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High sensitivity makes hyperpolarized 3He an attractive signal source for visualizing gas flow with magnetic resonance (MR) imaging. Its rapid Brownian motion, however, can blur observed flow lamina and alter measured diffusion rates when excited nuclei traverse shear-induced velocity gradients during data acquisition. Here, both effects are described analytically, and predicted values for measured transport during laminar flow through a straight, 3.2-mm-diameter pipe are validated using two-dimensional (2D) constant-time images of different binary gas mixtures. Results show explicitly how measured transport in narrow conduits is characterized by apparent values that depend on underlying gas dynamics and imaging time. In ventilated rats, this is found to obscure acquired airflow images. Nevertheless, flow splitting at airway branches is still evident and use of 3D vector flow mapping is shown to reveal surprising detail that highlights the correlation between gas dynamics and lung structure.

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...

Jacob RE, Minard KR, Laicher G, Timchalk C. 3D3 He diffusion MRI as a local in vivo morphometric tool to evaluate emphysematous rat lungs. J Appl Physiol 105: 1291-1300, 2008. First published August 21, 2008 doi:10.1152/japplphysiol.90375.2008In this work, we investigate 3 He magnetic resonance imaging as a noninvasive morphometric tool to assess emphysematous disease state on a local level. Emphysema was induced intratracheally in rats with 25 U/100 g body wt of porcine pancreatic elastase dissolved in 200 l saline. Rats were then paired with saline-dosed controls. Nine threedimensional (3D) 3 He diffusion-weighted images were acquired at 1, 2, or 3 wk postdose, after which the lungs were harvested and prepared for histological analysis. Recently introduced indexes sensitive to the heterogeneity of the air space size distribution were calculated. These indexes, D1 and D2, were derived from the moments of the mean equivalent airway diameters. Averaged over the entire lung, it is shown that the average 3 He diffusivity (Dave) correlates well with histology (R ϭ 0.85, P Ͻ 0.0001). By matching small (0.046 cm 2 ) regions in 3 He images with corresponding regions in histological slices, Dave correlates significantly with both D1 and D2 (R ϭ 0.88 and R ϭ 0.90, respectively, with P Ͻ 0.0001). It is concluded that 3 He MRI is a viable noninvasive morphometric tool for localized in vivo emphysema assessment. hyperpolarized gas; elastase; lung histology; diffusion anisotropy EMPHYSEMA is a chronic obstructive pulmonary disease (COPD) typified by tissue destruction and airway expansion (40). Emphysema, particularly the early stages, may be characterized by a heterogeneous distribution of air space sizes (13). Indeed, McLaughlin and Tueller (23) showed that in apparently normal lungs of smokers harvested at autopsy (none of the deaths were attributed to COPD), numerous localized regions of tissue destruction were surrounded by normal tissue. Because early detection of COPD can play a significant role in managing the disease and improving patient outcomes (2, 20), a locally specific and sensitive method of detection may prove beneficial. Hyperpolarized (HP) 3 He and 129 Xe gas have been exploited in clinical and preclinical magnetic resonance imaging (MRI) studies to evaluate lung tissue structure (5,6,8,18,22,33), although perfluorinated gases have also been used (14). In several studies, 3 He MRI has been demonstrated to be sensitive to mild or early emphysema (10,28,34,38). Gas-phase MRI is well suited for detecting emphysema because the diffusivity (Brownian motion) of gas is strongly affected by restrictive barriers, such as alveolar walls. Additionally, the gas contained in larger air spaces contributes proportionally more to the MRI signal in each voxel, making the signal within each voxel a volume-weighted average sensitive to the presence of enlarged air spaces or blebs. Therefore, MRI provides noninvasive, localized information about lung structure while allowing for frequent assessment of disease state wit...

We have measured longitudinal nuclear relaxation rates of 129 Xe in Xe-N 2 mixtures at densities below 0.5 amagats in a magnetic field of 8.0 T. We find that intrinsic spin relaxation in this regime is principally due to fluctuations in the intramolecular spin-rotation ͑SR͒ and chemical-shift-anisotropy ͑CSA͒ interactions, mediated by the formation of 129 Xe-Xe persistent dimers. Our results are consistent with previous work done in one case at much lower applied fields where the CSA interaction is negligible and in another case at much higher gas densities where transient xenon dimers mediate the interactions. We have verified that a large applied field suppresses the persistent-dimer mechanism, consistent with standard relaxation theory, allowing us to measure room-temperature gas-phase relaxation times T 1 for 129 Xe greater than 25 h at 8.0 T. These data also yield a maximum possible low-field T 1 for pure xenon gas at room temperature of 5.45± 0.2 h. The coupling strengths for the SR and CSA interactions that we extract are in fair agreement with estimates based both on previous experimental work and on ab initio calculations. Our results have potential implications for the production and storage of large quantities of hyperpolarized 129 Xe for use in various applications.

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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.