Recycling of 3He from lung magnetic resonance imaging.

We have developed the means to recycle (3) He exhaled by patients after imaging the lungs using magnetic resonance of hyperpolarized (3) He. The exhaled gas is collected in a helium leak proof bag and further compressed into a steel bottle. The collected gas contains about 1-2% of (3) He, depending on the amount administered and the number of breaths collected to wash out the (3) He gas from the lungs. (3) He is separated from the exhaled air using zeolite molecular sieve adsorbent at 77 K followed by a cold head at 8 K. Residual gaseous impurities are finally absorbed by a commercial nonevaporative getter. The recycled (3) He gas features high purity, which is required for repolarization by metastability exchange optical pumping. At present, we achieve a collection efficiency of 80-84% for exhaled gas from healthy volunteers and cryogenic separation efficiency of 95%.

Assessment of a single-acquisition imaging sequence for oxygen-sensitive (3)He-MRI.

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.

(3)He MRI in healthy volunteers: preliminary correlation with smoking history and lung volumes.

MRI with hyperpolarized helium-3 ((3)He) provides high-resolution imaging of ventilated airspaces. The first aim of this (3)He-study was to compare observations of localized signal defects in healthy smokers and non-smokers. A second aim was to describe relationships between parameters of lung function, volume of inspired (3)He and signal-to-noise ratio. With Ethics Committee approval and informed consent, 12 healthy volunteers (seven smokers and five non-smokers) were studied. Imaging was performed in a 1.5 T scanner using a two-dimensional FLASH sequence at 30V transmitter amplitude (TR/TE/alpha = 11 ms/4.2 ms/<10 degrees ). Known amounts of (3)He were inhaled from a microprocessor-controlled delivery device and imaged during single breath-holds. Images were evaluated visually, and scored using a prospectively defined 'defect-index'. Signal-to-noise ratio of the images were correlated with localization, (3)He volumes and static lung volumes. Due to poor image quality studies of two smokers were not eligible for the evaluation. Smokers differed from non-smokers in total number and size of defects: the 'defect-index' of smokers ranged between 0.8 and 6.0 (median = 1.1), that of non-smokers between 0.1 and 0.8 (median = 0.4). Intraindividually, an anteroposterior gradient of signal-to-noise ratio was apparent. Signal-to-noise ratio correlated with the estimated amount of hyperpolarization administered (r = 0. 77), but not with static lung volumes. We conclude that (3)He MRI is a sensitive measure to detect regional abnormalities in the distribution of ventilation in clinically healthy persons with normal pulmonary function tests.

(3)he-MRI-based measurements of intrapulmonary p(O2) and its time course during apnea in healthy volunteers: first results, reproducibility, and technical limitations.

We applied a recently developed method of following the time course of the intrapulmonary oxygen partial pressure p(O2)(t) during apnea by (3)He MRI to healthy volunteers. Using two imaging series with different interscan times during two breathholds (double acquisition technique), relaxation of (3)He due to paramagnetic oxygen and depolarization by RF pulses were discriminated. In all four subjects, the temporal evolution of p(O2) was found to be linear, and was described by an initial partial pressure p(0) and a decrease rate R. Also, regional differences of both p(0) and R were observed. A correlation between p(0) and R was apparent. Finally, we discuss limitations of the double acquisition approach.

[Ultrafast MRI of lung ventilation using hyperpolarized helium-3]. / Ultraschnelle MRT der Lungenventilation mittels hochpolarisiertem Helium-3.

OBJECTIVE: Assessment of the temporal and spatial dynamics of hyperpolarized Helium-3 (3He) distribution in the lung with ultrafast gradient-echo magnetic-resonance imaging. MATERIAL AND METHODS: Coronal images of the lung were acquired using ultrafast gradient-echo pulse sequences with TR/TE = 3.3 ms/1.3 ms (slice thickness, 40 mm) and TR/TE = 2.0 ms/0.7 ms (without slice selection). A series of 80 or 160 projection images was obtained with 210 ms or 130 ms temporal resolution, respectively. Imaging was performed during several respiratory cycles after application of a single bolus of 300 mL hyperpolarized 3He. Measurements were performed in six healthy volunteers (spontaneous breathing). RESULTS: Different phases of in- and expiration could be visualized. During the course of consecutive respiratory cycles the 3He signal decreased due to dilution of 3He in residual alveolar gas and by inspired air, relaxation due to oxygen and the RF pulses, and due to Helium-3 washout. The signal of a single bolus of 3He was detected in the lung for up to four respiratory cycles. Anatomical structures were better visualized on slice selective images than on images without slice selection. CONCLUSION: Distribution of inspired 3He within the tracheobronchial tree and alveolar space and its washout can be visualized by ultrafast imaging of a single bolus of hyperpolarized 3He gas. This method may allow for regional analysis of lung function with temporal and spatial resolution superior to conventional methods.

