Fast dynamic ventilation MRI of hyperpolarized 129 Xe using spiral imaging.

PURPOSE: To develop and optimize a rapid dynamic hyperpolarized 129 Xe ventilation (DXeV) MRI protocol and investigate the feasibility of capturing pulmonary signal-time curves in human lungs. THEORY AND METHODS: Spiral k-space trajectories were designed with the number of interleaves Nint = 1, 2, 4, and 8 corresponding to voxel sizes of 8 mm, 5 mm, 4 mm, and 2.5 mm, respectively, for field of view = 15 cm. DXeV images were acquired from a gas-flow phantom to investigate the ability of Nint = 1, 2, 4, and 8 to capture signal-time curves. A finite element model was constructed to investigate gas-flow dynamics corroborating the experimental signal-time curves. DXeV images were also carried out in six subjects (three healthy and three chronic obstructive pulmonary disease subjects). RESULTS: DXeV images and numerical modelling of signal-time curves permitted the quantification of temporal and spatial resolutions for different numbers of spiral interleaves. The two-interleaved spiral (Nint = 2) was found to be the most time-efficient to obtain DXeV images and signal-time curves of whole lungs with a temporal resolution of 624 ms for 13 slices. Signal-time curves were well matched in three healthy volunteers. The Spearman's correlations of chronic obstructive pulmonary disease subjects were statistically different from three healthy subjects (P < 0.05). CONCLUSION: The Nint = 2 spiral demonstrates the successful acquisition of DXeV images and signal-time curves in healthy subjects and chronic obstructive pulmonary disease patients. Magn Reson Med 79:2597-2606, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Multiple breath washout of hyperpolarized 129 Xe and 3 He in human lungs with three-dimensional balanced steady-state free-precession imaging.

PURPOSE: To compare quantitative fractional ventilation measurements from multiple breath washout imaging (MBW-I) using hyperpolarized 3 He with both spoiled gradient echo (SPGR) and balanced steady-state free precession (bSSFP) three-dimensional (3D) pulse sequences and to evaluate the feasibility of MBW-I with hyperpolarized 129 Xe. METHODS: Seven healthy subjects were scanned using 3 He MBW-I with 3D SPGR and bSSFP sequences. Five also underwent MBW-I with 129 Xe. A dual-tuned coil was used to acquire MBW-I data from both nuclei in the same subject position, enabling direct comparison of regional information. RESULTS: High-quality MBW images were obtained with bSSFP sequences using a reduced dose (100 mL) of inhaled hyperpolarized 3 He. 3D MBW-I with 129 Xe was also successfully demonstrated with a bSSFP sequence. Regional quantitative ventilation measures derived from 3 He and 129 Xe MBW-I correlated well in all subjects (P < 0.001) with mean Pearson's correlation coefficients of r = 0.61 and r = 0.52 for 3 He SPGR-bSSFP and 129 Xe-3 He (bSSFP) comparisons. The average intersubject mean difference (and standard deviation) in fractional ventilation in SPGR-bSSFP and 129 Xe-3 He comparisons was 15% (28%) and 9% (38%), respectively. CONCLUSIONS: Improved sensitivity in MBW-I can be achieved with polarization-efficient bSSFP sequences. Same scan-session 3D MBW-I with 3 He and 129 Xe has been demonstrated using a dual-tuned coil. Magn Reson Med 77:2288-2295, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Reproducibility of quantitative indices of lung function and microstructure from 129 Xe chemical shift saturation recovery (CSSR) MR spectroscopy.

