Magnetic Resonance Imaging

Research Emphasis

The mission of the Center for Advanced Magnetic Resonance Technology at Stanford is to develop innovative magnetic resonance (MR) techniques for fundamental anatomic, physiologic, and pathophysiologic studies involving animals and humans, and to serve the academic and scientific community through collaborations, education, and access to center facilities and resources. The core technology development encompasses these five areas:

Reconstruction methods: Improved reconstruction methods and fast imaging sequences that gather data in non-Cartesian coordinates, including a Web-based repository for data with a variety of k-space trajectories that documents and provides datasets, accepts datasets from users, and provides reference reconstruction algorithms. Imaging of brain activation: Optimizing 2-D and 3-D spiral trajectories for BOLD contrast, susceptibility robust techniques, deconvolution and motion-reduction methods for event-related imaging. Diffusion and perfusion imaging methods: Improved techniques for visualizing and mapping tissue microvasculature, including diffusion tensor, exogenous and endogenous tracer perfusion, and arterial spin-tagging techniques. MR spectroscopy and multinuclear imaging: Novel techniques for multivoxel 2-D MR spectroscopy, volumetric ¹H metabolic imaging, and ultra-short TE in vivo spectroscopy and imaging. Cardiovascular structure and function: Techniques for visualizing cardiac and vascular anatomy and for quantitating blood flow and hemodynamics. Interventional imaging methods: Improved MR thermometry in the presence of susceptibility artifacts from interventional devices, methods for real-time feedback of thermometry data, and integrated X-ray fluoroscopy system within an interventional MR system.

Current Research

Reconstruction methods: Spiral sequences with variable density for improved resolution. Imaging of brain activation: Motion correction software for reduction of cardiac and respiration artifacts. Diffusion and perfusion imaging methods: Spiral and EPI DTI sequences and analysis software. MR spectroscopy and multinuclear imaging: Rapid automated shimming sequence and GUI. Cardiovascular structure and function: 4-D CINE sequences for flow and motion visualization. Interventional imaging methods: Interventional MR technique development.

BIRN

The center also is a partner in the Biomedical Informatics Research Network (BIRN) effort of NCRR.

Resource Capabilities

The center spans the School of Medicine and the School of Engineering. The central facility is the Richard M. Lucas Center for Magnetic Resonance Spectroscopy and Imaging, which has 18,000 square feet of space, a 1.5 T GE Signa CVi MRI system and high-performance 3 T whole-body MRI system. Complete facilities for functional MRI experiments. Computer-controlled flow and motion phantoms. 4.7 T 40 cm with Varian Inova MR system utilized for animal studies. Siemens Angiostar digital X-ray fluoroscopic/angiographic system. Another 1.5 T system and a GE Signa-SP interventional system support the R&D; efforts.

1. Tsai, C.-M. and Nishimura, D. G., Reduced aliasing artifacts using variable-density k-space sampling trajectories. Magnetic Resonance in Medicine 43:452–458, 2000.

Research Emphasis

Current Research

Develop and validate automated methods for segmentation of cortical and subcortical structures in the human brain based on statistical atlas technologies, and for detection and quantification of morphometric changes associated with disease.

Combine simultaneous functional MRI/EEG data with simultaneous EEG/MEG data in order to produce robust spatiotemporal maps that combine the temporal information available in EEG and MEG with the spatial resolution available with fMRI. Develop recording cap technology that will also allow for simultaneous fMRI/EEG and optical measurements.

Develop and test the utility of new statistical methods for event-related fMRI and for a physiologically based statistical model and estimation procedure for signal and noise in fMRI.

Develop the next generation of near-infrared imaging devices using both continuous-wave (CW) and radio-frequency phase-resolved techniques, design and validate improved reconstruction algorithms, and integrate DOT and fMRI in order to enable systematic in vivo validation of DOT performance.

BIRN

The center also is a partner in the Biomedical Informatics Research Network (BIRN) of NCRR.

