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Background Although the aetiology of multiple sclerosis (MS) remains elusive, it is clear that Epstein Barr virus (EBV) and possibly other viruses play a role in the pathogenesis of MS. Laboratory evidence suggests that human endogenous retroviruses (HERVs) could also have a role, but no interventional therapy has determined what will happen if HERVs are suppressed. Recent epidemiological evidence indicates patients with HIV infection have a significantly lower risk of developing MS and that HIV antiretroviral therapies may be coincidentally inhibiting HERVs, or other retroelements, that could be implicated in MS. Objectives To systematically investigate the effects of an HIV integrase strand inhibitor, raltegravir, on the number of gadolinium (Gd)-enhanced MRI lesions in people with active relapsing MS. Methods This is a Phase 2a clinical trial where twenty participants were enrolled in a 3 month baseline phase followed by 3 months of treatment with raltegravir 400 mg twice a day. Patients had monthly Gd-enhanced MRI, saliva collection to test for EBV shedding, blood sampling for safety monitoring, virology (including HERVs), measurement of immunological and inflammatory markers; and physical, neurological and quality-of-life assessments. Results All patients completed the six months trial period.The primary outcome measure of MS disease activity was the number of Gd-enhancing lesions observed, and raltegravir had no significant effect on the rate of development of Gd-enhancing lesions during the treatment phase compared with the baseline phase. Additionally, there was no change in secondary outcomes of either disability or quality-of-life measures that could reasonably be attributed to the intervention. There was a significant positive between HERV-W/MSRV (multiple sclerosis related virus) Gag Flix (Fluorescence index) B cells and the number of Gd-enhanced lesions at any visit (p = 0.029), which was independent of any potential influence of the trial drug administration. Regarding EBV shedding, there was no significant correlation between the amount of EBV shedding and the number of lesions. No change was detected in inflammatory markers (IL-8, IL-1β, IL-6, IL-10, TNF, IL-12p70 and HCRP), which were all within normal limits both before and after the intervention. Serum CD163 expression was also unchanged by raltegravir. Conclusions Raltegravir did not have any impact on MS disease activity. This could be due to the choice of antiretroviral agent used in this study, the need for a combination of agents, as used in treating HIV infection, the short treatment period or dosing regimen, or the lack of a role of HERV expression in MS once the disease is established. Borderline significance for the association between EBV shedding and the total number of lesions, probably driven by new lesion development, may indicate EBV shedding as a marker of inflammatory disease activity. In conclusion, interesting correlations between HERV-W markers, EBV shedding and new MRI lesions, independent from treatment effects, were found.

Some of the clinical manifestations of multiple sclerosis, such as memory impairment and depression, are, at least partly, related to involvement of the hippocampus. Pathological studies have shown extensive demyelination, neuronal damage, and synaptic abnormalities in the hippocampus of patients with multiple sclerosis, and improvements in MRI technology have provided novel ways to assess hippocampal involvement in vivo. It is now accepted that clinical manifestations related to the hippocampus are due not only to focal hippocampal damage, but also to disconnection of the hippocampus from several brain networks. Evidence suggests anatomical and functional subspecialisation of the different hippocampal subfields, resulting in variability between regions in the extent to which damage and repair occur. The hippocampus also has important roles in plasticity and neurogenesis, both of which potentially contribute to functional preservation and restoration. These findings underline the importance of evaluation of the hippocampus not only to improve understanding of the clinical manifestations of multiple sclerosis, but also as a potential future target for treatment.

To investigate if quantitative apparent diffusion coefficient (ADC) measurements can predict genetic subtypes of non-gadolinium-enhancing gliomas, comparing whole tumour against single slice analysis. Volumetric T2-derived masks of 44 gliomas were co-registered to ADC maps with ADC mean (ADCmean) calculated. For the slice analysis, two observers placed regions of interest in the largest tumour cross-section. The ratio (ADCratio) between ADCmean in the tumour and normal appearing white matter was calculated for both methods. Isocitrate dehydrogenase (IDH) wild-type gliomas showed the lowest ADC values throughout (p < 0.001). ADCmean in the IDH-mutant 1p19q intact group was significantly higher than in the IDH-mutant 1p19q co-deleted group (p < 0.01). A volumetric ADCmean threshold of 1201 × 10−6 mm2/s identified IDH wild-type with a sensitivity of 83% and a specificity of 86%; a volumetric ADCratio cut-off value of 1.65 provided a sensitivity of 80% and a specificity of 92% (area under the curve (AUC) 0.9–0.94). A slice ADCratio threshold for observer 1 (observer 2) of 1.76 (1.83) provided a sensitivity of 80% (86%), specificity of 91% (100%) and AUC of 0.95 (0.96). The intraclass correlation coefficient was excellent (0.98). ADC measurements can support the distinction of glioma subtypes. Volumetric and two-dimensional measurements yielded similar results in this study. • Diffusion-weighted MRI aids the identification of non-gadolinium-enhancing malignant gliomas • ADC measurements may permit non-gadolinium-enhancing glioma molecular subtyping • IDH wild-type gliomas have lower ADC values than IDH-mutant tumours • Single cross-section and volumetric ADC measurements yielded comparable results in this study

Deep brain stimulation (DBS) for Parkinson's disease is a highly effective treatment in controlling otherwise debilitating symptoms. Yet the underlying brain mechanisms are currently not well understood. Whole-brain computational modeling was used to disclose the effects of DBS during resting-state functional Magnetic Resonance Imaging in ten patients with Parkinson's disease. Specifically, we explored the local and global impact that DBS has in creating asynchronous, stable or critical oscillatory conditions using a supercritical bifurcation model. We found that DBS shifts global brain dynamics of patients towards a Healthy regime. This effect was more pronounced in very specific brain areas such as the thalamus, globus pallidus and orbitofrontal regions of the right hemisphere (with the left hemisphere not analyzed given artifacts arising from the electrode lead). Global aspects of integration and synchronization were also rebalanced. Empirically, we found higher communicability and coherence brain measures during DBS-ON compared to DBS-OFF. Finally, using our model as a framework, artificial in silico DBS was applied to find potential alternative target areas for stimulation and whole-brain rebalancing. These results offer important insights into the underlying large-scale effects of DBS as well as in finding novel stimulation targets, which may offer a route to more efficacious treatments, In this work, Gustavo Deco is supported by the ERC Advanced Grant: DYSTRUCTURE (n. 295129), by the Spanish Research Project PSI2016-75688-P and by the the European Union's Horizon 2020 research and innovation programme under grant agreement n. 720270 (HBP SGA1). Morten Kringelbach is supported by the ERC Consolidator Grant CAREGIVING (n. 615539) and the Center for Music in the Brain, funded by the Danish National Research Foundation (DNRF117). Victor M Saenger is supported by the Research Personnel Training program PSI2013-42091-P funded by the Spanish Ministry of Economy and Competitiveness., info:eu-repo/semantics/publishedVersion

The design and operation of a facility in which a magnetic resonance imaging (MRI) scanner is incorporated into a room used for surgical or endovascular cardiac interventions presents several challenges. MR safety must be maintained in the presence of a much wider variety of equipment than is found in a diagnostic unit, and of staff unfamiliar with the MRI environment, without compromising the safety and practicality of the interventional procedure. Both the MR-guided cardiac interventional unit at Kings College London and the intraoperative imaging suite at the National Hospital for Neurology and Neurosurgery are single-room interventional facilities incorporating 1.5 T cylindrical-bore MRI scanners. The two units employ similar strategies to maintain MR safety, both in original design and day-to-day operational workflows, and between them over a decade of incident-free practice has been accumulated. This article outlines these strategies, highlighting both similarities and differences between the units, as well as some lessons learned and resulting procedural changes made in both units since installation.

