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Qing X Yang,
Sebastian Rupprecht,
Wei Luo,
Christopher Sica,
Zachary Herse,
Jianli Wang,
Zhipeng Cao,
Jeffrey Vesek,
Michael T Lanagan,
Giuseppe Carluccio,
Yeun-Chul Ryu,
Christopher M Collins
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ABSTRACT: PURPOSE: To investigate the use of a new high-dielectric constant (HDC) material for improving SNR and transmission efficiency for clinical MRI applications at 3 Tesla (T) with cervical spine imaging. MATERIALS AND METHODS: Human subjects were imaged using a commercial cervical spine receive array coil on a clinical system with and without pads containing Barium Titanate beads in deuterium water placed around the neck. Numerical electromagnetic field simulations of the same configuration were also performed. RESULTS: Experimental and simulated maps of transmit and receive fields showed greater efficiency for imaging the cervical spine when the pads were present. Experimental measurements showed a significant improvement in SNR with the pads present and an average input power reduction of 46%. CONCLUSION: Use of HDC material can enhance SNR and transmission efficiency for clinical imaging of the cervical spine at 3.0T. J. Magn. Reson. Imaging 2012;. © 2012 Wiley Periodicals, Inc.
Journal of Magnetic Resonance Imaging 01/2013; · 2.70 Impact Factor
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ABSTRACT: Passive dielectric materials have been used to improve aspects of MRI by affecting the distribution of radiofrequency electromagnetic fields. Recently, interest in such materials has increased with the number of high-field MRI sites. Here, we introduce a new material composed of sintered high-permittivity ceramic beads in deuterated water. This arrangement maintains the ability to create flexible pads for conforming to individual subjects. The properties of the material are measured and the performance of the material is compared to previously used materials in both simulation and experiment at 3 T. Results show that both permittivity of the beads and effect on signal-to-noise ratio and required transmit power in MRI are greater than those of materials consisting of ceramic powder in water. Importantly, use of beads results in both higher permittivity and lower conductivity than use of powder. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Magnetic Resonance in Medicine 08/2012; · 2.96 Impact Factor
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ABSTRACT: In numerical analyses of radiofrequency (RF) fields for MRI, RF power is often permitted to radiate out of the problem region. In reality, RF power will be confined by the magnet bore and RF screen enclosing the magnet room. We present numerical calculations at different frequencies for various surface and volume coils, with samples from simple spheres to the human body in environments from free space to a shielded RF room. Results for calculations within a limited problem region show radiated power increases with frequency. When the magnet room RF screen is included, nearly all the power is dissipated in the human subject. For limited problem regions, inclusion of a term for radiation loss results in an underestimation of transmit efficiency compared to results including the complete bore and RF screen. If the term for radiated power is not included, calculated coil efficiencies are slightly overestimated compared to the complete case. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Magnetic Resonance in Medicine 04/2012; · 2.96 Impact Factor
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Colin A Roopnariane,
Yeun-Chul Ryu,
Mohammad-Reza Tofighi,
Patti A Miller,
Sukhoon Oh,
Jianli Wang,
Bu Sik Park,
Lukas Ansel,
Christopher A Lieu,
Thyagarajan Subramanian, Qing X Yang,
Christopher M Collins
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ABSTRACT: We present a quadrature volume coil designed for brain imaging of a macaque monkey fixed in a sphinx position (facing down the bore) within a stereotactic frame at 3 T, where the position of the monkey and presence of the frame preclude use of existing coils. Requirements include the ability to position and remove the coil without disturbing the position of the monkey in the frame. A saddle coil and a solenoid were combined on a modified cylindrical former and connected in quadrature as to produce a homogeneous circularly polarized field throughout the brain. To allow the loops of the saddle coil to encompass the ear posts, partial disassembly and reassembly were facilitated by embedding pin and socket contacts into separate pieces of the former. Coil design included simulation of the electromagnetic fields for the coil containing a 3D model of a monkey's head. The resulting coil produced adequate homogeneity and signal-to-noise ratio throughout the brain.