PURPOSE: To evaluate the reproducibility of indices of lung microstructure and function derived from 129 Xe chemical shift saturation recovery (CSSR) spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD), and to study the sensitivity of CSSR-derived parameters to pulse sequence design and lung inflation level. METHODS: Preliminary data were collected from five volunteers on three occasions, using two implementations of the CSSR sequence. Separately, three volunteers each underwent CSSR at three different lung inflation levels. After analysis of these preliminary data, five COPD patients were scanned on three separate days, and nine age-matched volunteers were scanned three times on one day, to assess reproducibility. RESULTS: CSSR-derived alveolar septal thickness (ST) and surface-area-to-volume (S/V) ratio values decreased with lung inflation level (P < 0.001; P = 0.057, respectively). Intra-subject standard deviations of ST were lower than the previously measured differences between volunteers and subjects with interstitial lung disease. The mean coefficient of variation (CV) values of ST were 3.9 ± 1.9% and 6.0 ± 4.5% in volunteers and COPD patients, respectively, similar to CV values for whole-lung carbon monoxide diffusing capacity. The mean CV of S/V in volunteers and patients was 14.1 ± 8.0% and 18.0 ± 19.3%, respectively. CONCLUSION: 129 Xe CSSR presents a reproducible method for estimation of alveolar septal thickness. Magn Reson Med 77:2107-2113, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Hyperpolarized (129) Xe MRI using isobutene as a new quenching gas.

The use of a quenching gas, isobutene, with a low vapor pressure was investigated to enhance the utility of hyperpolarized (129) Xe (HP Xe) MRI. Xenon mixed with isobutene was hyperpolarized using a home-built apparatus for continuously producing HP Xe. The isobutene was then readily liquefied and separated almost totally by continuous condensation at about 173 K, because the vapor pressure of isobutene (0.247 kPa) is much lower than that of Xe (157 kPa). Finally, the neat Xe gas was continuously delivered to mice by spontaneous inhalation. The HP Xe MRI was enhanced twofold in polarization level and threefold in signal intensity when isobutene was adopted as the quenching gas instead of N2 . The usefulness of the HP Xe MRI was verified by application to pulmonary functional imaging of spontaneously breathing mice, where the parameters of fractional ventilation (ra ) and gas exchange (fD ) were evaluated, aiming at future extension to preclinical studies. This is the first application of isobutene as a quenching gas for HP Xe MRI.

Hyperpolarized (129) Xe imaging of the rat lung using spiral IDEAL.

PURPOSE: To implement and optimize a single-shot spiral encoding strategy for rapid 2D IDEAL projection imaging of hyperpolarized (Hp) (129) Xe in the gas phase, and in the pulmonary tissue (PT) and red blood cells (RBCs) compartments of the rat lung, respectively. THEORY AND METHODS: A theoretical and experimental point spread function analysis was used to optimize the spiral k-space read-out time in a phantom. Hp (129) Xe IDEAL images from five healthy rats were used to: (i) optimize flip angles by a Bloch equation analysis using measured kinetics of gas exchange and (ii) investigate the feasibility of the approach to characterize the exchange of Hp (129) Xe. RESULTS: A read-out time equal to approximately 1.8 × T2* was found to provide the best trade-off between spatial resolution and signal-to-noise ratio (SNR). Spiral IDEAL approaches that use the entire dissolved phase magnetization should give an SNR improvement of a factor of approximately three compared with Cartesian approaches with similar spatial resolution. The IDEAL strategy allowed imaging of gas, PT, and RBC compartments with sufficient SNR and temporal resolution to permit regional gas exchange measurements in healthy rats. CONCLUSION: Single-shot spiral IDEAL imaging of gas, PT and RBC compartments and gas exchange is feasible in rat lung using Hp (129) Xe. Magn Reson Med 76:566-576, 2016. © 2015 Wiley Periodicals, Inc.

Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma.

