Hyperpolarized Helium-3 MRI of exercise-induced bronchoconstriction during challenge and therapy

Stanley J Kruger, David J Niles, Bernard Dardzinski, Amy Harman, Nizar N Jarjour, Marcella Ruddy, Scott K Nagle, Christopher J Francois, Ronald L Sorkness, Ryan M Burton, Alejandro Munoz del Rio, Sean B Fain, Stanley J Kruger, David J Niles, Bernard Dardzinski, Amy Harman, Nizar N Jarjour, Marcella Ruddy, Scott K Nagle, Christopher J Francois, Ronald L Sorkness, Ryan M Burton, Alejandro Munoz del Rio, Sean B Fain

Abstract

Purpose: To investigate the utility of hyperpolarized He-3 MRI for detecting regional lung ventilated volume (VV) changes in response to exercise challenge and leukotriene inhibitor montelukast, human subjects with exercise induced bronchoconstriction (EIB) were recruited. This condition is described by airway constriction following exercise leading to reduced forced expiratory volume in 1 second (FEV1) coinciding with ventilation defects on hyperpolarized He-3 MRI.

Materials and methods: Thirteen EIB subjects underwent spirometry and He-3 MRI at baseline, postexercise, and postrecovery at multiple visits. On one visit montelukast was given and on two visits placebo was given. Regional VV was calculated in the apical/basilar dimension, in the anterior/posterior dimension, and for the entire lung volume. The whole lung VV was used as an end-point and compared with spirometry.

Results: Postchallenge FEV1 dropped with placebo but not with treatment, while postchallenge VV dropped more with placebo than treatment. Sources of variability for VV included region (anterior/posterior), scan, and treatment. VV correlated with FEV1/ forced vital capacity (FVC) and forced expiratory flow between 25 and 75% of FVC and showed gravitational dependence after exercise challenge.

Conclusion: A paradigm testing the response of ventilation to montelukast revealed both a whole-lung and regional response to exercise challenge and therapy in EIB subjects.

Keywords: asthma; exercise; helium; imaging; therapy.

Copyright © 2013 Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
Timeline of spirometry and image acquisition (baseline, A; post-challenge, B; and recovery, C). Measures were repeated at each of three visits (2 placebo, 1 treatment).
Figure 2
Figure 2
Representative coronal hyperpolarized He-3 MRI image with outlined regions indicating segmented lung volume (green boundary) and defect regions (red boundaries).
Figure 3
Figure 3
Correlations between postchallenge ventilated volume and spirometric measures (a) FEV1/FVC, (b) FEF 25%-75%, (c) FEV1, and (d) FVC percent predicted (%P). The significant correlations were between VV and FEV1/FVC (r = 0.61, p<0.05), and between VV and FEF 25%-75% (r = 0.62, p<0.05).
Figure 4
Figure 4
He-3 lung images from site A (Subject 8, Table 1) showing a strong VV response to challenge and treatment. Challenge-induced defects are observable and postchallenge decreases in FEV1 for this subject coincide with decreases in VV.
Figure 5
Figure 5
Response of FEV1 to (a) placebo compared with (b) montelukast treatment, and response of VV to (c) placebo compared with (d) montelukast treatment for all 13 subjects.
Figure 6
Figure 6
Anterior-posterior dependence of VV for (a) placebo visits and (b) drug treatment visits. Boxes extend from lower to upper quartile with hashes at the median. Whiskers extend to 150% of the interquartile range of the sample. Outliers are denoted with + signs. P-values comparing region that are significant at the .05 level are indicated by an asterisk.
Figure 7
Figure 7
Apical-basilar dependence of VV for (a) placebo visits and (b) drug treatment visits. Boxes extend from lower to upper quartile with hashes at the median. Whiskers extend to 150% of the interquartile range of the sample. Outliers are denoted with + signs. P-values comparing region that are significant at the .05 level are indicated by an asterisk.

Source: PubMed

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