Intensity warping for multisite MRI harmonization.

In multisite neuroimaging studies there is often unwanted technical variation across scanners and sites. These "scanner effects" can hinder detection of biological features of interest, produce inconsistent results, and lead to spurious associations. We propose mica (multisite image harmonization by cumulative distribution function alignment), a tool to harmonize images taken on different scanners by identifying and removing within-subject scanner effects. Our goals in the present study were to (1) establish a method that removes scanner effects by leveraging multiple scans collected on the same subject, and, building on this, (2) develop a technique to quantify scanner effects in large multisite studies so these can be reduced as a preprocessing step. We illustrate scanner effects in a brain MRI study in which the same subject was measured twice on seven scanners, and assess our method's performance in a second study in which ten subjects were scanned on two machines. We found that unharmonized images were highly variable across site and scanner type, and our method effectively removed this variability by aligning intensity distributions. We further studied the ability to predict image harmonization results for a scan taken on an existing subject at a new site using cross-validation.

FLAIR* to visualize veins in white matter lesions: A new tool for the diagnosis of multiple sclerosis?

OBJECTIVE: To explore the potential of a post-processing technique combining FLAIR and T2* (FLAIR*) to distinguish between lesions caused by multiple sclerosis (MS) from cerebral small vessel disease (SVD) in a clinical setting. METHODS: FLAIR and T2* head datasets acquired at 3T of 25 people with relapsing MS (pwRMS) and ten with pwSVD were used. After post-processing, FLAIR* maps were used to determine the proportion of white matter lesions (WML) showing the 'vein in lesion' sign (VIL), a characteristic histopathological feature of MS plaques. Sensitivity and specificity of MS diagnosis were examined on the basis of >45% VIL+ and >60% VIL+ WML, and compared with current dissemination in space (DIS) MRI criteria. RESULTS: All pwRMS had >45% VIL+ WML (range 58-100%) whilst in pwSVD the proportion of VIL+ WML was significantly lower (0-64%; mean 32±20%). Sensitivity based on >45% VIL+ was 100% and specificity 80% whilst with >60% VIL+ as the criterion, sensitivity was 96% and specificity 90%. DIS criteria had 96% sensitivity and 40% specificity. CONCLUSION: FLAIR* enables VIL+ WML detection in a clinical setting, facilitating differentiation of MS from SVD based on brain MRI. KEY POINTS: • FLAIR* in a clinical setting allows visualization of veins in white matter lesions. • Significant proportions of MS lesions demonstrate a vein in lesion on MRI. • Microangiopathic lesions demonstrate a lower proportion of intralesional veins than MS lesions. • Intralesional vein-based criteria may complement current MRI criteria for MS diagnosis.

Oligoclonal bands in multiple sclerosis reactive against two herpesviruses and association with magnetic resonance imaging findings.

BACKGROUND: Two human herpesviruses, human herpesvirus 6 (HHV-6), and Epstein-Barr virus (EBV), have been repeatedly linked to multiple sclerosis (MS). OBJECTIVE: The aim of this study was to investigate HHV-6 and EBV reactive oligoclonal bands (OCBs), and viral DNA in the intrathecal compartment in MS. METHODS: The reactivity of OCBs in cerebrospinal fluid (CSF) for EBV and HHV-6 antigens and stability of virus reactive OCBs over time were studied in a well-characterized MS patient cohort. Associations between virus reactive OCBs and viral DNA in CSF (and any clinical and/or radiological findings) were investigated. RESULTS: Of patients with MS, 38% had OCBs reactive to either one of the viruses studied, compared to none in the patients with other inflammatory neurological diseases (p=0.005). The banding pattern of virus reactive OCBs remained the same over time. Furthermore, MS patients with viral DNA in CSF had more contrast enhancing lesions (CELs). CONCLUSION: The stable presence of herpesvirus reactive OCBs in CSF further strengthens the association of MS with these viruses. The finding that herpesviruses might be linked to the appearance of active lesions warrants investigation of new therapeutic strategies to treat these viruses in MS.

Rapid, high-resolution, whole-brain, susceptibility-based MRI of multiple sclerosis.

