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Cognitive impairment is common in Parkinson's disease (PD), yet with large heterogeneity in the range and course of deficits. In a cross-sectional study, 124 PD patients underwent extensive clinical and neuropsychological assessment as well as a 3T MRI scan of the brain. Our aim was to identify differences in grey matter volume and thickness, as well as cortical folding, across different cognitive profiles as defined through a data-driven exploratory cluster analysis of neuropsychological data. The identified cognitive groups ranged from cognitively intact patients to patients with severe deficits in all cognitive domains, whilst showing comparable levels of motor disability and disease duration. Each group was compared to the cognitively intact PD group using voxel- and vertex-based morphometry. Results revealed widespread age-related grey matter abnormalities associated with progressive worsening of cognitive functions in mild PD. When adjusted for age, significant differences were only seen between cognitively intact and severely affected PD patients and these were restricted to the right posterior cingulate and the right precuneus. Reduced cortical thickness was seen in the right inferior temporal gyrus and reduced folding in the right temporal region. As these differences were not associated with age, we assume that they are associated with underlying pathology of the cognitive decline. Given the limited involvement of grey matter differences, and the absence of differences in vascular changes across the groups, we hypothesize a more important role for white matter tract changes in cognitive decline in PD. (C) 2019 Elsevier Ltd. All rights reserved.

AimsThe aim of this study is to evaluate whether agreement with autopsy-determined cause of death (COD) increases by use of postmortem CT (PMCT) or PMCT in combination with postmortem sampling (PMS), when compared with clinical assessment only.MethodsThis prospective observational study included deceased patients from the intensive care unit and internal medicine wards between October 2013 and August 2017. The primary outcome was percentage agreement on COD between the reference standard (autopsy) and the alternative postmortem examinations (clinical assessment vs PMCT or PMCT+PMS). In addition, the COD of patient groups with and without conventional autopsy were compared with respect to involved organ systems and pathologies.ResultsOf 730 eligible cases, 144 could be included for analysis: 63 underwent PCMT without autopsy and 81 underwent both PMCT and autopsy. Agreement with autopsy-determined COD was significantly higher for both PMCT with PMS (42/57, 74%), and PMCT alone (53/81, 65%) than for clinical assessment (40/81, 51%; p=0.007 and p=0.03, respectively). The difference in agreement between PMCT with PMS and PMCT alone was not significant (p=0.13). The group with autopsy had a significantly higher prevalence of circulatory system involvement and perfusion disorders, and a lower prevalence of pulmonary system involvement.ConclusionPMCT and PMS confer additional diagnostic value in establishing the COD. Shortcomings in detecting vascular occlusions and perfusion disorders and susceptibility to pulmonary postmortem changes could in future be improved by additional techniques. Both PMCT and PMS are feasible in clinical practice and an alternative when autopsy cannot be performed.

The aim of this study is to assess the added value of post-mortem computed tomography (PMCT) in fatal shooting incidents compared with autopsy findings. For this study, the analysis was restricted to the following four features: location of the entrance and exit wounds, internal injuries, location of projectiles or metal fragments and course of the trajectories. These features were selected because they provide essential information on the cause and manner of death. All data were retrospectively collected from medical forensic examinations of fatal shooting incidents in the Netherlands that occurred in 2010-2014. Twenty-one fatal shooting victims were included in this study, with a total of 100 trajectories. For all 100 trajectories, the forensic radiologist and pathologist came to a consensus on which examination had the highest diagnostic value for each of the four features. PMCT provides superior information on the presence of metal fragments, internal injuries and the course of trajectories. PMCT provides limited information on the discrimination of entrance and exit wounds. In conclusion, PMCT provides additional relevant information in over 60% of forensic medical examinations of deceased victims of shooting incidents. We therefore recommend adding PMCT as a standard examination in these cases.

Purpose Forensic investigations could benefit from non-invasive in situ characterization of bullets. Therefore, the use of CT imaging was explored for the analysis of bullet geometry and composition. Bullet visualization with CT is challenging as the metal constituents suffer from excessive X-ray attenuation due to their high atomic number, density, and geometry. Methods A metal reference phantom was developed containing small discs of various common metals (aluminum, iron, stainless steel, copper, brass, tungsten, and lead). CT images were acquired with 70–150 kVp and 200–400 mAs and were reconstructed using an extended Hounsfield unit (HU) scale (− 10,240 to + 30,710). For each material, the mean CT number (HU) was measured to construct a metal database. Different bullets (n = 11) were scanned in a soft tissue-mimicking phantom. Bullet size and shape were measured, and composition was evaluated by comparison with the metal database. Also, the effect of bullet orientation within the CT scanner was evaluated. Results In the reference phantom, metals were classified into three groups according to their atomic number (Z): low (Z ≤ 13; HU 30,000). External bullet contours could be accurately delineated. Internal interfaces between jacket and core could not be identified. Cross-sectional spatial profile plots of the CT number along bullets’ short axis revealed beam hardening and photon starvation effects that depended on bullet size, shape, and orientation within the CT scanner. Therefore, the CT numbers of bullets were unreliable and could not be used for material characterization by comparison with the reference phantom. Conclusion CT-based characterization of bullets was feasible in terms of size and shape but not composition.

ObjectiveWe used magnetization transfer imaging to assess white matter tissue integrity in migraine, to explore whether white matter microstructure was more diffusely affected beyond visible white matter hyperintensities (WMHs), and to explore whether focal invisible microstructural changes precede visible focal WMHs in migraineurs.MethodsWe included 137 migraineurs (79 with aura, 58 without aura) and 74 controls from the Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis (CAMERA) study, a longitudinal population-based study on structural brain lesions in migraine patients, who were scanned at baseline and at a 9-year follow-up. To assess microstructural brain tissue integrity, baseline magnetization transfer ratio (MTR) values were calculated for whole brain white matter. Baseline MTR values were determined for areas of normal-appearing white matter (NAWM) that had progressed into MRI-detectable WMHs at follow-up and compared to MTR values of contralateral NAWM.ResultsMTR values for whole brain white matter did not differ between migraineurs and controls. In migraineurs, but not in controls, NAWM that later progressed to WMHs at follow-up had lower mean MTR (mean [SD] 0.354 [0.009] vs 0.356 [0.008], p = 0.047) at baseline as compared to contralateral white matter.ConclusionsWe did not find evidence for widespread microstructural white matter changes in migraineurs compared to controls. However, our findings suggest that a gradual or stepwise process might be responsible for evolution of focal invisible microstructural changes into focal migraine-related visible WMHs.

It is often difficult to predict seizure recurrence in subjects who have suffered a first-ever epileptic seizure. In this study, the predictive value of physiological signals measured using Electroencephalography (EEG) and functional MRI (fMRI) is assessed. In particular those patients developing epilepsy (i.e. a second unprovoked seizure) that were initially evaluated as having a low risk of seizure recurrence are of interest.In total, 26 epilepsy patients, of which 8 were initially evaluated as having a low risk of seizure recurrence (i.e. converters), and 17 subjects with only a single seizure were included. All subjects underwent routine EEG as well as fMRI measurements. For diagnostic classification, features related to the temporal dynamics were determined for both the processed EEG and fMRI data. Subsequently, a logistic regression classifier was trained on epilepsy and first-seizure subjects. The trained model was tested using the clinically relevant converters group.The sensitivity, specificity, and AUC (mean +/- SD) of the regression model including metrics from both modalities were 74 +/- 19%, 82 +/- 18%, and 0.75 +/- 0.12, respectively. Positive and negative predictive values (mean SD) of the regression model with both EEG and fMRI features are 84 +/- 14% and 78 +/- 12%. Moreover, this EEG/fMRI model showed significant improvements compared to the clinical diagnosis, whereas the models using metrics from either EEG or fMRI do not reach significance (p > 0.05).Temporal metrics computationally derived from EEG and fMRI time signals may clinically aid and synergistically improve the predictive value in a first-seizure sample. (C) 2020 The Author(s). Published by Elsevier Inc.

