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Am J Physiol Lung Cell Mol Physiol 283: L22-L30, 2002. First published February 1, 2002; doi:10.1152/ajplung.00373.2001
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Vol. 283, Issue 1, L22-L30, July 2002

Noninvasive detection of endotoxin-induced mucus hypersecretion in rat lung by MRI

Nicolau Beckmann1, Bruno Tigani1, Rosemary Sugar2, Alan D. Jackson2, Gareth Jones2, Lazzaro Mazzoni3, and John R. Fozard3

1 Central Technologies and 3 Respiratory Diseases Therapeutic Area, Novartis Pharma, CH-4002 Basel, Switzerland; and 2 Novartis Horsham Research Centre, Horsham RH12 5AB, United Kingdom

Using magnetic resonance imaging (MRI), we detected a signal in the lungs of Brown Norway rats after intratracheal administration of endotoxin [lipopolysaccharide (LPS)]. The signal had two components: one, of diffuse appearance and higher intensity, was particularly prominent up to 48 h after LPS; the second, showing an irregular appearance and weaker intensity, was predominant later. Bronchoalveolar lavage fluid analysis indicated that generalized granulocytic (especially neutrophilic) inflammation was a major contributor to the signal at the early time points, with mucus being a major factor contributing at the later time points. The facts that animals can breathe freely during data acquisition and that neither respiration nor cardiac triggering is applied render this MRI approach attractive for the routine testing of anti-inflammatory drugs. In particular, the prospect of noninvasively detecting a sustained mucus hypersecretory phenotype in the lung brings an important new perspective to models of chronic obstructive pulmonary diseases in animals.

edema; goblet cell; lipopolysaccharide; chronic obstructive pulmonary disease; lung inflammation; magnetic resonance imaging


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