Reinhard Surkau

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.

MRI using hyperpolarized noble gases

Abstract. 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.

Realization of a broad band neutron spin filter with compressed, polarized 3He gas☆

The strongly spin dependent absorption of neutrons in nuclear spin polarized 3He opens the possibility to polarize beams of thermal and epithermal neutrons. An effective 3He neutron spin filter (NSF) requires high 3He nuclear polarization as well as a filter thickness corresponding to a gas amount of the order of 1 barl. We realized such a filter using direct optical pumping of metastable 3He∗ atoms in a 3He plasma at 1 mbar. Metastable exchange scattering transfers the angular momentum to the whole ensemble of 3He atoms. At present 3 × 1018 3He-atoms/s are polarized up to 64%. Subsequent polarization preserving compression by a two stage compressor system enables to prepare NSF cells of about 300 cm3 volume with 3 bar of polarized 3He within 2 h. 3He polarizations up to 53% were measured in a cell with a filter length of about 15 cm. By this cell a thermal neutron beam from the Mainz TRIGA reactor was polarized. A wavelength selective polarization analysis by means of Bragg scattering revealed a neutron polarization of 84% at a total transmission of 12% for a neutron wavelength of 1 A.

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

MRI of the lungs using hyperpolarized helium‐3 (3He) allows the determination of intrapulmonary oxygen partial pressures (pO2). 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 pO2 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 pO2 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 3He hyperpolarization within the lungs were performed to evaluate the accuracy of this measurement technique, and its limitations. Magn Reson Med 47:105–114, 2002.

3He-MRI-based measurements of intrapulmonary pO2 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 pO2(t) during apnea by 3He MRI to healthy volunteers. Using two imaging series with different interscan times during two breathholds (double acquisition technique), relaxation of 3He due to paramagnetic oxygen and depolarization by RF pulses were discriminated. In all four subjects, the temporal evolution of pO2 was found to be linear, and was described by an initial partial pressure p0 and a decrease rate R. Also, regional differences of both p0 and R were observed. A correlation between p0 and R was apparent. Finally, we discuss limitations of the double acquisition approach. Copyright

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

MRI with hyperpolarized helium‐3 (3He) provides high‐resolution imaging of ventilated airspaces. The first aim of this 3He‐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 3He 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/α = 11 ms/4.2 ms/<10°). Known amounts of 3He 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, 3He 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 3He MRI is a sensitive measure to detect regional abnormalities in the distribution of ventilation in clinically healthy persons with normal pulmonary function tests. Copyright

Interdisciplinary experiments with polarized 3He

Abstract Optical pumping of metastable 3 He atoms is a very efficient method to produce large quantities of nuclear spin-polarized 3 He. Recent developments in mechanical compression of the gas, its storage and transport allow for its flexible use in different fields of physics and applied science. Among these are (1) scattering experiments of polarized beams from polarized 3 He-targets, (2) 3 He as neutron spin filter to polarize neutron beams at research reactors, and (3) polarized 3 He gas inhaled into the lungs to perform magnetic resonance imaging. The paper discusses the different topics along with results obtained in a first round of experiments.

Polarimetry on dense samples of spin-polarized 3He by magnetostatic detection

A very sensitive low-field fluxgate magnetometer is used to detect the static magnetic field produced by dense samples of spin-polarized 3He gas contained in spherical glass cells at pressures around several bars. The 3He nuclear polarization can be extracted with high precision ΔPP < 1% by utilizing magnetostatic detection in combination with adiabatic fast-passage spin reversal. The polarization losses can be kept well below 0.1% thus making this type of polarimetry almost non-destructive. More simply even, P can be measured with reduced accuracy by the change of field when the cell is removed from the fluxgate. In this case the accuracy is limited to about 10% due to the uncertainties about the susceptibilities of the cell walls.

Recycling of 3He from lung magnetic resonance imaging

We have developed the means to recycle 3He exhaled by patients after imaging the lungs using magnetic resonance of hyperpolarized 3He. 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 3He, depending on the amount administered and the number of breaths collected to wash out the 3He gas from the lungs. 3He 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 3He 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%. Magn Reson Med, 2011.

Determination of the neutron electric formfactor in quasielastic collisions of polarized electrons with 3He and 2D. Collaboration A3 at MAMI

The determination of the neutron electric formfactor from quasielastic reactions 3H↘e(e↘,e′n) and D(e↘,e′,n↘) respectively is one of the present goals of experiments with polarized electrons at the Mainz race track microtron MAMI. A GaAsP‐photoelectron source is used at MAMI to get an 855 MeV electron beam spinpolarized to a degree of 35% at a current of 10 μA. Polarized 3He‐nuclei are produced by optical pumping metastable 3He. Scattered electrons are detected in coincidence with the recoil neutrons, the transverse spinpolarization of the neutrons may be analyzed by neutron‐proton scattering in a double wall plastic scintillator detector. A subset of the final detector set‐up has been tested successfully now by investigating the polarization transfer to the proton in reactions H(e↘,e′p↘) and D(e↘,e′p↘) and to the neutron in D(e↘,e′n↘) at a 4‐momentum transfer with −Q2=8fm−2. First data from the exclusive quasielastic collision 3H↘e(e↘,e′n) indicate a value of the neutron electric formfactor of GnE=0.035±...