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1 Department of Biomedical Engineering, Boston University, Boston, MA, USA
2 Bioengineering Institute, The University of Auckland, Auckland, New Zealand
3 Department of Anesthesia and Critical Care, Radiology and Medicine (Pulmonary and Critical Care Unit), Massachusetts General Hosptial, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: noratgav{at}bu.edu.
We present an Image Functional Modeling (IFM) 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 asthmatics post- bronchoconstriction. We also measured lung resistance and elastance (RL and EL) from 0.15 - 8 Hz. The first step in IFM involves mapping ventilation 3D images to the computational model and identifying the largest size airways of the model that, if selectively constricted, could precisely match the size and anatomical location of ventilation defects imaged by PET. In data from six asthmatics, these airways had diameters < 2.39 mm and mostly d<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 in order to match the measured RL and EL 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 smaller than 2.4 mm alone, or a simultaneous constriction of small and large airways, but not just large airways alone. In summary, while larger airway constriction may contribute to mechanical dysfunction during asthma, degradation in ventilation function requires heterogeneous distribution of near closures confined to small airways.
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