? Historically, lung ventilation has been difficult to image. Although other imaging modalities provide insight into airway anatomy and reactivity (e.g., MDCT) or ventilation (e.g., dynamic CT, radio-nuclear imaging including PET), to date only CT can combine a view of both structure and function. However, the associated radiation, particularly in children, is driving a search for alternative methodologies. The unique work of our group forms an essential part of this effort to limit radiation exposure while improving our ability to depict the structural and functional mechanics of lung ventilation. To this end, we propose to establish HP 3He MRI as a clinically safe imaging modality that enables us to visualize ventilation function and airway constriction. However, a number of challenges regarding our ability to quantitate structure and function using this modality remain. As imaging moves into the arena of quantitative regional functional assessment of the lung, our drive to establish HP 3He MRI as an acceptable alternative or as a complimentary modality to current CT technologies could not be better timed. ? ? We further propose to combine HP 3He MRI with sensitive measures of airway function to determine the specific constriction conditions associated with asthma. We will test the hypothesis that HP 3He MRI provides similar airway resolution to MDCT, as well as additional functional ventilation information. This will entail 1) optimizing our current dynamic HP 3He MRI methodology to obtain high-resolution images of the airways; 2) developing both airway and ventilation quantification methods for the HP 3He MR images; 3) calculating HP 3He MRI airway diameters for both healthy and asthmatic subjects; and 4) comparing these measurements to those obtained from MDCT lung imaging and 3D airway reconstruction. We will then test the hypothesis that airway constriction in asthmatics is highly heterogeneous and is primarily characterized by airway closures in the small airways, and that airway dilation during a deep inspiration is diminished with increased asthma severity. ? ? Specifically, we will systematically investigate the distinctive nature of pulmonary airway narrowing and expansion in healthy versus asthmatic lungs both pre- and post-methacholine challenge using hyperpolarized (HP) 3He MRI and, as an overarching objective, discern its implication for the diagnosis and treatment of asthma. We will also investigate the frequency dependence of dynamic lung resistance and elastance and calculate the airway resistance during both normal breathing and a deep inspiration. Finally, we will correlate structural defects in airway constriction and ventilation with functional defects. ? ? At a minimum, successful proof-of-concept will establish HP 3He MRI as an important complement to MDCT. Indeed, by offering both functional information as well as a degree of airway resolution comparable to MDCT, all without the need for radiation exposure, we are confident the use HP 3He MRI will ultimately lead to improved asthma management across the spectrum--from diagnosis to treatment to enhanced quality of life. ? ?

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Exploratory/Developmental Grants Phase II (R33)
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Special Emphasis Panel (ZCA1-SRRB-9 (J2))
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Mclaughlin, Alan Charles
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University of Massachusetts Medical School Worcester
Schools of Medicine
United States
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Walvick, Ronn P; Roche, John P; Reno, Austin L et al. (2016) Evaluation of oxygen sensitivity of hyperpolarized helium imaging for the detection of pulmonary ischemia. Magn Reson Med 75:2050-4
Sun, Yanping; Butler, James P; Ferrigno, Massimo et al. (2013) ""Ventilatory alternans"": a left-right alternation of inspiratory airflow in humans. Respir Physiol Neurobiol 185:468-71
Mullally, William; Betke, Margrit; Albert, Mitchell et al. (2009) Explaining clustered ventilation defects via a minimal number of airway closure locations. Ann Biomed Eng 37:286-300
Sun, Yanping; Butler, James P; Lindholm, Peter et al. (2009) Marked pericardial inhomogeneity of specific ventilation at total lung capacity and beyond. Respir Physiol Neurobiol 169:44-9
Tzeng, Yang-Sheng; Hoffman, Eric; Cook-Granroth, Janice et al. (2008) Investigation of hyperpolarized 3He magnetic resonance imaging utility in examining human airway diameter behavior in asthma through comparison with high-resolution computed tomography. Acad Radiol 15:799-808
Tzeng, Yang-Sheng; Hoffman, Eric; Cook-Granroth, Janice et al. (2007) Comparison of airway diameter measurements from an anthropomorphic airway tree phantom using hyperpolarized 3He MRI and high-resolution computed tomography. Magn Reson Med 58:636-42
Bates, Jason H T; Lutchen, Kenneth R (2005) The interface between measurement and modeling of peripheral lung mechanics. Respir Physiol Neurobiol 148:153-64