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

Hyperpolarized xenon-129 is a noninvasive 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 (three 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 (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.

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

RATIONALE AND OBJECTIVES: Hyperpolarized gases such as (129)Xe and (3)He have high potential as imaging agents for functional lung magnetic resonance imaging (MRI). We present new technology offering (129)Xe 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 continuous-flow system capable of producing large quantities of highly-polarized (129)Xe 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.