Aim and objectives We aim to illustrate the diagnostic performance of diffusional kurtosis imaging (DKI) in the diagnosis of gliomas. Methods and materials A review protocol was developed according to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P), registered in the international prospective register of systematic reviews, PROSPERO and published. Literature search in 4 databases was performed using the keywords “glioma” and “diffusional kurtosis”.After applying a robust inclusion/exclusion criteria, included articles were independently evaluated according to the QUADAS-2 tool.Data extraction was done in a pre-designed pro forma.Reported sensitivities and specificities were used to construct 2x2 tables and paired forest plots using the Review Manager (RevMan®) software.Random-effect model was pursued using the hierarchical summary receiver operator characteristics. Results Initially, 216 hits were retrieved. Considering duplicates and inclusion criteria; 23 articles were eligible for full-text reading. Ultimately, 19 studies were deemed to be eligible for final inclusion. Quality assessment revealed 9 studies with low risk of bias in the 4 domains. Using a bivariate random-effect model for data synthesis; summary ROC curve showed pooled area under the curve (AUC) of 0.92 and estimated sensitivity of 0.87 (95% CI: 0.78 - 0.92) in high/low grade gliomas’ differentiation.A mean difference in Mean Kurtosis (MK) value between HGG and LGG of 0.22 [95% CI: 0.25 - 0.19] was illustrated (p value = 0.0014) and a moderate degree of heterogeneity (I²= 73.8%). Conclusion DKI shows good diagnostic accuracy in high/low grade gliomas’ differentiation; which might qualify it to be part of the routine clinical practice, however; further evidence is deemed for technique standardization.

Purpose To compare the influence of two limb positions and slice prescription using scout-image–based and surface-anatomy–based methods on the reproducibility of quantitative MRI of lower-limb muscles. Materials and Methods Ten healthy subjects were scanned at 3 Tesla with a two-dimensional turbo spin-echo T1-weighted acquisition. Imaging was performed at thigh and calf level in two subject limb positions and independently repeated by a second operator. Regions-of-interest (ROI) were drawn on three muscles at thigh and calf levels on axial slices at fixed distance from the knee joint and at a level determined by surface anatomy. Results Test–retest reliability of muscle cross-sectional area and ROI area overlap were similar for both limb positioning methods. Changing limb position between scans reduced ROI overlap (P

We assessed the presence, frequency and pattern of MRI abnormalities in non-dystrophic myotonia patients. We reviewed T1-weighted and STIR (short-tau-inversion-recovery) 3T MRI sequences of lower limb muscles at thigh and calf level in 21 patients with genetically confirmed non-dystrophic myotonia: 11 with CLCN1 mutations and 10 with SCN4A mutations, and 19 healthy volunteers. The MRI examinations of all patients showed hyperintensity within muscles on either T1-weighted or STIR images. Mild extensive or marked T1-weighted changes were noted in 10/21 patients and no volunteers. Muscles in the thigh were equally likely to be affected but in the calf there was sparing of tibialis posterior. Oedema was common in calf musculature especially in the medial gastrocnemius with STIR hyperintensity observed in 18/21 patients. In 10/11 CLCN1 patients this included a previously unreported “central stripe”, also present in 3/10 SCN4A patients but no volunteers. Degree of fatty infiltration correlated with age (rho=0.46, p

Introduction Sensory ganglionopathies are uncommon but potentially very disabling. They have heterogeneous etiologies including autoimmune, paraneoplastic, toxic, and inflammatory although many remain idiopathic despite intensive investigation. Asymmetric sensory loss is relatively common at the onset, but with time, symptoms usually spread to involve all limbs symmetrically. Methods We report 6 patients with a persistent strikingly asymmetrical sensory ganglionopathy with acute or subacute onset and slow progression. Results Peripheral nerve biopsies in 5 patients showed axonal loss without significant inflammation; a dorsal root ganglion biopsy in 1 patient showed neuronal loss and inflammatory infiltrate. Four patients received immunomodulatory treatment, but overall the response to treatment was poor. Conclusions Asymmetrical sensory ganglionopathies may have an inflammatory basis. Immunomodulatory therapy may be considered early in the disease course, although in this series there was a limited response to treatment. Muscle Nerve, 2013

Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be classified according to previously suggested radiologic characteristics and how this classification relates to prognosis. Searching the databases of eight tertiary referral centres we identified 90 adult patients (61 women, 29 men; mean age 34 years) with ≥1 AIIDL. We collected their demographic, clinical and magnetic resonance imaging data and obtained follow-up (FU) information on 77 of these patients over a mean duration of 4 years. The AIIDLs presented as a single lesion in 72 (80 %) patients and exhibited an infiltrative (n = 35), megacystic (n = 16), Baló (n = 10) or ring-like (n = 16) lesion appearance in 77 (86 %) patients. Additional multiple sclerosis (MS)-typical lesions existed in 48 (53 %) patients. During FU, a further clinical attack occurred rarely (23-35 % of patients) except for patients with ring-like AIIDLs (62 %). Further attacks were also significantly more often in patients with coexisting MS-typical lesions (41 vs. 10 %, p < 0.005). New AIIDLs developed in six (7 %), and new MS-typical lesions in 29 (42 %) patients. Our findings confirm the previously reported subtypes of AIIDLs. Most types confer a relatively low risk of further clinical attacks, except for ring-like lesions and the combination with MS-typical lesions. © 2013 Springer-Verlag Berlin Heidelberg.

BACKGROUND AND PURPOSE: Inherited prion diseases represent over 15% of human prion cases and are a frequent cause of early onset dementia. The purpose of this study was to define the distribution of changes in cerebral volumetric and microstructural parenchymal tissues in a specific inherited human prion disease mutation combining VBM with VBA of cerebral MTR and MD. MATERIALS AND METHODS: VBM and VBA of cerebral MTR and MD were performed in 16 healthy control participants and 9 patients with the 6-OPRI mutation. An analysis of covariance consisting of diagnostic grouping with age and total intracranial volume as covariates was performed. RESULTS: On VBM, there was a significant reduction in gray matter volume in patients compared with control participants in the basal ganglia, perisylvian cortex, lingual gyrus, and precuneus. Significant MTR reduction and MD increases were more anatomically extensive than volume differences on VBM in the same cortical areas, but MTR and MD changes were not seen in the basal ganglia. CONCLUSIONS: Gray matter and WM changes were seen in brain areas associated with motor and cognitive functions known to be impaired in patients with the 6-OPRI mutation. There were some differences in the anatomic distribution of MTR-VBA and MD-VBA changes compared with VBM, likely to reflect regional variations in the type and degree of the respective pathophysiologic substrates. Combined analysis of complementary multiparameter MR imaging data furthers our understanding of prion disease pathophysiology. ABBREVIATIONS: IPD inherited prion disease; MD mean diffusivity; MTR magnetization transfer ratio; VBA voxel-based analysis; VBM voxel-based morphometry

