Pulmonary oedema measured by MRI correlates with late-phase response to allergen challenge

Purpose: Asthma is associated with reversible airway obstruction, leucocyte infiltration, airways hyperresponsiveness (AHR) and airways remodelling. Fluid accumulation causes pulmonary oedema contributing to airways obstruction. We examined the temporal relationship between the late asthmatic response (LAR) following allergen challenge of sensitised guinea-pigs and pulmonary oedema measured by magnetic resonance imaging (MRI). Materials and Methods: Ovalbumin (OVA) sensitised guinea-pigs received either a single OVA inhalation (acute) or nine OVA inhalations at 48 h intervals (chronic). Airways obstruction was measured as specific airways conductance (sGaw) by whole body plethysmography. AHR to inhaled histamine and bronchoalveolar lavage for leucocyte counts were measured 24 h after a single or the final chronic ovalbumin challenges. MRI was performed at intervals after OVA challenge and high intensity oedemic signals quantified. Results: Ovalbumin caused early bronchoconstriction, followed at 7 h by a LAR and at 24 h AHR and leucocyte influx. The bright intensity MRI oedema signal, peaking at 7 h, was significantly (P<0.05) greater after chronic (9.0±0.7x103 mm3) than acute OVA (7.6±0.2x103 mm3). Dexamethasone treatment before acute OVA abolished the AHR and LAR and significantly reduced eosinophils and the bright intensity MRI oedema from 9.1±1.0 to 6.4±0.3x103 mm3. Conclusion: We show a temporal relationship between oedema and the LAR and their parallel reduction, along with eosinophils and AHR, by dexamethasone. This suggests a close causative association between pulmonary oedema and impaired airways function

Pulmonary edema measured by MRI correlates with late-phase response to allergen challenge

Purpose: Asthma is associated with reversible airway obstruction, leucocyte infiltration, airways hyperresponsiveness (AHR) and airways remodelling. Fluid accumulation causes pulmonary oedema contributing to airways obstruction. We examined the temporal relationship between the late asthmatic response (LAR) following allergen challenge of sensitised guinea-pigs and pulmonary oedema measured by magnetic resonance imaging (MRI). Materials and Methods: Ovalbumin (OVA) sensitised guinea-pigs received either a single OVA inhalation (acute) or nine OVA inhalations at 48 h intervals (chronic). Airways obstruction was measured as specific airways conductance (sGaw) by whole body plethysmography. AHR to inhaled histamine and bronchoalveolar lavage for leucocyte counts were measured 24 h after a single or the final chronic ovalbumin challenges. MRI was performed at intervals after OVA challenge and high intensity oedemic signals quantified. Results: Ovalbumin caused early bronchoconstriction, followed at 7 h by a LAR and at 24 h AHR and leucocyte influx. The bright intensity MRI oedema signal, peaking at 7 h, was significantly (P<0.05) greater after chronic (9.0±0.7x103 mm3) than acute OVA (7.6±0.2x103 mm3). Dexamethasone treatment before acute OVA abolished the AHR and LAR and significantly reduced eosinophils and the bright intensity MRI oedema from 9.1±1.0 to 6.4±0.3x103 mm3. Conclusion: We show a temporal relationship between oedema and the LAR and their parallel reduction, along with eosinophils and AHR, by dexamethasone. This suggests a close causative association between pulmonary oedema and impaired airways function

Repeatability and reproducibility of longitudinal relaxation rate in 12 small-animal MRI systems

Background: Many translational MR biomarkers derive from measurements of the water proton longitudinal relaxation rate R 1 , but evidence for between-site reproducibility of R 1 in small-animal MRI is lacking. Objective: To assess R 1 repeatability and multi-site reproducibility in phantoms for preclinical MRI. Methods: R 1 was measured by saturation recovery in 2% agarose phantoms with five nickel chloride concentrations in 12 magnets at 5 field strengths in 11 centres on two different occasions within 1–13 days. R 1 was analysed in three different regions of interest, giving 360 measurements in total. Root-mean-square repeatability and reproducibility coefficients of variation (CoV) were calculated. Propagation of reproducibility errors into 21 translational MR measurements and biomarkers was estimated. Relaxivities were calculated. Dynamic signal stability was also measured. Results: CoV for day-to-day repeatability (N = 180 regions of interest) was 2.34% and for between-centre reproducibility (N = 9 centres) was 1.43%. Mostly, these do not propagate to biologically significant between-centre error, although a few R 1 -based MR biomarkers were found to be quite sensitive even to such small errors in R 1 , notably in myocardial fibrosis, in white matter, and in oxygen-enhanced MRI. The relaxivity of aqueous Ni 2+ in 2% agarose varied between 0.66 s −1 mM −1 at 3 T and 0.94 s −1 mM −1 at 11.7T. Interpretation: While several factors affect the reproducibility of R 1 -based MR biomarkers measured preclinically, between-centre propagation of errors arising from intrinsic equipment irreproducibility should in most cases be small. However, in a few specific cases exceptional efforts might be required to ensure R 1 -reproducibility