DeepFLAIR: A neural network approach to mitigate signal and contrast loss in temporal lobes at 7 Tesla FLAIR images.

BACKGROUND AND PURPOSE: Higher magnetic field strength introduces stronger magnetic field inhomogeneities in the brain, especially within temporal lobes, leading to image artifacts. Particularly, T2-weighted fluid-attenuated inversion recovery (FLAIR) images can be affected by these artifacts. Here, we aimed to improve the FLAIR image quality in temporal lobe regions through image processing of multiple contrast images via machine learning using a neural network. METHODS: Thirteen drug-resistant MR-negative epilepsy patients (age 29.2 ± 9.4y, 5 females) were scanned on a 7 T MRI scanner. Magnetization-prepared (MP2RAGE) and saturation-prepared with 2 rapid gradient echoes, multi-echo gradient echo with four echo times, and the FLAIR sequence were acquired. A voxel-wise neural network was trained on extratemporal-lobe voxels from the acquired structural scans to generate a new FLAIR-like image (i.e., deepFLAIR) with reduced temporal lobe inhomogeneities. The deepFLAIR was evaluated in temporal lobes through signal-to-noise (SNR), contrast-to-noise (CNR) ratio, the sharpness of the gray-white matter boundary and joint-histogram analysis. Saliency mapping demonstrated the importance of each input image per voxel. RESULTS: SNR and CNR in both gray and white matter were significantly increased (p < 0.05) in the deepFLAIR's temporal ROIs, compared to the FLAIR. The gray-white matter boundary sharpness was either preserved or improved in 10/13 right-sided temporal regions and was found significantly increased in the ROIs. Multiple image contrasts were influential for the deepFLAIR reconstruction with the MP2RAGE second inversion image being the most important. CONCLUSIONS: The deepFLAIR network showed promise to restore the FLAIR signal and reduce contrast attenuation in temporal lobe areas. This may yield a valuable tool, especially when artifact-free FLAIR images are not available.

Advances in Image Processing for Epileptogenic Zone Detection with MRI.

Focal epilepsy is a common and severe neurologic disorder. Neuroimaging aims to identify the epileptogenic zone (EZ), preferably as a macroscopic structural lesion. For approximately a third of patients with chronic drug-resistant focal epilepsy, the EZ cannot be precisely identified using standard 3.0-T MRI. This may be due to either the EZ being undetectable at imaging or the seizure activity being caused by a physiologic abnormality rather than a structural lesion. Computational image processing has recently been shown to aid radiologic assessments and increase the success rate of uncovering suspicious regions by enhancing their visual conspicuity. While structural image analysis is at the forefront of EZ detection, physiologic image analysis has also been shown to provide valuable information about EZ location. This narrative review summarizes and explains the current state-of-the-art computational approaches for image analysis and presents their potential for EZ detection. Current limitations of the methods and possible future directions to augment EZ detection are discussed.

Efficacy of postmortem CT and tissue sampling in establishing the cause of death in clinical practice: a prospective observational study.

AIMS: The 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. METHODS: This 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. RESULTS: Of 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. CONCLUSION: PMCT 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.

Postmortem Fetal Temperature Estimation with Magnetic Resonance Imaging: Apparent Diffusion Coefficient Measurements in the Vitreous Body and Cerebrospinal Fluid.

OBJECTIVES: Magnetic resonance imaging (MRI) is increasingly used in postmortem fetal imaging. Several factors influence the quality of MRI in this setting, such as small size, autolytic and maceration changes, and temperature. Knowing the fetal temperature at the time of scanning can improve the MRI interpretation. Temperature can be calculated using diffusion-weighted imaging with measurements of the apparent diffusion coefficient (ADC) in the cerebrospinal fluid (CSF). However, this is complicated by small ventricle size and hemorrhage and, therefore, may be unreliable in postmortem imaging. The current study evaluated the feasibility and reliability of using the ADC for temperature measurements of the vitreous body compared to that of CSF. MATERIALS AND METHODS: Two lambs were scanned postmortem at five different time points over 28 hours. Furthermore, 10 stillborn fetuses were scanned once, at 4 to 62 hours after birth. The temperature was measured with a digital thermometer and calculated using the ADCs of the vitreous body (lambs and fetuses) and CSF (fetuses). RESULTS: There was an excellent correlation between measured and calculated temperatures in vitreous bodies of lambs (r = 0.997, P < 0.001) and fetuses (r = 0.970, P < 0.001). The correlation between measured and calculated temperatures in the CSF was poor (r = 0.522, P = 0.122). CONCLUSION: The calculation of the temperature based on the ADC of the vitreous body is feasible and reliable for postmortem fetal imaging.

Postmortem Diffusion-Weighted Magnetic Resonance Imaging of the Brain in Perinatal Death: An Animal Control Study to Detect the Influence of Postmortem Interval.