Resource Capabilities

Instruments

1.5, 3.0, and 7.0 Tesla Siemens Sonata, Trio and Allegra magnetic resonance imaging instruments, CW DOT imager, NeuroMag VectorView system with 306 MEG channels and 128 EEG channels, 24-node Beowulf distributed processing computational cluster.

1. Liu, A. K., Dale, A. M., and Belliveau, J. W., Monte Carlo simulation studies of EEG and MEG localization accuracy. Human Brain Mapping 16:47–62, 2002.
2. Fischl, B., Salat, D. H., Albert, M., et al., Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33:341–355, 2002.
3. Boas, D. A., Culver, J. P., Stott, J. J., and Dunn, A. K., Three dimensional Monte Carlo code for photon migration through complex heterogeneous media including the adult human head. Optics Express 10:159–170, 2002.

Research Emphasis

The overall objective of this resource is to develop high magnetic field magnetic resonance imaging (MRI) and spectroscopy technologies and methodologies for the study of significant biomedical problems. The major drive is to support development of existing programs on magnets in the Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) facility, in particular the world’s first 11.1 T/40 cm system and world’s second 750-MHz wide-bore (89 mm) system. The proposed developments will directly impact studies ranging from molecules through single cells, ex vivo tissues, perfused tissues, small animals, and ultimately (though not directly supported) humans. Our resource centers on three main cores:

High-field small-animal imaging: As field strength is increased, so too is the operating frequency of the radiofrequency (RF) coil, bringing with it new design challenges for construction and optimization. For the larger coils, conventional RF engineering approaches are inadequate and a move to cavity concepts is required. The goal of this core is to develop cavity engineering concepts for larger coils. Phased array technology for use on the higher field magnets (4.7 T and 11.1 T animal instruments) will also be developed. Microscopy and spatially localized microspectroscopy: High magnetic fields coupled with small RF coils have facilitated a new expansion of MR imaging into the microscopic regime. The goal of this core is to develop microcoils to optimize the sensitivity of high field MR on small samples and also investigate the utility of microphased array coils. This core also will develop improved gradient coil systems (multiplayer designs) and develop high field imaging sequences. This includes line narrowing sequences and an investigation of dipolar field imaging at high fields. High-sensitivity and high-throughput solution nuclear magnetic resonance (NMR): Ways to maximize the signal-to-noise ratio at a given field strength will be explored for high-resolution spectroscopy. The first option is through the development of microcoils for high-resolution spectroscopy, which offer improved sensitivity for mass limited samples. Second, multiple microcoils capable of simultaneous operation for increased throughput will be explored on the 750-MHz machine, taking advantage of the space in the wide-bore magnet. Third, a triple tuned superconducting NMR probe for use on the 750-MHz wide-bore system will be developed.

Resource Capabilities

The resource primarily accesses the AMRIS facility at the McKnight Brain Institute at the University of Florida. The facility operates in partnership with the National High Magnetic Field Laboratory in Tallahassee. AMRIS houses 500- and 600-MHz narrow-bore vertical spectrometers and a 750-MHz wide-bore imager/spectrometer, a 4.7 T/33 cm and a 11.1 T/40 cm horizontal small animal imager/spectrometer (both with phased array) with a recently acquired 3 T Sieman human head scanner also used for animal studies. Access to a 3 T and two 1.5 T clinical systems is also available. Extensive optical, X-ray, and computing facilities and a radiofrequency lab are nearby.

1. Beck, B., Plant, D. H., et al., Progress in high field MRI at the University of Florida. MAGMA 13:152–157, 2002.
2. Beck, B. and Blackband, S. J., Phased array imaging on a 4.7T/33cm animal research system. Review of Scientific Instruments 72:4292–4294, 2001.

Research Emphasis

The goals of the Duke Center for In Vivo Microscopy (CIVM) are the development of magnetic resonance (MR) microscopy and creative application to fields as diverse as toxicology, tumor biology, embryology, histology, neurobiology, stroke, models of pulmonary disease, drug discovery, and molecular biology.