Quantification of regional intrapulmonary oxygen partial pressure evolution during apnea by (3)He MRI.

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.

Analysis of intrapulmonary O(2) concentration by MR imaging of inhaled hyperpolarized helium-3.

Inhalation of hyperpolarized (3)He allows magnetic resonance imaging (MRI) of ventilated airspaces. (3)He hyperpolarization decays more rapidly when interacting with paramagnetic O(2). We describe a method for in vivo determination of intrapulmonary O(2) concentrations ([O(2)]) based on MRI analysis of the fate of measured amounts of inhaled hyperpolarized (3)He in imaged regions of the lung. Anesthetized pigs underwent controlled normoventilation in a 1.5-T MRI unit. The inspired O(2) fraction was varied to achieve different end-tidal [O(2)] fractions (FET(O(2))). With the use of a specifically designed applicator, (3)He (100 ml, 35-45% polarized) was administered at a predefined time within single tidal volumes. During subsequent inspiratory apnea, serial two-dimensional images of airways and lungs were acquired. At least once in each animal studied, the radio-frequency excitation used for imaging was doubled at constant FET(O(2)). Signal intensity measurements in regions of interest of the animals' lungs (volume range, 54-294 cm(3)), taken at two different radio-frequency excitations, permitted calculation of [O(2)] in these regions of interest. The [O(2)] fractions in the regions of interest correlated closely with FET(O(2)) (R = 0.879; P < 0.0001). O(2)-sensitive (3)He-MRI may allow noninvasive study of regional distribution of ventilation and alveolar PO(2) in the lung.

[A new method for imaging ventilation-distribution with 3Helium in magnetic resonance tomography]. / Neue Methode zur Darstellung der Verteilung der Ventilation mittels polarisiertem 3Helium in der Magnetresonanztomographie (MRT).

BACKGROUND: Conventional 1H-MRI of the lung is restricted by susceptibility effects and low proton density: Recently, imaging of lung ventilation in MRI has become feasible using hyperpolarised inert gases with a spin of I = 1/2, such as 3He and 129Xe, as inhalative "contrast agents". New technical developments, preclinical and clinical application of this method are described. MATERIALS AND METHODS: With optical laser pumping high polarisation rates can be achieved, resulting in a high signal-to-noise ratio (S/N). A dedicated application system allows accurate administration of 3He boli at different time points during inspiration. Thus, dynamic ventilation imaging becomes possible. Prerequisites for this method include a dedicated coil as well as a spectroscopy option at the MRI system. Fast sequences and low flip angles are employed to comply with the relaxation of hyperpolarise 3He in vivo. RESULTS: Overall homogeneous signal intensity (SI) represents physiological conditions. Obstructive lung disease is associated with generalised or localised signal inhomogeneity. Different time constants of specific lung regions are probably responsible for this kind of inhomogeneous inspiratory distribution of ventilation. Tumours show a clear ventilation deficit, correlating with non-ventilated lung areas. CONCLUSION: 3He MRI is a promising new modality for the evaluation of ventilation distribution under different pathological conditions. This may include obstructive lung disease and assessment of ventilation distribution before and after thoracic surgery. Furthermore, evaluation of patients with acute lung failure and validation of ventilator settings in anaesthesia may be performed.

MRI using hyperpolarized noble gases.

