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The response of the NMR relaxation times (T1, CPMG T2, and Hahn T2) 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 (T2f and T2i, 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 (T2s) showed no significant changes. The response of T1 and the slow component of the Hahn T2 was, on the whole, similar to that of CPMG T2f and T2i. T1 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. T1 and T2 data were directly correlated with lung water content and inversely correlated with collagen content. Our results indicate that NMR relaxation time measurements (particularly T2) reflect the structural changes associated with bleomycin injury. The prolonged T2 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-T2 and Hahn-T2 measurements can be valuable as a potentially noninvasive method for characterizing bleomycin-induced lung injury and pathologically related lung disorders. Magn Reson Med 47:246–256, 2002. © 2002 Wiley-Liss, Inc.

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.

We compared in vivo and in vitro Hahn echo T2 measurements in rat lungs in both imaging and nonimaging modes. All measurements could be characterized by multiexponential functions consisting of either two or three exponentials. Essentially the same values of the time constants were observed for spontaneously breathing rats and for excised lungs. © 1991 Academic Press, Inc.

Inflated lungs are characterized by a short nuclear magnetic resonance (NMR) free induction decay (rapid disappearance of NMR signal), likely due to internal (tissue-induced) magnetic field inhomogeneity produced by the alveolar air-tissue interface. This phenomenon can also be detected using temporally symmetric and asymmetric NMR spin-echo sequences; these sequences generate a pair of NMR images from which a difference signal (delta) is obtained (reflecting the signal from lung water experiencing the air-tissue interface effect). We measured delta in normal excised rat lungs at inflation pressures of 0-30 cmH2O for asymmetry times (a) of 1-6 ms. Delta was low in degassed lungs and increased markedly with alveolar opening when measured at a = 6 ms (delta 6 ms); delta 6 ms varied little during the rest of the inflation-deflation cycle. Delta 1 ms (a = 1 ms) did not vary significantly on inflation and deflation. Measurements of delta at a = 3 and 5 ms generally lay between those of delta 1 ms and delta 6 ms. These findings, which are consistent with theoretical predictions, suggest that measurements of delta at appropriate asymmetry times are particularly sensitive to alveolar opening and may provide a means of distinguishing alveolar recruitment from alveolar distension in the pressure-volume behavior of the lung.

Estimates of lung water content obtained from nuclear magnetic resonance (NMR) and morphometric and gravimetric measurements were compared in normal and experimentally injured rats. Average lung water density (rho H2O) was measured by an NMR technique in excised unperfused rat lungs (20 normal lungs and 12 lungs with oleic acid-induced edema) at 0 (full passive deflation) and 30 cmH2O lung inflation pressure and in vivo (4 normal rats and 8 rats with lung injury induced by oleic acid or rapid saline infusion). The rho H2O values were compared with morphometric measurements of lung tissue volume density (Vv) obtained from the same lungs fixed at corresponding liquid-instillation pressures. A close correlation was observed between rho H2O and Vv in normal and injured excised lungs [correlation coefficient (r) = 0.910, P < 0.01]. In vivo rho H2O was also closely correlated with Vv (r = 0.897, P < 0.01). The correlation coefficients between rho H2O and gravimetric lung water content (LWGr) were lower in the excised lung group (r = 0.663 and 0.692, respectively, for rho H2O at 0 and 30 cmH2O lung inflation pressure, P < 0.01) than in the in vivo study (r = 0.857, P < 0.01). Our results indicate that NMR techniques, which are noninvasive and nondestructive, provide reliable estimates of lung water density and that the influence of lung inflation on rho H2O is important (compared with the effect of lung water accumulation in lung injury) only in the presence of deliberately induced very large variations in the lung inflation level.

