Open-Access, Low-Magnetic-Field MRI System for Lung Research

An open-access magnetic resonance imaging (MRI) system is being developed for use in research on orientational/gravitational effects on lung physiology and function. The open-access geometry enables study of human subjects in diverse orientations. This system operates at a magnetic flux density, considerably smaller than the flux densities of typical other MRI systems, that can be generated by resistive electromagnet coils (instead of the more-expensive superconducting coils of the other systems). The human subject inhales air containing He-3 or Xe-129 atoms, the nuclear spins of which have been polarized by use of a laser beam to obtain a magnetic resonance that enables high-resolution gas space imaging at the low applied magnetic field. The system includes a bi-planar, constant-current, four-coil electromagnet assembly and associated electronic circuitry to apply a static magnetic field of 6.5 mT throughout the lung volume; planar coils and associated circuitry to apply a pulsed magnetic-field-gradient for each spatial dimension; a single, detachable radio-frequency coil and associated circuitry for inducing and detecting MRI signals; a table for supporting a horizontal subject; and electromagnetic shielding surrounding the electromagnet coils

Optical pumping system design for large production of hyperpolarized Xe-129

We present a design for a spin-exchange optical pumping system to produce large quantities of highly polarized Xe-129. Low xenon concentrations in the flowing gas mixture allow the laser to maintain high Rb polarization. The large spin-exchange rate between Rb and Xe-129 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

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. (c) 2005 Optical Society of America

Hybrid spin-exchange optical pumping of He-3

We demonstrate spin-exchange optical pumping of He-3 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 He-3 atoms then transfer the angular momentum to the He-3 with much greater efficiency than Rb-He-3. 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

Multiple-exchange-time xenon polarization transfer contrast (MXTC) MRI:initial results in animals and healthy volunteers

Hyperpolarized xenon-129 is a non-invasive contrast agent for lung MRI, which upon inhalation dissolves in parenchymal structures, thus mirroring the gas-exchange process for oxygen in the lung. Multiple-exchange-time Xenon polarization Transfer Contrast (MXTC) MRI is an implementation of the XTC MRI technique in four dimensions (3 spatial dimensions plus exchange time). The aim of this study was to evaluate the sensitivity of MXTC MRI for the detection of microstructural deformations of the healthy lung in response to gravity-induced tissue compression and the degree of lung inflation. MXTC MRI was performed in four rabbits and in three healthy human volunteers. Two lung function parameters, one related to tissue- to alveolar-volume ratio and the other to average septal-wall thickness, were determined regionally. A significant gradient in MXTC MRI parameters, consistent with gravity-induced lung tissue deformation in the supine imaging position, was found at low lung volumes. At high lung volumes, parameters were generally lower and the gradient in parameter values was less pronounced. Results show that MXTC MRI permits the quantification of subtle changes in healthy lung microstructure. Further, only structures participating in gas exchange are represented in MXTC MRI data, which potentially makes the technique especially sensitive to pathological changes in lung microstructure affecting gas exchange

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 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 \u3e= 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

Hyperpolarized Xe-129 MRI: A viable functional lung imaging modality?

The majority of researchers investigating hyperpolarized gas MRI as a candidate functional lung imaging modality have used He-3 as their imaging agent of choice rather than Xe-129. This preference has been predominantly due to, He-3 providing stronger signals due to higher levels of polarization and higher gyromagnetic ratio, as well as its being easily available to more researchers due to availability of polarizers (USA) or ease of gas transport (Europe). Most researchers agree, however, that hyperpolarized Xe-129 Will ultimately emerge as the imaging agent of choice due to its unlimited supply in nature and its falling cost. Our recent polarizer technology delivers vast improvements in hyperpolarized Xe-129 output. Using this polarizer, we have demonstrated the unique property of xenon to measure alveolar surface area noninvasively. In this article, we describe our human protocols and their safety, and our results for the measurement of the partial pressure of pulmonary oxygen (pO(2)) by observation of Xe-129 signal decay. We note that the measurement of pO(2) by observation of Xe-129 signal decay is more complex than that for He-3 because of an additional signal loss mechanism due to interphase diffusion of Xe-129 from alveolar gas spaces to septal tissue. This results in measurements of an equivalent pO(2) that accounts for both traditional T-1 decay from pO(2) and that from interphase diffusion. We also provide an update on new technological advancements that form the foundation for an improved compact design polarizer as well as improvements that provide another order-of-magnitude scale-up in xenon polarizer output. (c) 2007 Elsevier Ireland Ltd. All rights reserved