Background The aim of this systematic review was (1) to identify the brain regions involved in anxiety in Parkinson's disease (PD) based on neuroimaging studies and (2) to interpret the findings against the background of dysfunction of the fear circuit and limbic cortico‐striato‐thalamocortical circuit. Methods Studies assessing anxiety symptoms in PD patients and studies using magnetic resonance imaging, positron emission tomography, or single‐photon emission computed tomography were included. Results The severity of anxiety was associated with changes in the fear circuit and the cortico‐striato‐thalamocortical limbic circuit. In the fear circuit, a reduced gray‐matter volume of the amygdala and the anterior cingulate cortex (ACC); an increased functional connectivity (FC) between the amygdala and orbitofrontal cortex (OFC) and hippocampus and between the striatum and the medial prefrontal cortex (PFC), temporal cortex, and insula; and a reduced FC between the lateral PFC and the OFC, hippocampus, and amygdala were reported. In the cortico‐striato‐thalamocortical limbic circuit, a reduced FC between the striatum and ACC; a reduced dopaminergic and noradrenergic activity in striatum, thalamus, and locus coeruleus; and a reduced serotoninergic activity in the thalamus were reported. Conclusion To conclude, anxiety is associated with structural and functional changes in both the hypothesized fear and the limbic cortico‐striato‐thalamocortical circuits. These circuits overlap and may well constitute parts of a more extensive pathway, of which different parts play different roles in anxiety. The neuropathology of PD may affect these circuits in different ways, explaining the high prevalence of anxiety in PD and also the associated cognitive, motor, and psychiatric symptoms. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Highlights • This review discusses 16 studies using 7T MRI to evaluate patients with chronic focal epilepsy. • UHF MRI increases the sensitivity to detect an epileptogenic lesion. • Diagnostic gain of 7T over conventional MRI was between 8 and 67%, pooled gain was 31% • FCD, gliosis and HS were the most frequently diagnosed histopathological lesions. • No conclusion can be drawn whether 7T improves surgical treatment and seizure outcome., Rationale Resective epilepsy surgery is an evidence-based curative treatment option for patients with drug-resistant focal epilepsy. The major preoperative predictor of a good surgical outcome is detection of an epileptogenic lesion by magnetic resonance imaging (MRI). Application of ultra-high field (UHF) MRI, i.e. field strengths ≥ 7 Tesla (T), may increase the sensitivity to detect such a lesion. Methods A keyword search strategy was submitted to Pubmed, EMBASE, Cochrane Database and clinicaltrials.gov to select studies on UHF MRI in patients with epilepsy. Follow-up study selection and data extraction were performed following PRISMA guidelines. We focused on I) diagnostic gain of UHF- over conventional MRI, II) concordance of MRI-detected lesion, seizure onset zone and surgical decision-making, and III) postoperative histopathological diagnosis and seizure outcome. Results Sixteen observational cohort studies, all using 7T MRI were included. Diagnostic gain of 7T over conventional MRI ranged from 8% to 67%, with a pooled gain of 31%. Novel techniques to visualize pathological processes in epilepsy and lesion detection are discussed. Seizure freedom was achieved in 73% of operated patients; no seizure outcome comparison was made between 7T MRI positive, 7T negative and 3T positive patients. 7T could influence surgical decision-making, with high concordance of lesion and seizure onset zone. Focal cortical dysplasia (54%), hippocampal sclerosis (12%) and gliosis (8.1%) were the most frequently diagnosed histopathological entities. Significance UHF MRI increases, yet variably, the sensitivity to detect an epileptogenic lesion, showing potential for use in clinical practice. It remains to be established whether this results in improved seizure outcome after surgical treatment. Prospective studies with larger cohorts of epilepsy patients, uniform scan and sequence protocols, and innovative post-processing technology are equally important as further increasing field strengths. Besides technical ameliorations, improved correlation of imaging features with clinical semiology, histopathology and clinical outcome has to be established.

OBJECTIVE Structural brain abnormalities are key risk factors for brain diseases, such as dementia, stroke, and depression, in type 2 diabetes. It is unknown whether structural brain abnormalities already occur in prediabetes. Therefore, we investigated whether both prediabetes and type 2 diabetes are associated with lacunar infarcts (LIs), white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), and brain atrophy. RESEARCH DESIGN and METHODS We used data from 2,228 participants (1,373 with normal glucose metabolism [NGM], 347 with prediabetes, and 508 with type 2 diabetes (oversampled); mean age 59.2 ± 8.2 years; 48.3% women) of the Maastricht Study, a population-based cohort study. Diabetes status was determined with an oral glucose tolerance test. Brain imaging was performed with 3 Tesla MRI. Results were analyzed with multivariable logistic and linear regression analyses. RESULTS Prediabetes and type 2 diabetes were associated with the presence of LIs (odds ratio 1.61 [95% CI 0.98–2.63] and 1.67 [1.04–2.68], respectively; Ptrend = 0.027), larger WMH (β 0.07 log10-transformed mL [log-mL] [95% CI 0.00–0.15] and 0.21 log-mL [0.14–0.28], respectively; Ptrend CONCLUSIONS Prediabetes is associated with structural brain abnormalities, with further deterioration in type 2 diabetes. These results indicate that, in middle-aged populations, structural brain abnormalities already occur in prediabetes, which may suggest that the treatment of early dysglycemia may contribute to the prevention of brain diseases.

Medical images are an integral part of oncological patient records and they are reviewed by many different specialists. Therefore, it is important that besides imaging experts, other clinicians are also aware that the diagnostic value of a scan is influenced by the applied imaging protocol. Based on two clinical lung cancer trials, we experienced that, even within a study protocol, there is a large variability in imaging parameters, which has direct impact on the interpretation of the image. These two trials were: 1) the NTR3628 in which the added value of gadolinium magnetic resonance imaging (Gd-MRI) to dedicated contrast enhanced computed tomography (CE-CT) for detecting asymptomatic brain metastases in stage III non-small cell lung cancer (NSCLC) was investigated and 2) a sub-study of the NVALT 12 trial (NCT01171170) in which repeated 18 F-fludeoxyglucose positron emission tomography (18F-FDG-PET) imaging for early response assessment was investigated. Based on the problems encountered in the two trials, we provide recommendations for non-radiology clinicians, which can be used in daily interpretation of imaging. Variations in image parameters cannot only influence trial results, but sub-optimal imaging can also influence treatment decisions in daily lung cancer care, when a physician is not aware of the scanning details.

Purpose: To study possible detection of structural abnormalities on 7T MRI that were not detected on 3T MRI and estimate the added value of MEG-guidance. For abnormalities found, analysis of convergence between clinical, MEG and 7T MRI localization of suspected epileptogenic foci.Methods: In adult patients with well-documented localization-related epilepsy in whom a previous 3T MRI did not demonstrate an epileptogenic lesion but MEG indicated a plausible epileptogenic focus, 7T MRI was performed. Based on semiologic data, visual analysis of the 7T images was performed as well as based on prior MEG results. Correlation with other data from the patient charts, for as far as these were available, was analysed. To establish the level of concordance between the three observers the generalized or Fleiss kappa was calculated.Results: In 3/19 patients abnormalities that, based on semiology, could plausibly represent an epileptogenic lesion were detected using 7T MRI. In an additional 3/19 an abnormality was detected after MEG-guidance. However, in these later cases there was no concordance among the three observers with regard to the presence of a structural abnormality. In one of these three cases intracranial recording was performed, proving the possible abnormality on 7T MRI to be the epileptogenic focus.Conclusions: In 32% of patients 7T MRI showed abnormalities that could indicate an epileptogenic lesion whereas previous 3T MRI did not, especially when visual inspection was guided by the presence of focal interictal MEG abnormalities.

