Early detection and integrated care for adolescents and young adults with severe psychotic disorders: rationales and design of the Integrated Care in Early Psychosis Study (ACCESS III).

AIM: The Integrated Care in Early Psychosis (ACCESS III) Study examined the efficacy and cost-effectiveness of a combined intervention consisting of strategies to improve early detection and quality of care (integrated care including therapeutic assertive community treatment) in adolescents and young adults in the early phase of a severe psychotic disorder from 2011 to 2014. METHODS: This is a prospective, single-centre, 1-year cohort study comparing an intervention condition (early detection plus integrated care, n = 120) to the historical control condition (standard care, SC, n = 105) for adolescents and young adults aged 12-29 years suffering from a severe, early-phase psychotic disorder (i.e. within 2 years of treatment). RESULTS: Primary outcome is the rate of combined symptomatic (i.e. Positive and Negative Syndrome Scale (PANSS) criteria) and functional (i.e. Global Assessment of Functioning scale (GAF) ≥ 60 points criterion) remission over at least 6 months at study endpoint. Secondary outcome comprises the comparison of the reduction in the duration of untreated psychosis within the 4-year study duration between integrated care and SC, course of psychopathology, functioning, quality of life, satisfaction with care, cost and quality-adjusted life years (QALYs) in comparison to a historical control group. CONCLUSION: To the authors' knowledge, this is the first study assessing the efficacy and cost-effectiveness of a combined intervention consisting of early detection strategies and strategies to improve quality of care in both adolescents and young adults with early-phase psychosis. The results will be published in 2016.

Influence of different reconstruction parameters in the visualization of intracranial stents using C-arm flat panel CT angiography: experience in an animal model.

BACKGROUND: C-arm flat panel computed tomography angiography (CA-CTA) is a relatively new imaging modality. Consequently, knowledge about postprocessing parameters and their influence on image quality is still limited, especially for the visualization of implanted microstents. PURPOSE: To optimize reconstruction parameters by evaluating the influence of these different parameters for CA-CTA visualization of microstents in an animal model. MATERIAL AND METHODS: Eleven microstents were implanted within the left common carotid artery of 11 New Zealand white rabbits. Both CA-CTA, using intra-venous delivery of contrast material, and conventional digital subtraction angiography (DSA) was performed. CA-CTA datasets were reconstructed using three different image characteristics (normal, sharp, smooth). Two experienced neuroradiologists evaluated the image quality and performed measurements of inner and outer stent diameters as well as measurements of the lumen area. RESULTS: Stent deployment was performed successfully in all animals. Inter-observer correlation coefficient for all measurements was high (r = 0.87-0.92). Lumen area and inner stent diameter were significantly smaller in image characteristic "smooth" (P < 0.01) than in "sharp" and "normal". Outer stent diameter was larger in "smooth" than in "sharp" and "normal" (P < 0.01). Stent strut size was significantly wider using image characteristic "smooth". "Sharp" and "normal" compared best to DSA, with "sharp" providing the closest match to DSA measurements, with the trade-off of significantly more noise than in the "normal" reconstructions. CONCLUSION: The use of different image characteristics in the postprocessing of CA-CTA datasets has an influence on the visualization of implanted stents. Image characteristic "sharp" and "normal" compared best to DSA.

[Early Detection and Integrated Care in Adolescents and Young Adults with Severe Psychotic Illnesses]. / Früherkennung und integrierte Versorgung von Jugendlichen und jungen Erwachsenen mit schweren psychotischen Erkrankungen.

This is a prospective 1-year follow-up study comparing a combined intervention consisting of multidimensional early detection strategies with age- and interdisciplinary integrated care (intervention group, n = 120) with standard care (historical control group, n = 105) in adolescents and young adults within the early phase of psychosis. Data at study entry indicate a high complexity and severity of illness. Primary outcome is the 6-month rate of combined symptomatic and functional remission at study endpoint.

Flat-detector computed tomography evaluation in an experimental animal aneurysm model after endovascular treatment: A pilot study.

