Characterization of bleomycin lung injury by nuclear magnetic resonance: Correlation between NMR relaxation times and lung water and collagen content

Abstract

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...

Lung parenchymal signal intensity in MRI: A technical review with educational aspirations regarding reversible versus irreversible transverse relaxation effects in common pulse sequences

“…The three T 2 values became significantly prolonged in deflated lungs (27). Overall, their results were consistent with in vivo (28) and in vitro (29) T 2 studies of rat lungs using Hahn spin echo and multi-echo CPMG sequences. Furthermore, using cardiac-triggered SSFSE/HASTE sequences, Hatabu et al reported relatively long T 2 values of 60 to 100 ms in vivo in humans (17).…”

“…In particular, the fact that longer T 2 values are found when multiple spin echo sequences are used is consistent with bodily spin motion, e.g. perfusion and/or diffusion, within the background microscopic field gradients created by the multiple air/tissue interfaces within lung parenchyma, as discussed in the original articles (3,26-29). This same mechanism is most probably responsible for later observations by Ohno et al of an inter echo spacing dependence of lung signal from SSFSE/HASTE sequences (30).…”

“…Though somewhat simplified, the horse race analogy loosely explains the link between broad frequency distributions (a wide variation in constant horse speeds) and the short lung T 2 * values (rapid dephasing) as measured by several groups (19-25). Let us review these reports as well as studies designed to measure the irreversible relaxation rate R 2 (17,26-29), beginning with the latter.…”

Noninvasive Imaging of Experimental Lung Fibrosis

“…It has been reported that lung fibrosis in BLM-treated mice is manifested by an increased T 2 , whereas lung inflammation is associated with decreased T 2 , suggesting that spinspin relaxation time may differentiate inflammation and fibrosis in the lung (27). However, an apparently opposite result has been observed in BLM-treated rats (28). To date, most of the studies suggest that signal intensity (S 0 ) measurements help differentiate lung inflammation and fibrosis (25,26,29,30).…”

Texture analysis using proton density and T2 relaxation in patients with histological usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP)

“…The feasibility of measuring lung water content and distribution by MRI techniques has been well recognized since the 1980s [22–25]. However, so far quantitative techniques such as T2 relaxation and PD for inflammatory activity assessment in chronic interstitial lung disease have only been performed on animal models of bleomycin induced fibrosis [26–28]. We aim to investigate for the first time the clinical utility of these methods applied to a cohort of patients with NSIP using a clinical 1.5T MRI scanner.…”