Current Research

Technical developments are globally focused on new methods for functional and structural phenotyping in the rodent: mouse, guinea pig, and rat; extending projection imaging from 3-D to 4-D in the heart to look at time-resolved 3-D images throughout the cardiac cycle; developing new methods for pulmonary imaging using hyperpolarized ³He as a marker for functional flow, and higher resolution structural measurements of both vascular and pulmonary structure in 3-D. Magnetic resonance histology (MRH) has been extended to support isotropic 3-D images of perfusion fixed specimens at spatial resolution down to 25 microns (1.6 times 10^-5 mm³), more than 300,000 X higher resolution than is common in a routine clinical scan.

BIRN

The center also is a partner in the Biomedical Informatics Research Network (BIRN) of NCRR.

Resource Capabilities

MR Microscopes

Three fully integrated MR systems are available, which operate at 2.0 T (85 MHz), 30 cm horizontal bore; 7.0 T (300 MHz), 21 cm horizontal bore; and 9.4 T (400 MHz), 8.9 cm vertical bore. All systems are controlled by GE Signa consoles modified to perform MR microscopy. Conversion of the scanners to the next generation of GE consoles (EXCITE) is currently under way.

Hardware and Software

The CIVM supports state-of-the-art high-speed (switched 100 MB/sec) general purpose LINUX and Mac computers and high-end SGI workstations. A dedicated SGI Challenge 300 workstation with fiber channel disks serves as a robust reconstruction engine for very large 3-D Fourier transform (FT) and projection encoding reconstruction. Multiple SGI O2s and an SGI Onyx2 with 2 GB memory and V 12 graphics provide high-end visualization with several commercial software packages. An aggressive effort is under way to develop an integrated visual informatics infrastructure using Internet2 to develop a gridded database structure to accommodate images across a wide range of scales.

Commercial, public domain, and in-house software permit special-purpose reconstruction using 3-D FT algorithms and projection reconstruction of multidimensional volumetric arrays (2563 times 8 to 20483). Analysis packages include quantitative calculation of spin density, T1, T2, diffusion coefficients, etc., from regions of interest or pixel by pixel. Volumetric packages (VoxelView, Vitrea, Voxblast, and Amira) allow interactive reformatting, visualization, and tissue volume quantitation.

Special Features

The CIVM has pioneered methods for the physiological support and monitoring of cardiac and respiratory synchronization of small animals under study in the complicated imaging environment of a high-field magnet. Special purpose radio frequency coils are constructed with on-site CAD, photolithography, etching, and micro-machining facilities. The CIVM has its own system to polarize ³He and ¹²⁹Xe using an Amersham/Nycomed polarizer.

1. Johnson, G. A., et al., Morphologic phenotyping with magnetic resonance microscopy: The visible mouse. Radiology 222:789–793, 2002.
2. Johnson, G. A., et al., Registered ¹H and ³He magnetic resonance microscopy of the lung. Magnetic Resonance in Medicine, 45:365–370, 2001.

Research Emphasis

The focus of this resource is on developing magnetic resonance (MR) methods that utilize potential advantages of ultrahigh magnetic fields for investigating human brain function, anatomy and neurochemistry, cancer detection, and cardiac physiology and biochemistry.

Current Research

Functional imaging in the human brain; mechanisms of functional contrast and specificity; applications of functional imaging in the human brain to the motor cortex, the visual system, and cognitive tasks. Mapping connectivity between functional areas in the human brain using MR methods. Development of B1 insensitive imaging approaches. Development of new and novel B1 insensitive adiabatic pulses for spectroscopic and imaging applications using coils that are intrinsically inhomogeneous in their radiofrequency (RF) field profiles, such as surface coils. High-frequency RF interactions with human brain and body. High-field RF coil design. Spectroscopic localization techniques, spectroscopic editing techniques combined with spectroscopic localization, multiple quantum techniques. Improved methods for chemical shift imaging. Carbon-13 and proton MR spectroscopy studies of neurochemistry in health and disease in humans and animal models. 17_O imaging using high fields and applications to study cerebral energetics.

