MR grid-tagging using hyperpolarized helium-3 for regional quantitative assessment of pulmonary biomechanics and ventilation.

A new technique is demonstrated in six healthy human subjects that combines grid-tagging and hyperpolarized helium-3 MRI to assess regional lung biomechanical function and quantitative ventilation. 2D grid-tagging, achieved by applying sinc-modulated RF-pulse trains along the frequency- and phase-encoding directions, was followed by a multislice fast low-angle shot (FLASH)-based acquisition at inspiration and expiration. The displacement vectors, first and second principal strains, and quantitative ventilation were computed, and mean values were calculated for the upper, middle, and lower lung regions. Displacements in the lower region were significantly greater than those in either the middle or upper region (P < 0.005), while there were no significant differences between the three regions for the two principal strains and quantitative ventilation (P = 0.11-0.92). Variations in principal strains and ventilation were greater between subjects than between lung zones within individual subjects. This technique has the potential to provide insight into regional biomechanical alterations of lung function in a variety of lung diseases.

Hyperpolarized 3He lung ventilation imaging with B1-inhomogeneity correction in a single breath-hold scan.

The signal-to-noise ratio (SNR) of hyperpolarized noble gas MR images is sensitive to the flip angle used. Variations in flip angle due to B1-inhomogeneity of the RF coil cause intensity variation artifacts in lung ventilation images which may mask or mimic disease. We show these artifacts can be minimized by using the optimal flip angle and corrected if the local flip angle is known. Hyperpolarized 3He lung images were obtained in ten healthy subjects using both a conventional gradient-echo sequence and a new hybrid pulse sequence designed to simultaneously acquire lung ventilation images and corresponding flip-angle maps in comparable imaging time. Flip-angle maps and corrected images were calculated from the hybrid scan and compared with conventional images. The qualitative theoretical dependence of flip angle on SNR was verified. Ventilation images and flip-angle maps were successfully obtained with the hybrid sequence. Corrections to image intensity calculated from the flip-angle maps appeared reasonable for images acquired using an average flip angle near optimal. Use of the optimal flip angle is crucial to the quality of lung ventilation images. Artifactual intensity variations due to RF-coil inhomogeneity may be identified and potentially corrected using our hybrid sequence.

Dynamic spiral MRI of pulmonary gas flow using hyperpolarized (3)He: preliminary studies in healthy and diseased lungs.

An optimized interleaved-spiral pulse sequence, providing high spatial and temporal resolution, was developed for dynamic imaging of pulmonary ventilation with hyperpolarized (3)He, and tested in healthy volunteers and patients with lung disease. Off-resonance artifacts were minimized by using a short data-sampling period per interleaf, and gradient-fidelity errors were compensated for by using measured k-space trajectories for image reconstruction. A nonsequential acquisition order was implemented to improve image quality during periods of rapid signal change, such as early inspiration. Using a sliding-window reconstruction, cine-movies with a frame rate of 100 images per second were generated. Dynamic images demonstrating minimal susceptibility- and motion-induced artifacts were obtained in sagittal, coronal, and axial orientations. The pulse sequence had the flexibility to image multiple slices almost simultaneously. Our initial experience in healthy volunteers and subjects with lung pathology demonstrated the potential of this new tool for capturing the features of lung gas-flow dynamics.

Hyperpolarized 3He MR lung ventilation imaging in asthmatics: preliminary findings.

Asthma is a disease characterized by chronic inflammation and reversible obstruction of the small airways resulting in impaired pulmonary ventilation. Hyperpolarized 3He magnetic resonance (MR) lung imaging is a new technology that provides a detailed image of lung ventilation. Hyperpolarized 3He lung imaging was performed in 10 asthmatics and 10 healthy subjects. Seven asthmatics had ventilation defects distributed throughout the lungs compared with none of the normal subjects. These ventilation defects were more numerous and larger in the two symptomatic asthmatics who had abnormal spirometry. Ventilation defects studied over time demonstrated no change in appearance over 30-60 minutes. One asthmatic subject was studied twice in a three-week period and had ventilation defects which resolved and appeared in that time. This same subject was studied before and after bronchodilator therapy, and all ventilation defects resolved after therapy. Hyperpolarized 3He lung imaging can detect the small, reversible ventilation defects that characterize asthma. The ability to visualize lung ventilation offers a direct method of assessing asthmatics and their response to therapy.

Magnetic resonance hysterography and hysterosalpingography using hyperpolarized (3)He: demonstration of feasibility in an animal model.

