Christoph Stippich

Patients with atrial fibrillation (AF) have an increased risk of cognitive decline, potentially resulting from clinically unrecognized vascular brain lesions.This study sought to assess the relationships between cognitive function and vascular brain lesions in patients with AF.Patients with known AF were enrolled in a multicenter study in Switzerland. Brain magnetic resonance imaging (MRI) and cognitive testing using the Montreal Cognitive Assessment (MoCA) were performed in all participants. Large noncortical or cortical infarcts (LNCCIs), small noncortical infarcts (SNCIs), microbleeds, and white matter lesions were quantified by a central core laboratory. Clinically silent infarcts were defined as infarcts on brain MRI in patients without a clinical history of stroke or transient ischemic attack.The study included 1,737 patients with a mean age of 73 ± 8 years (28% women, 90% taking oral anticoagulant agents). On MRI, LNCCIs were found in 387 patients (22%), SNCIs in 368 (21%), microbleeds in 372 (22%), and white matter lesions in 1715 (99%). Clinically silent infarcts among the 1,390 patients without a history of stroke or transient ischemic attack were found in 201 patients with LNCCIs (15%) and 245 patients with SNCIs (18%). The MoCA score was 24.7 ± 3.3 in patients with and 25.8 ± 2.9 in those without LNCCIs on brain MRI (p < 0.001). The difference in MoCA score remained similar when only clinically silent LNCCIs were considered (24.9 ± 3.1 vs. 25.8 ± 2.9; p < 0.001). In a multivariable regression model including all vascular brain lesion parameters, LNCCI volume was the strongest predictor of a reduced MoCA (β = -0.26; 95% confidence interval: -0.40 to -0.13; p < 0.001).Patients with AF have a high burden of LNCCIs and other brain lesions on systematic brain MRI screening, and most of these lesions are clinically silent. LNCCIs were associated with worse cognitive function, even among patients with clinically silent infarcts. Our findings raise the question of MRI screening in patients with AF.

The human primary sensorimotor cortex was investigated for somatotopic organization during motor imagery (IM) which was compared to motor execution (EM). Block designed BOLD (blood oxygen level dependent)-functional magnetic resonance imaging at 1.5 Tesla was applied in 14 right handed volunteers during imagined and executed tongue, finger and toe movements. BOLD-clusters were assessed for anatomically correct sensorimotor localization. Euklidian coordinates, relative signal change and correlation to the applied reference function were determined. Statistical means were calculated. IM recruited somatotopically organized primary sensorimotor representations of the precentral gyrus that reflected the homunculus and overlapped in part with EM representations. Mean BOLD-signals ranged from 1.93 to 3.18% for EM, and from 0.73 to 1.47% for IM. The results support the hypothesis that the primary sensorimotor cortex is active during IM and that IM and EM share common functional circuits.

Impaired cognitive-behavioral flexibility is regarded as a trait marker in anorexia nervosa patients. The authors sought to investigate the neural correlates of this deficit in executive functioning in anorexia nervosa.Fifteen women with anorexia nervosa and 15 age-matched healthy comparison women underwent event-related functional MRI while performing a target-detection task. The task distinguished between shifts in behavioral response and shifts in cognitive set. It involved infrequent target and non-target distractor stimuli embedded in a sequence of prepotent standard stimuli.Relative to comparison subjects, anorexia nervosa patients showed a significantly higher error rate in behavioral response shifting, independent of whether those runs also involved cognitive set shifting. During behavioral response shifting, patients showed reduced activation in the left and right thalamus, ventral striatum, anterior cingulate cortex, sensorimotor brain regions, and cerebellum that differed significantly from the comparison group but showed dominant activation in frontal and parietal brain regions. These differential activations in patients and comparison subjects were specific to shifts in behavioral response: except for thalamic activation, they were not observed in response to non-target distractor trials that required no alteration in behavioral response.Impaired behavioral response shifting in anorexia nervosa seems to be associated with hypoactivation in the ventral anterior cingulate-striato-thalamic loop that is involved in motivation-related behavior. In contrast, anorexia nervosa patients showed predominant activation of frontoparietal networks that is indicative of effortful and supervisory cognitive control during task performance.

The present study employs a new framework to categorise the heterogeneous findings on the relationship between impaired reward processing and negative and affective symptoms of schizophrenia. Based on previous behavioural and neuroimaging studies we postulate that "wanting" (i.e. anticipation) of a reward is specifically related to apathy, whereas "liking" (i.e. hedonic impact) is related to anhedonia and depression--symptoms commonly observed in schizophrenia. Fifteen patients with schizophrenia or schizoaffective disorder treated with atypical antipsychotic drugs and fifteen healthy controls performed a probabilistic monetary incentive delay task while undergoing functional magnetic resonance imaging. At the group level we found no significant differences between patients and controls in neural activation during anticipation or receipt of a reward. However, in patients with schizophrenia specific relationships between ventral-striatal activation and symptoms were observed. Ventral-striatal activation during reward anticipation was negatively correlated with apathy, while activation during receipt of reward was negatively correlated with severity of depressive symptoms. These results suggest that the link between negative symptoms and reward anticipation might specifically relate to apathy, i.e. a lack of motivation and drive. Impaired hedonic reward processing might contribute to the development of depressive symptoms in patients with schizophrenia, but it is not directly associated with self-rated anhedonia. These results indicate the necessity of more specifically differentiating negative and affective symptoms in schizophrenia in order to understand the role of the reward system in their pathogenesis.

Simultaneous interictal EEG and magnetoencephalography (MEG) recordings were used for noninvasive analysis of epileptogenicity in focal cortical dysplasia (FCD). The results of two different approach methods (multiple source analysis of averaged spikes and single dipole peak localization of single spikes) were compared with pre- and postoperative anatomic magnetic resonance imaging (MRI).We studied nine children and adolescents (age, 3.5-15.9 years) with localization-related epilepsy and FCD diagnosis based on MRI. Five patients underwent epilepsy surgery, two of them after long-term recording with subdural grid electrodes, and one after intraoperative electrocorticography.The 122-channel whole-head MEGs and 33-channel EEGs were recorded simultaneously for 25 to 40 min. Interictal spikes were identified visually and used as templates to search for similar spatiotemporal spike patterns throughout the recording. With the BESA program, similar spikes (r > 0.85) were detected, averaged, high-pass filtered (5 Hz) to enhance spike onset, and subjected to multiple spatiotemporal source analysis with a multishell spherical head model. Peak activity from single spikes was modeled by single dipoles for the same subset of spikes. Source localization was visualized by superposition on T1-weighted MRI and compared with the lesion identified in T1- and T2-weighted MRI. In the five cases undergoing epilepsy surgery, the results were correlated with invasive recordings, postoperative MRI, and outcome.In all cases, the analysis of averaged spikes showed a localization of onset- and peak-related sources within the visible lesion for both EEG and MEG. Of the single spikes, 128 (45%; total 284) were localizable at the peak in MEG, and 170 (60%) in EEG. Of these, 91% localized within the lesion with MEG, and 93.5% with EEG. In three of five patients operated on, the resected area included the onset zones of averaged EEG and MEG spike activity. These patients had excellent postoperative outcome, whereas the others did not become seizure free.Consistent MEG and EEG spike localization in the lesional zone confirmed the hypothesis of intrinsic epileptogenicity in FCD.

Chronic subthreshold stimulation of the contralateral precentral gyrus is used in patients with intractable neuropathic pain for more than 15 years. The aim of this study was to analyse retrospectively our own patient group with long term follow-up of 10 years. Seventeen patients with chronic neuropathic pain were treated with contralateral epidural stimulation electrodes. In 10 cases, trigeminal neuropathic pain (TNP) and in seven cases post-stroke pain (PSP) were diagnosed. The placement of the electrodes was performed in local anaesthesia using neuronavigation and intraoperative neuromonitoring. A test trial of minimum one week including double-blind testing was conducted and pain intensity was measured using a visual analogue scale (VAS). Correct placement of the electrode was achieved in all patients using intraoperative neurophysiological monitoring. Double-blind testing was able to identify 6 (35%) non-responders. In 5 of 10 (50%) with TNP and 3 of 7 (43%) with PSP a positive effect with pain reduction ≥50% was observed. The mean follow-up period was 3.6 years (range 1–10 years) and includes a patient with 10 years of positive stimulation effect. Stimulation of the motor cortex is a treatment option for patients with chronic neuropathic pain localized in the face or upper extremity. Double-blind testing can identify non-responders. Patients with TNP profit more than patients with PSP. The positive effect can last for ten years in long-term follow-up.

The neural processing of reward can be differentiated into two sub-components with different functions, "wanting" (i.e., the expectation of a reward which includes appetitive and motivational components) and "liking" (i.e., the hedonic impact experienced during the receipt of a reward), involving distinct neural systems. We hypothesize that variability in neural reward processing previously observed in healthy subjects could reflect inter-individual differences in personality. Therefore, the aim of this study was to investigate how the neural processing during expectation and reception of a reward depends on interpersonal differences in reward sensitivity, more specifically the tendency to approach vs. avoid reward-related situations. We employed event-related functional magnetic resonance imaging during a monetary incentive delay task. Subjects with a high approach motivation showed more activation of the Ventral Striatum (VS) during the receipt of a reward, and more medial orbitofrontal activity during both the receipt and omission of a reward. Subjects with a high behavioral inhibition showed less activation in the VS during the receipt of a reward. These findings indicate that the tendency to approach or avoid reward-related situations exhibits a distinct relation with neural reward processing. Specifically, subjects with high behavioral approach appear to be sensitive mainly to positive outcomes and to a lesser extent to the omissions of rewards, whereas subjects with low behavioral approach as well as those with a high inhibition tendency display a blunted response to rewards.

Understanding long-term disability in multiple sclerosis (MS) is a key goal of research; it is relevant to how we monitor and treat the disease.The Magnetic Imaging in MS (MAGNIMS) collaborative group sought to determine the relationship of brain lesion load, and brain and spinal cord atrophy, with physical disability in patients with long-established MS.Patients had a magnetic resonance imaging (MRI) scan of their brain and spinal cord, from which we determined brain grey (GMF) and white matter (WMF) fractional volumes, upper cervical spinal cord cross-sectional area (UCCA) and brain T2-lesion volume (T2LV). We assessed patient disability using the Expanded Disability Status Scale (EDSS). We analysed associations between EDSS and MRI measures, using two regression models (dividing cohort by EDSS into two and four sub-groups).In the binary model, UCCA (p < 0.01) and T2LV (p = 0.02) were independently associated with the requirement of a walking aid. In the four-category model UCCA (p < 0.01), T2LV (p = 0.02) and GMF (p = 0.04) were independently associated with disability.Long-term physical disability was independently linked with atrophy of the spinal cord and brain T2 lesion load, and less consistently, with brain grey matter atrophy. Combinations of spinal cord and brain MRI measures may be required to capture clinically-relevant information in people with MS of long disease duration.

Background and Purpose: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. Methods: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. Results: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. Conclusions: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.

Absolute pitch (AP) perception is the auditory ability to effortlessly recognize the pitch of any given tone without external reference. To study the neural substrates of this rare phenomenon, we developed a novel behavioral test, which excludes memory-based interval recognition and permits quantification of AP proficiency independently of relative pitch cues. AP- and non-AP-possessing musicians were studied with morphological and functional magnetic resonance imaging (fMRI) and magnetoencephalography. Gray matter volume of the right Heschl's gyrus (HG) was highly correlated with AP proficiency. Right-hemispheric auditory evoked fields were increased in the AP group. fMRI revealed an AP-dependent network of right planum temporale, secondary somatosensory, and premotor cortices, as well as left-hemispheric “Broca's” area. We propose the right HG as an anatomical marker of AP and suggest that a right-hemispheric network mediates AP “perception,” whereas pitch “labeling” takes place in the left hemisphere.

<h2>Summary</h2><h3>Background</h3> Cervical artery dissection is a major cause of stroke in young people (aged <50 years). Historically, clinicians have preferred using oral anticoagulation with vitamin K antagonists for patients with cervical artery dissection, although some current guidelines—based on available evidence from mostly observational studies—suggest using aspirin. If proven to be non-inferior to vitamin K antagonists, aspirin might be preferable, due to its ease of use and lower cost. We aimed to test the non-inferiority of aspirin to vitamin K antagonists in patients with cervical artery dissection. <h3>Methods</h3> We did a multicentre, randomised, open-label, non-inferiority trial in ten stroke centres across Switzerland, Germany, and Denmark. We randomly assigned (1:1) patients aged older than 18 years who had symptomatic, MRI-verified, cervical artery dissection within 2 weeks before enrolment, to receive either aspirin 300 mg once daily or a vitamin K antagonist (phenprocoumon, acenocoumarol, or warfarin; target international normalised ratio [INR] 2·0–3·0) for 90 days. Randomisation was computer-generated using an interactive web response system, with stratification according to participating site. Independent imaging core laboratory adjudicators were masked to treatment allocation, but investigators, patients, and clinical event adjudicators were aware of treatment allocation. The primary endpoint was a composite of clinical outcomes (stroke, major haemorrhage, or death) and MRI outcomes (new ischaemic or haemorrhagic brain lesions) in the per-protocol population, assessed at 14 days (clinical and MRI outcomes) and 90 days (clinical outcomes only) after commencing treatment. Non-inferiority of aspirin would be shown if the upper limit of the two-sided 95% CI of the absolute risk difference between groups was less than 12% (non-inferiority margin). This trial is registered with ClinicalTrials.gov, NCT02046460. <h3>Findings</h3> Between Sept 11, 2013, and Dec 21, 2018, we enrolled 194 patients; 100 (52%) were assigned to the aspirin group and 94 (48%) were assigned to the vitamin K antagonist group. The per-protocol population included 173 patients; 91 (53%) in the aspirin group and 82 (47%) in the vitamin K antagonist group. The primary endpoint occurred in 21 (23%) of 91 patients in the aspirin group and in 12 (15%) of 82 patients in the vitamin K antagonist group (absolute difference 8% [95% CI −4 to 21], non-inferiority p=0·55). Thus, non-inferiority of aspirin was not shown. Seven patients (8%) in the aspirin group and none in the vitamin K antagonist group had ischaemic strokes. One patient (1%) in the vitamin K antagonist group and none in the aspirin group had major extracranial haemorrhage. There were no deaths. Subclinical MRI outcomes were recorded in 14 patients (15%) in the aspirin group and in 11 patients (13%) in the vitamin K antagonist group. There were 19 adverse events in the aspirin group, and 26 in the vitamin K antagonist group. <h3>Interpretation</h3> Our findings did not show that aspirin was non-inferior to vitamin K antagonists in the treatment of cervical artery dissection. <h3>Funding</h3> Swiss National Science Foundation, Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, Academic Society Basel.

