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Background and Purpose: A substantial fraction of those who had Alzheimer's Disease (AD) pathology on autopsy did not have dementia in life. While biomarkers for AD pathology are well-developed, biomarkers specific to cognitive domains affected by early AD are lagging. Diffusion MRI (dMRI) of the fornix is a candidate biomarker for early AD-related cognitive changes but is susceptible to bias due to partial volume averaging (PVA) with cerebrospinal fluid. The purpose of this work is to leverage multi-shell dMRI to correct for PVA and to evaluate PVA-corrected dMRI measures in fornix as a biomarker for cognition in AD., Methods: Thirty-three participants in the Cleveland Alzheimer's Disease Research Center (CADRC) (19 with normal cognition (NC), 10 with mild cognitive impairment (MCI), 4 with dementia due to AD) were enrolled in this study. Multi-shell dMRI was acquired, and voxelwise fits were performed with two models: 1) diffusion tensor imaging (DTI) that was corrected for PVA and 2) neurite orientation dispersion and density imaging (NODDI). Values of tissue integrity in fornix were correlated with neuropsychological scores taken from the Uniform Data Set (UDS), including the UDS Global Composite 5 score (UDSGC5)., Results: Statistically significant correlations were found between the UDSGC5 and PVA-corrected measure of mean diffusivity (MDc, r = -0.35, p < 0.05) from DTI and the intracelluar volume fraction (ficvf, r = 0.37, p < 0.04) from NODDI. A sensitivity analysis showed that the relationship to MDc was driven by episodic memory, which is often affected early in AD, and language., Conclusion: This cross-sectional study suggests that multi-shell dMRI of the fornix that has been corrected for PVA is a potential biomarker for early cognitive domain changes in AD. A longitudinal study will be necessary to determine if the imaging measure can predict cognitive decline., Competing Interests: Declaration of competing interest Sakaie: none. Koenig: none. Lerner: none. Appleby: Research support from CDC, NIH, CJD Foundation, Ionis, Alector. Consultant for Acadia, Ionis, and Sangamo. Royalties from Wolters-Kluwer. Ogrocki: none. Pillai received grant support from the National Institute on Aging (NIA), Department of Defense and the Keep Memory Alive Foundation and received compensation for serving as a section editor for Springer Nature. Rao received grant support from the NIA. Leverenz received (a) Scientific Advisory Board of Vaxxinity and (b) grant support from GE Healthcare and National Institutes of Health. Lowe: received grant support from the NIA., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cognitive dysfunction is a known symptom of multiple sclerosis (MS), with memory recognized as a frequently impacted domain. Here, we used high-resolution MRI at 7 tesla to build on cross-sectional work by evaluating the longitudinal relationship of diffusion tensor imaging (DTI) measures of the fornix to episodic memory performance., Methods: A sample of 80 people with multiple sclerosis (mean age 51.9 ± 8.1 years; 24% male) underwent baseline clinical evaluation, neuropsychological assessment, and MRI. Sixty-four participants had follow-up neuropsychological testing after 1-2 years. Linear regression was used to assess the relationship of baseline imaging measures to follow-up episodic memory performance, measured using the Selective Reminding Test and Brief Visuospatial Memory Test. A reduced prediction model included cognitive function at baseline, age, sex, and disease course., Results: Radial (β = -0.222, p  < 0.026; likelihood ratio test (LRT) p  < 0.018), axial (β = -0.270, p  < 0.005; LRT p  < 0.003), and mean (β = -0.242, p  < 0.0139; LRT p  < 0.009) diffusivity of the fornix significantly added to the model, with follow-up analysis indicating that a longer prediction interval may increase accuracy., Conclusion: These results suggest that fornix DTI has predictive value specific to memory function in MS and warrants additional investigation in the drive to develop predictors of disease progression., Competing Interests: K.S. has received salary support from Genzyme and from Novartis. K.R.M. is funded by NIH NINDS and has received consultation fees from Bristol-Myers Squibb and Genentech. K.N. has received licensing fees from Biogen and fees from INmune Bio., (© The Author(s), 2024.)

