The FRESH Study: Treatment of Intracranial Aneurysms with the New FRED X Flow Diverter with Antithrombotic Surface Treatment Technology-First Multicenter Experience in 161 Patients.

BACKGROUND AND PURPOSE: Flow diverters with antithrombotic coatings are increasingly used to improve the safety of flow diverter treatments of intracranial aneurysms. This study aimed to investigate the safety and short-term efficacy of the new FRED X flow diverter. MATERIALS AND METHODS: Medical charts and procedural and imaging data of a consecutive series of patients with intracranial aneurysms who were treated with the FRED X at 9 international neurovascular centers were retrospectively analyzed. RESULTS: One hundred sixty-one patients (77.6% women; mean age, 55 years) with 184 aneurysms (11.2% acutely ruptured) were included in this study. Most aneurysms were located in the anterior circulation (77.0%), most frequently at the ICA (72.7%). The FRED X was successfully implanted in all procedures. Additional coiling was performed in 29.8%. In-stent balloon angioplasty was necessary in 2.5%. The rate of major adverse events was 3.1%. Thrombotic events occurred in 7 patients (4.3%) with 4 intra- and 4 postprocedural in-stent thromboses, respectively (1 patient had both peri- and postprocedural thrombosis). Of these thrombotic events, only 2 (1.2%) led to major adverse events (ischemic strokes). Postinterventional neurologic morbidity and mortality were observed in 1.9% and 1.2%, respectively. The rate of complete aneurysm occlusion after a mean follow-up of 7.0 months was 66.0%. CONCLUSIONS: The new FRED X is a safe and feasible device for aneurysm treatment. In this retrospective multicenter study, the rate of thrombotic complications was low, and the short-term occlusion rates are satisfactory.

Prediction of response to Certolizumab-Pegol in rheumatoid arthritis (PreCePRA) by functional MRI of the brain - Study protocol for a randomized double-blind controlled study.

BACKGROUND: Tumor necrosis factor inhibitors (TNFi) signify a major advance in the treatment of rheumatoid arthritis (RA). However, treatment success initially remains uncertain as approximately half of the patients do not respond adequately to TNFi. Thus, an unmet need exists to better predict therapeutic outcome of biologicals. OBJECTIVES: We investigated whether brain activity associated with arthritis measured by functional magnetic resonance imaging (fMRI) of the brain can serve as a predictor of response to TNFi in RA patients. METHODS: PreCePRA is a multi-center, randomized, double-blind, placebo-controlled fMRI trial on patients with RA [1] [2]. Active RA patients failing csDMARDs therapy with a DAS28 > 3.2 and at least three tender and/or swollen joints underwent a brain BOLD (blood-oxygen-level dependent) fMRI scan upon joint compression at screening. Patients were then randomized into a 12-week double-blinded treatment phase with 200 mg Certolizumab Pegol (CZP) every two weeks (arm 1: fMRI BOLD signal activated volume > 2000 voxel, i.e. 2 cm3; arm 2: fMRI BOLD signal activated volume <2000 voxel) or placebo (arm 3). DAS28 low disease activity at 12 weeks was assigned as primary endpoint. A 12-week follow-up phase in which patients were switched from the placebo to the treatment arm followed the blinded phase. fMRI was carried out at screening as well as after 12 and 24 weeks of receiving CZP or placebo. CONCLUSION: We hypothesize that high-level central nervous representation of pain in patients with rheumatoid arthritis predicts response to the TNFi CZP which we further investigate in the PreCePRA trial.

[Interdisciplinary neurovascular networks: state of the art]. / Interdisziplinäre neurovaskuläre Netzwerke: eine Standortbestimmung.