BACKGROUND: Susceptibility-based MRI offers a unique opportunity to study neurological diseases such as multiple sclerosis (MS). In this work, we assessed a three-dimensional segmented echo-planar-imaging (3D-EPI) sequence to rapidly acquire high-resolution T2 -weighted and phase contrast images of the whole brain. We also assessed if these images could depict important features of MS at clinical field strength, and we tested the effect of a gadolinium-based contrast agent (GBCA) on these images. MATERIALS AND METHODS: The 3D-EPI acquisition was performed on four healthy volunteers and 15 MS cases on a 3T scanner. The 3D sagittal images of the whole brain were acquired with a voxel size of 0.55 × 0.55 × 0.55 mm(3) in less than 4 minutes. For the MS cases, the 3D-EPI acquisition was performed before, during, and after intravenous GBCA injection. RESULTS: Both T2-weighted and phase-contrast images from the 3D-EPI acquisition were sensitive to the presence of lesions, parenchymal veins, and tissue iron. Conspicuity of the veins was enhanced when images were obtained during injection of GBCA. CONCLUSIONS: We propose this rapid imaging sequence for investigating, in a clinical setting, the spatiotemporal relationship between small parenchymal veins, iron deposition, and lesions in MS patient brains.

Central vein sign: A diagnostic biomarker in multiple sclerosis (CAVS-MS) study protocol for a prospective multicenter trial.

The specificity and implementation of current MRI-based diagnostic criteria for multiple sclerosis (MS) are imperfect. Approximately 1 in 5 of individuals diagnosed with MS are eventually determined not to have the disease, with overreliance on MRI findings a major cause of MS misdiagnosis. The central vein sign (CVS), a proposed MRI biomarker for MS lesions, has been extensively studied in numerous cross sectional studies and may increase diagnostic specificity for MS. CVS has desirable analytical, measurement, and scalability properties. "Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS)" is an NIH-supported, 2-year, prospective, international, multicenter study conducted by the North American Imaging in MS Cooperative (NAIMS) to evaluate CVS as a diagnostic biomarker for immediate translation into clinical care. Study objectives include determining the concordance of CVS and McDonald Criteria to diagnose MS, the sensitivity of CVS to detect MS in those with typical presentations, and the specificity of CVS among those with atypical presentations. The study will recruit a total of 400 participants (200 with typical and 200 with atypical presentations) across 11 sites. T2*-weighted, high-isotropic-resolution, segmented echo-planar MRI will be acquired at baseline and 24 months on 3-tesla scanners, and FLAIR* images (combination of FLAIR and T2*) will be generated for evaluating CVS. Data will be processed on a cloud-based platform that contains clinical and CVS rating modules. Imaging quality control will be conducted by automated methods and neuroradiologist review. CVS will be determined by Select6* and Select3* lesion methods following published criteria at each site and by central readers, including neurologists and neuroradiologists. Automated CVS detection and algorithms for incorporation of CVS into McDonald Criteria will be tested. Diagnosis will be adjudicated by three neurologists who served on the 2017 International Panel on the Diagnosis of MS. The CAVS-MS study aims to definitively establish CVS as a diagnostic biomarker that can be applied broadly to individuals presenting for evaluation of the diagnosis of MS.

MRI of the corpus callosum in multiple sclerosis: association with disability.

Inflammatory demyelination and axon damage in the corpus callosum are prominent features of multiple sclerosis (MS) and may partially account for impaired performance on complex tasks. The objective of this article was to characterize quantitative callosal MRI abnormalities and their association with disability. In 69 participants with MS and 29 healthy volunteers, lesional and extralesional callosal MRI indices were estimated via diffusion tensor tractography. expanded disability status scale (EDSS) and MS functional composite (MSFC) scores were recorded in 53 of the participants with MS. All tested callosal MRI indices were diffusely abnormal in MS. EDSS score was correlated only with age (r = 0.51). Scores on the overall MSFC and its paced serial auditory addition test (PASAT) and 9-hole peg test components were correlated with callosal fractional anisotropy (r = 0.27, 0.35, and 0.31, respectively) and perpendicular diffusivity (r = -0.29, -0.30, and -0.31) but not with overall callosal volume or callosal lesion volume; the PASAT score was more weakly correlated with callosal magnetization-transfer ratio (r = 0.21). Anterior callosal abnormalities were associated with impaired PASAT performance and posterior abnormalities with slow performance on the 9-hole peg test. In conclusion, abnormalities in the corpus callosum can be assessed with quantitative MRI and are associated with cognitive and complex upper-extremity dysfunction in MS.