BACKGROUND AND PURPOSE: Focal cortical dysplasia is a common cause of intractable epilepsy for which neurosurgery is an option. Delineations of a focal cortical dysplasia lesion on structural brain images may not necessarily reflect the functional borders of normal tissue. Our objective was to determine whether abnormalities in spontaneous blood oxygen level- dependent fluctuations arise in focal cortical dysplasia lesions and proximal regions. MATERIALS AND METHODS: Fourteen patients with focal cortical dysplasia-related epilepsy and 16 healthy controls underwent structural and resting-state functional MR imaging. Three known blood oxygen level- dependent measures were determined, including the fractional amplitude of low-frequency fluctuations, regional homogeneity, and wavelet entropy. These measures were evaluated in the lesion and perilesional zone and normalized to the contralateral cortex of patients with focal cortical dysplasia and healthy controls. RESULTS: Patients showed significantly decreased fractional amplitude of low-frequency fluctuations and increased wavelet entropy in the focal cortical dysplasia lesion and the perilesional zone (2 cm) relative to the contralateral homotopic cortex and the same regions in healthy controls. Regional homogeneity was significantly increased in the focal cortical dysplasia lesion compared with the contralateral homotopic cortex and healthy controls. CONCLUSIONS: Abnormalities in spontaneous blood oxygen level- dependent fluctuations were seen up to 2 cm distant from the radiologically visible boundary. It was demonstrated that functional boundaries go beyond structural boundaries of focal cortical dysplasia lesions. Validation is required to reveal whether this information is valuable for surgical planning and outcome evaluation of focal cortical dysplasia lesions and comparing current results with electrophysiologic analysis.

Purpose The brains of patients with epilepsy may exhibit various morphological abnormalities, which are often not directly visible on structural MR images, as they may be focally subtle or related to a more large-scale inconspicuous disorganization of brain structures. To explore the relation between structural brain organization and epilepsy characteristics, including severity and cognitive co-morbidity, we determined structural covariance networks (SCNs). SCNs represent interregional correlations of morphologic measures, for instance in terms of cortical thickness, between various large-scale distributed brain regions. Methods Thirty-eight patients with focal seizures of all subtypes and 21 healthy controls underwent structural MRI, neurological, and IQ assessment. Cortical thickness was derived from the structural MRIs using FreeSurfer. Subsequently, SCNs were constructed on a group-level based on correlations of the cortical thicknesses between various brain regions. Individual SCNs for the epilepsy patients were extracted by adding the respective patient to the control group prior to the SCN construction (i.e. add-one-patient approach). Calculated network measures, i.e. path length, clustering coefficient and betweenness centrality were correlated with characteristics related to the severity of epilepsy, including seizure history and age at onset of epilepsy, and cognitive performance. Results Stronger clustering in the individual SCN was associated with a higher number of focal to bilateral tonic-clonic seizures during life time, a younger age at onset, and lower cognitive performance. The path length of the individual SCN was not related to the severity of epilepsy or cognitive performance. Higher betweenness centrality of the left cuneus and lower betweenness centrality of the right rostral middle frontal gyrus were associated with increased drug load and younger age at onset, respectively. Conclusions These results indicate that the correlations between interregional variations of cortical thickness reflect disease characteristics or responses to the disease and deficits in patients with epilepsy with focal seizures., Highlights • Interregional cortical thicknesses relations reflect the severity of epilepsy • Stronger clustering is associated with more seizures in patients with epilepsy • Stronger clustering is associated with younger onset age in patients with epilepsy • Stronger clustering is associated with lower IQ in patients with epilepsy • Betweenness centrality is associated with drug load and age at onset

The brain can be considered a network, existing of multiple interconnected areas with various functions. MRI provides opportunities to map the large-scale network organization of the brain. We tap into the neurobiochemical dimension of these networks, as neuronal functioning and signal trafficking across distributed brain regions relies on the release and presence of neurotransmitters. Using high-field MR spectroscopic imaging at 7.0 T, we obtained a non-invasive snapshot of the spatial distribution of the neurotransmitters GABA and glutamate, and investigated interregional associations of these neurotransmitters. We demonstrate that interregional correlations of glutamate and GABA concentrations can be conceptualized as networks. Furthermore, patients with epilepsy display an increased number of glutamate and GABA connections and increased average strength of the GABA network. The increased glutamate and GABA connectivity in epilepsy might indicate a disrupted neurotransmitter balance. In addition to epilepsy, the ‘neurotransmitter networks’ concept might also provide new insights for other neurological diseases., Highlights • We introduce the concept of “neurotransmitter networks”. • Ultrahigh field spectroscopic images of the brain were obtained. • Interregional correlations of Glutamate and GABA are conceptualized as networks. • Increased glutamate and GABA connectivity are shown in patients with epilepsy. • Neurotransmitter networks might provide new insights for neurological diseases.

Introduction Post-mortem computed tomography (PMCT) and post-mortem magnetic resonance imaging (PMMR) are frequently used as an addition to autopsy. However, there is no research that determined the diagnostic value of these imaging techniques in forensic cases. The aim of this review is to evaluate the available literature with regard to the correlation between autopsy and imaging findings in the forensic investigation of gunshot victims to arrive at an the diagnostic value of PMCT and PMMR. Materials & methods The review process was set out as a systematic review according to the Cochrane guidelines. A systematic search was performed in MEDLINE and EMBASE to identify studies comparing autopsy and imaging techniques after fatal gunshot incidents. Autopsy and imaging techniques were compared for forensically relevant items: entrance wounds, exit wounds, trajectory of the bullet through the body, detection of metal fragments and identification of relevant injuries. The autopsy was the reference standard in all studies. Results In each study a minimum of one and a maximum of five items could be compared between the imaging techniques and the autopsy. In total seven studies complied with the inclusion criteria. The overall quality and level of detail of these studies did not allow for a formal meta-analysis. For the detection of the entrance wound five studies provide data and the correlation between imaging and autopsy was 100% in four studies, and 69.2% in one study. Five studies provide data on the exit wound and there was a 100% correlation in four, and 52.2% in one study. Six studies provide data on the bullet path and the correlation between techniques and autopsy was 100% in four studies and respectively 72.1% and 80% in the other two studies. For the detection of metal fragments three studies provide data and all these studies showed a 100% correlation between imaging and autopsy. Two studies provide data on detecting injuries with a correlation between imaging and autopsy of 100% and 87.2% respectively. Conclusion Despite the concerns on the quality of the reviewed studies, the literature shows that PMMCT has a high sensitivity in identifying the main forensic items in gunshot victims compared to the standard of reference; an autopsy. Forensic radiology and autopsy can be complementary in a forensic medical investigation.