Background: In this cross sectional study, we used MRF to investigate tissue properties of normal-appearing white matter, gray matter, and lesions in relapsing remitting MS (n = 21), secondary progressive MS (n = 16) and healthy controls (n = 9). A FISP-based MRF sequence was used for acquisition, imaging time 5 min 15 s. MRF T1 and T2 relaxation times were measured from lesional tissue, normal-appearing frontal white matter, corpus callous, thalamus, and caudate. Differences between healthy controls and MS were examined using ANCOVA adjusted for age and sex. Spearman rank correlations were assessed between T1 and T2 relaxation times and clinical measures., Objectives: To examine brain T1 and T2 values using magnetic resonance fingerprinting (MRF) in healthy controls and MS., Methods: The subjects included 21 relapsing-remitting (RR) MS, 16 secondary progressive (SP) MS, and 9 age- and sex-matched HC without manifest neurological disease participating in a longitudinal MRI study. A 3T/ FISP-based MRF sequence was acquired. Regions of interest were drawn for lesions and normal appearing white matter. ANCOVA adjusted for age and sex were used to compare the groups with significance set at 0.05., Results: A step-wise increase in T1 and T2 relaxation times was found between healthy controls, relapsing remitting MS, and secondary progressive MS. Significant differences were found in T1 and T2 between MS and healthy controls in the frontal normal-appearing white matter, corpus callosum, and thalamus (p < 0.04 for all). Significant differences in T1 and T2 between RR and SPMS were found in the frontal normal-appearing white matter and T2 lesions (p < 0.02 for all). T1 relaxation from the frontal normal-appearing white matter correlated with the Expanded Disability Status Scale [ρ = 0.62, p < 0.001], timed 25 foot walk (ρ = 0.45, p = 0.01), 9 hole peg test (ρ = 0.62, p < 0.001), and paced auditory serial addition test (ρ = -0.4, p = 0.01)., Conclusion: These results suggest that MRF may be a clinically feasible quantitative approach for characterizing tissue damage in MS., Competing Interests: Declaration of Competing Interest All authors have reviewed and approve the contents of the manuscript and all authors take full responsibility fotrthe analyses, interpretation, and conduct of the research, all had full access to all of the data and the right to publish all the data.. The manuscript is not under consideration for review elsewhere. All authors authorize the ISMRM to publish this financial disclosure with the article if deemed appropriate. DO: has received research support from National Multiple Sclerosis Society, National Institutes of Health, Patient Centered Outcomes Research Institute, Race to Erase MS Foundation, Genentech, Novartis, and Genzyme. He has also received consulting fees from Biogen Idec, Genentech/Roche, Genzyme, and Merck. VG: Grant support to CWRU by Siemens Healthineers. Patents on MR Fingerprinting, which have been licensed by Siemens Healthineers. AD: is a co-inventor on related patents which have been licensed by Siemens Healthcare. AS: Nothing to report. DG: Nothing to report. YJ: Nothing to Report. DM: Grant support to CWRU by Siemens Healthineers. Patents on MR Fingerprinting, which have been licensed by Siemens Healthineers. EF: Was an employee of and holds stock in Biogen at the time of publication, but not during data collection. RR: Was an employee of and holds stock in Biogen at the time of publication, but not during data collection. PR: Nothing to report. MK: Nothing to report. JAC:Personal compensation for consulting for Alkermes, Biogen, Convelo, EMD Serono, ERT, Gossamer Bio, Novartis, and ProValuate; speaking for Mylan and Synthon; and serving as an Editor of Multiple Sclerosis Journal. KS: Grant support from Genzyme and Novartis. ML: Research support from the National Multiple Sclerosis Society, the National Institutes of Health, the Department of Defense and consulting fees from Siemens Healthineers. MG: Grant support to CWRU by Siemens Healthineers. Patents on MR Fingerprinting, which have been licensed by Siemens Healthineers. KN: has received research support from National Multiple Sclerosis Society, National Institutes of Health, Patient Centered Outcomes Research Institute, Department of Defense, Biogen, Sanofi Genzyme, and Novartis; personal fee for consulting from NeuroRx, for speaking from Sanofi Genzyme, and for licensing fee from Biogen., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: A combined resting state functional connectivity MRI (fcMRI) and diffusion tensor imaging (DTI) metric called structural and functional connectivity index (SFCI) was recently proposed for tracking disease status and progression in multiple sclerosis (MS). The metric combines fcMRI and transverse diffusivity (TD) along different functional pathways involved in principle symptomatic domains of MS. In a longitudinal study of patients with MS receiving the same MS therapy, initial worsening of transcallosal (TC) motor and frontoparietal (FP) cognitive networks, as measured by fcMRI and DTI over the first year was followed by stabilization in the second year of follow-up. In this study we have (i) probed relationships between individual and composite neurological measures of MS with SFCI and its individual components along TC motor and FP cognitive pathways and (ii) compared sensitivity of SFCI to treatment-induced longitudinal changes with each individual imaging measure., Methods: Twenty five patients with MS (15 female, age 42 ± 8 y) participated in this study and were scanned at 3 T whole body MRI scanner with diffusion tensor imaging (DTI) and resting-state functional connectivity MRI (fcMRI) scan protocol at baseline and 6, 12, 18 and 24 months after starting fingolimod. fcMRI and TD along TC and FP pathways were combined to form structural and functional connectivity index (SFCI) at each time point. Correlations between individual/combined neurological measures and individual imaging components/SFCI at baseline and were evaluated and compared. In addition, efficacies of individual and combined imaging metrics in tracking network integrity were compared., Results: Individual TD along the TC pathway was significantly inversely correlated with all individual/composite neurological scores. There were moderate correlations of TC and FP components of SFCI with most of the neurological scores, and the pathway-combined SFCI was significantly correlated with all neurological scores. Trend-level increases of both TC and FP fcMRI were observed during the second year of follow-up, both TC and FP TD increased significantly in the first year and then stabilized during the second year. A trend toward a decrease in combined imaging metrics along TC and FP were observed during the first year, followed by a trend toward an increase in these metrics during the second year, while a significant decrease in SFCI during the first year followed by a significant increase during the second year was observed., Conclusions: SFCI was more effective in tracking network integrity/disease progression than individual pathway-specific components, which supports its use as an imaging marker for MS disease status and progression., Competing Interests: Declaration of Competing Interest Pallab K. Bhattacharyya: past salary support from Novartis. Robert J. Fox: personal consulting fees from AB Science, Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Immunic, INmune Bio, Janssen, Lily, Novartis, Sanofi, Siemens, and TG Therapeutics, service on advisory committees for AB Science, Biogen, Immunic, Janssen, Novartis, and Sanofi, and clinical trial contract and research grant fundings from Biogen, Novartis, and Sanofi. Ken E. Sakaie: salary support from Novartis and Genzyme, consulting fees from INmune Bio. Tucker Harvey: none. Jim Bena: none. Paola Raska: none. Jian Lin: past salary support from Novartis. Mark J. Lowe: personal consulting fees from INmune Bio., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Transcranial direct current stimulation (tDCS) targeting the primary motor cortex is modestly effective for promoting upper-limb motor function following stroke. The premotor cortex (PMC) represents an alternative target based on its higher likelihood of survival and dense motor-network connections. Objective: The objective of this study was to determine whether ipsilesional PMC tDCS affects motor network functional connectivity (FC) in association with reduction in motor impairment, and to determine whether this relationship is influenced by baseline motor severity. Methods: Participants with chronic stroke were randomly assigned to receive active-PMC or sham-tDCS with rehabilitation for 5 weeks. Resting-state functional magnetic resonance imaging was acquired to characterize change in FC across motor-cortical regions. Results: Our results indicated that moderate-to-severe participants who received active-tDCS had greater increases in PMC-to-PMC interhemispheric FC compared to those who received sham; this increase was correlated with reduction in proximal motor impairment. There was also an increase in intrahemispheric dorsal premotor cortex-primary motor cortex FC across participants regardless of severity or tDCS group assignment; this increase was correlated with a reduction in proximal motor impairment in only the mild participants. Conclusions: Our findings have significance for developing targeted brain stimulation approaches. While participants with milder impairments may inherently recruit viable substrates within the ipsilesional hemisphere, stimulation of PMC may enhance interhemispheric FC in association with recovery in more impaired participants. Trial Registration: ClinicalTrials.gov Identifier: NCT01539096; Registration date: February 21, 2012.

Background and Purpose: The clinical correlation of gadolinium-based contrast agents (GBCAs) has not been well studied in multiple sclerosis (MS). We investigated the extent to which the number of GBCA administrations relates to self-reported disability and performance measures., Methods: A cohort of MS patients was analyzed in this retrospective observational study. The main outcome was the association between the cumulative number of GBCA exposures (linear or macrocyclic GBCA), Patient-Determined Disease Steps (PDDS), and measures of physical and cognitive performance (walking speed test, manual dexterity test [MDT], and processing speed test [PST]). The analysis was performed first cross-sectionally and then longitudinally., Results: The cross-sectional data included 1059 MS patients with a mean age of 44.0 years (standard deviation = 11.2). While the contrast ratio in globus pallidus weakly correlated with PDDS, MDT, and PST in a univariate correlational analysis (coefficients, 95% confidence interval [CI] = 0.11 [0.04, 0.18], 0.15 [0.08, 0.21], and -0.16 [-0.10, -0.23], respectively), the associations disappeared after covariate adjustment. A significant association was found between number of linear GBCA administrations and PDDS (coefficient [CI] = -0.131 [-0.196, -0.067]), and MDT associated with macrocyclic GBCA administrations (-0.385 [-0.616, -0.154]), but their signs indicated better outcomes in patients with greater GBCA exposures. The longitudinal data showed no significant detrimental effect of macrocyclic GBCA exposures., Conclusion: No detrimental effects were observed between GBCA exposure and self-reported disability and standardized objective measures of physical and cognitive performance. While several weak associations were found, they indicated benefit on these measures., (© 2022 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Background: The data burden for resting-state fMRI analysis rises with increasing resolutions available at ultrahigh fields. Therefore, a fundamental preprocessing step in brain network analysis is to reduce the data, usually by performing some kind of data parcellation. Most functional parcellations based on rsfMRI connectivity are synthesized from the dense connectome. In contrast, most network analyses begin by reducing each parcel to a single exemplar time series. This disconnect between parcel formation and usage assumes that parcel exemplars adequately represent their member voxels, which is not always the case for commonly used parcellations., New Method: We propose to parcellate the brain based on parcel cohesion, a measure of similarity between a parcel's exemplar and its member voxels. A spatially constrained agglomerative hierarchical framework is used to synthesize parcels based on a minimum cohesion threshold, rather than a predetermined number of parcels., Results: Cohesive parcellation generally results in more parcels than existing approaches. The number of parcels scales with the amount of smoothing in preprocessing, yet retains adequate information to extract common intrinsic functional networks., Comparison With Previous Methods: Cohesive parcellation performs better than several widely used anatomical, functional, and data-driven parcellations on the basis of parcel cohesion and comparably using several traditional measures of cluster validity., Conclusion: Cohesive parcellation ensures that the way parcels are synthesized directly corresponds to the way they are used in subsequent analyses. The resulting parcels are straightforward to interpret and optimal for downstream analysis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Hemodynamic cardiac and respiratory-cycle fluctuations are a source of unwanted non-neuronal signal components, often called physiologic noise, in resting state (rs-) fMRI studies. Here, we use image-based retrospective correction of physiological motion (RETROICOR) with externally measured physiologic signals to investigate cardiac and respiratory hemodynamic phase functions reflected in rs-fMRI data. We find that the cardiac phase function is time shifted locally, while the respiratory phase function is described as single, fixed phase form across the brain. In light of these findings, we propose an update to Physiologic EStimation by Temporal ICA (PESTICA), our publically available software package that estimates physiologic signals when external physiologic measures are not available. This update incorporates: 1) auto-selection of slicewise physiologic regressors and generation of physiologic fixed phase regressors with total slices/TR sampling rate, 2) Fourier series expansion of the cardiac fixed phase regressor to account for time delayed cardiac noise 3) removal of cardiac and respiratory noise in imaging data. We compare the efficacy of the updated method to RETROICOR., Competing Interests: Conflict of interest statement Wanyong Shin does not have any conflict of interest, Katherine A. Koenig does not have any conflict of interest, Mark J. Lowe does not have any conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Background and Objectives: Naming decline after left temporal lobe epilepsy (TLE) surgery is common and difficult to predict. Preoperative language fMRI may predict naming decline, but this application is still lacking evidence. We performed a large multicenter cohort study of the effectiveness of fMRI in predicting naming deficits after left TLE surgery., Methods: At 10 US epilepsy centers, 81 patients with left TLE were prospectively recruited and given the Boston Naming Test (BNT) before and ≈7 months after anterior temporal lobectomy. An fMRI language laterality index (LI) was measured with an auditory semantic decision-tone decision task contrast. Correlations and a multiple regression model were built with a priori chosen predictors., Results: Naming decline occurred in 56% of patients and correlated with fMRI LI ( r = -0.41, p < 0.001), age at epilepsy onset ( r = -0.30, p = 0.006), age at surgery ( r = -0.23, p = 0.039), and years of education ( r = 0.24, p = 0.032). Preoperative BNT score and duration of epilepsy were not correlated with naming decline. The regression model explained 31% of the variance, with fMRI contributing 14%, with a 96% sensitivity and 44% specificity for predicting meaningful naming decline. Cross-validation resulted in an average prediction error of 6 points., Discussion: An fMRI-based regression model predicted naming outcome after left TLE surgery in a large, prospective multicenter sample, with fMRI as the strongest predictor. These results provide evidence supporting the use of preoperative language fMRI to predict language outcome in patients undergoing left TLE surgery., Classification of Evidence: This study provides Class I evidence that fMRI language lateralization can help in predicting naming decline after left TLE surgery., (© 2022 American Academy of Neurology.)

