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Publication Record


Selective Inversion Recovery Quantitative Magnetization Transfer Brain MRI at 7T: Clinical and Postmortem Validation in Multiple Sclerosis.
Bagnato F, Hametner S, Franco G, Pawate S, Sriram S, Lassmann H, Gore J, Smith SE, Dortch R
(2018) J Neuroimaging 28: 380-388
MeSH Terms: Adult, Aged, Brain, Echo-Planar Imaging, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, White Matter, Young Adult
Show Abstract · Added October 24, 2018
BACKGROUND AND PURPOSE - An imaging biomarker of myelin integrity is an unmet need in multiple sclerosis (MS). Selective inversion recovery (SIR) quantitative magnetization transfer imaging (qMT) provides assays of myelin content in the human brain. We previously translated the SIR method to 7T and incorporated a rapid turbo field echo (TFE) readout for whole-brain imaging within clinically acceptable scan times. We herein provide histological validation and test in vivo feasibility and applicability of the SIR-TFE protocol in MS.
METHODS - Clinical (T - and T -weighted) and SIR-TFE MRI scans were performed at 7T in a postmortem MS brain and MRI data were acquired in 10 MS patients and 14 heathy volunteers in vivo. The following parameters were estimated from SIR data: the macromolecular-to-free water pool-size-ratio (PSR), the spin-lattice relaxation rate of water (R ), and the MT exchange rate (k ). Differences in SIR parameters across tissue types, eg, white matter lesions (WM-Ls) and normal appearing WM (NAWM) in patients, and normal white matter (NWM) in heathy volunteers were evaluated. Associations between SIR parameters and disability scores were assessed.
RESULTS - For postmortem scans, correspondence was observed between WM-Ls and NAWM from histology and PSR/R values. In vivo differences were detected for PSR, R , and k between WM-Ls and NWM (P ≤ .041). Associations were seen between WM-Ls/ NAWM PSR and disability scores (r ≤ -.671, P ≤ .048).
CONCLUSIONS - SIR-qMT at 7T provides sensitive, quantitative measures of myelin integrity for clinical and research applications.
Copyright © 2018 by the American Society of Neuroimaging.
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12 MeSH Terms
Functional connectivity and activity of white matter in somatosensory pathways under tactile stimulations.
Wu X, Yang Z, Bailey SK, Zhou J, Cutting LE, Gore JC, Ding Z
(2017) Neuroimage 152: 371-380
MeSH Terms: Adult, Brain Mapping, Diffusion Tensor Imaging, Echo-Planar Imaging, Female, Humans, Male, Physical Stimulation, Somatosensory Cortex, Touch, Touch Perception, White Matter, Young Adult
Show Abstract · Added April 6, 2017
Functional MRI has proven to be effective in detecting neural activity in brain cortices on the basis of blood oxygenation level dependent (BOLD) contrast, but has relatively poor sensitivity for detecting neural activity in white matter. To demonstrate that BOLD signals in white matter are detectable and contain information on neural activity, we stimulated the somatosensory system and examined distributions of BOLD signals in related white matter pathways. The temporal correlation profiles and frequency contents of BOLD signals were compared between stimulation and resting conditions, and between relevant white matter fibers and background regions, as well as between left and right side stimulations. Quantitative analyses show that, overall, MR signals from white matter fiber bundles in the somatosensory system exhibited significantly greater temporal correlations with the primary sensory cortex and greater signal power during tactile stimulations than in a resting state, and were stronger than corresponding measurements for background white matter both during stimulations and in a resting state. The temporal correlation and signal power under stimulation were found to be twice those observed from the same bundle in a resting state, and bore clear relations with the side of stimuli. These indicate that BOLD signals in white matter fibers encode neural activity related to their functional roles connecting cortical volumes, which are detectable with appropriate methods.
Copyright © 2017 Elsevier Inc. All rights reserved.
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13 MeSH Terms
Neural correlates of out-group bias predict social impairment in patients with schizophrenia.