Purpose: Dynamic contrast-enhanced (DCE) MRI can be used to measure blood-brain barrier (BBB) leakage. In neurodegenerative disorders such as small vessel disease and dementia, the leakage can be very subtle and the corresponding signal can be rather noisy. For these reasons, an optimized DCE-MRI measurement and study design is required. To this end, a new measure indicative of the spatial extent of leakage is introduced and the effects of scan time and sample size are explored.Methods: Dual-time resolution DCE-MRI was performed in 16 patients with early Alzheimer's disease (AD) and 17 healthy controls. The leakage rate (K-i) and volume fraction of detectable leaking tissue (v(L)) to quantify the spatial extent of BBB leakage were calculated in cortical gray matter and white matter using noise-corrected histogram analysis of leakage maps. Computer simulations utilizing realistic K-i histograms, mimicking the strong effect of noise and variation in K-i values, were performed to understand the influence of scan time on the estimated leakage.Results: The mean K-i was very low (order of 10(-4) min(-1)) and highly influenced by noise, causing the K-i to be increasingly overestimated at shorter scan times. In the white matter, the K-i was not different between patients with early AD and controls, but was higher in the cortex for patients, reaching significance after 14.5 min of scan time. To detect group differences, v(L) proved more suitable, showing significantly higher values for patients compared with controls in the cortex after 8 minutes of scan time, and in white matter after 15.5 min.Conclusions: Several ways to improve the sensitivity of a DCE-MRI experiment to subtle BBB leakage were presented. We have provided v(L) as an attractive and potentially more time-efficient alternative to detect group differences in subtle and widespread blood-brain barrier leakage compared with leakage rate K-i. Recommendations on group size and scan time are made based on statistical power calculations to aid future research. (C) 2017 American Association of Physicists in Medicine

Purpose: To assess the wavelet entropy for the characterization of intrinsic aberrant temporal irregularities in the time series of resting-state blood-oxygen-level-dependent (BOLD) signal fluctuations. Further, to evaluate the temporal irregularities (disorder/order) on a voxel-by-voxel basis in the brains of children with Rolandic epilepsy. Materials and Methods: The BOLD time series was decomposed using the discrete wavelet transform and the wavelet entropy was calculated. Using a model time series consisting of multiple harmonics and nonstationary components, the wavelet entropy was compared with Shannon and spectral (Fourier-based) entropy. As an application, the wavelet entropy in 22 children with Rolandic epilepsy was compared to 22 age-matched healthy controls. The images were obtained by performing resting-state functional magnetic resonance imaging (fMRI) using a 3T system, an 8-element receive-only head coil, and an echo planar imaging pulse sequence (T2 * -weighted). The wavelet entropy was also compared to spectral entropy, regional homogeneity, and Shannon entropy. Results: Wavelet entropy was found to identify the nonstationary components of the model time series. In Rolandic epilepsy patients, a significantly elevated wavelet entropy was observed relative to controls for the whole cerebrum (P = 0.03). Spectral entropy (P = 0.41), regional homogeneity (P = 0.52), and Shannon entropy (P = 0.32) did not reveal significant differences. Conclusion: The wavelet entropy measure appeared more sensitive to detect abnormalities in cerebral fluctuations represented by nonstationary effects in the BOLD time series than more conventional measures. This effect was observed in the model time series as well as in Rolandic epilepsy. These observations suggest that the brains of children with Rolandic epilepsy exhibit stronger nonstationary temporal signal fluctuations than controls. Level of Evidence: 2. Technical Efficacy: Stage 3. J. Magn. Reson. Imaging 2017;46:1728–1737.

Objective: The diagnosis of epilepsy cannot be reliably made prior to a patient's second seizure in most cases. Therefore, adequate diagnostic tools are needed to differentiate subjects with a first seizure from those with a seizure preceding the onset of epilepsy. The objective was to explore spontaneous blood oxygen level-dependent (BOLD) fluctuations in subjects with a first-ever seizure and patients with new-onset epilepsy (NOE), and to find characteristic biomarkers for seizure recurrence after the first seizure.Methods: We examined 17 first-seizure subjects, 19 patients with new-onset epilepsy (NOE), and 18 healthy controls. All subjects underwent clinical investigation and received electroencephalography and resting-state functional magnetic resonance imaging (MRI). The BOLD time series were analyzed in terms of regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFFs).Results: We found significantly stronger amplitudes (higher fALFFs) in patients with NOE relative to first-seizure subjects and healthy controls. The frequency range of 73-198 mHz (slow-3 subband) appeared most useful for discriminating patients with NOE from first-seizure subjects. The ReHo measure did not show any significant differences.Significance: The fALFF appears to be a noninvasive measure that characterizes spontaneous BOLD fluctuations and shows stronger amplitudes in the slow-3 subband of patients with NOE relative first-seizure subjects and healthy controls. A larger study population with follow-up is required to determine whether fALFF holds promise as a potential biomarker for identifying subjects at increased risk to develop epilepsy.

Purpose Increased blood–brain barrier (BBB) permeability has been shown to play a significant role in the pathophysiology of cerebrovascular disease and it may provide an early functional marker of progression or treatment effects. The aim of the study was to investigate the test–retest reproducibility and influencing factors of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in measuring subtle leakage in patients with cerebrovascular disease. Material and Methods DCE-MRI (3T) was performed on two separate days in 16 patients (age 66 ± 9 years) with cerebrovascular disease, prospectively. The leakage rate was quantified for white matter (WM) and gray matter (GM) using the Patlak graphical approach with individual vascular input functions (VIFs). Furthermore, the influence of session-averaged VIFs, the average of the VIFs obtained on two days, and shorter scan times (range 5–25 minutes) on the reproducibility were evaluated in WM and GM. Results Coefficients of variation (CV) ≤14.4% (WM and GM), intraclass correlation coefficients (ICCs) of 0.77 (WM) and 0.49 (GM), were observed for the leakage rate. Session-averaged VIFs hardly affected these results (CV ≤13.4%). The repeatability coefficients (RCs) of the leakage rate decreased from 2.7·10−3 to 0.4·10−3 min−1 in WM (P < 0.01) and 4.4·10−3 to 0.9·10−3 min−1 in GM (P < 0.01) with increasing scan time (range 5–25 minutes). Conclusion Based on the moderate CVs and moderate-to-excellent ICCs, we demonstrate that measuring subtle BBB leakage using DCE-MRI is moderate-to-excellent reproducible. Longer scan times improve the reproducibility. The provided RCs at various scan times may assist future clinical studies investigating BBB leakage using DCE-MRI. Level of Evidence: 2 J. Magn. Reson. Imaging 2017

Objective:As blood–brain barrier (BBB) dysfunction may occur in normal aging but may also play a pivotal role in the pathophysiology of cerebral small vessel disease (cSVD), we used dynamic contrast-enhanced (DCE)–MRI to quantify the rate and the spatial extent of BBB leakage in patients with cSVD and age- and sex-matched controls to discern cSVD-related BBB leakage from aging-related leakage.Methods:We performed structural brain MRI and DCE-MRI in 80 patients with clinically overt cSVD and 40 age- and sex-matched controls. Using the Patlak pharmacokinetic model, we calculated the leakage rate. The mean leakage rate and relative leakage volume were calculated using noise-corrected histogram analysis. Leakage rate and leakage volume were compared between patients with cSVD and controls for the normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical gray matter (CGM), and deep gray matter.Results:Multivariable linear regression analyses adjusting for age, sex, and cardiovascular risk factors showed that the leakage volume of the NAWM, WMH, and CGM was significantly larger in patients with cSVD compared with controls. No significant difference was found for leakage rate in any of the tissue regions.Conclusion:We demonstrated a larger tissue volume with subtle BBB leakage in patients with cSVD than in controls. This was shown in the NAWM, WMH, and CGM, supporting the generalized nature of cSVD.

Introduction Cerebral small vessel disease (cSVD) is associated with microvascular and parenchymal alterations. Intravoxel incoherent motion (IVIM) MRI has been proposed to simultaneously measure both the microvascular perfusion and parenchymal diffusivity. This study aimed to evaluate the application of IVIM in cSVD to assess the microvasculature and parenchymal microstructure. Methods Seventy-three patients with cSVD (age 70 ± 11 y) and thirty-nine controls (age 69 ± 12 y) underwent IVIM imaging (3T). Group differences of the perfusion volume fraction f and the parenchymal diffusivity D were investigated using multivariable linear regression accounted for age, sex and cardiovascular factors. To examine the relation between the IVIM measures and the disease severity on structural MRI, white matter hyperintensity (WMH) load served as surrogate measure of the disease severity. Results Patients had a larger f (p, Highlights • The application of IVIM in cSVD was investigated. • IVIM shows a predicted microstructure impairment in cSVD. • Unexpected increased perfusion volume fraction is observed using IVIM. • Perfusion volume fraction and parenchymal diffusivity increase with disease severity. • IVIM imaging may provide a potential surrogate marker for the progression of cSVD.

