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Objective: Dynamic ventilation (3)He-MRI is a new method to assess pulmonary gas inflow. As differing airway diameters throughout the ventilatory cycle can influence gas inflow this study intends to investigate the influence of volume and timing of a He gas bolus with respect to the beginning of the tidal volume on inspiratory gas distribution., Materials and Methods: An ultrafast 2-dimensional spoiled gradient echo sequence (temporal resolution 100 milliseconds) was used for dynamic ventilation (3)He-MRI of 11 anesthetized and mechanically ventilated pigs. The applied (3)He gas bolus was varied in volume between 100 and 200 mL. A 150-mL bolus was varied in its application time after the beginning of the tidal volume between 0 and 1200 milliseconds. Signal kinetics were evaluated using an in-house developed software after definition of parameters for the quantitative description of (3)He gas inflow., Results: The signal rise time (time interval between signal in the parenchyma reaches 10% and 90% of its maximum) was prolonged with increasing bolus volume. The parameter was shortened with increasing delay of (3)He application after the beginning of the tidal volume. Timing variation as well as volume variation showed no clear interrelation to the signal delay time 10 (time interval between signal in the trachea reaches 50% of its maximum and signal in the parenchyma reaches 10% of its maximum)., Conclusions: Dynamic ventilation (3)He-MRI is able to detect differences in bolus geometry performed by volume variation. Pulmonary gas inflow as investigated by dynamic ventilation (3)He-MRI tends to be accelerated by an increasing application delay of a (3)He gas bolus after the beginning of the tidal volume.

Purpose: To study the influence of admixing inert buffer gases to laser-polarized (3)He in terms of resulting diffusion coefficients and the consequences for image contrast and resolution., Materials and Methods: The diffusion coefficient of (3)He was altered by admixing buffer gases of various molecular weights ((4)He, N(2), and SF(6)). The influence of the pulse sequence and the diffusion coefficient on the appearance of MRI of (laser-polarized) gases was analyzed by comparison of basic theoretical concepts with demonstrative experiments., Results: Excellent agreement between theoretical description and observed signal in simple gradient echoes was observed. A maximum signal gain can be predicted and was experimentally validated. Images acquired under such conditions revealed improved resolution. The nature and concentration of the admixed gas defines a structural threshold for the observed apparent diffusion coefficient (ADC) as demonstrated with diffusion-weighted MRI on a pig's lung flooded with suitable gas mixtures., Conclusion: A novel procedure is proposed to control the diffusion coefficient of gases in MRI by admixture of inert buffer gases. Their molecular mass and concentration enter as additional parameters into the equations that describe structural contrast. This allows for setting a structural threshold up to which structures contribute to the image. For MRI of the lung this enables images of very small structural elements (alveoli) only, or in the other extreme, all airways can be displayed with minimal signal loss due to diffusion., ((c) 2006 Wiley-Liss, Inc.)

Imaging methods to study the lung are traditionally based on x-ray or on radioactive contrast agents. Conventional magnetic resonance imaging (MRI) has only limited applications for lung imaging because of the low tissue density of protons concentration of hydrogen atoms, which are usually the basis for the imaging. The introduction of hyperpolarized noble gases as a contrast agent in MRI has opened new possibilities for lung diagnosis. The present paper describes this new technique. Diffusion-weighted MRI for assessment of the lung microstructure is presented here as an example of the new possibilities of functional imaging. Studies to determine the sensitivity of the diffusion measurement and regarding the correlation with traditionally established methods are also presented, along with results of the measurement of the reproducibility determined in a clinical pilot study on healthy volunteers and patients. Furthermore, a pilot measurement of the 3He diffusion tensor in the lung is presented.

The aim of this study was to validate oxygen-sensitive 3He-MRI in noninvasive determination of the regional, two- and three-dimensional distribution of oxygen partial pressure. In a gas-filled elastic silicon ventilation bag used as a lung phantom, oxygen sensitive two- and three-dimensional 3He-MRI measurements were performed at different oxygen concentrations which had been equilibrated in a range of normal and pathologic values. The oxygen partial pressure distribution was determined from 3He-MRI using newly developed software allowing for mapping of oxygen partial pressure. The reference bulk oxygen partial pressure inside the phantom was measured by conventional respiratory gas analysis. In two-dimensional measurements, image-based and gas-analysis results correlated with r=0.98; in three-dimensional measurements the between-methods correlation coefficient was r=0.89. The signal-to-noise ratio of three-dimensional measurements was about half of that of two-dimensional measurements and became critical (below 3) in some data sets. Oxygen-sensitive 3He-MRI allows for noninvasive determination of the two- and three-dimensional distribution of oxygen partial pressure in gas-filled airspaces.