Background The anatomy of the substantia nigra on conventional MRI is controversial. Even using histological techniques it is difficult to delineate with certainty from surrounding structures. We sought to define the anatomy of the SN using high field spin-echo MRI of pathological material in which we could study the anatomy in detail to corroborate our MRI findings in controls and Parkinson's disease and progressive supranuclear palsy. Methods 23 brains were selected from the Queen Square Brain Bank (10 controls, 8 progressive supranuclear palsy, 5 Parkinson's disease) and imaged using high field 9.4 Tesla spin-echo MRI. Subsequently brains were cut and stained with Luxol fast blue, Perls stain, and immunohistochemistry for substance P and calbindin. Once the anatomy was defined on histology the dimensions and volume of the substantia nigra were determined on high field magnetic resonance images. Results The anterior border of the substantia nigra was defined by the crus cerebri. In the medial half it was less distinct due to the deposition of iron and the interdigitation of white matter and the substantia nigra. The posterior border was flanked by white matter bridging the red nucleus and substantia nigra and seen as hypointense on spin-echo magnetic resonance images. Within the substantia nigra high signal structures corresponded to confirmed nigrosomes. These were still evident in Parkinson's disease but not in progressive supranuclear palsy. The volume and dimensions of the substantia nigra were similar in Parkinson's disease and controls, but reduced in progressive supranuclear palsy. Conclusions We present a histologically validated anatomical description of the substantia nigra on high field spin-echo high resolution magnetic resonance images and were able to delineate all five nigrosomes. In accordance with the pathological literature we did not observe changes in the nigrosome structure as manifest by volume or signal characteristics within the substantia nigra in Parkinson's disease whereas in progressive supranuclear palsy there was microarchitectural destruction., Highlights • We demonstrate the substantia nigra anatomy using high field spin-echo MRI. • MRI - pathological correlation validates our findings. • We were able to delineate the subcompartments of the substantia nigra - the nigrosomes. • In Parkinson's disease nigrosome structure was maintained but it was lost in progressive supranuclear palsy.

Functional magnetic resonance imaging (fMRI) has become a mainstream neuroimaging modality in the assessment of patients being evaluated for brain tumour and epilepsy surgeries. Thus, it is important for doctors in primary care settings to be well acquainted with the present and potential future applications, as well as limitations, of this modality.The objective of this article is to introduce the theoretical principles and state-of-the-art clinical applications of fMRI in brain tumour and epilepsy surgery, with a focus on the implications for clinical primary care.fMRI enables non-invasive functional mapping of specific cortical tasks (eg motor, language, memory-based, visual), revealing information about functional localisation, anatomical variation in cortical function, and disease effects and adaptations, including the fascinating phenomenon of brain plasticity. fMRI is currently ordered by specialist neurologists and neurosurgeons for the purposes of pre-surgical assessment, and within the context of an experienced multidisciplinary team to prepare, conduct and interpret the scan. With an increasing number of patients undergoing fMRI, general practitioners can expect questions about the current and emerging role of fMRI in clinical care from these patients and their families.

Deep brain stimulation (DBS) for Parkinson's disease is a highly effective treatment in controlling otherwise debilitating symptoms yet the underlying brain mechanisms are currently not well understood. We used whole-brain computational modeling to disclose the effects of DBS ON and OFF during collection of resting state fMRI in ten Parkinson's Disease patients. Specifically, we explored the local and global impact of DBS in creating asynchronous, stable or critical oscillatory conditions using a supercritical bifurcation model. We found that DBS shifts the global brain dynamics of patients nearer to that of healthy people by significantly changing the bifurcation parameters in brain regions implicated in Parkinson's Disease. We also found higher communicability and coherence brain measures during DBS ON compared to DBS OFF. Finally, by modeling stimulation we identified possible novel DBS targets. These results offer important insights into the underlying effects of DBS, which may in time offer a route to more efficacious treatments.

The interplay between each of the stakeholder’s responsibilities and desires clearly has resulted in continued widespread use of natalizumab with substantial risks and an ongoing quest for better risk mitigation. In the United States, regulatory actions codified the process of risk acceptance—and risk transfer—by escalating monitoring and information transfer to physicians and patients. Management of medication-related risks is a core function of regulatory agencies such as the Food and Drug Administration (FDA), European Medicines Agency (EMA), and the medical community. The interaction among stakeholders in medicine, pharma, regulatory bodies, physicians, and patients, sometimes has changed without overt review and discussion. Such is the case for natalizumab, an important and widely used disease-modifying therapy for multiple sclerosis. A rather silent but very considerable shift, effectively transferring increased risk for progressive multifocal leukoencephalopathy (PML) to the physicians and patients, has occurred in the past decade. We believe this changed risk should be clearly recognized and considered by all the stakeholders.

OBJECTIVE: A number of promising experimental therapies for Duchenne muscular dystrophy (DMD) are emerging. Clinical trials currently rely on invasive biopsies or motivation-dependent functional tests to assess outcome. Quantitative muscle magnetic resonance imaging (MRI) could offer a valuable alternative and permit inclusion of non-ambulant DMD subjects. The aims of our study were to explore the responsiveness of upper-limb MRI muscle-fat measurement as a non-invasive objective endpoint for clinical trials in non-ambulant DMD, and to investigate the relationship of these MRI measures to those of muscle force and function. METHODS: 15 non-ambulant DMD boys (mean age 13.3 y) and 10 age-gender matched healthy controls (mean age 14.6 y) were recruited. 3-Tesla MRI fat-water quantification was used to measure forearm muscle fat transformation in non-ambulant DMD boys compared with healthy controls. DMD boys were assessed at 4 time-points over 12 months, using 3-point Dixon MRI to measure muscle fat-fraction (f.f.). Images from ten forearm muscles were segmented and mean f.f. and cross-sectional area recorded. DMD subjects also underwent comprehensive upper limb function and force evaluation. RESULTS: Overall mean baseline forearm f.f. was higher in DMD than in healthy controls (p

Human prion diseases are fatal neurodegenerative disorders caused by misfolding of the prion protein. There are no useful biomarkers of disease progression. Cerebral cortex spongiform change, one of the classical pathological features of prion disease, resolves in prion-infected transgenic mice following prion protein gene knockout. We investigated the cross-sectional, longitudinal and post-mortem cerebral magnetization transfer ratios as a surrogate for prion disease pathology. Twenty-three prion disease patients with various prion protein gene mutations and 16 controls underwent magnetization transfer ratio and conventional magnetic resonance imaging at 1.5 T. For each subject, whole-brain, white and grey matter magnetization transfer ratio histogram mean, peak height, peak location, and magnetization transfer ratio at 25th, 50th and 75th percentile were computed and correlated with several cognitive, functional and neuropsychological scales. Highly significant associations were found between whole brain magnetization transfer ratio and prion disease (P < 0.01). Additionally, highly significant correlations were found between magnetization transfer ratio histogram parameters and clinical, functional and neuropsychological scores (P < 0.01). Longitudinally, decline in the Clinician's Dementia Rating scale was correlated with decline in magnetization transfer ratio. To investigate the histological correlates of magnetization transfer ratio, formalin-fixed cerebral and cerebellar hemispheres from 19 patients and six controls underwent magnetization transfer ratio imaging at 1.5 T, with mean magnetization transfer ratio calculated from six regions of interest, and findings were followed-up in six variant Creutzfeldt-Jakob disease cases with 9.4 T high-resolution magnetization transfer imaging on frontal cortex blocks, with semi-quantitative histopathological scoring of spongiosis, astrocytosis and prion protein deposition. Post-mortem magnetization transfer ratios was significantly lower in patients than controls in multiple cortical and subcortical regions, but not frontal white matter. Measurements (9.4 T) revealed a significant and specific negative correlation between cortical magnetization transfer ratios and spongiosis (P = 0.02), but not prion protein deposition or gliosis. The magnetic resonance imaging measurement of magnetization transfer ratios may be an in vivo surrogate for spongiform change and has potential utility as a therapeutic biomarker in human prion disease.

