Gradient-induced longitudinal relaxation of hyperpolarized noble gases in the fringe fields of superconducting magnets used for magnetic resonance.

When hyperpolarized noble gases are brought into the bore of a superconducting magnet for magnetic resonance imaging (MRI) or spectroscopy studies, the gases must pass through substantial field gradients, which can cause rapid longitudinal relaxation. In this communication, we present a means of calculating this spatially dependent relaxation rate in the fringe field of typical magnets. We then compare these predictions to experimental measurements of (3)He relaxation at various positions near a medium-bore 2-T small animal MRI system. The calculated and measured relaxation rates on the central axis of the magnet agree well and show a maximum (3)He relaxation rate of 3.83×10(-3) s(-1) (T(1)=4.4 min) at a distance of 47 cm from the magnet isocenter. We also show that if this magnet were self-shielded, its minimum T(1) would drop to 1.2 min. In contrast, a typical self-shielded 1.5-T clinical MRI scanner will induce a minimum on-axis T(1) of 12 min. Additionally, we show that the cylindrically symmetric fields of these magnets enable gradient-induced relaxation to be calculated using only knowledge of the on-axis longitudinal field, which can either be measured directly or calculated from a simple field model. Thus, while most MRI magnets employ complex and proprietary current configurations, we show that their fringe fields and the resulting gradient-induced relaxation are well approximated by simple solenoid models. Finally, our modeling also demonstrates that relaxation rates can increase by nearly an order of magnitude at radial distances equivalent to the solenoid radius

Pulmonary perfusion and xenon gas exchange in rats: MR imaging with intravenous injection of hyperpolarized 129Xe.

PURPOSE: To develop and demonstrate a method for regional evaluation of pulmonary perfusion and gas exchange based on intravenous injection of hyperpolarized xenon 129 ((129)Xe) and subsequent magnetic resonance (MR) imaging of the gas-phase (129)Xe emerging in the alveolar airspaces. MATERIALS AND METHODS: Five Fischer 344 rats that weighed 200-425 g were prepared for imaging according to an institutional animal care and use committee-approved protocol. Rats were ventilated, and a 3-F catheter was placed in the jugular (n = 1) or a 24-gauge catheter in the tail (n = 4) vein. Imaging and spectroscopy of gas-phase (129)Xe were performed after injecting 5 mL of half-normal saline saturated with (129)Xe hyperpolarized to 12%. Corresponding ventilation images were obtained during conventional inhalation delivery of hyperpolarized (129)Xe. RESULTS: Injections of (129)Xe-saturated saline were well tolerated and produced a strong gas-phase (129)Xe signal in the airspaces that resulted from (129)Xe transport through the pulmonary circulation and diffusion across the blood-gas barrier. After a single injection, the emerging (129)Xe gas could be detected separately from (129)Xe remaining in the blood and was imaged with an in-plane resolution of 1 x 1 mm and a signal-to-noise ratio of 25. Images in one rat revealed a matched ventilation-perfusion deficit, while images in another rat showed that xenon gas exchange was temporarily impaired after saline overload, with recovery of function 1 hour later. CONCLUSION: MR imaging of gas-phase (129)Xe emerging in the pulmonary airspaces after intravenous injection has the potential to become a sensitive and minimally invasive new tool for regional evaluation of pulmonary perfusion and gas exchange. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/2513081550/DC1

Enhanced Efficiency of ¹³C Dynamic Nuclear Polarization by Superparamagnetic Iron Oxide Nanoparticle Doping

The attainment of high NMR signal enhancements is crucial to the success of in vitro or in vivo hyperpolarized NMR or imaging (MRI) experiments. In this work, we report on the use of a superparamagnetic iron oxide nanoparticle (SPION) MRI contrast agent Feraheme (ferumoxytol) as a beneficial additive in ¹³C samples for dissolution dynamic nuclear polarization (DNP). Our DNP data at 3.35 T and 1.2 K reveal that the addition of 11 mM elemental iron concentration of Feraheme in trityl OX063-doped 3 M [1-¹³C] acetate samples resulted in a substantial improvement of ¹³C DNP signal by a factor of almost three-fold. Concomitant with the large DNP signal increase is the narrowing of the ¹³C microwave DNP spectra for samples doped with SPION. W-band electron paramagnetic resonance (EPR) spectroscopy data suggest that these two prominent effects of SPION doping on ¹³C DNP can be ascribed to the shortening of trityl OX063 electron <i>T</i>₁, as explained within the thermal mixing DNP model. Liquid-state ¹³C NMR signal enhancements as high as 20,000-fold for SPION-doped samples were recorded after dissolution at 9.4 T and 297 K, which is about three times the liquid-state NMR signal enhancement of the control sample. While the presence of SPION in hyperpolarized solution drastically reduces ¹³C <i>T</i>₁, this can be mitigated by polarizing smaller aliquots of DNP samples. Moreover, we have shown that Feraheme nanoparticles (∼30 nm in size) can be easily and effectively removed from the hyperpolarized liquid by simple mechanical filtration, and thus one can potentially incorporate an in-line filtration for these SPIONS along the dissolution pathway of the hyperpolarizer, a significant advantage over other DNP enhancers such as the lanthanide complexes. The overall results suggest that the commercially available and FDA-approved Feraheme is a highly efficient DNP enhancer that could be readily translated for use in clinical applications of dissolution DNP