Magnetic resonance imaging of the apparent diffusion coefficient (ADC) of hyperpolarized Helium-3 is a new technique for probing pulmonary microstructure in vivo. The aim of this study was the assessment of potential sources of systematic errors of the ADC measurement. The influence of macroscopic motion was determined by measurements at two different delays after initiating the breath-hold, and before and after cardiac arrest. An intercentre comparison was performed in two age- and lung function-matched groups of lung-healthy volunteers at two research sites. Moreover, measurements of diffusion anisotropy were performed. We found no dependency of the ADC as a function of the delay after stop of inspiration. The influence of cardiac motion was less than 10%. In the intercentre comparison study, an excellent agreement between the two sites was found. First measurements of the diffusion tensor of intrapulmonary Helium-3 are shown.

With the use of hyperpolarized gases, a great number of experiments have been carried out in order to improve the diagnostics of the lung, both from a structural and a functional point of view. 3He is best suited for structural studies, whereas 129Xe gives more detailed information about the functionality of the lung because it enters the bloodstream. In this work, we propose the use of a gas mixture to perform consecutive analysis of lung structure and functionality upon the delivery of a single bolus of gas. We show images of a helium-xenon gas mixture in the presence of a small amount of liquid toluene in order to demonstrate how both nuclei can be detected independently, extracting the spectroscopic information provided by the 129Xe spectra and obtaining an image with high sensitivity for 3He. A second experiment performed on a dissected mouse lung was used to demonstrate how the mixture of gases can enhance sensitivity in the larger airways of the lung.

Purpose: To develop a software tool for quantitative analysis of alveolar oxygen partial pressure (p(A)O(2)) as well as its time course during apnea., Material and Methods: T (1)-relaxation times of hyperpolarized (3)He are reduced by paramagnetic oxygen rendering (3)He-MRI sensitive to oxygen and thus allowing the assessment of the local oxygen partial pressure in the pulmonary airspaces. Oxygen-related relaxation and loss of polarization by RF-excitation can be discriminated by acquiring two image series with varying interscan delay and/or flip angles. Software was developed to calculate the p(A)O(2) and the decay rate in user-defined regions of interest (ROIs) automatically. Moreover, parameter maps can be calculated. In addition to the analysis of 2-dimensional data sets, the software allows the evaluation of 3-dimensional measurements for the first time. Artifacts due to lung motion were reduced by implementing a motion correction algorithm., Results: The software was successfully applied to data sets from healthy volunteers and from patients with various lung diseases. The parameter maps demonstrated a more homogeneous distribution of p(A)O(2) for the volunteers than for the patients. A regional increase in p(A)O(2) was found in a few patients., Conclusion: The described software allows the absolute quantification of p(A)O(2) as well as its variation over time. In the future, therefore, the software may gain importance for detecting mismatches between ventilation and perfusion, e. g., in patients with pulmonary embolism or chronic obstructive lung diseases.

Purpose: (3)He-MRI is able to visualize the regional distribution of lung ventilation with a temporal and spatial resolution so far unmatched by any other technique. The aim of the study was the development of a new software tool for quantification of dynamic ventilation parameters in absolute physical units., Materials and Methods: During continuous breathing, a bolus of hyperpolarized (3)He (300 ml) was applied at inspiration and a series of 168 coronal projection images simultaneously acquired using a 2D FLASH-sequence. Postprocessing software was developed to analyze the (3)He distribution in the lung. After correction for lung motion, several ventilation parameters (rise time, delay time, (3)He amount and (3)He peak flow) were calculated. Due to normalization of signal intensities, these parameters are presented in absolute physical units. The data sets were analyzed on a ROI basis as well as on a pixel-by-pixel basis., Results: Using the developed software, the measurements were analyzed in 6 lung-healthy volunteers, in one patient after lung transplantation, and in one patient with lung emphysema. The volunteers' parameter maps of the pixel-based analysis showed an almost homogeneous distribution of the ventilation parameters within the lung. In the parameter maps of both patients, regions with poor ventilation were observed., Conclusion: The developed software permits an objective and quantitative analysis of regional lung ventilation in absolute physical units. The clinical significance of the parameters, however, has to be determined in larger clinical studies. The software may become valuable in grading and following pulmonary function as well as in monitoring any therapy.