In recent years, criteria for the diagnosis of multiple sclerosis (MS) have changed, mainly due to the incorporation of new MRI criteria. While the new criteria are a logical step forward, they are complex and-not surprisingly-a good working knowledge of them is not always evident among neurologists and neuroradiologists. In some circumstances, several MRI examinations are needed to achieve an accurate and prompt diagnosis. This provides an incentive for continued efforts to refine the incorporation of MRI-derived information into the diagnostic workup of patients presenting with a clinically isolated syndrome. Within the European multicenter collaborative research network that studies MRI in MS (MAGNIMS), a workshop was held in London in November 2007 to review information that may simplify the existing MS diagnostic criteria, while maintaining a high specificity that is essential to minimize false positive diagnoses. New data that are now published were reviewed and discussed and together with a new proposal are integrated in this position paper.

Quantifying muscle water T 2 (T 2‐water) independently of intramuscular fat content is essential in establishing T 2‐water as an outcome measure for imminent new therapy trials in neuromuscular diseases. IDEAL‐CPMG combines chemical shift fat–water separation with T 2 relaxometry to obtain such a measure. Here we evaluate the reproducibility and B 1 sensitivity of IDEAL‐CPMG T 2‐water and fat fraction (f.f.) values in healthy subjects, and demonstrate the potential of the method to quantify T 2‐water variation in diseased muscle displaying varying degrees of fatty infiltration. The calf muscles of 11 healthy individuals (40.5 ± 10.2 years) were scanned twice at 3 T with an inter‐scan interval of 4 weeks using IDEAL‐CPMG, and 12 patients with hypokalemic periodic paralysis (HypoPP) (42.3 ± 11.5 years) were also imaged. An exponential was fitted to the signal decay of the separated water and fat components to determine T 2‐water and the fat signal amplitude muscle regions manually segmented. Overall mean calf‐level muscle T 2‐water in healthy subjects was 31.2 ± 2.0 ms, without significant inter‐muscle differences (p = 0.37). Inter‐subject and inter‐scan coefficients of variation were 5.7% and 3.2% respectively for T 2‐water and 41.1% and 15.4% for f.f. Bland–Altman mean bias and ±95% coefficients of repeatability were for T 2‐water (0.15, −2.65, 2.95) ms and f.f. (−0.02, −1.99, 2.03)%. There was no relationship between T 2‐water (ρ = 0.16, p = 0.07) or f.f. (ρ = 0.03, p = 0.7761) and B 1 error or any correlation between T 2‐water and f.f. in the healthy subjects (ρ = 0.07, p = 0.40). In HypoPP there was a measurable relationship between T 2‐water and f.f. (ρ = 0.59, p

Objective A number of promising experimental therapies for Duchenne muscular dystrophy (DMD) are emerging. Clinical trials currently rely on invasive biopsies or motivation-dependent functional tests to assess outcome. Quantitative muscle magnetic resonance imaging (MRI) could offer a valuable alternative and permit inclusion of non-ambulant DMD subjects. The aims of our study were to explore the responsiveness of upper-limb MRI muscle-fat measurement as a non-invasive objective endpoint for clinical trials in non-ambulant DMD, and to investigate the relationship of these MRI measures to those of muscle force and function. Methods 15 non-ambulant DMD boys (mean age 13.3 y) and 10 age-gender matched healthy controls (mean age 14.6 y) were recruited. 3-Tesla MRI fat-water quantification was used to measure forearm muscle fat transformation in non-ambulant DMD boys compared with healthy controls. DMD boys were assessed at 4 time-points over 12 months, using 3-point Dixon MRI to measure muscle fat-fraction (f.f.). Images from ten forearm muscles were segmented and mean f.f. and cross-sectional area recorded. DMD subjects also underwent comprehensive upper limb function and force evaluation. Results Overall mean baseline forearm f.f. was higher in DMD than in healthy controls (p

In a multicenter setting, we applied voxel‐based methods to different structural MR imaging modalities to define the relative contributions of focal lesions, normal‐appearing white matter (NAWM), and gray matter (GM) damage and their regional distribution to cognitive deficits as well as impairment of specific cognitive domains in multiple sclerosis (MS) patients. Approval of the institutional review boards was obtained, together with written informed consent from all participants. Standardized neuropsychological assessment and conventional, diffusion tensor and volumetric brain MRI sequences were collected from 61 relapsing‐remitting MS patients and 61 healthy controls (HC) from seven centers. Patients with ≥2 abnormal tests were considered cognitively impaired (CI). The distribution of focal lesions, GM and WM atrophy, and microstructural WM damage were assessed using voxel‐wise approaches. A random forest analysis identified the best imaging predictors of global cognitive impairment and deficits of specific cognitive domains. Twenty‐three (38%) MS patients were CI. Compared with cognitively preserved (CP), CI MS patients had GM atrophy of the left thalamus, right hippocampus and parietal regions. They also showed atrophy of several WM tracts, mainly located in posterior brain regions and widespread WM diffusivity abnormalities. WM diffusivity abnormalities in cognitive‐relevant WM tracts followed by atrophy of cognitive‐relevant GM regions explained global cognitive impairment. Variable patterns of NAWM and GM damage were associated with deficits in selected cognitive domains. Structural, multiparametric, voxel‐wise MRI approaches are feasible in a multicenter setting. The combination of different imaging modalities is needed to assess and monitor cognitive impairment in MS. Hum Brain Mapp 37:1627‐1644, 2016. © 2016 Wiley Periodicals, Inc.

Conventional magnetic resonance imaging (cMRI) is often used to aid the diagnosis of progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), but its ability to predict the histopathological diagnosis has not been systematically studied. cMRI from 48 neuropathologically confirmed cases, including PSP (n = 22), MSA (n = 13), Parkinson's disease (PD) (n = 7), and corticobasal degeneration (n = 6), and controls (n = 9) were assessed blinded to clinical details and systematically rated for reported abnormalities. Clinical diagnosis and macroscopic postmortem findings were retrospectively assessed. Radiological assessment of MRI was correct in 16 of 22 (72.7%) PSP cases and 10 of 13 (76.9%) MSA cases with substantial interrater agreement (Cohen's kappa 0.708; P < .001); no PSP case was misclassified as MSA or vice versa. MRI was less sensitive but more specific than clinical diagnosis in PSP and both more sensitive and specific than clinical diagnosis in MSA. The "hummingbird" and "morning glory" signs were highly specific for PSP, and "the middle cerebellar peduncle sign" and "hot cross bun" for MSA, but sensitivity was lower (up to 68.4%) and characteristic findings may not be present even at autopsy. cMRI, clinical diagnosis, and macroscopic examination at postmortem have similar sensitivity and specificity in predicting a neuropathological diagnosis. We have validated specific radiological signs in pathologically confirmed PSP and MSA. However, the low sensitivity of these and macroscopic findings at autopsy suggest a need for imaging techniques sensitive to microstructural abnormalities without regional atrophy.