PURPOSE: Asthma is a disease of increasing worldwide importance that calls for new investigative methods. Ex vivo lung tissue is being increasingly used to study functional respiratory parameters independent of confounding systemic considerations but also to reduce animal numbers and associated research costs. In this work, a straightforward laboratory method is advanced to probe dynamic changes in gas inhalation patterns by using an ex vivo small animal ovalbumin (OVA) model of human asthma. METHODS: Hyperpolarized (hp) (129) Xe was actively inhaled by the excised lungs exposed to a constant pressure differential that mimicked negative pleural cavity pressure. The method enabled hp (129) Xe MRI of airway responsiveness to intravenous methacholine (MCh) and airway challenge reversal through salbutamol. RESULTS: Significant differences were demonstrated between control and OVA challenged animals on global lung hp (129) Xe gas inhalation with P < 0.05 at MCh dosages above 460 µg. Spatial mapping of the regional hp gas distribution revealed an approximately three-fold increase in heterogeneity for the asthma model organs. CONCLUSION: The experimental results from this proof of concept work suggest that the ex vivo hp noble gas imaging arrangement and the applied image analysis methodology may be useful as an adjunct to current diagnostic techniques. Magn Reson Med 76:1224-1235, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Feasibility of human lung ventilation imaging using highly polarized naturally abundant xenon and optimized three-dimensional steady-state free precession.

PURPOSE: To demonstrate the potential for high quality MRI of pulmonary ventilation using naturally abundant xenon (NAXe) gas. METHODS: MRI was performed at 1.5 Tesla (T) and 3 T on one healthy smoker and two healthy never-smokers. 129Xe gas was polarized to ∼25% using an in-house spin-exchange optical pumping polarizer fitted with a laser diode array with integrated volume holographic grating and optical train system. Volunteers inhaled 1 L of NAXe for an 8 to 15 s breathhold while MR images were acquired with full-lung coverage using a three-dimensional steady-state free precession sequence, optimized for maximum signal-to-noise ratio (SNR) at a given spatial resolution. For the purpose of image quality comparison, the MR acquisition was repeated at 1.5 T with 400 mL enriched xenon and 200 mL 3He. RESULTS: All NAXe lung images were of high quality, with mean SNRs of 25-40 (voxel 4.2 × 4.2 × 8/10 mm3) and ∼30% improvement at 3 T versus 1.5 T. The high SNR permitted identification of minor ventilation defects in the healthy smoker's lungs. NAXe images were of comparable SNR to those obtained with enriched xenon and 3He. CONCLUSION: Optimization of MR pulse sequences and advances in polarization technology have facilitated high quality pulmonary ventilation imaging with inexpensive NAXe gas.

Pulmonary hyperpolarized (129) Xe morphometry for mapping xenon gas concentrations and alveolar oxygen partial pressure: Proof-of-concept demonstration in healthy and COPD subjects.

PURPOSE: Diffusion-weighted (DW) hyperpolarized (129) Xe morphometry magnetic resonance imaging (MRI) can be used to map regional differences in lung tissue micro-structure. We aimed to generate absolute xenon concentration ([Xe]) and alveolar oxygen partial pressure (pA O2 ) maps by extracting the unrestricted diffusion coefficient (D0 ) of xenon as a morphometric parameter. METHODS: In this proof-of-concept demonstration, morphometry was performed using multi b-value (0, 12, 20, 30 s/cm(2) ) DW hyperpolarized (129) Xe images obtained in four never-smokers and four COPD ex-smokers. Morphometric parameters and D0 maps were computed and the latter used to generate [Xe] and pA O2 maps. Xenon concentration phantoms estimating a range of values mimicking those observed in vivo were also investigated. RESULTS: Xenon D0 was significantly increased (P = 0.035) in COPD (0.14 ± 0.03 cm(2) /s) compared with never-smokers (0.12 ± 0.02 cm(2) /s). COPD ex-smokers also had significantly decreased [Xe] (COPD = 8 ± 7% versus never-smokers = 13 ± 8%, P = 0.012) and increased pA O2 (COPD = 18 ± 3% versus never-smokers = 15 ± 3%, P = 0.009) compared with never-smokers. Phantom measurements showed the expected dependence of D0 on [Xe] over the range of concentrations anticipated in vivo. CONCLUSION: DW hyperpolarized (129) Xe MRI morphometry can be used to simultaneously map [Xe] and pA O2 in addition to providing micro-structural biomarkers of emphysematous destruction in COPD. Phantom measurements of D0 ([Xe]) supported the hypotheses that differences in subjects may reflect differences in functional residual capacity.