Blackford JU, Williams LE, Heckers S
(2015) Schizophr Res 164: 203-9
MeSH Terms: Adult, Brain, Brain Mapping, Echo-Planar Imaging, Female, Functional Laterality, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Oxygen, Psychiatric Status Rating Scales, Schizophrenia, Social Behavior Disorders, Statistics as Topic
Show Abstract · Added February 22, 2016
BACKGROUND - Social impairments are a hallmark feature of schizophrenia and are a key predictor of functional disability. Deficits in social information processing likely underlie social impairment; however, this relationship is understudied. We previously demonstrated that patients with schizophrenia fail to habituate to neutral faces, providing evidence for an alteration in basic social information processing. It remains unknown whether patients with schizophrenia also show deficits in processing of more complex social information. Out-group bias provides an excellent opportunity to test complex social information processing because the bias requires basic face processing skills, the ability to discriminate between groups, as well as the ability to categorize oneself into a salient social group.
METHODS - Study participants were 23 patients with schizophrenia and 21 controls. Using functional magnetic resonance imaging, habituation of response to 120 s of repeated presentations of faces was assessed in participants who viewed either same-gender faces or opposite-gender faces. The interaction between face gender (same/opposite) and group was examined in three key regions: amygdala, hippocampus, and visual cortex. Social impairment was measured using the PANSS and correlations between social impairment and out-group effect (main effect of face type) were performed in patients.
RESULTS - Patients with schizophrenia had aberrant neural responses to opposite-gender faces (interaction, p<.05 corrected). Healthy controls showed an immediate heightened response to opposite-gender faces relative to same-gender faces; but in patients this effect was substantially delayed (~70s). In patients with schizophrenia, the out-group bias was significantly correlated with social impairment. Patients with no social impairment showed a heightened neural response to opposite-gender faces after 30s, whereas patients with mild-moderate social impairment failed to ever show a heightened response.
CONCLUSION - Alterations in neural responses during out-group processing predicted degree of social impairment in patients with schizophrenia; thus, neural responses to opposite-gender faces may provide a novel measure for studies of treatment response and disease outcome.
Copyright © 2015 Elsevier B.V. All rights reserved.
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16 MeSH Terms
Evaluation of a multiple spin- and gradient-echo (SAGE) EPI acquisition with SENSE acceleration: applications for perfusion imaging in and outside the brain.
Skinner JT, Robison RK, Elder CP, Newton AT, Damon BM, Quarles CC
(2014) Magn Reson Imaging 32: 1171-80
MeSH Terms: Acceleration, Adult, Algorithms, Brain, Brain Neoplasms, Contrast Media, Echo-Planar Imaging, Female, Fourier Analysis, Glioma, Humans, Image Processing, Computer-Assisted, Leg, Magnetic Resonance Imaging, Male, Muscle, Skeletal, Muscles, Oxygen, Perfusion Imaging, Reperfusion, Software
Show Abstract · Added September 8, 2014
Perfusion-based changes in MR signal intensity can occur in response to the introduction of exogenous contrast agents and endogenous tissue properties (e.g. blood oxygenation). MR measurements aimed at capturing these changes often implement single-shot echo planar imaging (ssEPI). In recent years ssEPI readouts have been combined with parallel imaging (PI) to allow fast dynamic multi-slice imaging as well as the incorporation of multiple echoes. A multiple spin- and gradient-echo (SAGE) EPI acquisition has recently been developed to allow measurement of transverse relaxation rate (R2 and R2(*)) changes in dynamic susceptibility contrast (DSC)-MRI experiments in the brain. With SAGE EPI, the use of PI can influence image quality, temporal resolution, and achievable echo times. The effect of PI on dynamic SAGE measurements, however, has not been evaluated. In this work, a SAGE EPI acquisition utilizing SENSE PI and partial Fourier (PF) acceleration was developed and evaluated. Voxel-wise measures of R2 and R2(*) in healthy brain were compared using SAGE EPI and conventional non-EPI multiple echo acquisitions with varying SENSE and PF acceleration. A conservative SENSE factor of 2 with PF factor of 0.73 was found to provide accurate measures of R2 and R2(*) in white (WM) (rR2=[0.55-0.79], rR2*=[0.47-0.71]) and gray (GM) matter (rR2=[0.26-0.59], rR2*=[0.39-0.74]) across subjects. The combined use of SENSE and PF allowed the first dynamic SAGE EPI measurements in muscle, with a SENSE factor of 3 and PF factor of 0.6 providing reliable relaxation rate estimates when compared to multi-echo methods. Application of the optimized SAGE protocol in DSC-MRI of high-grade glioma patients provided T1 leakage-corrected estimates of CBV and CBF as well as mean vessel diameter (mVD) and simultaneous measures of DCE-MRI parameters K(trans) and ve. Likewise, application of SAGE in a muscle reperfusion model allowed dynamic measures of R2', a parameter that has been shown to correlate with muscle oxy-hemoglobin saturation.