Background Rupture of a vulnerable carotid atherosclerotic plaque is an important underlying cause of ischemic stroke. Increased leaky plaque microvasculature may contribute to plaque vulnerability. These immature microvessels may facilitate entrance of inflammatory cells into the plaque. The objective of the present study is to investigate whether there is a difference in plaque microvasculature (the volume transfer coefficient K trans ) between the ipsilateral symptomatic and contralateral asymptomatic carotid plaque using noninvasive dynamic contrast‐enhanced magnetic resonance imaging. Methods and Results Eighty‐eight patients with recent transient ischemic attack or ischemic stroke and ipsilateral >2 mm carotid plaque underwent 3 T magnetic resonance imaging to identify plaque components and to determine characteristics of plaque microvasculature. The volume transfer coefficient K trans , indicative for microvascular density, flow, and permeability, was calculated for the ipsilateral and asymptomatic plaque, using a pharmacokinetic model (Patlak). Presence of a lipid‐rich necrotic core, intraplaque hemorrhage, and a thin and/or ruptured fibrous cap was assessed on multisequence magnetic resonance imaging . We found significantly lower K trans in the symptomatic carotid plaque compared with the asymptomatic side (0.057±0.002 min −1 versus 0.062±0.002 min −1 ; P =0.033). There was an increased number of slices with intraplaque hemorrhage (0.9±1.6 versus 0.3±0.8, P =0.002) and lipid‐rich necrotic core (1.4±1.9 versus 0.8±1.4, P =0.016) and a higher prevalence of plaques with a thin and/or ruptured fibrous cap (32% versus 17%, P =0.023) at the symptomatic side. Conclusions K trans was significantly lower in symptomatic carotid plaques, indicative for a decrease of plaque microvasculature in symptomatic plaques. This could be related to a larger amount of necrotic tissue in symptomatic plaques. Clinical Trial Registration URL : http://www.clinicaltrials.gov.uk . Unique identifier: NCT 01208025.

Cognitive deficits are common in Parkinson's disease and we suspect that dysfunctions of connected brain regions can be the source of these deficits. The aim of the present study was to investigate changes in whole-brain intrinsic functional connectivity according to differences in cognitive profiles in Parkinson's disease. 119 participants were enrolled and divided into four groups according to their cognitive phenotypes (determined by a cluster analysis): (i) 31 cognitively intact patients (G1), (ii) 31 patients with only slight mental slowing (G2), (iii) 43 patients with mild to moderate deficits mainly in executive functions (G3), (iv) 14 patients with severe deficits in all cognitive domains (G4-5). Rs-fMRI whole-brain connectivity was examined by two complementary approaches: graph theory for studying network functional organization and network-based statistics (NBS) for exploring functional connectivity amongst brain regions. After adjustment for age, duration of formal education and center of acquisition, there were significant group differences for all functional organization indexes: functional organization decreased (G1 > G2 > G3 > G4-5) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, P

Type 2 diabetes is associated with cognitive decrements, accelerated cognitive decline, and increased risk for dementia. Patients with the metabolic syndrome, a major risk factor for diabetes, may display comparable cognitive decrements as seen in type 2 diabetes. Currently, the impact of diabetes and prediabetes on cognition and the underlying organization of functional brain networks still remain to be elucidated. This study investigated whether functional brain networks are affected in type 2 diabetes and prediabetes. Forty-seven participants with diabetes, 47 participants with prediabetes, and 45 control participants underwent detailed cognitive testing and 3-Tesla resting state functional MRI. Graph theoretical network analysis was performed to investigate alterations in functional cerebral networks. Participants with diabetes displayed altered network measures, characterized by a higher normalized cluster coefficient and higher local efficiency, compared with control participants. The network measures of the participants with prediabetes fell between those with diabetes and control participants. Lower processing speed was associated with shorter path length and higher global efficiency. Participants with type 2 diabetes have altered functional brain networks. This alteration is already apparent in the prediabetic stage to a somewhat lower level, hinting at functional reorganization of the cerebral networks as a compensatory mechanism for cognitive decrements.

Trauma patients at risk for, or suspected of, spinal injury are frequently transported to hospital using full spinal immobilisation. At the emergency department, immobilisation is often maintained until radiological work-up is completed. In this study, we examined how these devices for spinal stabilization influence visual image quality. Image quality was judged for both patient CT scans and phantom CT scans. CT scans of 217 patients were assessed retrospectively by two radiologists for visual scoring of image quality, scoring both quantity and impact of artifacts caused by the immobilization devices. For the phantom CT scans, eight set-ups were made, using a vacuum mattress without headblocks and a rigid and a soft-layered spineboard without headblocks, with standard soft-foam headblocks, or with new design headblocks. Overall, artifacts were found in 67 % of CT scans of patients on immobilization devices, which hampered diagnosis in 10 % of the cases. In the phantom CT scans, artifacts were present in all set-ups with one or more devices present and were seen in 20 % of all scan slices. The presence of headblocks resulted in more artifacts in both the patient CT scans and the phantom CT scans. Considerable effort should therefore be made to adjust the design of the immobilization devices and to remove the headblocks before CT scans are made.

Background and objective: The current literature describing the use of minimally invasive autopsy in clinical care is mainly focused on the cause of death. However, the identification of unexpected findings is equally important for the evaluation and improvement of daily clinical care. The purpose of this study was to analyze unexpected post-mortem computed tomography (PMCT) findings of hospitalized patients and assess their clinical relevance. Materials and methods: This observational study included patients admitted to the internal medicine ward. Consent for PMCT and autopsy was requested from the next of kin. Decedents were included when consent for at least PMCT was obtained. Consent for autopsy was not obtained for all decedents. All findings reported by PMCT were coded with an International Classification of Diseases (ICD) code. Unexpected findings were identified and subsequently categorized for their clinical relevance by the Goldman classification. Goldman class I and III were considered clinically relevant. Additionally, correlation with autopsy results and ante-mortem imaging was performed. Results: In total, 120 decedents were included and evaluated for unexpected findings on PMCT. Of them, 57 decedents also underwent an autopsy. A total of 1020 findings were identified, 111 correlated with the cause of death (10.9%), 508 were previously reported (49.8%), 99 were interpreted as post-mortem changes (9.7%), and 302 were classified as unexpected findings (29.6%). After correlation with autopsy (in 57 decedents), 24 clinically relevant unexpected findings remained. These findings were reported in 18 of 57 decedents (32%). Interestingly, 25% of all unexpected findings were not reported by autopsy. Conclusion: Many unexpected findings are reported by PMCT in hospitalized patients, a substantial portion of which is clinically relevant. Additionally, PMCT is able to identify pathology and injuries not reported by conventional autopsy. A combination of PMCT and autopsy can thus be considered a more comprehensive and complete post-mortem examination.

