Prospective safety evaluation of automated iomeprol 400 injections for CT through peripheral venous cannulas.

AIM: To evaluate prospectively the safety of contrast medium injection through standard peripheral intravenous cannulas at standard injection sites during clinical routine using iomeprol 400, a contrast agent with high viscosity. MATERIALS AND METHODS: Three thousand, five hundred and fourteen clinical CT examinations undertaken at Saarland University Medical Center were included in this prospective observational trial. The size and site of the cannula as well as the contrast medium injection rate and volume were assessed for each patient. In addition, the ability to aspirate blood though the cannula and the occurrence of complications, such as extravasation or abortion of injection by the automated injector, were recorded. RESULTS: The overall complication rate was 30/3,514 (0.85%). With 22 G cannulas, the complication rate was 8/541 (1.48%) applying flow rates of 1-3.5 ml/s (mean 2.1 ml/s). With 20 G cannulas, complications occurred in 21/2,601 cases (0.81%) with flow rates of 1.5-5 ml/s (mean 3 ml/s). The complication rate using 18 G cannulas was 1/377 (0.26%) for flow rates of 2-6 ml/s (mean 3.5 ml/s). No relationship between the site and size of the cannula to the occurrence of complications was found. The inability to aspirate blood correlated with the development of extravasation. CONCLUSIONS: The injection of contrast agent using standard peripheral venous cannulas is a safe and reliable procedure yielding diagnostic image contrast, even when using highly viscous contrast agents such as iomeprol 400; an aspiration test should be performed before each injection.

[Gadolinium deposition-"gadolinium deposition disease"]. / Gadoliniumablagerungen ­ Morbus Gadolinium.

Gadolinium (Gd)-based contrast agents have been routinely used worldwide in diagnostic MRI since 1988. All routinely applied contrast agents for clinical use were considered extremely safe with regard to tolerance, adverse effects and diagnostic efficacy and when used at Food and Drug Administration-approved doses. With the identification of Gd-associated disorders, namely nephrogenic systemic fibrosis and adverse reactions, and in the longer term Gd-retention in the brain, this view changed and led to the withdrawal or restriction of approval of linear Gd chelates in Europe. Even though Gd deposition in different human body areas was described very early, recently published literature of intracerebral accumulation of contrast agents as well as deposition in bone have created surprising attention. Not only was the fact of Gd deposition in the body well known for many years, but there is currently no clinical evidence of patient symptoms and no resulting health issues of patients have been observed yet. The expression "gadolinium deposition disease" has been termed by active patient advocacy groups with an online presence with reports of individual members stating a broad spectrum of disorders yielding a large symptom complex after administration of Gd-based contrast agents without evidence of any pre-existing or otherwise underlying disease process which could explain the mentioned disorder.

Source-reconstruction of the sensorimotor network from resting-state macaque electrocorticography.

The discovery of hemodynamic (BOLD-fMRI) resting-state networks (RSNs) has brought about a fundamental shift in our thinking about the role of intrinsic brain activity. The electrophysiological underpinnings of RSNs remain largely elusive and it has been shown only recently that electric cortical rhythms are organized into the same RSNs as hemodynamic signals. Most electrophysiological studies into RSNs use magnetoencephalography (MEG) or scalp electroencephalography (EEG), which limits the spatial resolution with which electrophysiological RSNs can be observed. Due to their close proximity to the cortical surface, electrocorticographic (ECoG) recordings can potentially provide a more detailed picture of the functional organization of resting-state cortical rhythms, albeit at the expense of spatial coverage. In this study we propose using source-space spatial independent component analysis (spatial ICA) for identifying generators of resting-state cortical rhythms as recorded with ECoG and for reconstructing their functional connectivity. Network structure is assessed by two kinds of connectivity measures: instantaneous correlations between band-limited amplitude envelopes and oscillatory phase-locking. By simulating rhythmic cortical generators, we find that the reconstruction of oscillatory phase-locking is more challenging than that of amplitude correlations, particularly for low signal-to-noise levels. Specifically, phase-lags can both be over- and underestimated, which troubles the interpretation of lag-based connectivity measures. We illustrate the methodology on somatosensory beta rhythms recorded from a macaque monkey using ECoG. The methodology decomposes the resting-state sensorimotor network into three cortical generators, distributed across primary somatosensory and primary and higher-order motor areas. The generators display significant and reproducible amplitude correlations and phase-locking values with non-zero lags. Our findings illustrate the level of spatial detail attainable with source-projected ECoG and motivates wider use of the methodology for studying resting-state as well as event-related cortical dynamics in macaque and human.