Radiofrequency pulse design for the selective excitation of dissolved 129Xe.

PURPOSE: To optimize radiofrequency (RF) pulses for the selective excitation of dissolved phase (129)Xe that take into account the very short T2*, while simultaneously, minimally exciting the much larger gas signal. METHODS: Numerical simulations of Shinnar le-Roux pulses and binomial coefficient composite-element pulses were performed and experimentally implemented on a 1.5 Tesla (T) clinical scanner. These were compared with pulses commonly used for short T2* imaging from the literature. The pulses were then experimentally tested in vivo with healthy volunteers inhaling hyperpolarized (129)Xe using nuclear MR spectroscopy on a 1.5T clinical scanner. RESULTS: Standard RF excitation pulses inadvertently excite the gas compartment, or are long enough that the T2* of the dissolved compartment deteriorates the received signal. Amplitude modulated binomial composite pulses perform well being short and having high selectivity, however, deteriorate at high amplifier gain setting. Composite pulses using pulse width modulation provide the desired frequency response even in these nonlinear, high gain regimes. CONCLUSION: Composite pulses provide a means of very narrow band frequency selectivity in a short duration pulse that is well suited to dissolved (129)Xe imaging. Pulse width modulation maintains the desired frequency response even in the presence of amplitude distortion.

Regional mapping of gas uptake by blood and tissue in the human lung using hyperpolarized xenon-129 MRI.

PURPOSE: To develop a breathhold acquisition for regional mapping of ventilation and the fractions of hyperpolarized xenon-129 (Xe129) dissolved in tissue (lung parenchyma and plasma) and red blood cells (RBCs), and to perform an exploratory study to characterize data obtained in human subjects. MATERIALS AND METHODS: A three-dimensional, multi-echo, radial-trajectory pulse sequence was developed to obtain ventilation (gaseous Xe129), tissue, and RBC images in healthy subjects, smokers, and asthmatics. Signal ratios (total dissolved Xe129 to gas, tissue-to-gas, RBC-to-gas, and RBC-to-tissue) were calculated from the images for quantitative comparison. RESULTS: Healthy subjects demonstrated generally uniform values within coronal slices, and a gradient in values along the anterior-to-posterior direction. In contrast, images and associated ratio maps in smokers and asthmatics were generally heterogeneous and exhibited values mostly lower than those in healthy subjects. Whole-lung values of total dissolved Xe129 to gas, tissue-to-gas, and RBC-to-gas ratios in healthy subjects were significantly larger than those in diseased subjects. CONCLUSION: Regional maps of tissue and RBC fractions of dissolved Xe129 were obtained from a short breathhold acquisition, well tolerated by healthy volunteers and subjects with obstructive lung disease. Marked differences were observed in spatial distributions and overall amounts of Xe129 dissolved in tissue and RBCs among healthy subjects, smokers and asthmatics.

MOXE: a model of gas exchange for hyperpolarized 129Xe magnetic resonance of the lung.

We present a model of gas exchange for hyperpolarized (129)Xe in the lung, which we refer to as the Model of Xenon Exchange. The model consists of two expressions and characterizes uptake of dissolved xenon in the lung at two different resonance frequencies. The two expressions are governed by the following five critical pulmonary parameters that characterize both lung function and structure: the surface-area-to-volume ratio, barrier-to-septum ratio (ratio between air-blood barrier thickness and septal thickness), hematocrit, gas-exchange time constant, and pulmonary capillary transit time. The model is first validated by computer simulation. We show that Model of Xenon Exchange can be used to measure the pulmonary parameters mentioned above under various pathological or physiological conditions and is robust against moderate noise. Model of Xenon Exchange is further used to fit an existing data set of xenon uptake, thereby we demonstrate that the data can be well interpreted with Model of Xenon Exchange and reasonable parameters from the fitting routine. The good results obtained in both simulation and fitting to real data indicate that the model is sensitive to various functional and structural changes of the lung, and that it will allow for screening for a variety of pulmonary diseases by using hyperpolarized (129)Xe of the lung.

