, emphysematous regions. While LVR has traditionally been implemented through surgical resection, the development of less invasive bronchoscopic techniques (BLVR) is ongoing and represents an extremely promising arena of COPD therapy. This application proposes to develop a hyperpolarized 129Xe magnetic resonance imaging (HP 129Xe MRI) approach for planning BLVR intervention and assessing its pulmonary effects. The core problem faced by all LVR approaches is that they have demonstrated highly variable outcomes; it consequently remains unclear exactly what types of patient will benefit most from this therapy and why. Clinicians currently base their decisions of whether to carry out LVR and which regions to target using high-resolution computed tomography (HRCT) to measure the extent of emphysema and its distribution. While HRCT is highly capable of accurately assessing these features, it does not provide the functional information necessary to gain a comprehensive understanding of an individual patient's regional pulmonary status. We thus posit that the incorporation of functional parameters obtained with HP 129Xe MRI will allow for more informed decision-making in regards to which patients should undergo LVR and how the procedure should be tailored according to the lung health of the particular patient. In applying HP 129Xe MRI to this medical area of need, a corollary goal will be achieved: the refinement of this hyperpolarized technique such that it can extract pulmonary information with the sensitivity of the more well-established HP 3He MRI approach. 3He has become drastically more expensive in recent years due to its scarcity, and the hyperpolarized community recognizes that a shift to the much less expensive and more easily obtainable 129Xe is necessary to ensure the translational applicability of this important technology. We seek here to use Xe to derive three lung parameters-specific ventilation (SV), alveolar oxygen tension (pAO2), 129 and apparent diffusion coefficient (ADC)-with approximately the same sensitivity and efficiency that we have previously attained using 3He. This development will enhance the clinical future of hyperpolarized MRI not only in the area of LVR, but also in the non-invasive assessment of COPD and lung diseases more broadly.

Public Health Relevance

The proposed project applies hyperpolarized 129Xe magnetic resonance imaging (HP 129Xe MRI) to the planning and evaluation of bronchoscopic lung volume reduction (BLVR). BLVR is a rapidly developing approach for the treatment of advanced chronic obstructive pulmonary disease (COPD) that enhances lung performance through eliminating poorly functioning tissue. HP 129Xe MRI provides several parameters of regional pulmonary function that can better inform decisions on when and how to perform BLVR.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL129805-04
Application #
9676911
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Punturieri, Antonello
Project Start
2016-03-01
Project End
2021-02-28
Budget Start
2019-03-01
Budget End
2021-02-28
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Ruppert, Kai; Amzajerdian, Faraz; Hamedani, Hooman et al. (2018) Assessment of flip angle-TR equivalence for standardized dissolved-phase imaging of the lung with hyperpolarized 129Xe MRI. Magn Reson Med :
Ruppert, Kai; Hamedani, Hooman; Amzajerdian, Faraz et al. (2018) Assessment of Pulmonary Gas Transport in Rabbits Using Hyperpolarized Xenon-129 Magnetic Resonance Imaging. Sci Rep 8:7310
Ruppert, Kai; Amzajerdian, Faraz; Hamedani, Hooman et al. (2018) Rapid assessment of pulmonary gas transport with hyperpolarized 129Xe MRI using a 3D radial double golden-means acquisition with variable flip angles. Magn Reson Med 80:2439-2448
Xin, Yi; Cereda, Maurizio; Kadlecek, Stephen et al. (2017) Hyperpolarized gas diffusion MRI of biphasic lung inflation in short- and long-term emphysema models. Am J Physiol Lung Cell Mol Physiol 313:L305-L312