The aim of this study was to review the physical basis of MRI using hyperpolarized noble gases as well as the present status of preclinical and clinical applications. Non-radioactive noble gases with a nuclear spin 1/2 (He-3, Xe-129) can be hyperpolarized by optical pumping. Polarization is transferred from circularly polarized laser light to the noble-gas atoms via alkali-metal vapors (spin exchange) or metastable atoms (metastability exchange). Hyperpolarization results in a non-equilibrium polarization five orders of magnitude higher than the Boltzmann equilibrium compensating for the several 1000 times lower density of noble gases as compared with liquid state hydrogen concentrations in tissue and allows for short imaging times. Hyperpolarization can be stored sufficiently long (3 h to 6 days) to allow for transport and application. Magnetic resonance systems require a broadband radio-frequency system - which is generally available for MR spectroscopy - and dedicated coils. The hyperpolarized gases are administered as inhalative "contrast agents" allowing for imaging of the airways and airspaces. Besides the known anesthetic effect of xenon, no adverse effects are observed in volunteers or patients. Pulse sequences are optimized to effectively use the non-renewable hyperpolarization before it decays or is destroyed, using fast low-flip-angles strategies to allow for dynamic/breath-hold imaging of highly diffusible (He) or soluble (Xe) gases with in vivo T1-times well below 1 min. Since helium is not absorbed in considerable amounts, its application is restricted to the lung. Xe-129 is also under investigation for imaging of white matter disease and functional studies of cerebral perfusion. Magnetic resonance imaging using hyperpolarized gases is emerging as a technical challenge and opportunity for the MR community. Preliminary experience suggests potential for functional imaging of pulmonary ventilation and cerebral perfusion.

Imaging of the lungs using 3He MRI: preliminary clinical experience in 18 patients with and without lung disease.

The purpose of this study was to describe the 3He MRI findings of normal pulmonary ventilation in healthy volunteers and to evaluate abnormalities in patients with different lung diseases. Hyperpolarized 3He gas (300 ml, 3 x 10(5) Pa, polarized to 35-45% by optical pumping, provided in special glass cells) was inhaled by 8 healthy volunteers and 10 patients with different lung diseases. Imaging was performed with a three-dimensional fast low-angle shot (FLASH) sequence (TR = 11.8 msec; TE = 5 msec; transmitter amplitude, 5-8 V; corresponding flip angle, < 5 degrees) in a single breath-hold (22-42 seconds). Clinical and radiological examinations were available for correlation. The studies were performed successfully in eight of eight volunteers and in 8 of 10 patients. The lung parenchyma of volunteers with normal ventilatory function exhibited rather homogeneous intermediate to high signal, whereas patients with chronic obstructive lung disease or bronchiectasis presented with severe signal inhomogeneities with patchy or wedge-shaped defects. The mass effect of bronchogenic carcinoma, chronic empyema, lymphadenopathy, or pleural effusion caused large signal defects, representing the lesion and adjacent hypoventilation, the extent of which had not been presumed from chest x-ray or CT. 3He MRI is a promising new modality for the assessment of pulmonary ventilation and its abnormalities. Additional studies are needed to determine its potential clinical role.

[The helium-3 MRT of pulmonary ventilation: the initial clinical applications]. / Helium-3-MRT der Lungenventilation: erste klinische Anwendungen.

PURPOSE: of the study is the visualisation of normal pulmonary ventilation in healthy volunteers and the evaluation of abnormalities in patients with different lung diseases using 3He magnetic resonance imaging (3He-MRI). MATERIAL AND METHODS: Hyperpolarized 3He gas (V = 300 ml, p = 3 x 10(5) Pa, polarised to 35-45% by optical pumping, provided in special glass cells) was inhaled by eight healthy volunteers and ten patients with different lung diseases. A 3D FLASH sequence (TR = 11.8 ms; TE = 5 ms; matrix 144 x 256, FOV 350 mm, section thickness 7-10 mm, coronal orientation) was performed in a single breath-hold (22-42 s). Clinical and radiological examinations were available for correlation. RESULTS: The studies were successfully carried out in 8/8 volunteers and in 8/10 patients. The central airways were constantly visualised with intermediate to high signal intensity. The lung parenchyma of volunteers with normal ventilatory function showed rather homogeneous intermediate to high signal, whereas patients with chronic obstructive lung disease and/or pneumonia presented severe signal inhomogeneities. Space-occupying lesions and pleural effusion caused large areas with little or no signal. The represented the lesion and adjacent ventilatory disturbances whose extent had not been presumed from chest x-ray or CT. The spatial resolution was higher than in ventilation scintigraphy. CONCLUSION: 3He MRI is a promising new modality for the assessment of pulmonary ventilation and its anomalies.