Copyright © 2014 Elsevier Inc. All rights reserved.
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4 Members
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21 MeSH Terms
Comparison of twice refocused spin echo versus stimulated echo diffusion tensor imaging for tracking muscle fibers.
Noehren B, Andersen A, Feiweier T, Damon B, Hardy P
(2015) J Magn Reson Imaging 41: 624-32
MeSH Terms: Adult, Anisotropy, Diffusion Tensor Imaging, Echo-Planar Imaging, Female, Humans, Magnetic Resonance Imaging, Male, Muscle, Skeletal, Reference Values, Signal-To-Noise Ratio, Thigh
Show Abstract · Added May 29, 2014
PURPOSE - To compare the precision of measuring the pennation angle and fiber length in the vastus lateralis (VL) using two distinctly different diffusion tensor imaging (DTI) sequences.
MATERIALS AND METHODS - We imaged the thigh of 10 normal subjects on a 3T magnetic resonance (MR) imager with twice refocused spin echo (TRSE) and stimulated echo (STEAM) DTI-MRI techniques. Both techniques took the same total acquisition time and employed the same diffusion weighting and gradient directions. Using the diffusion tensor images produced by each sequence, muscle fiber bundles were tracked from the aponeurosis by following the first eigenvector of the diffusion tensor. From these tracks we calculated the pennation angle and fiber length.
RESULTS - The STEAM acquisition resulted in significantly higher signal-to-noise ratio (SNR), lower apparent diffusion coefficient (ADC), higher fractional anisotropy (FA) values, and longer fibers than TRSE. Although no difference in the pennation angle between the two acquisitions was found, the TRSE sequence had a significantly greater within-subject dispersion in the pennation angle of tracked fibers, which may indicate a reduction in the coherence of fiber bundles.
CONCLUSION - DTI of muscle using a STEAM acquisition resulted in significant improvements in the SNR and FA, resulting in tracking a larger number of muscle fiber bundles over longer distances and with less within-subject dispersion.
© 2014 Wiley Periodicals, Inc.
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1 Members
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12 MeSH Terms
Quantitative magnetization transfer imaging of rodent glioma using selective inversion recovery.
Xu J, Li K, Zu Z, Li X, Gochberg DF, Gore JC
(2014) NMR Biomed 27: 253-60
MeSH Terms: Animals, Brain Neoplasms, Cell Line, Tumor, Computer Simulation, Echo-Planar Imaging, Glioma, Magnetic Resonance Imaging, Male, Rats, Rats, Inbred F344, Spin Labels
Show Abstract · Added March 27, 2014
Magnetization transfer (MT) provides an indirect means to detect noninvasively variations in macromolecular contents in biological tissues, but, so far, there have been only a few quantitative MT (qMT) studies reported in cancer, all of which used off-resonance pulsed saturation methods. This article describes the first implementation of a different qMT approach, selective inversion recovery (SIR), for the characterization of tumor in vivo using a rodent glioma model. The SIR method is an on-resonance method capable of fitting qMT parameters and T1 relaxation time simultaneously without mapping B0 and B1 , which is very suitable for high-field qMT measurements because of the lower saturation absorption rate. The results show that the average pool size ratio (PSR, the macromolecular pool versus the free water pool) in rat 9 L glioma (5.7%) is significantly lower than that in normal rat gray matter (9.2%) and white matter (17.4%), which suggests that PSR is potentially a sensitive imaging biomarker for the assessment of brain tumor. Despite being less robust, the estimated MT exchange rates also show clear differences from normal tissues (19.7 Hz for tumors versus 14.8 and 10.2 Hz for gray and white mater, respectively). In addition, the influence of confounding effects, e.g. B1 inhomogeneity, on qMT parameter estimates is investigated with numerical simulations. These findings not only help to better understand the changes in the macromolecular contents of tumors, but are also important for the interpretation of other imaging contrasts, such as chemical exchange saturation transfer of tumors.