[New developements in endovascular infrarenal aortic aneurysm treatment]. / Aktuelle Neuerungen bei der endovaskulären Versorgung infrarenaler Aortenaneurysmen.

CLINICAL/METHODICAL ISSUE: New technical developments in endovascular aortic repair (EVAR) have broadened the range of patients eligible for minimally invasive aneurysm treatment. Optimization of delivery sheaths and catheters by considerable downsizing of diameters, increase of pushability and stability combined with flexibility are important parameters. PERFORMANCE: Especially patients characterized by small and tortuous iliac access vessels can nowadays be treated by EVAR. Ease and effectiveness of applicability guarantee safety and quality improvement, which results in better treatment of patients. Progress in stent-graft design with integrated options for repositioning, active positioning and aneurysm sealing facilitate treatment of angulated vessel segments or hitherto unsuitable sealing zones. PRACTICAL RECOMMENDATIONS: Interventionalists have to be familiar with all available stent-graft materials and techniques. Profound knowledge helps to choose the best material for a patient's individual anatomy, confident application and long-term satisfactory results.

Alpha power indexes task-related networks on large and small scales: A multimodal ECoG study in humans and a non-human primate.

Performing different tasks, such as generating motor movements or processing sensory input, requires the recruitment of specific networks of neuronal populations. Previous studies suggested that power variations in the alpha band (8-12Hz) may implement such recruitment of task-specific populations by increasing cortical excitability in task-related areas while inhibiting population-level cortical activity in task-unrelated areas (Klimesch et al., 2007; Jensen and Mazaheri, 2010). However, the precise temporal and spatial relationships between the modulatory function implemented by alpha oscillations and population-level cortical activity remained undefined. Furthermore, while several studies suggested that alpha power indexes task-related populations across large and spatially separated cortical areas, it was largely unclear whether alpha power also differentially indexes smaller networks of task-related neuronal populations. Here we addressed these questions by investigating the temporal and spatial relationships of electrocorticographic (ECoG) power modulations in the alpha band and in the broadband gamma range (70-170Hz, indexing population-level activity) during auditory and motor tasks in five human subjects and one macaque monkey. In line with previous research, our results confirm that broadband gamma power accurately tracks task-related behavior and that alpha power decreases in task-related areas. More importantly, they demonstrate that alpha power suppression lags population-level activity in auditory areas during the auditory task, but precedes it in motor areas during the motor task. This suppression of alpha power in task-related areas was accompanied by an increase in areas not related to the task. In addition, we show for the first time that these differential modulations of alpha power could be observed not only across widely distributed systems (e.g., motor vs. auditory system), but also within the auditory system. Specifically, alpha power was suppressed in the locations within the auditory system that most robustly responded to particular sound stimuli. Altogether, our results provide experimental evidence for a mechanism that preferentially recruits task-related neuronal populations by increasing cortical excitability in task-related cortical areas and decreasing cortical excitability in task-unrelated areas. This mechanism is implemented by variations in alpha power and is common to humans and the non-human primate under study. These results contribute to an increasingly refined understanding of the mechanisms underlying the selection of the specific neuronal populations required for task execution.

Areas V1 and V2 show microsaccade-related 3-4-Hz covariation in gamma power and frequency.

Neuronal gamma-band synchronization (25-80 Hz) in visual cortex appears sustained and stable during prolonged visual stimulation when investigated with conventional averages across trials. However, recent studies in macaque visual cortex have used single-trial analyses to show that both power and frequency of gamma oscillations exhibit substantial moment-by-moment variation. This has raised the question of whether these apparently random variations might limit the functional role of gamma-band synchronization for neural processing. Here, we studied the moment-by-moment variation in gamma oscillation power and frequency, as well as inter-areal gamma synchronization, by simultaneously recording local field potentials in V1 and V2 of two macaque monkeys. We additionally analyzed electrocorticographic V1 data from a third monkey. Our analyses confirm that gamma-band synchronization is not stationary and sustained but undergoes moment-by-moment variations in power and frequency. However, those variations are neither random and nor a possible obstacle to neural communication. Instead, the gamma power and frequency variations are highly structured, shared between areas and shaped by a microsaccade-related 3-4-Hz theta rhythm. Our findings provide experimental support for the suggestion that cross-frequency coupling might structure and facilitate the information flow between brain regions.

A DCM study of spectral asymmetries in feedforward and feedback connections between visual areas V1 and V4 in the monkey.