Direct imaging of hyperpolarized 129Xe alveolar gas uptake in a mouse model of emphysema.

MRI of hyperpolarized (129)Xe dissolved in pulmonary tissues, and blood has the potential to offer a new tool for regional evaluation of pulmonary gas exchange and perfusion; however, the extremely short T2* and low magnetization density make it difficult to acquire the image. In this study, an ultrashort echo-time sequence was introduced, and its feasibility to quantitatively assess emphysema-like pulmonary tissue destruction by a combination of dissolved- and gas-phase (129)Xe lung MRI was investigated. The ultrashort echo-time has made it possible to acquire dissolved (129)Xe images with reasonably high spatial resolution of 0.625 × 0.625 mm(2) and to obtain T2* of 0.67 ± 0.30 ms in a spontaneously breathing mouse at 9.4 T. The regional dynamic alveolar gas uptake as well as subsequent transport by pulmonary blood flow was also visualized. The ratio of (129)Xe magnetization that diffused into the septa relative to the gas-phase magnetization F was regionally evaluated. The mean F value of elastase-treated mice was 2.28 ± 0.46%, which was significantly reduced from that of control mice 3.41 ± 0.48% (P = 0.0052). This reflects the reduced uptake efficiency due to alveolar tissue destruction and is correlated with the histologically derived alveolar surface-to-volume ratio.

Regional ventilation mapping of the rat lung using hyperpolarized ¹²9Xe magnetic resonance imaging.

Lung ventilation was mapped in seven healthy male Sprague-Dawley rats (433 ± 24 g) using hyperpolarized ¹²9Xe magnetic resonance imaging (MRI) at 3.0 T, and validated with hyperpolarized ³He MRI under similar ventilator conditions. Ventilation maps were obtained using flip angle variation for offset of RF and relaxation (FAVOR) which is a multiple breath imaging technique that extracts the fractional ventilation parameter, r, on a pixel-by-pixel basis from the dynamic signal enhancement. r is defined as the fractional refreshment of gas per breath. Under the ventilator conditions used in this work, whole-lung measurements of fractional ventilation obtained using hyperpolarized ¹²9Xe were not significantly different from those obtained using hyperpolarized ³He (p = 0.8125 by a Wilcoxon matched pairs test). Fractional ventilation gradients calculated in the superior/inferior (S/I) and anterior/posterior (A/P) directions obtained using hyperpolarized ¹²9Xe were not significantly different from those obtained using hyperpolarized ³He (p = 0.9375 and p = 0.1563, for the S/I and A/P directions, respectively). Following baseline fractional ventilation measurements, one representative rat was challenged with methacholine and fractional ventilation measurements were performed over a time course of 10 min. A reduction and subsequent recovery in whole-lung r values were detected using the FAVOR method.

Origin of dissolved-phase hyperpolarized 129Xe signal in the mouse chest based on experimental evidence from extensive magnetic resonance measurements.

Pulmonary study using hyperpolarized (HP) (129)Xe gas as an imaging medium must focus on dissolved-phase signals to make the most of the characteristic affinity of xenon for biological tissues, including blood. However, the spectral pattern of these signals differs between mice and other animals, including rats, canines, and humans. Dissolved-phase study has been reported only scarcely in mice, so spectral assignment has been an important subject for HP (129)Xe magnetic resonance (MR) spectroscopy (MRS) and MR imaging for its wider application. We performed MRS, including magnetization transfer experiments, and MR imaging studies to confirm the origin of dissolved-phase signals of mice ex vivo and in vivo and obtained evidence to assign dissolved-phase signals at 192 ppm for epicardial fat, 196 ppm for lung parenchyma, and 200 ppm for blood. These results were the first to show the possibility of fast exchange of xenon between plasma and red blood cells.