Concepts in Magnetic Resonance Part B Magnetic Resonance Engineering 02/2012; 41B(1):22-27. · 0.79 Impact Factor
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ABSTRACT: The goal of this study was to address the need for comprehensive reference data regarding maturational and aging effects on regional transverse relaxation rates (R(2)) of the brain in normal humans. Regional R(2)s were measured in twenty-five brain structures from a sample of seventy-seven normal volunteers 9 to 85 years of age. The relationships between regional R(2) and age were determined using generalized additive models, without the constraint of a specified a priori model. Data analysis demonstrated that the brain tissue R(2)-age correlations followed various time courses with both linear and non-linear characteristics depending on the particular brain structure. Most anatomical structures studied exhibited non-linear characteristics, including the amygdala, hippocampus, thalamus, globus pallidus, putamen, caudate nucleus, red nucleus, substantia nigra, orbitofrontal white matter and temporal white matter. Linear trends were detected in occipital white matter and in the genu of corpus callosum. These results indicate the complexity of age-related R(2) changes in the brain while providing normative reference data that can be utilized in clinical examinations and studies utilizing quantitative transverse relaxation.
PLoS ONE 01/2012; 7(2):e31907. · 4.09 Impact Factor
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ABSTRACT: Restless legs syndrome (RLS) is a neurological disorder characterized by a strong urge to move the legs and has been shown in many studies with abnormally low brain iron. Iron deficiency is associated with hypomyelination in brains of animals. Therefore we hypothesized that a myelin deficit should be present in the brains of patients with RLS.
We performed Western blot analysis on myelin isolated from RLS (n=11) and control (n=11) brain tissue obtained at autopsy for the expression of the integral myelin proteins, myelin basic protein (MBP), and proteolipid protein (PLP) and the oligodendrocyte specific enzyme 3'5'-cyclic nucleotide phosphohydrolase (CNPase). To expand the postmortem findings to in vivo, we analyzed the brains of RLS patients (n=23) and controls (n=23) using voxel-based morphometry (VBM).
The expression of MBP, PLP and CNPase in the myelin from RLS was decreased by approximately 25% (p<0.05) compared to controls. The amounts of transferrin (Tf) and H-ferritin (H-Frt) in the myelin fraction were also significantly decreased in RLS compared to controls. The imaging analysis revealed significant small decreases in white matter volume in RLS patients compared to controls in the corpus callosum, anterior cingulum and precentral gyrus.
A decrease in myelin similar to that reported in animal models of iron deficiency was found in the brains of individuals with RLS. The evidence for less myelin and loss of myelin integrity in RLS brains, coupled with decreased ferritin and transferrin in the myelin fractions, is a compelling argument for brain iron insufficiency in RLS. These data also indicate the need to look beyond the sensorimotor symptoms that typically define the syndrome and its assumed relation to the dopaminergic system. Understanding the full range of RLS pathology may help us better understand the complex, intermittent nature and diversity of the clinical features of RLS and expand our consideration of treatment options for RLS.
Sleep Medicine 06/2011; 12(6):614-9. · 3.40 Impact Factor
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ABSTRACT: Alzheimer's disease (AD) and mild cognitive impairment (MCI), continue to be
widely studied. While there is no consensus on whether MCIs actually "convert"
to AD, the more important question is not whether MCIs convert, but what is the
best such definition. We focus on automatic prognostication, nominally using
only a baseline image brain scan, of whether an MCI individual will convert to
AD within a multi-year period following the initial clinical visit. This is in
fact not a traditional supervised learning problem since, in ADNI, there are no
definitive labeled examples of MCI conversion. Prior works have defined MCI
subclasses based on whether or not clinical/cognitive scores such as CDR
significantly change from baseline. There are concerns with these definitions,
however, since e.g. most MCIs (and ADs) do not change from a baseline CDR=0.5,
even while physiological changes may be occurring. These works ignore rich
phenotypical information in an MCI patient's brain scan and labeled AD and
Control examples, in defining conversion. We propose an innovative conversion
definition, wherein an MCI patient is declared to be a converter if any of the
patient's brain scans (at follow-up visits) are classified "AD" by an
(accurately-designed) Control-AD classifier. This novel definition bootstraps
the design of a second classifier, specifically trained to predict whether or
not MCIs will convert. This second classifier thus predicts whether an
AD-Control classifier will predict that a patient has AD. Our results
demonstrate this new definition leads not only to much higher prognostic
accuracy than by-CDR conversion, but also to subpopulations much more
consistent with known AD brain region biomarkers. We also identify key
prognostic region biomarkers, essential for accurately discriminating the
converter and nonconverter groups.