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

Rationale and Objectives: Using a novel Xe-129 polarizer with high throughput (1-2 L/hour) and high polarization (similar to 55%), our objective was to demonstrate and characterize human pulmonary applications at 0.2T. Specifically, we investigated the ability of 129Xe 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\u27s 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 Xe-129 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 Xe-129 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 IL 86% Xe-129 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 similar to 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 Xe-129 human imaging and spectroscopy are very promising methods to provide functional information about the lung

Single-breath xenon polarization transfer contrast (SB-XTC):Implementation and initial results in healthy humans

PURPOSE: To implement and characterize a single-breath xenon transfer contrast (SB-XTC) method to assess the fractional diffusive gas transport F in the lung: to study the dependence of F and its uniformity as a function of lung volume; to estimate local alveolar surface area per unit gas volume S(A)/V(Gas) from multiple diffusion time measurements of F; to evaluate the reproducibility of the measurements and the necessity of B(1) correction in cases of centric and sequential encoding. MATERIALS AND METHODS: In SB-XTC three or four gradient echo images separated by inversion/saturation pulses were collected during a breath-hold in eight healthy volunteers, allowing the mapping of F (thus S(A)/V(Gas)) and correction for other contributions such as T(1) relaxation, RF depletion and B(1) inhomogeneity from inherently registered data. RESULTS: Regional values of F and its distribution were obtained; both the mean value and heterogeneity of F increased with the decrease of lung volume. Higher values of F in the bases of the lungs in supine position were observed at lower volumes in all volunteers. Local S(A)/V(Gas) (with a mean ± standard deviation of [Formula: see text]) was estimated in vivo near functional residual capacity. Calibration of SB-XTC on phantoms highlighted the necessity for B(1) corrections when k-space is traversed sequentially; with centric ordering B(1) distribution correction is dispensable. CONCLUSION: SB-XTC technique is implemented and validated for in vivo measurements of local S(A)/V(Gas)

Large production system for hyperpolarized Xe-129 for human lung imaging studies

Rationale and Objectives. Hyperpolarized gases such as Xe-129 and He-3 have high potential as imaging agents for functional lung magnetic resonance imaging (MRI). We present new technology offering Xe-129 production rates with order-of-magnitude improvement over existing systems, to liter per hour at 50% polarization., Human lung imaging studies with xenon, initially limited by the modest quantity and quality of hyperpolarized gas available, can now be performed with multiliter quantities several times daily. Materials and Methods. The polarizer is a continuolis-flow system capable of producing large quantities of highly-polarized 129Xe through rubidium spin-exchange optical pumping. The low-pressure, high-velocity operating regime takes advantage of the enhancement in the spin exchange rate provided by van der Waals molecules dominating the atomic interactions. The long polarizing column moves the flow of the gas opposite to the laser direction, allowing efficient extraction of the laser light. Separate sections of the system assure full rubidium vapor saturation and removal. Results. The system is capable of producing 64% polarization at 0.3 L/hour Xe production rate. Increasing xenon flow reduces output polarization. Xenon polarization was studied as a function of different system operating parameters. A novel xenon trapping design was demonstrated to allow full recovery of the xenon polarization after the freeze-thaw cycle. Delivery methods of the gas to an offsite MRI facility were demonstrated in both frozen and gas states. Conclusions. We demonstrated a new concept for producing large quantities of highly polarized xenon. The system is operating in an MRI facility producing liters of hyperpolarized gas for human lung imaging studies