Noninvasive detection of pulmonary tissue destruction in a mouse model of emphysema using hyperpolarized 129Xe MRS under spontaneous respiration.

In the present study, a chemical shift saturation recovery method in hyperpolarized (129)Xe MR spectroscopy measurements was applied to two groups of spontaneously breathing mice, an elastase-induced emphysema model and a control group. Parameters detected were those related to lung structures and functions, such as alveolar septal thickness, h, the ratio of the alveolar septal volume relative to gas space volume, V(s)/V(a), and the transit time of blood through the gas exchange region, τ. To investigate the potential of these parameters as biomarkers, an attempt was made to detect physiologic changes in the lungs of elastase-treated mice. Our results showed that V(s)/V(a) was significantly reduced in elastase-treated mice, reflecting emphysema-like destruction of the alveolar wall. Compared with histologic results, this degree of reduction was shown to reflect the severity of wall destruction. On the other hand, significant changes in other parameters, h and τ, were not shown. This study is the first application of hyperpolarized (129)Xe MR spectroscopy to a mouse model of emphysema and shows that the V(s)/V(a) volume ratio is an effective biomarker for emphysema that could become useful in drug research and development through noninvasive detection of pathologic changes in small rodents.

Pulmonary perfusion and xenon gas exchange in rats: MR imaging with intravenous injection of hyperpolarized 129Xe.

PURPOSE: To develop and demonstrate a method for regional evaluation of pulmonary perfusion and gas exchange based on intravenous injection of hyperpolarized xenon 129 ((129)Xe) and subsequent magnetic resonance (MR) imaging of the gas-phase (129)Xe emerging in the alveolar airspaces. MATERIALS AND METHODS: Five Fischer 344 rats that weighed 200-425 g were prepared for imaging according to an institutional animal care and use committee-approved protocol. Rats were ventilated, and a 3-F catheter was placed in the jugular (n = 1) or a 24-gauge catheter in the tail (n = 4) vein. Imaging and spectroscopy of gas-phase (129)Xe were performed after injecting 5 mL of half-normal saline saturated with (129)Xe hyperpolarized to 12%. Corresponding ventilation images were obtained during conventional inhalation delivery of hyperpolarized (129)Xe. RESULTS: Injections of (129)Xe-saturated saline were well tolerated and produced a strong gas-phase (129)Xe signal in the airspaces that resulted from (129)Xe transport through the pulmonary circulation and diffusion across the blood-gas barrier. After a single injection, the emerging (129)Xe gas could be detected separately from (129)Xe remaining in the blood and was imaged with an in-plane resolution of 1 x 1 mm and a signal-to-noise ratio of 25. Images in one rat revealed a matched ventilation-perfusion deficit, while images in another rat showed that xenon gas exchange was temporarily impaired after saline overload, with recovery of function 1 hour later. CONCLUSION: MR imaging of gas-phase (129)Xe emerging in the pulmonary airspaces after intravenous injection has the potential to become a sensitive and minimally invasive new tool for regional evaluation of pulmonary perfusion and gas exchange. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/2513081550/DC1.

A simple method for quantitative measurement and analysis of hyperpolarized (129)Xe uptake dynamics in mouse brain under controlled flow.