Manganese-Enhanced MRI in Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: Cellular uptake of the manganese ion, when administered as a contrast agent for MR imaging, can noninvasively highlight cellular activity and disease processes in both animals and humans. The purpose of this study was to explore the enhancement profile of manganese in patients with multiple sclerosis. MATERIALS AND METHODS: Mangafodipir is a manganese chelate that was clinically approved for MR imaging of liver lesions. We present a case series of 6 adults with multiple sclerosis who were scanned at baseline with gadolinium, then injected with mangafodipir, and followed at variable time points thereafter. RESULTS: Fourteen new lesions formed during or shortly before the study, of which 10 demonstrated manganese enhancement of varying intensity, timing, and spatial pattern. One gadolinium-enhancing extra-axial mass, presumably a meningioma, also demonstrated enhancement with manganese. Most interesting, manganese enhancement was detected in lesions that formed in the days after mangafodipir injection, and this enhancement persisted for several weeks, consistent with contrast coming from intracellular uptake of manganese. Some lesions demonstrated a diffuse pattern of manganese enhancement in an area larger than that of both gadolinium enhancement and T2-FLAIR signal abnormality. CONCLUSIONS: This work demonstrates the first use of a manganese-based contrast agent to enhance MS lesions on MR imaging. Multiple sclerosis lesions were enhanced with a temporal and spatial profile distinct from that of gadolinium. Further experiments are necessary to uncover the mechanism of manganese contrast enhancement as well as cell-specific uptake.

Independent and redundant information in nearby cortical neurons.

In the primary visual cortex (V1), nearby neurons are tuned to similar stimulus features, and, depending on the manner and time scale over which neuronal signals are analyzed, the resulting redundancy may mitigate deleterious effects of response variability. We estimated information rates in the short-time scale responses of clusters of up to six simultaneously recorded nearby neurons in monkey V1. Responses were almost independent if we kept track of which neuron fired each spike but were redundant if we summed responses over the cluster. Redundancy was independent of cluster size. Summing neuronal responses to reduce variability discards potentially useful information, and the discarded information increases with cluster size.

The Central Vein Sign in Radiologically Isolated Syndrome.

BACKGROUND AND PURPOSE: Radiologically isolated syndrome describes asymptomatic individuals with incidental radiologic abnormalities suggestive of multiple sclerosis. Recent studies have demonstrated that >40% of white matter lesions in MS (and often substantially more) have visible central veins on MR imaging. This "central vein sign" reflects perivenous inflammatory demyelination and can assist in differentiating MS from other white matter disorders. We therefore hypothesized that >40% of white matter lesions in cases of radiologically isolated syndrome would show the central vein sign. MATERIALS AND METHODS: We recruited 20 participants diagnosed with radiologically isolated syndrome after evaluation by a neurologist. We performed 3T MR imaging of the brain and cervical spinal cord. White matter lesions were analyzed for the central vein sign. RESULTS: Of 391 total white matter lesions, 292 (75%) demonstrated the central vein sign (central vein sign+). The median proportion of central vein sign+ lesions per case was 87% (range, 29%-100%). When the "40% rule" that has been proposed to distinguish MS from other disorders was applied, of 20 participants, 18 cases of radiologically isolated syndrome (90%) had ≥40% central vein sign+ lesions (range, 55%-100%). Two participants (10%) had <40% central vein sign+ lesions (29% and 31%). When the simpler "rule of 6" was applied, 19 participants (95%) met these criteria. In multivariable models, the number of spinal cord and infratentorial lesions was associated with a higher proportion of central vein sign+ lesions (P = .002; P = .06, respectively). CONCLUSIONS: Most cases of radiologically isolated syndrome had a high proportion of central vein sign+ lesions, suggesting that lesions in these individuals reflect perivenous inflammatory demyelination. Moreover, we found correlations between the proportion of central vein sign+ lesions and spinal cord lesions, a known risk factor for radiologically isolated syndrome progressing to MS. These findings raise the possibility, testable prospectively, that the central vein sign may have prognostic value in distinguishing patients with radiologically isolated syndrome at risk of developing clinical MS from those with white matter lesions of other etiologies.

Manganese-Enhanced MRI of the Brain in Healthy Volunteers.

