Search

PURPOSE: To reduce scan duration in hyperpolarized (129)Xe 1-point Dixon gas exchange imaging by utilizing flip angle (FA)/TR equivalence. METHODS: Images were acquired in 12 subjects (N = 3 radiation therapy, N = 1 unexplained dyspnea, N = 8 Healthy) using both standard (TR = 15 ms, FA = 20°, Duration = 15 s, 998 projections) and “fast” (TR = 5.4 ms, FA = 12°, Duration = 11.3 s, 2100 projections) acquisition parameters. For the “fast” acquisition, three image sets were reconstructed using subsets of 1900, 1500, and 1000 projections. From the resulting ventilation, tissue (“barrier”), and red blood cell (RBC) images, image metrics and biomarkers were compared to assess agreement between methods. RESULTS: Images acquired using both FA/TR settings had similar qualitative appearance. There were no significant differences in SNR, image mean, or image standard deviation between images. Moreover, the percentage of the lungs in “defect”, “normal”, and “high” bins for each image (ventilation, RBC, Barrier) was not significantly different among the acquisition types. After registration, comparison of 3D image metrics (Dice, volume similarity, average distance) agreed well between bins. Images using 1000 projections for reconstruction had no significant differences from images using all projections. CONCLUSION: Using flip angle/TR equivalence, hyperpolarized (129)Xe gas exchange images can be acquired via the 1-point Dixon technique in as little as 6 s, compared to ~15 s for previously reported parameter settings. The resulting images from this accelerated scan have no significant differences from the standard method in qualitative appearance or quantitative metrics.

Magnetic resonance (MR) imaging and spectroscopy using dissolved hyperpolarized (HP) (129)Xe have expanded the ability to probe lung function regionally and noninvasively. In particular, HP (129)Xe imaging has been used to quantify impaired gas uptake by the pulmonary tissues. Whole-lung spectroscopy has also been used to assess global cardiogenic oscillations in the MR signal intensity originating from (129)Xe dissolved in the red blood cells of pulmonary capillaries. Herein, we show that the magnitude of these cardiogenic dynamics can be mapped three dimensionally using radial MRI, because dissolved (129)Xe dynamics are encoded directly in the raw imaging data. Specifically, 1-point Dixon imaging is combined with postacquisition keyhole image reconstruction to assess regional blood volume fluctuations within the pulmonary microvasculature throughout the cardiac cycle. This “oscillation mapping” was applied in healthy subjects (mean amplitude 9% of total RBC signal) and patients with pulmonary arterial hypertension (PAH; mean 4%) and idiopathic pulmonary fibrosis (IPF; mean 14%). Whole-lung mean values from these oscillation maps correlated strongly with spectroscopy and clinical pulmonary function testing, but exhibited significant regional heterogeneity, including gravitationally dependent gradients in healthy subjects. Moreover, regional oscillations were found to be sensitive to disease state. Greater percentages of the lungs exhibit low-amplitude oscillations in PAH patients, and longitudinal imaging shows high-amplitude oscillations increase significantly over time (4–14 mo, P = 0.02) in IPF patients. This technique enables regional dynamics within the pulmonary capillary bed to be measured, and in doing so, provides insight into the origin and progression of pathophysiology within the lung microvasculature. NEW & NOTEWORTHY Spatially heterogeneous abnormalities within the lung microvasculature contribute to pathology in various cardiopulmonary diseases but are difficult to assess noninvasively. Hyperpolarized (129)Xe MRI is a noninvasive method to probe lung function, including regional gas exchange between pulmonary air spaces and capillaries. We show that cardiogenic oscillations in the raw dissolved (129)Xe MRI signal from pulmonary capillary red blood cells can be imaged using a postacquisition reconstruction technique, providing a new means of assessing regional lung microvasculature function and disease state.

PURPOSE: Hyperpolarized (129)Xe MRI characterizes regional lung ventilation in a variety of disease populations, with high sensitivity to airway obstruction in early disease. However, ventilation images are usually limited to a single breath-hold and most-often acquired using gradient-recalled echo sequences with thick slices (~10–15 mm), which increases partial-volume effects, limits ability to observe small defects, and suffers from imperfect slice selection. We demonstrate higher-resolution ventilation images, in shorter breath-holds, using FLORET (Fermat Looped ORthogonally Encoded Trajectories), a center-out 3D-spiral UTE sequence. METHODS: In vivo human adult (N = 4; 2 healthy, 2 with cystic fibrosis) (129)Xe images were acquired using 2D gradient-recalled echo, 3D radial, and FLORET. Each sequence was acquired at its highest possible resolution within a 16-second breath-hold with a minimum voxel dimension of 3 mm. Images were compared using (129)Xe ventilation defect percentage, SNR, similarity coefficients, and vasculature cross-sections. RESULTS: The FLORET sequence obtained relative normalized SNR, 40% greater than 2D gradient-recalled echo (P = .012) and 26% greater than 3D radial (P = .067). Moreover, the FLORET images were acquired with 3-fold-higher nominal resolution in a 15% shorter breath-hold. Finally, vasculature was less prominent in FLORET, likely due to diminished susceptibility-induced dephasing at shorter TEs afforded by UTE sequences. CONCLUSION: The FLORET sequence yields higher SNR for a given resolution with a shorter breath-hold than traditional ventilation imaging techniques. This sequence more accurately measures ventilation abnormalities and enables reduced scan times in patients with poor compliance and severe lung disease.

