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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.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.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.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.

Background and ObjectivesNaming 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.MethodsAt 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.ResultsNaming 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.DiscussionAn 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 EvidenceThis study provides Class I evidence that fMRI language lateralization can help in predicting naming decline after left TLE surgery.

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

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.

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.

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.

Objective Ultra-high-field 7-Tesla (7T) magnetic resonance imaging (MRI) offers increased signal-to-noise and contrast-to-noise ratios, which may improve visualization of cortical malformations. We aim to assess the clinical value of in vivo structural 7T MRI and its post-processing for the noninvasive identification of epileptic brain lesions in patients with pharmacoresistant epilepsy and nonlesional 3T MRI who are undergoing presurgical evaluation. Methods Sixty-seven patients were included who had nonlesional 3T MRI by official radiology report. Epilepsy protocols were used for the 3T and 7T acquisitions. Post-processing of the 7T T1-weighted magnetization-prepared two rapid acquisition gradient echoes sequence was performed using the morphometric analysis program (MAP) with comparison to a normal database consisting of 50 healthy controls. Review of 7T was performed by an experienced board-certified neuroradiologist and at the multimodal patient management conference. The clinical significance of 7T findings was assessed based on intracranial electroencephalography (ICEEG) ictal onset, surgery, postoperative seizure outcomes, and histopathology. Results Unaided visual review of 7T detected previously unappreciated subtle lesions in 22% (15/67). When aided by 7T MAP, the total yield increased to 43% (29/67). The location of the 7T-identified lesion was identical to or contained within the ICEEG ictal onset in 13 of 16 (81%). Complete resection of the 7T-identified lesion was associated with seizure freedom (P = .03). Histopathology of the 7T-identified lesions encountered mainly focal cortical dysplasia (FCD). 7T MAP yielded 25% more lesions (6/24) than 3T MAP, and showed improved conspicuity in 46% (11/24). Significance Our data suggest a major benefit of 7T with post-processing for detecting subtle FCD lesions for patients with pharmacoresistant epilepsy and nonlesional 3T MRI.

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.

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.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.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.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.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.

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.

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 0.5). 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.

Background Conventional MRI can be limited in detecting subtle epileptic lesions or identifying active/epileptic lesions among widespread, multifocal lesions. Purpose We developed a high-resolution 3D MR fingerprinting (MRF) protocol to simultaneously provide quantitative T1 , T2 , proton density, and tissue fraction maps for detection and characterization of epileptic lesions. Study type Prospective. Population National Institute of Standards and Technology (NIST) / International Society for Magnetic Resonance in Medicine (ISMRM) phantom, five healthy volunteers and 15 patients with medically intractable epilepsy undergoing presurgical evaluation with noninvasive or invasive electroclinical data. Field strength/sequence 3D MRF scans and routine clinical epilepsy MR protocols were acquired at 3 T. Assessment The accuracy of the T1 and T2 values were first evaluated using the NIST/ISMRM phantom. The repeatability was then estimated with both phantom and volunteers based on the coefficient of variance (CV). For epilepsy patients, all the maps were qualitatively reviewed for lesion detection by three independent reviewers (S.E.J., M.L., I.N.) blinded to clinical data. Region of interest (ROI) analysis was performed on T1 and T2 maps to quantify the multiparametric signal differences between lesion and normal tissues. Findings from qualitative review and quantitative ROI analysis were compared with patients' electroclinical data to assess concordance. Statistical tests Phantom results were compared using R-squared, and patient results were compared using linear regression models. Results The phantom study showed high accuracy with the standard values, with an R2 of 0.99. The volunteer study showed high repeatability, with an average CV of 4.3% for T1 and T2 in various tissue regions. For the 15 patients, MRF showed additional findings in four patients, with the remaining 11 patients showing findings consistent with conventional MRI. The additional MRF findings were highly concordant with patients' electroclinical presentation. Data conclusion The 3D MRF protocol showed potential to identify otherwise inconspicuous epileptogenic lesions from the patients with negative conventional MRI diagnosis, as well as to correlate with different levels of epileptogenicity when widespread lesions were present. Level of evidence 3. Technical Efficacy Stage: 3. J. Magn. Reson. Imaging 2019;49:1333-1346.