The alveolar air/tissue interface markedly affects the NMR properties of lungs by causing an NMR signal loss as a result of internal (tissue-induced) magnetic field inhomogeneity. The signal loss can be measured as the difference in NMR signal intensity (difference signal delta) between a pair of images obtained using temporally symmetric and asymmetric spin-echo sequences. Previous data indicate that the difference signal measured at an asymmetry time of 6 ms (delta 6ms) is very low in degassed lungs and increases markedly with alveolar opening. Theoretically, the NMR behavior of edematous lungs is expected to differ from that of normal nondegassed lungs because alveolar flooding and collapse are equivalent to partial (regional) degassing. To test this prediction, we measured delta 6ms in normal and edematous (oleic acid-injured) excised unperfused rat lungs at 5, 10, 20, 30, and 0 (full passive deflation) cm H2O inflation pressure (PL). Lung volume changes were estimated from NMR lung water density (pH2O) measurements. In normal lungs, delta 6ms did not vary with PL. In edematous lungs delta 6ms was, as predicted, significantly lower than normal at 5 and 10 cm H2O PL but rose markedly (to about normal) as PL was further increased. Upon subsequent deflation from 30 to 0 cm H2O PL, delta 6ms did not vary significantly or decreased. On the basis of our theoretical models, the data could be interpreted as reflecting the loss of alveolar air/tissue interface as a result of alveolar flooding and the relative contributions of airspace recruitment and distension to the lung volume changes. Histologic and morphometric data obtained from the same lungs supported this interpretation.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-Evans male adult rats were exposed for sixteen weeks to 2450-MHz CW microwaves at an average power density of mW/cm2. The resulting dose rate was 1.23 (+/- 0.25SEM) mW/g. The animals were exposed eight hours a day, five days a week, for a total of 640 h in a monopole-above-ground radiation chamber while housed in Plexiglas holding cages. Daily measures of body mass and of food and water intakes indicated no statistically significant effects of microwave irradiation. Biweekly stabilimetric tests immediately after exposure revealed a significant depression of behavioral activity by 15 microwave-exposed rats as compared with 15 sham-exposed animals. Measures of locomotor activity based on revolutions of a running wheel, which were obtained during 12-h periods between each 8-h exposure, showed no significant effect of irradiation. Blood sampled after 2, 6, 10, and 14 weeks of exposure indicated slight alterations of sulfhydryl groups, and of red and white blood-cell counts. Measures of levels of 17-ketosteroids in urine at weeks 1, 5, 9, and 12 of exposure, and mass of adrenals, heart, and liver at the end of the sixteen-week period of exposure, revealed no indications of stress.

The present study was designed to determine the value of nuclear magnetic resonance (NMR) imaging as a technique for quantifying lung water distribution and to estimate the degree of spatial resolution achieved by this technique. The spatial distribution of water was determined in six small (0.76 ml) rat lung tissue specimens by an NMR line-scan technique. After NMR imaging, each lung specimen was frozen and subdivided into slices; the gravimetric lung water content for each lung slice was compared with the integrated NMR water content over the volume corresponding to the same lung slice. In each tissue specimen, NMR and gravimetric lung water values were significantly correlated; the correlation coefficient for the pooled data for all six lung specimens was 0.91 (P less than 0.01). In two lung specimens, NMR values tended to be slightly higher than the gravimetric values. The magnitude of the difference between NMR and gravimetric values was generally less than 20% and only occasionally exceeded 25%. Our results suggest that the NMR-imaging method provides satisfactory estimates of lung water content and its distribution; the resolving power of the technique is excellent, as shown by its ability to detect water content differences between lung tissue slices of volume as small as 0.076 ml.

Long-Evans male adult rats were exposed for 16 weeks to 915-MHz CW microwaves at an average power density of 5 mW/cm2. The resulting dose rate was 2.46 (+/- 0.29 SEM) mW/g. The animals were exposed eight hours a day, five days a week, for a total of 640 h in a monopole-above ground radiation chamber while housed in Plexiglas cages. Daily measures of body mass and of food and water intake indicated no statistically significant effects of microwave irradiation. Measures by activity wheels and stabilimetric platforms of spontaneous locomotion indicate than mean activity levels increased about 25% after microwave exposure, but the findings are doubtful statistical significance (Ps.10 but.05). Studies of blood sampled after 2, 6, 10, and 14 weeks of exposure revealed alterations of free sulfhydryls. Measures of levels of urinary 17-ketosteroids at weeks 1, 5, 9, and 12 of exposure, and measures of brain hypothalamic tissue, and of mass of adrenals, heart, and liver at the end of the 16-week period, revealed no significant differences between irradiated and control animals. Cortical EEGs sampled after conclusion of microwave exposures also revealed no significant differences.

