Characterization of bleomycin lung injury by nuclear magnetic resonance: correlation between NMR relaxation times and lung water and collagen content.
The response of the NMR relaxation times (T(1), CPMG T(2), and Hahn T(2)) to bleomycin-induced lung injury was studied in excised, unperfused rat lungs. NMR, histologic, and biochemical (collagen content measurement) analyses were performed 1, 2, 4, and 8 weeks after intratracheal instillation of saline (control lungs) or 10 U/kg bleomycin sulfate. The control lungs showed no important NMR, water content, histologic, or collagen content changes. The spin-spin relaxation times for the fast and intermediate components of the CPMG decay (T(2f) and T(2i), respectively) increased 1 week after bleomycin injury (acute inflammatory stage) and then progressively decreased during the following 2-8 weeks (i.e., with the development of the chronic, fibrotic stage of the injury). The slow component (T(2s)) showed no significant changes. The response of T(1) and the slow component of the Hahn T(2) was, on the whole, similar to that of CPMG T(2f) and T(2i). T(1) changes were very small. Lung water content increased 1 week after injury. Histologic and biochemical assessment of collagen showed that collagen content was close to control at 1 week, but markedly increased at 2, 4, and 8 weeks. T(1) and T(2) data were directly correlated with lung water content and inversely correlated with collagen content. Our results indicate that NMR relaxation time measurements (particularly T(2)) reflect the structural changes associated with bleomycin injury. The prolonged T(2) relaxation times observed in the acute stage are related to the presence of edema, whereas the subsequent decrease in these values marks the stage of the collagen deposition (fibrotic stage). CPMG-T(2) and Hahn-T(2) measurements can be valuable as a potentially noninvasive method for characterizing bleomycin-induced lung injury and pathologically related lung disorders.
Cutillo
Antonio G
AG
Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA. acutillo@med.utah.edu
Chan
Pei H
PH
Ailion
David C
DC
Watanabe
Suetaro
S
Rao
Narayanam V
NV
Hansen
Christopher B
CB
Albertine
Kurt H
KH
Laicher
Gernot
G
Durney
Carl H
CH
D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D003094:Collagen / Q000378:metabolism*; D015633:Extravascular Lung Water / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001761:Bleomycin; D003094:Collagen