Intimate partner violence (IPV) survivors frequently report face, head, and neck as their injury site. Many mild traumatic brain injuries (TBIs) are undiagnosed or underreported among IPV survivors while these injuries may be linked to changes in brain function or pathology. TBI sustained due to IPV often occurs over time and ranges in severity. The aim of this case-series study was to explore risk factors, symptoms, and brain changes unique to survivors of intimate partner violence with suspicion of TBI. This case-series exploratory study examines the potential relationships among IPV, mental health issues, and TBI. Participants of this study included six women: 3 women with a history of IPV without any experience of concussive blunt force to the head, and 3 women with a history of IPV with concussive head trauma. Participants completed 7T MRI of the brain, self-report psychological questionnaires regarding their mental health, relationships, and IPV, and the Structured Clinical Interview. MRI scans were analyzed for cerebral hemorrhage, white matter disturbance, and cortical thinning. Results indicated significant differences in resting-state connectivity among survivors of partner violence as well as differences in relationship dynamics and mental health symptoms. White matter hyperintensities are also observed among the survivors. Developing guidelines and recommendations for TBI-risk screening, referrals, and appropriate service provision is crucial for the effective treatment of TBI-associated IPV. Early and accurate characterization of TBI in survivors of IPV may relieve certain neuropsychological consequences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Karakurt, Whiting, Jones, Lowe and Rao.)

Purpose: Ultrahigh field (UHF) resting state functional magnetic resonance imaging (rsfMRI) has become increasingly available for clinical and basic research, bringing improvements in resolution and contrast over standard high field imaging. Despite these improvements, UHF connectivity studies present several challenges, including increased sensitivity to physiological confounds and a vastly increased data burden. We present a direct quantitative assessment of test-retest reliability of functional connectivity in several standard functional networks between subjects scanned at 3T and 7T., Methods: Five healthy subjects were scanned over four sessions each in a scan-rescan design at both 3T and 7T field strengths. Resting state fMRI data were segmented into four major intrinsic connectivity networks, and seed-based peak correlations within and between these networks examined. The reliability of these correlations was assessed using intra-class correlation coefficients (ICC)., Results: Across all data, over 4000 peak correlations were extracted for assessment. The reliability over all intrinsic networks was greater at 7T than 3T (median ICC 0.40 vs. 0.33, p ≤ 0.0014), with each network individually showing improvement. Inter-network reliability was stronger than intra-network reliability, but intra-network reliability showed the greatest improvement between field strengths., Conclusion: We demonstrate significantly increased reliability of resting state connectivity at UHF strengths over conventional field strengths using a novel hybrid seed-based analysis. This result adds to the growing body of work supporting the migration of functional imaging studies to UHFs., (© 2021 American Association of Physicists in Medicine.)

Cognitive impairment is a common symptom in individuals with Multiple Sclerosis (MS), but meaningful, reliable biomarkers relating to cognitive decline have been elusive, making evaluation of the impact of therapeutics on cognitive function difficult. Here, we combine pathway-based MRI measures of structural and functional connectivity to construct a metric of functional decline in MS. The Structural and Functional Connectivity Index (SFCI) is proposed as a simple, z-scored metric of structural and functional connectivity, where changes in the metric have a simple statistical interpretation and may be suitable for use in clinical trials. Using data collected at six time points from a 2-year longitudinal study of 20 participants with MS and 9 age- and sex-matched healthy controls, we probe two common symptomatic domains, motor and cognitive function, by measuring structural and functional connectivity in the transcallosal motor pathway and posterior cingulum bundle. The SFCI is significantly lower in participants with MS compared to controls (p = 0.009) and shows a significant decrease over time in MS (p = 0.012). The change in SFCI over two years performed favorably compared to measures of brain parenchymal fraction and lesion volume, relating to follow-up measures of processing speed (r = 0.60, p = 0.005), verbal fluency (r = 0.57, p = 0.009), and score on the Multiple Sclerosis Functional Composite (r = 0.67, p = 0.003). These initial results show that the SFCI is a suitable metric for longitudinal evaluation of functional decline in MS., Competing Interests: The authors have declared that no competing interests exist.

Background: Hardware changes can be an unavoidable confound in imaging trials. Understanding the impact of such changes may play an important role in the analysis of imaging data., Objective: To characterize the effect of equipment changes in a longitudinal, multi-site multiple sclerosis trial., Methods: Using data from a clinical trial in progressive multiple sclerosis, we explored how major changes in imaging hardware affected data. We analyzed the extent to which these changes affected imaging biomarkers and the estimated treatment effects by including such changes as a time-dependent covariate., Results: Significant differences whole brain atrophy (brain parenchymal fraction, BPF) and microstructure (transverse diffusivity, TD) between scans with and without changes were found and depended on the type of hardware change. A switch from GE HDxt to Siemens Skyra led to significant shifts in BPF (p < 0.04) and TD (p < 0.0001). However, we could not detect the influence of hardware changes on overall trial outcomes- differences between placebo and treatment arms in change over time of BPF and TD (p > 0.5)., Conclusions: The results suggest that differences among hardware types should be considered when planning and analyzing brain atrophy and diffusivity in a longitudinal clinical trial., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KS has received salary support from Genzyme and Novartis. RJF has received personal consulting fees from AB Science, Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, Sanofi, Teva, and TG Therapeutics, has served on advisory committees for Actelion, Biogen, Immunic, Novartis, and Sanofi, and has received clinical trial contract and research grant funding from Biogen and Novartis. JKF, JWY, KN, JD, MJL and PR have no relevant conflicts to disclose., (© The Author(s) 2021.)