BACKGROUND: In order to treat the complete spectrum of neurovascular diseases at a high level of quality, which goes beyond the purely acute treatment of stroke, the German Stroke Society (DSG) together with the German Societies for Neurosurgery and Neuroradiology developed a certification procedure for neurovascular networks (NVN). Structurally, a NVN consists of a coordinating center with at least three neurovascular network partners with a certified stroke unit. From 2018 to 2020 a total of 15 NVN have so far been audited and certified according to this new standard. OBJECTIVE: How efficient are the NVN? Are high standards maintained? MATERIAL AND METHODS: The reports of the audits were analyzed. The data were taken from the period 2017-2019. RESULTS: The 15 NVN treated a total of 86,510 stroke patients in the years examined and were networked with a total of 107 partner clinics, which were situated an average of 25 km from the coordinating center and transferred a total of 2726 patients. The coordinating centers performed 2463 thrombectomies and treated 2383 patients with nontraumatic intracerebral bleeding. In 712 patients with acute aneurysmatic subarachnoid hemorrhages endovascular treatment was carried out and clipping in 401. The audit was successful in the majority of the NVN. CONCLUSION: The certification process of NVN has been successfully established and the audits proved to be a useful instrument for quality control and improvement. The 15 NVN are highly efficient and treat more than one quarter of stroke patients in German stroke units.

The effects of thin film homogeneity on the performance of ferroelectric tunnel junctions.

The compelling physical properties of the recently discovered ferroelectric phase in thin film Hf x Zr1-x O2 have opened a window for applications such as non-volatile resistive switching memory devices with high retention known as ferroelectric tunnel junctions. In this article, we investigate the stability of these two-terminal, polarization induced resistance-switching devices with respect to the statistical reproducibility of constitutive electrical parameters based on surface thickness inhomogeneities. We provide a straightforward, quantitative model to estimate tunneling currents dependent on thickness variations, and the resulting tunneling electroresistance (TER) ratios and breakdown probability. An analytical expression for the probability distribution of tunneling currents for normally distributed thicknesses is given. Using material parameters of a TiN/HZO/Pt heterostructure, practical design requirements are deduced and an estimation with respect to the surface roughness is given for practical ferroelectric layer thicknesses and voltages below 4 nm and 1 V, respectively. In this regime, the simple model of a ballistic, direct tunneling mechanism can be used to adequately model the thickness and voltage dependence of the resistivity.

N2+(2Σg) and Rb(2S) in a hybrid trap: modeling ion losses from radiative association paths.

By employing ab initio computed intermolecular potential energy surfaces we calculate the radiative association probabilities and rates for two different associative mechanisms involving trapped molecular ions N2+(2Σg) interacting either directly with ultracold Rb atoms or undergoing charge-exchange (CE) processes leading to the formation of complexes of the strongly exothermic products N2(X1Σg) plus Rb+(1S0). The two processes are expected to provide possible paths to ion losses in the trap within the timescale of experiments. The present calculations suggest that the associative rates for the 'vibrational' direct process are too small to be of any significant importance at the millikelvin temperatures considered in the experiments, while the 'vibronic' path into radiatively associating the CE products has a probability of occurring which is several orders of magnitude larger. However the reaction rate constants attributed to non-adiabatic CE [F. H. J. Hall and S. Willist, Phys. Rev. Lett., 2012, 109, 233202] are in turn several orders of magnitude larger than the radiative ones calculated here, thereby making the primary experimental process substantially unaffected by the radiative losses channel.

FLAIRfusion Processing with Contrast Inversion : Improving Detection and Reading Time of New Cerebral MS Lesions.

PURPOSE: To evaluate the performance of an innovative image processing approach for detection of T2-weighted hyperintense multiple sclerosis (MS) lesions. METHODS: In this study 20 consecutive patients with inflammatory demyelinating lesions were retrospectively evaluated of whom 10 patients featured progressive disease and 10 a stable lesion load. 3 mm transversal FLAIRfusion imaging was processed and archived. Image processing was performed through landmark-based 3D co-registration of the previous and current isotropic FLAIR examination followed by inversion of image contrast. Thereby, the hyperintense signals of the unchanged MS plaques extinguish each other, while newly developed lesions appear bright on FLAIRfusion. Diagnostic performance was evaluated by 4 experienced readers. Consensus reading supplied the reference standard. Sensitivity, specificity, NPV (negative predictive value), PPV (positive predictive value), interreader agreement and reading time were the outcome measures analyzed. RESULTS: Combined sensitivity was 100% at a specificity of 88.2%, with PPV ranging from 83.3% to 90.1% and NPV at 100%. Reading time was nearly 5­fold faster than conventional side by side comparison (35.6 s vs. 163.7 s, p < 0.001). Cohen's kappa was excellent (>0.75; p < 0.001) and Cronbach's alpha was 0.994. CONCLUSION: FLAIRfusion provides reliable detection of newly developed MS lesions along with strong interreader agreement across all levels of expertise in 35 s of reading time.

