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Results: 1 to 10 of 53

Publication Record


White matter differences between essential tremor and Parkinson disease.
Juttukonda MR, Franco G, Englot DJ, Lin YC, Petersen KJ, Trujillo P, Hedera P, Landman BA, Kang H, Donahue MJ, Konrad PE, Dawant BM, Claassen DO
(2019) Neurology 92: e30-e39
MeSH Terms: Aged, Anisotropy, Cohort Studies, Diffusion Tensor Imaging, Essential Tremor, Female, Humans, Image Processing, Computer-Assisted, Leukoencephalopathies, Logistic Models, Male, Middle Aged, Parkinson Disease
Show Abstract · Added June 22, 2019
OBJECTIVE - To assess white matter integrity in patients with essential tremor (ET) and Parkinson disease (PD) with moderate to severe motor impairment.
METHODS - Sedated participants with ET (n = 57) or PD (n = 99) underwent diffusion tensor imaging (DTI) and fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity values were computed. White matter tracts were defined using 3 well-described atlases. To determine candidate white matter regions that differ between ET and PD groups, a bootstrapping analysis was applied using the least absolute shrinkage and selection operator. Linear regression was applied to assess magnitude and direction of differences in DTI metrics between ET and PD populations in the candidate regions.
RESULTS - Fractional anisotropy values that differentiate ET from PD localize primarily to thalamic and visual-related pathways, while diffusivity differences localized to the cerebellar peduncles. Patients with ET exhibited lower fractional anisotropy values than patients with PD in the lateral geniculate body ( < 0.01), sagittal stratum ( = 0.01), forceps major ( = 0.02), pontine crossing tract ( = 0.03), and retrolenticular internal capsule ( = 0.04). Patients with ET exhibited greater radial diffusivity values than patients with PD in the superior cerebellar peduncle ( < 0.01), middle cerebellar peduncle ( = 0.05), and inferior cerebellar peduncle ( = 0.05).
CONCLUSIONS - Regionally, distinctive white matter microstructural values in patients with ET localize to the cerebellar peduncles and thalamo-cortical visual pathways. These findings complement recent functional imaging studies in ET but also extend our understanding of putative physiologic features that account for distinctions between ET and PD.
© 2018 American Academy of Neurology.
0 Communities
1 Members
0 Resources
13 MeSH Terms
The VALiDATe29 MRI Based Multi-Channel Atlas of the Squirrel Monkey Brain.
Schilling KG, Gao Y, Stepniewska I, Wu TL, Wang F, Landman BA, Gore JC, Chen LM, Anderson AW
(2017) Neuroinformatics 15: 321-331
MeSH Terms: Animals, Anisotropy, Brain, Diffusion Magnetic Resonance Imaging, Female, Male, Saimiri
Show Abstract · Added August 17, 2017
We describe the development of the first digital atlas of the normal squirrel monkey brain and present the resulting product, VALiDATe29. The VALiDATe29 atlas is based on multiple types of magnetic resonance imaging (MRI) contrast acquired on 29 squirrel monkeys, and is created using unbiased, nonlinear registration techniques, resulting in a population-averaged stereotaxic coordinate system. The atlas consists of multiple anatomical templates (proton density, T1, and T2* weighted), diffusion MRI templates (fractional anisotropy and mean diffusivity), and ex vivo templates (fractional anisotropy and a structural MRI). In addition, the templates are combined with histologically defined cortical labels, and diffusion tractography defined white matter labels. The combination of intensity templates and image segmentations make this atlas suitable for the fundamental atlas applications of spatial normalization and label propagation. Together, this atlas facilitates 3D anatomical localization and region of interest delineation, and enables comparisons of experimental data across different subjects or across different experimental conditions. This article describes the atlas creation and its contents, and demonstrates the use of the VALiDATe29 atlas in typical applications. The atlas is freely available to the scientific community.
