Propagation of dynamic nuclear polarization across the xenon cluster boundaries: elucidation of the spin-diffusion bottleneck.

Earlier Dynamic Nuclear Polarization (DNP) experiments with frozen xenon/1-propanol/trityl mixtures have demonstrated spontaneous formation of pure xenon clusters above 120 K, enabling spectrally-resolved real-time measurements of (129)Xe nuclear magnetization in the clusters and in the surrounding radical-rich matrix. A spin-diffusion bottleneck was postulated to explain the peculiar time evolution of (129)Xe signals in the clusters as well as the apparent discontinuity of (129)Xe polarization across the cluster boundaries. A self-contained ab initio model of nuclear spin diffusion in heterogeneous systems is developed here, incorporating the intrinsic T1 relaxation towards the temperature-dependent equilibrium polarization and the spin-diffusion coefficients based on the measured NMR line widths and the known atomic densities in each compartment. This simple model provides the physical basis for the observed spin-diffusion bottleneck and is in a good quantitative agreement with the earlier measurements. A simultaneous fit of the model to the time-dependent NMR data at two different DNP frequencies provides excellent estimates of the cluster size, the intrinsic sample temperature, and (129)Xe T1 constants. The model was also applied to the NMR data acquired during relaxation towards the thermal equilibrium after the microwaves were turned off, to estimate T1 relaxation time constants inside and outside the clusters. Fitting the model to the data during and after DNP provides consistent estimates of the cluster size.

Lineshape-based polarimetry of dynamically-polarized (15)N2O in solid-state mixtures.

Dynamic nuclear polarization (DNP) of (15)N2O, known for its long-lived singlet-state order at low magnetic field, is demonstrated in organic solvent/trityl mixtures at ∼1.5 K and 5 T. Both (15)N polarization and intermolecular dipolar broadening are strongly affected by the sample's thermal history, indicating spontaneous formation of N2O clusters. In situ (15)N NMR reveals four distinct powder-pattern spectra, attributed to the chemical-shift anisotropy (CSA) tensors of the two (15)N nuclei, further split by the intramolecular dipolar coupling between their magnetic moments. (15)N polarization is estimated by fitting the free-induction decay (FID) signals to the analytical model of four single-quantum transitions. This analysis implies (10.2±2.2)% polarization after 37 h of DNP, and provides a direct, instantaneous probe of the absolute (15)N polarization, without a need for time-consuming referencing to a thermal-equilibrium NMR signal.

Cluster formation restricts dynamic nuclear polarization of xenon in solid mixtures.

During dynamic nuclear polarization (DNP) at 1.5 K and 5 T, (129)Xe nuclear magnetic resonance (NMR) spectra of a homogeneous xenon/1-propanol/trityl-radical solid mixture exhibit a single peak, broadened by (1)H neighbors. A second peak appears upon annealing for several hours at 125 K. Its characteristic width and chemical shift indicate the presence of spontaneously formed pure Xe clusters. Microwave irradiation at the appropriate frequencies can bring both peaks to either positive or negative polarization. The peculiar time evolution of (129)Xe polarization in pure Xe clusters during DNP can be modelled as an interplay of spin diffusion and T(1) relaxation. Our simple spherical-cluster model offers a sensitive tool to evaluate major DNP parameters in situ, revealing a severe spin-diffusion bottleneck at the cluster boundaries and a significant sample overheating due to microwave irradiation. Subsequent DNP system modifications designed to reduce the overheating resulted in four-fold increase of (129)Xe polarization, from 5.3% to 21%.

Metabolism of hyperpolarized [1-¹³C]pyruvate in the isolated perfused rat lung - an ischemia study.

We report studies of the effect of ischemia on the metabolic activity of the intact perfused lung and its restoration after a period of reperfusion. Two groups of rat lungs were studied using hyperpolarized 1-(13) C pyruvate to compare the rate of lactate labeling differing only in the temporal ordering of ischemic and normoxic acquisitions. In both cases, a several-fold increase in lactate labeling was observed immediately after a 25-min ischemia event as was its reversal back to the baseline after 30-40 min of resumed perfusion (n = 5, p < 0.025 for both comparisons). These results were corroborated by (31) P spectroscopy and correspond well to measured changes in lactate pool size determined by (1) H spectroscopy of freeze-clamped specimens.