We established a simple method for measuring and quantifying uptake dynamics of hyperpolarized (HP) (129)Xe in mouse brain, which includes application of a saturation recovery pulse sequence under controlled flow of HP (129)Xe. The technique allows pursuit of the time-dependent change in (129)Xe nuclear magnetic resonance signal in the uptake process without effect from radiofrequency destruction of the polarization and the dynamics in mouse lung. The uptake behavior is well described by a simple model that depends only on a decay rate constant comprising cerebral blood flow and the longitudinal relaxation rate of HP (129)Xe in the brain tissue. The improved analysis enabled precise determination of the decay rate constant as 0.107+/-0.013 s(-1) (+/-standard deviation, n=5), leading to estimation of longitudinal relaxation time, T(1i), as 15.3+/-3.5 s.

Functional lung imaging using hyperpolarized gas MRI.

The noninvasive assessment of lung function using imaging is increasingly of interest for the study of lung diseases, including chronic obstructive pulmonary disease (COPD) and asthma. Hyperpolarized gas MRI (HP MRI) has demonstrated the ability to detect changes in ventilation, perfusion, and lung microstructure that appear to be associated with both normal lung development and disease progression. The physical characteristics of HP gases and their application to MRI are presented with an emphasis on current applications. Clinical investigations using HP MRI to study asthma, COPD, cystic fibrosis, pediatric chronic lung disease, and lung transplant are reviewed. Recent advances in polarization, pulse sequence development for imaging with Xe-129, and prototype low magnetic field systems dedicated to lung imaging are highlighted as areas of future development for this rapidly evolving technology.

Analysis of hyperpolarized 129Xe dynamics in mouse lungs under spontaneous respiration for separate determination of lung functional parameters and relaxation time.

Magnetic resonance spectroscopy (MRS) was used to investigate the dynamics of hyperpolarized (HP) 129Xe respiration in the chests of mice under spontaneous respiration. The washout curve was analyzed using Kety's exchange model of inert gases, and the 3 factors that affect the slope of the washout curve, i.e., the RF flip angle, respiratory parameters, and apparent relaxation time (which comprises terms including the relaxation time in alveoli, T1air, and perfusion), were determined separately. Flip angle was determined precisely using the dual flip angle method, and ventilation volume was determined using SF6 gas at thermal equilibrium. Furthermore, an attempt was made to separate out the terms of T1air and perfusion from the apparent relaxation time after exploiting the ventilation model of lungs in steady state. Values of relaxation time T1air=30.5 s and perfusion term lambdaQ/VA=0.016 s-1 were obtained, supporting the applicability of the ventilation model proposed.

Measurement of xenon diffusing capacity in the rat lung by hyperpolarized 129Xe MRI and dynamic spectroscopy in a single breath-hold.

We used the dual capability of hyperpolarized 129Xe for spectroscopy and imaging to develop new measures of xenon diffusing capacity in the rat lung that (analogously to the diffusing capacity of carbon monoxide or DLCO) are calculated as a product of total lung volume and gas transfer rate constants divided by the pressure gradient. Under conditions of known constant pressure breath-hold, the volume is measured by hyperpolarized 129Xe MRI, and the transfer rate is measured by dynamic spectroscopy. The new quantities (xenon diffusing capacity in lung parenchyma (DLXeLP)), xenon diffusing capacity in RBCs (DLXeRBC), and total lung xenon diffusing capacity (DLXe)) were measured in six normal rats and six rats with lung inflammation induced by instillation of fungal spores of Stachybotrys chartarum. DLXeLP, DLXeRBC, and DLXe were 56 +/- 10 ml/min/mmHg, 64 +/- 35 ml/min/mmHg, and 29 +/- 9 ml/min/mmHg, respectively, for normal rats, and 27 +/- 9 ml/min/mmHg, 42 +/- 27 ml/min/mmHg, and 16 +/- 7 ml/min/mmHg, respectively, for diseased rats. Lung volumes and gas transfer times for LP (TtrLP) were 16 +/- 2 ml and 22 +/- 3 ms, respectively, for normal rats and 12 +/- 2 ml and 35 +/- 8 ms, respectively, for diseased rats. Xenon diffusing capacities may be useful for measuring changes in gas exchange associated with inflammation and other lung diseases.