0 Communities
3 Members
0 Resources
7 MeSH Terms
Subject-specific regional measures of water diffusion are associated with impairment in chronic spinal cord injury.
Choe AS, Sadowsky CL, Smith SA, van Zijl PCM, Pekar JJ, Belegu V
(2017) Neuroradiology 59: 747-758
MeSH Terms: Adult, Aged, Anisotropy, Biomarkers, Body Water, Chronic Disease, Female, Humans, Image Interpretation, Computer-Assisted, Injury Severity Score, Male, Middle Aged, Sensitivity and Specificity, Spinal Cord Injuries
Show Abstract · Added April 10, 2019
PURPOSE - We aimed to identify non-invasive imaging parameters that can serve as biomarkers for the integrity of the spinal cord, which is paramount to neurological function. Diffusion tensor imaging (DTI) indices are sensitive to axonal and myelin damage, and have strong potential to serve as such biomarkers. However, averaging DTI indices over large regions of interest (ROIs), a common approach to analyzing the images of injured spinal cord, leads to loss of subject-specific information. We investigated if DTI-tractography-driven, subject-specific demarcation approach can yield measures that are more specific to impairment.
METHODS - In 18 individuals with chronic spinal cord injury (SCI), subject-specific demarcation of the injury region was performed using DTI tractography, which yielded three regions relative to injury (RRI; regions superior to, at, and below injury epicenter). DTI indices averaged over each RRI were correlated with measures of residual motor and sensory function, obtained using the International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI).
RESULTS - Total ISNCSCI score (ISNCSCI-tot; sum of ISNCSCI motor and sensory scores) was significantly (p < 0.05) correlated with fractional anisotropy and axial and radial diffusivities. ISNCSCI-tot showed strongest correlation with indices measured from the region inferior to the injury epicenter (IRRI), the degree of which exceeded that of those measured from the entire cervical cord-suggesting contribution from Wallerian degeneration.
CONCLUSION - DTI tractography-driven, subject-specific injury demarcation approach provided measures that were more specific to impairment. Notably, DTI indices obtained from the IRRI region showed the highest specificity to impairment, demonstrating their strong potential as biomarkers for the SCI severity.
0 Communities
1 Members
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MeSH Terms
Biophysical and neural basis of resting state functional connectivity: Evidence from non-human primates.
Chen LM, Yang PF, Wang F, Mishra A, Shi Z, Wu R, Wu TL, Wilson GH, Ding Z, Gore JC
(2017) Magn Reson Imaging 39: 71-81
MeSH Terms: Animals, Anisotropy, Brain, Brain Mapping, Electrophysiological Phenomena, Haplorhini, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Models, Animal, Neural Pathways, Neurons, Primates, White Matter
Show Abstract · Added February 6, 2017
Functional MRI (fMRI) has evolved from simple observations of regional changes in MRI signals caused by cortical activity induced by a task or stimulus, to task-free acquisitions of images in a resting state. Such resting state signals contain low frequency fluctuations which may be correlated between voxels, and strongly correlated regions are deemed to reflect functional connectivity within synchronized circuits. Resting state functional connectivity (rsFC) measures have been widely adopted by the neuroscience community, and are being used and interpreted as indicators of intrinsic neural circuits and their functional states in a broad range of applications, both basic and clinical. However, there has been relatively little work reported that validates whether inter-regional correlations in resting state fluctuations of fMRI (rsfMRI) signals actually measure functional connectivity between brain regions, or to establish how MRI data correlate with other metrics of functional connectivity. In this mini-review, we summarize recent studies of rsFC within mesoscopic scale cortical networks (100μm-10mm) within a well defined functional region of primary somatosensory cortex (S1), as well as spinal cord and brain white matter in non-human primates, in which we have measured spatial patterns of resting state correlations and validated their interpretation with electrophysiological signals and anatomic connections. Moreover, we emphasize that low frequency correlations are a general feature of neural systems, as evidenced by their presence in the spinal cord as well as white matter. These studies demonstrate the valuable role of high field MRI and invasive measurements in an animal model to inform the interpretation of human imaging studies.