The optic radiation is a key white matter structure at risk during epilepsy surgery involving the temporal, parietal or occipital lobes. It shows considerable anatomical variability, cannot be delineated on clinical MRI sequences and damage may cause a disabling visual field deficit. Diffusion tensor imaging tractography allows non-invasive mapping of this pathway. Numerous methods have been published but direct comparison is difficult as patient, acquisition and analysis parameters differ. Two methods for delineating the optic radiation were applied to 6 healthy controls and 4 patients with epileptogenic lesions near the optic radiation. By comparing methods with the same datasets, many of the parameters could be controlled. The first method was previously developed to accurately identify Meyer's loop for planning anterior temporal lobe resection. The second aimed to address limitations of this method by using a more automated technique to reduce operator time and to depict the entire optic radiation. Whilst the core of the tract was common to both methods, there was significant variability between the methods. Method 1 gave a more consistent depiction of Meyer's loop with fewer spurious tracts. Method 2 gave a better depiction of the entire optic radiation, particularly in more posterior portions, but did not identify Meyer's loop in one patient. These results show that whilst tractography is a promising technique, there is significant variability depending on the method chosen even when the majority of parameters are fixed. Different methods may need to be chosen for surgical planning depending on the individual clinical situation.

The potential of MRI to provide quantitative measures of neuromuscular pathology for use in therapeutic trials is being increasingly recognised. Magnetisation transfer (MT) imaging shows particular promise in this context, being sensitive to pathological changes, particularly in skeletal muscle, where measurements correlate with clinically measured muscle strength. Radiofrequency (RF) transmit field (B(1)) inhomogeneities can be particularly problematic in measurements of the MT ratio (MTR) and may obscure genuine muscle MTR changes caused by disease. In this work, we evaluate, for muscle imaging applications, a scheme previously proposed for the correction of RF inhomogeneity artefacts in cerebral MTR maps using B(1) information acquired in the same session. We demonstrate the theoretical applicability of this scheme to skeletal muscle using a two-pool model of pulsed quantitative MT. The correction scheme is evaluated practically in MTR imaging of the lower limbs of 28 healthy individuals and in two groups of patients with representative neuromuscular diseases: Charcot-Marie-Tooth disease type 1A and inclusion body myositis. The correction scheme was observed to reduce both the within-subject and between-subject variability in the calf and thigh muscles of healthy subjects and patient groups in histogram- and region-of-interest-based approaches. This method of correcting for RF inhomogeneity effects in MTR maps using B(1) data may markedly improve the sensitivity of MTR mapping indices as measures of pathology in skeletal muscle.

Background Over 75,000 patients have undergone deep brain stimulation (DBS) procedures worldwide. Magnetic resonance imaging (MRI) is an important clinical and research tool in analyzing electrode location, documenting postoperative complications, and investigating novel symptoms in DBS patients. Functional MRI may shed light on the mechanism of action of DBS. MRI safety in DBS patients is therefore an important consideration. Methods We report our experience with MRI in patients with implanted DBS hardware and examine the literature for clinical reports on MRI safety with implanted DBS hardware. Results A total of 262 MRI examinations were performed in 223 patients with intracranial DBS hardware, including 45 in patients with an implanted pulse generator. Only 1 temporary adverse event occurred related to patient agitation and movement during immediate postoperative MR imaging. Agitation resolved after a few hours, and an MRI obtained before implanted pulse generator implantation revealed edema around both electrodes. Over 4000 MRI examinations in patients with implanted DBS hardware have been reported in the literature. Only 4 led to adverse events, including 2 hardware failures, 1 temporary and 1 permanent neurological deficit. Adverse neurological events occurred in a unique set of circumstances where appropriate safety protocols were not followed. MRI guidelines provided by DBS hardware manufacturers are inconsistent and vary among devices. Conclusions The importance of MRI in modern medicine places pressure on industry to develop fully MRI-compatible DBS devices. Until then, the literature suggests that, when observing certain precautions, cranial MR images can be obtained with an extremely low risk in patients with implanted DBS hardware.

Among the repertoire of motor functions, although hand movement and speech production tasks have been investigated widely by functional neuroimaging, paradigms combining both movements have been studied less so. Such paradigms are of particular interest in Parkinson's disease, in which patients have specific difficulties performing two movements simultaneously. In 9 unmedicated patients with Parkinson's disease and 15 healthy control subjects, externally cued tasks (i.e., hand movement, speech production, and combined hand movement and speech production) were performed twice in a random order and functional magnetic resonance imaging detected cerebral activations, compared to the rest. F-statistics tested within-group (significant activations at P values 10 voxels). For control subjects, the combined task activations comprised the sum of those obtained during hand movement and speech production performed separately, reflecting the neural correlates of performing movements sharing similar programming modalities. In patients with Parkinson's disease, only activations underlying hand movement were observed during the combined task. We interpreted this phenomenon as patients' potential inability to recruit facilitatory activations while performing two movements simultaneously. This lost capacity could be related to a functional prioritization of one movement (i.e., hand movement), in comparison with the other (i.e., speech production). Our observation could also reflect the inability of patients with Parkinson's disease to intrinsically engage the motor coordination necessary to perform a combined task.

Muscle damage, edema, and fat infiltration are hallmarks of a range of neuromuscular diseases. The T-2 of water, T-2,T-w, in muscle lengthens with both myocellular damage and inflammation and is typically measured using multiple spin-echo or Carr-Purcell-Meiboom-Gill acquisitions. However, microscopic fat infiltration in neuromuscular diseases prevents accurate T-2,T-w quantitation as the longer T-2 of fat, T-2,T-f, masks underlying changes in the water component. Fat saturation can be inconsistent across the imaging volume and removes valuable physiological fat information. A new method is presented that combines iterative decomposition of water and fat with echo asymmetry and least squares estimation with a Carr-Purcell-Meiboom-Gill-sequence. The sequence results in water and fat separated images at each echo time for use in T-2,T-w and T-2, f quantification. With knowledge of the T-2,T-w and T-2,T-f, a T-2-corrected fat fraction map can also be calculated. Monte-Carlo simulations and measurements in phantoms, volunteers, and a patient with inclusion body myositis are demonstrated. In healthy volunteers, uniform T-2,T-w and T-2-corrected fat fraction maps are present within all muscle groups. However, muscle-specific patterns of fat infiltration and edema are evident in inclusion body myositis, which demonstrates the power of separating and quantifying the fat and water components. Magn Reson Med 66: 1293-1302, 2011. (C) 2011 Wiley Periodicals, Inc.