OBJECTIVES: Diffusion-weighted imaging may be useful as part of a postmortem magnetic resonance imaging protocol. However, apart from the effect of temperature on apparent diffusion coefficient (ADC), normal postmortem ADC changes can influence the interpretation. Therefore, this study was conducted to evaluate the correlation between normal ADC changes and postmortem intervals (PMIs) and develop a reference standard for postmortem changes after temperature correction. MATERIALS AND METHODS: Six premature lambs were scanned at different PMIs. ADC values were measured at different parenchymal locations. Correlation and linear regression between ADC values and PMI were analyzed for all locations, both uncorrected and corrected for temperature. RESULTS: All locations showed a significant negative correlation between the PMI and ADC value, with (R2 = 0.581-0.837, P < 0.001) and without (R2 = 0.183-0.555, P < 0.001-0.018) temperature correction. CONCLUSIONS: The postmortem interval is negatively correlated with ADC values in the brain. A correlation coefficient for the PMI can be calculated after temperature correction to predict ADC changes. However, further research is required to evaluate its clinical application in humans.

The application of CT for 3D visualization of concealed bodies.

In forensic radiology, computed tomography (CT) is often used as a medical imaging technique to identify the cause and manner of death of deceased victims of a possible crime. In this study, medical imaging is used to examine concealed bodies and packaging materials. Medical imaging techniques, mainly CT scan, were used to scan packaged or concealed bodies inside containers to identify clues and evidence indicating whether a crime might have been committed. Also, scene integrity and scene safety along with a systematic search for relevant evidentiary items value were considered. Eighteen concealed bodies that had been assessed using medical imaging techniques between 2010 and 2018 at the request of the Dutch National Police were selected. The file records of each case contained imaging data, a photographic record of the unpacking procedure, a list of all items and traces found in the package, and the forensic pathology report. The images were assessed with respect to the different aspects of the case and through a systematic approach. The packages included adult males, adult females, newborn infants, and animals. All human cases were related to criminal offences. In nine adult cases, evidence of a possible violent death could be determined using CT imaging. The cause of death in newborn infants, however, could not be determined. In cases of dismemberment, the completeness of the body could be determined by CT imaging, and the cutting surfaces of bones could be matched on CT images. Regarding scene safety and integrity, in this study all relevant macroscopic items were detected on the CT images. The CT-scans were supplemented with fiduciary markers to better map CT data with the real objects. This information in combination with 2D and 3D images provided the forensic investigator with information on how to unwrap the package layer by layer and help determine different types of packaging materials. Different textiles could not always be identified. The orientation of the body within the packages was provided in all cases, and advice could be given on the optimal approach to access the contents. The overall detection rate of items was 78%. This is one of the first studies to illustrate the contribution of medical imaging, specifically CT scan, to the analysis of concealed bodies and packaging materials prior to unpacking. This demonstrates its contribution to a systematic approach of the investigation by ensuring the safety and health of the investigator while documenting and maintaining the integrity of the crime scene. Imaging also provides information that can be helpful to determine whether a crime might have been committed and reducing the risk of damaging a concealed body. Medical imaging also provides the forensic investigator with information to draw up a workplan prior to unpacking, minimising loss of evidence and determining whether different forensic specialists (e.g., digital or DNA) are needed. It is therefore strongly recommended to use medical imaging, especially CT scanning, before opening a package containing a concealed body.

Predictive value of functional MRI and EEG in epilepsy diagnosis after a first seizure.

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 ±â€¯SD) of the regression model including metrics from both modalities were 74 ±â€¯19%, 82 ±â€¯18%, and 0.75 ±â€¯0.12, respectively. Positive and negative predictive values (mean ±â€¯SD) of the regression model with both EEG and fMRI features are 84 ±â€¯14% and 78 ±â€¯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.

Neuroimaging of Anxiety in Parkinson's Disease: A Systematic Review.

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.

Introduction of postmortem CT increases the postmortem examination rate without negatively impacting the rate of traditional autopsy in daily practice: an implementation study.

AIM: The aim of this implementation study was to assess the effect of postmortem CT (PMCT) and postmortem sampling (PMS) on (traditional) autopsy and postmortem examination rates. Additionally, the feasibility of PMCT and PMS in daily practice was assessed. METHODS: For a period of 23 months, PMCT and PMS were used as additional modalities to the autopsy at the Department of Internal Medicine. The next of kin provided consent for 123 postmortem examinations. Autopsy rates were derived from the Dutch Pathology Registry, and postmortem examination rates were calculated for the period before, during and after the study period, and the exclusion rate, table time, time interval to informing the referring clinicians with results and the time interval to the Multidisciplinary Mortality Review Board (MMRB) meeting were objectified to assess the feasibility. RESULTS: The postmortem examination rate increased (from 18.8% to 32.5%, p<0.001) without a decline in the autopsy rate. The autopsy rate did not change substantially after implementation (0.2% decrease). The exclusion rate was 2%, the table time was 23 min, and a median time interval of 4.1 hours between PMCT and discussing its results with the referring clinicians was observed. Additionally, more than 80% of the MMRB meetings were held within 8 weeks after the death of the patient. CONCLUSIONS: Our study shows that the implementation of a multidisciplinary postmortem examination is feasible in daily practice and does not adversely affect the autopsy rate, while increasing the postmortem examination rate.