Copyright © 2017 Elsevier Inc. All rights reserved.
0 Communities
2 Members
0 Resources
13 MeSH Terms
Peripheral sphingolipids are associated with variation in white matter microstructure in older adults.
Gonzalez CE, Venkatraman VK, An Y, Landman BA, Davatzikos C, Ratnam Bandaru VV, Haughey NJ, Ferrucci L, Mielke MM, Resnick SM
(2016) Neurobiol Aging 43: 156-63
MeSH Terms: Aged, Aging, Anisotropy, Ceramides, Cognition, Diffusion Magnetic Resonance Imaging, Female, Humans, Male, Middle Aged, Sphingolipids, Sphingomyelins, White Matter
Show Abstract · Added November 2, 2016
Sphingolipids serve important structural and functional roles in cellular membranes and myelin sheaths. Plasma sphingolipids have been shown to predict cognitive decline and Alzheimer's disease. However, the association between plasma sphingolipid levels and brain white matter (WM) microstructure has not been examined. We investigated whether plasma sphingolipids (ceramides and sphingomyelins) were associated with magnetic resonance imaging-based diffusion measures, fractional anisotropy (FA), and mean diffusivity, 10.5 years later in 17 WM regions of 150 cognitively normal adults (mean age 67.2). Elevated ceramide species (C20:0, C22:0, C22:1, and C24:1) were associated with lower FA in multiple WM regions, including total cerebral WM, anterior corona radiata, and the cingulum of the cingulate gyrus. Higher sphingomyelins (C18:1 and C20:1) were associated with lower FA in regions such as the anterior corona radiata and body of the corpus callosum. Furthermore, lower sphingomyelin to ceramide ratios (C22:0, C24:0, and C24:1) were associated with lower FA or higher mean diffusivity in regions including the superior and posterior corona radiata. However, although these associations were significant at the a priori p < 0.05, only associations with some regional diffusion measures for ceramide C22:0 and sphingomyelin C18:1 survived correction for multiple comparisons. These findings suggest plasma sphingolipids are associated with variation in WM microstructure in cognitively normal aging.
Copyright © 2016 Elsevier Inc. All rights reserved.
0 Communities
1 Members
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13 MeSH Terms
Quantifying the impact of underlying measurement error on cervical spinal cord diffusion tensor imaging at 3T.
By S, Smith AK, Dethrage LM, Lyttle BD, Landman BA, Creasy JL, Pawate S, Smith SA
(2016) J Magn Reson Imaging 44: 1608-1618
MeSH Terms: Adult, Algorithms, Anisotropy, Cerebrospinal Fluid, Diffusion Tensor Imaging, Female, Humans, Image Enhancement, Image Interpretation, Computer-Assisted, Male, Reference Values, Reproducibility of Results, Sensitivity and Specificity, Spinal Cord
Show Abstract · Added November 2, 2016
PURPOSE - To empirically characterize and quantify the impact of gradient weighting schemes on the appearance and fidelity of diffusion tensor imaging of the human spinal cord in vivo in clinically relevant scan time equivalents (STE).
MATERIALS AND METHODS - In five healthy controls at 3T, we evaluated test-retest reproducibility and performed voxelwise analysis of diffusion tensor imaging (DTI)-derived indices (fractional anisotropy [FA], mean [MD], axial [AD], and radial [RD] diffusivity) in the cervical spinal cord to assess spatial dependencies of measurement error and differences across three different sampling schemes (6, 15, and 32 directions) at STE of 4.5, 9, and 18 minutes. A subjective assessment was also performed.