Assessment of the uterine cavity and patency of the fallopian tubes remains a difficult goal with magnetic resonance imaging (MRI). The purpose of this paper is to describe the development of a new magnetic resonance hysterography (MR-HG) and hysterosalpingography (MR-HSG) technique employing hyperpolarized (3)He. Two-dimensional (2D) and 3D gradient-echo imaging sequences were developed and optimized using a phantom. An optimized sequence was then applied in swine cadavers. J. Magn. Reson. Imaging 2000;12:1009-1013.

MR virtual colonography using hyperpolarized (3)He as an endoluminal contrast agent: demonstration of feasibility.

Hyperpolarized gas MR virtual colonography was performed in plastic phantoms and in the dog colon. (3)He was laser polarized in a prototype commercial system. 2D and 3D gradient echo sequences were used to image the noble gas-filled structures. The hyperpolarized (3)He within the plastic tube and colon lumen produced high signal, providing excellent contrast from the surrounding structures. The virtual colonoscopic analysis of the canine dataset allowed visualization of the colonic features and the colonic wall from inside the colon. (3)He colonoscopy is a novel technique to visualize the colon with MRI with the application of an inert gaseous endoluminal contrast agent.

Probing lung physiology with xenon polarization transfer contrast (XTC).

One of the major goals of hyperpolarized-gas MRI has been to obtain (129)Xe dissolved-phase images in humans. So far, this goal has remained elusive, mainly due to the low concentration of xenon that dissolves in tissue. A method is proposed and demonstrated in dogs that allows information about the dissolved phase to be obtained by imaging the gas phase following the application of a series of RF pulses that selectively destroy the longitudinal magnetization of xenon dissolved in the lung parenchyma. During the delay time between consecutive RF pulses, the depolarized xenon rapidly exchanges with the gas phase, thus lowering the gas polarization. It is demonstrated that the resulting contrast in the (129)Xe gas image provides information about the local tissue density. It is further argued that minor pulse-sequence modifications may provide information about the alveolar surface area or lung perfusion.

Optimized single-slab three-dimensional spin-echo MR imaging of the brain.

The development and optimization of spin-echo-based, single-slab, three-dimensional techniques for magnetic resonance imaging of the whole brain are described. T1-weighted and T2-weighted image sets with a volume resolution of 1 mm(3) and fluid-attenuated inversion-recovery image sets with a volume resolution of 3 mm(3) were obtained in acquisition times of less than 10 minutes per image set.

NMR of hyperpolarized (129)Xe in the canine chest: spectral dynamics during a breath-hold.

One of the major goals of hyperpolarized-gas MR imaging has been to obtain (129)Xe dissolved-phase images in humans. Since the dissolved-phase signal is much weaker than the gas-phase signal, highly optimized MR pulse sequences are required to obtain adequate images during a single breath-hold. In particular, a solid understanding of the temporal dynamics of xenon as it passes from the lung gas spaces into the parenchyma, the blood and other downstream compartments is absolutely essential. Spectroscopy experiments were performed in the canine chest to elucidate the behavior of xenon exchange in the lung. The experiments covered a time range from 1 ms to 9 s and therefore considerably extend the data currently available in the literature. It was found that the integrals of the dissolved-phase resonances approached plateau values within approximately 200 ms, and then increased again after approximately 1 s. This behavior suggests an early saturation of the parenchyma before xenon reaches downstream compartments. Mono-exponential recovery curves with time constants on the order of 100 ms were fit to the data. These results potentially provide information on several underlying physiological parameters of the lung, including the parenchymal and blood volumes as well as the diffusion properties of lung tissue.

Spin-Echo planar spectroscopic imaging for fast lipid characterization in bone marrow.

Lipid characterization of bone marrow in vivo with proton magnetic resonance spectroscopy was performed using Spin-Echo Planar Spectroscopic Imaging sequences. The methods are shown capable of rapidly generating two-dimensional chemical shift imaging data sets suitable for measuring lipid indices that reflect unsaturation levels among triglycerides, as demonstrated in oil phantoms and bone marrow from a healthy volunteer. The volume coverage, spatial resolution, acquisition speed, and spectral characteristics of Spin-Echo Planar Spectroscopic Imaging should make it attractive for clinical studies of diseases affecting normal lipid chemical composition.

Consequences of (129)Xe-(1)H cross relaxation in aqueous solutions.