BACKGROUND AND PURPOSE: The manganese ion is used as an intracellular MR imaging contrast agent to study neuronal function in animal models, but it remains unclear whether manganese-enhanced MR imaging can be similarly useful in humans. Using mangafodipir (Teslascan, a chelated manganese-based contrast agent that is FDA-approved), we evaluated the dynamics of manganese enhancement of the brain and glandular structures in the rostral head and neck in healthy volunteers. MATERIALS AND METHODS: We administered mangafodipir intravenously at a rate of 1 mL/minute for a total dose of 5 µmol/kg body weight. Nine healthy adult volunteers (6 men/3 women; median age, 43 years) completed baseline history and physical examination, 3T MR imaging, and blood work. MR imaging also followed mangafodipir administration at various time points from immediate to 7 days, with delayed scans at 1-3 months. RESULTS: The choroid plexus and anterior pituitary gland enhanced within 10 minutes of infusion, with enhancement persisting up to 7 and 30 days, respectively. Exocrine (parotid, submandibular, sublingual, and lacrimal) glands also enhanced avidly as early as 1 hour postadministration, generally resolving by 1 month; 3 volunteers had residual exocrine gland enhancement, which resolved by 2 months in 1 and by 3 months in the other 2. Mangafodipir did not affect clinical parameters, laboratory values, or T1-weighted signal in the basal ganglia. CONCLUSIONS: Manganese ions released from mangafodipir successfully enable noninvasive visualization of intra- and extracranial structures that lie outside the blood-brain barrier without adverse clinical effects, setting the stage for future neuroradiologic investigation in disease.

Identification of Chronic Active Multiple Sclerosis Lesions on 3T MRI.

BACKGROUND AND PURPOSE: MR imaging-pathologic studies have reported that paramagnetic rims on 7T susceptibility-based MR imaging identify, in vivo, the subset of MS lesions with compartmentalized inflammation at the lesion edge and associated remyelination failure. Here, we assessed the reliability of detecting these rims on high-resolution 3T phase images. MATERIALS AND METHODS: High-resolution T2* and phase MR imaging was collected in 20 patients with MS at 3T (3D segmented EPI, 0.65 mm3) and 7T (2D gradient-echo, 0.2 × 0.2 × 1 mm) MR imaging. In each case, 5 discrete chronic (nonenhancing) MS lesions were selected on T2 FLAIR images for rim evaluation. Five raters experienced in MS imaging contributed to the rim assessment, of whom 3 worked independently on 3T data, and 2, on 7T data. Consensus agreement was reached for both 3T and 7T rim evaluations. Discrepancies between 3T and 7T were discussed, and consensus was reached. RESULTS: Phase rims were seen in 34 lesions at 7T and in 36 lesions at 3T by consensus. Inter- and intrarater reliability were "substantial/good" both at 3T and 7T analysis (Cohen κ, >0.71). Based on consensus agreement, the reliability of rim visualization at 3T versus 7T was 0.78 (κ) with a pair-wise agreement of 90%. More lesions were judged to be false-positive or false-negative at 3T than at 7T. CONCLUSIONS: Nearly all 7T paramagnetic rims can also be seen at 3T. Imaging at 3T opens the possibility of implementing paramagnetic rims as an outcome measure in multicenter, MR imaging-based clinical trials aimed at treating perilesional persistent inflammation and its potential effects on remyelination.

Automated Integration of Multimodal MRI for the Probabilistic Detection of the Central Vein Sign in White Matter Lesions.

BACKGROUND AND PURPOSE: The central vein sign is a promising MR imaging diagnostic biomarker for multiple sclerosis. Recent studies have demonstrated that patients with MS have higher proportions of white matter lesions with the central vein sign compared with those with diseases that mimic MS on MR imaging. However, the clinical application of the central vein sign as a biomarker is limited by interrater differences in the adjudication of the central vein sign as well as the time burden required for the determination of the central vein sign for each lesion in a patient's full MR imaging scan. In this study, we present an automated technique for the detection of the central vein sign in white matter lesions. MATERIALS AND METHODS: Using multimodal MR imaging, the proposed method derives a central vein sign probability, πij, for each lesion, as well as a patient-level central vein sign biomarker, ψi. The method is probabilistic in nature, allows site-specific lesion segmentation methods, and is potentially robust to intersite variability. The proposed algorithm was tested on imaging acquired at the University of Vermont in 16 participants who have MS and 15 participants who do not. RESULTS: By means of the proposed automated technique, participants with MS were found to have significantly higher values of ψ than those without MS (ψMS = 0.55 ± 0.18; ψnon-MS = 0.31 ± 0.12; P < .001). The algorithm was also found to show strong discriminative ability between patients with and without MS, with an area under the curve of 0.88. CONCLUSIONS: The current study presents the first fully automated method for detecting the central vein sign in white matter lesions and demonstrates promising performance in a sample of patients with and without MS.