RESULTS - With six directions, column-specific errors are highest (effect size = 2.9%, 4.4%, 7.2% for FA in dorsal column, lateral column, and gray matter) and different than the 15-direction scheme (P < 0.05). STE sequences with 15 and 32 directions exhibited small differences in error (P > 0.05). For FA and AD, measurement errors are prevalent in gray matter, while partial volume effects with cerebrospinal fluid heavily influence RD. Measurement errors decreased with increasing scan time (P < 0.01), albeit with diminishing returns at scan times longer than 9 minutes (P < 0.05).
CONCLUSION - A 15-direction scheme of 9 minutes yields measurements of the cervical spinal cord with low error. J. Magn. Reson. Imaging 2016;44:1608-1618.
© 2016 International Society for Magnetic Resonance in Medicine.
0 Communities
2 Members
0 Resources
14 MeSH Terms
ZOOM or Non-ZOOM? Assessing Spinal Cord Diffusion Tensor Imaging Protocols for Multi-Centre Studies.
Samson RS, Lévy S, Schneider T, Smith AK, Smith SA, Cohen-Adad J, Gandini Wheeler-Kingshott CA
(2016) PLoS One 11: e0155557
MeSH Terms: Anisotropy, Diffusion, Diffusion Tensor Imaging, Humans, Image Interpretation, Computer-Assisted, Signal-To-Noise Ratio, Spinal Cord
Show Abstract · Added April 6, 2017
The purpose of this study was to develop and evaluate two spinal cord (SC) diffusion tensor imaging (DTI) protocols, implemented at multiple sites (using scanners from two different manufacturers), one available on any clinical scanner, and one using more advanced options currently available in the research setting, and to use an automated processing method for unbiased quantification. DTI parameters are sensitive to changes in the diseased SC. However, imaging the cord can be technically challenging due to various factors including its small size, patient-related and physiological motion, and field inhomogeneities. Rapid acquisition sequences such as Echo Planar Imaging (EPI) are desirable but may suffer from image distortions. We present a multi-centre comparison of two acquisition protocols implemented on scanners from two different vendors (Siemens and Philips), one using a reduced field-of-view (rFOV) EPI sequence, and one only using options available on standard clinical scanners such as outer volume suppression (OVS). Automatic analysis was performed with the Spinal Cord Toolbox for unbiased and reproducible quantification of DTI metrics in the white matter. Images acquired using the rFOV sequence appear less distorted than those acquired using OVS alone. SC DTI parameter values obtained using both sequences at all sites were consistent with previous measurements made at 3T. For the same scanner manufacturer, DTI parameter inter-site SDs were smaller for the rFOV sequence compared to the OVS sequence. The higher inter-site reproducibility (for the same manufacturer and acquisition details, i.e. ZOOM data acquired at the two Philips sites) of rFOV compared to the OVS sequence supports the idea that making research options such as rFOV more widely available would improve accuracy of measurements obtained in multi-centre clinical trials. Future multi-centre studies should also aim to match the rFOV technique and signal-to-noise ratios in all sequences from different manufacturers/sites in order to avoid any bias in measured DTI parameters and ensure similar sensitivity to pathological changes.
0 Communities
1 Members
0 Resources
7 MeSH Terms
Identification and Optimization of Anthranilic Acid Based Inhibitors of Replication Protein A.
