Distant dipolar fields in laser-polarized gases on macroscopic scales.

Distant dipolar fields among nuclear spins on macroscopic scales in the gas phase are reported for the first time. Their observation via interatomic multiple quantum coherences requires high nuclear spin polarization corresponding to spin temperatures of a few mK, which is generated in laser-polarized 3He, and proper control of the gas diffusion through a heavier buffer gas. This combination of physics at low and ambient temperatures opens up new ways of studying the relative translational diffusion of atoms and of gas diffusion in structures with a large range of length scales.

Intrapulmonary 3He gas distribution depending on bolus size and temporal bolus placement.

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.

Oxygen-sensitive 3He-MRI in bronchiolitis obliterans after lung transplantation.

Oxygen-sensitive 3He-MRI was studied for the detection of differences in intrapulmonary oxygen partial pressure (pO2) between patients with normal lung transplants and those with bronchiolitis obliterans syndrome (BOS). Using software developed in-house, oxygen-sensitive 3He-MRI datasets from patients with normal lung grafts (n = 8) and with BOS (n = 6) were evaluated quantitatively. Datasets were acqiured on a 1.5-T system using a spoiled gradient echo pulse sequence. Underlying diseases were pulmonary emphysema (n = 10 datasets) and fibrosis (n = 4). BOS status was verified by pulmonary function tests. Additionally, 3He-MRI was assessed blindedly for ventilation defects. Median intrapulmonary pO2 in patients with normal lung grafts was 146 mbar compared with 108 mbar in patients with BOS. Homogeneity of pO2 distribution was greater in normal grafts (standard deviation pO2 34 versus 43 mbar). Median oxygen decrease rate during breath hold was higher in unaffected patients (-1.75 mbar/s versus -0.38 mbar/s). Normal grafts showed fewer ventilation defects (5% versus 28%, medians). Oxygen-sensitive 3He-MRI appears capable of demonstrating differences of intrapulmonary pO2 between normal lung grafts and grafts affected by BOS. Oxygen-sensitive 3He-MRI may add helpful regional information to other diagnostic techniques for the assessment and follow-up of lung transplant recipients.

Spin echo formation in the presence of stochastic dynamics.

Spin echo formation in magnetic field gradients in the presence of fast stochastic motion is studied for hyperpolarized 3He gas at different diffusivities. The fast translational motion leads to frequency shifts already during echo formation, which can be described analytically for a linear gradient. Despite complete signal loss at the position of the spin echo itself, considerable intensity can be preserved at an earlier time (sqrt[2]tau rather than 2tau, where tau is the pulse delay). Hence, the phenomenon is designated as a pseudo spin echo.

Controlling diffusion of 3He by buffer gases: a structural contrast agent in lung MRI.

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.

[Microstructure of the lung: diffusion measurement of hyperpolarized 3Helium]. / Mikrostruktur der Lunge: Untersuchung mittels Diffusionsmessung von hochpolarisiertem 3Helium.

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.

Assessment of lung microstructure with magnetic resonance imaging of hyperpolarized Helium-3.

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.

Diffusion-weighted MRI of the lung with hyperpolarized helium-3: a study of reproducibility.

PURPOSE: To determine the reproducibility of several parameters of the ADC measurement by calculating the scan-to-scan intrasubject variability. MATERIALS AND METHODS: Measurements were performed using a gradient-echo sequence with a bipolar gradient for diffusion weighting (b=3.89 sec/cm2). Five patients with pulmonary emphysema, and six healthy-lung volunteers were included in the study. Images were acquired after inspiration of 3He during a single inspiratory breath-hold. To assess the reproducibility, the measurement was performed twice (time between measurements=20 minutes) without repositioning the subjects. Analysis was performed on the basis of region-of-interest (ROI) analysis and global lung ADC histograms. RESULTS: The mean ADC of a ROI varied by 5.1% between two measurements for volunteers and by 6.1% for patients. In the global evaluation, the 75th percentile demonstrated the best reproducibility (2%), while other parameters showed variations up to 12%. Only the variation of the standard deviation (SD) and the measure of homogeneity of the ADC map showed a significant difference between patients and volunteers. CONCLUSION: Diffusion-weighted imaging (DWI) is a well-reproducible method for assessing the lung microstructure.

Hyperpolarized 3He MRI and 81mKr SPECT in chronic obstructive pulmonary disease.

PURPOSE: During recent years, magnetic resonance imaging (MRI) using hyperpolarised (HP) 3He gas has emerged as a promising new method for the imaging of lung ventilation. However, systematic comparisons with nuclear medicine techniques have not yet been performed. The aim of this study was to compare ventilation imaging methods in 26 patients with chronic obstructive pulmonary disease (COPD) and nine lung healthy volunteers. METHODS: HP 3He MRI, 81mKr single-photon emission computed tomography (SPECT), high-resolution computed tomography (HRCT) and pulmonary function tests were performed. The three scans were scored visually as percentage of non-ventilated/diseased lung, and a computer-based objective measure of the ventilated volume in HP 3He MRI and 81mKr SPECT and an emphysema index in HRCT were calculated. RESULTS: We found a good correlation between HP 3He MRI and 81mKr SPECT for both visual defect score (r=0.80, p<0.0001) and objective estimate of ventilation (r=0.45, p=0.0157). In addition, both scans were well correlated with reference methods for the diagnosis of emphysema (pulmonary function test and HRCT). The defect scores were largest on 81mKr SPECT (the score on HP 3He MRI was one-third less than that on 81mKr SPECT), but the difference was reduced after normalisation for different breathing depths (HP 3He MRI at total lung capacity; 81mKr SPECT at tidal breathing at functional residual capacity). CONCLUSION: HP 3He MRI provides detailed ventilation distribution images and defect scores are comparable on HP 3He MRI and 81mKr SPECT. Additionally, new insights into the regional pulmonary microstructure via the apparent diffusion coefficient measurements are provided by HP 3He MRI. HP 3He MRI is a promising new diagnostic tool for the assessment of ventilation distribution.

Functional analysis in single-lung transplant recipients: a comparative study of high-resolution CT, 3He-MRI, and pulmonary function tests.

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.

Magnetic resonance imaging using hyperpolarized 3He-Gas.

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.