Introduction Non–small-cell lung cancer (NSCLC) guidelines advise to screen stage III NSCLC patients for brain metastases (BMs), preferably by magnetic resonance imaging (MRI) or when contraindicated or not accessible a dedicated contrast enhanced–computed tomography (dCE-CT), which can be incorporated in the staging 18Fluodeoxoglucose–positron emission tomography (18FDG-PET-CE-CT). In daily practice, often a dCE-CT is performed instead of a MRI. The aim of the current study is to evaluate the additive value of MRI after dCE-CT, incorporated in the 18FDG-PET-CE-CT. Patients and methods It is an observational prospective multicentre study (NTR3628). Inclusion criteria included stage III NSCLC patients with a dCE-CT of the brain incorporated in the 18FDG-PET and an additional MRI of the brain. Primary end-point is percentage of patients with BM on MRI without suspect lesions on dCE-CT. Secondary end-points are percentage of patients with BM on dCE-CT and percentage of patients with BM ≤ 1 year of a negative staging MRI. Results Sixteen (7%) patients with extracranial stage III had BM on dCE-CT and were excluded. One hundred forty-nine patients were enrolled. 7/149 (4.7%) had BM on MRI without suspect lesions on dCE-CT. One hundred eighteen patients had a follow-up of at least 1 year (four with BM on baseline MRI); eight of the remaining 114 (7%) patients developed BM ≤ 1 year after a negative staging brain MRI. Conclusion Although in 7% of otherwise stage III NSCLC patients, BMs were detected on staging dCE-CT, MRI brain detected BMs in an additional 4.7%, which we consider clinically relevant. Within 1 year after a negative staging MRI, 7% developed BM.

Contains fulltext : 183400.pdf (Publisher’s version ) (Open Access) Introduction: Autism spectrum disorder (ASD) is mainly characterized by functional and communication impairments as well as restrictive and repetitive behavior. The leading hypothesis for the neural basis of autism postulates globally abnormal brain connectivity, which can be assessed using functional magnetic resonance imaging (fMRI). Even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic, or resting-state, connectivity. Global default connectivity in individuals with autism versus controls is not well characterized, especially for a high-functioning young population. The aim of this study is to test whether high-functioning adolescents with ASD (HFA) have an abnormal resting-state functional connectivity. Materials and Methods: We performed spatial and temporal analyses on resting-state networks (RSNs) in 13 HFA adolescents and 13 IQ- and age-matched controls. For the spatial analysis, we used probabilistic independent component analysis (ICA) and a permutation statistical method to reveal the RSN differences between the groups. For the temporal analysis, we applied Granger causality to find differences in temporal neurodynamics. Results: Controls and HFA display very similar patterns and strengths of resting-state connectivity. We do not find any significant differences between HFA adolescents and controls in the spatial resting-state connectivity. However, in the temporal dynamics of this connectivity, we did find differences in the causal effect properties of RSNs originating in temporal and prefrontal cortices. Conclusion: The results show a difference between HFA and controls in the temporal neurodynamics from the ventral attention network to the salience-executive network: a pathway involving cognitive, executive, and emotion-related cortices. We hypothesized that this weaker dynamic pathway is due to a subtle trigger challenging the cognitive state prior to the resting state. 10 p.

As a large number of patients with epilepsy do not respond favorably to antiepileptic drugs (AEDs), a better understanding of treatment failure and the cause of adverse side effects is required. The working mechanisms of AEDs also alter neurotransmitter concentrations and brain activity, which can be measured using MR spectroscopy and functional MR imaging, respectively. This review presents an overview of clinical research of MR spectroscopy and functional MR imaging studies to the effects of AEDs on the brain. Despite the scarcity of studies associating MR findings to the effectiveness of AEDs, the current research shows clear potential regarding this matter. Several GABAergic AEDs have been shown to increase the GABA concentration, which was related to seizure reductions, while language problems due to topiramate have been associated with altered activation patterns measured with functional MR imaging. MR spectroscopy and functional MR imaging provide biomarkers that may predict individual treatment outcomes, and enable the assessment of mechanisms of treatment failure and cognitive side effects.

Purpose Multi-detector computed tomography (MDCT) has proven to be of value for the reconstruction of trajectories of projectiles and the assessment of the injuries in deceased gunshot victim. For the depiction of soft tissue injury, MRI is superior to MDCT and MRI may be of value to assess trajectories. In a clinical setting, there are guidelines for the application of MRI in patients with projectiles or projectile fragments and with precautions MRI is safe for these patients. However, this has not been studied for the postmortem application of MRI from a forensic point of view. Subjects and method To assess the behaviour of projectiles, two ferromagnetic and one non-ferromagnetic projectile were exposed to the magnetic field of a 1.5- and 3-T MRI. Projectiles were placed in six phantoms with the characteristics of human muscle tissue, with and without a simulated trajectory in the gel. Before and after exposure to the magnetic field, the gelatine phantoms were imaged with MDCT to assess the position of the projectiles. Results The ferromagnetic projectiles rotate to a position where their long axis is parallel to the z-axis of the magnetic field and five out of the six projectiles moved through, either through the simulated trajectory or through a new trajectory. This was observed in both the 1.5- and 3-T systems. Conclusion Ferromagnetic projectiles can rotate and migrate in a gelatine phantom. It is very likely that these projectiles will also migrate in a human body in a MRI system. Therefore, from a forensic point of view, postmortem MR will make a reconstruction of the trajectories in the body and of the reconstruction of the incident as a whole less reliable.

Use of radiography and fluoroscopy in Disaster Victim Identification Positional statement of the members of the Disaster Victim Identification working group of the International Society of Forensic Radiology and Imaging Mark D. Viner , Abdullah Alminyah , Mario Apostol , Alison Brough , Wim Develter , Chris O’Donnell , Denise Elliott , Sarah Heinze , Paul Hofman , Guillaume Gorincour , Mansharan Kaur Chainchel Singh , Morio Iino , Yohsuke Makino , Artur Moskala , Bruno Morgan , Guy N. Rutty , Jacquie Vallis , Chiara Villa , Krzysztof Woźniak 2

OBJECTIVE Type 2 diabetes is associated with accelerated cognitive decline, especially regarding memory for which the hippocampus plays an essential role. The pathophysiological mechanisms still remain to be elucidated. The purpose of this study is to examine whether hippocampal microvascular and microstructural changes are related to type 2 diabetes (based on status or based on fasting blood glucose [FBG] levels) and verbal memory performance. RESEARCH DESIGN AND METHODS Thirty-nine participants with type 2 diabetes (64.5 ± 6.1 years old) and 34 participants without type 2 diabetes (58.3 ± 9.2 years old) underwent detailed cognitive assessments and 3-Tesla MRI using intravoxel incoherent motion (IVIM) MRI. Multivariate regression analyses controlling for age, sex, education level, BMI, systolic blood pressure, hematocrit level, and relative hippocampal volume were performed to examine associations between hippocampal IVIM measures, type 2 diabetes (status and FBG), and memory performance. RESULTS For the microvasculature, blood perfusion volume (f) was larger in participants with type 2 diabetes, f and blood flow (fD*) increased with higher FBG levels, and microvascular pseudodiffusion (D*) and fD*, which are indicative of altered microvasculature, were higher in participants with both relatively high FBG levels and low memory performance. In addition, fD* increased with lower memory performance. For the parenchymal microstructure, the diffusion (D), indicative of injured microstructure, was higher with reduced memory performance. CONCLUSIONS In addition to the parenchymal microstructure, especially the microvascular properties of the hippocampus are altered in participants with both type 2 diabetes and memory problems and possibly hint at an underlying vascular mechanism.

