Proton MRI of lung parenchyma reflects allergen-induced airway remodeling and endotoxin-aroused hyporesponsiveness: a step toward ventilation studies in spontaneously breathing rats.
Proton signals from lung parenchyma were detected with the use of a gradient-echo sequence to noninvasively obtain information on pulmonary function in models of airway diseases in rats. Initial measurements carried out in artificially ventilated control rats revealed a highly significant negative correlation between the parenchymal signal and the partial pressure of oxygen (pO2) in the blood, for different amounts of oxygen administered. The magnitude of the signal intensity variations caused by changes in the oxygen concentration was larger than expected solely from the paramagnetic properties of molecular oxygen. Inhomogeneous line-broadening induced by lung inflation may explain the observed signal amplification. Experiments carried out in spontaneously breathing animals challenged with allergen or endotoxin revealed parenchymal signal changes that reflected the oxygenation status of the lungs and were consistent with airway remodeling or hyporesponsiveness. The results suggest that proton MRI of parenchymal tissue is a sensitive tool for probing the functional status of the lung in rat models of respiratory diseases. The method is complementary to the recently described noninvasive assessment by MRI of pulmonary inflammation in small rodents. Overall, these techniques provide invaluable information for profiling anti-inflammatory drugs in models of airway diseases.
Discovery Technologies Center, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Nicolau
N
Beckmann
Catherine
C
Cannet
Stefan
S
Zurbruegg
Markus
M
Rudin
Bruno
B
Tigani
D000485:Allergens / Q000276:immunology; D000704:Analysis of Variance; D000818:Animals; D004731:Endotoxins / Q000276:immunology; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000276:immunology; D011654:Pulmonary Edema / Q000175:diagnosis* / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D015203:Reproducibility of Results; D012119:Respiration; D012121:Respiration, Artificial
D000485:Allergens; D004731:Endotoxins; D010047:Ovalbumin