We have investigated the transfer of polarization from (129)Xe to solute protons in aqueous solutions to determine the feasibility of using hyperpolarized xenon to enhance (1)H sensitivity in aqueous systems at or near room temperatures. Several solutes, each of different molecular weight, were dissolved in deuterium oxide and although large xenon polarizations were created, no significant proton signal enhancement was detected in l-tyrosine, alpha-cyclodextrin, beta-cyclodextrin, apomyoglobin, or myoglobin. Solute-induced enhancement of the (129)Xe spin-lattice relaxation rate was observed and depended on the size and structure of the solute molecule. The significant increase of the apparent spin-lattice relaxation rate of the solution phase (129)Xe by alpha-cyclodextrin and apomyoglobin indicates efficient cross relaxation. The slow relaxation of xenon in beta-cyclodextrin and l-tyrosine indicates weak coupling and inefficient cross relaxation. Despite the apparent cross-relaxation effects, all attempts to detect the proton enhancement directly were unsuccessful. Spin-lattice relaxation rates were also measured for Boltzmann (129)Xe in myoglobin. The cross-relaxation rates were determined from changes in (129)Xe relaxation rates in the alpha-cyclodextrin and myoglobin solutions. These cross-relaxation rates were then used to model (1)H signal gains for a range of (129)Xe to (1)H spin population ratios. These models suggest that in spite of very large (129)Xe polarizations, the (1)H gains will be less than 10% and often substantially smaller. In particular, dramatic (1)H signal enhancements in lung tissue signals are unlikely.

Lung air spaces: MR imaging evaluation with hyperpolarized 3He gas.

Thirty-two magnetic resonance imaging examinations of the lungs were performed in 16 subjects after inhalation of 1-2 L of helium 3 gas that was laser polarized to 10%-25%. The distribution of the gas was generally uniform, with visualization of the fissures in most cases. Ventilation defects were demonstrated in smokers and in a subject with allergies. The technique has potential for evaluating small airways disease.

MR imaging and spectroscopy using hyperpolarized 129Xe gas: preliminary human results.

Using a new method of xenon laser-polarization that permits the generation of liter quantities of hyperpolarized 129Xe gas, the first 129Xe imaging results from the human chest and the first 129Xe spectroscopy results from the human chest and head have been obtained. With polarization levels of approximately 2%, cross-sectional images of the lung gas-spaces with a voxel volume of 0.9 cm3 (signal-to-noise ratio (SNR), 28) were acquired and three dissolved-phase resonances in spectra from the chest were detected. In spectra from the head, one prominent dissolved-phase resonance, presumably from brain parenchyma, was detected. With anticipated improvements in the 129Xe polarization system, pulse sequences, RF coils, and breathing maneuvers, these results suggest the possibility for 129Xe gas-phase imaging of the lungs with a resolution approaching that of current conventional thoracic proton imaging. Moreover, the results suggest the feasibility of dissolved-phase imaging of both the chest and brain with a resolution similar to that obtained with the gas-phase images.

Off-resonance image artifacts in interleaved-EPI and GRASE pulse sequences.

Echo-time shifting (ETS) is used in GRASE and interleaved-EPI sequences to improve the phase evolutions for off-resonance signal sources. However, even with ETS the phase evolutions still exhibit discontinuities. In this work, we extend previous studies of ETS by quantitatively evaluating the magnitude and form of the image artifacts that result from these phase discontinuities. The functional form of the phase evolution is used to derive the general conditions under which artifacts are expected. The artifacts for two sequence structures are then evaluated as a function of off-resonance frequency and data sampling period by calculating point spread functions and simulated images. It was found that even when ETS is used to improve the phase evolutions, periodic phase discontinuities may degrade image quality by producing ghosting artifacts of edges. These artifacts are similar to those that commonly occur with periodic motion. From our results recommendations are derived for limiting the ghosting artifacts.

Spoiling of transverse magnetization in gradient-echo (GRE) imaging during the approach to steady state.

The signal evolution behaviors and corresponding image appearances for different methods of spoiling or refocusing the transverse magnetization in short TR gradient-echo imaging during the approach to steady state were investigated experimentally and using computer simulations based on the Bloch equations. Specifically, ideally spoiled, gradient-spoiled, gradient-refocused, and RF-spoiled pulse sequence configurations were studied. This study showed that, for the gradient-spoiled configuration, the signal evolution is position and phase-encoding order-dependent and, under typical imaging conditions, can deviate substantially from the ideally spoiled signal evolution at some spatial positions, resulting in intensity banding image artifacts. For the gradient-refocused configuration, the signal evolution oscillates toward the steady state and, generally, does not closely approximate that of ideal spoiling, resulting in different image contrast or image blurring. Using RF spoiling, the signal evolution closely approximates the ideally spoiled case for flip angles less than approximately 20 degrees and T2 values of less than approximately 200 ms and results in relatively artifact-free images. Also, this study showed that, for RF spoiling, an RF-pulse phase-difference increment other than 117 degrees, such as 84 degrees may be optimal for gradient-echo imaging during the approach to steady state.