This paper reports a dynamic causal modeling study of electrocorticographic (ECoG) data that addresses functional asymmetries between forward and backward connections in the visual cortical hierarchy. Specifically, we ask whether forward connections employ gamma-band frequencies, while backward connections preferentially use lower (beta-band) frequencies. We addressed this question by modeling empirical cross spectra using a neural mass model equipped with superficial and deep pyramidal cell populations-that model the source of forward and backward connections, respectively. This enabled us to reconstruct the transfer functions and associated spectra of specific subpopulations within cortical sources. We first established that Bayesian model comparison was able to discriminate between forward and backward connections, defined in terms of their cells of origin. We then confirmed that model selection was able to identify extrastriate (V4) sources as being hierarchically higher than early visual (V1) sources. Finally, an examination of the auto spectra and transfer functions associated with superficial and deep pyramidal cells confirmed that forward connections employed predominantly higher (gamma) frequencies, while backward connections were mediated by lower (alpha/beta) frequencies. We discuss these findings in relation to current views about alpha, beta, and gamma oscillations and predictive coding in the brain.

Contrast gain control and horizontal interactions in V1: a DCM study.

Using high-density electrocorticographic recordings - from awake-behaving monkeys - and dynamic causal modelling, we characterised contrast dependent gain control in visual cortex, in terms of synaptic rate constants and intrinsic connectivity. Specifically, we used neural field models to quantify the balance of excitatory and inhibitory influences; both in terms of the strength and spatial dispersion of horizontal intrinsic connections. Our results allow us to infer that increasing contrast increases the sensitivity or gain of superficial pyramidal cells to inputs from spiny stellate populations. Furthermore, changes in the effective spatial extent of horizontal coupling nuance the spatiotemporal filtering properties of cortical laminae in V1 - effectively preserving higher spatial frequencies. These results are consistent with recent non-invasive human studies of contrast dependent changes in the gain of pyramidal cells elaborating forward connections - studies designed to test specific hypotheses about precision and gain control based on predictive coding. Furthermore, they are consistent with established results showing that the receptive fields of V1 units shrink with increasing visual contrast.

Adding dynamics to the Human Connectome Project with MEG.

The Human Connectome Project (HCP) seeks to map the structural and functional connections between network elements in the human brain. Magnetoencephalography (MEG) provides a temporally rich source of information on brain network dynamics and represents one source of functional connectivity data to be provided by the HCP. High quality MEG data will be collected from 50 twin pairs both in the resting state and during performance of motor, working memory and language tasks. These data will be available to the general community. Additionally, using the cortical parcellation scheme common to all imaging modalities, the HCP will provide processing pipelines for calculating connection matrices as a function of time and frequency. Together with structural and functional data generated using magnetic resonance imaging methods, these data represent a unique opportunity to investigate brain network connectivity in a large cohort of normal adult human subjects. The analysis pipeline software and the dynamic connectivity matrices that it generates will all be made freely available to the research community.

Substantially improved gene transfer to interneurons with second-generation glutamate receptor-targeted DART-AAV vectors.

BACKGROUND: Adeno-associated viral vectors (AAVs) are a widely used gene transfer platform in neuroscience. Although naturally AAV serotypes can have preferences for certain tissues, selectivity for particular cell types in the CNS does not exist. Towards interneuron targeting, capsid engineering of AAV2 including display of the designed ankyrin repeat protein (DARPin) 2K19 specific for the glutamate receptor subunit 4 (GluA4) at the N-terminus of the VP2 capsid protein has been established. The resulting AAV-VP2N is highly specific for interneurons, but exhibits rather moderate transduction efficiencies. METHODS: Two alternative insertion sites for 2K19 in the GH2/GH3 loop of capsid proteins VP1 (AAV-VP1L) or VP2 (AAV-VP2L) were exploited to yield second generation GluA4-AAVs. Having packaged reporter genes under ubiquitous promoters, the vectors were characterized for biochemical properties as well as gene delivery into cell lines and rat hippocampal slice cultures. Electrophysiological recordings monitored the functional properties of transduced cells. RESULTS: Compared to AAV-VP2N, the second-generation vectors, especially AAV-VP1L, achieved about 2-fold higher genomic titers as well as a substantially improved GluA4 binding. Improvements in gene transfer activities were 18-fold on GluA4-overexpressing A549 cells and five-fold on rat hippocampal organotypic slice cultures reaching approximately 60 % of all parvalbumin positive interneurons upon a single administration. The spiking behaviour of transduced cells was unaltered and characteristic for a heterogeneous group of interneurons. CONCLUSION: The substantially improved gene transfer activity of the second generation GluA4-targeted AAV combined with low toxicity makes this vector an attractive tool for interneuron-directed gene transfer with unrestricted promotor and transgene choice.