Objective: To develop and evaluate a postprocessing tool to quantify ventilated split-lung volumes on the basis of (3)He-MRI and to apply it in patients after single-lung transplantation (SLTX). High-resolution CT (HRCT) was employed as a reference modality providing split air-filled lung volumes. Lung volumes derived from pulmonary function test results served as clinical parameters and were used as the "gold standard.", Material and Methods: Eight patients (mean age, 54 years) with emphysema and six patients (mean age, 58 years) with idiopathic pulmonary fibrosis. All patients were evaluated following SLTX. HRCT was performed during inspiration (slice thickness, 1 mm; increment, 10 mm). For correlation with (3)He-MRI, HRCT images were reconstructed in coronal orientation to match the same anatomic levels. Aerated lung was determined by threshold-based segmentation of CT. (3)He-MRI was performed on a 1.5-T scanner using a two-dimensional, fast low-angle shot sequence in coronal orientation covering the whole lung after inhalation of a 300-mL bolus of hyperpolarized (3)He gas followed by normal room air for the rest of the tidal volume. Lung segmentation on (3)He-MRI was done using different thresholds., Results: In emphysematous patients, (3)He-MRI showed excellent correlation (r = 0.9) with vital capacity, while CT correlated (r = 0.8) with total lung capacity. (3)He-MRI correlated well with CT (r > 0.8) for grafts and native fibrotic lungs. In emphysematous lungs, MRI showed a good correlation (r = 0.7) with the nonemphysematous lung volume from CT. Increasing thresholds in (3)He-MRI reveal differences between aerated and ventilated lung areas with a different distribution in emphysema and fibrosis., Conclusions: (3)He-MRI is superior to CT in emphysema to demonstrate ventilated lung areas that participate in gas exchange. In fibrosis, (3)He-MRI and CT have a similar impact. The decrease pattern and the intraindividual ratio between ventilation of native and transplanted lungs will have to be investigated as a new surrogate for the ventilatory follow-up in patients undergoing SLTX.

Rationale and Objectives: Current imaging procedures of the lung concentrate on visualization of morphology. Computed tomography is the imaging method of choice for the majority of pulmonary diseases. Functional data are commonly obtained from arterial blood gas analysis, spirometry, and body plethysmography, which all suffer from lack of regional information., Materials and Methods: Magnetic resonance imaging (MRI) of the lung has been advanced recently by the use of hyperpolarized 3He as a new contrast mechanism. Four different image acquisition modes are performed during a typical patient study., Results: 3He-MRI yields functional information about the lung with a high spatial and temporal resolution, avoiding the risks of ionizing radiation. The method is currently limited by high costs and restricted availability of the gas., Conclusion: In this article, the experience obtained at the University of Mainz, being Europe's most experienced center performing 3He-MRI in humans, is reviewed against the international background.

Rationale and Objectives: The ability of motion corrected dynamic 3He-magnetic resonance imaging (MRI) to discriminate distributional patterns of inhaled hyperpolarized 3He between different groups of lung transplant recipients was evaluated., Methods: An ultrafast low-angle shot 2D sequence (temporal resolution 128 ms) was used for ventilation 3He-MRI of 11 single and 6 double lung transplant recipients. After digital motion correction, signal kinetics were evaluated in a tracheal and 7 pulmonary regions of interest. Results from grafts and native lungs as well as from normal and rejected grafts were compared with each other and to reference values from healthy subjects., Results: In emphysema patients, median alveolar rise time, a parameter for increase of alveolar signal, was 0.28 seconds for the graft and 0.48 seconds for the native lung, in fibrosis patients its median was 0.46 seconds for the graft and 0.21 seconds for the native lung. In double lung recipients, alveolar rise time was 0.29 seconds in normal and clinically rejected grafts., Conclusions: Dynamic ventilation 3He-MRI discriminated normal lung grafts from diseased native lungs in single lung recipients. Graft rejection in double lung recipients could not be discriminated.