<h3>Objective</h3> Cross-sectional studies have shown that spinal cord volume (SCV) loss is related to disease severity in multiple sclerosis (MS). However, long-term data are lacking. Our aim was to evaluate SCV loss as a biomarker of disease progression in comparison to other MRI measurements in a large cohort of patients with relapse-onset MS with 6-year follow-up. <h3>Methods</h3> The upper cervical SCV, the total brain volume, and the brain T2 lesion volume were measured annually in 231 patients with MS (180 relapsing-remitting [RRMS] and 51 secondary progressive [SPMS]) over 6 years on 3-dimensional, T1-weighted, magnetization-prepared rapid-acquisition gradient echo images. Expanded Disability Status Scale (EDSS) score and relapses were recorded at every follow-up. <h3>Results</h3> Patients with SPMS had lower baseline SCV (<i>p</i> &lt; 0.01) but no accelerated SCV loss compared to those with RRMS. Clinical relapses were found to predict SCV loss over time (<i>p</i> &lt; 0.05) in RRMS. Furthermore, SCV loss, but not total brain volume and T2 lesion volume, was a strong predictor of EDSS score worsening over time (<i>p</i> &lt; 0.05). The mean annual rate of SCV loss was the strongest MRI predictor for the mean annual EDSS score change of both RRMS and SPMS separately, while correlating stronger in SPMS. Every 1% increase of the annual SCV loss rate was associated with an extra 28% risk increase of disease progression in the following year in both groups. <h3>Conclusion</h3> SCV loss over time relates to the number of clinical relapses in RRMS, but overall does not differ between RRMS and SPMS. SCV proved to be a strong predictor of physical disability and disease progression, indicating that SCV may be a suitable marker for monitoring disease activity and severity.

Patients with schizophrenia routinely fail to perform affect recognition tasks as accurately as healthy controls. The investigation of performance-related changes in cerebral activation in healthy subjects may facilitate the understanding of adaptation processes to different levels of difficulty and help to interpret the activation changes found in schizophrenic patients. Nine first hospitalized partly remitted schizophrenic patients and 10 healthy controls participated in an fMRI study with a facial affect discrimination and labeling task. Seven of the 10 healthy subjects were reexamined with changed stimulus conditions adapted according to the mean accuracy scores detected in schizophrenic patients. Controls showed a significantly increased activation of the right gyrus frontalis medialis with rising task difficulty during both tasks. The schizophrenic patients demonstrated a significantly decreased activation of the anterior cingulate during facial affect discrimination and of the amygdala-hippocampal complex bilaterally during facial affect labeling. In addition, an increased activation of the gyrus frontalis medialis bilaterally became apparent in the schizophrenic patients. It is suggested that the latter may reflect a compensatory effort for deficits in more basal limbic functions.

To prospectively assess the feasibility of standardized presurgical functional magnetic resonance (MR) imaging for localizing the Broca and Wernicke areas and for lateralizing language function.The study was approved by the responsible ethics commission, and patients gave written informed consent. Eighty-one patients (36 female and 45 male patients; age range, 7-75 years) with different brain tumors underwent blood oxygen level-dependent functional MR imaging at 1.5 T with two paradigms: sentence generation (SG) and word generation (WG). Functional MR imaging measurements, data processing, and evaluation were fully standardized by using dedicated software. Four regions of interest were evaluated in each patient: the Broca and Wernicke areas and their anatomic homologues in the right hemisphere. Statistics were calculated.The SG and WG paradigms were successfully completed by all (100%) and 70 (86%) patients, respectively. Success rates in localizing and lateralizing language were 96% for the Broca and Wernicke areas with the SG paradigm, 81% for the Broca area and 80% for the Wernicke area with the WG paradigm, and 98% for both areas when the SG and WG paradigms were used in combination. Functional localizations were consistent for SG and WG paradigms in the inferior frontal gyrus (Broca area) and the superior temporal, supramarginal, and angular gyri (Wernicke area). Surgery was not performed in seven patients (9%) and was modified in two patients (2%) because of functional MR imaging findings.Functional MR imaging proved to be feasible during routine diagnostic neuroimaging for localizing and lateralizing language function preoperatively.

Unilateral sensory stimulation reliably elicits contralateral somatotopic activation of primary (SI) and secondary (SII) somatosensory cortex. There is an ongoing debate about the occurrence and nature of concomitant ipsilateral SI and SII activation. Here we used functional magnetic resonance imaging (fMRI) in healthy human subjects with unilateral tactile stimulation of fingers and lips, to compare somatosensory activation patterns from distal and proximal body parts. We hypothesized that fMRI in humans should reflect the functional connectivity of somatosensory cortex as predicted by animal studies. We show that both unilateral finger and lip stimulations activate contra- and ipsilateral SI and SII cortices with high detection frequency. Correlations of BOLD-signals to the applied hemodynamic reference function were significantly higher in contralateral as compared to ipsilateral SI and SII cortices for both finger and lip stimulation, reflecting strong contribution of contralateral thalamocortical input. Furthermore, BOLD-signal correlations were higher in SI than in SII activations on the contralateral but not on the ipsilateral side. While these asymmetries within and across hemispheres were consistent for finger and lip stimulations, indicating analogous underlying organizing principles, they were less prominent for lip stimulation. Somatotopic organization was detected in SI but not in SII representations of fingers and lips. These results qualitatively and quantitatively support the prevalent concepts of anatomical and functional connectivity in the somatosensory system and therefore may allow interpretation of sensory evoked fMRI signals in terms of normal human brain function. Thus, the assessment of human somatosensory function with fMRI may permit in the future investigations of pathological conditions.

We studied the trigeminal nerve in seven healthy volunteers and six patients with trigeminal neuralgia using the diffusion tensor imaging derived parameter fractional anisotropy (FA). While controls did not show a difference between both sides, there was a reduction of FA in the affected nerve in three of six patients with accompanying nerve-vessel conflict and atrophy. Reversibility of abnormally low FA values was demonstrated in one patient successfully treated with microvascular decompression.

Reliable imaging of eloquent tumour-adjacent brain areas is necessary for planning function-preserving neurosurgery. This study evaluates the potential diagnostic benefits of presurgical functional magnetic resonance imaging (fMRI) in comparison to a detailed analysis of morphological MRI data.Standardised preoperative functional and structural neuroimaging was performed on 77 patients with rolandic mass lesions at 1.5 Tesla. The central region of both hemispheres was allocated using six morphological and three functional landmarks.fMRI enabled localisation of the motor hand area in 76/77 patients, which was significantly superior to analysis of structural MRI (confident localisation of motor hand area in 66/77 patients; p < 0.002). FMRI provided additional diagnostic information in 96% (tongue representation) and 97% (foot representation) of patients. FMRI-based presurgical risk assessment correlated in 88% with a positive postoperative clinical outcome.Routine presurgical FMRI allows for superior assessment of the spatial relationship between brain tumour and motor cortex compared with a very detailed analysis of structural 3D MRI, thus significantly facilitating the preoperative risk-benefit assessment and function-preserving surgery. The additional imaging time seems justified. FMRI has the potential to reduce postoperative morbidity and therefore hospitalisation time.

The cerebellum is known to be involved not only in motor but also cognitive and affective processes. Structural changes in the cerebellum in relation to cognitive dysfunction are an emerging topic in the field of neuro-psychiatric disorders. In Multiple Sclerosis (MS) cerebellar motor and cognitive dysfunction occur in parallel, early in the onset of the disease, and the cerebellum is one of the predilection sites of atrophy. This study is aimed at determining the relationship between cerebellar volumes, clinical cerebellar signs, cognitive functioning and fatigue in MS. Cerebellar volumetry was conducted using T1-weighted MPRAGE magnetic resonance imaging of 172 MS patients. All patients underwent a clinical and brief neuropsychological assessment (information processing speed, working memory), including fatigue testing. Patients with and without cerebellar signs differed significantly regarding normalized cerebellar total volume (nTCV), normalized brain volume (nBV) and whole brain T2 lesion volume (LV). Patients with cerebellar dysfunction likewise performed worse in cognitive tests. A regression analysis indicated that age and nTCV explained 26.3% of the variance in SDMT (symbol digit modalities test) performance. However, only age, T2 LV and nBV remained predictors in the full model (r(2) = 0.36). The full model for the prediction of PASAT (Paced Auditory Serial Addition Test) scores (r(2) = 0.23) included age, cerebellar and T2 LV. In the case of fatigue, only age and nBV (r(2) = 0.17) emerged as significant predictors. These data support the view that cerebellar abnormalities contribute to disability, including cognitive impairment in MS. However, this contribution does not seem to be independent of, and may even be dominated by wider spread MS pathology as reflected by nBV and T2 LV.

Strong memory of a traumatic event is thought to contribute to the development and symptoms of posttraumatic stress disorder (PTSD). Therefore, a genetic predisposition to build strong memories could lead to increased risk for PTSD after a traumatic event. Here we show that genetic variability of the gene encoding PKCα (PRKCA) was associated with memory capacity--including aversive memory--in nontraumatized subjects of European descent. This finding was replicated in an independent sample of nontraumatized subjects, who additionally underwent functional magnetic resonance imaging (fMRI). fMRI analysis revealed PRKCA genotype-dependent brain activation differences during successful encoding of aversive information. Further, the identified genetic variant was also related to traumatic memory and to the risk for PTSD in heavily traumatized survivors of the Rwandan genocide. Our results indicate a role for PKCα in memory and suggest a genetic link between memory and the risk for PTSD.

Several studies found that patients with atrial fibrillation (AF) have an increased risk of cognitive decline and dementia over time. However, the magnitude of the problem, associated risk factors and underlying mechanisms remain unclear.This article describes the design and methodology of the Swiss Atrial Fibrillation (Swiss-AF) Cohort Study, a prospective multicentre national cohort study of 2400 patients across 13 sites in Switzerland. Eligible patients must have documented AF. Main exclusion criteria are the inability to provide informed consent and the presence of exclusively short episodes of reversible forms of AF. All patients undergo extensive phenotyping and genotyping, including repeated assessment of cognitive functions, quality of life, disability, electrocardiography and cerebral magnetic resonance imaging. We also collect information on health related costs, and we assemble a large biobank. Key clinical outcomes in Swiss-AF are death, stroke, systemic embolism, bleeding, hospitalisation for heart failure and myocardial infarction. Information on outcomes and updates on other characteristics are being collected during yearly follow-up visits.Up to 7 April 2017, we have enrolled 2133 patients into Swiss-AF. With the current recruitment rate of 15 to 20 patients per week, we expect that the target sample size of 2400 patients will be reached by summer 2017.Swiss-AF is a large national prospective cohort of patients with AF in Switzerland. This study will provide important new information on structural and functional brain damage in patients with AF and on other AF related complications, using a large variety of genetic, phenotypic and health economic parameters.

The stereotypical pattern of neurofibrillary tangle spreading in the earliest stages of typical Alzheimer's dementia (AD) predicts that medial perirhinal cortex (mPRC) atrophy precedes entorhinal cortex (ERC) atrophy, whereas the status of the parahippocampal cortex (PHC) remains unclear. Atrophy studies have focused on more advanced rather than early AD patients, and usually segment the entire PRC as opposed to the mPRC versus lateral PRC (lPRC). The present study therefore determined the extent of ERC, mPRC, lPRC, and PHC atrophy in very early AD (mean Mini-Mental State Examination score = 26) patients and its presumed prodrome amnestic mild cognitive impairment (mean Mini-Mental State Examination score = 28) compared to demographically matched controls. PHG structures were manually segmented (blinded rater) and cortical thicknesses extracted. ERC and mPRC were similarly atrophied in both patient groups. The lPRC was atrophied in the AD group only. Thus, atrophic changes in very early AD broadly map onto the pattern of neurofibrillary tangle spreading and suggest that mPRC, ERC, and lPRC, but not PHC-associated functional impairments, characterize very early-stage AD.

Complex vascular anatomy might increase the risk of procedural stroke during carotid artery stenting (CAS). Randomized controlled trial evidence that vascular anatomy should inform the choice between CAS and carotid endarterectomy (CEA) has been lacking.One-hundred eighty-four patients with symptomatic internal carotid artery stenosis who were randomly assigned to CAS or CEA in the ICSS (International Carotid Stenting Study) underwent magnetic resonance (n=126) or computed tomographic angiography (n=58) at baseline and brain magnetic resonance imaging before and after treatment. We investigated the association between aortic arch configuration, angles of supra-aortic arteries, degree, length of stenosis, and plaque ulceration with the presence of ≥1 new ischemic brain lesion on diffusion-weighted magnetic resonance imaging (DWI+) after treatment.Forty-nine of 97 patients in the CAS group (51%) and 14 of 87 in the CEA group (16%) were DWI+ (odds ratio [OR], 6.0; 95% confidence interval [CI], 2.9-12.4; P<0.001). In the CAS group, aortic arch configuration type 2/3 (OR, 2.8; 95% CI, 1.1-7.1; P=0.027) and the degree of the largest internal carotid artery angle (≥60° versus <60°; OR, 4.1; 95% CI, 1.7-10.1; P=0.002) were both associated with DWI+, also after correction for age. No predictors for DWI+ were identified in the CEA group. The DWI+ risk in CAS increased further over CEA if the largest internal carotid artery angle was ≥60° (OR, 11.8; 95% CI, 4.1-34.1) than if it was <60° (OR, 3.4; 95% CI, 1.2-9.8; interaction P=0.035).Complex configuration of the aortic arch and internal carotid artery tortuosity increase the risk of cerebral ischemia during CAS, but not during CEA. Vascular anatomy should be taken into account when selecting patients for stenting.URL: http://www.isrctn.com/ISRCTN25337470. Unique identifier: ISRCTN25337470.

Background and Purpose Standard operating procedures (SOP) incorporating plasma levels of rivaroxaban might be helpful in selecting patients with acute ischemic stroke taking rivaroxaban suitable for IVthrombolysis (IVT) or endovascular treatment (EVT). Methods This was a single-center explorative analysis using data from the Novel-Oral-Anticoagulants-in-Stroke-Patients-registry (clinicaltrials.gov:NCT02353585) including acute stroke patients taking rivaroxaban (September 2012 to November 2016). The SOP included recommendation, consideration, and avoidance of IVT if rivaroxaban plasma levels were <20 ng/mL, 20‒100 ng/mL, and >100 ng/mL, respectively, measured with a calibrated anti-factor Xa assay. Patients with intracranial artery occlusion were recommended IVT+EVT or EVT alone if plasma levels were ≤100 ng/mL or >100 ng/mL, respectively. We evaluated the frequency of IVT/EVT, door-to-needle-time (DNT), and symptomatic intracranial or major extracranial hemorrhage. Results Among 114 acute stroke patients taking rivaroxaban, 68 were otherwise eligible for IVT/EVT of whom 63 had plasma levels measured (median age 81 years, median baseline National Institutes of Health Stroke Scale 6). Median rivaroxaban plasma level was 96 ng/mL (inter quartile range [IQR] 18‒259 ng/mL) and time since last intake 11 hours (IQR 4.5‒18.5 hours). Twenty-two patients (35%) received IVT/EVT (IVT n=15, IVT+EVT n=3, EVT n=4) based on SOP. Median DNT was 37 (IQR 30‒60) minutes. None of the 31 patients with plasma levels >100 ng/mL received IVT. Among 14 patients with plasma levels ≤100 ng/mL, the main reason to withhold IVT was minor stroke (n=10). No symptomatic intracranial or major extracranial bleeding occurred after treatment. Conclusions Determination of rivaroxaban plasma levels enabled IVT or EVT in one-third of patients taking rivaroxaban who would otherwise be ineligible for acute treatment. The absence of major bleeding in our pilot series justifies future studies of this approach. Keywords: Rivaroxaban; Stroke; Plasma levels; Thrombolysis

Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH.We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis.Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; P=0.40). There was a signal for interaction with onset-to-treatment time (Pinteraction=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; P=0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; P=0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation.In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH.URL: https://clinicaltrials.gov; Unique identifier: NCT02866838.