Copyright © 2013 John Wiley & Sons, Ltd.
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2 Members
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11 MeSH Terms
Localized high-resolution DTI of the human midbrain using single-shot EPI, parallel imaging, and outer-volume suppression at 7T.
Wargo CJ, Gore JC
(2013) Magn Reson Imaging 31: 810-9
MeSH Terms: Adult, Algorithms, Brain, Diffusion Tensor Imaging, Echo-Planar Imaging, Female, Humans, Image Enhancement, Image Interpretation, Computer-Assisted, Imaging, Three-Dimensional, Male, Mesencephalon, Middle Aged, Multimodal Imaging, Nerve Fibers, Myelinated, Reproducibility of Results, Sensitivity and Specificity, Subtraction Technique
Show Abstract · Added March 7, 2014
Localized high-resolution diffusion tensor images (DTI) from the midbrain were obtained using reduced field-of-view (rFOV) methods combined with SENSE parallel imaging and single-shot echo planar (EPI) acquisitions at 7T. This combination aimed to diminish sensitivities of DTI to motion, susceptibility variations, and EPI artifacts at ultra-high field. Outer-volume suppression (OVS) was applied in DTI acquisitions at 2- and 1-mm(2) resolutions, b=1000s/mm(2), and six diffusion directions, resulting in scans of 7- and 14-min durations. Mean apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in various fiber tract locations at the two resolutions and compared. Geometric distortion and signal-to-noise ratio (SNR) were additionally measured and compared for reduced-FOV and full-FOV DTI scans. Up to an eight-fold data reduction was achieved using DTI-OVS with SENSE at 1mm(2), and geometric distortion was halved. The localization of fiber tracts was improved, enabling targeted FA and ADC measurements. Significant differences in diffusion properties were observed between resolutions for a number of regions suggesting that FA values are impacted by partial volume effects even at a 2-mm(2) resolution. The combined SENSE DTI-OVS approach allows large reductions in DTI data acquisition and provides improved quality for high-resolution diffusion studies of the human brain.
Copyright © 2013 Elsevier Inc. All rights reserved.
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18 MeSH Terms
Axial 3D gradient-echo imaging for improved multiple sclerosis lesion detection in the cervical spinal cord at 3T.
Ozturk A, Aygun N, Smith SA, Caffo B, Calabresi PA, Reich DS
(2013) Neuroradiology 55: 431-9
MeSH Terms: Adult, Aged, Algorithms, Cervical Vertebrae, Echo-Planar Imaging, Female, Humans, Image Enhancement, Image Interpretation, Computer-Assisted, Imaging, Three-Dimensional, Male, Middle Aged, Multiple Sclerosis, Reproducibility of Results, Sensitivity and Specificity, Spinal Cord
Show Abstract · Added February 13, 2015
INTRODUCTION - In multiple sclerosis (MS), spinal cord imaging can help in diagnosis and follow-up evaluation. However, spinal cord magnetic resonance imaging (MRI) is technically challenging, and image quality, particularly in the axial plane, is typically poor compared to brain MRI. Because gradient-recalled echo (GRE) images might offer improved contrast resolution within the spinal cord at high magnetic field strength, both without and with a magnetization transfer prepulse, we compared them to T2-weighted fast-spin-echo (T2-FSE) images for the detection of MS lesions in the cervical cord at 3T.
METHODS - On a clinical 3T MRI scanner, we studied 62 MS cases and 19 healthy volunteers. Axial 3D GRE sequences were performed without and with off-resonance radiofrequency irradiation. To mimic clinical practice, all images were evaluated in conjunction with linked images from a sagittal short tau inversion recovery scan, which is considered the gold standard for lesion detection in MS. Two experienced observers recorded image quality, location and size of focal lesions, atrophy, swelling, and diffuse signal abnormality independently at first and then in consensus.
RESULTS - The number and volume of lesions detected with high confidence was more than three times as high on both GRE sequences compared to T2-FSE (p < 0.0001). Approximately 5 % of GRE scans were affected by artifacts that interfered with image interpretation, not significantly different from T2W-FSE.
