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 ¼ 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-PurcellMeilboom-Gill (CPMG) sequence with 6 ms echo spacing. Signal intensity (S 0 ) and T 2 were calculated on a pixel-bypixel 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 ÂT 2 significantly correlated with water and collagen content in the high-dose group (P ¼ 0.004 and P ¼ 0.03, respectively). However, S 0 and T 2 of abnormal tissue were correlated for all time points (r ¼ 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.

Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230

“…It has been shown earlier that proton MRI techniques are able to noninvasively follow the progression of bleomycininduced lung injury in rats (2,16,24,25) and mice (3,16). The signals quantified by MRI in the lung showed high correlation to histological analysis of collagen and to hydroxyproline content.…”

“…Moreover, target identification and development of therapeutics against pulmonary fibrosis are challenging. The use of magnetic resonance imaging (MRI) to noninvasively follow the course of lung injury induced by bleomycin administration to mice (3,16) and rats (2,16,24,25) has been reported earlier. The ability of MRI to noninvasively quantify lung injury in bleomycin-treated animals facilitates in vivo pharmacological studies in the model.…”

A View on Imaging in Drug Research and Development for Respiratory Diseases

“…Proton MRI has also been used to follow bleomycin-induced injury in mice and rats Jacob et al, 2010;Babin et al, 2011) (Fig. 8, C and D).…”

CHAPTER 17. Magnetic Resonance Imaging in Respiratory Diseases: From Diagnosis to Pharmaceutical Research and Development

“…103,104 Proton MRI has been used to follow bleomycin-induced injury in rats. [105][106][107] The initial response in rats, in the first two weeks post-insult, characterized predominantly by diffuse MRI signals, was primarily inflammation-related. At later time points, up to 70 days post-bleomycin, increased MRI signals reflected tissue remodeling involved in fibrosis development, as suggested by histology revealing prominent collagen deposition in the same areas where MRI signals had been detected in vivo (Figure 17.9).…”