Interaction of simultaneous tactile input at two finger sites in primary (SI) and secondary somatosensory cortex (SII) was studied by whole-head magnetoencephalography. Short pressure pulses were delivered to fingers of the right and left hand at an interstimulus interval of 1.6 s. The first phalanx of the left digit 1 and four other sites were stimulated either separately or simultaneously. We compared four sites with increasing distance: the second phalanx of left digit 1, left digit 5, and digits 1 and 5 of the right hand. The temporal evolution of source activity in the contralateral SI and bilateral SII was calculated using spatiotemporal source analysis. Interaction was assessed by comparing the source activity during simultaneous stimulation with the sum of the source activities elicited by separate stimulation. Significant suppressive interaction was observed in contralateral SI only for stimuli at the same hand, decreasing with distance. In SII, all digits of the same and the opposite hand interacted significantly with left digit 1. When stimulating bilaterally, SII source waveforms closely resembled the time course of the response to separate stimulation of the opposite hand. Thus, in bilateral simultaneous stimulation, the contralateral input arriving first in SII appeared to inhibit the later ipsilateral input. Similarly, the separate response to input at two unilateral finger sites which arrived slightly earlier in SII dominated the simultaneous response. Our results confirm previous findings of considerable overlap in the cortical hand representation in SII and illustrate hemispheric specialization to contralateral input when simultaneous stimuli occur bilaterally.

Abstract The goal of this study was to evaluate the feasibility of active deep brain stimulation (DBS) during the application of standard clinical sequences for functional MRI (fMRI) in phantom measurements. During active DBS, we investigated induced voltage, temperature at the electrode tips and lead, forces on the electrode and lead, consequences of defective leads and loose connections, proper operation of the neurostimulator, and image quality. Sequences for diffusion‐ and perfusion‐weighted imaging, fMRI, and morphologic MRI were used. The DBS electrode and lead were placed in a NaCl solution‐filled phantom. The results indicate that there are severe potential hazards for patients. Strong heating, high induced voltage, and even sparking at defects in the connecting cable could be observed. However, it was demonstrated that under certain conditions, safe MR examinations during active DBS are feasible. Certain safety precautions are recommended in this report. Magn Reson Med 51:380–388, 2004. © 2004 Wiley‐Liss, Inc.

Brain tumors affecting language-relevant areas may influence language lateralization. The purpose of this study was to systematically investigate language lateralization in brain tumor patients using clinical language fMRI, comparing the results with a group of healthy volunteers.Fifty-seven strictly right-handed patients with left-hemispheric-space intracranial masses (mainly neoplastic) affecting either the Broca area (n = 19) or Wernicke area (n = 38) were prospectively enrolled in this study. Fourteen healthy volunteers served as a control group. Standardized clinical language fMRI, using visually triggered sentence- and word-generation paradigms, was performed on a 1.5T MR scanner. Semiautomated analyses of all functional data were conducted on an individual basis using BrainVoyager. A regional lateralization index was calculated for Broca and Wernicke areas separately versus their corresponding right-hemisphere homologs.In masses affecting the Broca area, a significant decrease in the lateralization index was found when performing word generation (P = .0017), whereas when applying sentence generation, the decrease did not reach statistical significance (P = .851). Masses affecting the Wernicke area induced a significant decrease of the lateralization index when performing sentence generation (P = .0007), whereas when applying word generation, the decrease was not statistically significant (P = .310).Clinical language fMRI was feasible for patients with brain tumors and provided relevant presurgical information by localizing essential language areas and determining language dominance. A significant effect of the brain masses on language lateralization was observed, with a shift toward the contralesional, nondominant hemisphere. This may reflect compensatory mechanisms of the brain to maintain communicative abilities.

Little is known on longer term changes of spinal cord volume (SCV) in primary progressive multiple sclerosis (PPMS).Longitudinal evaluation of SCV loss in PPMS and its correlation to clinical outcomes, compared to relapse-onset multiple sclerosis (MS) subtypes.A total of 60 MS age-, sex- and disease duration-matched patients (12 PPMS, each 24 relapsing-remitting (RRMS) and secondary progressive MS (SPMS)) were analysed annually over 6 years of follow-up. The upper cervical SCV was measured on 3D T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) images using a semi-automatic software (CORDIAL), along with the total brain volume (TBV), brain T2 lesion volume (T2LV) and Expanded Disability Status Scale (EDSS).PPMS showed faster SCV loss over time than RRMS ( p < 0.01) and by trend ( p = 0.066) compared with SPMS. In contrast to relapse-onset MS, in PPMS SCV loss progressed independent of TBV and T2LV changes. Moreover, in PPMS, SCV was the only magnetic resonance imaging (MRI) measurement associated with EDSS increase over time ( p < 0.01), as opposed to RRMS and SPMS.SCV loss is a strong predictor of clinical outcomes in PPMS and has shown to be faster and independent of brain MRI metrics compared to relapse-onset MS.

Abstract Introduction In geriatric clinical diagnostics, gait analysis with cognitive‐motor dual tasking is used to predict fall risk and cognitive decline. To date, the neural correlates of cognitive‐motor dual tasking processes are not fully understood. To investigate these underlying neural mechanisms, we designed an fMRI paradigm to reproduce the gait analysis. Methods We tested the fMRI paradigm’s feasibility in a substudy with fifteen young adults and assessed 31 healthy older adults in the main study. First, gait speed and variability were quantified using the GAITR ite © electronic walkway. Then, participants lying in the MRI ‐scanner were stepping on pedals of an MRI ‐compatible stepping device used to imitate gait during functional imaging. In each session, participants performed cognitive and motor single tasks as well as cognitive‐motor dual tasks. Results Behavioral results showed that the parameters of both gait analyses, GAITR ite © and fMRI , were significantly positively correlated. FMRI results revealed significantly reduced brain activation during dual task compared to single task conditions. Functional ROI analysis showed that activation in the superior parietal lobe ( SPL ) decreased less from single to dual task condition than activation in primary motor cortex and in supplementary motor areas. Moreover, SPL activation was increased during dual tasks in subjects exhibiting lower stepping speed and lower executive control. Conclusion We were able to simulate walking during functional imaging with valid results that reproduce those from the GAITR ite © gait analysis. On the neural level, SPL seems to play a crucial role in cognitive‐motor dual tasking and to be linked to divided attention processes, particularly when motor activity is involved.

Radiologists are among the first physicians to be directly affected by advances in computer technology. Computers are already capable of analysing medical imaging data, and with decades worth of digital information available for training, will an artificial intelligence one day signal the end of the human radiologist? With the ever increasing work load combined with the looming doctor shortage, radiologists will be pushed far beyond their current estimated 3 seconds allotted time-of-analysis per image; an artificial intelligence with super human capabilities might seem like a logical replacement. We feel, however, that artificial intelligence will lead to an augmentation rather than a replacement of the radiologist. The artificial intelligence will be relied upon to handle the tedious, time consuming tasks of detecting and segmenting outliers while possibly generating new, unanticipated results which can then be used as sources of medical discovery. This will affect not only radiologists, but all physicians and also researchers dealing with medical imaging. Therefore, we must embrace future technology and collaborate interdisciplinary to spearhead the next revolution in medicine.

The clinical application of functional magnetic resonance imaging (fMRI) requires time-saving protocols insensitive to artifacts that provide robust localization and important information on brain function. A fully automated, pneumatically driven tactile stimulation is presented, that reproducibly localizes postcentral lip, finger and toe representations in contralateral primary somatosensory cortex (SI) with mean correlation coefficients (cc) and relative BOLD signal changes (dS) of cc approximately 0.59, dS approximately 1.95% (fingers); cc approximately 0.52, dS approximately 1.35% (lips); cc approximately 0.47, dS approximately 1.42% (toes). Bilateral somatotopic mapping requires 21 min of scanning time and has become a clinical routine fMRI application in patients with perirolandic tumors. Normative data may also be useful in monitoring cerebral plasticity and reorganization, e.g. in sensorimotor recovery after cerebral ischemia or in understanding mechanisms of supraspinal pain processing.

FUNCTIONAL magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) were performed in six subjects during self-paced finger movement performance, tactile somatosensory stimulation and binaural auditory stimulation using identical stimulation paradigms. Both functional imaging modalities localized brain activity in adjacent areas of anatomically correct cortex. The mean distances measured between fMRI activity and the corresponding MEG dipoles were 10.1 mm (motor), 10.7 mm (somatosensory), 13.5 mm (auditory right hemisphere) and 14.3 mm (auditory left hemisphere). The distances found may reflect the correlation between electrophysiological and hemodynamic responses due to the different underlying substrates of neurophysiology measured by fMRI and MEG: BOLD contrast vs neuronal biomagnetic activity.

To establish a passive motor paradigm for clinical functional MRI (fMRI) that could be beneficial for patients with motor or attention deficits who are not able to perform active motor tasks.A novel standardized sensorimotor fMRI protocol was applied in 16 healthy volunteers at 3 Tesla (T) using active and passive motor tasks as well as sensory stimulation of hands and feet. Data analysis was carried out individually using a dynamic thresholding routine.Active motor tasks yielded time efficient and robust blood-oxygen-level-dependent (BOLD) signals in primary motor cortex. Noteworthy, it was possible to achieve equal activation levels within identical anatomical localization for passive and active motor tasks with these paradigms.Patients unable to perform active movements can benefit from paradigms with passive motor and sensory stimulation. Therefore, we recommend these paradigms for functional somatotopic mapping of the central region at 3T in clinical routine.

Background and purpose Olfactory bulb atrophy is associated with cognitive dysfunction in Parkinson's and Alzheimer's disease, and with major depression. It has been suggested that olfactory bulb atrophy or dysfunction is therefore a marker of neurodegeneration. Multiple sclerosis ( MS ) is now also recognized as having a significant neurodegenerative component. Thus, the aim of this study was to investigate associations between physical and cognitive disability, depression and olfactory bulb volume in MS . Methods In total, 146 patients with MS (mean age 49.0 ± 10.9 years, disease duration 21.2 ± 9.3 years, median Expanded Disability Status Scale ( EDSS ) score 3.0 (range 0–7.5), 103 relapsing−remitting, 35 secondary progressive and eight primary progressive MS) underwent a standardized neurological examination, comprehensive neuropsychological testing and magnetic resonance imaging ( MRI ); data of 27 healthy people served as age‐ and gender‐matched control subjects. The olfactory bulb was semi‐automatically segmented on high‐resolution three‐dimensional T1‐weighted MRI . Results Mean olfactory bulb volume was lower in MS patients than healthy controls ( 183.9 ± 40.1 vs. 209.2 ± 59.3 μl; P = 0.018 adjusted to intracranial volume). Olfactory bulb volume was similar across clinical disease subtypes and did not correlate with cognitive performance, EDSS scores or total proton density/T2 white matter lesion volume. However, in progressive MS , the mean olfactory bulb volume correlated with depression scores (Spearman's rho = −0.38, P &lt; 0.05) confirmed using a multivariate linear regression analysis including cognitive fatigue scores. This association was not observed in relapsing−remitting MS . Conclusion Olfactory bulb volume was lower in MS than in healthy controls. Olfactory bulb volume does not seem to mirror cognitive impairment in MS ; however, it is associated with higher depression scores in progressive MS .

Previous studies have demonstrated that white matter (WM) lesions bias automated brain tissue classifications and cerebral volume measurements. However, filling WM lesions using the intensity of neighbouring normal-appearing WM has been shown to increase the accuracy of automated volume measurements in the brain. In the present study, we investigate the influence of WM lesions on cortical thickness (CTh) measures and assessed the impact of lesion filling on both cross-sectional/longitudinal and global/regional measurements of CTh in multiple sclerosis (MS) patients.Fifty MS patients were studied at baseline as well as after three and six years of follow-up. CTh was estimated using a fully automated pipeline (CIVET) on T1-weighted magnetic resonance images data acquired at 1.5 Tesla without (original) and with WM lesion filling (filled). WM lesions were semi-automatically segmented and then filled with the mean intensity of the neighbouring voxels. For both original and filled T1 images we investigated and compared the main CIVET's steps: tissue classification, surfaces generation and CTh measurement.On the original T1 images, the majority of WM lesion volume (72%) was wrongly classified as gray matter (GM). After lesion filling the accuracy of WM lesions classification improved significantly (p < 0.001, 94% of WM lesion volume correctly classified) as well as the WM surface generation (p < 0.0001). The mean CTh computed on the original T1 images, overall time points, was significantly thinner (p < 0.001) compared the CTh estimated on the filled T1 images. The vertex-wise longitudinal analysis performed on the filled T1 images showed an increased number of vertices in the fronto-temporal region with a significantly decrease of CTh over time compared the analysis performed on the original images.These results indicate that WM lesions bias the CTh estimation both cross-sectionally as well as longitudinally. The lesion filling approach significantly improved the accuracy of the regional CTh estimation and has an impact also on the global estimation of CTh.

Deep gray matter (DGM) atrophy has been reported in patients with multiple sclerosis (MS) already at early stages of the disease and progresses throughout the disease course. We studied DGM volume and shape and their relation to disability in a large cohort of clinically well-described MS patients using new subcortical segmentation methods and shape analysis. Structural 3D magnetic resonance images were acquired at 1.5 T in 118 patients with relapsing remitting MS. Subcortical structures were segmented using a multiatlas technique that relies on the generation of an automatically generated template library. To localize focal morphological changes, shape analysis was performed by estimating the vertex-wise displacements each subject must undergo to deform to a template. Multiple linear regression analysis showed that the volume of specific thalamic nuclei (the ventral nuclear complex) together with normalized gray matter volume explains a relatively large proportion of expanded disability status scale (EDSS) variability. The deformation-based displacement analysis confirmed the relation between thalamic shape and EDSS scores. Furthermore, white matter lesion volume was found to relate to the shape of all subcortical structures. This novel method for the analysis of subcortical volume and shape allows depicting specific contributions of DGM abnormalities to neurological deficits in MS patients. The results stress the importance of ventral thalamic nuclei in this respect.

The mechanisms leading to disability and the long-term efficacy and safety of disease modifying drugs (DMDs) in multiple sclerosis (MS) are unclear. We aimed at building a prospective cohort of MS patients with standardized collection of demographic, clinical, MRI data and body fluids that can be used to develop prognostic indicators and biomarkers of disease evolution and therapeutic response. The Swiss MS Cohort (SMSC) is a prospective observational study performed across seven Swiss MS centers including patients with MS, clinically isolated syndrome (CIS), radiologically isolated syndrome or neuromyelitis optica. Neurological and radiological assessments and biological samples are collected every 6-12 months. We recruited 872 patients (clinically isolated syndrome [CIS] 5.5%, relapsing-remitting MS [RRMS] 85.8%, primary progressive MS [PPMS] 3.5%, secondary progressive MS [SPMS] 5.2%) between June 2012 and July 2015. We performed 2,286 visits (median follow-up 398 days) and collected 2,274 serum, plasma and blood samples, 152 cerebrospinal fluid samples and 1,276 brain MRI scans. 158 relapses occurred and expanded disability status scale (EDSS) scores increased in PPMS, SPMS and RRMS patients experiencing relapses. Most RRMS patients were treated with fingolimod (33.4%), natalizumab (24.5%) or injectable DMDs (13.6%). The SMSC will provide relevant information regarding DMDs efficacy and safety and will serve as a comprehensive infrastructure available for nested research projects.