Improved Visualization of Cortical Lesions in Multiple Sclerosis Using 7T MP2RAGE.

BACKGROUND AND PURPOSE: Cortical lesions are common and often extensive in multiple sclerosis but are difficult to visualize by MRI, leaving important questions about their clinical implications and response to therapy unanswered. Our aim was to determine whether cortical lesions are better visualized using magnetization prepared 2 rapid acquisition gradient echoes (MP2RAGE) than T2*-weighted imaging on 7T MR imaging. MATERIALS AND METHODS: Brain MR imaging using T1-weighted MP2RAGE at 500-µm isotropic resolution, T2*-weighted gradient-echo, and T2*-weighted segmented echo-planar imaging sequences were collected for 13 patients with MS and 5 age-matched neurologically healthy controls on a 7T research system. One MS case underwent postmortem MR imaging including gradient-echo and MP2RAGE sequences, after which cortical lesions seen on MR imaging were assessed with immunohistochemistry. RESULTS: MP2RAGE detected 203 cortical lesions (median, 16 lesions/case; interquartile range, 15), compared to 92 with T2*gradient-echo (median, 7; interquartile range, 8; P < .001) and 81 with T2*EPI (median, 7; interquartile range, 5; P < .001). This increase in lesion number detected on MP2RAGE versus T2* was observed for juxtacortical, leukocortical, and intracortical lesions. Forty-three percent of all cortical lesions were identified only on MP2RAGE. White matter lesion volume correlated with total juxtacortical (r = 0.86, P < .001) and leukocortical lesion volume (r = 0.70, P < .01) but not intracortical lesion volume, suggesting that pathophysiology may differ by lesion type. Of 4 suspected lesions seen on postmortem imaging, 3 were found to be true cortical lesions while 1 represented postmortem tissue damage. CONCLUSIONS: A combination of MP2RAGE and T2*-weighted imaging at 7T improved detection of cortical lesions and should enable longitudinal studies to elucidate their spatiotemporal dynamics and clinical implications.

An Automated Statistical Technique for Counting Distinct Multiple Sclerosis Lesions.

BACKGROUND AND PURPOSE: Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with clinical outcome. Lesion count, which encapsulates the natural history of lesion formation and is thought to provide complementary information, is difficult to assess in patients with confluent (ie, spatially overlapping) lesions. We introduce a statistical technique for cross-sectionally counting pathologically distinct lesions. MATERIALS AND METHODS: MR imaging was used to assess the probability of a lesion at each location. The texture of this map was quantified using a novel technique, and clusters resembling the center of a lesion were counted. Validity compared with a criterion standard count was demonstrated in 60 subjects observed longitudinally, and reliability was determined using 14 scans of a clinically stable subject acquired at 7 sites. RESULTS: The proposed count and the criterion standard count were highly correlated (r = 0.97, P < .001) and not significantly different (t59 = -.83, P = .41), and the variability of the proposed count across repeat scans was equivalent to that of lesion load. After accounting for lesion load and age, lesion count was negatively associated (t58 = -2.73, P < .01) with the Expanded Disability Status Scale. Average lesion size had a higher association with the Expanded Disability Status Scale (r = 0.35, P < .01) than lesion load (r = 0.10, P = .44) or lesion count (r = -.12, P = .36) alone. CONCLUSIONS: This study introduces a novel technique for counting pathologically distinct lesions using cross-sectional data and demonstrates its ability to recover obscured longitudinal information. The proposed count allows more accurate estimation of lesion size, which correlated more closely with disability scores than either lesion load or lesion count alone.

Transverse relaxation of cerebrospinal fluid depends on glucose concentration.