BIRN

The center also is a partner in the Biomedical Informatics Research Network (BIRN) effort of NCRR.

Resource Capabilities

Instruments

4 Tesla/90 cm bore, 7 Tesla/90 cm bore, 9.4 T/31 cm bore magnetic resonance imaging and spectroscopy instrument. Extensive computational capabilities for image analysis. RF analysis and test equipment. Radiofrequency probes designed for human applications at high frequencies; ultra-quiet preamplifiers for high frequencies to be coupled with RF coils.

Special Features

High magnetic field imaging instrumentation and methodology for human studies.

1. Gruetter, R., Seaquist, E. R., and Ugurbil, K., A mathematical model of compartmentalized neurotransmitter metabolism in the human brain. American Journal of Physiology Endocrinology and Metabolism 281:E100–112, 2001.
2. Yacoub, E., Shmuel, A., et al., Imaging brain function in humans at 7 Tesla. Magnetic Resonance Medicine 45:588–594, 2001.
3. Vaughan, J. T., Garwood, M., et al., 7T vs. 4T: RF power, homogeneity, and signal-to-noise comparison in head images. Magnetic Resonance Medicine 46:24–30, 2001.

Research Emphasis

The focus of this resource is on developing instrumentation, methodologies, and data analysis techniques for the quantitative assessment of functional, structural, and metabolic parameters in humans utilizing multinuclear magnetic resonance, novel spectral, perfusion, functional, and optical imaging techniques.

Current Research

Development of multinuclear magnetic resonance techniques for early diagnosis of diseases such as breast cancer, Alzheimer’s disease, arthritis, emphysema, HIV, and cardiovascular disorders; design and development of targeted magnetite-based contrast agents for diagnosis and assessing gene expression; new techniques and instrumentation for near-infrared, optical imaging, and spectroscopy; integrated optical and MR imaging in humans; perfusion and functional neuroimaging and hyperpolarized gas imaging.

Resource Capabilities

4 T whole-body magnet system capable of multinuclear MRI; 2 T, 1 meter bore, magnet system with a versatile spectrometer for multinuclear spectroscopy and imaging with in-magnet exercise capability; 4.7 T, 30 cm diameter and 9.4 T, 10 cm diameter vertical magnets for animal imaging; specialized radiofrequency probes for various nuclei; local magnetic field gradient sets; workstations for data analysis; electronic test equipment; physiological monitoring equipment; in-magnet exercise apparatus; and bioelectric amplifiers and recorders. Metabolic spectroscopy including (but not limited to) ¹H, ¹³C, ¹⁵N, ²³Na, ⁷Li, ¹⁹F, ³¹P, and ¹⁷O, equipped for physiological synchronization (gating) and decoupling, magnetization transfer experiments, 2-D, multiple quantum spectroscopy, and in-magnet exercise. Software and hardware support for all NMR experiments, including sodium and phosphorus imaging, chemical shift imaging, Hadamard spectroscopic imaging, ³He, ¹²⁶Xe imaging, and high-resolution proton imaging and flow. Facilities and expertise for generating hyperpolarized helium and xenon gases, specialized coil design, and construction are available, as are body positioning devices for specific experiments (i.e., in-magnet exercise; heart, brain, and liver studies). Expertise and infrastructure for state-of-the-art functional perfusion imaging and integrated optical and MRI experiments.

1. Insko, E. K., Clayton, D. B., Elliott, M. A., In vivo sodium MR imaging of the intervertebral disk at 4 T. Academic Radiology 9:800–804, 2002.
2. Borthakur, A., Shapiro, E. M., et al., Effect of IL-1beta-induced macromolecular depletion on residual quadrupolar interaction in articular cartilage. Journal of Magnetic Resonance Imaging 15:315–323, 2002.
3. Markel, V. and Schotland, J., Inverse problem in optical diffusion tomography, II. Role of boundary conditions. Journal of the Optical Society of America A. 19:558–566, 2002.
4. Lipson, D. A., Roberts, D. A., et al., Pulmonary ventilation and perfusion scanning using hyperpolarized helium-3 MRI and arterial spin-tagging in healthy subjects, pulmonary embolism, and in orthotopic lung transplant recipients. Magnetic Resonance in Medicine 47:1073–1074, 2002.
5. Shapiro, E. M., Borthakur, A., Gougoutas, A., and Reddy, R., ²³Na MRI accurately measures fixed charge density in articular cartilage. Magnetic Resonance in Medicine 47:284–291, 2002.

