Hyperpolarized 129Xe MRI, 99mTc scintigraphy, and SPECT in lung ventilation imaging: a quantitative comparison.

RATIONALE AND OBJECTIVES: The current clinical standard for functional imaging of patients with lung ailments is nuclear medicine scintigraphy and Single Photon Emission Computed Tomography (SPECT) which detect the gamma decay of inhaled radioactive tracers. Hyperpolarized (HP) Xenon-129 MRI (XeMRI) of the lungs has recently been FDA approved and provides similar functional images of the lungs with higher spatial resolution than scintigraphy and SPECT. Here we compare Technetium-99m (99mTc) diethylene-triamine-pentaacetate scintigraphy and SPECT with HP XeMRI in healthy controls, asthma, and chronic obstructive pulmonary disorder (COPD) patients. MATERIALS AND METHODS: 59 subjects, healthy, with asthma, and with COPD, underwent 99mTc scintigraphy/SPECT, standard spirometry, and HP XeMRI. XeMRI and SPECT images were registered for direct voxel-wise signal comparisons. Images were also compared using ventilation defect percentage (VDP), and a standard 6-compartment method. VDP calculated from XeMRI and SPECT images was compared to spirometry. RESULTS: Median Pearson correlation coefficient for voxel-wise signal comparison was 0.698 (0.613-0.782) between scintigraphy and XeMRI and 0.398 (0.286-0.502) between SPECT and XeMRI. Correlation between VDP measures was r = 0.853, p < 0.05. VDP separated asthma and COPD from the control group and was significantly correlated with FEV1, FEV1/FVC, and FEF 25-75. CONCLUSION: HP XeMRI provides equivalent information to 99mTc SPECT and standard spirometry measures. Additionally, XeMRI is non-invasive, hence it could be used for longitudinal studies for evaluating emerging treatment for lung ailments.

New insights into lung diseases using hyperpolarized gas MRI.

Hyperpolarized (HP) gases are a new class of contrast agents that permit to obtain high temporal and spatial resolution magnetic resonance images (MRI) of the lung airspaces. HP gas MRI has become important research tool not only for morphological and functional evaluation of normal pulmonary physiology but also for regional quantification of pathologic changes occurring in several lung diseases. The purpose of this work is to provide an introduction to MRI using HP noble gases, describing both the basic principles of the technique and the new information about lung disease provided by clinical studies with this method. The applications of the technique in normal subjects, smoking related lung disease, asthma, and cystic fibrosis are reviewed.

Hyperpolarized Xenon-129 gas-exchange imaging of lung microstructure: first case studies in subjects with obstructive lung disease.

PURPOSE: To develop and test a method to noninvasively assess the functional lung microstructure. MATERIALS AND METHODS: The Multiple exchange time Xenon polarization Transfer Contrast technique (MXTC) encodes xenon gas-exchange contrast at multiple delay times permitting two lung-function parameters to be derived: (i) MXTC-F, the long exchange-time depolarization value, which is proportional to the tissue to alveolar-volume ratio and (ii) MXTC-S, the square root of the xenon exchange-time constant, which characterizes thickness and composition of alveolar septa. Three healthy volunteers, one asthmatic, and two chronic obstructive pulmonary disease (COPD) (GOLD stage I and II) subjects were imaged with MXTC MRI. In a subset of subjects, hyperpolarized xenon-129 ADC MRI and CT imaging were also performed. RESULTS: The MXTC-S parameter was found to be elevated in subjects with lung disease (P-value = 0.018). In the MXTC-F parameter map it was feasible to identify regional loss of functional tissue in a COPD patient. MXTC-F maps showed excellent regional correlation with CT and ADC (P ≥ 0.90) in one COPD subject. CONCLUSION: The functional tissue-density parameter MXTC-F showed regional agreement with other imaging techniques. The newly developed parameter MXTC-S, which characterizes the functional thickness of alveolar septa, has potential as a novel biomarker for regional parenchymal inflammation or thickening.

Human pulmonary imaging and spectroscopy with hyperpolarized 129Xe at 0.2T.