Abstract Background and purpose Clinical outcomes vary substantially among individuals with large vessel occlusion (LVO) stroke. A small infarct core and large imaging mismatch were found to be associated with good recovery. The aim of this study was to investigate whether those imaging variables would improve individual prediction of functional outcome after early (&lt;6 h) endovascular treatment (EVT) in LVO stroke. Methods We included 222 patients with acute ischemic stroke due to middle cerebral artery (MCA)‐M1 occlusion who received EVT. As predictors, we used clinical variables and region of interest (ROI)‐based magnetic resonance imaging features. We developed different machine‐learning models and quantified their prediction performance according to the area under the receiver‐operating characteristic curves and the Brier score. Results The rate of successful recanalization was 78%, with 54% patients having a favorable outcome (modified Rankin scale score 0–2). Small infarct core was associated with favorable functional outcome. Outcome prediction improved only slightly when imaging was added to patient variables. Age was the driving factor, with a sharp decrease in likelihood of favorable functional outcome above the age of 78 years. Conclusions In patients with MCA‐M1 occlusion strokes referred to EVT within 6 h of symptom onset, infarct core volume was associated with outcome. However, ROI‐based imaging variables led to no significant improvement in outcome prediction at an individual patient level when added to a set of clinical predictors. Our study is in concordance with current practice, where imaging mismatch or collateral readouts are not recommended as factors for excluding patients with MCA‐M1 occlusion for early EVT.

Abstract Human auditory cortex (AC) organization resembles the core-belt-parabelt organization in nonhuman primates. Previous studies assessed mostly spatial characteristics; however, temporal aspects were little considered so far. We employed co-registration of functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in musicians with and without absolute pitch (AP) to achieve spatial and temporal segregation of human auditory responses. First, individual fMRI activations induced by complex harmonic tones were consistently identified in four distinct regions-of-interest within AC, namely in medial Heschl’s gyrus (HG), lateral HG, anterior superior temporal gyrus (STG), and planum temporale (PT). Second, we analyzed the temporal dynamics of individual MEG responses at the location of corresponding fMRI activations. In the AP group, the auditory evoked P2 onset occurred ~25 ms earlier in the right as compared with the left PT and ~15 ms earlier in the right as compared with the left anterior STG. This effect was consistent at the individual level and correlated with AP proficiency. Based on the combined application of MEG and fMRI measurements, we were able for the first time to demonstrate a characteristic temporal hierarchy (“chronotopy”) of human auditory regions in relation to specific auditory abilities, reflecting the prediction for serial processing from nonhuman studies.

We investigated whether attention to different stimulus attributes (location, intensity) has different effects on the activity of the secondary (SII) somatosensory cortex. Tactile stimuli were applied to the left index finger and somatosensory evoked fields (SEFs) were recorded using a whole-head magnetoencephalography (MEG) system. Two oddball paradigms with stimuli varying in location or intensity were performed in an ignore and an attend condition. Brain sources were estimated by magnetic source imaging. No attention effect was observed for the primary SI area. However, attention enhanced SII activity bilaterally from 55 to 130 ms by 52% in the spatial and 64% in the intensity discrimination task. SII attentional enhancement was very similar in both paradigms and occurred both for deviants and standards.

An optimized clinical functional magnetic resonance imaging (fMRI) protocol with a total scanning time of 8 min is presented that localizes Broca's and Wernicke's areas robustly and determines hemispheric dominance. Language function was visualized using two different sentence generation (SG) and word generation (WG) tasks. Block designed blood oxygenation level dependent (BOLD) fMRI was applied in 14 right-handed volunteers at 1.5 T during visual stimulation. BOLD-clusters were assessed individually for anatomical localization. Reference data are provided for the maximum correlation of the measured BOLD-signal time course to the applied reference function (r(max)), for the maximum relative signal change (dS%), cluster size and Euklidian coordinates of Broca and Wernicke activation and of the anatomical homologues in the right hemispheres. Statistical means and a lateralization index (LI) were calculated. Broca activation focussed on the inferior frontal gyrus, and Wernicke activation on the superior temporal, supramarginal or middle temporal gyri. Mean BOLD-signals for Broca ranged from 1.53% (SG) to 2.56% (WG), and for Wernicke from 1.47% (SG) to 1.80% (WG). LI indicated left language dominance. The data provided further evidence for the high anatomical variability of language areas, which underlined the relevance of an individual language localization and lateralization prior to brain surgery.

PURPOSE: To assess the prognostic value of quantitative analyses of region-of-interest (ROI) magnetic resonance (MR) imaging data in patients with acute facial nerve palsy. MATERIALS AND METHODS: In a single-blinded study, MR images were obtained in 39 patients (32 men and seven women; age range, 18–75 years; average age, 37.9 years) with acute facial nerve palsy. MR images were obtained before the 6th day of illness, on the first day of standard inpatient treatment with high-dose steroids. Signal intensity (SI) was measured at ROIs in each of five segments (internal auditory canal [IAC]; geniculate ganglion; and labyrinth, tympanic, and mastoid segments) of the intratemporal portion of the facial nerve and quantitatively analyzed. The SI measurements in the five segments were summed and divided by 100 to provide a basis for establishing an MR imaging index. SI increases and MR imaging indexes were compared with available clinical findings and electrophysiologic data. RESULTS: Data for all 39 patients could be analyzed. The MR imaging index was significantly higher in patients with poor outcomes than in patients with favorable outcomes (specificity, 97%; sensitivity, 75%; P < .01). The SI increases in the IAC were significantly different between patients who progressed to full recovery (mean increase, 45.7%) and patients who developed chronic facial paralysis (mean increase, 156.5%) (sensitivity, 100%; specificity, 97%; P < .001). The results of differentiating between patients with good and those with poor outcomes on the basis of SI measurements in the IAC were found to be in complete agreement with electrophysiologic data. CONCLUSION: Quantitative analysis of ROI MR imaging data is a valid method of predicting the outcome of acute facial nerve palsy during the first days after onset of symptoms and thus at a time when it is not yet possible to obtain valuable prognostic information by using electrophysiologic methods. © RSNA, 2003

In the context of the present study spatial perspective taking refers to the ability to translocate one's own egocentric viewpoint to somebody else's viewpoint in space. We adopted a spatial perspective taking paradigm and performed a functional magnetic resonance imaging study to assess gender differences of neural activity during perspective taking. 24 healthy subjects (12 male/12 female) were asked to systematically either take their own (first-person-perspective, 1PP) or another person's perspective (third-person-perspective, 3PP). Presented stimuli consisted of a virtual scenery with an avatar and red balls around him that had to be counted, if visible, from 1PP or 3PP. Reaction time was increased and correctness scores were decreased during the cognitively more effortful 3PP condition. Correctness scores showed a trend towards a more pronounced decline of performance during 3PP as compared to 1PP in female subjects. Female subjects correctness scores declined by 6.7% from 1PP to 3PP, while in male subjects this performance decline was only 2.7%. Debriefings after the experiment, reaction times depending on angle of rotation and error rates suggest that males are more likely to employ an object-based strategy in contrast to a consistently employed egocentric perspective transformation in females. In the whole group, neural activity was increased in the parieto-occipital, right inferior frontal and supplementary motor areas, confirming previous studies. With respect to gender, male subjects showed stronger activation in the precuneus and the right inferior frontal gyrus than female subjects in a region-of-interest approach. In a subgroup of male subjects whose strategy reports suggest object-based strategies these differences seem to be more pronounced. In conclusion, the differential recruitment of brain regions most likely reflects different strategies in solving this spatial perspective taking task.

Unilateral voluntary movements are accompanied by robust activation of contralateral primary motor cortex (M1) in a somatotopic fashion. Occasionally, coactivation of M1 (M1-CoA) ipsilateral to the movement was described. In a study with brain tumor patients, we consistently observed additional somatotopic M1-CoAs and hypothesized that they might represent a basic feature of movement execution. To test this hypothesis, we used BOLD functional magnetic resonance imaging in healthy subjects and show that unilateral voluntary movements of the fingers or toes go along not only with contralateral M1 activation, but also with ipsilateral M1-CoA of the respective homotopic representation and bilateral M1-CoA of different heterotopic representations not directly involved in the executed movement. Moreover, bilateral M1-CoA of heterotopic representations was observed in tongue movements. All M1-CoAs respected the correct somatotopy; however, their Euclidean coordinates were shifted and resembled to those obtained for imagined movements rather than for actual movements. BOLD signal intensities and correlations to the applied hemodynamic reference function were lower in M1-CoAs as compared to the M1 activations driving the movement but did not differ between homo- and heterotopic M1-CoAs. Thus, we propose that specific unilateral voluntary movements are accompanied by a global activation of primary motor areas, reflecting an overall increase in neuronal activity and unraveling the fundamental principle of distributed processing in M1. Executive motor function may rely on a balance of inhibitory and excitatory neuronal activity, where actual movement would result from a shift towards excitation.

The evidence for traumatic brain injury in amateur boxers is controversial. Hypothetically, sudden acceleration of the head due to the impact of the blow during the boxing fight might result in diffuse axonal injury or contusion. We wanted to determine whether cerebral microhemorrhages occur more often in amateur boxers than in nonboxers.In 42 male, classical amateur boxers and in 37 healthy, nonboxing male volunteers we performed cranial MR imaging at 3T. The study protocol included a transverse dual spin-echo MR imaging sequence, a 3D sagittal magnetization-prepared rapid acquisition of gradient echo sequence, a coronal T2*-weighted sequence, and an axial time-of-flight MR angiography sequence. MR imaging data were made anonymous before 2 neuroradiologists independently evaluated the images. In addition, the following risk factors were assessed: total numbers of fights and knockouts, weight division, and duration of boxing. We compared the group proportions of microhemorrhages with Fisher test of exact probability.There was a statistically higher prevalence of cerebral microhemorrhages in the group of boxers (3 of 42; 7.1%) than in nonboxing persons (0 of 37; 0%). This difference was not statistically significant, however (P = .2479; Fisher exact test).Although we detected more microhemorrhages in amateur boxers than in nonboxing persons, this difference did not prove to be significant.

Rationale and Objectives The aim of this study was to assess the intrasubject and intersubject reproducibility of functional magnetic resonance imaging (fMRI) language paradigms on language localization and lateralization. Materials and Methods Fourteen healthy volunteers were enrolled prospectively and underwent language fMRI using visually triggered covert and overt sentence generation (SG) and word generation (WG) paradigms. Semiautomated analysis of all functional data was performed using Brain Voyager on an individual basis. Regions of interest for Broca's area, Wernicke's area, and their contralateral homologues were drawn. The Euclidean coordinates of the center of gravidity (x, y, and z) of the respective blood oxygenation level–dependent (BOLD) activation cluster, and the correlation of the measured hemodynamic response to the applied reference function (r), relative BOLD signal change as BOLD signal characteristics were measured in each region of interest. Regional lateralization indexes were calculated for Broca's area, Wernicke's area, and their contralateral homologues separately. Wilcoxon's signed-rank test was applied for statistical comparisons (P values < .05 were considered significant). Ten of the 14 volunteers had three repeated measurements to test intrasession reproducibility and intersession reproducibility. Results Overall activation rates for the four paradigms were 89% for covert SG, 82% for overt SG, 89% for covert WG, and 100% for overt WG. When comparing covert and overt paradigms, language localization was significantly different in 17% (Euclidean coordinates) and 19% (BOLD signal characteristics), respectively. Language lateralization was significantly different in 75%. Intrasubject and intersubject reproducibility was excellent, with 3.3% significant differences among all five parameters for language localization and 0% significant differences for language lateralization using covert paradigms. Conclusions Covert language paradigms (SG and WG) provided highly robust and reproducible localization and lateralization of essential language centers for scans performed on the same and different days. Their overt counterparts achieved confirmatory localization but lower lateralization capabilities. Reference data for presurgical application are provided. The aim of this study was to assess the intrasubject and intersubject reproducibility of functional magnetic resonance imaging (fMRI) language paradigms on language localization and lateralization. Fourteen healthy volunteers were enrolled prospectively and underwent language fMRI using visually triggered covert and overt sentence generation (SG) and word generation (WG) paradigms. Semiautomated analysis of all functional data was performed using Brain Voyager on an individual basis. Regions of interest for Broca's area, Wernicke's area, and their contralateral homologues were drawn. The Euclidean coordinates of the center of gravidity (x, y, and z) of the respective blood oxygenation level–dependent (BOLD) activation cluster, and the correlation of the measured hemodynamic response to the applied reference function (r), relative BOLD signal change as BOLD signal characteristics were measured in each region of interest. Regional lateralization indexes were calculated for Broca's area, Wernicke's area, and their contralateral homologues separately. Wilcoxon's signed-rank test was applied for statistical comparisons (P values < .05 were considered significant). Ten of the 14 volunteers had three repeated measurements to test intrasession reproducibility and intersession reproducibility. Overall activation rates for the four paradigms were 89% for covert SG, 82% for overt SG, 89% for covert WG, and 100% for overt WG. When comparing covert and overt paradigms, language localization was significantly different in 17% (Euclidean coordinates) and 19% (BOLD signal characteristics), respectively. Language lateralization was significantly different in 75%. Intrasubject and intersubject reproducibility was excellent, with 3.3% significant differences among all five parameters for language localization and 0% significant differences for language lateralization using covert paradigms. Covert language paradigms (SG and WG) provided highly robust and reproducible localization and lateralization of essential language centers for scans performed on the same and different days. Their overt counterparts achieved confirmatory localization but lower lateralization capabilities. Reference data for presurgical application are provided.

In patients with stroke attributable to cervical artery dissection, we compared endovascular therapy to intravenous thrombolysis regarding three-month outcome, recanalisation and complications.In a multicentre intravenous thrombolysis/endovascular therapy-register-based cohort study, all consecutive cervical artery dissection patients with intracranial artery occlusion treated within 6 h were eligible for analysis. Endovascular therapy patients (with or without prior intravenous thrombolysis) were compared to intravenous thrombolysis patients regarding (i) excellent three-month outcome (modified Rankin Scale score 0-1), (ii) symptomatic intracranial haemorrhage, (iii) recanalisation of the occluded intracranial artery and (iv) death. Upon a systematic literature review, we performed a meta-analysis comparing endovascular therapy to intravenous thrombolysis in cervical artery dissection patients regarding three-month outcome using a random-effects Mantel-Haenszel model.Among 62 cervical artery dissection patients (median age 48.8 years), 24 received intravenous thrombolysis and 38 received endovascular therapy. Excellent three-month outcome occurred in 23.7% endovascular therapy and 20.8% with intravenous thrombolysis patients. Symptomatic intracranial haemorrhage occurred solely among endovascular therapy patients (5/38 patients, 13.2%) while four (80%) of these patients had bridging therapy; 6/38 endovascular therapy and 0/24 intravenous thrombolysis patients died. Four of these 6 endovascular therapy patients had bridging therapy. Recanalisation was achieved in 84.2% endovascular therapy patients and 66.7% intravenous thrombolysis patients (odds ratio 3.2, 95% confidence interval [0.9-11.38]). Sensitivity analyses in a subgroup treated within 4.5 h revealed a higher recanalisation rate among endovascular therapy patients (odds ratio 3.87, 95% confidence interval [1.00-14.95]), but no change in the key clinical findings. In a meta-analysis across eight studies (n = 212 patients), cervical artery dissection patients (110 intravenous thrombolysis and 102 endovascular therapy) showed identical odds for favourable outcome (odds ratio 0.97, 95% confidence interval [0.38-2.44]) among endovascular therapy patients and intravenous thrombolysis patients.In this cohort study, there was no clear signal of superiority of endovascular therapy over intravenous thrombolysis in cervical artery dissection patients, which - given the limitation of our sample size - does not prove that endovascular therapy in these patients cannot be superior in future studies. The observation that symptomatic intracranial haemorrhage and deaths in the endovascular therapy group occurred predominantly in bridging patients requires further investigation.