DCM for complex-valued data: cross-spectra, coherence and phase-delays.

This note describes an extension of Bayesian model inversion procedures for the Dynamic Causal Modeling (DCM) of complex-valued data. Modeling complex data can be particularly useful in the analysis of multivariate ergodic (stationary) time-series. We illustrate this with a generalization of DCM for steady-state responses that models both the real and imaginary parts of sample cross-spectra. DCM allows one to infer underlying biophysical parameters generating data (like synaptic time constants, connection strengths and conduction delays). Because transfer functions and complex cross-spectra can be generated from these parameters, one can also describe the implicit system architecture in terms of conventional (linear systems) measures; like coherence, phase-delay or cross-correlation functions. Crucially, these measures can be derived in both sensor and source-space. In other words, one can examine the cross-correlation or phase-delay functions between hidden neuronal sources using non-invasive data and relate these functions to synaptic parameters and neuronal conduction delays. We illustrate these points using local field potential recordings from the subthalamic nucleus and globus pallidus, with a special focus on the relationship between conduction delays and the ensuing phase relationships and cross-correlation time lags between population activities.

A 13-year-old girl with arterial hypertension - mid-aortic syndrome.

Mid-aortic stenosis (MAS) is a rare clinical entity that is characterised by profound narrowing of the abdominal aorta. MAS usually presents with severe hypertension. Treatment modalities include antihypertensive medication, angioplasty, and surgery. If adequate treatment is initiated long-term prognosis is favourable. Here, we report on 13-year-old girl with MAS who presented to our hospital with arterial hypertension. Initial diagnostic work-up and treatment in patients with MAS are presented.

Severe respiratory distress syndrome unresponsive to intensive care treatment--diagnostic and therapeutic considerations.

Respiratory Distress Syndrome (RDS) is a common complication in preterm neonates. If RDS is not responding to conventional treatment modalities (surfactant therapy, ventilatory support, etc.), an underlying pathology (pulmonary lymphangiectasia, capillary alveolar dysplasia, alpha-1 antitrypsin deficiency, etc.) other then prematurity should be taken into consideration.Here, we report on a preterm neonate with the unusual simultaneous occurrence of pulmonary and systemic lymphangiectasia and homozygous alpha-1 antitrypsin deficiency who developed severe RDS that was refractory to conventional treatment. The diagnostic and therapeutic approach in this patient is presented.

Lanthanide complexes of DOTA-nitroxide conjugates for redox imaging: spectroelectrochemistry, CEST, relaxivity, and cytotoxicity.

The lanthanide(iii) complexes (Gd, Eu, Dy, and Yb) of DOTA tris(amide) and bis(amide) derivatives (L1 and L2) featuring one redox active TEMPO arm were prepared. Ligand L2 harbours an alkyne fragment for further functionalization. The X-ray crystal structure of ligand L2 in complexation with Na+ was solved. The complexes showed in their CV one oxidation wave (0.26-0. 34 V vs. Fc+/Fc) due to an oxoammonium/nitroxide redox couple and a broad reduction corresponding to the nitroxide/hydroxylamine system. The Eu complexes demonstrated the presence of one water molecule in their coordination sphere. The nitroxide complexes were characterized by EPR spectroscopy, showing the typical 3-line pattern in the high temperature regime, which is quenched upon the addition of ascorbate (reduction into hydroxylamine). In their nitroxide form, the complexes show essentially no CEST peak. Conversely, the reduced complexes demonstrate a 12% CEST peak at 51 ppm, corresponding to the metal bound water molecule. Fast exchange precluded the CEST activity for the amide protons. All the complexes proved to be essentially non-toxic for M21 cells at concentrations up to 50 µM.

Inverse mapping the neuronal substrates of face categorizations.

Face perception is a complex process involving a network of brain structures, dynamically processing information to enable judgments about a face to be made (e.g., familiarity, identity, and expression). Here we introduce an analysis methodology that makes it possible to directly study this information processing in the brain from spatially and temporally resolved magnetoencephalographic signals. We apply our methodology to the study of 2 face categorization tasks, gender and expressiveness, and track the processing of 3 key visual features that underlie behavioral performance, over time and throughout the cortex. We find information processing correlates beginning from 90 ms following stimulus onset, where features are processed in isolation in occipital extrastriate regions. Over time, processing of successively more features and feature combinations takes place in occipitotemporal regions, with maximal information processing of visual information coinciding with the well-established face-selective M170 component at 170 ms. Later still, around 250-400 ms, cortical activity responds significantly more to task-specific features and their complex combinations. These results indicate a complex process of visual information processing during face perception with face parts processed in isolation at very early stages, and task-specific processing of combinations of features taking place within 300 ms. Crucially, our approach specifically establishes which information in the visual stimulus the brain signal is responding to and how this varies with time, cortical location, and task demands to establish a more precise tracking of information processing mechanisms in the cortex during face perception.