Introduction: Dorsal pathway dysfunctions are thought to underlie visuospatial processing problems in Alzheimer disease (AD). Prior studies reported compensatory mechanisms in the dorsal or ventral pathway in response to these functional changes. Since functional and structural connectivity are interrelated, these functional changes could be interpreted as a disconnection between both pathways. To better understand functional alterations in the dorsal pathway, we combined functional imaging with diffusion tensor imaging (DTI) in patients with mild cognitive impairment (MCI), a likely prodromal stage of AD. Methods: Eighteen older male individuals with amnestic MCI (aMCI) and 18 male cognitively healthy individuals, matched for age (range 59-75 years) and education, performed an object recognition task in the Magnetic Resonance Imaging (MRI) scanner. Neural activation was measured during recognition of non-canonically versus canonically oriented objects. Regions showing activation differences between groups were also investigated by DTI. Results: Recognition of non-canonical objects elicited increased frontal, temporal and parietal activation. Combining the functional MRI (fMRI) with the DTI results showed less deactivation in areas with decreased diffusion (mediolateral parietal and orbitofrontal) and increased activation in areas with increased diffusion (parietal and temporal) in aMCI patients. Finally, in aMCI patients decreased diffusion was found in the hippocampal cingulum, connecting both pathways. Conclusions: Our results showed increased activation in early AD patients in ventral and dorsal pathways. A decrease in deactivation and diffusion suggests functional reorganization, while increased activation and diffusion suggests compensatory processes. This is the first study showing structural evidence for functional reorganization, which may be related to connectivity loss in the cingulum. (C) 2012 Elsevier Ltd. All rights reserved.

AIMTo increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug (AED) treatment.METHODSThe relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients with epilepsy with a different risk profile for developing cognitive side effects were included: A "low risk" category (lamotrigine or levetiracetam, n = 16), an "intermediate risk" category (carbamazepine, oxcarbazepine, phenytoin, or valproate, n = 34) and a "high risk" category (topiramate, n = 5). Brain connectivity was assessed using resting state functional magnetic resonance imaging and graph theoretical network analysis. The Computerized Visual Searching Task was used to measure central information processing speed, a common cognitive side effect of AED treatment.RESULTSCentral information processing speed was lower in patients taking AEDs from the intermediate and high risk categories, compared with patients from the low risk category. The effect of risk category on global efficiency was significant (P 0.2). Also no significant associations between information processing speed and global efficiency or the clustering coefficient (linear regression analysis, P > 0.15) were observed.CONCLUSIONOnly the four patients taking topiramate show aberrant network measures, suggesting that alterations in functional brain network organization may be only subtle and measureable in patients with more severe cognitive side effects. (C) The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.

Type 2 diabetes mellitus is associated with accelerated cognitive decline and various cerebral abnormalities visible on MRI. The exact pathophysiological mechanisms underlying cognitive decline in diabetes still remain to be elucidated. In addition to conventional images, MRI offers a versatile set of novel contrasts, including blood perfusion, neuronal function, white matter microstructure, and metabolic function. These more-advanced multiparametric MRI contrasts and the pertaining parameters are able to reveal abnormalities in type 2 diabetes, which may be related to cognitive decline. To further elucidate the nature of the link between diabetes, cognitive decline, and brain abnormalities, and changes over time thereof, biomarkers are needed which can be provided by advanced MRI techniques. This review summarizes to what extent MRI, especially advanced multiparametric techniques, can elucidate the underlying neuronal substrate that reflects the cognitive decline in type 2 diabetes.

This paper presents the outcome of the first international forensic radiology and imaging research summit, organized by the International Society of Forensic Radiology and Imaging, the International Association of Forensic Radiographers, the National Institute of Justice of the United States of America, and the Netherlands Forensic Institute. During this meeting, an international and multidisciplinary panel of forensic scientists discussed the current state of science in forensic radiology, and drafted a research agenda to further advance the field. Four groups for further research focus were identified: big data and statistics, identification and biological profiling, multimodal imaging, and visualization and presentation. This paper describes each of these research topics and thereby hopes to contribute to the development of this exciting new field of forensic medical science.

To assess the feasibility of dual energy computed tomography (DE-CT) in intra-arterially treated acute ischaemic stroke patients to discriminate between contrast extravasation and intracerebral haemorrhage. Thirty consecutive acute ischaemic stroke patients following intra-arterial treatment were examined with DE-CT. Simultaneous imaging at 80 kV and 140 kV was employed with calculation of mixed images. Virtual unenhanced non-contrast (VNC) images and iodine overlay maps (IOM) were calculated using a dedicated brain haemorrhage algorithm. Mixed images alone, as “conventional CT”, and DE-CT interpretations were evaluated and compared with follow-up CT. Eight patients were excluded owing to a lack of follow-up or loss of data. Mixed images showed intracerebral hyperdense areas in 19/22 patients. Both haemorrhage and residual contrast material were present in 1/22. IOM suggested contrast extravasation in 18/22 patients; in 16/18 patients this was confirmed at follow-up. The positive predictive value (PPV) of mixed imaging alone was 25 %, with a negative predictive value (NPV) of 91 % and accuracy of 63 %. The PPV for detection of haemorrhage with DE-CT was 100 %, with an NPV of 89 % and accuracy improved to 89 %. Dual energy computed tomography improves accuracy and diagnostic confidence in early differentiation between intracranial haemorrhage and contrast medium extravasation in acute stroke patients following intra-arterial revascularisation. • Contrast material and haemorrhage have similar density on conventional 120-kV CT. • Contrast material hinders interpretation of CT in stroke patients after recanalisation. • Iodine and haemorrhage have different attenuation at lower kVs. • Dual energy CT improves accuracy in early differentiation of haemorrhage and contrast extravasation. • Early differentiation between iodine and haemorrhage helps to initiate therapy promptly.

Objectives Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE). Its etiology remains unknown. With diffusion tensor imaging, we have studied cerebral white matter properties and associations with cognitive functioning in children with FLE and healthy controls. Methods Thirty children aged 8–13 years with FLE of unknown cause and 39 healthy age-matched controls underwent neuropsychological assessment, structural and diffusion-weighted brain MRI. Patients were grouped as cognitively impaired or unimpaired, and their white matter diffusion properties were compared with the controls. Results Children with FLE had reduced apparent diffusion coefficients in various posteriorly located tract bundles, a reduced fractional anisotropy (FA) of the white matter tract between the right frontal and right occipital lobe, and smaller volumes of several collections of interlobar bundle tracts, compared with controls. The cognitively impaired patient group demonstrated significant increases in FA of the white matter of both occipital lobes, a reduced FA of white matter tract bundles between the right frontal and both left occipital lobe and subcortical white matter area, and smaller volumes of two collections of tract bundles connecting the frontal lobe with the temporal and parietal lobes, compared with controls. Conclusions Children with FLE had white matter abnormalities mainly in posterior brain regions, not confined to the area of the seizure focus. Cognitively impaired children with FLE showed the most pronounced white matter abnormalities. These possibly reflect disturbed maturation and might be part of the etiology of the cognitive impairment.

In many brain diseases it can be qualitatively observed that spatial patterns in blood oxygenation level dependent (BOLD) activation maps appear more (diffusively) distributed than in healthy controls. However, measures that can quantitatively characterize this spatial distributiveness in individual subjects are lacking. In this study, we propose a number of spatial heterogeneity measures to characterize brain activation maps. The proposed methods focus on different aspects of heterogeneity, including the shape (compactness), complexity in the distribution of activated regions (fractal dimension and co-occurrence matrix), and gappiness between activated regions (lacunarity). To this end, functional MRI derived activation maps of a language and a motor task were obtained in language impaired children with (Rolandic) epilepsy and compared to age-matched healthy controls. Group analysis of the activation maps revealed no significant differences between patients and controls for both tasks. However, for the language task the activation maps in patients appeared more heterogeneous than in controls. Lacunarity was the best measure to discriminate activation patterns of patients from controls (sensitivity 74%, specificity 70%) and illustrates the increased irregularity of gaps between activated regions in patients. The combination of heterogeneity measures and a support vector machine approach yielded further increase in sensitivity and specificity to 78% and 80%, respectively. This illustrates that activation distributions in impaired brains can be complex and more heterogeneous than in normal brains and cannot be captured fully by a single quantity. In conclusion, heterogeneity analysis has potential to robustly characterize the increased distributiveness of brain activation in individual patients., Highlights • A number of spatial heterogeneity measures of activation maps were explored in children with Rolandic epilepsy and language impairment • Proposed measures capture the complexity, shape and distribution of brain activation patterns • For a language task all proposed measures revealed that patients exhibit more heterogeneous activation patterns than controls, whereas for a motor task no differences appeared • Spatial heterogeneity of activation patterns is a complex feature that cannot be captured by one single measure, but shape and lacunarity represented the best descriptive measures

