Rationale and Objectives
Although multiple detector computed tomography (MDCT) and hyperpolarized gas magnetic resonance imaging (HP MRI) have demonstrated ability to detect structural and ventilation abnormalities in asthma, few studies have sought to exploit or cross-validate the regional information provided by these techniques. The purpose of this work is to assess regional disease in asthma by evaluating the association of sites of ventilation defect on HP MRI with other regional markers of airway disease, including air trapping on MDCT and inflammatory markers on bronchoscopy.
Materials and Methods
Both HP MRI using helium-3 and MDCT were acquired in the same patients. Supervised segmentation of the lung lobes on MRI and MDCT facilitated regional comparisons of ventilation abnormalities in the lung parenchyma. The percentage of spatial overlap was evaluated between regions of ventilation defect on HP MRI and hyperlucency on MDCT to determine associations between obstruction and likely regions of gas trapping. Similarly, lung lobes with high defect volume were compared to lobes with low defect volume for differences in inflammatory cell number and percentage using bronchoscopic assessment.
Results
There was significant overlap between sites of ventilation defect on HP MRI and hyperlucency on MDCT suggesting that sites of airway obstruction and air trapping are associated in asthma. The percent ( r = 0.68; P = .0039) and absolute ( r = 0.61; P = .0125) number of neutrophils on bronchoalveolar lavage for the sampled lung lobe also directly correlated with increased defect volume.
Conclusions
These results show promise for using image guidance to assess specific regions of ventilation defect or air trapping in heterogeneous obstructive lung diseases such as asthma.
Asthma affects millions of people worldwide and trends indicate increasing incidence, especially in children ( ). Subjects with asthma experience periodic wheezing and shortness of breath that manifests on pulmonary function tests as reduced forced expiratory lung volume in 1 second (FEV 1 ) and increased lung residual volume normalized to the total lung capacity (RV/TLC) compared with normal subjects. Bronchodilation with beta agonists such as albuterol can partially reverse this obstructive physiology by relaxing airway smooth muscle, but evidence from airway biopsies suggests that obstruction is also accompanied by chronic inflammation and airway remodeling ( ).
Functional imaging in the lungs has great potential for mechanistic studies of lung disease, particularly for identifying regional patterns of obstruction that test physiologic hypotheses ( ). Regional mosaics of reduced parenchymal density, apparently from air trapping, are associated with asthma on computed tomography (CT) ( ). More recently, CT, and especially multidetector CT (MDCT), have been used to quantitatively measure lung parenchymal density and correlate these measures to obstructive physiology ( ).
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Materials and methods
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Pulmonary Function and Bronchoscopy
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Image Acquisition
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Table 1
Multidetector Computed Tomography Scan Parameters
Parameter 16 Detector 64 Detector Collimation 1.25 mm 1.25 mm Pitch 1.675 0.984 Source current/voltage 50 mA/120 kVp 50 mA/120 kVp Gantry speed 0.5 second/rotation Matrix 512 × 512 Lung volume Functional residual capacity (expiratory) and total lung capacity (inspiratory) Reconstruction kernel “Standard” and “lung” Reconstructed slice thickness 0.625 mm (quantitative) and 5 mm (qualitative)
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Table 2
Magnetic Resonance Imaging Scan Parameters
Parameter T1-Weighted Fast Spin Echo Hyperpolarized 3 He Magnetic Resonance Imaging Repetition time/echo time ∞/8 milliseconds 8.4/3.1 milliseconds Flip angle 90° 7° Bandwidth 31.25 kHz 31.25 kHz Acquisition matrix 128 × 64 128 × 128 Imaging time 7–8 seconds 18–24 seconds Axial plane field of view 32–38 × 24–29 cm 2 Slice field of view 13–19 × 1.5 cm slices
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Image Measurement
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Statistical Analyses
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Results
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Table 3
Statistical Summary (Mean ± Standard Deviation) of Image Metrics and Pulmonary Function with Asthma Severity for Subjects Included in the Regional Analysis
Parameter Severe (n = 6) Nonsevere (n = 15) Overall (n = 21) Defect score 16.7 ± 12.3 11.0 ± 9.5 12.6 ± 10.4 Percent defect volume (%) 7.6 ± 4.2 5.4 ± 4.5 6.0 ± 4.4 Expiratory densitometry: Percent below −850 HU 4.7 ± 2.1 8.0 ± 7.3 7.0 ± 6.4 Percent below −910 HU 0.9 ± 1.0 1.5 ± 1.7 1.3 ± 1.6 Percent below −950 HU 0.3 ± 0.5 0.4 ± 0.7 0.4 ± 0.6 FEV 1 (% predicted) 82.7 ± 11.1 91.5 ± 15.1 89.0 ± 14.3 FEF 25–75 (% predicted) 71.7 ± 36.3 69.4 ± 23.4 70.0 ± 26.8 FEV 1 /FVC (% predicted) 94.4 ± 13.6 89.2 ± 8.6 90.7 ± 10.2 RV/TLC 0.323 ± 0.098 0.308 ± 0.052 0.312 ± 0.066 BAL % Neutrophils 0.86 ± 0.86 2.48 ± 2.93 2.01 ± 2.58 % Eosinophils 0.74 ± 0.73 0.63 ± 0.67 0.66 ± 0.67 % Macrophage 91.3 ± 2.9 85.5 ± 11.2 87.2 ± 9.8
HU: Hounsfield unit; FEV 1 : forced expiratory volume in 1 second; FEF 25–75 : forced expiratory flow rate at 25–75% FVC; FVC: forced vital capacity; RV: residual volume; TLC: total lung capacity; BAL: bronchoalveolar lavage.
Table 4
Spearman Correlations Between Image, Pulmonary Lung Function, and BAL Measures
Parameter Correlate FEV 1 % Predicted FEV 1 /FVC % Predicted FEF 25–75 % Predicted RV/TLC % Predicted BAL % Neutrophils BAL Total Neutrophils (10 6 cells) Defect score (n = 21) −0.76 P = .0002 −0.24 P = .31 −0.54 P = .03 0.58 P = .02 0.23 P = .17 0.06 P = .82 Expiratory densitometry (n = 45) Percent below −850 HU −0.37 P = .04 −0.52 P = .02 −0.55 P = .002 0.53 P = .003 0.16 P = .54 0.18 P = .51 % Defect volume Whole lung (n = 21) −0.57 P = .007 −0.23 P = .31 −0.43 P = .08 0.37 P = .15 0.41 P = .11 0.30 P = .27 @BAL site (n = 17) — — — — 0.68 P = .0039 0.61 P = .0125
HU: Hounsfield unit; FEV 1 : forced expiratory volume in 1 second; FEF 25–75 : forced expiratory flow rate at 25–75% FVC; FVC: forced vital capacity; RV: residual volume; TLC: total lung capacity; BAL: bronchoalveolar lavage.
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MDCT Measures
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MRI Measures
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MDCT and MRI Comparison
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Discussion
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