Twenty-five years ago, when this journal was initiated, imaging of movement disorders was in its infancy. Since that time, magnetic resonance imaging has become a standard technique that is routinely performed in patients with movement disorders in order to exclude secondary causes and in some instances to provide specific information that aids in making the diagnosis of a neurodegenerative condition. Transcranial sonography is a more recent advance and is now widely employed to aid in the diagnosis of Parkinson's disease and possibly in detecting individuals in the premotor phases of the disease. Investigations are currently under way to evaluate the value of this technique in other movement disorders.

Objectives To investigate the relative somatotopic organization of the motor corticospinal/corticobulbar foot, hand, lip and tongue fascicles by combining fMRI with DTI and to examine the influence of subjacent intrinsic tumours on these fascicles. Methods The study was approved by the local ethics committee. Seven male and three female volunteers (median age: 35 years) and one female and eight male patients with brain tumours (median age: 37 years) were scanned on a 1.5-T MRI scanner. fMRI data, analysed using SPM5, identified the motor task-driven fMRI grey matter activations of the hand, foot, lips and tongue as seed regions for probabilistic tractography. The relationship between the components of the CST was assessed and the distances between them were measured. A statistical comparison was performed comparing these distances in the group of healthy hemispheres with those of the group of non-affected hemispheres and healthy hemispheres. Results Hand fascicles were identified in all subjects (38/38, 100%), followed by foot (32/38, 84%), lip (31/38, 81%) and tongue fascicles (28/38, 74%). At superior levels, the hand fascicles were anterolateral to the foot fascicles in 77–93% of healthy hemispheres (HH), in 50–71% of non-affected patients' hemispheres (pH) and in 67–89% of affected PH. At inferior levels, the hand fascicles were either anteromedial in 46–45% of HH or anterior in 75% of non-affected PH and in 67–83% of affected PH. Tongue and lip fascicles overlapped in 25–45% of HH, in 10–20% of non-affected PH and in 15–25% of affected PH. No significant difference was found between the group of affected hemispheres and that of healthy and non-affected hemispheres. Conclusion The somatotopy of the hand fascicles in relation to the foot fascicles was anterolateral in patients and volunteers at superior levels but anteromedial in volunteers and mostly anterior in patients at inferior levels. The lip and tongue fascicles generally overlapped. Intracranial tumours displaced the motor fascicles without affecting their relative somatotopy., Highlights • Functional and diffusion tensor MRI can detect relationships between particular body regions (such as hands, feet, lips and tongue) represented in the corresponding bundles of brain motor tracts. • fMRI-DTI can detect somatotopy of CST/CBT-bundles & effect of brain tumours on them to avoid disability during tumour resection. • These MRI techniques can also detect the effect of brain tumours on these motor bundles. • This approach can help neurosurgeons avoid these vital motor bundles during tumour resection to prevent any postoperative motor disability.

BG-12, an immunomodulatory agent, reduces frequency of new gadolinium-enhancing (Gd+) lesions in relapsing multiple sclerosis (MS). This study reports the effect of 240 mg BG-12 orally three times daily (tid) for 24 weeks on the evolution of new Gd+ lesions to T1-hypointense lesions. Brain magnetic resonance imaging (MRI) scans from patients in placebo and 240 mg BG-12 tid arms of a phase 2b study were examined retrospectively. Included patients had at least one new Gd+ lesion from weeks 4 to 12. Week 24 scans were analyzed for number and proportion of new Gd+ lesions that evolved to T1-hypointense lesions. Eighteen patients receiving BG-12 and 38 patients receiving placebo were included in the analysis. The analysis tracked 147 new Gd+ lesions in patients from the BG-12 group and 221 Gd+ lesions in patients from the placebo group. The percentage of Gd+ lesions that evolved to T1-hypointense lesions was 34% lower with BG-12 treatment versus placebo (29%, BG-12; 44%, placebo; odds ratio 0.51; 95% confidence interval 0.43, 0.61; p < 0.0001). In addition to reducing frequency of new Gd+ lesions, BG-12 significantly reduced probability of their evolution to T1-hypointense lesions in patients with MS compared with placebo.

Background Intracerebral haemorrhage (ICH) is an uncommon but devastating complication of regular antiplatelet use: identifying high-risk patients before treatment could potentially reduce this hazard. Brain microbleeds on gradient-recalled echo (GRE) T2*-weighted MRI are considered a biomarker for bleeding-prone small-vessel diseases. The authors hypothesised that microbleeds are a risk factor for antiplatelet-related ICH, and investigated this in a hospital-based matched case–control study. Methods Cases of spontaneous ICH were ascertained, using overlapping methods, from a prospective database of 1017 consecutive unselected patients referred to our stroke unit and associated clinics. For each case of antiplatelet-related ICH, two controls matched for age, sex and hypertension without history of ICH on antiplatelet therapy were selected. Microbleeds were identified by a trained observer blinded to clinical details. Results Microbleeds were more frequent in antiplatelet users with ICH than in matched antiplatelet users without ICH (13/16 (81%) vs 6/32 (19%), p=0.004) and patients with non-antiplatelet-related ICH (13/16 (81%) vs 15/33 (45%), p=0.03). The frequency of lobar microbleeds was 11/16 (69%) in antiplatelet-related ICH versus 11/33 (33%) in non antiplatelet-related ICH (p=0.032). Microbleeds were more numerous in antiplatelet users with ICH compared with controls (p=0.016). The number of microbleeds was associated with the risk of antiplatelet-related ICH (adjusted OR 1.33 per additional microbleed, 95% CI 1.06 to 1.66, p=0.013). Conclusions Brain microbleeds are associated with antiplatelet-related ICH. In patients with a large number of lobar microbleeds, the risk of ICH could outweigh the benefits of antiplatelet therapy. Larger prospective studies to investigate the prognostic significance of microbleeds in regular antiplatelet users are warranted.

Importance Deep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a treatment option for Parkinson disease dementia. Objective To evaluate the safety and potential symptomatic effects of NBM DBS in patients with Parkinson disease dementia. Design, Setting, and Participants A randomized, double-blind, crossover clinical trial evaluated the results of 6 patients with Parkinson disease dementia who were treated with NBM DBS at a neurosurgical referral center in the United Kingdom from October 26, 2012, to July 31, 2015. Eligible patients met the diagnostic criteria for Parkinson disease dementia, had motor fluctuations, were appropriate surgical candidates aside from the coexistence of dementia, were age 35 to 80 years, were able to give informed consent, had a Mini-Mental State Examination score of 21 to 26, had minimal atrophy seen on results of brain magnetic resonance imaging, and lived at home with a caregiver-informant. Interventions After surgery, patients were assigned to receive either active stimulation (bilateral, low-frequency [20 Hz] NBM DBS) or sham stimulation for 6 weeks, followed by the opposite condition for 6 weeks. Main Outcomes and Measures The primary outcome was the difference in scores on each item of an abbreviated cognitive battery (California Verbal Learning Test-II, Wechsler Adult Intelligence Scale-III digit span, verbal fluency, Posner covert attention test, and simple and choice reaction times) between the 2 conditions. Secondary outcomes were exploratory and included differences in scores on standardized measurements of cognitive, psychiatric, and motor symptoms and resting state functional magnetic resonance imaging. Results Surgery and stimulation were well tolerated by all 6 patients (all men; mean [SD] age, 65.2 [10.7] years), with no serious adverse events during the trial. No consistent improvements were observed in the primary cognitive outcomes or in results of resting state functional magnetic resonance imaging. An improvement in scores on the Neuropsychiatric Inventory was observed with NBM DBS (8.5 points [range, 4-26 points]) compared with sham stimulation (12 points [range, 8-38 points]; median difference, 5 points; 95% CI, 2.5-8.5 points; P = .03) and the preoperative baseline (13 points [range, 5-25 points]; median difference, 2 points; 95% CI, −8 to 5.5 points; P = .69). Conclusions and Relevance Low-frequency NBM DBS was safely conducted in patients with Parkinson disease dementia; however, no improvements were observed in the primary cognitive outcomes. Further studies may be warranted to explore its potential to improve troublesome neuropsychiatric symptoms. Trial Registration clinicaltrials.gov Identifier:NCT01701544

