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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.)

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 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.)

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.)

Background: The events leading up to the development of new multiple sclerosis (MS) lesions on conventional imaging are unknown. The purpose of this study is to use diffusion tensor imaging (DTI) to investigate prelesional changes in MS to better understand the pathological changes that lead to lesion development., Methods: Twenty-one patients with relapsing MS starting natalizumab therapy underwent serial DTI for 12-18 months. Regions of interest were outlined within normal-appearing white matter and new gadolinium-enhancing lesions that developed over the course of the study. Images from all time points were coregistered and nonparametric regression was used to assess DTI changes prior to lesion appearance., Results: A total of 31 newly enhancing lesions were identified. Significant changes in transverse diffusivity (TD) (P < .001), longitudinal diffusivity (LD) (P = .025), mean diffusivity (MD) (P < .001), and fractional anisotropy (FA) (P = .04) were observed prior to gadolinium enhancement. A progressive increase in TD and LD occurred up to 10 months prior to lesion development. DTI measures in normal appearing white matter remained unchanged over the study period., Conclusions: A significant change in diffusion measures can be seen prior to gadolinium enhancement. Changes in TD drove changes in FA and MD, providing evidence for impaired myelin integrity prior to gadolinium enhancement. DTI may be a sensitive measure for early detection of inflammatory disease activity in MS., (Copyright © 2014 by the American Society of Neuroimaging.)

Purpose: To assess for associations between hippocampal atrophy and measures of cognitive function, hippocampal magnetization transfer ratio (MTR), and diffusion measures of the fornix, the largest efferent white matter tract from the hippocampus, in patients with multiple sclerosis (MS) and controls., Materials and Methods: A total of 53 patients with MS and 20 age- and sex-matched healthy controls participated in cognitive testing and scanning including high spatial-resolution diffusion imaging and a T1-MPRAGE scan. Hippocampal volume and fornicial thickness measures were calculated and compared to mean values of fornicial transverse diffusivity, mean diffusivity, longitudinal diffusivity, fractional anisotropy, mean hippocampal MTR, and scores on measures of episodic memory, processing speed, and working memory tasks., Results: In patients with MS, hippocampal volume was significantly related to fornicial diffusion measures (P<7×10(-4)) and to measures of verbal (P=0.030) and visual spatial (P=0.004) episodic memory and a measure of information processing speed (P<0.037)., Discussion: These results highlight the role of the hippocampus in cognitive dysfunction in patients with MS and suggest that measures of hippocampal atrophy could be used to capture aspects of disease progression., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A number of studies are now collecting diffusion tensor imaging (DTI) data across sites. While the reliability of anatomical images has been established by a number of groups, the reliability of DTI data has not been studied as extensively. In this study, five healthy controls were recruited and imaged at eight imaging centers. Repeated measures were obtained across two imaging protocols allowing intra-subject and inter-site variability to be assessed. Regional measures within white matter were obtained for standard rotationally invariant measures: fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity. Intra-subject coefficient of variation (CV) was typically <1% for all scalars and regions. Inter-site CV increased to ~1%-3%. Inter-vendor variation was similar to inter-site variability. This variability includes differences in the actual implementation of the sequence.