Objectives Analysis of a single slice of a tumor to extract biomarkers for texture analysis may result in loss of information. We investigated correlation of fractional volumes to entire tumor volumes and introduced expanded regions of interest (ROIs) outside the visual tumor borders in glioblastoma. Materials and Methods Retrospective slice-by-slice volumetric texture analysis on 46 brain magnetic resonance imaging subjects with histologically confirmed glioblastoma was performed. Fractional volumes were analyzed for correlation to total volume. Expanded ROIs were analyzed for significant differences to conservative ROIs. Results As fractional tumor volumes increased, correlation with total volume values for mean, SD, mean of positive pixels, skewness, and kurtosis increased. Expanding ROI by 2 mm resulted in significant differences in all textural values. Conclusions Fractional volumes may provide an optimal trade-off for texture analysis in the clinical setting. All texture parameters proved significantly different with minimal expansion of the ROI, underlining the susceptibility of texture analysis to generating misrepresentative tumor information.

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a mitochondrial cytopathy caused by mutations in mitochondrial DNA. Clinical manifestation is typically before the age of 40. We present the case of a 63-year-old female in whom the symptoms of MELAS were initially misdiagnosed as episodes of recurrent ischemic strokes. Brain imaging including MRI, clinical and laboratory findings that lent cues to the diagnosis of MELAS are discussed. In addition, MRI findings in MELAS in comparison to imaging mimics of MELAS are presented. This case underscores the importance of considering MELAS as a potential cause of recurrent stroke-like events if imaging findings are untypical for cerebral infarction, even among middle-aged patients with vascular risk factors.

Multiple source analysis of interictal EEG and MEG spikes was used to identify irritative zones in polymicrogyria (PMG). Spike onset times and source localization were compared between both modalities. PMG is characterized by a marked loss of deep cortical fissures. Hence, differences between EEG and MEG were expected since MEG signals are predominantly generated from tangentially orientated neurons in fissures.We studied 7 children and young adults (age 7.5 to 19 years) with localization-related epilepsy and unilateral polymicrogyria (PMG) as defined from anatomical MRI.122-channel whole-head MEG and 32-channel EEG were recorded simultaneously for 25 to 40 min. Using the BESA program, interictal spikes were identified visually and used as templates to search for similar spatio-temporal spike patterns throughout the recording. Detected similar spikes (r > 0.85) were averaged, high-pass filtered (5 Hz) to enhance spike onset, and subjected to multiple spatio-temporal source analysis. Source localization was visualized by superposition on T1-weighted MRI and compared to the lesion.Nine spike types were identified in seven patients (2 types in 2 patients). Eight out of nine EEG sources and seven MEG sources modeling spike onset were localized within the visible lesion. EEG spike onset preceded MEG significantly in two spike types by 19 and 25 ms. This was related to radial onset activity in EEG while MEG localized propagated activity. In one case, the earliest MEG spike activity was localized to the normal hemisphere while the preceding radial EEG onset activity was localized within the lesion. Distances between EEG and MEG onset sources varied markedly between 9 and 51 mm in the eight spike types with concordant lateralization.Interictal irritative zones were localized within the lesion in PMG comparable to other malformations, e.g., FCD. Discrepancies in MEG and EEG were related to the lack of deep fissures in PMG. In two cases, MEG was blind to the onset of radial interictal spike activity and localized propagated spike activity. In two other cases, MEG localized to the more peripheral parts of the irritative zone. Simultaneous EEG recordings with MEG and multiple source analysis are required to avoid problems of MEG interpretation.

Chiari II-malformation is a complex congenital deformity of the brain which is frequently associated with hydrocephalus. Abnormalities of the corpus callosum are known to occur in the majority of patients. The objective of the present study was to study the microstructure of the corpus callosum (CC) and the anterior commissure (AC) to differentiate between different mechanisms of damage to these structures. We investigated 6 patients with Chiari II-malformation and 6 well-matched healthy volunteers employing T1-weighted 3D imaging and diffusion tensor imaging (DTI) to determine the fractional anisotropy (FA) and cross-sectional area of the CC and AC, as well as with neuropsychological testing. Four patients showed hydrocephalus, two patients had callosal dysplasia and four had a hypoplastic CC. The callosal FA in the patients was significantly reduced which was less pronounced for the genu alone. The area of CC was also reduced in Chiari II-patients. There was a strong correlation between the size and FA of the CC in the patients. In contrast, the thickness of the AC was significantly increased and was associated with higher FA in the patients. In psychological tests all patients showed reduced verbal memory; all but one patient showed reduced IQ as well as impaired visuo-spatial performance, indicating deficits in tasks requiring parieto-occipital integration. The existence of callosal dysplasia in two patients, the diminished FA reduction in the genu and the correlation of the cross-sectional area and FA in the patients point to a developmental white matter damage beside that exerted by hydrocephalus alone.

Functional magnetic resonance imaging in a Go/Nogo task was employed to investigate the relationship between trait impulsivity and brain activation during motor response inhibition. We found a positive correlation between motor impulsivity and activation of bilateral ventrolateral prefrontal cortex during successful inhibitions, which suggests stronger recruitment to maintain task performance.

Cerebellar dysfunction is an important contributor to disability in patients with multiple sclerosis (MS), however, few in vivo studies focused on cerebellar volume loss so far. This relates to technical challenges regarding the segmentation of the cerebellum. In this study, we evaluated the semi-automatic ECCET software for performing cerebellar volumetry using high-resolution 3D T1-MR scans in patients with MS and healthy volunteers. We performed test-retest as well as inter-observer reliability testing of cerebellar segmentation and compared the ECCET results with a fully automatic cerebellar segmentation using the FreeSurfer software pipeline in 15 MS patients. In a pilot matched-pair analysis with another data set from 15 relapsing-remitting MS patients and 15 age- and sex-matched healthy controls (HC), we assessed the feasibility of the ECCET approach to detect MS-related cerebellar volume differences. For total normalized cerebellar volume as well as grey and white matter volumes, intrarater (intraclass correlation coefficient (ICC) = 0.99, 95 % CI = 0.98-0.99) and interobserver agreement (ICC = 0.98, 95 % CI = 0.74-0.99) were strong. Comparison between ECCET and FreeSurfer results likewise yielded a good intraclass correlation (ICC = 0.86, 95 % CI = 0.58-0.95). Compared to HC, MS patients had significantly reduced normalized total brain, total cerebellar, and grey matter volumes (p ≤ 0.05). ECCET is a suitable tool for cerebellar segmentation showing excellent test-retest and inter-observer reliability. Our matched-pair analysis between MS patients and healthy volunteers suggests that the method is sensitive and reliable in detecting cerebellar atrophy in MS.

Hemispheric lateralization is a frequently encountered phenomenon of cortical function. It describes the functional specialization of a region on one side of the brain for a given task. It is well characterized in motor and sensory, as well as language systems and becomes more and more known for various cognitive domains. While in the adult healthy brain hemispheric lateralization is mostly set, pathological processes may lead to cortical reorganization. In these cases neuroplasticity of the corresponding region in the non-dominant hemisphere seems to play an important role. In a previous study we investigated language associated regions in right-handed patients with frontal and temporal tumors of the left hemisphere. We observed a marked change of language lateralization in these patients towards the non-dominant hemisphere as measured by functional MRI (Partovi et al., 2012). In the present study we evaluated activation and lateralization of cortical motor areas in patients with tumors of the central region. BOLD fMRI was performed during unilateral voluntary movements of the contralesional hand in 87 patients. Individual correlations of measured BOLD-signals with the model hemodynamic reference function were determined on a ROI basis in single subjects and compared to those of 16 healthy volunteers. In volunteers the strongest activation is usually found in the M1 hand representation contralateral to the movement, while a weaker homotopic co-activation is observed in ipsilateral M1 (Stippich et al., 2007a). In the patient group our results show significant changes of motor activations, ranging from a reduction of M1 lateralization to equalization of M1 activations or even inversion of M1 lateralization during contralesional movements. This study corroborates in a large patient group the idea that lesions affecting M1 may lead to functional reorganization of cortical motor systems and in particular equalize hemispheric lateralization. However, it is not yet clear whether these changes are only an epiphenomenon or indeed reflect an attempt of recovery of brain function.

Neurofibrillary pathology in Alzheimer's dementia (AD) is associated with cognitive impairments and cortical thinning, and begins in medial perirhinal cortex (mPRC) before entering entorhinal cortex (ERC). Thus, mPRC dysfunction (e.g., semantic object memory impairments) may predate or accompany ERC (i.e., episodic memory) dysfunction in the preclinical course of typical AD. We developed formulae estimating mPRC and ERC integrity (i.e., cortical thickness) using common neuropsychological tests in 31 healthy individuals and 58 early AD patients. These formulae estimated the longitudinal courses of mPRC and ERC functioning in independent groups of 28 optimally healthy individuals who developed AD (NC-AD) over 2.8-13.4 years and 28 pairwise-matched, stable, healthy individuals (NC-NC). Mixed models demonstrated significantly worse NC-AD than NC-NC estimated mPRC and ERC functioning at the earliest observation, 12 years preceding diagnosis, and a significant decline 4 years preceding the AD diagnosis. These findings demonstrate that specific neuropsychological impairments occur early in the course of preclinical AD and that tasks measuring mPRC functioning may serve as additional, powerful markers of preclinical AD.

Abstract Crossed cerebellar diaschisis (CCD) in internal carotid artery (ICA) stroke refers to attenuated blood flow and energy metabolism in the contralateral cerebellar hemisphere. CCD is associated with an interruption of cerebro-cerebellar tracts, but the precise mechanism is unknown. We hypothesized that in patients with ICA occlusions, CCD might indicate severe hemodynamic impairment in addition to tissue damage. Duplex sonography and clinical data from stroke patients with unilateral ICAO who underwent blood oxygen-level-dependent MRI cerebrovascular reserve (BOLD-CVR) assessment were analysed. The presence of CCD (either CCD+ or CCD−) was inferred from BOLD-CVR. We considered regions with negative BOLD-CVR signal as areas suffering from hemodynamic steal. Twenty-five patients were included (11 CCD+ and 14 CCD−). Stroke deficits on admission and at 3 months were more severe in the CCD+ group. While infarct volumes were similar, CCD+ patients had markedly larger BOLD steal volumes than CCD− patients (median [IQR] 122.2 [111] vs. 11.6 [50.6] ml; p &lt; 0.001). Furthermore, duplex revealed higher peak-systolic flow velocities in the intracranial collateral pathways. Strikingly, posterior cerebral artery (PCA)-P2 velocities strongly correlated with the National Institute of Health Stroke Scale on admission and BOLD-CVR steal volume. In patients with strokes due to ICAO, the presence of CCD indicated hemodynamic impairment with larger BOLD-defined steal volume and higher flow in the ACA/PCA collateral system. Our data support the concept of a vascular component of CCD as an indicator of hemodynamic failure in patients with ICAO.

Professional musicians are a model population for exploring basic auditory function, sensorimotor and multisensory integration, and training-induced neuroplasticity. The brain of musicians exhibits distinct structural and functional cortical features; however, little is known about how these features evolve during aging. This multiparametric study aimed to examine the functional and structural neural correlates of lifelong musical practice in elderly professional musicians.Sixteen young musicians, 16 elderly musicians (age >70), and 15 elderly non-musicians participated in the study. We assessed gray matter metrics at the whole-brain and region of interest (ROI) levels using high-resolution magnetic resonance imaging (MRI) with the Freesurfer automatic segmentation and reconstruction pipeline. We used BrainVoyager semiautomated segmentation to explore individual auditory cortex morphotypes. Furthermore, we evaluated functional blood oxygenation level-dependent (BOLD) activations in auditory and non-auditory regions by functional MRI (fMRI) with an attentive tone-listening task. Finally, we performed discriminant function analyses based on structural and functional ROIs.A general reduction of gray matter metrics distinguished the elderly from the young subjects at the whole-brain level, corresponding to widespread natural brain atrophy. Age- and musicianship-dependent structural correlations revealed group-specific differences in several clusters including superior, middle, and inferior frontal as well as perirolandic areas. In addition, the elderly musicians exhibited increased gyrification of auditory cortex like the young musicians. During fMRI, the elderly non-musicians activated predominantly auditory regions, whereas the elderly musicians co-activated a much broader network of auditory association areas, primary and secondary motor areas, and prefrontal and parietal regions like, albeit weaker, the young musicians. Also, group-specific age- and musicianship-dependent functional correlations were observed in the frontal and parietal regions. Moreover, discriminant function analysis could separate groups with high accuracy based on a set of specific structural and functional, mainly temporal and occipital, ROIs.In conclusion, despite naturally occurring senescence, the elderly musicians maintained musicianship-specific structural and functional cortical features. The identified structural and functional brain regions, discriminating elderly musicians from non-musicians, might be of relevance for the aging musicians' brain. To what extent lifelong musical activity may have a neuroprotective impact needs to be addressed further in larger longitudinal studies.

In patients with perimesencephalic subarachnoid hemorrhage (pSAH) DSA is recommended to exclude aneurysms to due false negative findings in CT-angiography. However, whether a second DSA is indicated during the clinical course to exclude--in addition to aneurysms--fistulas, too, is still under debate. We aimed to evaluate the benefit of repeated DSA in patients with pSAH.The source of data was a prospective database set up at the neurological, neurosurgical and neuroradiological departments in our institution. A total of 69 patients with pSAH were enrolled and analyzed by reviewing the medical records and neuroradiological findings.68 patients presented with Hunt & Hess Grade I-II and one patient with Hunt & Hess Grade III. Median in-hospital stay was 8 days (3-22). In 2 patients mild vasospasm were diagnosed. DSA was performed in all patients at least once. DSA was repeated in 38 patients (55%) after a median of 7 (3-21) days. None of the repeated DSA did show any additional distinctive features with respect to the first DSA.In our opinion the procedure of repeating DSA in patients with pSAH is likely to become obsolete. One DSA should be performed prior to discharge--and subsequent to possible vasospasm--to exclude hemorrhage caused by aneurysms of the posterior circulation mimicking a perimesencephalic SAH pattern.

To assess whether it is possible to measure tooth vitality using magnetic resonance imaging (MRI).Signal intensity measurements were conducted using T(1) and T(2) sequences at the region of interest in 211 teeth (35 patients).Clinical findings showed that 17.3% of the teeth were avital, whereas 82.7% were found to be vital. Neither the T(2) sequence nor the non-contrast-enhanced T(1) sequence showed significant differences between vital and avital teeth. However, the contrast-enhanced sequence and, in particular, a comparison of signal intensities between the non-contrast-enhanced T(1) sequence and the contrast-enhanced sequence showed a significant difference between vital and avital teeth.Contrast-enhanced MRI enables us to draw conclusions on pulpal perfusion in vivo.