Background: Ultra-high spatial resolution imaging of whole, ex vivo brains provides new opportunities to understand neurological disease. Recent work has demonstrated that 100 μm isotropic resolution can reveal anatomical details that are otherwise difficult to appreciate, but relied on fabrication facilities, fabrication expertise and programming expertise that is not available at clinical imaging sites that lack a dedicated research staff and resources. The purpose of this work is to describe a whole-brain, ultra-high spatial resolution imaging procedure for ex vivo specimens using equipment that can be purchased, assembled and implemented by most clinical sites. We provide enough detail so that other groups can readily reproduce the approach., Methods: A container and hardware for holding the brain fixed for long scan times was developed, along with a procedure for removing bubbles, which can cause artifact. Imaging was performed on a standard knee coil on a whole-body 7 T MRI at 170 μm isotropic spatial resolution. Five specimens were examined in Fomblin or formalin to evaluate consistency of image quality., Results: High quality images were acquired on all specimens. Anatomical features that are not readily observed at standard resolution, such as subthalamic nuclei, are readily observed. Disease-related features such as microscopic infarcts are also readily observed., Conclusions: Ultra-high spatial resolution, whole-brain images can be readily achieved without specialized hardware and software development. The approach is expected to be valuable as a complement to histology and to discover relationships among pathology located at different places throughout the brain., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Deep brain stimulation (DBS) for pain has largely been implemented in an uncontrolled manner to target the somatosensory component of pain, with research leading to mixed results. We have previously shown that patients with poststroke pain syndrome who were treated with DBS targeting the ventral striatum/anterior limb of the internal capsule (VS/ALIC) demonstrated a significant improvement in measures related to the affective sphere of pain. In this study, we sought to determine how DBS targeting the VS/ALIC modifies brain activation in response to pain., Materials and Methods: Five patients with poststroke pain syndrome who were blinded to DBS status (ON/OFF) and six age- and sex-matched healthy controls underwent functional magnetic resonance imaging (fMRI) measuring blood oxygen level-dependent activation in a block design. In this design, each participant received heat stimuli to the affected or unaffected wrist area. Statistical comparisons were performed using fMRI z-maps., Results: In response to pain, patients in the DBS OFF state showed significant activation (p < 0.001) in the same regions as healthy controls (thalamus, insula, and operculum) and in additional regions (orbitofrontal and superior convexity cortical areas). DBS significantly reduced activation of these additional regions and introduced foci of significant inhibitory activation (p < 0.001) in the hippocampi when painful stimulation was applied to the affected side., Conclusions: These findings suggest that DBS of the VS/ALIC modulates affective neural networks., (© 2020 International Neuromodulation Society.)

Background: Fingolimod, an oral drug, has been reported to reduce relapse rate in multiple sclerosis (MS). However disease progression may still occur in spite of control of inflammation. Functional imbalances within and between cerebral networks associated with disruption of structural and functional network integrity, have been reported in MS. An effective therapy is expected to stabilize such functional network integrity., Objective: The purpose of this study was to investigate changes in structural and resting-state functional connectivity of motor and cognitive networks, and associated changes in neurologic scores in MS, during 2 years of fingolimod therapy., Methods: Twenty five subjects with MS were recruited for this study. Subjects were scanned with diffusion tensor imaging (DTI) and resting-state functional connectivity MRI (fcMRI) scan protocol at 3 T with 6-month interval over a period of 2 years. Neurologic performance scores of motor and cognitive performances were also obtained., Results: DTI measures worsened during the 1st year and then stabilized; any trend of stabilization of fcMRI was delayed until the 2nd year. While motor performance did not change, cognitive performance showed improvement. Several baseline DTI measures correlated with relevant neurologic scores., Conclusion: Initial worsening of motor and cognitive network was reported after 1 year of treatment, but seems DTI and fcMRI measures seem to stabilize after around one year fingolimod therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To determine if the Argus II retinal prosthesis can operate during functional MRI (fMRI) and diffusion tensor imaging (DTI) acquisitions and if currents induced in the prosthesis by imaging are at safe levels., Materials and Methods: One Argus II retinal prosthesis was modified to enable current measurements during imaging. Active electronics were modified to enable operation during scans. Induced current was measured during diagnostic scans, which were previously shown to be safe for implanted patients, and during fMRI and DTI scans. All measurements were performed using an ASTM phantom to ensure reproducible placement., Results: The prosthesis was able to maintain communication with the external RF coil during the fMRI and DTI scans except briefly during pre-scans. Current levels induced during fMRI and DTI scans were consistently below those measured during diagnostic scans., Conclusions: fMRI and DTI may be safely performed while the Argus II retinal prosthesis is operating., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To define left temporal lobe regions where surgical resection produces a persistent postoperative decline in naming visual objects., Methods: Pre- and postoperative brain magnetic resonance imaging data and picture naming (Boston Naming Test) scores were obtained prospectively from 59 people with drug-resistant left temporal lobe epilepsy. All patients had left hemisphere language dominance at baseline and underwent surgical resection or ablation in the left temporal lobe. Postoperative naming assessment occurred approximately 7 months after surgery. Surgical lesions were mapped to a standard template, and the relationship between presence or absence of a lesion and the degree of naming decline was tested at each template voxel while controlling for effects of overall lesion size., Results: Patients declined by an average of 15% in their naming score, with wide variation across individuals. Decline was significantly related to damage in a cluster of voxels in the ventral temporal lobe, located mainly in the fusiform gyrus approximately 4-6 cm posterior to the temporal tip. Extent of damage to this region explained roughly 50% of the variance in outcome. Picture naming decline was not related to hippocampal or temporal pole damage., Significance: The results provide the first statistical map relating lesion location in left temporal lobe epilepsy surgery to picture naming decline, and they support previous observations of transient naming deficits from electrical stimulation in the basal temporal cortex. The critical lesion is relatively posterior and could be avoided in many patients undergoing left temporal lobe surgery for intractable epilepsy., (© 2020 International League Against Epilepsy.)

Background: Neck of Femur (NOF) fractures are a common injury in comorbid elderly patients which are associated with increased rates of morbidity and mortality following fracture. Because of their injury, patients can experience reductions in quality of life and independent living leading to transfer to nursing home or dependent levels of care. Numerous factors are associated with either complications or reductions in survival following fractured NOF. From the VISION cohort there is evidence that troponin elevation in the post-operative period following a diverse range of non-cardiac surgical procedures may lead to an increased risk of mortality in the absence of classical ischaemic or cardiac symptoms. The aim of this systematic review and meta-analysis is to validate the utility of perioperative troponin elevation as a prognostic indicator for mortality and cardiac morbidity in those with fractured NOF., Methods: The PRISMA guidelines for the conduct of meta-analyses were followed. An electronic search was conducted of the EMBASE, MEDLINE (Ovid) and Biosis databases. Studies were included for analysis if they stratified outcomes by perioperative troponin elevation in surgically managed fractured NOF and reported sufficient data on troponin elevation and mortality following surgery. Primary and secondary outcomes assessed were all-cause post-operative mortality and a composite measure of cardiac complications (myocardial infarction, cardiac failure and arrhythmia) respectively., Results: Eleven studies met inclusion criteria giving a total of 1363 patients. Overall, 497 patients (36.5%) experienced an elevation in troponin levels following surgery. Perioperative troponin elevation was significantly associated with all-cause mortality (OR 2.6; 95% CI 1.5 - 4.6; p <0.001) and cardiac complications (OR 7.4; 95% CI 3.5 - 15.8; p <0.001). Patient factors significantly associated with troponin elevation included pre-existing coronary artery disease, cardiac failure, hypertension, previous stroke and previous myocardial infarction., Conclusion: Perioperative troponin elevation is significantly associated with increased mortality and post-operative cardiac complications following fractured NOF and may be a useful prognostic indicator in these patients. Future research should further stratify patients by the magnitude of troponin elevation and further refine the risk factors., Competing Interests: Declaration of Competing Interest The senior author (NJL) has previously received honoraria, travel and accommodation expenses unrelated to the subject of this paper from Merck, Sharp and Dohme. No authors received any benefits for this study that would constitute a conflict of interest., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Episodic memory loss is one of the most common cognitive symptoms in patients with multiple sclerosis (MS), but the pathophysiology of this symptom remains unclear. Both the hippocampus and thalamus have been implicated in episodic memory and show regional atrophy in patients with MS., Objective: In this work, we used functional magnetic resonance imaging (fMRI) during a verbal episodic memory task, lesion load, and volumetric measures of the hippocampus and thalamus to assess the relative contributions to verbal and visual-spatial episodic memory., Methods: Functional activation, lesion load, and volumetric measures from 32 patients with MS and 16 healthy controls were used in a predictive analysis of episodic memory function., Results: After adjusting for disease duration, immediate recall performance on a visual-spatial episodic memory task was significantly predicted by hippocampal volume ( p < 0.003). Delayed recall on the same task was significantly predicted by volume of the left thalamus ( p < 0.003). For both memory measures, functional activation of the thalamus during encoding was more predictive than that of volume measures ( p < 0.002)., Conclusion: Our results suggest that functional activation may be useful as a predictive measure of episodic memory loss in patients with MS.