04/2011;
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ABSTRACT: Previous works have shown that placement of a high-dielectric pad can improve image intensity in a region adjacent to the pad, or that placement of dielectric pads around a large surface of the head can improve image homogeneity on an entire plane through the head in high-field MRI. Here, experimental results show that use of high-dielectric pads around the human head can reduce the required input radiofrequency power by 50% while enhancing image signal-to-noise ratio by 20-40% throughout the cerebrum at 3 T. Thus, dielectric pads may be used to provide a relatively simple and low-cost method for improving quality and safety of MRI in a variety of applications at 3 T.
Magnetic Resonance in Medicine 02/2011; 65(2):358-62. · 2.96 Impact Factor
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ABSTRACT: Alzheimer's disease (AD) and mild cognitive impairment (MCI) are of great current research interest. While there is no consensus on whether MCIs actually "convert" to AD, this concept is widely applied. Thus, the more important question is not whether MCIs convert, but what is the best such definition. We focus on automatic prognostication, nominally using only a baseline brain image, of whether an MCI will convert within a multi-year period following the initial clinical visit. This is not a traditional supervised learning problem since, in ADNI, there are no definitive labeled conversion examples. It is not unsupervised, either, since there are (labeled) ADs and Controls, as well as cognitive scores for MCIs. Prior works have defined MCI subclasses based on whether or not clinical scores significantly change from baseline. There are concerns with these definitions, however, since, e.g., most MCIs (and ADs) do not change from a baseline CDR = 0.5 at any subsequent visit in ADNI, even while physiological changes may be occurring. These works ignore rich phenotypical information in an MCI patient's brain scan and labeled AD and Control examples, in defining conversion. We propose an innovative definition, wherein an MCI is a converter if any of the patient's brain scans are classified "AD" by a Control-AD classifier. This definition bootstraps design of a second classifier, specifically trained to predict whether or not MCIs will convert. We thus predict whether an AD-Control classifier will predict that a patient has AD. Our results demonstrate that this definition leads not only to much higher prognostic accuracy than by-CDR conversion, but also to subpopulations more consistent with known AD biomarkers (including CSF markers). We also identify key prognostic brain region biomarkers.
PLoS ONE 01/2011; 6(10):e25074. · 4.09 Impact Factor
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Jianli Wang,
Paul J Eslinger,
Richard L Doty,
Erin K Zimmerman,
Robert Grunfeld,
Xiaoyu Sun,
Mark D Meadowcroft,
James R Connor,
Joseph L Price,
Michael B Smith, Qing X Yang
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ABSTRACT: Alzheimer's disease (AD) is accompanied by smell dysfunction, as measured by psychophysical tests. Currently, it is unknown whether AD-related alterations in central olfactory system neural activity, as measured by functional magnetic resonance imaging (fMRI), are detectable beyond those observed in healthy elderly. Moreover, it is not known whether such changes are correlated with indices of odor perception and dementia. To investigate these issues, 12 early stage AD patients and 13 nondemented controls underwent fMRI while being exposed to each of three concentrations of lavender oil odorant. All participants were administered the University of Pennsylvania Smell Identification Test (UPSIT), the Mini-Mental State Examination (MMSE), the Mattis Dementia Rating Scale-2 (DRS-2), and the Clinical Dementia Rating Scale (CDR). The blood oxygen level-dependent (BOLD) signal at primary olfactory cortex (POC) was weaker in AD than in HC subjects. At the lowest odorant concentration, the BOLD signals within POC, hippocampus, and insula were significantly correlated with UPSIT, MMSE, DRS-2, and CDR scores. The BOLD signal intensity and activation volume within the POC increased significantly as a function of odorant concentration in the AD group, but not in the control group. These findings demonstrate that olfactory fMRI is sensitive to the AD-related olfactory and cognitive functional decline.