Functional magnetic resonance imaging (fMRI) permits noninvasive imaging of the "human brain at work" under physiological conditions. This is the first textbook on clinical fMRI. It is devoted to preo

Response inhibition is the capacity to suppress inappropriate actions and is considered to be a fundamental executive function. This study investigated whether the neural correlates of response inhibition are organized along supramodal or modality-specific principles. For this purpose, we used event-related functional magnetic resonance imaging in a go-nogo task with auditory and visual stimuli. Common activation relating to response inhibition across modalities was observed in a frontoparietal network including the ventrolateral prefrontal cortex. In contrast, there was no modality-specific activation related to response inhibition in the prefrontal cortex. These findings suggest that the neural correlates of response inhibition have a supramodal organization, which is consistent with its role as a core executive function.

Brain atrophy has been identified as an important contributing factor to the development of disability in multiple sclerosis (MS). In this respect, more and more interest is focussing on the role of deep grey matter (DGM) areas. Novel data analysis pipelines are available for the automatic segmentation of DGM using three-dimensional (3D) MRI data. However, in clinical trials, often no such high-resolution data are acquired and hence no conclusions regarding the impact of new treatments on DGM atrophy were possible so far. In this work, we used FMRIB's Integrated Registration and Segmentation Tool (FIRST) to evaluate the possibility of segmenting DGM structures using standard two-dimensional (2D) T1-weighted MRI. In a cohort of 70 MS patients, both 2D and 3D T1-weighted data were acquired. The thalamus, putamen, pallidum, nucleus accumbens, and caudate nucleus were bilaterally segmented using FIRST. Volumes were calculated for each structure and for the sum of basal ganglia (BG) as well as for the total DGM. The accuracy and reliability of the 2D data segmentation were compared with the respective results of 3D segmentations using volume difference, volume overlap and intra-class correlation coefficients (ICCs). The mean differences for the individual substructures were between 1.3% (putamen) and -25.2% (nucleus accumbens). The respective values for the BG were -2.7% and for DGM 1.3%. Mean volume overlap was between 89.1% (thalamus) and 61.5% (nucleus accumbens); BG: 84.1%; DGM: 86.3%. Regarding ICC, all structures showed good agreement with the exception of the nucleus accumbens. The results of the segmentation were additionally validated through expert manual delineation of the caudate nucleus and putamen in a subset of the 3D data. In conclusion, we demonstrate that subcortical segmentation of 2D data are feasible using FIRST. The larger subcortical GM structures can be segmented with high consistency. This forms the basis for the application of FIRST in large 2D MRI data sets of clinical trials in order to determine the impact of therapeutic interventions on DGM atrophy in MS.

Background and purpose To determine the frequency of new ischaemic or hemorrhagic brain lesions on early follow‐up magnetic resonance imaging ( MRI ) in patients with cervical artery dissection ( CAD ) and to investigate the relationship with antithrombotic treatment. Methods This prospective observational study included consecutive CAD patients with ischaemic or non‐ischaemic symptoms within the preceding 4 weeks. All patients had baseline brain MRI scans at the time of CAD diagnosis and follow‐up MRI scans within 30 days thereafter. Ischaemic lesions were detected by diffusion‐weighted imaging ( DWI ), intracerebral bleeds ( ICB s) by paramagnetic‐susceptible sequences. Outcome measures were any new DWI lesions or ICB s on follow‐up MRI scans. K aplan– M eier statistics and calculated odds ratios with 95% confidence intervals were used for lesion occurrence, baseline characteristics and type of antithrombotic treatment (antiplatelet versus anticoagulant). Results Sixty‐eight of 74 (92%) CAD patients were eligible for analysis. Median (interquartile range) time interval between baseline and follow‐up MRI scans was 5 (3–10) days. New DWI lesions occurred in 17 (25%) patients with a cumulative 30‐day incidence of 41.3% (standard error 8.6%). Occurrence of new DWI lesions was associated with stroke or transient ischaemic attack at presentation [7.86 (2.01–30.93)], occlusion of the dissected vessel [4.09 (1.24–13.55)] and presence of DWI lesions on baseline MRI [6.67 (1.70–26.13)]. The type of antithrombotic treatment had no impact either on occurrence of new DWI lesions [1.00 (0.32–3.15)] or on functional 6‐month outcome [1.27 (0.41–3.94)]. No new ICB s were observed. Conclusion New ischaemic brain lesions occurred in a quarter of CAD patients, independently of the type of antithrombotic treatment. MRI findings could potentially serve as surrogate outcomes in pilot treatment trials.

The second, revised edition of this successful textbook provides an up-to-date description of the use of preoperative fMRI in patients with brain tumors and epilepsies. State of the art fMRI procedure

Tumor related contralateral motor deficits complicate preoperative functional magnetic resonance imaging (fMRI). In plegic patients the localization of the sensorimotor cortex is often impossible. In this context we developed a clinical fMRI protocol dedicated to patients with motor deficits using the unaffected ipsilateral hand. Based on the hypothesis that selfpaced finger movements recruit more and larger neuronal populations with rising task complexity, different motor tasks were tested regarding ipsilateral localization in ten right handed volunteers. Complex finger opposition localized the ipsilateral premotor cortex (Brodman area 6) robustly and was introduced to preoperative fMRI in hemiparetic patients as functional landmark to identify the precentral gyrus on the tumors side. Additional contralateral automated tactile stimulation localized the primary somatosensory cortex and completed the protocol.

Abstract OBJECTIVE: Most so-called idiopathic trigeminal neuralgias (TN) are caused by neurovascular compression. Does the size of the cerebellopontine cistern play a role in favoring a neurovascular conflict? The aim of this prospective study was to measure the volume of the parapontine cistern in patients with idiopathic TN and to perform a comparison with healthy controls. METHODS: In 25 patients with unilateral idiopathic TN and 17 healthy participants, high-resolution 1.5-T magnetic resonance imaging scans of the parapontine region and the trigeminal nerve were performed. A coronal T2-weighted, true fast imaging steady-state precession sequence with a slice thickness of 0.9 mm was used to define the surrounding cerebrospinal fluid space from the trigeminal root entry zone to Meckel's cave. The volume of the pontomesencephalic cistern was calculated using a standardized method. RESULTS: The mean difference of the volume of the affected and opposite side was 13% in patients with TN. In all patients, a significantly smaller volume of the cistern was found on the affected side (P &amp;lt; 0.01). Healthy controls showed a mean volumetric side difference of 9%, which was not significant (P &amp;gt; 0.05). CONCLUSION: High-resolution magnetic resonance imaging scans are able to demonstrate significant volumetric differences of the pontomesencephalic cistern in patients with unilateral TN. A smaller cistern may be correlated with the occurrence of a neurovascular compression, and these findings support the neurovascular compression theory in idiopathic TN.

HomeRadiologyVol. 253, No. 1 PreviousNext Case 150: Van Buchem Disease (Hyperostosis Corticalis Generalisata)Martina Wengenroth, Gergely Vasvari, Philipp A. Federspil, Johanna Mair, Peter Schneider, Christoph StippichMartina Wengenroth, Gergely Vasvari, Philipp A. Federspil, Johanna Mair, Peter Schneider, Christoph StippichAuthor Affiliations1From the Departments of Neuroradiology (M.W., P.S., C.S.), Oto-Rhino-Laryngology (G.V., P.A.F.), and Neurology (J.M.), University of Heidelberg Medical School, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.Address correspondence to M.W. (e-mail: [email protected]).Martina WengenrothGergely VasvariPhilipp A. FederspilJohanna MairPeter SchneiderChristoph StippichPublished Online:Oct 1 2009https://doi.org/10.1148/radiol.2531080011MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In AbstractA combination of clinical and MR examinations should be used to assess the severity of Van Buchem disease, particularly in respect to intracranial pressure. References 1. Balemans W, Cleiren E, Siebers U, Horst J, Van Hul W. A generalized skeletal hyperostosis in two siblings caused by a novel mutation in the SOST gene. Bone 2005;36:943–947. Crossref, Medline, Google Scholar2. Renton T, Odell E, Drage NA. Differential diagnosis and treatment of autosomal dominant osteosclerosis of the mandible. Br J Oral Maxillofac Surg 2002;40:55–59. Crossref, Medline, Google Scholar3. Cleiren E, Benichou O, Van Hul Eet al.. Albers-Schonberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. Hum Mol Genet 2001;10:2861–2867. Crossref, Medline, Google Scholar4. Andersen PE Jr, Bollerslev J. Heterogeneity of autosomal dominant osteopetrosis. Radiology 1987;164:223–225. Link, Google Scholar5. de Vernejoul MC. Sclerosing bone disorders. Best Pract Res Clin Rheumatol 2008;22:71–83. Crossref, Medline, Google Scholar6. Gelman MI. Autosomal dominant osteosclerosis. Radiology 1977;125:289–296. Link, Google Scholar7. Gorlin RJ, Glass L. Autosomal dominant osteosclerosis. Radiology 1977;125:547–548. Link, Google Scholar8. Janssens K, Vanhoenacker F, Bonduelle Met al.. Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment. J Med Genet 2006;43:1–11. Crossref, Medline, Google Scholar9. Beighton P, Barnard A, Hamersma H, van der Wouden A. The syndromic status of sclerosteosis and van Buchem disease. Clin Genet 1984;25:175–181. Crossref, Medline, Google Scholar10. Stein SA, Witkop C, Hill Set al.. Sclerosteosis: neurogenetic and pathophysiologic analysis of an American kinship. Neurology 1983;33:267–277. Crossref, Medline, Google Scholar11. Van Hul W, Balemans W, Van Hul Eet al.. Van Buchem disease (hyperostosis corticalis generalisata) maps to chromosome 17q12-q21. Am J Hum Genet 1998;62:391–399. Crossref, Medline, Google Scholar12. Gorlin RJ. Craniotubular bone disorders. Pediatr Radiol 1994;24:392–406. Crossref, Medline, Google Scholar13. Balemans W, Patel N, Ebeling Met al.. Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet 2002;39:91–97. Crossref, Medline, Google Scholar14. Wergedal JE, Veskovic K, Hellan Met al.. Patients with Van Buchem disease, an osteosclerotic genetic disease, have elevated bone formation markers, higher bone density, and greater derived polar moment of inertia than normal. J Clin Endocrinol Metab 2003;88:5778–5783. Crossref, Medline, Google Scholar15. Van Buchem FS, Hadders HN, Ubbens R. An uncommon familial systemic disease of the skeleton: hyperostosis corticalis generalisata familiaris. Acta Radiol 1955;44:109–120. Crossref, Medline, Google Scholar16. Eastman JR, Bixler D. Generalized cortical hyperostosis (Van Buchem disease): nosologic considerations. Radiology 1977;125:297–304. Link, Google Scholar17. Fryns JP, Van den Berghe H. Facial paralysis at the age of 2 months as a first clinical sign of van Buchem disease (endosteal hyperostosis). Eur J Pediatr 1988;147:99–100. Crossref, Medline, Google Scholar18. Dixon JM, Cull RE, Gamble P. Two cases of Van Buchem's disease. J Neurol Neurosurg Psychiatry 1982;45:913–918. Crossref, Medline, Google Scholar19. Scopelliti D, Orsini R, Ventucci E, Carratelli D. Van Buchem disease: maxillofacial changes, diagnostic classification and general principles of treatment [in Italian]. Minerva Stomatol 1999;48:227–234. Medline, Google ScholarArticle HistoryReceived January 4, 2008; revision requested February 27; revision received April 29; accepted May 13; final version accepted August 7.Published in print: Oct 2009 FiguresReferencesRelatedDetailsCited ByPosterior Vault Distraction for Multi-Suture Craniosynostosis in a Patient with Craniometaphyseal Dysplasia: A Case ReportDianaKennedy, IanLoh, Helen M.Branson, Christopher R.Forrest2022 | Craniomaxillofacial Research & Innovation, Vol. 7Van Buchem Disease: First Case Report from the Indian Subcontinent with an Early PresentationSaurabhMaheshwari, SonamYangzom, K. UdayBhanu, UddandamRajesh, AshokNarayan2021 | Journal of Child Science, Vol. 11, No. 01Sclerostin Antibody–Induced Changes in Bone Mass Are Site Specific in Developing CraniaAmanda LScheiber, David KBarton, Basma MKhoury, Joan CMarini, Donald LSwiderski, Michelle SCaird, Kenneth MKozloff2019 | Journal of Bone and Mineral Research, Vol. 34, No. 12Neuroradiology - Expect the UnexpectedMartinaŠpero2018Association of reduced sclerostin expression with collapse process in patients with osteonecrosis of the femoral headXiao-JunChen, FanYang, Zhen-QiuChen, Min-CongHe, Guo-JuHong, Jun-YuanHuang, Ying-ChunZhou, Yi-XianQin, Qiu-ShiWei, WeiHe2018 | International Orthopaedics, Vol. 42, No. 7Sclerostin deficiency in humansAntoon Hvan Lierop, Natasha MAppelman-Dijkstra, Socrates EPapapoulos2017 | Bone, Vol. 96Maladie de Van BuchemKawtarNassar, WafaeRachidi, SaadiaJanani, OuafaMkinsi2017 | Revue du Rhumatisme, Vol. 84, No. 5Van Buchem diseaseShang-FuHsu, Chen-ChunLin2017 | Medicine, Vol. 96, No. 50Genetic Diagnosis of Endocrine DisordersMurray J.Favus2016Van Buchem's DiseaseKawtarNassar, WafaeRachidi, SaadiaJanani, OuafaMkinsi2016 | Joint Bone Spine, Vol. 83, No. 6Craniometaphyseal dysplasia in a 14-month old: a case report and review of imaging differential diagnosisSumitSingh, CurtisQin, SrikanthMedarametla, Shilpa V.Hegde2016 | Radiology Case Reports, Vol. 11, No. 3Sclerosteosis caused by a novel nonsense mutation of SOST in a consanguineous familyWen‐TaoHe, ChenChen, ChuPan, Mu‐XunZhang, Xue‐FengYu, Dao‐WenWang, Shu‐HongHu2016 | Clinical Genetics, Vol. 89, No. 2Sclerostin and Bone Aging: A Mini-ReviewEricHay, WafaBouaziz, ThomasFunck-Brentano, MartineCohen-Solal2016 | Gerontology, Vol. 62, No. 6The canonical Wnt/β-catenin pathway: From the history of its discovery to clinical applicationT AGrebennikova, Zh EBelaya, L YaRozhinskaya, G AMelnichenko2016 | Terapevticheskii arkhiv, Vol. 88, No. 10Decompressive surgery in a patient with hyperostosis corticalis generalisata for relief of cognitive disability and dysaesthesiaMirjamDatema, Natasha M.Appelman-Dijkstra, Stefan. A.Hoyng, Marco. J.T.Verstegen, Radboud. W.Koot2015 | Acta Neurochirurgica, Vol. 157, No. 7Radiopaedia.orgFrancisFortin, CraigHacking2015Diffuse osteosclerosis in a patient with prostate cancerN.Üstün, I.Üstün, T.Özgür, N.Atci, F.Aydoğan, A. T.Sümbül, A. D.Turhanoğlu2014 | Osteoporosis International, Vol. 25, No. 3Van Buchem disease: Clinical, biochemical, and densitometric features of patients and disease carriersAntoon Hvan Lierop, Neveen ATHamdy, Martje Evan Egmond, EgbertBakker, Freek GDikkers, Socrates EPapapoulos2013 | Journal of Bone and Mineral Research, Vol. 28, No. 4The Role of Sclerostin in the Pathophysiology of Sclerosing Bone DysplasiasA. H.van Lierop, N. A. T.Hamdy, R. L.van Bezooijen, C. W.Löwik, S. E.Papapoulos2012 | Clinical Reviews in Bone and Mineral Metabolism, Vol. 10, No. 2A rare cause of facial nerve palsy in children: Hyperostosis corticalis generalisata (Van Buchem disease). Three new pediatric cases and a literature reviewM.E.van Egmond, F.G.Dikkers, A.M.Boot, A.H.J.M.van Lierop, S.E.Papapoulos, O.F.Brouwer2012 | European Journal of Paediatric Neurology, Vol. 16, No. 6Anabolic TherapiesNancy E.Lane, Stuart L.Silverman2010 | Current Osteoporosis Reports, Vol. 8, No. 1SclerostinStuart L.Silverman2010 | Journal of Osteoporosis, Vol. 2010Recommended Articles Skull Base–related Lesions at Routine Head CT from the Emergency Department: Pearls, Pitfalls, and Lessons LearnedRadioGraphics2019Volume: 39Issue: 4pp. 1161-1182Cranial Nerve Disorders in Children: MR Imaging FindingsRadioGraphics2016Volume: 36Issue: 4pp. 1178-1194CT of Skull Base Fractures: Classification Systems, Complications, and ManagementRadioGraphics2021Volume: 41Issue: 3pp. 762-782MRI of the Internal Auditory Canal, Labyrinth, and Middle Ear: How We Do ItRadiology2020Volume: 297Issue: 2pp. 252-265Diagnosis of Skull Base OsteomyelitisRadioGraphics2021Volume: 41Issue: 1pp. 156-174See More RSNA Education Exhibits Don't Get Nervous: Simple Approach to Learning Cranial Nerve Anatomy and PathologyDigital Posters2018Imaging of Traumatic Cranial Nerve InjuriesDigital Posters2019Dedicated Lower Cranial Nerve MRI Imaging, Anatomy, and Common PathologiesDigital Posters2018 RSNA Case Collection Chiari 1 malformation RSNA Case Collection2020Trigeminal schwannomaRSNA Case Collection2020Treacher Collins SyndromeRSNA Case Collection2022 Vol. 253, No. 1 Metrics Altmetric Score PDF download