BACKGROUND AND PURPOSE: DWI using a standard b-value of 1000s/mm(2) has emerged as the most sensitive sequence for the diagnosis of CJD. The purpose of this study was to investigate whether DWI at a high b-value (b = 3000 s/mm(2)) and ADC measurements in the basal nuclei improve the diagnosis of vCJD and sCJD compared with visual assessment of DWI at a standard b-value (b = 1000 s/mm(2)). MATERIALS AND METHODS: Eight patients with vCJD, 9 patients with sCJD, and 5 healthy volunteers underwent DWI at b = 1000 s/mm(2), and 5 vCJD patients, 4 sCJD patients, and 1 growth hormone-related CJD patient underwent DWI at b = 3000 s/mm(2). Two consultant neuroradiologists performed a visual comparison of the b = 1000 and b = 3000 images. Mean MR SI and ADC values were determined for C, P, and DM thalamus ROIs bilaterally at each b-value. SI ratios for each ROI relative to white matter were calculated. RESULTS: In 9 out of 10 patients, the higher b-value images were more sensitive to SI change, particularly in cortex and thalamus, with higher SI ratios at b = 3000 in the DM thalamus. For sCJD at b = 1000, we found significantly lower ADC values in the C and P compared with controls (mean C ADC = 587.3 ± 84.7 mm(2)/s in sCJD patients versus 722.7 ± 16.6 mm(2)/s in controls; P = .007), and at b = 3000, the differences were more pronounced. In comparison, in vCJD at b = 1000, ADC values were elevated in the Pu (mean Pu ADC = 837.6 ± 33.0 mm/s(2) in vCJD patients versus 748.0 ± 17.3 mm/s(2) in controls; P < .001) but failed to reach significance at b = 3000. CONCLUSIONS: Our results demonstrate that b = 3000 DWI, being more sensitive to slowly diffusing tissue water, is more sensitive to pathology in sCJD than is conventional DWI. High-b-value DWI increases confidence in the radiologic diagnosis of human prion disease.

Saccades, smooth pursuit, and optokinetic nystagmus (OKN) are three basic eye movements in our ocular motor repertoire that enable us to explore the visual field. These eye movements are cortically controlled in different cortical eye fields, including the frontal eye fields (FEF) and parietal eye fields (PEF), as well as the motion-sensitive visual area MT+/V5. It is not known if this cortical control is organized in parallel cortico-cortical networks or in adjacent subregions of one system. Nor do we know where the specific eye fields are exactly located. Functional magnetic resonance imaging (fMRI) was used to investigate these open questions about the FEF, PEF, and MT+/V5. Activations of the cortical network of eye-movement control were found in the frontal, parietal, and occipital cortex. While the activation pattern for OKN was not a combination of the patterns for saccades and smooth pursuit, the results suggest that cortical control of OKN occurs in a network parallel to that of saccades and smooth pursuit. Furthermore, a division of the FEF and the PEF into two parts was confirmed for the three ocular motor tasks, as well as a division within each of the three paradigms. MT+/V5 showed two partitions only for saccades, but not for smooth pursuit or OKN.

BACKGROUND: Progressive brain atrophy in multiple sclerosis (MS) may reflect neuroaxonal and myelin loss and MRI measures of brain tissue loss are used as outcome measures in MS treatment trials. This study investigated sample sizes required to demonstrate reduction of brain atrophy using three outcome measures in a parallel group, placebo-controlled trial for secondary progressive MS (SPMS).METHODS: Data were taken from a cohort of 43 patients with SPMS who had been followed up with 6-monthly T1-weighted MRI for up to 3 years within the placebo arm of a therapeutic trial. Central cerebral volumes (CCVs) were measured using a semiautomated segmentation approach, and brain volume normalized for skull size (NBV) was measured using automated segmentation (SIENAX). Change in CCV and NBV was measured by subtraction of baseline from serial CCV and SIENAX images; in addition, percentage brain volume change relative to baseline was measured directly using a registration-based method (SIENA). Sample sizes for given treatment effects and power were calculated for standard analyses using parameters estimated from the sample.RESULTS: For a 2-year trial duration, minimum sample sizes per arm required to detect a 50% treatment effect at 80% power were 32 for SIENA, 69 for CCV, and 273 for SIENAX. Two-year minimum sample sizes were smaller than 1-year by 71% for SIENAX, 55% for CCV, and 44% for SIENA.CONCLUSION: SIENA and central cerebral volume are feasible outcome measures for inclusion in placebo-controlled trials in secondary progressive multiple sclerosis.

Short-term adaptation indicates the attenuation of the functional MRI (fMRI) response during repeated task execution. It is considered to be a physiological process, but it is unknown whether short-term adaptation changes significantly in patients with brain disorders, such as multiple sclerosis (MS). In order to investigate short-term adaptation during a repeated right-hand tapping task in both controls and in patients with MS, we analyzed the fMRI data collected in a large cohort of controls and MS patients who were recruited into a multi-centre European fMRI study. Four fMRI runs were acquired for each of the 55 controls and 56 MS patients at baseline and 33 controls and 26 MS patients at 1-year follow-up. The externally cued (1 Hz) right hand tapping movement was limited to 3 cm amplitude by using at all sites (7 at baseline and 6 at follow-up) identically manufactured wooden frames. No significant differences in cerebral activation were found between sites. Furthermore, our results showed linear response adaptation (i.e. reduced activation) from run 1 to run 4 (over a 25 minute period) in the primary motor area (contralateral more than ipsilateral), in the supplementary motor area and in the primary sensory cortex, sensory-motor cortex and cerebellum, bilaterally. This linear activation decay was the same in both control and patient groups, did not change between baseline and 1-year follow-up and was not influenced by the modest disease progression observed over 1 year. These findings confirm that the short-term adaptation to a simple motor task is a physiological process which is preserved in MS.

We performed a prospective multi-centre study using functional magnetic resonance imaging (fMRI) to better characterize the relationships between clinical expression and brain function in patients with multiple sclerosis (MS) at eight European sites (56 MS patients and 60 age-matched, healthy controls). Patients showed greater task-related activation bilaterally in brain regions including the pre- and post-central, inferior and superior frontal, cingulate and superior temporal gyri and insula (P < 0.05, all statistics corrected for multiple comparisons). Both patients and healthy controls showed greater brain activation with increasing age in the ipsilateral pre-central and inferior frontal gyri (P < 0.05). Patients, but not controls, showed greater brain activation in the anterior cingulate gyrus and the bilateral ventral striatum (P < 0.05) with less hand dexterity. An interaction between functional activation changes in MS and age was found. This large fMRI study over a broadly selected MS patient population confirms that movement for patients demands significantly greater cognitive 'resource allocation' and suggests age-related differences in brain responses to the disease. These observations add to evidence that brain functional responses (including potentially adaptive brain plasticity) contribute to modulation of clinical expression of MS pathology and demonstrate the feasibility of a multi-site functional MRI study of MS.