[Diffusion tensor imaging of the visual pathway in glaucomatous optic nerve atrophy]. / Diffusionsbildgebung der Sehbahn bei glaukomatöser Optikusatrophie.

In Germany more than one million inhabitants suffer from glaucoma, more than 100,000 are threatened with blindness because glaucoma is often diagnosed too late or not at all. Diagnosis and monitoring is usually carried out "only" by examination of the retina and not the whole visual pathway. However, the eye is just "the tip of the iceberg" of the actual visual pathway, which extends through the brain to the visual cortex. The interdisciplinary holistic assessment of the whole visual pathway in glaucoma is of crucial importance because glaucoma is a complex neurodegenerative disease. Subtypes, such as normal tension glaucoma (NTG), seem to originate from primary damage to the intracranial visual pathway with secondary retrograde retinal degeneration. Recent studies including glaucoma patients and healthy controls could show that diffusion tensor imaging with calculation of diffusion coefficients, i.e. fractional anisotropy (FA), mean and radial diffusivity (MD and RD) as markers of axonal integrity, provide the potential to assess the intracranial visual pathway with a high correlation to established ophthalmological examinations. In particular, calculation of FA maps of the visual pathway and accompanying voxel-based approaches, can be integrated into clinical routine. Thus, detection of glaucoma-related intracranial alterations, even in early stages of the disease, as well as differentiation of different glaucoma subtypes, is made possible. Furthermore, the diagnosis of normal tension glaucoma seems to be possible much earlier with these new imaging techniques compared to established ophthalmological work-up. Moreover, holistic imaging provides new insights into the pathophysiology of this form of glaucoma. This review article gives an overview of these novel magnetic resonance imaging techniques for assessment of the visual pathway in glaucomatous optic nerve atrophy and reveals the potential of an interdisciplinary approach.

Clinically significant CMV (re)activation during or after radiotherapy/chemotherapy of the brain : Correlation with neurological deterioration and improvement upon antiviral treatment.

INTRODUCTION: For both patients with high-grade gliomas and multiple cerebral metastases, radio(chemo)therapy is the standard therapy. Neurological decline during treatment is rarely attributed to infections of the brain but to tumor progression or side effects of radiotherapy. CASE REPORTS: We present 4 cases of cytomegalovirus (CMV) viremia associated with neurological deterioration, which occurred during or shortly after radiotherapy and/or chemotherapy of the brain (brain metastases 2, high-grade glioma 1, carcinoma infiltrating brain 1). In all cases, neurological decline was sudden and unexpected, and causes such as increased intracranial pressure or tumor progression could be excluded radiologically. Treatment with dexamethasone and mannitol had no or only very short-term effects. General infections were either excluded or receding before the neurological symptoms occurred. All patients presented with decreasing levels of thrombocytes. In all cases, CMV (re)activation could be proven using blood test for CMV-DNA. The anti-CMV-IgG status suggested reactivation rather than a primary infection. One patient died within 72 h of onset of the symptoms (results of CMV tests were received postmortem). Diagnosis of 3 patients allowed successful administration of antiviral treatment, which greatly improved the general and neurological conditions of the patients within 48 h. DISCUSSION: Neurological deterioration during RT is hardly ever attributed to viral infections. These cases suggest that CMV reactivation and subsequent infection might actually be causative and has to be considered and treated. CONCLUSION: Further prospective studies verifying and investigating this observation in terms of frequency and clinical relevance seem indicated.

[Radiation dose in cerebral angiography and flat detector CT applications in neuroradiology]. / Strahlendosis bei zerebraler Angiographie und Flachdetektor-CT-Applikationen in der Neuroradiologie.