Hyperpolarized noble gas MRI shows promise in the functional imaging of the pulmonary air spaces. The production of hyperpolarized (HP) gas requires specialized laser optical pumping apparatus, which is not likely to be home built in the majority of clinical MRI radiology centres. There are two routes through which HP gas will be made available to hospitals for clinical use: either the apparatus will be installed locally at a considerable expense to the centre, or a central facility will produce the gas and then deliver it to remote MRI sites as and when required. In this study, the feasibility of transporting large quantities of HP gas for in vivo MR imaging from a remote production facility in Mainz, Germany, by airfreight to Sheffield, UK, was successfully demonstrated.

Purpose: To elucidate the ability of 3He-MRI to detect ventilation defects in lung transplant recipients, 3He-MRI was compared to CT for concordance., Materials and Methods: We examined 14 lung recipients using 3He-MRI on a 1.5 T MR scanner. CT served as a reference method. Up to four representative ventilation defects were defined for each lung on 3He-MRI and compared to corresponding areas on CT., Results: Altogether, 59 representative ventilation defects were defined on 3He-MRI. Plausible CT correlates were found for 29 ventilation defects; less plausible CT correlates were found for eight defects. In 22 defects (37%) no corresponding CT changes were detected. CT demonstrated correlates for ventilation defects seen on 3He-MRI in only 63% of the cases., Conclusion: 3He-MRI yields a clear increase in the number of detected ventilation defects compared to CT. This may have an important impact on the early detection of bronchiolitis obliterans in lung transplant recipients.

Rationale and Objectives: Software was developed to correct for lung motion to improve the description of hyperpolarized (3)He gas distribution in the lung., Methods: Five volunteers were studied by dynamic ventilation (3)He-MRI using an ultrafast FLASH 2D sequence with a temporal resolution of 128 milliseconds. Signal kinetics were evaluated in the trachea and seven parenchymal Regions of Interest. Reference ranges for healthy subjects were defined for motion-corrected and uncorrected images., Results: Motion correction was successfully performed. Reference ranges were 0.11-1.21 seconds for tracheal transit time, 0-0.02 seconds for trachea-alveolar interval, 0.22-0.62 seconds for alveolar rise time and 0-76.6 arbitrary units for alveolar amplitude for motion corrected images, and 0-1.09 seconds, 0-0.11 seconds, 0.26-0.85 seconds, 46.4-99.8 arbitrary units for uncorrected images., Conclusions: Evaluation of (3)He-distribution in the lung using motion correction of dynamic (3)He-ventilation imaging is feasible and gives more narrow reference ranges.

MRI of the lungs using hyperpolarized helium-3 ((3)He) allows the determination of intrapulmonary oxygen partial pressures (p(O2)). The need to separate competing processes of signal loss has hitherto required two different imaging series during two different breathing maneuvers. In this work, a new imaging strategy to measure p(O2) by a single series of consecutive scans is presented. The feasibility of the method is demonstrated in three healthy human volunteers. Maps and histograms of intrapulmonary p(O2) are calculated. Changes in the oxygen concentration of the inhaled gas mixture are well reproduced in the histograms. Monte Carlo (MC) simulations of the temporal evolution of (3)He hyperpolarization within the lungs were performed to evaluate the accuracy of this measurement technique, and its limitations., (Copyright 2002 Wiley-Liss, Inc.)

We present a new method to determine in vivo the temporal evolution of intrapulmonary oxygen concentrations by functional lung imaging with hyperpolarized (3)Helium ((3)He-->). Single-breath, single-bolus visualization of (3)He--> administered to the airspaces is used to analyze nuclear spin relaxation caused by the local oxygen partial pressure p(O(2))(t). We model the dynamics of hyperpolarization in the lung by rate equations. Based hereupon, a double acquisition technique is presented to separate depolarization by RF pulses and oxygen induced relaxation. It permits the determination of p(O(2)) with a high accuracy of up to 3% with simultaneous flip angle calibration using no additional input parameters. The time course of p(O(2)) during short periods of breathholding is found to be linear in a pig as well as in a human volunteer. We also measured the wall relaxation time in the lung and deduced a lower limit of 4.3 min., (Copyright 1999 Academic Press.)