Purpose: To assess intrascanner repeatability and cross-scanner comparability for diffusion tensor imaging (DTI) metrics in a multicenter clinical trial., Methods: DTI metrics (including longitudinal diffusivity [LD], fractional anisotropy [FA], mean diffusivity [MD], and transverse diffusivity [TD]) from pyramidal tracts for healthy controls were calculated from images acquired on twenty-seven 3T MR scanners (Siemens and GE) with 6 different scanner models and 7 different software versions as part of the NN102/SPRINT-MS clinical trial. Each volunteer underwent two scanning sessions on the same scanner. Signal-to-noise ratio (SNR) and signal-to-noise floor ratio (SNFR) were also assessed., Results: DTI metrics showed good scan-rescan repeatability. There were no significant differences between scans and rescans in LD, FA, MD, or TD values. Although the cross-scanner coefficient of variation (CV) values for all DTI metrics were <5.7%, significant differences were observed for LD (p < 3.3e-5) and FA (p < 0.0024) when GE scanners were compared with Siemens scanners. Significant differences were also observed for SNR when comparing GE scanners and Siemens Skyra scanners (p < 1.4e-7) and when comparing Siemens Skyra scanners and TIM Trio scanners (p < 1.0e-10). Analysis of background signal also demonstrated differences between GE and Siemens scanners in terms of signal statistics. The measured signal intensity from a background noise region of interest was significantly higher for GE scanners than for Siemens scanners (p < 1.2e-12). Significant differences were also observed for SNFR when comparing GE scanners and Siemens Skyra scanners (p < 2.5e-11), GE scanners and Siemens Trio scanners (p < 7.5e-11), and Siemens Skyra scanners and TIM Trio scanners (p < 2.5e-9)., Conclusions: The good repeatability of the DTI metrics among the 27 scanners used in this study confirms the feasibility of combining DTI data from multiple centers using high angular resolution sequences. Our observations support the feasibility of longitudinal multicenter clinical trials using DTI outcome measures. The noise floor level and SNFR are important parameters that must be assessed when comparing studies that used different scanner models., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: There are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis., Methods: We enrolled patients with primary or secondary progressive multiple sclerosis in a phase 2 randomized trial of oral ibudilast (≤100 mg daily) or placebo for 96 weeks. The primary efficacy end point was the rate of brain atrophy, as measured by the brain parenchymal fraction (brain size relative to the volume of the outer surface contour of the brain). Major secondary end points included the change in the pyramidal tracts on diffusion tensor imaging, the magnetization transfer ratio in normal-appearing brain tissue, the thickness of the retinal nerve-fiber layer, and cortical atrophy, all measures of tissue damage in multiple sclerosis., Results: Of 255 patients who underwent randomization, 129 were assigned to ibudilast and 126 to placebo. A total of 53% of the patients in the ibudilast group and 52% of those in the placebo group had primary progressive disease; the others had secondary progressive disease. The rate of change in the brain parenchymal fraction was -0.0010 per year with ibudilast and -0.0019 per year with placebo (difference, 0.0009; 95% confidence interval, 0.00004 to 0.0017; P=0.04), which represents approximately 2.5 ml less brain-tissue loss with ibudilast over a period of 96 weeks. Adverse events with ibudilast included gastrointestinal symptoms, headache, and depression., Conclusions: In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression. (Funded by the National Institute of Neurological Disorders and Stroke and others; NN102/SPRINT-MS ClinicalTrials.gov number, NCT01982942 .).

Background: Dorsal raphe nucleus (DRN) and ventral tegmental area (VTA) are major brainstem monamine nuclei consisting of serotonin and dopamine neurons respectively. Animal studies show that firing patterns in both nuclei are altered when animals exhibit depression like behaviors. Functional MRI studies in humans have shown reduced VTA activation and DRN connectivity in depression. This study for the first time aims at investigating the functional integrity of local neuronal firing concurrently in both the VTA and DRN in vivo in humans using spectral analysis of resting state low frequency fluctuation fMRI. Method: A total of 97 medication-free subjects-67 medication-free young patients (ages 18-30) with major depressive disorder and 30 closely matched healthy controls were included in the study to detect aberrant dynamics in DRN and VTA. For the investigation of altered localized dynamics we conducted power spectral analysis and above this spectral cross correlation between the two groups. Complementary to this, spectral dependence of permutation entropy, an information theoretical measure, was compared between groups. Results: Patients displayed significant spectral slowing in VTA vs. controls ( p = 0.035, corrected). In DRN, spectral slowing was less pronounced, but the amount of slowing significantly correlated with 17-item Hamilton Depression Rating scores of depression severity ( p = 0.038). Signal complexity as assessed via permutation entropy showed spectral alterations inline with the results on spectral slowing. Conclusion: Our results indicate that altered functional dynamics of VTA and DRN in depression can be detected from regional fMRI signal. On this basis, impact of antidepressant treatment and treatment response can be assessed using these markers in future studies.