RATIONALE AND OBJECTIVES: Using a novel (129)Xe polarizer with high throughput (1-2 L/hour) and high polarization (approximately 55%), our objective was to demonstrate and characterize human pulmonary applications at 0.2T. Specifically, we investigated the ability of (129)Xe to measure the alveolar surface area per unit volume of gas, S(A)/V(gas). MATERIALS AND METHODS: Variable spin echo time (TE) gradient and radiofrequency (RF) echoes were used to obtain estimates of the lung's contribution to both T(2)* and T(2). Standard multislice ventilation images were obtained and signal-to-noise ratio (SNR) determined. Whole-lung, time-dependent measurements of (129)Xe diffusion from gas to septal tissue were obtained with a chemical shift saturation recovery (CSSR) method. Four healthy subjects were studied, and the Butler et al CSSR formalism (J Phys Condensed Matter 2002; 14:L297-L304) was used to calculate S(A)/V(gas). A single-breath version of the xenon transfer contrast (SB-XTC) method was implemented and used to image (129)Xe diffusion between alveolar gas and septal tissue. A direct comparison of CSSR and SB-XTC was performed. RESULTS: T(2)*=135+/-29 ms amd T(2)=326.2+/-9.5 ms. Maximum SNR=36 for ventilation images from inhalation of 1L 86% (129)Xe and voxel volume =0.225 mL. CSSR analysis showed S(A)/V(gas) decreased with increasing lung volume in a manner very similar to that observed from histology measurements; however, the absolute value of S(A)/V(gas) was approximately 40% smaller than histology values. SB-XTC images in different postures demonstrate gravitationally dependent values. Initial comparison of CSSR with XTC showed fairly good agreement with expected ratios. CONCLUSIONS: Hyperpolarized (129)Xe human imaging and spectroscopy are very promising methods to provide functional information about the lung.

Optical pumping system design for large production of hyperpolarized.

We present a design for a spin-exchange optical pumping system to produce large quantities of highly polarized 129Xe. Low xenon concentrations in the flowing gas mixture allow the laser to maintain high Rb polarization. The large spin-exchange rate between Rb and 129Xe through the long-lived van der Waals molecules at low pressure, combined with a high flow rate, results in large production rates of hyperpolarized xenon. We report a maximum polarization of 64% achieved for a 0.3 l/h Xe flow rate, and maximum magnetization output of 6 l/h at 22% polarization. Our findings regarding the polarization dependence on temperature, nitrogen partial pressure, and gas mixture flow velocity are also reported.

A System for Open-Access He Human Lung Imaging at Very Low Field.

We describe a prototype system built to allow open-access very-low-field MRI of human lungs using laser-polarized (3)He gas. The system employs an open four-coil electromagnet with an operational B(0) field of 4 mT, and planar gradient coils that generate gradient fields up to 0.18 G/cm in the x and y direction and 0.41 G/cm in the z direction. This system was used to obtain (1)H and (3)He phantom images and supine and upright (3)He images of human lungs. We include discussion on challenges unique to imaging at 50 -200 kHz, including noise filtering and compensation for narrow-bandwidth coils.

Spectrally narrowed external-cavity high-power stack of laser diode arrays.

We describe an effective external cavity for narrowing the spectral linewidth of a multiarray stack of laser diode arrays. For a commercially available 279-W free-running five-array laser diode array operating at 60 A, we narrow the spectral linewidth to 0.40 nm at FWHM with 115 W of cw power output. This technique leads to the possibility of higher-efficiency, lower-cost production of hyperpolarized noble gases for magnetic resonance imaging.

3He lung imaging in an open access, very-low-field human magnetic resonance imaging system.

The human lung and its functions are extremely sensitive to gravity; however, the conventional high-field magnets used for most laser-polarized (3)He MRI of the human lung restrict subjects to lying horizontally. Imaging of human lungs using inhaled laser-polarized (3)He gas is demonstrated in an open-access very-low-magnetic-field (<5 mT) MRI instrument. This prototype device employs a simple, low-cost electromagnet, with an open geometry that allows variation of the orientation of the imaging subject in a two-dimensional plane. As a demonstration, two-dimensional lung images were acquired with 4-mm in-plane resolution from a subject in two orientations: lying supine and sitting in a vertical position with one arm raised. Experience with this prototype device will guide optimization of a second-generation very-low-field imager to enable studies of human pulmonary physiology as a function of subject orientation.

Measurement of Parity Violation in np Capture: the NPDGamma Experiment.

The NPDGamma experiment will measure the parity-violating directional gamma ray asymmetry A γ in the reaction [Formula: see text]. Ultimately, this will constitute the first measurement in the neutron-proton system that is sensitive enough to challenge modern theories of nuclear parity violation, providing a theoretically clean determination of the weak pion-nucleon coupling. A new beam-line at the Los Alamos Neutron Science Center (LANSCE) delivers pulsed cold neutrons to the apparatus, where they are polarized by transmission through a large volume polarized (3)He spin filter and captured in a liquid para-hydrogen target. The 2.2 MeV gamma rays from the capture reaction are detected in an array of CsI(Tl) scintillators read out by vacuum photodiodes operated in current mode. We will complete commissioning of the apparatus and carry out a first measurement at LANSCE in 2004-05, which would provide a statistics-limited result for A γ accurate to a standard uncertainty of ±5 × 10(-8) level or better, improving on existing measurements in the neutron-proton system by a factor of 4. Plans to move the experiment to a reactor facility, where the greater flux would enable us to make a measurement with a standard uncertainty of ±1 × 10(-8), are actively being pursued for the longer term.

