Bleomycin-induced lung injury assessed noninvasively and in spontaneously breathing rats by proton MRI.
OBJECTIVE
To apply proton magnetic resonance imaging (MRI) techniques to assess noninvasively and in spontaneously breathing rats, structural changes following a single intratracheal administration of bleomycin (BLM).


METHODS
Rats were scanned by MRI prior to BLM or vehicle administration and at six hours, 24 hours, week 1, and at weeks 2, 3, 6, and 8 after treatment. Bronchoalveolar lavage (BAL) fluid and histological analyses were performed at 24 hours, and at weeks 1 and 8 (histology only).


RESULTS
Prominent MRI fluid signals were detected in the lungs of BLM-treated rats one week after challenge. These signals correlated with increased inflammatory parameters in BAL fluid and with marked perivascular and parenchymal infiltration with inflammatory cells in histological slices. At week 2 the MRI signals due to edema resolved, but nevertheless an increase in MRI signal intensity from the lung parenchyma was apparent. In some areas of the right lung the MRI signal intensity in the parenchyma decreased between weeks 2 and 8. These observations were in line with histology demonstrating collagen deposition and atelectasis (hallmarks of fibrosis) at week 1 and a partial recovery of the lung parenchyma at week 8.


CONCLUSIONS
The data demonstrate the ability of proton MRI to detect BLM-induced lung fibrosis as well as the acute inflammatory response caused by the agent.
Karmouty-Quintana
Harry
H
Discovery Technologies, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Cannet
Catherine
C
Zurbruegg
Stefan
S
Blé
François-Xavier
FX
Fozard
John R
JR
Page
Clive P
CP
Beckmann
Nicolau
N
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D018893:Bronchoalveolar Lavage; D005355:Fibrosis; D007091:Image Processing, Computer-Assisted; D007249:Inflammation; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D055370:Lung Injury; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011522:Protons; D001261:Pulmonary Atelectasis / Q000473:pathology; D051381:Rats; D012119:Respiration; D012492:Salts / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D011522:Protons; D012492:Salts; D001761:Bleomycin