As the use of ultra-high field (UHF; ≥7T) magnetic resonance (MR) imaging expands, there is an increasing need to establish high-resolution MR imaging protocols for patients with neurological disease. Magnetization transfer (MT) imaging has been used to provide information about changes in the magnitude of the restricted protons that are caused by tissue damages. Several studies have found that MTR has a good sensitivity to measure changes in myelin concentration within the brain. Because of the much higher specific absorption rate (SAR) of tissue and longer acquisition time required for UHF, however, in-vivo studies using conventional pulsed MT sequences at UHF have not been well utilized. In this study, we introduce a new MT data acquisition approach using a 7T MR system, variable density magnetization transfer (vdMT) imaging, which can be reasonably included in a routine patient scan protocol with a much shorter scan time and reduced discomfort to the patient. To reduce SAR and scan time while maintaining at least similar MTR image quality to that obtained with the conventional method, a higher density of MT RF pulses was applied in the center of k-space, and sparsely applied MT RF pulses were used in the outer part of k-space. The fraction of k-space receiving 100% MT RF density and TR were optimized based on in-vivo ROI analysis, and results were confirmed with high-resolution MTR map using a vdMT approach from healthy controls and patients with multiple sclerosis (MS). The experimental results confirmed that vdMT imaging can cover a whole brain volume in an acceptable scan time for routine patient scans while providing MTR image quality at least similar to that obtained with conventional MT imaging (correlation coefficient=0.95 in an agar-gel phantom [MT offset frequency=1kH], 0.90 in a postmortem MS brain, and 0.85 in the 4 healthy volunteers). MS lesions were associated with signal reductions in the postmortem MS brains and in the patients with MS. In this study, we have described a new approach for acquiring high-resolution MTR map of the whole brain volume using 7T MR imaging. This vdMT method provides similar image quality to that obtained with the conventional method, and shortens the scan time by reducing SAR. These results suggest that vdMT approach is a method that could be used for UHF scans of patients with neurological disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To explore the relative robustness of functional MRI (fMRI) activation volume and blood oxygen level-dependent (BOLD) signal change as fMRI metric, and to study the effect of relative robustness on the correlation between fMRI activation and cortical gamma amino butyric acid (GABA) in healthy controls and patients with multiple sclerosis (MS)., Methods: fMRI data were acquired from healthy controls and patients with MS, with the subjects peforming self paced bilateral finger tapping in block design. GABA spectroscopy was performed with voxel placed on the area of maximum activation during fMRI. Activation volume and BOLD signal changes at primary motor cortex (M1), as well as GABA concentration were calculated for each patient., Results: Activation volume correlated with BOLD signal change in healthy controls, but no such correlation was observed in patients with MS. This difference was likely the result of higher intersubject noise variance in the patient population. GABA concentration correlated with M1 activation volume in patients but not in controls, and did not correlate with any fMRI metric in patients or controls., Conclusion: Our data suggest that activation volume is a more robust measure than BOLD signal change in a group with high intersubject noise variance as in patients with MS. Additionally, this study demonstrated difference in correlation behavior between GABA concentration and the 2 fMRI metrics in patients with MS, suggesting that GABA - activation volume correlation is more appropriate measure in the patient group., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The pain matrix is comprised of an extensive network of brain structures involved in sensory and/or affective information processing. The thalamus is a key structure constituting the pain matrix. The thalamus serves as a relay center receiving information from multiple ascending pathways and relating information to and from multiple cortical areas. However, it is unknown how thalamocortical networks specific to sensory-affective information processing are functionally integrated. Here, in a proof-of-concept study in healthy humans, we aimed to understand this connectivity using transcranial direct current stimulation (tDCS) targeting primary motor (M1) or dorsolateral prefrontal cortices (DLPFC). We compared changes in functional connectivity (FC) with DLPFC tDCS to changes in FC with M1 tDCS. FC changes were also compared to further investigate its relation with individual's baseline experience of pain. We hypothesized that resting-state FC would change based on tDCS location and would represent known thalamocortical networks. Ten right-handed individuals received a single application of anodal tDCS (1 mA, 20 min) to right M1 and DLPFC in a single-blind, sham-controlled crossover study. FC changes were studied between ventroposterolateral (VPL), the sensory nucleus of thalamus, and cortical areas involved in sensory information processing and between medial dorsal (MD), the affective nucleus, and cortical areas involved in affective information processing. Individual's perception of pain at baseline was assessed using cutaneous heat pain stimuli. We found that anodal M1 tDCS and anodal DLPFC tDCS both increased FC between VPL and sensorimotor cortices, although FC effects were greater with M1 tDCS. Similarly, anodal M1 tDCS and anodal DLPFC tDCS both increased FC between MD and motor cortices, but only DLPFC tDCS modulated FC between MD and affective cortices, like DLPFC. Our findings suggest that M1 stimulation primarily modulates FC of sensory networks, whereas DLPFC stimulation modulates FC of both sensory and affective networks. Our findings when replicated in a larger group of individuals could provide useful evidence that may inform future studies on pain to differentiate between effects of M1 and DLPFC stimulation. Notably, our finding that individuals with high baseline pain thresholds experience greater FC changes with DLPFC tDCS implies the role of DLPFC in pain modulation, particularly pain tolerance.

Knowledge of acoustic properties is crucial for ultrasonic or sonic imaging and signal detection in nondestructive evaluation (NDE), medical imaging, and seismology. Accurately and reliably obtaining these is particularly challenging for the NDE of high-density polyethylene (HDPE), such as is used in many water or gas pipes, because the properties vary greatly with frequency, temperature, direction and spatial location. Therefore the work reported here was undertaken in order to establish a basis for such a multiparameter description. The approach is general but the study specifically addresses HDPE and includes measured data values. Applicable to any such multiparameter acoustic properties dataset is a devised regression method that uses a neural network algorithm. This algorithm includes constraints to respect the Kramers-Kronig causality relationship between speed and attenuation of waves in a viscoelastic medium. These constrained acoustic properties are fully described in a multidimensional parameter space to vary with frequency, depth, temperature, and direction. The resulting uncertainties in acoustic properties dependence on the above variables are better than 4% and 2%, respectively, for attenuation and phase velocity and therefore can prevent major defect imaging errors.

A phantom-based quality assurance (QA) protocol was developed for a multicenter clinical trial including high angular resolution diffusion imaging (HARDI). A total of 27 3T MR scanners from 2 major manufacturers, GE (Discovery and Signa scanners) and Siemens (Trio and Skyra scanners), were included in this trial. With this protocol, agar phantoms doped to mimic relaxation properties of brain tissue are scanned on a monthly basis, and quantitative procedures are used to detect spiking and to evaluate eddy current and Nyquist ghosting artifacts. In this study, simulations were used to determine alarm thresholds for minimal acceptable signal-to-noise ratio (SNR). Our results showed that spiking artifact was the most frequently observed type of artifact. Overall, Trio scanners exhibited less eddy current distortion than GE scanners, which in turn showed less distortion than Skyra scanners. This difference was mainly caused by the different sequences used on these scanners. The SNR for phantom scans was closely correlated with the SNR from volunteers. Nearly all of the phantom measurements with artifact-free images were above the alarm threshold, suggesting that the scanners are stable longitudinally. Software upgrades and hardware replacement sometimes affected SNR substantially but sometimes did not. In light of these results, it is important to monitor longitudinal SNR with phantom QA to help interpret potential effects on in vivo measurements. Our phantom QA procedure for HARDI scans was successful in tracking scanner performance and detecting unwanted artifacts., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The scattering treated here arises when elastic waves propagate within a heterogeneous medium defined by random spatial fluctuation of its elastic properties. Whereas classical analytical studies are based on lower-order scattering assumptions, numerical methods conversely present no such limitations by inherently incorporating multiple scattering. Until now, studies have typically been limited to two or one dimension, however, owing to computational constraints. This article seizes recent advances to realize a finite-element formulation that solves the three-dimensional elastodynamic scattering problem. The developed methodology enables the fundamental behaviour of scattering in terms of attenuation and dispersion to be studied. In particular, the example of elastic waves propagating within polycrystalline materials is adopted, using Voronoi tessellations to randomly generate representative models. The numerically observed scattering is compared against entirely independent but well-established analytical scattering theory. The quantitative agreement is found to be excellent across previously unvisited scattering regimes; it is believed that this is the first quantitative validation of its kind which provides significant support towards the existence of the transitional scattering regime and facilitates future deployment of numerical methods for these problems.

Background and Purpose: DTI is an MR imaging measure of brain tissue integrity. Little is known regarding the long-term longitudinal evolution of lesional and nonlesional tissue DTI parameters in multiple sclerosis and the present study examines DTI evolution over 4 years., Materials and Methods: Twenty-one patients with multiple sclerosis were imaged for up to 48 months after starting natalizumab therapy. Gadolinium-enhancing lesions at baseline, chronic T2 lesions, and normal-appearing white matter were followed longitudinally. T2 lesions were subclassified as black holes and non-black holes. Within each ROI, the average values of DTI metrics were derived by using Analysis of Functional Neuro Images software. The longitudinal trend in DTI metrics was estimated by using a mixed-model regression analysis., Results: A significant increase was observed for axial diffusivity (P < .001) in gadolinium-enhancing lesions and chronic T2 lesions during 4 years. No significant change in radial diffusivity either in normal-appearing white matter or lesional tissue was observed. The evolution of axial diffusivity was different in gadolinium-enhancing lesions (P < .001) and chronic T2 lesions (P = .02) compared with normal-appearing white matter., Conclusions: An increase in axial diffusion in both gadolinium-enhancing lesions and T2 lesions may relate to the complex evolution of chronically demyelinated brain tissue. Pathologic changes in normal-appearing white matter are likely more subtle than in lesional tissue and may explain the stability of these measures with DTI., (© 2017 by American Journal of Neuroradiology.)