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.

Neuronal-related activity can be estimated from functional magnetic resonance imaging (fMRI) data with no knowledge of the timings of blood oxygenation level-dependent (BOLD) events by means of deconvolution with regularized least-squares. This work proposes two improvements on the deconvolution algorithm of sparse paradigm free mapping (SPFM): a new formulation that enables the estimation of neuronal events with long, sustained activity; and the implementation of a subsampling approach based on stability selection that avoids the choice of any regularization parameter. The proposed method is evaluated on real fMRI data and compared with both the original SPFM algorithm and conventional analysis with a general linear model (GLM) that is aware of the temporal model of the neuronal-related activity. We demonstrate that the novel stability-based SPFM algorithm yields activation maps with higher resemblance to the maps obtained with GLM analyses and offers improved detection of neuronal-related events over SPFM, particularly in scenarios with low contrast-to-noise ratio.

Numerous studies have shown that surgical resection of the left anterior temporal lobe (ATL) is associated with a decline in object naming ability (Hermann et al., 1999). In contrast, few studies have examined the effects of left ATL surgery on auditory description naming (ADN) or category-specific naming. Compared with object naming, which loads heavily on visual recognition processes, ADN provides a more specific measure of concept retrieval. The present study examined ADN declines in a large group of patients who were tested before and after left ATL surgery, using a 2 × 2 × 2 factorial manipulation of uniqueness (common vs. proper nouns), taxonomic category (living vs. nonliving things), and time (pre- vs. postsurgery). Significant declines occurred across all categories but were substantially larger for proper living (PL) concepts, i.e., famous individuals. The disproportionate decline in PL noun naming relative to other conditions is consistent with the notion that the left ATL is specialized not only for retrieval of unique entity concepts, but also plays a role in processing social concepts and person-specific features.

BackgroundThere 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.MethodsWe 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.ResultsOf 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.ConclusionsIn 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: 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 Conclusion: Our results suggest that functional activation may be useful as a predictive measure of episodic memory loss in patients with MS.

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.

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.

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 3 T 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.

Background: This study has, for the first time, investigated the dorsal raphe nucleus (DRN) and ventral tegmental area (VTA) resting state whole-brain functional connectivity in medication-free young adults with major depression (MDD), at baseline and in relationship to treatment response. Method: A total of 119 subjects: 78 MDD (24 ± 4 years.) and 41 Healthy Controls (HC) (24 ± 3 years) were included in the analysis. DRN and VTA ROIs anatomical templates were used to extract resting state fluctuations and used to derive whole-brain functional connectivity. Differences between MDD and HCs were examined, as well as the correlation of baseline Hamilton Depression and Anxiety scale scores to the baseline DRN and VTA connectivity. The relationship to treatment response was examined by investigating the correlation of the percentage decrease in depression and anxiety scale scores with baseline connectivity measures. Results: There was a significant decrease (p = 0.05; cluster-wise corrected) in DRN connectivity with the prefrontal and mid-cingulate cortex in the MDD group, compared with the HC group. DRN connectivity with temporal areas, including the hippocampus and amygdala, positively correlated with baseline depression scores (p = 0.05; cluster-wise corrected). VTA connectivity with the cuneus-occipital areas correlated with a change in depression scores (p = 0.05; cluster-wise corrected). Conclusion: Our results indicate the presence of DRN-prefrontal and DRN-cingulate cortex connectivity abnormalities in young medication-free depressed subjects when compared to HCs and that the severity of depressive symptoms correlates with DRN-amygdala/hippocampus connectivity. VTA connectivity with the parietal and occipital areas is related to antidepressant treatment associated with a decrease in depressive symptoms. Future studies need to be carried out in larger and different age group populations to confirm the findings of the study.

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.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.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.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.

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. (JINS, 2016, 22, 105–119)