Quantification of Pulmonary Inflammation after Segmental Allergen Challenge Using Turbo-Inversion Recovery-Magnitude Magnetic Resonance Imaging

Rationale: There is a need to develop novel noninvasive imaging biomarkers that help to evaluate antfinflammatory asthma treatments. Objectives: To investigate whether the extent of the segmental lung edema measured noninvasively using turbo-inversion recovery-magnitude magnetic resonance imaging (TIRM MRI)corresponds to the severity of the regional allergic reaction determined by the percentage of eosinophils in bronchoalveolar lavage fluid (BAL) 24 hours after segmental allergen challenge in patients with asthma compared with normal control subjects. Methods: Eleven volunteers with allergic asthma and flue healthy volunteers underwent segmental challenges with different allergen doses by two bronchoscopies 24 hours apart. They had lung MRI at baseline and 6 and 24 hours after segmental challenge. Mill TIRM scores were correlated with the eosinophilic response at 24 hours. Measurements and Main Results: In patients with asthma, there were significant differences of eosinophil percentages in BAL at 24 hours from segments given standard-dose, low-dose, or no allergen (saline) (P < 0.001). Correspondingly significant differences between the TIRM score in allergen standard-dose, low-dose, and salinetreated segments were observed at 24 hours post-challenge (P < 0.001). With increasing TIRM score at 24 hours the percent eosinophils per segment 24 hours post-challenge also increased accoidingly (P < 0.001). There was interobserver agreement for TIRM score grading (kappa = 0.72 for 24-h time point). Conclusions: The MRI-based noninvasive TIRM score is a promising biomarker for the noninvasive detection of the inflammatory response after segmental allergen challenge in patients with asthma and may serve to monitor the therapeutic effectiveness of novel antiinflammatory drugs in future human trials.