Multilayered plate and shell structures play an important role in many engineering settings where, for instance, coated pipes are commonplace such as in the petrochemical, aerospace, and power generation industries. There are numerous demands, and indeed requirements, on nondestructive evaluation (NDE) to detect defects or to measure material properties using guided waves; to choose the most suitable inspection approach, it is essential to know the properties of the guided wave solutions for any given multilayered system and this requires dispersion curves computed reliably, robustly, and accurately. Here, the circumstances are elucidated, and possible layer combinations, under which guided wave solutions, in multilayered systems composed of generally anisotropic layers in flat and cylindrical geometries, have specific properties of coupling and parity; the partial wave decomposition of the wave field is utilised to unravel the behaviour. A classification into five families is introduced and the authors claim that this is the fundamental way to approach generally anisotropic waveguides. This coupling and parity provides information to be used in the design of more efficient and robust dispersion curve tracing algorithms. A critical benefit is that the analysis enables the separation of solutions into categories for which dispersion curves do not cross; this allows the curves to be calculated simply and without ambiguity.

The application of long-range guided-wave testing to pipes embedded in concrete results in unpredictable test-ranges. The influence of the circumferential extent of the embedding-concrete around a steel pipe on the guided wave propagation is investigated. An analytical model is used to study the axisymmetric fully embedded pipe case, while explicit finite-element and semi-analytical finite-element simulations are utilised to investigate a partially embedded pipe. Model predictions and simulations are compared with full-scale guided-wave tests. The transmission-loss of the T(0,1)-mode in an 8 in. steel pipe fully embedded over an axial length of 0.4 m is found to be in the range of 32-36 dB while it reduces by a factor of 5 when only 50% of the circumference is embedded. The transmission-loss in a fully embedded pipe is mainly due to attenuation in the embedded section while in a partially embedded pipe it depend strongly on the extent of mode-conversion at entry to the embedded-section; low loss modes with energy concentrated in the region of the circumference not-covered with concrete have been identified. The results show that in a fully embedded pipe, inspection beyond a short distance will not be possible, whereas when the concrete is debonded over a fraction of the pipe circumference, inspection of substantially longer lengths may be possible.

Elastic waves scatter when the wavelength becomes comparable to random spatial fluctuations in the elastic properties of the propagation medium. It is postulated that within the long-wavelength Rayleigh regime, the scattering induced attenuation obeys a D = 1,2,3 dimensional dependence on wavenumber, k D +1 , whilst within the shorter-wavelength stochastic regime, it becomes independent of the dimensions and thus varies as k 2 . These predictions are verified numerically with a recently developed finite element method in three dimensions (3D), two dimensions (2D), and one dimension (1D), for the example of ultrasonic waves propagating within polycrystalline materials. These findings are thought to be practically useful given the increasing uptake of numerical methods to study highly scattering environments which exhibit multiple scattering, but often remain limited to 2D given computational constraints. It is hoped that these results lay the groundwork for eventually producing computationally efficient 2D simulations that are representative of 3D.

Corrosion damage in inaccessible regions presents a significant challenge to the petrochemical industry, and determining the remaining wall thickness is important to establish the remaining service life. Guided wave tomography is one solution to this and involves transmitting Lamb waves through the area of interest and, subsequently, using the received signals to reconstruct a thickness map of the remaining wall thickness. This avoids the need to access all points on the surface, making the technique well suited to inspection for areas with restricted access. The influence of these areas onto the ability to detect and size surface conditions, such as corrosion damage, using guided wave tomography is assessed. For that, a guided wave tomography system is employed, which is based on low-frequency A0 Lamb waves that are excited and detected with two arrays of electromagnetic acoustic transducers. Two different defect depths are considered with different contrasts relative to the nominal wall thickness, both of which are smoothly varying and well-defined. The influence of areas with restricted surface access, support locations, pipe clamps, and STOPAQ(R) coatings is experimentally tested, and their influence assessed through comparison to a baseline reconstruction without the respective restriction in place, demonstrating only a small influence on the detected value of the remaining wall thickness.

Purpose: While MP2RAGE shows the potential to generate B1 insensitive T1 contrast, the long TR of MP2RAGE (≥6s at 7T) is essential to provide the large dynamic range of apparent T1 relaxation for dual inversion time acquisitions. We present a 2 direction (2D) accelerated MP2RAGE, which provides an increased flip angle while maintaining similar dynamic recovery as 1D accelerated MP2RAGE., Method: Simulations were conducted to optimize 2D accelerated MP2RAGE parameters and healthy subjects were scanned with 1D and 2D accelerated MP2RAGE at 7T. Images were compared visually and contrast to noise (CNR) between brain tissues was measured., Result: Simulations showed that CNR is primarly determined by the TR, followed by the number of the first partition encoding steps in MP2RAGE. Keeping TR constant, a smaller number of partition encoding steps increases the achievable maximal CNR. In-vivo 2D MP2RAGE improves CNR between white and gray matters by 9% when compared to 1D accelerated MP2RAGE with identical voxel size., Conclusion: We presented 2D accelated MP2RAGE at 7T with the increased flip angle. We show that this leads to CNR improvement, and consequently a reduction of scan time to be compared to 1D accelerated MP2RAGE., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A three-dimensional generic hybrid model is developed for the simulation of elastic waves in applications in Non- Destructive Evaluation that efficiently links different solution strategies but, crucially, is independent of the particular schemes employed. This is an important step forward in facilitating rapid and accurate large-scale simulations and this advances the twodimensional generic hybrid methodology recently developed by the authors. The hybrid model provides an efficient and effective tool for creating highly accurate simulations that model the wave propagation and scattering, enabling the interpretation of inspection data; the new methodology is verified against other numerical simulations. Furthermore, its deployment to simulate wave reflection from side-drilled holes, comparing the results with experimental measurements, provides a realistic demonstration as well as further validation.

Introduction: Studies in animal models of Parkinson's disease (PD) have suggested that the rate of exercise performance is important in treatment efficacy and neuroprotection. In humans with PD, lower-extremity forced-exercise (FE) produced global improvements in motor symptoms based on clinical ratings and biomechanical measures of upper extremity function., Methods: fMRI was used to compare the underlying changes in brain activity in PD patients following the administration of anti-parkinsonian medication and following a session of FE., Results: Nine individuals with PD completed fMRI scans under each condition: off anti-PD medication, on anti-PD medication, and off medication + FE. Unified Parkinson's Disease Rating Motor Scale scores improved by 50% in the FE condition compared to the off-medication condition. The pattern of fMRI activation after FE was similar to that seen with anti-PD medication. Direct comparison of the fMRI activation patterns showed high correlation between FE and anti-PD medication., Conclusion: These findings suggest that medication and FE likely utilize the same pathways to produce symptomatic relief in individuals with PD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: Connectionist theories of brain function took hold with the seminal contributions of Norman Geschwind a half century ago. Modern neuroimaging techniques have expanded the scientific interest in the study of brain connectivity to include the intact as well as disordered brain., Methods: In this review, we describe the most common techniques used to measure functional and structural connectivity, including resting state functional MRI, diffusion MRI, and electroencephalography and magnetoencephalography coherence. We also review the most common analytical approaches used for examining brain interconnectivity associated with these various imaging methods., Results: This review presents a critical analysis of the assumptions, as well as methodological limitations, of each imaging and analysis approach., Conclusions: The overall goal of this review is to provide the reader with an introduction to evaluating the scientific methods underlying investigations that probe the human connectome.

Forced-rate lower-extremity exercise has recently emerged as a potential safe and low-cost therapy for Parkinson's disease (PD). The efficacy is believed to be dependent on pedaling rate, with rates above the subjects' voluntary exercise rates being most beneficial. In this study, we use functional connectivity magnetic resonance imaging (MRI) to further elucidate the mechanism underlying this effect. Twenty-seven PD patients were randomized to complete 8 weeks of forced-rate exercise (FE) or voluntary-rate exercise (VE). Exercise was delivered using a specialized stationary bicycle, which can augment patients' voluntary exercise rates. The FE group received assistance from the cycle. Imaging was conducted at baseline, end of therapy, and after 4 weeks of follow-up. Functional connectivity (FC) was determined via seed-based correlation analysis, using activation-based seeds in the primary motor cortex (M1). The change in FC after exercise was compared using linear correlation with pedaling rate. Results of the correlation analysis showed a strong positive correlation between pedaling rate and change in FC from the most affected M1 to the ipsilateral thalamus. This effect persisted after 4 weeks of follow-up. These results indicate that a plausible mechanism for the therapeutic efficacy of high-rate exercise in PD is that it improves thalamo-cortical connectivity.

