title: Proton MRI as a noninvasive tool to assess elastase-induced lung damage in spontaneously breathing rats.
abstract: Elastase-induced changes in lung morphology and function were detected in spontaneously breathing rats using conventional proton MRI at 4.7 T. A single dose of porcine pancreatic elastase (75 U/100 g body weight) or vehicle (saline) was administered intratracheally (i.t.) to male Brown Norway (BN) rats. MRI fluid signals were detected in the lungs 24 hr after administration of elastase and resolved within 2 weeks. These results correlated with perivascular edema and cellular infiltration observed histologically. Reductions in MRI signal intensity of the lung parenchyma, and increases in lung volume were detected as early as 2 weeks following elastase administration and remained uniform throughout the study, which lasted 8 weeks. Observations were consistent with air trapping resulting from emphysema detected histologically. In a separate experiment, animals were treated daily intraperitoneally (i.p.) with all-trans-retinoic acid (ATRA; 500 microg/kg body weight) or its vehicle (triglyceride oil) starting on day 21 after elastase administration and continuing for 12 days. Under these conditions, ATRA did not elicit a reversal of elastase-induced lung damage as measured by MRI and histology. The present approach complements other validated applications of proton MRI in experimental lung research as a method for assessing drugs in rat models of respiratory diseases.
authors.affiliation: Discovery Technologies, Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Harry Karmouty
authors.initials: HK
authors.lastname: Quintana
authors.forename: Catherine
authors.initials: C
authors.lastname: Cannet
authors.forename: Stefan
authors.initials: S
authors.lastname: Zurbruegg
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Blé
authors.forename: John R
authors.initials: JR
authors.lastname: Fozard
authors.forename: Clive P
authors.initials: CP
authors.lastname: Page
authors.forename: Nicolau
authors.initials: N
authors.lastname: Beckmann
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004646:Emphysema / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D010196:Pancreatic Elastase; D011379:Prognosis; D011522:Protons; D051381:Rats; D015656:Respiratory Mechanics; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage*
chemical_list: D011522:Protons; D014212:Tretinoin; D010196:Pancreatic Elastase