Preclinical MRI to quantify pulmonary disease severity and trajectories in poorly characterized mouse models: A pedagogical example using data from novel transgenic models of lung fibrosis

Structural remodeling in lung disease is progressive and heterogeneous, making temporally and spatially explicit information necessary to understand disease initiation and progression. While mouse models are essential to elucidate mechanistic pathways underlying disease, the experimental tools commonly available to quantify lung disease burden are typically invasive (e.g., histology). This necessitates large cross-sectional studies with terminal endpoints, which increases experimental complexity and expense. Alternatively, magnetic resonance imaging (MRI) provides information noninvasively, thus permitting robust, repeated-measures statistics. Although lung MRI is challenging due to low tissue density and rapid apparent transverse relaxation (T2* <1 ms), various imaging methods have been proposed to quantify disease burden. However, there are no widely accepted strategies for preclinical lung MRI. As such, it can be difficult for researchers who lack lung imaging expertise to design experimental protocols—particularly for novel mouse models. Here, we build upon prior work from several research groups to describe a widely applicable acquisition and analysis pipeline that can be implemented without prior preclinical pulmonary MRI experience. Our approach utilizes 3D radial ultrashort echo time (UTE) MRI with retrospective gating and lung segmentation is facilitated with a deep-learning algorithm. This pipeline was deployed to assess disease dynamics over 255 days in novel, transgenic mouse models of lung fibrosis based on disease-associated, loss-of-function mutations in Surfactant Protein-C. Previously identified imaging biomarkers (tidal volume, signal coefficient of variation, etc.) were calculated semi-automatically from these data, with an objectively-defined high signal volume identified as the most robust metric. Beyond quantifying disease dynamics, we discuss common pitfalls encountered in preclinical lung MRI and present systematic approaches to identify and mitigate these challenges. While the experimental results and specific pedagogical examples are confined to lung fibrosis, the tools and approaches presented should be broadly useful to quantify structural lung disease in a wide range of mouse models

Hyperpolarized Xe MR imaging of alveolar gas uptake in humans.

BACKGROUND: One of the central physiological functions of the lungs is to transfer inhaled gases from the alveoli to pulmonary capillary blood. However, current measures of alveolar gas uptake provide only global information and thus lack the sensitivity and specificity needed to account for regional variations in gas exchange. METHODS AND PRINCIPAL FINDINGS: Here we exploit the solubility, high magnetic resonance (MR) signal intensity, and large chemical shift of hyperpolarized (HP) (129)Xe to probe the regional uptake of alveolar gases by directly imaging HP (129)Xe dissolved in the gas exchange tissues and pulmonary capillary blood of human subjects. The resulting single breath-hold, three-dimensional MR images are optimized using millisecond repetition times and high flip angle radio-frequency pulses, because the dissolved HP (129)Xe magnetization is rapidly replenished by diffusive exchange with alveolar (129)Xe. The dissolved HP (129)Xe MR images display significant, directional heterogeneity, with increased signal intensity observed from the gravity-dependent portions of the lungs. CONCLUSIONS: The features observed in dissolved-phase (129)Xe MR images are consistent with gravity-dependent lung deformation, which produces increased ventilation, reduced alveolar size (i.e., higher surface-to-volume ratios), higher tissue densities, and increased perfusion in the dependent portions of the lungs. Thus, these results suggest that dissolved HP (129)Xe imaging reports on pulmonary function at a fundamental level

Gas-phase ¹²⁹Xe MR imaging.

<p><b>A.</b> Axial slice from an EC infusion image (EC flow ∼15 ml/min) acquired with a nominal isotropic resolution of 2×2×2 mm³. Black arrow indicates a signal void in the image corresponding to the location of a major airway. Red arrow indicates a hypointense region that likely corresponds to a large blood vessel. <b>B.</b> Axial slice from the corresponding ventilation image acquired with 1×1×2 mm³ nominal resolution. Black arrow indicates a large airway in the same location as the signal void in A (also marked by a black arrow). Red arrow points to a hypointense region corresponding to the red arrow in B. <b>C.</b> Complete 3D, gas-phase, EC infusion image (color) overlaid on the 3D ventilation image (grayscale). The signal intensity of the EC infusion image, in arbitrary units, is indicated in the legend.</p