Background-To prospectively apply an automated, quantitative 3-D approach to imaging and airway analysis to assess airway remodeling in asthma.

Rationale and Objectives Previous cross-sectional studies have demonstrated that airway wall thickness and air trapping are greater in subjects with severe asthma than in those with mild-to-moderate asthma. However, a better understanding of how airway remodeling and lung density change over time is needed. This study aims to evaluate predictors of airway wall remodeling and change in lung function and lung density over time in severe asthma. Materials and Methods Phenotypic characterization and quantitative multidetector computed tomography (MDCT) of the chest was performed at baseline and ∼2.6 years later in 38 participants with asthma (severe n=24, mild-moderate n=14) and 9 normal controls from the Severe Asthma Research Program. Results Subjects with severe asthma had a significant decline in post-bronchodilator FEV1% predicted over time (p = <0.001). Airway wall thickness measured by MDCT was increased at multiple airway generations in severe asthma compared to mild-to-moderate asthma (wall area percent (WA%): p <0.05) and normals (p <0.05) at baseline and year 2. Over time, there was an increase in WA% and wall thickness (WT%) in all subjects (p = 0.030 and 0.009 respectively) with no change in emphysema-like lung or air trapping. Baseline pre-bronchodilator FEV1% inversely correlated with WA% and WT% (both p = <0.05). In a multivariable regression model, baseline WA%, race and healthcare utilization were predictors of subsequent airway remodeling. Conclusions Severe asthma subjects have a greater decline in lung function over time than normal subjects or those with mild-to-moderate asthma. MDCT provides a noninvasive measure of airway wall thickness that may predict subsequent airway remodeling.

An anthropomorphic airway tree phantom was imaged with both hyperpolarized (HP) 3 He MRI using a dynamic projection scan and computed tomography (CT). Airway diameter measurements from the HP 3 He MR images obtained using a newly developed model-based algorithm were compared against their corresponding CT values quantified with a well-established method. Of the 45 airway segments that could be evaluated with CT, only 14 airway segments (31%) could be evaluated using HP 3 He MRI. No airway segments smaller than ϳ4 mm in diameter and distal to the fourth generation were adequate for analysis in MRI. For the 14 airway segments measured, only two airway segments yielded a non-equivalent comparison between the two imaging modalities, while eight more had inconclusive comparison results, leaving only four airway segments (29%) that satisfied the designed equivalence criteria. Some of the potential problems in airway diameter quantification described in the formulation of the model-based algorithm were observed in this study. These results suggest that dynamic projection HP Hyperpolarized (HP) 3 He MRI is an emerging modality for imaging the lungs. By introducing into the lungs 3 He gas hyperpolarized by five orders of magnitude, one can use HP 3 He MRI to visualize ventilation distribution in both animals (1-3) and humans (4 -6). Its clinical potential for diagnosing lung ailments was clearly demonstrated when lung ventilation patterns of subjects with lung disease visibly differed from those of healthy subjects (6,7).One of the respiratory diseases particularly suited for investigation with HP 3 He MRI is asthma. Asthma is a chronic respiratory disease characterized by inflammation, hyperresponsiveness, remodeling, and irreversible heterogeneous constriction of the airways. Because of airway constriction, regions within the lung may be deprived of ventilation. However, to date, HP 3 He MRI studies of asthma have focused on the resulting ventilation distribution (2,8,9) rather than the actual airway constriction.Through dynamic imaging protocols, the ability of HP 3 He MRI to image airways has been demonstrated in both animals (10 -13) and humans (13-16). However, no work prior to that of Lewis et al. (17) attempted to measure airway caliber from HP 3 He MR images. Now, encouraged by the promising results from Lewis et al.'s (17) preliminary airway diameter measurements, a rigorous model-based algorithm for quantifying airway caliber has been developed and validated on a phantom consisting of plastic tubes in series (18). The algorithm is capable of subpixel resolution, but its performance in measuring airway diameters from projection images may be hampered by the overlap of airway profiles.While the quantification of airway diameters using HP 3 He MRI is still in its infancy, computed tomography (CT) has been used to measure airway luminal area and wall thickness in both asthmatic and nonasthmatic subjects since the early 1990s (19 -23). Having had more than a decade to develop and mature, CT is the established imag...

Rationale and Objectives-Application of a previously developed model-based algorithm on hyperpolarized (HP) 3 He MR dynamic projection images of phantoms was extended to investigate the utility of HP 3 He MRI in quantifying airway caliber change associated with asthma.Materials and Methods-Airways of seven volunteers were imaged and measured using HP 3 He MRI and multidetector-row computed tomography (MDCT) before and after a methacholine (MCh) challenge. MDCT data was obtained at functional residual capacity (FRC) and one liter above FRC (FRC+1L).Results-Comparison of the resultant data showed that HP 3 He MRI did not match MDCT in measuring the ratios of airway calibers before and after the MCh challenge in 37%-43% of the airways from the first six generations at the two lung volumes tested. However, MDCT did lead to the observation that 49%-69% of these airways displayed bronchodilation following MCh challenge. Conclusion-The current implementation of HP 3 He MRI did not match the MCh-induced postchallenge to pre-challenge airway caliber ratios as measured with MDCT. Elevated parenchymal tethering due to bronchoconstriction-induced hyperinflation was proposed as a possible explanation for this airway dilation.

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