A surface integral equation (SIE) method is used to calculate the specific absorption rate (SAR) in spherically capped cylindrical models irradiated by an axially incident electromagnetic plane wave (K polarization) in a frequency range for which calculations previously have not been available (80-400 MHz for man models). In the SIE method, the electromagnetic (EM) field relations are formulated in terms of electric and magnetic currents on the surface of the model. The average SAR is calculated from the far scattered EM fields by means of the forward scattering theorem. SAR data calculated by the SIE method agree with data calculated by the extended boundary condition method (EBCM) for frequencies up to 80 MHz (the upper frequency limit of the EBCM) for man models. For rat models exposed to 1-3 GHz radiation, reasonable agreement was also obtained with the limited experimental data available.

Nuclear magnetic resonance imaging was used to determine quantitatively the water distribution of saline-filled and normal rat lungs in both isolated lung and in situ preparations. Regional lung edema was easily detected. Studies of an isolated lung fragment indicate an accuracy of better than 1 percent and images of H2O/D2O phantoms indicate an average error of 2.7 percent.

We have developed a new analytical method that uses nuclear magnetic resonance (NMR) imaging data to quantify lung water content and distribution. This new method generates a distribution of lung water density in which the fraction of voxels corresponding to a given water density is plotted on the vertical axis as a function of water density on the horizontal axis, thereby complementing the spatial information provided by the NMR image. We obtained reproducible lung water distribution data at comparable lung volumes in normal excised lungs and in intact living rats. In normal excised unperfused rat lungs, the distribution varied with the degree of inflation, but the changes were small compared with those associated with lung edema. The lung water density distribution changed markedly after induction of lung edema by intrabronchial saline instillation, intravenous oleic acid injection, and rapid intravenous saline infusion. Lung water density distribution data were well correlated (correlation coefficient = 0.948 for the excised lungs and 0.823 for the intact living rats) with gravimetric lung water measurements. The new analytical method is noninvasive, provides easily repeatable measurements, and is as sensitive as the gravimetric technique to lung water changes.

Inflated lung has a nuclear magnetic resonance (NMR) free-induction decay (FID) which is short compared with that of collapsed lung and those of other body tissues. An almost identically short FID is obtained from a slurry of 5-micron alumina particles in water. Interfaces between air and water in lung and between alumina and water in the slurry appear to be the source of spatial internal magnetic inhomogeneities which produce NMR line broadening and the short FID. Paired images that included lung, taken with paired symmetric and asymmetric NMR spin-echo sequences, permit the generation of an image, by subtraction, of the lung isolated from surrounding tissue. These new lung images are neither proton density, T1 (spin-lattice relaxation time), nor T2 (spin-spin relaxation time) images. They complement current NMR images and provide information about regional lung inflation. This previously unrecognized NMR property of lung tissue has potential application in NMR imaging, in quantitative determination of lung water and its distribution, and in the quantitation of regional lung inflation.

Continuous wave (cw) microwave irradiation at 960 MHz has caused bradycardia in isolated, perfused rat hearts maintained at 20°C. The observed bradycardia occurred at microwave dose rates that should have caused mild tachycardia in the heart based on the thermogenic properties of the irradiation. The observed bradycardia, moreover, exhibited neurologic features because atropinized hearts showed strong tachycardia during irradiation and hearts treated with propranolol showed significantly stronger bradycardia during irradiation than that seen without drugs. Use of the liquid-crystal optical-fiber (LCOF) temperature probe has shown, by calorimetric methods, that the microwave-induced bradycardia occurred at dose rates of 1.3 and 2.1 mW/g. We hypothesize that microwave energy interacts with the remaining portion of the autonomic nervous system within the heart to produce the observed chronotropic effects.