Brain research 10/2010; 1357:184-94. · 2.46 Impact Factor
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ABSTRACT: Feature selection for classification in high-dimensional spaces can improve generalization, reduce classifier complexity, and identify important, discriminating feature "markers." For support vector machine (SVM) classification, a widely used technique is recursive feature elimination (RFE). We demonstrate that RFE is not consistent with margin maximization, central to the SVM learning approach. We thus propose explicit margin-based feature elimination (MFE) for SVMs and demonstrate both improved margin and improved generalization, compared with RFE. Moreover, for the case of a nonlinear kernel, we show that RFE assumes that the squared weight vector 2-norm is strictly decreasing as features are eliminated. We demonstrate this is not true for the Gaussian kernel and, consequently, RFE may give poor results in this case. MFE for nonlinear kernels gives better margin and generalization. We also present an extension which achieves further margin gains, by optimizing only two degrees of freedom--the hyperplane's intercept and its squared 2-norm--with the weight vector orientation fixed. We finally introduce an extension that allows margin slackness. We compare against several alternatives, including RFE and a linear programming method that embeds feature selection within the classifier design. On high-dimensional gene microarray data sets, University of California at Irvine (UCI) repository data sets, and Alzheimer's disease brain image data, MFE methods give promising results.
IEEE Transactions on Neural Networks 02/2010; 21(5):701-17. · 2.95 Impact Factor
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ABSTRACT: Although some of the anatomical underpinnings of learning and memory systems have been identified, there remains little understanding of how the brain moves from acquiring new information to retaining it. This study was designed to further explore and elucidate the neural mechanisms underlying encoding and memory in a common real-life task, that is, face-name associations. One possible outcome is that the tasks will recruit different neural structures mediating these processes, which can be identified through contrast analysis of activations. Alternatively, it is possible that similar anatomical regions, such as the hippocampus and parahippocampal gyrus, may be involved in both tasks. In that case, analysis of blood oxygenation level dependent (BOLD) amplitude differences between the tasks in those common neural structures may be able to detect whether physiological activation differences occur in encoding versus memory.
Five healthy adult participants underwent high-field magnetic resonance imaging (MRI) while learning face-name pairs (encoding phase) and during a multiple-choice recognition task after a brief delay (memory phase). Average activation and BOLD response amplitudes in specific regions of interest and whole-brain activation maps were analyzed.
Common activations were observed in the encoding and recognition memory tasks in several regions of interest encompassing the medial temporal and inferior occipital regions. However, higher BOLD response amplitudes occurred in the right fusiform gyrus and the right hippocampus during encoding. In contrast, higher amplitudes were detected in the lingual gyrus bilaterally during recognition memory. Encoding activated distributed prefrontal and temporal cortical regions bilaterally, which mediate attentional, executive, language, and memory systems. Recognition memory recruited a different network of regions encompassing convergence zones in the left prefrontal cortex and the parietal-occipital-temporal region bilaterally, where multimodal visual association, language, memory, and decision-making systems interact.
Higher BOLD response amplitudes in the right fusiform gyrus and the right hippocampus during face-name encoding suggest a potentially specific binding pathway where disparate information might be neurally linked. In contrast, the increased BOLD response in the lingual gyrus during recognition memory may indicate a key neural substrate for memory consolidation and long-term knowledge of what is learned. Whole-brain activation maps revealed task-specific differences in areas of the prefrontal, temporal, and occipital-parietal-temporal junctions as well. Findings suggest that there are distinctive anatomical and physiological nodes for face-name learning and memory within large-scale cortical-subcortical networks. Hence, lesions in fairly widespread cerebral regions may potentially disrupt specific binding and/or memory consolidation processes.
Topics in magnetic resonance imaging: TMRI 10/2009; 20(5):271-8.
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ABSTRACT: This paper describes a Software Tool for Automated MRI Post-processing (STAMP) of multiple types of brain MRIs on a workstation and for parallel processing on a supercomputer (STAMPS). This software tool enables the automation of nonlinear registration for a large image set and for multiple MR image types. The tool uses standard brain MRI post-processing tools (such as SPM, FSL, and HAMMER) for multiple MR image types in a pipeline fashion. It also contains novel MRI post-processing features. The STAMP image outputs can be used to perform brain analysis using Statistical Parametric Mapping (SPM) or single-/multi-image modality brain analysis using Support Vector Machines (SVMs). Since STAMPS is PBS-based, the supercomputer may be a multi-node computer cluster or one of the latest multi-core computers.