&lt;b&gt;&lt;i&gt;Purpose:&lt;/i&gt;&lt;/b&gt; The role of endovascular treatment in cases of cervical artery dissection (CeAD) is debatable. With an increasing number of endovascular therapies such as endovascular recanalization and embolization the number of complications such as iatrogenic dissection is also rising. We report our experience with endovascular stenting in the treatment of patients presenting with CeAD. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We included all consecutive patients with CeAD (n = 168) treated in our hospital between 2001 and 2010 for our retrospective study. Patients with CeAD were considered eligible for stenting: (1) in iatrogenic dissections and (2) in noniatrogenic dissections if they suffered from recurrent ischemic events despite antithrombotic treatment. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; During our observation period 10 out of 168 patients presenting with CeAD were selected for stenting. Several types of stents were used. Stenting was technically successful in 8 but unsuccessful in 2 patients with complete arterial occlusion. Stent-related clinically apparent complications occurred in 3 of the 10 patients. All were transient. During a mean follow-up of 47 (±24.8) months none of the patients had new cerebrovascular ischemic events. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; In our patient sample stenting due to dissection is a rare procedure performed in less than 10% of CAD patients. It should be considered as a feasible rescue treatment in cases of impending stroke despite optimal antithrombotic therapy.

ABSTRACT BACKGROUND AND PURPOSE This study assesses whether magnetization transfer (MT) imaging provides additive information to conventional MRI in brain tumors. METHODS MT data of 26 patients with neoplastic and metastatic brain tumors were analyzed at 1.5 T. For the 3 largest tumor groups investigated in this study—glioblastoma multiforme (GBM), meningiomas, and metastases—statistical comparisons were performed. Analyzed MT parameters included the magnetization transfer ratio (MTR) and 4 quantitative MT parameters (qMT): Relaxation times (T1, T2), exchange rate (kf), and macromolecular content (F). Total imaging time of high‐resolution whole brain MTR and qMT imaging with balanced steady‐state free precession required 9 minutes. Five ROIs were chosen: Contrast‐enhancing (T1W‐CE), noncontrast‐enhancing (T1W‐non‐CE), proximal hyperintensity (T2W‐pSI), distal hyperintensity (T2W‐dSI), and a reference (ref). RESULTS Pathologies showed significant ( P &lt; .05) MT changes (MTR and qMT) compared to the reference. The T1W‐CE, T1W‐non‐CE, and T2W‐pSI ROIs of GBMs, meningiomas, and metastases showed significant differences in MTR and qMT estimates. Similar MTR with significant different qMT values were observed in several ROIs among different lesions. MT maps (MTR and qMT) indicated changes in tissue appearing unaffected on MRI in most glial tumors. CONCLUSIONS MTR and qMT imaging enables a better differentiation between brain tumors and provides additive information to MRI.

Magnetization transfer ratio (MTR) is a semi-quantitative measure that seems to correlate with the degree of myelin loss and generally tissue destruction in multiple sclerosis (MS). Our objective was to comprehensively assess the MTR of lesions and normal appearing (NA) tissue separately in the white matter (WM), the cortex, the thalamus and the basal ganglia (BG) and determine their relative contribution to disability. In this cross-sectional study 71 patients were included (59 with relapsing-remitting MS, 12 with secondary progressive MS). We used a three-dimensional MTR sequence with high spatial resolution, based on balanced steady-state free precession. Mean MTR was calculated for lesions and NA tissue separately for each tissue type. Lesional MTR was lower than normal-appearing MTR in WM, cortex and thalamus. In the regression analysis, MTR of cortical lesions (β = -0.23, p = 0.05) and MTR of WML (β = -0.21, p = 0.08) were related by trend to the expanded disability status scale. MTR of WML significantly predicted the paced auditory serial-addition test (β = 0.35, p = 0.004). MTR of normal-appearing tissue did not relate to any outcome. Our results suggest that MTR of lesions in the white matter and cortex rather than of normal-appearing tissue relates to disability in patients with MS.

Background Fingolimod is a first in class oral compound approved for the treatment of relapsing-remitting multiple sclerosis (RR-MS). The aim of this study was to evaluate clinical and neuroradiological responses to fingolimod as well as the safety and tolerability in RR-MS patients in clinical practice. In addition, a panel of pro-inflammatory serum cytokines was explored as potential biomarker for treatment response. Methods We conducted a retrospective, non-randomized, open-label, observational study in 105 patients with RR-MS and measured cytokines in longitudinal serum samples. Results Compared to the year before fingolimod start the annualized relapse rate was reduced by 44%. Also, the percentage of patients with a worsening of the EDSS decreased. Accordingly, the fraction of patients with no evidence of disease activity (no relapse, stable EDSS, no new active lesions in MRI) increased from 11% to 38%. The efficacy and safety were comparable between highly active patients or patients with relevant comorbidities and our general patient population. Conclusions The efficacy in reducing relapses was comparable to that observed in the phase III trials. In our cohort fingolimod was safe and efficacious irrespective of comorbidities and previous treatment.

The aim of this pilot study was to assess the clinical feasibility, diagnostic yield, advantages, and disadvantages of structured reporting for routine MRI-reading in patients with primary diagnosis of intracranial tumors as compared to traditional neuroradiological free text reporting.A structured MRI reporting template was developed covering pathological, anatomical, and functional aspects in an itemized fashion. Retrospectively, 60 consecutive patients with first diagnosis of an intracranial tumor were selected from the radiology information system/PACS system. Structured reporting was performed by a senior neuroradiologist, blinded to clinical and radiological data. Reporting times were measured per patient. The diagnostic content was compared to free text reporting which was independently performed on the same MRI exams by two other neuroradiologists. The comparisons were categorized per item as: "congruent," "partially congruent," "incongruent," or "not mentioned in free-style report."Tumor-related items: congruent findings were found for all items (17/17) with congruence rates ranging between 98 and 39% per item. Four items achieved congruence rates ≥90%, 5 items >80%, and 9 items ≥70%. Partially congruent findings were found for all items in up to 50% per item. Incongruent findings were present in 7/17 items in up to 5% per item. Free text reports did not mention 12 of 17 items (range 7-43% per item). Non-tumor-related items, including brain atrophy, microangiopathy, vascular pathologies, and various extracranial pathologies, which were not mentioned in free-text reports between 18 and 85% per item. Mean reporting time for structured reporting was 7:49 min (3:12-17:06 min).First results showed that expert structured reporting ensured reliable detection of all relevant brain pathologies along with reproducible documentation of all predefined diagnostic items, which was not always the case for free text reporting. A mean reporting time of 8 min per patient seems clinically feasible.

The clinical significance of ipsilateral thalamic diaschisis (ITD) occurring after stroke is unknown. To characterize ITD, we investigate its hemodynamic, structural, and clinical implications. A single-institution prospective cross-sectional study was conducted using 28 symptomatic cerebrovascular steno-occlusive patients undergoing both BOLD-CVR and Diamox-challenged 15(O)-H2O-PET. Follow-up was at least three months. In addition, 15 age-matched healthy subjects were included. ITD was diagnosed based on a BOLD-CVR thalamic asymmetry index (TAI) > +2 standard deviations from healthy subjects. Cerebral blood flow differences were assessed using a PET-based TAI before and after Diamox challenge. Thalamic volume masks were determined using Freesurfer. Neurological status at symptom onset and after three months was determined with NIHSS and mRS scores. ITD was diagnosed in 15 of 28 (57%) patients. PET-TAI before and after Diamox challenge were increased in patients with ITD, indicating an ipsilateral thalamic blood flow decrease. Patients with ITD exhibited a marked ipsilateral thalamic volume decrease as compared to patients without ITD and healthy subjects. Furthermore, patients with ITD had worse NIHSS and mRS at symptom onset and after three months follow-up, even after adjustment for stroke volume. The presence of ITD is characterized by thalamic volume reduction, reduced thalamic blood flow, and worse neurological performance unrelated to stroke volume.

Background In patients with steno‐occlusive disease, recent findings suggest that hemodynamic alterations may also be associated with crossed cerebellar diaschisis (CCD) rather than a functional disruption alone. Purpose To use a quantitative multiparametric hemodynamic MRI to gain a better understanding of hemodynamic changes related to CCD in patients with unilateral anterior circulation stroke. Study Type Prospective cohort study. Population Twenty‐four patients (25 datasets) with symptomatic unilateral anterior circulation stroke. Field Strength/Sequence 3T/two sequences: single‐shot (echo‐planar imaging) EPI sequence and T 2 * gradient echo perfusion‐weighted imaging study. Assessment The presence of CCD was inferred from the cerebellar asymmetry index (CAI) of the blood oxygenation‐level dependent cerebrovascular reactivity (BOLD‐CVR) exam, which was calculated from the mean BOLD‐CVR and standard deviation of the CAI of the healthy control group. For all perfusion‐weighted (PW)‐MRI parameters, the cerebellar and middle cerebral artery (MCA) territory asymmetry indices were calculated. Statistical Tests Independent Student's t ‐test to compare the variables from the CCD positive(+) and CCD negative(–) groups and analysis of covariance (ANCOVA) to statistically control the effect of covariates (infarct volume and time since ischemia onset). Results CCD was present in 33% of patients. In the MCA territory of the affected hemisphere, BOLD‐CVR was significantly more impaired in the CCD(+) group as compared to the CCD(–) group (mean BOLD‐CVR ± SD [%BOLD signal/ΔmmHgCO 2 ]: –0.03 ± 0.12 vs. 0.11 ± 0.13, P &lt; 0.05). Moreover, the mean transit time (MTT) (asymmetry index (%) CCD(+) vs. CCD(–): 28 ± 23 vs. 4 ± 11, P &lt; 0.05) and time to peak (TTP) (10 ± 10 vs. 2 ± 5, P &lt; 0.05) in the MCA territory of the affected hemisphere were significantly prolonged, while cerebral blood volume was, on average, increased in the CCD(+) group (25 ± 15 vs. 4 ± 19, P &lt; 0.05). Data Conclusion Our findings show that, in patients with symptomatic unilateral anterior circulation stroke, CCD is associated with hemodynamic impairment in the ipsilateral MCA territory, which further supports the concept of a vascular component of CCD. Level of Evidence 3 Technical Efficacy Stage 3

Background Comprehensive hemodynamic impairment mapping using blood oxygenation-level dependent (BOLD) cerebrovascular reactivity (CVR) can be used to identify hemodynamically relevant symptomatic unilateral carotid artery disease. Methods and Results This prospective cohort study was conducted between February 2015 and July 2020 at the Clinical Neuroscience Center of the University Hospital Zurich, Zurich, Switzerland. One hundred two patients with newly diagnosed symptomatic unilateral internal carotid artery (ICA) occlusion or with 70% to 99% ICA stenosis were included. An age-matched healthy cohort of 12 subjects underwent an identical BOLD functional magnetic resonance imaging examination. Using BOLD functional magnetic resonance imaging with a standardized CO2 stimulus, CVR impairment was evaluated. Moreover, embolic versus hemodynamic ischemic patterns were evaluated on diffusion-weighted imaging. Sixty-seven patients had unilateral ICA occlusion and 35 patients unilateral 70% to 99% ICA stenosis. Patients with ICA occlusion exhibited lower whole-brain and ipsilateral hemisphere mean BOLD-CVR values as compared with healthy subjects (0.12±0.08 versus 0.19±0.04, P=0.004 and 0.09±0.09 versus 0.18±0.04, P<0.001) and ICA stenosis cohort (0.12±0.08 versus 0.16±0.05, P=0.01 and 0.09±0.09 versus 0.15±0.05, P=0.01); however, only 40 (58%) patients of the cohort showed significant BOLD-CVR impairment. Conversely, there was no difference in mean BOLD-CVR values between healthy patients and patients with ICA stenosis, although 5 (14%) patients with ICA stenosis showed a significant BOLD-CVR impairment. No significant BOLD-CVR difference was discernible between patients with hemodynamic ischemic infarcts versus those with embolic infarct distribution (0.11±0.08 versus 0.13±0.06, P=0.12). Conclusions Comprehensive BOLD-CVR mapping allows for identification of hemodynamically relevant symptomatic unilateral carotid artery stenosis or occlusion.

A clinical functional magnetic resonance imaging (fMRI) protocol based on a fully automated tactile stimulation was optimized in 10 right-handed volunteers at 1.5 T for minimum scan time, high BOLD-signals and robust localization of the primary somatosensory cortex (S1) by systematically varying the applied block design. All volunteers had six different fMRI measurements of 5 stimulation/baseline cycles each with equal block duration that was changed between the measurements from 6 to 30 s. Data sets of 4, 3 and 2 cycles were generated post hoc resulting in a total of 240 data sets that were evaluated individually for BOLD-signal intensity (dS%), correlation to the hemodynamic reference function (r) and Euclidean coordinates (x, y, z). The protocol with 5 cycles, a block duration of 6 s and a total scan time of 66 s provided the best BOLD-signal characteristics (dS%=1.15, r=0.78). Compared to the mean scan time of other clinical fMRI protocols (174 s) a reduction of 62% was achieved.