Objective Dissociation is a mental process with psychological and somatoform manifestations, which is closely related to hypnotic suggestibility and essentially shows the ability to obtain distance from reality. An increased tendency to dissociate is a frequently reported characteristic of patients with functional neurological symptoms and syndromes (FNSS), which account for a substantial part of all neurological admissions. This review aims to investigate what heart rate variability (HRV), EEG and neuroimaging data (MRI) reveal about the nature of dissociation and related conditions. Methods Studies reporting HRV, EEG and neuroimaging data related to hypnosis, dissociation and FNSS were identified by searching the electronic databases Pubmed and ScienceDirect. Results The majority of the identified studies concerned the physiological characteristics of hypnosis; relatively few investigations on dissociation related FNSS were identified. General findings were increased parasympathetic functioning during hypnosis (as measured by HRV), and lower HRV in patients with FNSS. The large variety of EEG and functional MRI investigations with diverse results challenges definite conclusions, but evidence suggests that subcortical as well as (pre)frontal regions serve emotion regulation in dissociative conditions. Functional connectivity analyses suggest the presence of altered brain networks in patients with FNSS, in which limbic areas have an increased influence on motor preparatory regions. Conclusions HRV, EEG and (functional) MRI are sensitive methods to detect physiological changes related to dissociation and dissociative disorders such as FNSS, and can possibly provide more information about their aetiology. The use of such measures could eventually provide biomarkers for earlier identification of patients at risk and appropriate treatment of dissociative conditions.

Objective: The last decennia autopsies have been declining worldwide, whereas non-invasive methods have been proposed as an alternative for the conventional autopsy. Some of these methods add needle biopsies to imaging techniques to provide an alternative to histological examination of autopsy-derived tissue. The aim of this study was to investigate the representativeness of the histology of computed tomography (CT) -guided post-mortem needle biopsies in comparison to autopsy derived tissue from the same organ.Method: Consent of next of kin was obtained from relatives of deceased within the department of Internal Medicine to perform an autopsy, postmortem CT and CT-guided needle biopsies. The lungs and the liver were routinely sampled with CT-guided postmortem biopsies and during the autopsy. In some cases extra CT-guided biopsies of lesions reported on the CT were sampled. The biopsy and the autopsy reports were independently reported and retrospectively coded according to the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA). Three pathologists with an interest in autopsy pathology and three physicians of the department of internal medicine separately and independently interpreted all histological results in relation to the cause of death as formulated in the autopsy report. Fleiss's Kappa was calculated and a consensus grade was defined.Results: Fleiss's Kappa showed substantial agreement in both lungs and moderate agreement in the liver. Of the 60 included cases 44% of the CT-guided postmortem biopsies in the left lung and 30% in the right lung showed false negative findings, primarily concerning a bronchopneumonia. In contrast, 91% of the liver biopsies showed concordant results, however only 22% of all liver biopsies concerned a major diagnosis related to the cause of death. The positive predictive value of the biopsies of the left lung, right lung and the liver were respectively 86.6%, 88.8% and 100%. The negative predictive values of these biopsies were 32.4%, 50% and 92.7%.Conclusion: CT-guided postmortem biopsies of the lungs have a mediocre predictive value. Due to a low prevalence of relevant findings the overall usefulness of biopsies of the liver are limited. Conventional autopsy should still be preferred to biopsy-based postmortem examination. Postmortem biopsies are only an alternative if consent for an autopsy cannot be obtained. In the forensic setting, where no consent of the relatives is necessary, complete autopsy should always be the method of choice. (C) 2019 Elsevier B.V. All rights reserved.

Introduction: Rolandic epilepsy (RE) is an idiopathic focal childhood epilepsy with a well-established neuropsychological profile of language impairment. The aim of this study is to provide a functional correlate that links rolandic (sensorimotor) pathology to language problems using functional MRI. Materials and methods: Twenty-three children with RE (8-14 years old) and 21 matched controls underwent extensive language assessment (Clinical Evaluation of Language Fundamentals). fMRI was performed at rest and using word generation, reading, and finger tapping paradigms. Since no activation group differences were found, regions of interest (ROIs) were defined at pooled (patients and controls combined) activation maxima and in contralateral homotopic cortex, and used to assess language lateralization as well as for a resting-state connectivity analysis. Furthermore, the association between connection strength and language performance was investigated. Results: Reduced language performance was found in the children with RE. Bilateral activation was found for both language tasks with some predominance of the left hemisphere in both groups. Compared to controls, patient connectivity was decreased between the left sensorimotor area and right inferior frontal gyrus (p

BACKGROUND: The accurate localization of depth electrodes in epilepsy surgery is important for correct interpretation of stereoelectroencephalography recordings and neurosurgical resection. Unfortunately, image quality in postimplantation magnetic resonance imaging (MRI) is degraded by metal artifacts. The registration of postimplantation computed tomography (CT) or MRI to preimplantation (artifact-free) MRI facilitates electrode imaging and optimal visualization of brain anatomy. However, registration errors negatively affect electrode localization accuracy. OBJECTIVE: To compare the relative registration deviation between postimplantation CT and MRI with preimplantation MRI. METHODS: Retrospectively, 14 pharmacoresistant epilepsy patients were included who underwent stereotactic insertion of multiple depth electrodes and preimplantation and postimplantation MRI and postimplantation CT. Postimplantation MRI and CT image sets were registered to preimplantation MRI. The registration error between the registered postimplantation MRI and CT was quantified by measuring the geometrical distance between the electrodes of the registered postimplantation CT and the postimplantation MRI. RESULTS: The registration error of postimplantation imaging to preimplantation MRI was dependent on the algorithm used. After optimization, the smallest registration error was 1.22 6 +/- 0.29 mm (mean +/- SD) at the tip and 2.25 +/- 1.18 mm at the base of the electrode. CONCLUSION: The good correspondence between the CT/MRI and the MRI/MRI registration suggests that either postimplantation MRI or CT is sufficient for accurate electrode localization. In case of postoperative morphological brain deformations, postimplantation MRI is still recommended.

Background In clinical practice, Rolandic epilepsy is in many cases associated with developmental language impairment. However, from the literature it is unclear exactly which domains are affected; A wide variety of investigations are reported that each provide a different representation of language performance in these patients. Aims The aim of this study is to compare performance on the language domains between children with Rolandic epilepsy and healthy controls. Methods Prospective study of children with Rolandic epilepsy compared to healthy controls. 25 children (mean age 136.6 months, SD 23.0) with Rolandic epilepsy and 25 age-matched healthy controls were tested on their language function using the CELF-4 (Clinical evaluation of Language Fundamentals, Dutch edition). The healthy control were not matched regard to other important factors, particularly educational attainment and co-morbidity. Expressive language, receptive language, language content, language structure and language working memory were tested. Results In children with Rolandic epilepsy, the core language score was significant lower compared with healthy controls. They scored specifically lower on the receptive language index and language content index (both p = 0.002). A trend towards decreased expressive language index was observed ( p = 0.054). Language structure and language working memory were in the normal range. Conclusion Language was found to be impaired in children with typical Rolandic epilepsy. Especially semantic language processing including receptive language and language content was significantly impaired. The common denominator of these functions is semantic language processing.