Journal of Applied Physiology
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J Appl Physiol 99: 2388-2397, 2005. First published August 4, 2005; doi:10.1152/japplphysiol.00391.2005
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Identifying airways responsible for heterogeneous ventilation and mechanical dysfunction in asthma: an image functional modeling approach

Nora T. Tgavalekos,1 Merryn Tawhai,2 R. Scott Harris,3 Guido Mush,3 Marcos Vidal-Melo,3 Jose G. Venegas,3 and Kenneth R. Lutchen1

1Department of Biomedical Engineering, Boston University, Boston, Massachusetts; 2Bioengineering Institute, The University of Auckland, Auckland, New Zealand; and 3Departments of Anesthesia and Critical Care, Radiology, and Medicine (Pulmonary and Critical Care Unit), Massachusetts General Hospital, Boston, Massachusetts

Submitted 7 April 2005 ; accepted in final form 29 July 2005

We present an image functional modeling approach, which synthesizes imaging and mechanical data with anatomically explicit computational models. This approach is utilized to identify the relative importance of small and large airways in the simultaneous deterioration of mechanical function and ventilation in asthma. Positron emission tomographic (PET) images provide the spatial distribution and relative extent of ventilation defects in asthmatic subjects postbronchoconstriction. We also measured lung resistance and elastance from 0.15 to 8 Hz. The first step in image functional modeling involves mapping ventilation three-dimensional images to the computational model and identifying the largest sized airways of the model that, if selectively constricted, could precisely match the size and anatomic location of ventilation defects imaged by PET. In data from six asthmatic subjects, these airways had diameters <2.39 mm and mostly <0.44 mm. After isolating and effectively closing airways in the model associated with these ventilation defects, we imposed constriction with various means and standard deviations to the remaining airways to match the measured lung resistance and elastance from the same subject. Our results show that matching both the degree of mechanical impairment and the size and location of the PET ventilation defects requires either constriction of airways <2.4 mm alone, or a simultaneous constriction of small and large airways, but not just large airways alone. Also, whereas larger airway constriction may contribute to mechanical dysfunction during asthma, degradation in ventilation function requires heterogeneous distribution of near closures confined to small airways.

morphometric lung model; constriction; closure



Address for reprint requests and other correspondence: K. R. Lutchen, Dept. of Biomedical Engineering, Boston Univ., 44 Cummington St., Boston, MA 02215 (e-mail: klutch{at}bu.edu)




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