The difference in ventilation heterogeneity between asthmatic and healthy subjects quantified using hyperpolarized 3He MRI.

In this pilot study, algorithms for quantitatively evaluating the distribution and heterogeneity of human ventilation imaged with hyperpolarized (HP) (3)He MRI were developed for the goal of examining structure-function relationships within the asthmatic lung. Ten asthmatic and six healthy human subjects were imaged with HP (3)He MRI before bronchial challenge (pre-MCh), after bronchial challenge (post-MCh), and after a series of deep inspirations (post-DI) following challenge. The acquired images were rigidly coregistered. Local voxel fractional ventilation was computed by setting the sum of the pixel intensity within the lung region in each image to 1 liter of inhaled (3)He mixture. Local ventilation heterogeneity was quantified by computing regional signal coefficient of variation. Voxel fractional ventilation histograms and overall heterogeneity scores were then calculated. Asthmatic subjects had a higher ventilation heterogeneity to begin with (P = 0.025). A methacholine challenge elevated ventilation heterogeneity for all subjects (difference: P = 0.08). After a DI postchallenge, this heterogeneity reversed substantially toward the baseline state for healthy subjects but only minimally in asthmatic subjects. This difference was significant in absolute quantity (difference: P = 0.007) as well as relative to the initial increase (difference: P = 0.03). These findings suggest that constriction heterogeneity is not a characteristic unique to asthmatic airway trees but rather a behavior intrinsic to all airway trees when provoked. Once ventilation heterogeneity is established, it is the lack of reversal following DIs that distinguishes asthmatics from non-asthmatics.

[1]  J R Brookeman,et al.  Lung air spaces: MR imaging evaluation with hyperpolarized 3He gas. , 1999, Radiology.

[2]  M. Krueger,et al.  The spatial and temporal heterogeneity of regional ventilation: Comparison of measurements by two high-resolution methods , 2005, Respiratory Physiology & Neurobiology.

[3]  S M Mijailovich,et al.  Effects of lung motion and tracer kinetics corrections on PET imaging of pulmonary function. , 1997, Journal of applied physiology.

[4]  S. Lewis,et al.  Continuous distributions of specific ventilation recovered from inert gas washout. , 1978, Journal of applied physiology: respiratory, environmental and exercise physiology.

[5]  J. Kramer-Johansen,et al.  Distribution of pulmonary ventilation and perfusion measured simultaneously in awake goats. , 1997, Acta physiologica Scandinavica.

[6]  A Potthast,et al.  Normal and abnormal pulmonary ventilation: visualization at hyperpolarized He-3 MR imaging. , 1996, Radiology.

[7]  G. Johnson,et al.  Dynamic lung morphology of methacholine‐induced heterogeneous bronchoconstriction , 2004, Magnetic resonance in medicine.

[8]  M Salerno,et al.  Hyperpolarized noble gas MR imaging of the lung: potential clinical applications. , 2001, European journal of radiology.

[9]  J. Fish,et al.  Regulation of bronchomotor tone by lung inflation in asthmatic and nonasthmatic subjects. , 1981, Journal of applied physiology: respiratory, environmental and exercise physiology.

[10]  A. Forchel,et al.  Experimental and theoretical study of strain-induced AlGaAs/GaAs quantum dots using a self-organized GaSb island as a stressor , 1999 .

[11]  K. Horsfield,et al.  Morphology of the bronchial tree in man. , 1968, Journal of applied physiology.

[12]  M Paiva,et al.  Model simulations of gas mixing and ventilation distribution in the human lung. , 1990, Journal of applied physiology.

[13]  R. Pellegrino,et al.  Airway responsiveness to methacholine: effects of deep inhalations and airway inflammation. , 1999, Journal of applied physiology.

[14]  J. Venegas,et al.  Regional mapping of gas transport during high-frequency and conventional ventilation. , 1989, Journal of applied physiology.

[15]  R. Rizi,et al.  Hyperpolarized 3He MRI in asthma measurements of regional ventilation following allergic sensitization and challenge in mice--preliminary results. , 2005, Academic radiology.

[16]  H. Kauczor,et al.  3He MRI in healthy volunteers: preliminary correlation with smoking history and lung volumes , 2000, NMR in biomedicine.

[17]  R W Glenny,et al.  High-resolution maps of regional ventilation utilizing inhaled fluorescent microspheres. , 1997, Journal of applied physiology.

[18]  Robb W. Glenny,et al.  Physiological Implications of the Fractal Distribution of Ventilation and Perfusion in the Lung , 2000, Annals of Biomedical Engineering.

[19]  Peter Magnusson,et al.  Quantitative measurement of regional lung ventilation using 3He MRI , 2002, Magnetic resonance in medicine.

[20]  K. Beck,et al.  Contributions of ventilation and perfusion inhomogeneities to the VA/Q distribution. , 1992, Journal of applied physiology.