Measurements of the persistent singlet state of N2O in blood and other solvents--potential as a magnetic tracer.

The development of hyperpolarized tracers has been limited by short nuclear polarization lifetimes. The dominant relaxation mechanism for many hyperpolarized agents in solution arises from intramolecular nuclear dipole-dipole coupling modulated by molecular motion. It has been previously demonstrated that nuclear spin relaxation due to this mechanism can be removed by storing the nuclear polarization in long-lived, singlet-like states. In the case of N(2)O, storing the polarization of the nitrogen nuclei has been shown to substantially increase the polarization lifetime. The feasibility of utilizing N(2)O as a tracer is investigated by measuring the singlet-state lifetime of the N(2)O when dissolved in a variety of solvents including whole blood. Comparison of the singlet lifetime to longitudinal relaxation and between protonated and deuterated solvents is consistent with the dominance of spin-rotation relaxation, except in the case of blood.

Quantitative assessment of emphysema using hyperpolarized 3He magnetic resonance imaging.

In this experiment, Sprague-Dawley rats with elastase-induced emphysema were imaged using hyperpolarized (3)He MRI. Regional fractional ventilation r, the fraction of gas replaced with a single tidal breath, was calculated from a series of images in a wash-in study of hyperpolarized gas. We compared the regional fractional ventilation in these emphysematous rats to the regional fractional ventilations we calculated from a previous baseline study in healthy Sprague-Dawley rats. We found that there were differences in the maps of fractional ventilation and its associated frequency distribution between the healthy and emphysematous rat lungs. Fractional ventilation tended to be much lower in emphysematous rats than in normal rats. With this information, we can use data on fractional ventilation to regionally distinguish between healthy and emphysematous portions of the lung. The successful implementation of such a technique on a rat model could lead to work toward the future implementation of this technique in human patients.

A small animal model of regional alveolar ventilation using HP 3He MRI1.

RATIONALE AND OBJECTIVES: The aim of this study was to establish a standardized procedure for the measurement of regional fractional ventilation in a healthy rat model as a baseline for further studies of pulmonary disorder models. MATERIALS AND METHODS: The lungs of five healthy male Sprague-Dawley rats were imaged using hyperpolarized helium-3 magnetic resonance imaging. From these images, regional fractional ventilation was calculated and maps generated detailing the distribution of fractional ventilation in the lung. The 1.56 mm x 1.56 mm x 4 mm regions of interest were assigned on 5 cm x 5 cm field of view lung maps. Histograms were also generated showing the frequency distribution of fractional ventilation values. To compare fractional ventilation values between animals, the ventilation procedure was standardized to results from individual pulmonary function tests. Each animal's spontaneous tidal volume, respiratory rate, and inspiration percentage (percent of total respiratory cycle in inspiration) were used in their mechanical ventilation settings. RESULTS: Results were similar among all five healthy rats based on examination of ventilation distribution maps and frequency distribution histograms. Mean (0.13) and standard deviation (0.07) were calculated for fractional ventilation in each animal. However, these values were determined to be influenced by slice selection, and therefore the maps and histograms were favored in analysis of results. CONCLUSION: This study shows consistent results in healthy rat lungs and will serve as a baseline study for future measurements in emphysematous rat lungs.

Single-acquisition sequence for the measurement of oxygen partial pressure by hyperpolarized gas MRI.

Magnetic resonance imaging (MRI) with hyperpolarized 3-helium gas (HP 3He) offers the possibility of studying functional lung parameters such as the alveolar oxygen concentration and oxygen depletion rate. Until now, a double-acquisition technique has been utilized to extract these parameters. A complicated single-acquisition technique was previously developed to avoid the necessity of performing two identical breathing maneuvers. The results obtained with this technique were significantly less accurate than the results obtained with the double-acquisition method. In this work, a novel, easily implemented single-acquisition sequence is presented that provides results comparable to those obtained with the established double-acquisition method. This method is demonstrated in a phantom and a pig model on a 1.5 T scanner using a 2D fast low-angle shot (FLASH) gradient-echo sequence. Numerical simulations of the time evolution of the oxygen concentration were performed. Simulation results are presented to support the experimental data. Various parameter regimes were experimentally and numerically investigated.

Human knee: in vivo T1(rho)-weighted MR imaging at 1.5 T--preliminary experience.