Flat detectors (FD) have completely replaced image intensifiers in angiography. Due to this development not only the image quality of 2D digital subtraction angiography series (2-D-DSA) could be improved but also the acquisition of computed tomography (CT)-like cross-sectional images (FD-CT) within the angio suite became feasible. These techniques are now being used in daily clinical routine. Only little information about effective doses of these applications to patients has been published in the literature. We describe the effective patient dose of current applications in the field of angiography and demonstrate strategies to minimize the dose to the patient. In addition, we compare FD-CT applications to standard multislice CT applications.

[Cerebrovascular complications of immunologically mediated heparin-induced thrombocytopenia]. / Zerebrovaskuläre Komplikationen der Heparininduzierten Thrombozytopenie Typ II (HIT-II).

Immunologically mediated heparin-induced thrombocytopenia (HIT) is a thrombotic disease caused by antibodies occurring after heparin exposure. Thrombocytopenia occurs within a few days after heparin exposure, about half of HIT-patients develop venous or arterial thrombotic complications. Neurological complications of HIT are mainly ischaemic stroke and sinus vein thrombosis. To ensure the primary clinical diagnosis functional and immunological assays for antibody detection are available. The probability for the occurrence of HIT depends on the nature of heparin employed (LMWH vs. UFH) and individual patient characteristics such as gender and primary disease (medical vs. surgical patients). In the case of suspected HIT heparin administration should be discontinued immediately and replaced by an alternative anticoagulation to prevent the expansion or development of further thrombotic complications. Herein we report a case of a patient suffering from HIT-associated embolic cerebral ischaemic stroke.

Brain correlates of short-term habituation to repetitive electrical noxious stimulation.

BACKGROUND: Habituation to repetitive noxious stimuli is a well-known phenomenon. We investigated brain correlates of habituation to pain in a transdermal electrical pain model using functional magnetic resonance imaging (fMRI). METHODS: Electrical painful stimulation with 1 Hz was applied to the volar forearm of 48 healthy subjects for 45 min. Before and after conditioning stimulation, psychophysical testing and fMRI were performed. During fMRI sessions, the subjects underwent blockwise painful electrical stimulation with a fixed percept-adapted current intensity. After fMRI 1 and fMRI 2 subjects rated the individual pain intensity of the electrical stimulus. RESULTS: Substantial habituation occurred during conditioning electrical stimulation. Accordingly, areas typically involved in pain processing showed decreased activity after conditioning stimulation. The blood oxygen level-dependent signal of the subgenual anterior cingulate gyrus, the superior parietal lobule and the supplemental motor area correlated positively with habituation. In contrast, activity in the periaqueductal grey, thalamus and insula correlated negatively. The results of the correlation analyses did not survive correction for multiple comparisons. CONCLUSIONS: With this study, we identified central components associated with habituation to repetitive painful stimuli. The results suggest that an increase in tonic inhibitory activity in cortical pain processing areas is a major mechanism contributing to habituation to phasic noxious stimuli. Moreover, areas involved in descending pain modulation were differentially modulated. This may hint at a simultaneous activation of facilitating and inhibiting nociceptive systems that are both altered in the transdermal electrical pain model.

[Carotid artery stenting--an update]. / Karotisstents--eine Standortbestimmung.

CLINICAL/METHODICAL ISSUE: Therapy of carotid stenosis should be based on an accurate assessment of the stenosis and a differentiation between symptomatic and asymptomatic patients. STANDARD RADIOLOGICAL METHODS: According to current guidelines carotid artery stenting (CAS) can be considered as an established therapeutic alternative to carotid endarterectomy (CEA). METHODICAL INNOVATIONS: For the therapy of carotid stenosis CAS has become established as a minimally invasive alternative to CEA because the complication rate has been reduced due to growing experience, technical innovations and external quality assessment. PERFORMANCE: The CAS procedure should be performed in centers with documented complication rates of < 3 % for asymptomatic and < 6 % for symptomatic stenoses. ACHIEVEMENTS: Overall there are no significant differences between CAS and CEA in the treatment of carotid stenosis concerning the secondary prophylactic effect. PRACTICAL RECOMMENDATIONS: Ideally an interdisciplinary approach should be chosen for the therapy regime. Revascularization of asymptomatic stenoses should be considered critically as these patients might profit from optimized conservative medicinal therapy.