Commissioning of the NPDGamma Detector Array: Counting Statistics in Current Mode Operation and Parity Violation in the Capture of Cold Neutrons on B 4 C and (27) Al.

The NPDGamma γ-ray detector has been built to measure, with high accuracy, the size of the small parity-violating asymmetry in the angular distribution of gamma rays from the capture of polarized cold neutrons by protons. The high cold neutron flux at the Los Alamos Neutron Scattering Center (LANSCE) spallation neutron source and control of systematic errors require the use of current mode detection with vacuum photodiodes and low-noise solid-state preamplifiers. We show that the detector array operates at counting statistics and that the asymmetries due to B4C and (27)Al are zero to with- in 2 × 10(-6) and 7 × 10(-7), respectively. Boron and aluminum are used throughout the experiment. The results presented here are preliminary.

Hybrid spin-exchange optical pumping of 3He.

We demonstrate spin-exchange optical pumping of 3He using a "hybrid" K-Rb vapor mixture. The Rb atoms absorb light from a standard laser at 795 nm, then collisionally polarize the potassium atoms. Spin-exchange collisions of K and 3He atoms then transfer the angular momentum to the 3He with much greater efficiency than Rb-3He. For a K-rich vapor, the efficiency of the hybrid spin-exchange collisions approaches 1/4, an order of magnitude greater than achieved by pure Rb pumping. We present the first measurements of actual photon efficiencies (polarized nuclei produced per absorbed photon), and show that a new parasitic absorption process limits the total efficiencies for both hybrid and pure Rb pumping.

Q2 evolution of the generalized Gerasimov-Drell-Hearn integral for the neutron using a 3He target.

We present data on the inclusive scattering of polarized electrons from a polarized 3He target at energies from 0.862 to 5.06 GeV, obtained at a scattering angle of 15.5 degrees. Our data include measurements from the quasielastic peak, through the nucleon resonance region, and beyond, and were used to determine the virtual photon cross-section difference sigma(1/2)-sigma(3/2). We extract the extended Gerasimov-Drell-Hearn integral for the neutron in the range of four-momentum transfer squared Q2 of 0.1-0.9 GeV2.

Precision measurement of the spin-dependent asymmetry in the threshold region of 3He(e, e').

We present the first precision measurement of the spin-dependent asymmetry in the threshold region of 3He(e,e') at Q2 values of 0.1 and 0.2 (GeV/c)2. The agreement between the data and nonrelativistic Faddeev calculations which include both final-state interactions and meson-exchange current effects is very good at Q2 = 0.1 (GeV/c)2, while a small discrepancy at Q2 = 0.2 (GeV/c)2 is observed.

Dynamics of the 16O(e, e'p) reaction at high missing energies.

We measured the cross section and response functions for the quasielastic 16O(e,e'p) reaction for missing energies 25< or =E(m)< or =120 MeV at missing momenta P(m)< or =340 MeV/c. For 25

Transverse asymmetry AT' from the quasielastic 3He(e,e') process and the neutron magnetic form factor.

We have measured the transverse asymmetry A(T') in 3He(e,e(')) quasielastic scattering in Hall A at Jefferson Laboratory with high precision for Q2 values from 0.1 to 0.6 (GeV/c)(2). The neutron magnetic form factor G(n)(M) was extracted based on Faddeev calculations for Q2 = 0.1 and 0.2 (GeV/c)(2) with an experimental uncertainty of less than 2%.

A system for low field imaging of laser-polarized noble gas.

We describe a device for performing MRI with laser-polarized noble gas at low magnetic fields (<50 G). The system is robust, portable, inexpensive, and provides gas-phase imaging resolution comparable to that of high field clinical instruments. At 20.6 G, we have imaged laser-polarized (3)He (Larmor frequency of 67 kHz) in both sealed glass cells and excised rat lungs, using approximately 0.1 G/cm gradients to achieve approximately 1 mm(2) resolution. In addition, we measured (3)He T(2)(*) times greater than 100 ms in excised rat lungs, which is roughly 20 times longer than typical values observed at high ( approximately 2 T) fields. We include a discussion of the practical considerations for working at low magnetic fields and conclude with evidence of radiation damping in this system.

Low-field MRI of laser polarized noble gas.

NMR images of laser polarized 3He gas were obtained at 21 G using a simple, homebuilt instrument. At such low fields magnetic resonance imaging (MRI) of thermally polarized samples (e.g., water) is not practical. Low-field noble gas MRI has novel scientific, engineering, and medical applications. Examples include portable systems for diagnosis of lung disease, as well as imaging of voids in porous media and within metallic systems.