A fast spin-echo sequence weighted with a time constant that defines the magnetic relaxation of spins under the influence of a radio-frequency field (T1(rho)) was used in six subjects to measure magnetic resonance (MR) relaxation times in the knee joint with a 1.5-T MR imager. A quantitative comparison of T2- and T1(rho)-weighted MR images was also performed. Substantial T1(rho) dispersion was demonstrated in human articular cartilage, but muscle did not demonstrate much dispersion. T1(rho)-weighted images depicted a chondral lesion with 25% better signal-difference-to-noise ratios than comparable T2-weighted images. This technique may depict cartilage and muscular abnormalities.

Dynamic observation of pulmonary perfusion using continuous arterial spin-labeling in a pig model.

The continuous arterial spin-labeling (CASL) method of perfusion MRI is used to observe pulmonary perfusion dynamically in an animal model. Specifically, a respiratory-triggered implementation of the CASL method is used with approximate spatial resolution of 0.9 x 1.8 x 5.0 mm (0.008 cc) and 2-minute temporal resolution. Perfusion MRI is performed dynamically during repeated balloon occlusion of a segmental pulmonary artery, as well as during pharmacological stimulation. A total of three Yorkshire pigs were studied. The results demonstrate the ability of the endogenous spin-labeling method to characterize the dynamic changes in pulmonary perfusion that occur during important physiological alterations.

Detection and localization of pulmonary air leaks using laser-polarized (3)He MRI.

Pulmonary air leaks were created in the lungs of Yorkshire pigs. Dynamic, 3D MRI of laser-polarized (3)He gas was then performed using a gradient-echo pulse sequence. Coronal magnitude images of the helium distribution were acquired during gas inhalation with a voxel resolution of approximately 1.2 x 2.5 x 8 mm, and a time resolution of 5 sec. In each animal, the ventilation images reveal focal high-signal intensity within the pleural cavity at the site of the air leaks. In addition, a wedge-shaped region of increased parenchymal signal intensity was observed adjacent to the site of the air leak in one animal. (3)He MRI may prove helpful in the management of patients with pulmonary air leaks.

Intermolecular zero-quantum coherence imaging of the human brain.

The first intermolecular zero-quantum coherence (iZQC) MR images of the human brain at 4T are presented. To generate iZQC images, a modified echo-planar imaging pulse sequence was used which included an additional 45 degrees RF pulse and a correlation gradient. The observability and nonconventional contrast of human brain iZQC images at 4T is demonstrated. Axial images are presented for various pulse sequence parameters, and a zero-quantum relaxation map is obtained.

Demonstration of a compact compressor for application of metastability-exchange optical pumping of 3He to human lung imaging.

Hyperpolarized gas magnetic resonance imaging has recently emerged as a method to image lungs, sinuses, and the brain. The best lung images to date have been produced using hyperpolarized 3He, which is produced by either spin-exchange or metastability-exchange optical pumping. For hyperpolarized gas MRI, the metastable method has demonstrated higher polarization levels and higher polarizing rates, but it requires compression of the hyperpolarized gas. Prior to this work, compression of hyperpolarized gas had only been accomplished using a large, complex and expensive apparatus. Here, human lung ventilation images are presented that were obtained using a compact compressor that is relatively simple and inexpensive. For this test, 1.1 bar-L of 15% hyperpolarized 3He gas was produced at the National Institute of Standards and Technology using a modified commercial diaphragm pump. The hyperpolarized gas was transported to the University of Pennsylvania in a holding field provided by a portable solenoid.

Pulmonary perfusion: respiratory-triggered three-dimensional MR imaging with arterial spin tagging--preliminary results in healthy volunteers.

The authors used a spin-tagging method of magnetic resonance perfusion imaging to measure pulmonary perfusion in eight healthy volunteers with use of a respiratory-triggered three-dimensional pulse sequence. The average signal intensity (SI) decrease upon arterial labeling was 24%. The perfusion SI increased by 21% after exercise (P = .02). Focal blood flow abnormalities were observed in a patient with chronic obstructive pulmonary disease.

An MR imaging method for simultaneous measurement of gaseous diffusion constant and longitudinal relaxation time.