Patrone JD, Pelz NF, Bates BS, Souza-Fagundes EM, Vangamudi B, Camper DV, Kuznetsov AG, Browning CF, Feldkamp MD, Frank AO, Gilston BA, Olejniczak ET, Rossanese OW, Waterson AG, Chazin WJ, Fesik SW
(2016) ChemMedChem 11: 893-9
MeSH Terms: Anisotropy, Dose-Response Relationship, Drug, Fluorescence Polarization, High-Throughput Screening Assays, Models, Molecular, Molecular Structure, Replication Protein A, Structure-Activity Relationship, ortho-Aminobenzoates
Show Abstract · Added February 5, 2016
Replication protein A (RPA) is an essential single-stranded DNA (ssDNA)-binding protein that initiates the DNA damage response pathway through protein-protein interactions (PPIs) mediated by its 70N domain. The identification and use of chemical probes that can specifically disrupt these interactions is important for validating RPA as a cancer target. A high-throughput screen (HTS) to identify new chemical entities was conducted, and 90 hit compounds were identified. From these initial hits, an anthranilic acid based series was optimized by using a structure-guided iterative medicinal chemistry approach to yield a cell-penetrant compound that binds to RPA70N with an affinity of 812 nm. This compound, 2-(3- (N-(3,4-dichlorophenyl)sulfamoyl)-4-methylbenzamido)benzoic acid (20 c), is capable of inhibiting PPIs mediated by this domain.
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
0 Communities
1 Members
0 Resources
9 MeSH Terms
A comparison of solver performance for complex gastric electrophysiology models.
Sathar S, Cheng LK, Trew ML
(2015) Conf Proc IEEE Eng Med Biol Soc 2015: 1452-5
MeSH Terms: Anisotropy, Electrophysiological Phenomena, Stomach
Show Abstract · Added April 26, 2016
Computational techniques for solving systems of equations arising in gastric electrophysiology have not been studied for efficient solution process. We present a computationally challenging problem of simulating gastric electrophysiology in anatomically realistic stomach geometries with multiple intracellular and extracellular domains. The multiscale nature of the problem and mesh resolution required to capture geometric and functional features necessitates efficient solution methods if the problem is to be tractable. In this study, we investigated and compared several parallel preconditioners for the linear systems arising from tetrahedral discretisation of electrically isotropic and anisotropic problems, with and without stimuli. The results showed that the isotropic problem was computationally less challenging than the anisotropic problem and that the application of extracellular stimuli increased workload considerably. Preconditioning based on block Jacobi and algebraic multigrid solvers were found to have the best overall solution times and least iteration counts, respectively. The algebraic multigrid preconditioner would be expected to perform better on large problems.
0 Communities
1 Members
0 Resources
3 MeSH Terms
4.7-T diffusion tensor imaging of acute traumatic peripheral nerve injury.
Boyer RB, Kelm ND, Riley DC, Sexton KW, Pollins AC, Shack RB, Dortch RD, Nanney LB, Does MD, Thayer WP
(2015) Neurosurg Focus 39: E9
MeSH Terms: Acute Disease, Animals, Anisotropy, Diffusion Tensor Imaging, Disease Models, Animal, Female, Humans, Lower Extremity, Male, Peripheral Nerve Injuries, ROC Curve, Rats, Sprague-Dawley, Sciatic Neuropathy, Sensitivity and Specificity, Statistics as Topic
Show Abstract · Added January 26, 2016
Diagnosis and management of peripheral nerve injury is complicated by the inability to assess microstructural features of injured nerve fibers via clinical examination and electrophysiology. Diffusion tensor imaging (DTI) has been shown to accurately detect nerve injury and regeneration in crush models of peripheral nerve injury, but no prior studies have been conducted on nerve transection, a surgical emergency that can lead to permanent weakness or paralysis. Acute sciatic nerve injuries were performed microsurgically to produce multiple grades of nerve transection in rats that were harvested 1 hour after surgery. High-resolution diffusion tensor images from ex vivo sciatic nerves were obtained using diffusion-weighted spin-echo acquisitions at 4.7 T. Fractional anisotropy was significantly reduced at the injury sites of transected rats compared with sham rats. Additionally, minor eigenvalues and radial diffusivity were profoundly elevated at all injury sites and were negatively correlated to the degree of injury. Diffusion tensor tractography showed discontinuities at all injury sites and significantly reduced continuous tract counts. These findings demonstrate that high-resolution DTI is a promising tool for acute diagnosis and grading of traumatic peripheral nerve injuries.
0 Communities
1 Members
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15 MeSH Terms