PURPOSE: To evaluate the biophysical processes that generate specific T2 values and their relationship to specific cerebrospinal fluid (CSF) content. MATERIALS AND METHODS: CSF T2s were measured ex vivo (14.1T) from isolated CSF collected from human, rat and non-human primate. CSF T2s were also measured in vivo at different field strength in human (3 and 7T) and rodent (1, 4.7, 9,4 and 11.7T) using different pulse sequences. Then, relaxivities of CSF constituents were measured, in vitro, to determine the major molecule responsible for shortening CSF T2 (2s) compared to saline T2 (3s). The impact of this major molecule on CSF T2 was then validated in rodent, in vivo, by the simultaneous measurement of the major molecule concentration and CSF T2. RESULTS: Ex vivo CSF T2 was about 2.0s at 14.1T for all species. In vivo human CSF T2 approached ex vivo values at 3T (2.0s) but was significantly shorter at 7T (0.9s). In vivo rodent CSF T2 decreased with increasing magnetic field and T2 values similar to the in vitro ones were reached at 1T (1.6s). Glucose had the largest contribution of shortening CSF T2in vitro. This result was validated in rodent in vivo, showing that an acute change in CSF glucose by infusion of glucose into the blood, can be monitored via changes in CSF T2 values. CONCLUSION: This study opens the possibility of monitoring glucose regulation of CSF at the resolution of MRI by quantitating T2.

Photon-Counting CT of the Brain: In Vivo Human Results and Image-Quality Assessment.

BACKGROUND AND PURPOSE: Photon-counting detectors offer the potential for improved image quality for brain CT but have not yet been evaluated in vivo. The purpose of this study was to compare photon-counting detector CT with conventional energy-integrating detector CT for human brains. MATERIALS AND METHODS: Radiation dose-matched energy-integrating detector and photon-counting detector head CT scans were acquired with standardized protocols (tube voltage/current, 120 kV(peak)/370 mAs) in both an anthropomorphic head phantom and 21 human asymptomatic volunteers (mean age, 58.9 ± 8.5 years). Photon-counting detector thresholds were 22 and 52 keV (low-energy bin, 22-52 keV; high-energy bin, 52-120 keV). Image noise, gray matter, and white matter signal-to-noise ratios and GM-WM contrast and contrast-to-noise ratios were measured. Image quality was scored by 2 neuroradiologists blinded to the CT detector type. Reproducibility was assessed with the intraclass correlation coefficient. Energy-integrating detector and photon-counting detector CT images were compared using a paired t test and the Wilcoxon signed rank test. RESULTS: Photon-counting detector CT images received higher reader scores for GM-WM differentiation with lower image noise (all P < .001). Intrareader and interreader reproducibility was excellent (intraclass correlation coefficient, ≥0.86 and 0.79, respectively). Quantitative analysis showed 12.8%-20.6% less image noise for photon-counting detector CT. The SNR of photon-counting detector CT was 19.0%-20.0% higher than of energy-integrating detector CT for GM and WM. The contrast-to-noise ratio of photon-counting detector CT was 15.7% higher for GM-WM contrast and 33.3% higher for GM-WM contrast-to-noise ratio. CONCLUSIONS: Photon-counting detector brain CT scans demonstrated greater gray-white matter contrast compared with conventional CT. This was due to both higher soft-tissue contrast and lower image noise for photon-counting CT.

Volumetric Analysis from a Harmonized Multisite Brain MRI Study of a Single Subject with Multiple Sclerosis.

BACKGROUND AND PURPOSE: MR imaging can be used to measure structural changes in the brains of individuals with multiple sclerosis and is essential for diagnosis, longitudinal monitoring, and therapy evaluation. The North American Imaging in Multiple Sclerosis Cooperative steering committee developed a uniform high-resolution 3T MR imaging protocol relevant to the quantification of cerebral lesions and atrophy and implemented it at 7 sites across the United States. To assess intersite variability in scan data, we imaged a volunteer with relapsing-remitting MS with a scan-rescan at each site. MATERIALS AND METHODS: All imaging was acquired on Siemens scanners (4 Skyra, 2 Tim Trio, and 1 Verio). Expert segmentations were manually obtained for T1-hypointense and T2 (FLAIR) hyperintense lesions. Several automated lesion-detection and whole-brain, cortical, and deep gray matter volumetric pipelines were applied. Statistical analyses were conducted to assess variability across sites, as well as systematic biases in the volumetric measurements that were site-related. RESULTS: Systematic biases due to site differences in expert-traced lesion measurements were significant (P < .01 for both T1 and T2 lesion volumes), with site explaining >90% of the variation (range, 13.0-16.4 mL in T1 and 15.9-20.1 mL in T2) in lesion volumes. Site also explained >80% of the variation in most automated volumetric measurements. Output measures clustered according to scanner models, with similar results from the Skyra versus the other 2 units. CONCLUSIONS: Even in multicenter studies with consistent scanner field strength and manufacturer after protocol harmonization, systematic differences can lead to severe biases in volumetric analyses.