[Spinal tumors]. / Spinale Tumoren.

Spinal tumors can be intramedullary, intradural (within the meninges), or extradural (between the meninges and the bones), or they may extend secondary to the spine from other locations. Vertebral hemangioma represents the most common benign tumor of the spine. Metastases, lymphoma, and multiple myeloma are the most frequent malignant spinal tumors. Primary osseous tumors of the spine, in contrast, are rare conditions but may demonstrate typical imaging findings. For the differential diagnosis, the patient's age, the topographic localization of the mass, and morphologic features of the lesion as depicted by computed tomography and magnetic resonance imaging play important roles.

[Post-traumatic torticollis in a schoolchild: fracture, congenital anomaly or age-appropriate radiological findings of the atlas?]. / Posttraumatischer Tortikollis beim Schulkind : Fraktur, angeborene Fehlbildung oder altersentsprechender Normalbefund des Atlasbogens?

We describe the case of a 6-year-old girl with post-traumatic torticollis after falling on her head. The suspected fractures of the dens axis and/or atlas were ruled out after performing CT and MRI examinations as well as dynamic fluoroscopy. Radiological findings showed no further instability but there was a congenital non-fusion of the posterior arch and an age-appropriate non-fused anterior arch of the atlas. In addition to discoligamental injuries and fractures, congenital anomalies and normal variants of the immature anatomy of the cervical spine should also be considered in the diagnosis of the pediatric cervical spine after trauma.

Modulation of oscillatory neuronal synchronization by selective visual attention.

In crowded visual scenes, attention is needed to select relevant stimuli. To study the underlying mechanisms, we recorded neurons in cortical area V4 while macaque monkeys attended to behaviorally relevant stimuli and ignored distracters. Neurons activated by the attended stimulus showed increased gamma-frequency (35 to 90 hertz) synchronization but reduced low-frequency (<17 hertz) synchronization compared with neurons at nearby V4 sites activated by distracters. Because postsynaptic integration times are short, these localized changes in synchronization may serve to amplify behaviorally relevant signals in the cortex.

Rapid feature selective neuronal synchronization through correlated latency shifting.

Spontaneous brain activity could affect processing if it were structured. We show that neuron pairs in cat primary visual cortex exhibited correlated fluctuations in response latency, particularly when they had overlapping receptive fields or similar orientation preferences. Correlations occurred within and across hemispheres, but only when local field potentials (LFPs) oscillated in the gamma-frequency range (40-70 Hz). In this range, LFP fluctuations preceding response onset predicted response latencies; negative (positive) LFPs were associated with early (late) responses. Oscillations below 10 Hz caused covariations in response amplitude, but exhibited no columnar selectivity or coordinating effect on latencies. Thus, during high gamma activity, spontaneous activity exhibits distinct, column-specific correlation patterns. Consequently, cortical cells undergo coherent fluctuations in excitability that enhance temporal coherence of responses to contours that are spatially contiguous or have similar orientation. Because synchronized responses are more likely than dispersed responses to undergo rapid and joint processing, spontaneous activity may be important in early visual processes.

A wire transposition technique for recanalization of chronic complex central venous occlusions.

PURPOSE: A minimal-invasive interventional technique for recanalization of complex chronic central venous total occlusions is described to overcome difficulties in case of failure of common approaches. METHOD: We present a patient with a central venous occlusion that caused severe venous congestion of her upper extremity and significant impairment of her forearm hemodialysis shunt. Since the usual transbrachial and transfemoral attempts for recanalization of occluded right subclavian, brachiocephalic, superior vena cava, and proximal internal jugular veins (IJV) failed, the approach was changed to a transjugular access. Only the IJV and subclavian vein occlusions were passed from transjugular. RESULTS: The key procedure was the switch of a jugular-brachial wire to a femoral-brachial setting. The wire transposition was achieved by snaring the looped stiff end of the jugular-brachial wire outside the jugular sheath from the opposite femoral access. CONCLUSION: Different approaches should be considered for the recanalization of challenging central venous occlusions. After failed attempts via common access sites, a guidewire transposition maneuver using a combined approach may be particularly helpful for safe and effective endovascular treatment of complex situations.