CONCLUSIONS - Axial 3D GRE sequences are useful for MS lesion detection when compared to 2D T2-FSE sequences in the cervical spinal cord at 3T and should be considered when examining intramedullary spinal cord lesions.
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16 MeSH Terms
Comparison of dual-echo DSC-MRI- and DCE-MRI-derived contrast agent kinetic parameters.
Quarles CC, Gore JC, Xu L, Yankeelov TE
(2012) Magn Reson Imaging 30: 944-53
MeSH Terms: Animals, Brain Neoplasms, Cell Line, Tumor, Computer Simulation, Contrast Media, Echo-Planar Imaging, Gadolinium DTPA, Gliosarcoma, Image Enhancement, Image Interpretation, Computer-Assisted, Kinetics, Male, Models, Biological, Rats, Rats, Inbred F344, Rats, Wistar, Reproducibility of Results, Sensitivity and Specificity
Show Abstract · Added November 13, 2013
The application of dynamic susceptibility contrast (DSC) MRI methods to assess brain tumors is often confounded by the extravasation of contrast agent (CA). Disruption of the blood-brain barrier allows CA to leak out of the vasculature leading to additional T(1), T(2) and T(2) relaxation effects in the extravascular space, thereby affecting the signal intensity time course in a complex manner. The goal of this study was to validate a dual-echo DSC-MRI approach that separates and quantifies the T(1) and T(2) contributions to the acquired signal and enables the estimation of the volume transfer constant, K(trans), and the volume fraction of the extravascular extracellular space, v(e). To test the validity of this approach, DSC-MRI- and dynamic contrast enhanced (DCE) MRI-derived K(trans) and v(e) estimates were spatially compared in both 9L and C6 rat brain tumor models. A high degree of correlation (concordance correlation coefficients >0.83, Pearson's r>0.84) and agreement was found between the DSC-MRI- and DCE-MRI-derived measurements. These results indicate that dual-echo DSC-MRI can be used to simultaneously extract reliable DCE-MRI kinetic parameters in brain tumors in addition to conventional blood volume and blood flow metrics.
Copyright © 2012 Elsevier Inc. All rights reserved.
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18 MeSH Terms
Functional resting-state networks are differentially affected in schizophrenia.
Woodward ND, Rogers B, Heckers S
(2011) Schizophr Res 130: 86-93
MeSH Terms: Adult, Brain, Brain Mapping, Echo-Planar Imaging, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Psychiatric Status Rating Scales, Psychotic Disorders, Rest, Schizophrenia, Statistics as Topic, Young Adult
Show Abstract · Added February 12, 2015
Neurobiological theories posit that schizophrenia relates to disturbances in connectivity between brain regions. Resting-state functional magnetic resonance imaging is a powerful tool for examining functional connectivity and has revealed several canonical brain networks, including the default mode, dorsal attention, executive control, and salience networks. The purpose of this study was to examine changes in these networks in schizophrenia. 42 patients with schizophrenia and 61 healthy subjects completed a RS-fMRI scanning session. Seed-based region-of-interest correlation analysis was used to identify the default mode, dorsal attention, executive control, and salience networks. Compared to healthy subjects, individuals with schizophrenia demonstrated greater connectivity between the posterior cingulate cortex, a key hub of the default mode, and the left inferior gyrus, left middle frontal gyrus, and left middle temporal gyrus. Interestingly, these regions were more strongly connected to the executive control network in healthy control subjects. In contrast to the default mode, patients demonstrated less connectivity in the executive control and dorsal attention networks. No differences were observed in the salience network. The results indicate that resting-state networks are differentially affected in schizophrenia. The alterations are characterized by reduced segregation between the default mode and executive control networks in the prefrontal cortex and temporal lobe, and reduced connectivity in the dorsal attention and executive control networks. The changes suggest that the process of functional specialization is altered in schizophrenia. Further work is needed to determine if the alterations are related to disturbances in white matter connectivity, neurodevelopmental abnormalities, and genetic risk for schizophrenia.
Copyright © 2011 Elsevier B.V. All rights reserved.
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17 MeSH Terms