In vivo MRI of altered proton signal intensity and T2 relaxation in a bleomycin model of pulmonary inflammation and fibrosis

Abstract

PURPOSE: To investigate the ability of proton ((1)H) magnetic resonance imaging (MRI) to distinguish between pulmonary inflammation and fibrosis. MATERIALS AND METHODS: Three groups of Sprague-Dawley rats (n = 5) were instilled intratracheally with bleomycin (2.5 U/kg or 3.5 U/kg) in saline or with saline only. Rats were imaged at 2.0 Tesla using a multi-slice Carr-Purcell-Meilboom-Gill (CPMG) sequence with 6 ms echo spacing. Signal intensity (S(0)) and T(2) were calculated on a pixel-by-pixel basis using images collected before dosing and 1, 2, 4, and 7 weeks after. At each time point, data from dosed animals were compared with controls, and bivariate statistical analysis was used to classify image pixels containing abnormal tissue. At week 7, pulmonary function tests were performed, then all rats were killed, left lungs were formalin fixed and tri-chrome stained for histological analysis of collagen content, and right lungs were used to measure water and hydroxyproline (collagen) content. RESULTS: The product S(0)xT(2) significantly correlated with water and collagen content in the high-dose group (P = 0.004 and P = 0.03, respectively). However, S(0) and T(2) of abnormal tissue were correlated for all time points (r = 0.93, P < 0.001), and could not distinguish inflammation from fibrosis. CONCLUSION: MRI can be used to confidently localize pulmonary inflammation and fibrosis, but it lacks specificity.