CSF-suppressed T2-weighted three-dimensional MP-RAGE MR imaging.

Fluid-attenuated inversion recovery (FLAIR) is a pulse sequence used for acquiring T2-weighted images of the brain and spine in which the normally high signal intensity of CSF is greatly attenuated. The CSF-suppressed T2-weighted contrast of this technique may be more sensitive to a variety of disorders than that of conventional T2-weighted imaging. The primary disadvantage associated with conventional spin-echo implementations of FLAIR is the relatively limited anatomic coverage that can be achieved in a reasonable imaging time. We developed and optimized a three-dimensional magnetization-prepared rapid gradient-echo (3D MP-RAGE) pulse sequence that combines CSF-suppressed T2-weighted contrast similar to existing FLAIR techniques with anatomic coverage characteristic of 3D imaging. A preliminary evaluation of the new sequence was performed by imaging healthy volunteers and patients with multiple sclerosis.

Three-dimensional time-of-flight MR angiography using selective inversion recovery RAGE with fat saturation and ECG-triggering: application to renal arteries.

A three-dimensional (3D), ECG-triggered, selective inversion recovery (SIR) rapid gradient-echo (RAGE) technique is proposed to obtain MR angiograms of the main renal arteries. By using the selective inversion recovery and fat saturation, the background is significantly suppressed while blood maintains a high signal intensity as compared with conventional 3D time-of-flight (TOF) MR angiography. The sequence is ECG-triggered so that blood in-flow is maximized during systole, and intravoxel dephasing and pulsatile flow artifacts are minimized by collecting data during diastole. As a result, vessel boundary blurring and ghosting artifacts due to background motion are dramatically reduced, and the conspicuity and lumen definition of the arteries are significantly improved. High-quality MR angiograms of the main renal arteries with excellent blood/tissue contrast and suppression of motion artifacts have been consistently obtained for normal volunteers, with the length of visualization being 51 +/- 07 mm for the left, and 57 +/- 06 mm for the right renal arteries, significantly greater than using conventional 3D TOF pulse sequences. Statistical analysis was performed by using a one-sided Student's t test.

Optimization of parameter values for complex pulse sequences by simulated annealing: application to 3D MP-RAGE imaging of the brain.

A number of pulse sequence techniques, including magnetization-prepared gradient echo (MP-GRE), segmented GRE, and hybrid RARE, employ a relatively large number of variable pulse sequence parameters and acquire the image data during a transient signal evolution. These sequences have recently been proposed and/or used for clinical applications in the brain, spine, liver, and coronary arteries. Thus, the need for a method of deriving optimal pulse sequence parameter values for this class of sequences now exists. Due to the complexity of these sequences, conventional optimization approaches, such as applying differential calculus to signal difference equations, are inadequate. We have developed a general framework for adapting the simulated annealing algorithm to pulse sequence parameter value optimization, and applied this framework to the specific case of optimizing the white matter-gray matter signal difference for a T1-weighted variable flip angle 3D MP-RAGE sequence. Using our algorithm, the values of 35 sequence parameters, including the magnetization-preparation RF pulse flip angle and delay time, 32 flip angles in the variable flip angle gradient-echo acquisition sequence, and the magnetization recovery time, were derived. Optimized 3D MP-RAGE achieved up to a 130% increase in white matter-gray matter signal difference compared with optimized 3D RF-spoiled FLASH with the same total acquisition time. The simulated annealing approach was effective at deriving optimal parameter values for a specific 3D MP-RAGE imaging objective, and may be useful for other imaging objectives and sequences in this general class.

Improved T1-weighted two-dimensional MP-GRE imaging of the liver with variable flip angles for shaping the signal evolution.

The recently introduced method of shaping the transient signal evolution in magnetization-prepared gradient-echo (MP-GRE) imaging with variable flip angles has been applied to two-dimensional (2D) MP-GRE imaging of the abdomen. The technique was analyzed by using theoretical models and was implemented on a standard 1.5-T whole-body imager with a segmented acquisition. Theoretical models predicted that the variable-flip-angle 2D MP-GRE sequence would increase liver-spleen signal difference--to-noise ratios by 290%, 110%, and 160% compared with a 2D MP-GRE sequence with a flip angle of 10 degrees and sequential phase encoding, a 2D MP-GRE sequence with a flip angle of 30 degrees and centric phase encoding, and the fast low-angle shot sequence, respectively. Experimental measurements supported the theoretical predictions.