A magnetic resonance imaging method for simultaneous and accurate determination of gaseous diffusion constant and longitudinal relaxation time is presented. The method is based on direct observation of diffusive motion. Initially, a slice-selective saturation of helium-3 (3He) spins was performed on a 3He/O2 phantom (9 atm/2 atm). A time-delay interval was introduced after saturation, allowing spins to diffuse in and out of the labeled slice. Following the delay interval a one-dimensional (1-D) projection image of the phantom was acquired. A series of 21 images was collected, each subsequent image having been acquired with an increased delay interval. Gradual spreading of the slice boundaries due to diffusion was thus observed. The projection profiles were fit to a solution of the Bloch equation corrected for diffusive motion. The fitting procedure yielded a value of D3He = 0.1562+/-0.0013 cm2/s, in good agreement with a measurement obtained with a modified version of the standard pulsed-field gradient technique. The method also enabled us to accurately measure the longitudinal relaxation of 3He spins by fitting the change of the total area under the projection profiles to an exponential. A value of T1 = 1.67 s (2 T field) was recorded, in excellent agreement with an inversion recovery measurement.

Proton T1rho-dispersion imaging of rodent brain at 1.9 T.

Detection of H2(17)O with proton T1rho-dispersion imaging holds promise as a means of quantifying metabolism and blood flow with MRI. However, this technique requires a priori knowledge of the intrinsic T1rho dispersion of tissue. To investigate these properties, we implemented a T1rho imaging sequence on a 1.9-T Signa GE scanner. A series of T1rho images for different locking frequencies and locking durations were obtained from rat brain in vivo and compared with 5% (wt/vol) gelatin phantoms containing different concentrations of (17)O ranging from .037% (natural abundance) to 2.0 atom%. Results revealed that, although there is considerable T1rho-dispersion in phantoms doped with H2(17)O, the T1rho of rat brain undergoes minimal dispersion for spin-locking frequencies between .2 and 1.5 kHz. A small degree of T1rho dispersion is present below .2 kHz, which we postulate arises from natural-abundance H2(17)O. Moreover, the signal-to-noise ratios of T1rho-weighted images are significantly better than comparable T2-weighted images, allowing for improved visualization of tissue contrast. We have also demonstrated the feasibility of proton T1rho-dispersion imaging for detecting intravenous H2(17)O on a live mouse brain. The potential application of this technique to study brain perfusion is discussed.

MR imaging contrast enhancement based on intermolecular zero quantum coherences.

A new method for magnetic resonance imaging (MRI) based on the detection of relatively strong signal from intermolecular zero-quantum coherences (iZQCs) is reported. Such a signal would not be observable in the conventional framework of magnetic resonance; it originates in long-range dipolar couplings (10 micrometers to 1 millimeter) that are traditionally ignored. Unlike conventional MRI, where image contrast is based on variations in spin density and relaxation times (often with injected contrast agents), contrast with iZQC images comes from variations in the susceptibility over a distance dictated by gradient strength. Phantom and in vivo (rat brain) data confirm that iZQC images give contrast enhancement. This contrast might be useful in the detection of small tumors, in that susceptibility correlates with oxygen concentration and in functional MRI.

MRI of hyperpolarized 3He gas in human paranasal sinuses.

In this study, MRI of hyperpolarized 3He gas in human paranasal sinuses is presented. Helium images were obtained at 1.5 T, using a surface coil and a 2D, fast gradient-echo sequence with a nominal constant flip angle of 12 degrees. Coronal images of 20-mm thick slices were generated and compared with proton images of the corresponding sections. The images enable visualization of the paranasal sinuses and the nasal cavity, suggesting a potential use of this method not only in identifying the anatomical configuration of these pneumatic spaces, but also in assessing sinus ventilation.

Magnetic resonance imaging of the brain: blood partition coefficient for water: application to spin-tagging measurement of perfusion.

We describe the use of relative proton density imaging to obtain spatially resolved measurements of the brain:blood partition coefficient for water. Values of relative proton density and apparent-T1 were calculated by performing a multidimensional nonlinear least squares fit of progressive saturation image data. Correction for magnetic field inhomogeneity was included. The partition coefficient was calculated by dividing the relative proton density of brain by the relative proton density of blood water. Results obtained from healthy volunteers demonstrate significant spatial variation in the partition coefficient in brain. Direct measurement of this parameter eliminates a source of error in the calculation of regional perfusion using arterial spin-tagging techniques.