New insights into lung diseases using hyperpolarized gas MRI.

Hyperpolarized (HP) gases are a new class of contrast agents that permit to obtain high temporal and spatial resolution magnetic resonance images (MRI) of the lung airspaces. HP gas MRI has become important research tool not only for morphological and functional evaluation of normal pulmonary physiology but also for regional quantification of pathologic changes occurring in several lung diseases. The purpose of this work is to provide an introduction to MRI using HP noble gases, describing both the basic principles of the technique and the new information about lung disease provided by clinical studies with this method. The applications of the technique in normal subjects, smoking related lung disease, asthma, and cystic fibrosis are reviewed.

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 noble gas MR imaging of the lung: potential clinical applications.

Hyperpolarized noble gases are a new class of MR contrast agent. Since the first hyperpolarized gas MR images of the lung were reported, there has been considerable interest in using hyperpolarized gas to obtain high spatial and temporal resolution images of the air spaces of the lung. In addition to static images of lung ventilation, new techniques are being developed using hyperpolarized gas to obtain dynamic, diffusion and oxygen concentration images of the lung. In this article, we review the potential clinical applications of pulmonary hyperpolarized gas MRI and discuss the preliminary findings in a variety of lung diseases. Hyperpolarized gas MRI has the potential to provide a comprehensive morphologic and functional assessment of the lung.

Suppression of cerebrospinal fluid and blood flow artifacts in FLAIR MR imaging with a single-slab three-dimensional pulse sequence: initial experience.

The authors compared high-signal-intensity flow-related artifacts present with a conventional two-dimensional (2D) fluid-attenuated inversion recovery (FLAIR) sequence with those seen with a single-slab, three-dimensional (3D) FLAIR sequence. Four readers graded the subarachnoid space and intraventricular artifacts, the pulsation artifacts, and the conspicuity of cranial nerves in the posterior fossa. For all comparisons, differences between 2D and 3D images were highly statistically significant, with 3D imaging being superior in all cases.

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.

MRI-guided needle localization: technique.

Magnetic resonance imaging (MRI) is being used increasingly in breast cancer diagnosis. Such indications include the search for a breast primary in women with metastatic carcinoma in the axillary lymph nodes, improving surgical planning in women with a biopsy-proven breast cancer, and in screening very high-risk women. If a suspicious lesion is found by MRI, localization with either directed additional mammographic or sonographic views or with MRI-guided needle localization or biopsy is necessary. We describe the use of a biopsy device with embedded internal fiducial markers. The coordinates for needle placement are calculated by distances between the fiducial markers and the lesion. The technique is simple to master and is aided by the use of a practice phantom.

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.

White matter abnormalities in mobility-impaired older persons.

OBJECTIVE: To investigate the relationship between white matter abnormalities and impairment of gait and balance in older persons. METHODS: Quantitative MRI was used to evaluate the brain tissue compartments of 28 older individuals separated into normal and impaired groups on the basis of mobility performance testing using the Short Physical Performance Battery. In addition, individuals were tested on six indices of gait and balance. For imaging data, segmentation of intracranial volume into four tissue classes was performed using template-driven segmentation, in which signal-intensity-based statistical tissue classification is refined using a digital brain atlas as anatomic template. RESULTS: Both decreased white matter volume, which was age-related, and increased white matter signal abnormalities, which were not age-related, were observed in the mobility-impaired group compared with the control subjects. The average volume of white matter signal abnormalities for impaired individuals was nearly double that of control subjects. CONCLUSIONS: This cross-sectional study suggests that decreased white matter volume is age-related, whereas increased white matter signal abnormalities are most likely to occur as a result of disease. Both of these changes are independently associated with impaired mobility in older persons and therefore likely to be additive factors of motor disability.

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.

Improved three-dimensional GRASE imaging with the SORT phase-encoding strategy.

The phase-encoding strategy plays a critical role in determining the quality of gradient- and spin-echo (GRASE) images. Phase-encoding methods developed for two-dimensional GRASE imaging strive to achieve a balance between artifacts from T2-dependent signal amplitude modulations and off-resonance-dependent signal phase shifts, although no current method provides smooth and nonperiodic evolutions for both of these signal changes. In three-dimensional GRASE imaging, the use of two phase-encoding directions presents the opportunity for improved phase-encoding strategies. In this report a phase-encoding strategy for three-dimensional GRASE, termed SORT, is described; this strategy separates off-resonance and T2 effects, mapping one along each of the two phase-encoding directions. Thus, off-resonance-induced artifacts can be minimized while eliminating T2-dependent periodic signal modulations and allowing complete flexibility in the selection of echo time. The performance of the SORT phase-encoding method for T2-weighted GRASE imaging was compared with that of existing methods based on calculated point spread functions and simulated images. The predicted performance of SORT phase encoding was verified experimentally using T2-weighted three-dimensional GRASE imaging of the brain. Generally artifact-free images were obtained even in the presence of fat, susceptibility interfaces, and a wide range of T2 values.

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.

Overview of MR imaging pulse sequences.

This article reviews general pulse-sequence properties and the pulse-sequence techniques most commonly used for clinical MR imaging. The techniques are divided into three major categories: spin echo, gradient echo, and hybrids. The description of each technique emphasizes the basic structure of the pulse sequence, the manner in which transverse magnetization is generated and encoded, and the typical forms of image contrast. In addition, specific advantages or disadvantages of each method are discussed. The techniques described include only a few of the literally thousands of MR imaging pulse sequences that have been developed over the past 20 years. As this brief survey indicates, pulse sequences have been developed that furnish a great range of image contrast behaviors, acquisition speeds, and sensitivities to artifacts. The key to choosing clinically relevant techniques is the appropriate combination of these properties. Undoubtedly, many new MR imaging pulse sequences will join the ranks of the clinically relevant techniques during the next several years.

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.