Interictal magnetoencephalography used in magnetic resonance imaging-negative patients with epilepsy.

PURPOSE: This study aims to investigate the contributions of magnetoencephalography (MEG) in magnetic resonance imaging (MRI)-negative patients. METHODS: A total of 18 MRI-negative patients diagnosed with refractory epilepsy, subjected to MEG investigation, and subsequently underwent surgery were selected for retrospective analysis. A 1.5-tesla Magnetom Sonata with an eight-channel head array coil was used. MEG data were obtained using a 74/248-channel system. RESULTS: A total of 16 patients (16/18) had positive MEG results, comprising 12 patients with monofocal localizations, five with multifocal localizations, and one with unremarkable results in MEG. In addition, 12 patients had indicative single photon-emission computed tomography (SPECT), five had indicative fluorodeoxyglucose positron emission tomography (FDG-PET), and all the patients had intracranial electroencephalography (EEG) (14 with subdural electrodes and four with electrocorticography). The intracranial EEG recordings of nine patients were guided by MEG informative results. Among these 18 patients, 10 exhibited good postoperative outcomes (Engel I and II), four of which were completely seizure-free. All these ten patients had clear monofocal localization in MEG, including nine with accordant indicative metabolic changes in either SPECT or FDG-PET, or both. None of the five patients with multifocal localizations achieved good postoperative outcomes. CONCLUSION: For cases with negative MRI findings, epilepsy surgery may be an alternative option for pharmaco-resistant patients if epileptogenic focus localizations by MEG are present in multimodal evaluation.

High-resolution 3D-constructive interference in steady-state MR imaging and 3D time-of-flight MR angiography in neurovascular compression: a comparison between 3T and 1.5T.

BACKGROUND AND PURPOSE: High-resolution MR imaging is useful for diagnosis and preoperative planning in patients with NVC. Because high-field MR imaging promises higher SNR and resolution, the aim of this study was to determine the value of high-resolution 3D-CISS and 3D-TOF MRA at 3T compared with 1.5T in patients with NVC. MATERIALS AND METHODS: Forty-seven patients with NVC, trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia were examined at 1.5T and 3T, including high-resolution 3D-CISS and 3D-TOF MRA sequences. Delineation of anatomic structures, overall image quality, severity of artifacts, visibility of NVC, and assessment of the SNR and CNR were compared between field strengths. RESULTS: SNR and CNR were significantly higher at 3T (P < .001). Significantly better anatomic conspicuity, including delineation of CNs, nerve branches, and assessment of small vessels, was obtained at 3T (P < .02). Severity of artifacts was significantly lower at 3T (P < .001). Consequently, overall image quality was significantly higher at 3T. NVC was significantly better delineated at 3T (P < .001). Six patients in whom NVC was not with certainty identifiable at 1.5T were correctly diagnosed at 3T. CONCLUSIONS: Patients with NVC may benefit from the higher resolution and greater sensitivity of 3T for preoperative assessment of NVC, and 3T may be of particular value when 1.5T is equivocal.

[Integrity/demyelination of the optic radiation, morphology of the papilla, and contrast sensitivity in glaucoma patients]. / Integrität/Demyelinisierung der Radiatio optica, Morphologie der Papille und Kontrastsensitivität bei Glaukompatienten.