Computer methods and programs in biomedicine 05/2009; 95(2):146-57. · 1.14 Impact Factor
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ABSTRACT: To investigate the relationship between MR image contrast associated with beta-amyloid (Abeta) plaques and their histology and compare the histopathological basis of image contrast and the relaxation mechanism associated with Abeta plaques in human Alzheimer's disease (AD) and transgenic APP/PS1 mouse tissues.
With the aid of the previously developed histological coil, T(2) (*)-weighted images and R(2) (*) parametric maps were directly compared with histology stains acquired from the same set of Alzheimer's and APP/PS1 tissue slices.
The electron microscopy and histology images revealed significant differences in plaque morphology and associated iron concentration between AD and transgenic APP/PS1 mice tissue samples. For AD tissues, T(2) (*) contrast of Abeta-plaques was directly associated with the gradation of iron concentration. Plaques with significantly less iron load in the APP/PS1 animal tissues are equally conspicuous as the human plaques in the MR images.
These data suggest a duality in the relaxation mechanism where both high focal iron concentration and highly compact fibrillar beta-amyloid masses cause rapid proton transverse magnetization decay. For human tissues, the former mechanism is likely the dominant source of R(2) (*) relaxation; for APP/PS1 animals, the latter is likely the major cause of increased transverse proton relaxation rate in Abeta plaques. The data presented are essential for understanding the histopathological underpinning of MRI measurement associated with Abeta plaques in humans and animals.
Journal of Magnetic Resonance Imaging 05/2009; 29(5):997-1007. · 2.70 Impact Factor
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ABSTRACT: Human glioblastoma tumors selectively express receptors for interleukin 13 (IL-13). In a previous study, we showed that liposomes, when conjugated with IL-13, will deliver chemotherapeutics to a subcutaneous glioma tumor model in mice much more effectively than conventional unconjugated liposomes. Based on this observation, we developed an intracranial brain tumor model in nude mice using human U87 glioma cells. Mice receiving weekly i.p. injections of 15 mg/kg of doxorubicin encapsulated in IL-13-conjugated liposomes had a 5-fold reduction in the intracranial tumor volume over 6 weeks and four of seven animals survived >200 days after tumor implantation. In contrast, the animals receiving unconjugated liposomes with the same doxorubicin concentration did not survive beyond 35 days and there was no evidence of tumor size reduction. The presence of liposomes with doxorubicin in the tumor was shown by taking advantage of the selective expression of IL-13 receptors on the tumor cells and the endogenous fluorescence of doxorubicin. There was no increase in the indices of toxicity in animals receiving the doxorubicin-containing liposomes. Finally, a model of the blood-brain barrier was used to show that the nanovesicles do not harm the endothelial cells yet maintain their toxicity to astrocytoma cells. This approach is necessary to show the efficacy of this targeting platform for tumors in which the blood-brain barrier is not compromised and as a potential use of the nanovesicle system as a surveillance mechanism to prevent recurrence. These data show that IL-13 targeted nanovesicles are a viable option for the treatment of brain tumors.
Molecular Cancer Therapeutics 03/2009; 8(3):648-54. · 5.23 Impact Factor
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ABSTRACT: Recovery of function after early brain injury depends upon both reparative and compensatory processes that are minimally understood. Using functional magnetic resonance imaging (fMRI), this study investigated the reorganization of hemispheric brain activity of a 24 year old male who suffered right prefrontal cortex damage at 7 years of age related to ruptured arteriovenous malformation. His pattern of recovery has been examined and tracked over the past 17 years and evolved from initial significant impairments in executive, spatial and attentional abilities from the brain lesion to remarkable recovery of function.
High field fMRI studies were completed with experimental cognitive tasks sensitive to right prefrontal functions, including visuospatial relational reasoning, spatial working memory, go no-go, emotional face recognition, and coin calculation. Results were compared to a matched control group for total hemispheric activity patterns. Results: Analyses revealed that on fMRI activation tasks where the patient scored similar to controls, he activated a broader network of bilateral cortical regions than controls. On tasks where he scored lower than controls, there was under-activation of prefrontal cortical regions in comparison to controls.
Recovery of function after prefrontal cortex damage in childhood can occur and be associated with significant functional reorganization of hemispheric activity patterns (i.e. developmental cerebral plasticity). Although not all tasks showed recovery to the same extent in this case, those tasks with the most robust recovery entailed compensatory activation of additional cortical regions on fMRI. Further studies are needed to confirm and extend these findings.