Trigeminal neuralgia (TN) is a pain state characterized by intermittent unilateral pain attacks in one or several facial areas innervated by the trigeminal nerve. The somatosensory cortex is heavily involved in the perception of sensory features of pain, but it is also the primary target for thalamic input of nonpainful somatosensory information. Thus, pain and somatosensory processing are accomplished in overlapping cortical structures raising the question whether pain states are associated with alteration of somatosensory function itself. To test this hypothesis, we used functional magnetic resonance imaging to assess activation of primary (SI) and secondary (SII) somatosensory cortices upon nonpainful tactile stimulation of lips and fingers in 18 patients with TN and 10 patients with TN relieved from pain after successful neurosurgical intervention in comparison with 13 healthy subjects. We found that SI and SII activations in patients did neither depend on the affected side of TN nor differ between operated and nonoperated patients. However, SI and SII activations, but not thalamic activations, were significantly reduced in patients as compared to controls. These differences were most prominent for finger stimulation, an area not associated with TN. For lip stimulation SI and SII activations were reduced in patients with TN on the contra- but not on the ipsilateral side to the stimulus. These findings suggest a general reduction of SI and SII processing in patients with TN, indicating a long-term modulation of somatosensory function and pointing to an attempt of cortical adaptation to potentially painful stimuli.

We examined the influence of a single exercise session on quantitative muscle fat fraction MRI measurements. Ten healthy volunteers were scanned on a 3T body scanner before and after a session of bilateral squats until muscular fatigue. Axial in- and opposed phase images were acquired at a fixed distance from the knee joint and fat fractions were calculated using a 2-point Dixon technique as well as muscle cross sectional area at the same position. After the squat session, calculated fat fraction in the quadriceps bilaterally appeared to be significantly decreased, while all but one non-exercised muscles showed no change. In conclusion exercise might modify the measured apparent fat fraction. Trials using quantitative MRI should consider the timing of scanning sessions and physical examinations to avoid bias caused by the influence of exercise on measurements.

Although tumor size affects survival of patients with lower-grade glioma, a prognostic effect on patients with glioblastoma remains to be established. We performed a retrospective analysis of 61 patients using volumetric data of tumor compartments of 61 patients obtained by preoperative magnetic resonance images using the visual ABC/2 method. Preoperative enhancing, nonenhancing, necrosis, and edema volume, the preoperative tumor area (TA) as a product of the 2 largest tumor diameters perpendicular to each other on axial T1-weighted postcontrast images, as well as postoperative enhancing residual volumes, were measured. Multivariable Cox proportional hazard models were used to associate these parameters with overall survival, adjusting for potential confounders. The median preoperative enhancing tumor volume was 18.2 mL (interquartile range, 8.2–41.7 mL); the median remnant tumor volume was 1.3% (interquartile range, 0.0%–42.9%). During follow-up, 59 patients (92%) died; median survival time and median follow-up time were both 404 days. We found a statistically significant multiplicative effect of TA on survival: the hazard ratio (HR) was increased by 1.096 per unit increase of 200 mm2 (95% confidence interval [CI], 1.027–1.170; P < 0.01). The effect of remnant tumor on HR increased multiplicatively by 1.013 (95% CI, 1.001–1.026; P = 0.04) per unit increase of 1 log (day) and 1% in tumor remnant. HR associated with age at surgery increased by 1.503 per 5 years of age (95% CI, 1.243–1.817; P < 0.01). Preoperative TA proved to be the only glioblastoma size parameter that affects patient survival.

The literature on multiple intracranial aneurysms (MIA) in patients with aneurysmal subarachnoid hemorrhage (aSAH) focuses largely on risk factor analysis and consists essentially of retrospective cohort studies of limited sample size, or studies in populations outside Europe and North America. The purpose of this cohort study was to identify predictors for aneurysm multiplicity and to investigate the anatomic distribution of MIA in a representative Western cohort of patients with aSAH.The Swiss Study of Subarachnoid Hemorrhage (SOS) database includes anonymized data from all tertiary neurovascular facilities in Switzerland. The dataset for 2009-2014 was used to compare characteristics of patients with aSAH and MIA and those with a single intracranial aneurysm (SIA) by means of descriptive and multivariate regression analysis.Among 1689 unselected patients with aSAH, 467 had MIA (prevalence, 27.6%). The location of the ruptured index aneurysm was correlated with the probability of finding bystander aneurysms and predicted their likely anatomic distribution. Patients with a ruptured basilar artery aneurysm (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.30-3.44) or a ruptured middle cerebral artery aneurysm (OR, 1.86; 95% CI, 1.35-2.55) were at the greatest risk for having MIA. Larger size of the index aneurysm (OR per 1 mm, 1.03; 95% CI, 1.01-1.06) was also positively correlated with aneurysm multiplicity. Males were less likely than females to have MIA (OR, 0.79; 95% CI, 0.61-1.01).In patients with aSAH, the location of the ruptured index aneurysm is correlated with the probability of finding bystander aneurysms, and is predictive of the sites at which bystander aneurysms are most likely to be found.

Abstract Diffuse gliomas progress by invading neighboring brain tissue to promote postoperative relapse. Transcription factor SOX2 is highly expressed in invasive gliomas and maps to chromosome region 3q26 together with the genes for PI3K/AKT signaling activator PIK3CA and effector molecules of mitochondria fusion and cell invasion, MFN1 and OPA1. Gene copy number analysis at 3q26 from 129 glioma patient biopsies revealed mutually exclusive SOX2 amplifications (26%) and OPA1 losses (19%). Both forced SOX2 expression and OPA1 inactivation increased LN319 glioma cell invasion in vitro and promoted cell dispersion in vivo in xenotransplanted D. rerio embryos. While PI3 kinase activity sustained SOX2 expression, pharmacological PI3K/AKT pathway inhibition decreased invasion and resulted in SOX2 nucleus‐to‐cytoplasm translocation in an mTORC1‐independent manner. Chromatin immunoprecipitation and luciferase reporter gene assays together demonstrated that SOX2 trans‐ activates PIK3CA and OPA1 . Thus, SOX2 activates PI3K/AKT signaling in a positive feedback loop, while OPA1 deletion is interpreted to counteract OPA1 trans ‐activation. Remarkably, neuroimaging of human gliomas with high SOX2 or low OPA1 genomic imbalances revealed significantly larger necrotic tumor zone volumes, corresponding to higher invasive capacities of tumors, while autologous necrotic cells are capable of inducing higher invasion in SOX2 overexpressing or OPA1 knocked‐down relative to parental LN319. We thus propose necrosis volume as a surrogate marker for the assessment of glioma invasive potential. Whereas glioma invasion is activated by a PI3K/AKT‐SOX2 loop, it is reduced by a cryptic invasion suppressor SOX2‐OPA1 pathway. Thus, PI3K/AKT‐SOX2 and mitochondria fission represent connected signaling networks regulating glioma invasion.

Background and purpose To demonstrate the clinical feasibility of a novel MRI pulse sequence, Golden-angle radial sparse parallel MRI (GRASP) through comparison to the current imaging technique, dynamic T1- weighted contrast enhanced (DCE) imaging in terms of image quality and lesion depiction in the detection of microlesions (microadenomas and cysts) of the pituitary gland. 16 patients (11 microadenomas, 5 cysts) underwent two MRI examinations (Siemens 1.5T and 3T) on separate dates, one using standard DCE (temporal resolution 30 s) and the other using GRASP (temporal resolution of 4.4 s). Two neuroradiologists separately recorded measures of image quality (Scale 1–5, 5 = best), lesion size and contrast arrival times in terms of first and best lesion conspicuity. In qualitiative analysis there were no significant differences in terms of average visual image sharpness (DCE 3.9 ± 0.9, GRASP 3.9 ± 0.9) or visual contrast scores (DCE 4.1 ± 1.2, GRASP 4.4 ± 0.8). Pearson's correlation coefficients for interreader lesion measurements (width and height, mm) ranged from substantial to almost perfect agreement (r = 0.73 to 0.88). Analysis of contrast arrival times revealed an average lesion first-conspicuity time of 60.7 ± 16.7 s for DCE compared to 50.2 ± 10.3 s for GRASP with a difference of 10.5 ± 16.2 s (p = 0.023). Depiction of pituitary microlesions is feasible with GRASP, which has the potential to increase sensitivity through higher temporal resolutions combined with isotropic acquisition allowing for multi-planar reconstructions; this remains to be proven in larger cohorts.

Standardized, robust and time-efficient localization of the human secondary somatosensory cortex (S2) is a challenge in clinical blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). A fully automated tactile stimulation was optimized in seven right-handed volunteers at 1.5 T for minimum scan time, high BOLD signals and robust localization of S2 by systematically varying the applied block-design. All volunteers had six different fMRI measurements of five stimulation-baseline-cycles (sbc) each with equal block duration that was changed between the measurements from 6 s to 30 s. Additional data sets of 4, 3 and 2 cycles were generated post hoc resulting in a total of 168 data sets that were evaluated individually for BOLD-signal intensity (dS%), correlation to the hemodynamic reference function (r) and Euclidean coordinates (x, y, z). Using different block-designs the S2 activation was highly variable regarding the localization rate (lr), the hemispheric symmetry and the BOLD-signals. The protocol with 3 cycles, a block duration (dp) of 15 s and a total scan time (dt) of 105 s most robustly localized S2 (contralateral: lr = 71.4%, r = 0.65, dS = 1.01%; ipsilateral: lr = 100%, r = 0.6, dS = 1.14%) whereas the most time-efficient protocol to localize SI (sbc = 5, dp = 6 s, dt = 66 s) provided no robust localization of S2. Compared to other published fMRI protocols a scan time reduction up to 86% was achieved.

Magnetization transfer (MT) reflects the exchange of magnetization between protons bound to macromolecules, such as lipids and proteins, and protons in free liquid, and thus might be an early marker for subtle and undetermined pathologic changes in tissue. Detailed analysis of the entire MT phenomenon, however, commonly requires extensive data acquisition and scanning time, and hence is only of limited clinical interest. Therefore, in practice, magnetization transfer effects are commonly confined into a simple ratio measure, the so-called magnetization transfer ratio (MTR), calculated from a MT-weighted and a non-MT-weighted image. However, subtle physiologic and pathologic changes in tissue, invaluable for specific diagnostic imaging, may be lost since MTR-values depend not only on quantitative magnetization transfer (qMT) parameters but also on sequence parameters and relaxation properties. In order to evaluate and assess the diagnostic specificity of MTR versus qMT, high-resolution whole brain MT data was collected from twelve healthy volunteers using balanced steady-state free precession (bSSFP). In contrast to common MT imaging based on spoiled gradient echo (SPGR) sequences, whole brain qMT imaging can be performed with MT-sensitized bSSFP within a clinically feasible acquisition time. Hence, MT-sensitized bSSFP provides access to both MTR and qMT parameters within a clinical setting. The reliability and possible diagnostic value of MTR are analyzed for twelve white matter (WM) and eleven gray matter (GM) structures of the normal appearing brain. Strong correlations were found within and between longitudinal and transverse relaxation times (T1, T2) and MT parameters (ratio between macromolecular and water protons, F, and magnetization exchange rate, kf), whereas weaker correlations were observed between MTR-values and relaxation times or MT parameters. Structures with highly similar MTR-values, such as the crus cerebri and the anterior commissure in the WM, or the pallidum and the amygdala in the GM, however, were also found that showed significant differences in most quantitative parameters. This observation was confirmed from simulations revealing that the overall effect on MTR from an increase (decrease) in relaxation times may be counterbalanced with a decrease (increase) in MT parameters. These findings corroborate the expectation that qMT is superior to MTR imaging, especially for the evaluation and assessment of pathologic or physiological changes in healthy and pathologic brain tissue.

Blood flow velocity measurement with phase contrast magnetic resonance imaging (PC-MRI) is widely applied in clinical routine imaging. Usually, velocity and volumetric flow measurements are performed using unidirectional encoding of the through-plane velocity with a 2-dimensional (2D) acquisition. Single-slice acquisitions and measurements with unidirectional encoding, however, may lead to significant errors, especially in tortuous vessels, but might benefit from higher signal-to-noise ratios (SNRs). To evaluate the impact of volumetric acquisition and multidirectional velocity encoding, blood velocity measurements were performed at 3 locations in the distal internal carotid artery with a 3-dimensional, 3-directional time-resolved phase contrast (PC) sequence (4-dimensional [4D]) and a 2D acquisition with 3-directional (2D-3dir) and through-plane velocity encoding (2D-tp) derived from the same sequence.Twenty carotid arteries of 10 healthy volunteers (24-37 years) were evaluated. For each volunteer, 1 4D acquisition and 3 2D 3-directional PC measurements were placed according to a time-of-flight angiography. Unidirectionally encoded through-plane velocities were derived from the multidirectionally encoded 2D scan by discarding the in-plane components. Regions of interest were identified on the slab after postprocessing and visualization for the 4D data set as well as directly on the digital imaging and communications in medicine images for the 2D measurement. Blood flow velocity, volumetric flow, and SNRs were measured at carotid segments C4, C5, and C7 on both sides obtaining 20 values per vessel location. The quantities were tested for significant differences between each modality at all 3 locations with paired t tests.At the segments C5 and C7, the highest peak velocities (PVs) were measured with the 4D sequence, followed by 2D-3dir and 2D tp. The PV differences between the sequences were significant (P < 0.01) at both locations. At the proximal segment of the carotid siphon (C4), the PV values of the 2D-3dir sequence were significantly higher than the ones measured with 2D-tp. The mean PV value of the 4D sequence was located in between 2D-3dir and 2D-tp without significant differences to either of the 2D sequences. Volumetric flow measurements were also significantly different between 2D and 4D acquisitions, but without a discernible trend. The SNR analysis clearly favored 2D over 4D acquisitions because of higher inflow enhancement.The results of the current study show that velocity measurements with a unidirectional encoded through-plane PC sequence lead to a significant underestimation of velocity values in tortuous vessels. In all 3 evaluated segments of the distal internal carotid artery, multidirectional velocity encoding revealed significantly higher PV values than those of unidirectional velocity encoding. These results indicate that multidirectional encoding should be preferred to unidirectional encoding for velocity measurements in tortuous vessels. Furthermore, 4D PC-MRI is superior to 2D-3dir in 2 of 3 locations. However, single-slice measurements with multidirectional velocity encoding have higher SNR and may be an alternative to 4D PC-MRI with a scan time of only approximately 90 seconds per slice.

Preoperative functional magnetic resonance imaging (fMRI) localizes the primary motor and somatosensory cortex in relation to rolandic brain tumors and determines plastic cortical reorganization. Functional landmarks help to assess the indication for surgery and to plan for safer surgical procedures that protect the functional cortex during resection even when morphologic landmarks are no longer identifiable on anatomic images. Despite its successful application, preoperative fMRI has not yet reached the status of an established clinical diagnostic procedure since special stimulation systems, standardized fMRI protocols and medically approved software are still lacking. Following a brief review of the image display of the functional and morphologic anatomy, the different indications for preoperative fMRI in patients with rolandic brain tumors are presented. A robust preoperative protocol enables clinical MR units with magnetic field strengths of 1.0 Tesla or higher to perform reliable fMRI during contralateral hand movements. Optimized investigation strategies and stimulation modalities are proposed for patients with rolandic tumors distant from the cortical hand representation, for patients with preexisting sensorimotor deficits and for patients with poor compliance. Representative cases illustrate the clinical application. Possibilities and limitations of preoperative fMRI are presented and discussed.