Glassing matrix deuteration could be a beneficial sample preparation method for (13)C dynamic nuclear polarization (DNP) when large electron paramagnetic resonance (EPR) width free radicals are used. However, it could yield the opposite DNP effect when samples are doped with small EPR width free radicals. Herein, we have investigated the influence of solvent deuteration on the (13)C nuclear and electron relaxation that go along with the effects on (13)C DNP intensities at 3.35 T and 1.2 K. For (13)C DNP samples doped with trityl OX063, the (13)C DNP signals decreased significantly when the protons are replaced by deuterons in glycerol:water or DMSO:water solvents. Meanwhile, the corresponding solid-state (13)C T(1) relaxation times of trityl OX063-doped samples generally increased upon solvent deuteration. On the other hand, (13)C DNP signals improved by a factor of ∼1.5 to 2 upon solvent deuteration of samples doped with 4-oxo-TEMPO. Despite this (13)C DNP increase, there were no significant differences recorded in (13)C T(1) values of TEMPO-doped samples with nondeuterated or fully deuterated glassing matrices. While solvent deuteration appears to have a negligible effect on the electron T(1) relaxation of both free radicals, the electron T(2) relaxation times of these two free radicals generally increased upon solvent deuteration. These overall results suggest that while the solid-phase (13)C DNP signals are dependent upon the changes in total nuclear Zeeman heat capacity, the (13)C relaxation effects are related to (2)H/(1)H nuclear spin diffusion-assisted (13)C polarization leakage in addition to the dominant paramagnetic relaxation contribution of free radical centers.

Optimal efficiency of dissolution dynamic nuclear polarization (DNP) is essential to provide the required high sensitivity enhancements for in vitro and in vivo hyperpolarized 13C nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI). At the nexus of the DNP process are the free electrons which provide the high spin alignment that are transferred to the nuclear spins. Without changing DNP instrumental conditions, one way to improve 13C DNP efficiency is by adding trace amounts of paramagnetic additives such as lanthanide (e.g. Gd3+, Ho3+, Dy3+, Tb3+) complexes to the DNP sample which has been observed to increase solid state 13C DNP signals by 100–250%. Herein, we have investigated the effects of paramagnetic transition metal complex R-NOTA (R=Mn2+, Cu2+, Co2+) doping on the efficiency of 13C DNP using trityl OX063 as the polarizing agent. Our DNP results at 3.35 T and 1.2 K show that doping the 13C sample with 3 mM Mn2+-NOTA led to a substantial improvement of the solid-state 13C DNP signal by a factor of nearly 3-fold. However, the other transition metal complexes Cu2+-NOTA and Co2+-NOTA complexes, despite their paramagnetic nature, had essentially no impact on solid-state 13C DNP enhancement. W-band electron paramagnetic resonance (EPR) measurements reveal that the trityl OX063 electron T1 was significantly reduced in Mn2+-doped samples but not in Cu2+- and Co2+-doped DNP samples. This work demonstrates, for the first time, that not all paramagnetic additives are beneficial to DNP. In particular, our work provides a direct evidence that electron T1 reduction of the polarizing agent by a paramagnetic additive is an essential requirement for the improvement seen in solid-state 13C DNP signal.

Dynamic nuclear polarization (DNP) via the dissolution method has alleviated the insensitivity problem in liquid-state nuclear magnetic resonance (NMR) spectroscopy by amplifying the signals by several thousand-fold. This NMR signal amplification process emanates from the microwave-mediated transfer of high electron spin alignment to the nuclear spins at high magnetic field and cryogenic temperature. Since the interplay between the electrons and nuclei is crucial, the chemical composition of a DNP sample such as the type of free radical used, glassing solvents, or the nature of the target nuclei can significantly affect the NMR signal enhancement levels that can be attained with DNP. Herein, we have investigated the influence of 13C isotopic labeling location on the DNP of a model 13C compound, sodium acetate, at 3.35 T and 1.4 K using the narrow electron spin resonance (ESR) linewidth free radical trityl OX063. Our results show that the carboxyl 13C spins yielded about twice the polarization produced in methyl 13C spins. Deuteration of the methyl 13C group, while proven beneficial in the liquid-state, did not produce an improvement in the 13C polarization level at cryogenic conditions. In fact, a slight reduction of the solid-state 13C polarization was observed when 2H spins are present in the methyl group. Furthermore, our data reveal that there is a close correlation between the solid-state 13C T1 relaxation times of these samples and the relative 13C polarization levels. The overall results suggest the achievable solid-state polarization of 13C acetate is directly affected by the location of the 13C isotopic labeling via the possible interplay of nuclear relaxation leakage factor and cross-talks between nuclear Zeeman reservoirs in DNP.