Research Emphasis

The resource’s mission is to provide state-of-the-art magnetic resonance imaging (MRI) data acquisition and image-processing technology and unique MRI expertise to facilitate the functional brain imaging research of NIH-funded neuroscientists. The ultimate goal is a fast multimodality MRI study including imaging, spectroscopy, and fiber tracking in 15–30 minutes and quantitative integration of the different image datasets. Development is especially geared toward optimizing the study of children, the elderly, and subjects with neurological and psychiatric disorders. The core technology development: Functional MRI (fMRI) and quantitative physiology methods: (1) fMRI analysis approaches that can reveal brain activity not predicted in advance by simple models, allowing extension of fMRI to the study of rich naturalistic behaviors. (2) Enhancement of fMRI infrastructure for pediatric studies. (3) Quantification of blood flow analysis. Brain chemistry by MR spectroscopic imaging (MRSI) methods: Improved methods for fast MRSI using multi-echo and sensitivity encoding (SENSE) methodologies. New approaches for spin-editing, metabolite quantification, and low-power spin decoupling. Identification and characterization of brain connections: Novel data acquisition and processing methods for high-resolution 3-D diffusion tensor imaging (DTI) and fiber tracking/axonal mapping. Algorithmic methods for anatomical brain analysis: Advanced computational technology, including Bayesian segmentation, volume-surface matching approaches, and dynamic tracking of vector fields. Methods for combining all image modalities into a general brain reference frame.

Current Research

New fMRI data analysis: Extended independent component analysis allows inferences from group, as opposed to single-subject data. Spectroscopy: Developed adiabatic low-power radiofrequency decoupling schemes as well as CSF correction schemes for metabolite quantification. Fast spectroscopic imaging using SENSE. Diffusion tensor imaging: High-resolution 3-D fiber tracking in humans using SENSE at 1.5 T and 3 T. Mapping of cortico-cortical association fibers and brainstem fibers. Elucidating specific fiber properties using MRI relaxation times and magnetization transfer. Computational anatomy: Validation of Bayesian segmentation algorithms for reconstruction of gyral areas. Derivation of probability laws for DTI data, resulting in dynamic programming algorithm for DTI tract tracing.

BIRN

The center also is a partner in the Biomedical Informatics Research Network (BIRN) of the NCRR.

Resource Capabilities

The resource components are the F. M. Kirby Research Center at Kennedy Krieger Institute and the Center for Imaging Science (CIS) at Johns Hopkins University. The Kirby Center has whole-body short-bore 1.5 T and 3 T Philips scanners; CIS has an IBM supercomputer. The special design for fMRI includes optimal radiofrequency shielding and power conditioning to enhance MRI signal-to-noise ratio and temporal stability, integration of dedicated equipment for stimulus provision, and subject monitoring.

1. Miller, M. I., Trouve, A., and Younes, L., On the metrics and Euler-Lagrange equations of computational anatomy. Annual Review of Biomedical Engineering 4:375–405, 2002.
2. Mori, S., Kaufmann, W. E., et al., Imaging cortical association tracts in the human brain using diffusion-tensor-based axonal tracking. Magnetic Resonance Medicine 47:215–223, 2002.
3. Calhoun, V. D., Adali, T., Pearlson, G. D., and Pekar, J. J., A method for making group inferences from functional MRI data using independent component analysis. Human Brain Mapping 14:140–151, 2001.
4. Barker, P. B., Golay X., Artemov, D., et al., Broadband proton decoupling for in vivo brain spectroscopy in humans. Magnetic Resonance Medicine 45:226–232, 2001.