Background: Imaging can provide noninvasive neural markers of disease progression in multiple sclerosis (MS) that are related to behavioral and cognitive symptoms. Past work suggests that diffusion tensor imaging (DTI) provides a measure of white matter pathology, including demyelination and axonal counts., Objectives: In the current study, the authors investigate the relationship of DTI measures in the cingulum bundle to common deficits in MS, including episodic memory, working memory, and information processing speed., Methods: Fifty-seven patients with MS and 17 age- and education-matched controls underwent high-spatial resolution diffusion scans and cognitive testing. Probabilistic tracking was used to generate tracks from the posterior cingulate cortex to the entorhinal cortex., Results: Radial and axial diffusivity values were significantly different between patients and controls (p < 0.031), and in patients bilateral diffusion measures were significantly related to measures of episodic memory and speed of processing (p < 0.033)., Conclusions: The tractography-based measures of posterior cingulum integrity reported here support further development of DTI as a viable measure of axonal integrity and cognitive function in patients with MS., (© The Author(s), 2015.)

Finite element modelling is a promising tool for further progressing the development of ultrasonic non-destructive evaluation of polycrystalline materials. Yet its widespread adoption has been held back due to a high computational cost, which has restricted current works to relatively small models and to two dimensions. However, the emergence of sufficiently powerful computing, such as highly efficient solutions on graphics processors, is enabling a step improvement in possibilities. This article aims to realise those capabilities to simulate ultrasonic scattering of longitudinal waves in an equiaxed polycrystalline material in both two (2D) and three dimensions (3D). The modelling relies on an established Voronoi approach to randomly generate a representative grain morphology. It is shown that both 2D and 3D numerical data show good agreement across a range of scattering regimes in comparison to well-established theoretical predictions for attenuation and phase velocity. In addition, 2D parametric studies illustrate the mesh sampling requirements for two different types of mesh to ensure modelling accuracy and present useful guidelines for future works. Modelling limitations are also shown. It is found that 2D models reduce the scattering mechanism in the Rayleigh regime.

Defects which possess rough surfaces greatly affect ultrasonic wave scattering behavior, usually reducing the magnitude of reflected signals. Understanding and accurately predicting the influence of roughness on signal amplitudes is crucial, especially in nondestructive evaluation (NDE) for the inspection of safety-critical components. An extension of Kirchhoff theory has formed the basis for many practical applications; however, it is widely recognized that these predictions are pessimistic because of analytical approximations. A numerical full-field modeling approach does not fall victim to such limitations. Here, a finite element (FE) modeling approach is used to develop a realistic methodology for the prediction of expected backscattering from rough defects. The ultrasonic backscatter from multiple rough surfaces defined by the same statistical class is calculated for normal and oblique incidence. Results from FE models are compared with Kirchhoff theory predictions and experimental measurements to establish confidence in the new approach. At lower levels of roughness, excellent agreement is observed between Kirchhoff theory, FE, and experimental data, whereas at higher values, the pessimism of Kirchhoff theory is confirmed. An important distinction is made between the total, coherent, and diffuse signals and it is observed, significantly, that the total signal amplitude is representative of the information obtained during an inspection. This analysis provides a robust basis for a less sensitive, yet safe, threshold for inspection of rough defects.

It is challenging to inspect austenitic welds nondestructively using ultrasonic waves because the spatially varying elastic anisotropy of weld microstructures can lead to the deviation of ultrasound. Models have been developed to predict the propagation of ultrasound in such welds once the weld stiffness heterogeneity is known. Consequently, it is desirable to have a means of measuring the variation in elastic anisotropy experimentally so as to be able to correct for deviations in ultrasonic pathways for the improvement of weld inspection. This paper investigates the use of external nonintrusive ultrasonic array measurements to construct such weld stiffness maps, representing the orientation of the stiffness tensor according to location in the weld cross section. An inverse model based on a genetic algorithm has been developed to recover a small number of key parameters in an approximate model of the weld map, making use of ultrasonic array measurements. The approximate model of the weld map uses the Modeling of anIsotropy based on Notebook of Arcwelding (MINA) formulation, which is one of the representations that has been proposed by other researchers to provide a simple, yet physically based, description of the overall variations of orientations of the stiffness tensors over the weld cross section. The choice of sensitive ultrasonic modes as well as the best monitoring positions have been discussed to achieve a robust inversion. Experiments have been carried out on a 60-mm-thick multipass tungsten inert gas (TIG) weld to validate the findings of the modeling, showing very good agreement. This work shows that ultrasonic array measurements can be used on a single side of a butt-welded plate, such that there is no need to access the remote side, to construct an approximate but useful weld map of the spatial variations in anisotropic stiffness orientation that occur within the weld.

Mild to moderate traumatic brain injury (TBI) due to blast exposure is frequently diagnosed in veterans returning from the wars in Iraq and Afghanistan. However, it is unclear whether neural damage resulting from blast TBI differs from that found in TBI due to blunt-force trauma (e.g., falls and motor vehicle crashes). Little is also known about the effects of blast TBI on neural networks, particularly over the long term. Because impairment in working memory has been linked to blunt-force TBI, the present functional magnetic resonance imaging (fMRI) study sought to investigate whether brain activation in response to a working memory task would discriminate blunt-force from blast TBI. Twenty-five veterans (mean age = 29.8 years, standard deviation = 6.01 years, 1 female) who incurred TBI due to blast an average of 4.2 years prior to enrollment and 25 civilians (mean age = 27.4 years, standard deviation = 6.68 years, 4 females) with TBI due to blunt-force trauma performed the Sternberg Item Recognition Task while undergoing fMRI. The task involved encoding 1, 3, or 5 items in working memory. A group of 25 veterans (mean age = 29.9 years, standard deviation = 5.53 years, 0 females) and a group of 25 civilians (mean age = 27.3 years, standard deviation = 5.81 years, 0 females) without history of TBI underwent identical imaging procedures and served as controls. Results indicated that the civilian TBI group and both control groups demonstrated a monotonic relationship between working memory set size and activation in the right caudate during encoding, whereas the blast TBI group did not (p < 0.05, corrected for multiple comparisons using False Discovery Rate). Blast TBI was also associated with worse performance on the Sternberg Item Recognition Task relative to the other groups, although no other group differences were found on neuropsychological measures of episodic memory, inhibition, and general processing speed. These results could not be attributed to caudate atrophy or the presence of PTSD symptoms. Our results point to a specific vulnerability of the caudate to blast injury. Changes in activation during the Sternberg Item Recognition Task, and potentially other tasks that recruit the caudate, may serve as biomarkers for blast TBI.

Guided waves are now well established for some applications in the non-destructive evaluation of structures and offer potential for deployment in a vast array of other cases. For their development, it is important to have reliable and accurate information about the modes that propagate for particular waveguide structures. Essential information that informs choices of mode transducer, operating frequencies, and interpretation of signals, among other issues, is provided by the dispersion curves of different modes within various combinations of geometries and materials. In this paper a spectral collocation method is successfully used to handle the more complicated and realistic waveguide problems that are required in non-destructive evaluation; many pitfalls and limitations found in root-finding routines based on the partial wave method are overcome by using this approach. The general cases presented cover anisotropic homogeneous perfectly elastic materials in flat and cylindrical geometry. Non-destructive evaluation applications include complex waveguide structures, such as single or multi-layered fiber composites, lined, bonded and buried structures. For this reason, arbitrarily multi-layered systems with both solid and fluid layers are also addressed as well as the implementation of interface models of imperfect boundary conditions between layers.