Image-guided neurosurgery involves the display of MRI-based preoperative plans in an intraoperative reference frame. Interventional MRI (iMRI) can serve as a reference for non-rigid registration based propagation of preoperative MRI. Structural MRI images exhibit spatially varying intensity relationships, which can be captured by a local similarity measure such as the local normalized correlation coefficient (LNCC). However, LNCC weights local neighborhoods using a static spatial kernel and includes voxels from beyond a tissue or resection boundary in a neighborhood centered inside the boundary. We modify LNCC to use locally adaptive weighting inspired by bilateral filtering and evaluate it extensively in a numerical phantom study, a clinical iMRI study and a segmentation propagation study. The modified measure enables increased registration accuracy near tissue and resection boundaries.

We investigated safety issues and potential experimental confounds when performing functional magnetic resonance imaging (fMRI) investigations in human subjects with fully implanted, active, deep brain stimulation (DBS) systems. Measurements of temperature and induced voltage were performed in an in vitro arrangement simulating bilateral DBS during magnetic resonance imaging (MRI) using head transmit coils in both 1.5 and 3.0 T MRI systems. For MRI sequences typical of an fMRI study with coil-averaged specific absorption rates (SARs) less than 0.4 W/kg, no MRI-induced temperature change greater than the measurement sensitivity (0.1 degrees C) was detected at 1.5 T, and at 3 T temperature elevations were less than 0.5 degrees C, i.e. within safe limits. For the purposes of demonstration, MRI pulse sequences with SARs of 1.45 W/kg and 2.34 W/kg (at 1.5 T and 3 T, respectively) were prescribed and elicited temperature increases (>1 degrees C) greater than those considered safe for human subjects. Temperature increases were independent of the presence or absence of active stimulator pulsing. At both field strengths during echo planar MRI, the perturbations of DBS equipment performance were sufficiently slight, and temperature increases sufficiently low to suggest that thermal or electromagnetically mediated experimental confounds to fMRI with DBS are unlikely. We conclude that fMRI studies performed in subjects with subcutaneously implanted DBS units can be both safe and free from DBS-specific experimental confounds. Furthermore, fMRI in subjects with fully implanted rather than externalized DBS stimulator units may offer a significant safety advantage. Further studies are required to determine the safety of MRI with DBS for other MRI systems, transmit coil configurations and DBS arrangements.

In a 2-year, placebo-controlled trial (the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis [AFFIRM] study), involving 942 patients with relapsing multiple sclerosis (MS), natalizumab significantly reduced the relapse rate by 68% and progression of sustained disability by 42% vs placebo. We report the effect of natalizumab on MRI measures from the AFFIRM study.The number and volume of gadolinium (Gd)-enhancing, new or enlarging T2-hyperintense, and new T1-hypointense lesions and brain parenchymal fraction were measured from annual scans obtained at baseline, 1 year, and 2 years.Compared with placebo, natalizumab produced a 92% decrease in Gd-enhancing lesions (means 2.4 vs 0.2; p0.001), an 83% decrease in new or enlarging T2-hyperintense lesions (means 11.0 vs 1.9; p0.001), and a 76% decrease in new T1-hypointense lesions (means 4.6 vs 1.1; p0.001) over 2 years. Median T2-hyperintense lesion volume increased by 8.8% in the placebo group and decreased by 9.4% in the natalizumab group (p0.001); median T1-hypointense lesion volume decreased by 1.5% in the placebo group and decreased by 23.5% in the natalizumab group (p0.001). Brain atrophy was greater in year 1 and less in year 2 in natalizumab-treated patients.Natalizumab has a sustained effect in preventing the formation of new lesions in patients with relapsing multiple sclerosis.

Purpose of review This review will outline the imaging anatomy of the vestibular and visual pathways, using computed tomography and magnetic resonance imaging, with emphasis on the more recent developments in neuroimaging. Recent findings Technical advances in computed tomography and magnetic resonance imaging, such as the advent of multislice computed tomography and newer magnetic resonance imaging techniques such as T2-weighted magnetic resonance cisternography, have improved the imaging of the vestibular and visual pathways, allowing better visualization of the end organs and peripheral nerves. Higher field strength magnetic resonance imaging is a promising tool, which has been used to evaluate and resolve fine anatomic detail in vitro, as in the labyrinth. Advanced magnetic resonance imaging techniques such as functional magnetic resonance imaging and diffusion tractography have been used to identify cortical areas of activation and associated white matter pathways, and show potential for the future identification of complex neuronal relays involved in integrating these pathways. Summary The assessment of the various components of the vestibular and the visual systems has improved with more detailed research on the imaging anatomy of these systems, the advent of high field magnetic resonance scanners and multislice computerized tomography, and the wider use of specific techniques such as tractography which displays white matter tracts not directly accessible until now.

Because of concerns about direct visualization of the subthalamic nucleus (STN) on magnetic resonance imaging (MRI), many functional neurosurgeons continue to rely on atlas-based coordinates to reach this target. T2-weighted MRI does allow direct visualisation of the STN. In order to compare the coordinates of the target point within the visualised STN with those obtained from standard brain atlases, the preoperative stereotactic T2-weighted MRI used to implant 55 deep brain stimulation electrodes in the visualised STN of 29 consecutive patients with Parkinson's disease treated in two European centres were studied. The coordinates of the directly visualised STN were significantly different from those of the atlas target. Variability of the position of the STN may render direct visualisation a more accurate means of targeting this nucleus.

Background Cortical grey matter (GM) lesions are common in multiple sclerosis (MS), but little is known about their temporal evolution. We investigated this in people with relapsing–remitting (RR) and secondary progressive (SP) MS. Methods 27 people with RRMS, and 22 with SPMS were included in this study. Phase-sensitive inversion recovery scans were acquired on 2 occasions. Cortical GM lesions were classified as intracortical (IC, only involving GM) and leucocortical (LC, mixed GM–white matter (WM)); WM lesions touching the cortex as juxtacortical (JC). On follow-up scans, new IC, LC and JC lesions were identified, and any change in classification of lesions previously observed was noted. WM lesion counts in the whole brain were assessed on PD/T2-weighted scans. Results Over a mean (SD) of 21.0 (5.8) months, the number of new IC lesions per person per year was greater in SPMS (1.6 (1.9)) than RRMS (0.8 (1.9)) (Mann-Whitney p=0.039). All new LC lesions arose from previously seen IC lesions (SPMS 1.4 (1.8) per person per year, and RRMS 1.1 (1.0)), and none arose de novo, or from previously seen JC lesions. Changes in cortical GM (either new IC or IC converting to LC) lesion counts did not correlate with the changes in WM lesion counts. Conclusions New cortical GM lesions rarely arise from the WM and the rate of new IC lesion formation is not closely linked with WM lesion accrual. IC lesion formation appears to be more common in SPMS than RRMS.