[21]  B. Bake,et al.  Quantitative analysis of inhomogeneity in ventilation SPET , 2001, European Journal of Nuclear Medicine.

[22]  Jiangsheng Yu,et al.  Measurements of regional alveolar oxygen pressure using hyperpolarized 3He MRI. , 2005, Academic radiology.

[23]  A. Togias,et al.  Airway hyperresponsiveness in asthma: a problem of limited smooth muscle relaxation with inspiration. , 1995, The Journal of clinical investigation.

[24]  J. Hankinson,et al.  Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. , 2000, American journal of respiratory and critical care medicine.

[25]  R. Rizi,et al.  Single‐acquisition sequence for the measurement of oxygen partial pressure by hyperpolarized gas MRI , 2004, Magnetic resonance in medicine.

[26]  E. V. van Beek,et al.  Assessment and compensation of susceptibility artifacts in gradient echo MRI of hyperpolarized 3He gas , 2003, Magnetic resonance in medicine.

[27]  John P Mugler,et al.  Evaluation of asthma with hyperpolarized helium-3 MRI: correlation with clinical severity and spirometry. , 2006, Chest.

[28]  A. C. Young,et al.  Emptying pattern of lung compartments in normal man. , 1972, Journal of applied physiology.

[29]  R. Henkelman Measurement of signal intensities in the presence of noise in MR images. , 1985, Medical physics.

[30]  David W. Kaczka,et al.  Optimal ventilation waveforms for estimating low-frequency respiratory impedance. , 1993, Journal of applied physiology.

[31]  Alfred O. Berg,et al.  Clinical Guidelines And Primary Care Guidelines For The Diagnosis And Management Of Asthma , 2012 .

[32]  K. Lutchen,et al.  Airway remodeling in asthma amplifies heterogeneities in smooth muscle shortening causing hyperresponsiveness. , 1999, Journal of applied physiology.

[33]  E. Miron,et al.  Polarization of the nuclear spins of noble-gas atoms by spin exchange with optically pumped alkali-metal atoms , 1984 .

[34]  G. Guillot,et al.  Magnetic susceptibility matching at the air–tissue interface in rat lung by using a superparamagnetic intravascular contrast agent: Influence on transverse relaxation time of hyperpolarized helium‐3 , 2005, Magnetic resonance in medicine.

[35]  K. Finucane,et al.  Pulmonary conductance and elastic recoil relationships in asthma and emphysema. , 1973, Journal of applied physiology.

[36]  M. Lannoo,et al.  Calculation of the transverse acoustoelectric voltage in a piezoelectric-extrinsic semiconductor structure , 1989 .

[37]  B. Simon,et al.  Distribution of pulmonary ventilation using Xe-enhanced computed tomography in prone and supine dogs. , 2001, Journal of applied physiology.

[38]  Hans M. Hertz,et al.  Ultrasonic trapping in capillaries for trace-amount biomedical analysis , 2001 .

[39]  R. Glenny,et al.  Regional ventilation-perfusion distribution is more uniform in the prone position. , 2000, Journal of applied physiology.

[40]  Middleton,et al.  Nuclear relaxation of 3He in the presence of O2. , 1995, Physical review. A, Atomic, molecular, and optical physics.

[41]  T A Altes,et al.  Hyperpolarized 3He MR lung ventilation imaging in asthmatics: Preliminary findings , 2001, Journal of magnetic resonance imaging : JMRI.

[42]  John P Mugler,et al.  Imaging the lungs in asthmatic patients by using hyperpolarized helium-3 magnetic resonance: assessment of response to methacholine and exercise challenge. , 2003, The Journal of allergy and clinical immunology.

[43]  R. Glenny,et al.  Gravity is a minor determinant of pulmonary blood flow distribution. , 1991, Journal of applied physiology.

[44]  H. Kauczor,et al.  3He‐MRI‐based measurements of intrapulmonary p O2 and its time course during apnea in healthy volunteers: first results, reproducibility, and technical limitations , 2000, NMR in biomedicine.

[45]  K. Lutchen,et al.  Relationship between heterogeneous changes in airway morphometry and lung resistance and elastance. , 1997, Journal of applied physiology.

[46]  M Salerno,et al.  Dynamic spiral MRI of pulmonary gas flow using hyperpolarized 3He: Preliminary studies in healthy and diseased lungs , 2001, Magnetic resonance in medicine.

[47]  John P Mugler,et al.  The variability of regional airflow obstruction within the lungs of patients with asthma: assessment with hyperpolarized helium-3 magnetic resonance imaging. , 2007, The Journal of allergy and clinical immunology.

[48]  H. Gudbjartsson,et al.  The rician distribution of noisy mri data , 1995, Magnetic resonance in medicine.