Hyperpolarized gases--a new type of MR contrast agents?

The nuclear spin polarization of noble gases can be strongly enhanced by laser optical pumping followed by electron-nuclear polarization transfer. Direct optical pumping of metastable 3He atoms has been shown to produce enormous polarization in the order of 0.4-0.6. This is about 10(5) times greater than the polarization of water protons at thermal equilibrium used at conventional MR imaging. We demonstrate that hyperpolarized 3He gas can be applied to nuclear MR imaging of human organs with air-filled spaces. In vivo 3He MR experiments were performed in a whole-body MR scanner with a superconducting magnet ramped down to 0.8 T and at 1.5 T using a double resonant Helmholtz coil operating at 63.6 and 48.6 MHz for 1H and 3He, respectively. Anatomical details of the lungs of a volunteer were visualized with the FLASH technique demonstrating the potential of the method for fast imaging of airways in the human body and for pulmonary ventilation studies.

Normal and abnormal pulmonary ventilation: visualization at hyperpolarized He-3 MR imaging.

To assess the feasibility of helium-3 magnetic resonance (MR) imaging with a three-dimensional fast low-angle shot (FLASH) sequence, He-3 gas (volume, 300 mL; pressure, 3 x 10(5) Pa; polarized up to 45% by means of optimal pumping) was inhaled by five healthy volunteers and five patients with pulmonary diseases. All breath-hold examinations (22-42 seconds) were completed successfully. Normal ventilation was depicted with homogeneous high signal intensity, lesions were depicted as causing defects, and obstructive lung disease was depicted with severely inhomogeneous signal intensity.

Nuclear magnetic resonance imaging of airways in humans with use of hyperpolarized 3He.

The nuclear spin polarization of noble gases can be enhanced strongly by laser optical pumping followed by electron-nuclear polarization transfer. Direct optical pumping of metastable 3He atoms has been shown to produce enormous polarization on the order of 0.4-0.6. This is about 10(5) times larger than the polarization of water protons at thermal equilibrium used in conventional MRI. We demonstrate that hyperpolarized 3He gas can be applied to nuclear magnetic resonance imaging of organs with air-filled spaces in humans. In vivo 3He MR experiments were performed in a whole-body MR scanner with a superconducting magnet ramped down to 0.8 T. Anatomical details of the upper respiratory tract and of the lungs of a volunteer were visualized with the FLASH technique demonstrating the potential of the method for fast imaging of airways in the human body and for pulmonary ventilation studies.

Nuclear magnetic resonance imaging with hyperpolarised helium-3.

BACKGROUND: Magnetic resonance imaging (MRI) relies on magnetisation of hydrogen nuclei (protons) of water molecules in tissue as source of the signal. This technique has been valuable for studying tissues that contain significant amounts of water, but biological settings with low proton content, notably the lungs, are difficult to image. We report use of spin-polarised helium-3 for lung MRI. METHODS: A volunteer inhaled hyperpolarised 3He to fill the lungs, which were imaged with a conventional MRI detector assembly. The nuclear spin polarisation of helium, and other noble gases, can be greatly enhanced by laser optical pumping and is about 10(5) times larger than the polarisation of water protons. This enormous gain in polarisation easily overcomes the loss in signal due to the lower density of the gas. FINDINGS: The in-vivo experiment was done in a whole-body MRI scanner. The 3He image showed clear demarcation of the lung against diaphragm, heart, chest wall, and blood vessels (which gave no signal). The signal intensity within the air spaces was greatest in lung regions that are preferentially ventilated in the supine position; less well ventilated areas, such as the apices, showed a weaker signal. INTERPRETATION: MRI with hyperpolarised 3He gas could be an alternative to established nuclear medicine methods. The ability to image air spaces offers the possibility of investigating physiological and pathophysiological processes in pulmonary ventilation and differences in its regional distribution.