This proposal supports the creation of the infrastructure required for robust and safe pulmonary magnetic resonance imaging (MRI) in the pediatric patient population. Pediatric lung disease is challenging to evaluate and treat because existing tools for measuring disease severity are inadequate. Spirometry, including infant pulmonary function tests (PFTs), has been shown to be inadequate for the assessment of mild lung disease, especially in cystic fibrosis (CF) where X-ray CT and chest radiography have played an increasing role despite their use of ionizing radiation. Bronchopulmonary dysplasia (BPD), also diagnosed based on abnormal radiographic findings is a disease of prematurity, affecting at least 30% of babies born before 32 weeks with birth weights <1000g. In animal models of BPD, alveolarization and vascularization of the lung is arrested, resulting in poorly organized gas exchange units. However, non-invasive assessment of underlying structural and functional changes in BPD and other early lung diseases is not easily performed without using X-ray or radionuclide-based imaging methods that have limited sensitivity and spatial resolution. Childhood asthma is another, more prevalent disease, for which conventional lung function tests are insensitive due to the child's difficulty performing the necessary respiratory maneuvers and their insensitivity to early disease progression. Recent advances in pulmonary MRI have enabled functional imaging of ventilation in childhood asthma using novel fast MRI methods during single bolus delivery of hyperpolarized 3He gas, an inert noble gas of limited supply. Similar advances using 129Xe, a trace gas in the atmosphere, have been applied to lung MRI in adult asthma and COPD and promise a more widely available alternative to 3He. In addition, advances in radial MRI have markedly improved water proton signal from lung structures not previously detected to visualize parenchymal and airway structures and tissue perfusion. Thus, for the first time a clinically viable MRI protocol capable of imaging lung structure and function s available. The overall goal of this proposal is to translate this protocol into the clinic for reserch and validation in pediatric lung diseases.
The Specific Aims of the proposal are: 1. To develop the clinical infrastructure for pediatric lung MRI in the University of Wisconsin Department of Radiology inclusive of upgraded hardware on a new MR750w for multi- nuclear spectroscopy with 8 receiver channels, a cost and time-efficient commercial 129Xe gas polarizer to enable safe production and administration of gas, and a pediatric chest RF-coil designed for imaging both water protons and 129Xe gas under free breathing conditions for structure-function comparison, and 2. To apply ventilation/perfusion MRI to clinical research investigations of early disease in asthma, CF, and BPD, while supporting ongoing studies of adult lung disease and expansion to new opportunities.
|Zha, Wei; Kruger, Stanley J; Cadman, Robert V et al. (2018) Regional Heterogeneity of Lobar Ventilation in Asthma Using Hyperpolarized Helium-3 MRI. Acad Radiol 25:169-178|
|Mummy, David G; Kruger, Stanley J; Zha, Wei et al. (2018) Ventilation defect percent in helium-3 magnetic resonance imaging as a biomarker of severe outcomes in asthma. J Allergy Clin Immunol 141:1140-1141.e4|
|Hahn, Andrew D; Kammerman, Jeff; Fain, Sean B (2018) Removal of hyperpolarized 129 Xe gas-phase contamination in spectroscopic imaging of the lungs. Magn Reson Med 80:2586-2597|
|Shim, Sung Shine; Schiebler, Mark L; Evans, Michael D et al. (2018) Lumen area change (Delta Lumen) between inspiratory and expiratory multidetector computed tomography as a measure of severe outcomes in asthmatic patients. J Allergy Clin Immunol 142:1773-1780.e9|
|Zha, Wei; Kruger, Stanley J; Johnson, Kevin M et al. (2018) Pulmonary ventilation imaging in asthma and cystic fibrosis using oxygen-enhanced 3D radial ultrashort echo time MRI. J Magn Reson Imaging 47:1287-1297|
|Ebner, Lukas; Kammerman, Jeff; Driehuys, Bastiaan et al. (2017) The role of hyperpolarized 129xenon in MR imaging of pulmonary function. Eur J Radiol 86:343-352|
|Hahn, Andrew D; Higano, Nara S; Walkup, Laura L et al. (2017) Pulmonary MRI of neonates in the intensive care unit using 3D ultrashort echo time and a small footprint MRI system. J Magn Reson Imaging 45:463-471|
|Adamson, Erin B; Ludwig, Kai D; Mummy, David G et al. (2017) Magnetic resonance imaging with hyperpolarized agents: methods and applications. Phys Med Biol 62:R81-R123|
|Kruger, Stanley J; Nagle, Scott K; Couch, Marcus J et al. (2016) Functional imaging of the lungs with gas agents. J Magn Reson Imaging 43:295-315|