Clinical Relevance of Unexpected Findings of Post-Mortem Computed Tomography in Hospitalized Patients: An Observational Study.

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.

Volumetric and Functional Activity Lateralization in Healthy Subjects and Patients with Focal Epilepsy: Initial Findings in a 7T MRI Study.

BACKGROUND AND PURPOSE: In 30% of the patients with focal epilepsy, an epileptogenic lesion cannot be visually detected with structural MRI. Ultra-high field MRI may be able to identify subtle pathology related to the epileptic focus. We set out to assess 7T MRI-derived volumetric and functional activity lateralization of the hippocampus, hippocampal subfields, temporal and frontal lobe in healthy subjects and MRI-negative patients with focal epilepsy. METHODS: Twenty controls and 10 patients with MRI-negative temporal or frontal lobe epilepsy (TLE and FLE, respectively) underwent a 7T MRI exam. T1 -weigthed imaging and resting-state fMRI was performed. T1 -weighted images were segmented to yield volumes, while from fMRI data, the fractional amplitude of low frequency fluctuations was calculated. Subsequently, volumetric and functional lateralization was calculated from left-right asymmetry. RESULTS: In controls, volumetric lateralization was symmetric, with a slight asymmetry of the hippocampus and subiculum, while functional lateralization consistently showed symmetry. Contrarily, in epilepsy patients, regions were less symmetric. In TLE patients with known focus, volumetric lateralization in the hippocampus and hippocampal subfields was indicative of smaller ipsilateral volumes. These patients also showed clear functional lateralization, though not consistently ipsilateral or contralateral to the epileptic focus. TLE patients with unknown focus showed an obvious volumetric lateralization, facilitating the localization of the epileptic focus. Lateralization results in the FLE patients were less consistent with the epileptic focus. CONCLUSION: MRI-derived volume and fluctuation amplitude are highly symmetric in controls, whereas in TLE, volumetric and functional lateralization effects were observed. This highlights the potential of the technique.

The needle in the haystack: Histology of post-mortem computed tomography guided biopsies versus autopsy derived tissue.

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.

Microstructural white matter changes preceding white matter hyperintensities in migraine.

OBJECTIVE: We 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. METHODS: We 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. RESULTS: MTR 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. CONCLUSIONS: We 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.

Symptomatic Carotid Plaques Demonstrate Less Leaky Plaque Microvasculature Compared With the Contralateral Side: A Dynamic Contrast-Enhanced Magnetic Resonance Imaging Study.

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 Ktrans) 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 Ktrans, 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 Ktrans 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 Ktrans 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.

Structural covariance networks relate to the severity of epilepsy with focal-onset seizures.

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.

What you see is (not) what you get: tools for a non-radiologist to evaluate image quality in lung cancer.

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.

High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy.

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.

Brain resting-state networks in adolescents with high-functioning autism: Analysis of spatial connectivity and temporal neurodynamics.

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.

Pulsatility of Lenticulostriate Arteries Assessed by 7 Tesla Flow MRI-Measurement, Reproducibility, and Applicability to Aging Effect.

Characterization of flow properties in cerebral arteries with 1.5 and 3 Tesla MRI is usually limited to large cerebral arteries and difficult to evaluate in the small perforating arteries due to insufficient spatial resolution. In this study, we assessed the feasibility to measure blood flow waveforms in the small lenticulostriate arteries with 7 Tesla velocity-sensitive MRI. The middle cerebral artery was included as reference. Imaging was performed in five young and five old healthy volunteers. Flow was calculated by integrating time-varying velocity values over the vascular cross-section. MRI acquisitions were performed twice in each subject to determine reproducibility. From the flow waveforms, the pulsatility index and damping factor were deduced. Reproducibility values, in terms of the intraclass correlation coefficients, were found to be good to excellent. Measured pulsatility index of the lenticulostriate arteries significantly increased and damping factor significantly decreased with age. In conclusion, we demonstrate that blood flow through the lenticostriate arteries can be precisely measured using 7 Tesla MRI and reveal effects of arterial stiffness due to aging. These findings hold promise to provide relevant insights into the pathologies involving perforating cerebral arteries.

Chronic antiepileptic drug use and functional network efficiency: A functional magnetic resonance imaging study.

AIM: To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug (AED) treatment. METHODS: The 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. RESULTS: Central 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 < 0.05, ANCOVA), with a significantly higher global efficiency for patient from the low category compared with the high risk category (P < 0.05, post-hoc test). Risk category had no significant effect on the clustering coefficient (ANCOVA, 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. CONCLUSION: Only 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.