Developmental neurorehabilitation 01/2009; 12(5):298-312.
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ABSTRACT: In high-magnetic-field MRI, both valuable image contrast and undesirable artifacts associated with the magnetic susceptibility
effects are significantly increased. The magnetic field distortion in and by the human body is described with computer modeling
methods in the human head. The manifestations of the resultant image artifacts include signal loss, blurring, and geometric
distortion and are dependent on imaging methods. The treatments of the artifacts in the specific imaging sequences are described
and demonstrated with human studies at 3 and 7 Tesla and animal studies at field strengths as high as 14 Tesla. With these
in vivo studies, the enhanced image contrast produced by the increased field strength and the improved image quality by the
artifact reduction methods provide strong and stimulating evidence for exciting potential scientific applications of high
field MRI.
12/2007: pages 249-284;
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ABSTRACT: Direct imaging of a histological slice is challenging. The vast difference in dimension between planar size and the thickness of histology slices would require an RF coil to produce a uniform RF magnetic (B1) field in a 2D plane with minimal thickness. In this work a novel RF coil designed specifically for imaging a histology slice was developed and tested. The experimental data demonstrate that the coil is highly sensitive and capable of producing a uniform B1 field distribution in a planar region of histological slides, allowing for the acquisition of high-resolution T2 images and T2 maps from a 60-microm-thick histological sample. The image intensity and T2 distributions were directly compared with histological staining of the relative iron concentration of the same slice. This work demonstrates the feasibility of using a microimaging histological coil to image thin slices of pathologically diseased tissue to obtain a precise one-to-one comparison between stained tissue and MR images.
Magnetic Resonance in Medicine 06/2007; 57(5):835-41. · 2.96 Impact Factor
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ABSTRACT: The two-dimensional (2-D) prolate spheroidal wave function (2-D PSWF) method was previously introduced as an efficient method for trading off between spatial and temporal resolution in magnetic resonance imaging (MRI), with minimal penalty due to truncation and partial volume effects. In the 2-D PSWF method, the k-space sampling area and a matching 2-D PSWF filter, with optimal signal concentration and minimal truncation artifacts, are determined by the shape and size of a given convex region of interest (ROI). The spatial information in the reduced k-space data is used to calculate the total image intensity over a nonsquare ROI instead of producing a low-resolution image. This method can be used for tracking dynamic signals from non-square ROIs using a reduced k-space sampling area, while achieving minimal signal leakage. However, the previous theory is limited to the case of rectilinear sampling. In order to make the 2-D PSWF method more suitable for dynamic studies, this paper presents a generalized version of the 2-D PSWF theory that can be applied to nonrectilinear data acquisition methods. The method is applied to an fMRI study using a spiral trajectory, which illustrates the methods efficiency at tracking hemodynamic signals with high temporal resolution.
IEEE Transactions on Image Processing 10/2006; 15(9):2792-804. · 3.04 Impact Factor
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ABSTRACT: To investigate the effects of high dielectric material padding on RF field distribution in the human head at 7.0 T, and demonstrate the feasibility and effectiveness of RF passive shimming and focusing with such an approach.
The intensity distribution changes of gradient-recalled-echo (GRE) and spin-echo (SE) images of a human head acquired with water pads (dielectric constant = 78) placed in specified configurations around the head at 7.0 T were evaluated and compared with computer simulation results using the finite difference time domain (FDTD) method. The contributions to the B(1) field distribution change from the displacement current and conductive current of a given configuration of dielectric padding were determined with computer simulations.
MR image intensity distribution in the human head with an RF coil at 7.0 T can be changed drastically by placing water pads around the head. Computer simulations reveal that the high permittivity of water pads results in a strong displacement current that enhances image intensity in the nearby region and alters the intensity distribution of the entire brain.
The image intensity distribution in the human head at ultra-high field strengths can be effectively manipulated with high permittivity padding. Utilizing this effect, the B(1) field inside the human head of a given RF coil can be adjusted to reduce the B(1) field inhomogeneity artifact associated with the wave behavior (RF passive shimming) or to locally enhance the signal-to-noise ratio (SNR) in targeted regions of interest (ROIs; RF field focusing).
Journal of Magnetic Resonance Imaging 08/2006; 24(1):197-202. · 2.70 Impact Factor