BACKGROUND: In primary open angle glaucoma (POAG) and its non-barotraumatic subgroup, normal tension glaucoma (NTG), the pathophysiological differences are not clear. A participation of the 4th neuron of the visual pathway (optic radiation) appears possible on the basis of related experimental studies. The goal of the present study was the evaluation of the optic radiation by diffusion tensor imaging (DTI), which is based on the magnetic resonance imaging. The diffusion and anisotropy parameters of the optic radiation as a marker of axonal integrity and demyelination/damage of glial cells, respectively, were used to investigate the relation between the morphology of the papilla (BLDF, linear discriminant function of Burk) and the contrast sensitivity (FDT, frequency doubling test). PATIENTS AND METHODS: In this prospective observational study 13 POAG patients, 13 NTG patients, and 7 control patients of the same mean age were included. For segmentation of the optic radiation a semi-automated algorithm was applied and the diffusion and anisotropy parameters were calculated. The importance of the covariates age, BLDF, and FDT for the DTI parameters was determined using partial correlation analysis. RESULTS: Analysis of the covariates partially showed a clear autocorrelation. The correlations between the DTI parameters and BLDF were significant in all groups after correction of the measurement values for the covariates. FDT correlated with DTI parameters in controls and POAG. The NTG group did not show this correlation due to a strong spreading of the FDT values. CONCLUSION: After statistical elimination of the autocorrelation of the covariates age, BLDF, and FDT the morphology of the papilla correlated with the axonal integrity and demyelination/glia cell impairment of the optic radiation in controls and glaucoma. In NTG the impaired contrast sensitivity is highly variable and is not associated with the condition of the 3rd or 4th neuron, respectively, as compared to POAG. The autocorrelation between individual covariates represents an important element for the judgement of the visual pathway.

MR imaging of neoplastic central nervous system lesions: review and recommendations for current practice.

MR imaging is the preferred technique for the diagnosis, treatment planning, and monitoring of patients with neoplastic CNS lesions. Conventional MR imaging, with gadolinium-based contrast enhancement, is increasingly combined with advanced, functional MR imaging techniques to offer morphologic, metabolic, and physiologic information. This article provides updated recommendations to neuroradiologists, neuro-oncologists, neurosurgeons, and radiation oncologists on the practical applications of MR imaging of neoplastic CNS lesions in adults, with particular focus on gliomas, based on a review of the clinical trial evidence and personal experiences shared at a recent international meeting of experts in neuroradiology, neuro-oncology, neurosurgery, and radio-oncology.

Volume-of-interest imaging of the inner ear in a human temporal bone specimen using a robot- driven C-arm flat panel detector CT system.

VOI imaging can provide higher image quality at a reduced dose for a subregion. In this study with a robot-driven C-arm FDCT system, the goals were proof of feasibility for inner ear imaging, higher flexibility during data acquisition, and easier processing during reconstruction. First a low-dose OV scan was acquired allowing an orientation and enabling the selection of the VOI. The C-arm was then moved by the robotic system without a need for patient movement and the VOI was scanned with adapted parameters. Uncompromised artifact-free image quality was achieved by the 2-scan approach and the dose was reduced by 80%-90% in comparison with conventional MSCT and FPCT scans.

[Retrospective analysis of routine-MRI and correlation with aetiology of dementia, severity and neuropsychology in a memory-clinic population]. / Retrospektive Analyse der MRT-Routinebefunde und Korrelation mit Demenzätiologie, Schweregrad und neuropsychologischen Befunden von Patienten aus einer universitären Gedächtnisambulanz.

BACKGROUND: The contribution of potential treatable dementia aetiologies diagnosed using cerebral imaging varied considerably in previous studies and was not evaluated in a recent larger German sample of patients from a memory clinic. MATERIAL AND METHODS: MRI images of 502 patients were retrospectively reassessed. Beside the proportion of potentially treatable dementia aetiology, the extent of whole brain atrophy (semiquantitative) and vascular white matter lesions were assessed. RESULTS: Mean age of the patients was 63.7 ± 13.1 years; 49 % were female, mean MMST was 24.2 ± 5.5. In 74 % there was an agreement between the clinical dementia syndrome and MRI. 9 % (45 patients) had clearly discrepant imaging results, according to MRI criteria (21 × ischaemia, 20 × normal pressure hydrocephalus (NPH), 4 × intracerebral haemorrhage). These patients could not not be differentiated using age and MMST alone as clinical criteria. There was a significant correlation between global brain atrophy and MMST (r = -0.32; p < 0.001) and white matter lesion score (r = 0.28; p < 0.001). CONCLUSION: In 9 % there was a clear discrepancy between MRI results and the clinical syndrome diagnosis in memory-clinic patients. As known from earlier studies and current German 3 rd generation guidelines, it is reasonable to perform MRI imaging in dementia to improve the aetiological and differential diagnoses and to detect a different aetiology that can be missed using the clinical dementia criteria alone.