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. The study of the NMR relaxation properties of lung has important pathophysiological and, potentially, clinical implications. Simple theoretical models have been developed to explain the mechanisms of spin-lattice (T 1 ) and spin-spin (T 2 ) relaxation in biological systems on the basis of the interactions between water molecules and macromolecules (1-5). These theoretical models predict that structural changes occurring in experimental lung injury and clinical pulmonary disease will affect the NMR relaxation times. In particular, T 1 and T 2 are expected to reflect the different stages (i.e., acute inflammatory and chronic fibrotic stages) of certain diffuse interstitial lung disorders (e.g., bleomycin and radiation-induced lung toxicity). The existence of a relationship between NMR relaxation times and collagen accumulation was hypothesized by Shioya et al. (6) in a study of radiation-injured lungs, on the basis of a comparison between NMR measurements and histologic observations.Previous investigations designed to test the above theoretical predictions using the bleomycin animal model (7,8) generated conflicting results. These investigations provide a single value for T 2 . Measurements of T 2 (8) by the CarrPurcell-Meiboom-Gill (CPMG) technique (9,10) apparently ignore the multiexponentiality of the CPMG decay in lung. Furthermore, to the best of our knowledge, there are no published data describing the relationship between NMR relaxation time response and lung collagen content in bleomycin-induced injury. Therefore, the present study was designed to: 1) determine the T 1 and T 2 response to bleomycin injury in rats (using multiexponential analysis for the T 2 -decay curve); and 2) compare the NMR results with histologic data and lung water and collagen content measurements, in order to assess the role of various mechanisms in the T 1 and T 2 r...
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The effects of endotoxin injury on lung NMR relaxation times (T1, CPMG T2, and Hahn decay constant (Hahn T2)) were studied in excised unperfused rat lungs. Blinded histologic examination showed no clear-cut separation between endotoxin and control lungs. Morphometric lung tissue volume density and gravimetric lung water content did not differ significantly between the two groups. In contrast, the values of the fast, intermediate, and slow T2 components, obtained by multiexponential analysis of the CPMG decay curve, increased markedly after endotoxin administration, with minimal overlap between endotoxin and control values. The response of Hahn T2 was, in general, in the same direction as that of CPMG T2; however, Hahn T2 may be more affected by measurement errors and may be less sensitive to the presence of lung injury. T1 showed minimal changes after injury. The present data suggest that CPMG T2 measurements can consistently detect the presence of lung injury even when conventional histologic, morphometric, and gravimetric studies provide negative or equivocal results, and that the CMPG T2 method is superior, in this respect, to the Hahn decay method. T1 does not appear to be sensitive to lung injury in the absence of significant lung water accumulation.
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