Quantitative characterization of the corticospinal tract at 3T.

BACKGROUND AND PURPOSE: White matter tract-specific imaging will probably become a major component of clinical neuroradiology. Fiber tracking with diffusion tensor imaging (DTI) is widely used, but variability is substantial. This article reports the ranges of MR imaging appearance and right-left asymmetry of healthy corticospinal tracts (CST) reconstructed with DTI. METHODS: For 20 healthy volunteers, whole-brain DTI data were coregistered with maps of absolute T1 and T2 relaxation times and magnetization transfer ratio (MTR), all acquired at 3T. For each individual, the 2 reconstructed CSTs and their asymmetry were analyzed with respect to the number of fibers reconstructed; tract volume; and individual MR imaging parameters restricted to the tracts. Interscan variability was estimated by repeat imaging of 8 individuals. RESULTS: Reconstructed fiber number and tract volume are highly variable, rendering them insensitive to abnormalities in disease. Individual tract-restricted MR imaging parameters are more constrained, and their population averages and normal ranges are reported. The average population asymmetry is generally zero; therefore, normal ranges for an index of asymmetry are reported. By way of example, CST-restricted MR imaging parameters and their asymmetries are shown to be abnormal in an individual with multiple sclerosis who had a lesion affecting the CST. CONCLUSIONS: The results constitute a normative dataset for the following imaging parameters of the CST: T1, T2, MTR, fractional anisotropy, mean diffusivity, transverse diffusivity, and the 3 diffusion tensor eigenvalues. These data can be used to identify, characterize, and establish the significance of changes in diseases that affect the CST.

Revised Recommendations of the Consortium of MS Centers Task Force for a Standardized MRI Protocol and Clinical Guidelines for the Diagnosis and Follow-Up of Multiple Sclerosis.

An international group of neurologists and radiologists developed revised guidelines for standardized brain and spinal cord MR imaging for the diagnosis and follow-up of MS. A brain MR imaging with gadolinium is recommended for the diagnosis of MS. A spinal cord MR imaging is recommended if the brain MR imaging is nondiagnostic or if the presenting symptoms are at the level of the spinal cord. A follow-up brain MR imaging with gadolinium is recommended to demonstrate dissemination in time and ongoing clinically silent disease activity while on treatment, to evaluate unexpected clinical worsening, to re-assess the original diagnosis, and as a new baseline before starting or modifying therapy. A routine brain MR imaging should be considered every 6 months to 2 years for all patients with relapsing MS. The brain MR imaging protocol includes 3D T1-weighted, 3D T2-FLAIR, 3D T2-weighted, post-single-dose gadolinium-enhanced T1-weighted sequences, and a DWI sequence. The progressive multifocal leukoencephalopathy surveillance protocol includes FLAIR and DWI sequences only. The spinal cord MR imaging protocol includes sagittal T1-weighted and proton attenuation, STIR or phase-sensitive inversion recovery, axial T2- or T2*-weighted imaging through suspicious lesions, and, in some cases, postcontrast gadolinium-enhanced T1-weighted imaging. The clinical question being addressed should be provided in the requisition for the MR imaging. The radiology report should be descriptive, with results referenced to previous studies. MR imaging studies should be permanently retained and available. The current revision incorporates new clinical information and imaging techniques that have become more available.

Interspike intervals, receptive fields, and information encoding in primary visual cortex.

In the primate primary visual cortex (V1), the significance of individual action potentials has been difficult to determine, particularly in light of the considerable trial-to-trial variability of responses to visual stimuli. We show here that the information conveyed by an action potential depends on the duration of the immediately preceding interspike interval (ISI). The interspike intervals can be grouped into several different classes on the basis of reproducible features in the interspike interval histograms. Spikes in different classes bear different relationships to the visual stimulus, both qualitatively (in terms of the average stimulus preceding each spike) and quantitatively (in terms of the amount of information encoded per spike and per second). Spikes preceded by very short intervals (3 msec or less) convey information most efficiently and contribute disproportionately to the overall receptive-field properties of the neuron. Overall, V1 neurons can transmit between 5 and 30 bits of information per second in response to rapidly varying, pseudorandom stimuli, with an efficiency of approximately 25%. Although some (but not all) of our results would be expected from neurons that use a firing-rate code to transmit information, the evidence suggests that visual neurons are well equipped to decode stimulus-related information on the basis of relative spike timing and ISI duration.