Bleomycin‐induced lung injury in mice investigated by MRI: Model assessment for target analysis

Abstract

Magnetic resonance imaging (MRI) has been used to follow the course of bleomycin-induced lung injury in mice and to investigate two knockout mouse lines with the aim of providing potential therapeutic targets. Bleomycin (0.25 mg/kg) was administered intranasally six times, once a day. MRI was carried out on spontaneously breathing animals up to day 70 after bleomycin. Neither cardiac nor respiratory gating was applied during image acquisition. A long lasting response following bleomycin has been detected by MRI in the lungs of male C57BL/6 mice. Histology showed that, from day 14-70 after bleomycin, fibrosis was the predominant component of the injury. Female C57BL/6 mice displayed a smaller response than males. Bleomycin-induced injury was significantly more pronounced in C57BL/6 than in Balb/C mice. MRI and histology demonstrated a protection against bleomycin insult in female heterozygous and male homozygous cancer Osaka thyroid kinase knockout animals. In contrast, no protection was seen in cadherin-11 knockout animals. In summary, MRI can quantify, in spontaneously breathing mice, bleomycin-induced lung injury. With the ability for repetitive measurements in the same animal, the technique is attractive for in vivo target analysis and compound profiling in this murine model. Magn Reson Med 67:499-509,

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

“…10, B-D). Overall, these postmortem analyses were consistent with the development of fibrosis in the model, as examined extensively earlier (3,16).…”

“…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.…”

“…A three-dimensional (3D) ultrashort echo time (UTE) sequence (49,50,56,60) with the following parameters was used for acquisitions on rats and mice (whenever different, parameters for mice are provided in parentheses): repetition time (TR) 2.7 ms, echo time 0.02 ms, flip angle of the excitation pulse 2°(3°), 51360 (77086) projections, field-of-view (FOV) 50 ϫ 50 ϫ 70 (30 ϫ 30 ϫ 50) mm 3 , matrix 128 ϫ 128 ϫ 128 (192 ϫ 192 ϫ 192), 5 (2) averages. The acquisition times for the 3D acquisitions were of 11.6 and 6.9 min for rats and mice, respectively.…”

“…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.…”

Longitudinal, in vivo assessment of invasive pulmonary aspergillosis in mice by computed tomography and magnetic resonance imaging

“…31,32 Despite these challenges, the potential of MRI has motivated several groups to report the successful use of 1 H-MRI for preclinical imaging of lung fibrosis and lung neoplasms. [33][34][35] Recently, more advanced MR sequences were optimized to overcome sensitivity problems of lung MRI, in particular MRI using ultrashort echo times (UTEs) or zero echo times. These novel MR sequences were successfully used for lung fibrosis and emphysema imaging.…”