Regional pulmonary response to a methacholine challenge using hyperpolarized (3)He magnetic resonance imaging.
OBJECTIVE
Spirometry is insensitive to small airway abnormalities in asthma. Our objective was to evaluate regional lung structure and function using hyperpolarized (3)He magnetic resonance imaging (MRI) before, during and after a methacholine challenge (MCh).


METHODS
Twenty-five asthmatics (mean age = 34 ± 11 years) and eight healthy volunteers (HV) (mean age = 33 ± 11 years) underwent spirometry, plethysmography and hyperpolarized (3)He MRI prior to a MCh. MRI was repeated following the MCh and again 25 min after salbutamol administration. (3)He MRI gas distribution was quantified using semiautomated segmentation of the ventilation defect percent (VDP). Tissue microstructure was measured using the (3)He apparent diffusion coefficient (ADC). Analysis of variance with repeated measures was used to evaluate changes at each time point as well as to determine interactions between regions of interest (ROI) and subject group. Pearson's correlations were performed to evaluate associations between (3)He MRI measurements and established clinical measures.


RESULTS
In asthmatics, but not HV, whole-lung ADC was increased post-MCh (P < 0.01). In asthmatics only, ADC was increased post-MCh in posterior ROI (P < 0.01) and all ROI in the superior-inferior direction (P < 0.01). VDP was increased in posterior and inferior ROI (P < 0.001). There was a correlation between VDP and specific airway resistance (r = 0.74, P < 0.0001), dyspnoea score (r = 0.66, P < 0.01) and fractional exhaled nitric oxide (r = 0.45, P < 0.05).


CONCLUSIONS
We evaluated the regional pulmonary response to methacholine and salbutamol using (3)He MRI and showed heterogeneous VDP and ADC consistent with bronchoconstriction and gas trapping, respectively, post-MCh. These regional alterations resolved post-salbutamol.
Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada.
Stephen
S
Costella
Miranda
M
Kirby
Geoffrey N
GN
Maksym
David G
DG
McCormack
Nigel A M
NA
Paterson
Grace
G
Parraga
D000328:Adult; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000420:Albuterol / Q000008:administration & dosage; D001249:Asthma / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D005260:Female; D006371:Helium / Q000008:administration & dosage; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D008875:Middle Aged; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology; D012129:Respiratory Function Tests; D055815:Young Adult
D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D006371:Helium; D000420:Albuterol