We compared flat-detector computed tomography angiography (FD-CTA) to multislice computed tomography (MS-CTA) and digital subtracted angiography (DSA) for the visualization of experimental aneurysms treated with stents, coils or a combination of both.In 20 rabbits, aneurysms were created using the rabbit elastase aneurysm model. Seven aneurysms were treated with coils, seven with coils and stents, and six with self-expandable stents alone. Imaging was performed by DSA, MS-CTA and FD-CTA immediately after treatment. Multiplanar reconstruction (MPR) was performed and two experienced reviewers compared aneurysm/coil package size, aneurysm occlusion, stent diameters and artifacts for each modality.In aneurysms treated with stents alone, the visualization of the aneurysms was identical in all three imaging modalities. Residual aneurysm perfusion was present in two cases and visible in DSA and FD-CTA but not in MS-CTA. The diameter of coil-packages was overestimated in MS-CT by 56% and only by 16% in FD-CTA compared to DSA (p < 0.05). The diameter of stents was identical for DSA and FD-CTA and was significantly overestimated in MS-CTA (p < 0.05). Beam/metal hardening artifacts impaired image quality more severely in MS-CTA compared to FD-CTA.MS-CTA is impaired by blooming and beam/metal hardening artifacts in the visualization of implanted devices. There was no significant difference between measurements made with noninvasive FD-CTA compared to gold standard of DSA after stenting and after coiling/stent-assisted coiling of aneurysms. FD-CTA may be considered as a non-invasive alternative to the gold standard 2D DSA in selected patients that require follow up imaging after stenting.

Flat detector computed tomography angiography with intravenous contrast application: feasibility for visualization of cerebral arterial vasculature.

BACKGROUND AND PURPOSE: The aim of our study was to evaluate flat detector computed tomography angiography with peripheral intravenous contrast material application (FD-CTA) for visualization of cerebral arteries in comparison with intravenous multidetector computed tomography angiography (CTA) and intraarterial digital subtraction angiography (DSA). METHODS: The study was approved by the local institutional review board and informed consent was obtained by all participants. Ten patients underwent FD-CTA, CTA, and DSA of the cerebral arterial vasculature for suspected cerebrovascular disease. The image data were evaluated by two readers in consensus for the visualization of cerebral arterial segments on a 5-point scale (0 = vessel cannot be distinguished; 4 = excellent image quality). The Wilcoxon signed-rank test was used for statistical analysis. Note that P < .05 was considered to indicate a significant difference. RESULTS: The depiction of cerebral arterial segments with FD-CTA was significantly superior compared to CTA in most vessel segments (P < .05 in 20 of 23 anatomic regions) and was without significant difference compared with DSA in large and medium intracranial vessels. CONCLUSIONS: The results suggest that the cerebral arteries can be visualized by FD-CTA in high resolution, in many vessel segments comparable to DSA.

Measurement of quantifiable parameters by time-density curves in the elastase-induced aneurysm model: first results in the comparison of a flow diverter and a conventional aneurysm stent.

BACKGROUND: Quantifiable parameters to evaluate the effectiveness of flow diverters (FDs) are desirable. We measured time-density curves (TDCs) and calculated quantifiable parameters in the rabbit elastase-induced aneurysm model after stent (Neuroform [NF]) and FD (Pipeline embolisation device [PED]) treatment. METHODS: Sixteen rabbit elastase-induced aneurysms were treated with FD (n = 9) or NF (n = 5). Angiography was performed before and after treatment and TDCs were created. The time to peak (TTP), the full width at half maximum (FWHM) and the average slope of the curve which represent the inflow (IF) and outflow (OF) were calculated. RESULTS: Mean values before treatment were TTP = 0.8 s, FWHM = 1.2 s, IF = 153.5 and OF = -54.9. After PED treatment, the TTP of 1.8 s and FWHM of 47.8 s were extended. The IF was 31.2 and the OF was -11.5 and therefore delayed. The values after NF treatment (TTP = 1.1 s, FWHM = 1.8 s, IF = 152.9, OF = -33.2) changed only slightly. CONCLUSION: It was feasible to create TDCs in the rabbit aneurysm model. Parameters describing the haemodynamic effect of PED and NF were calculated and were different according to the type of device used. These parameters could possibly serve as predictive markers for aneurysm occlusion.

Angiographic CT with intravenous contrast agent application for monitoring of intracranial flow diverting stents.

INTRODUCTION: Intracranial flow diverting devices are increasingly used to treat cerebral aneurysms. A reliable, non-invasive follow-up modality would be desirable. Our aim was to compare intra-arterial digital subtraction angiography (ia DSA) to angiographic computed tomography with intravenous contrast agent application (iv ACT) in the visualisation of flow diverting devices and aneurysm lumina. METHODS: Follow-up monitoring by iv ACT (n = 36) and ia DSA (n = 25) in 14 patients treated with flow diverting devices for intracranial aneurysms was evaluated retrospectively. Images were evaluated by two neuroradiologists in anonymous consensus reading regarding the device deployment, wall apposition, neck coverage of the aneurysm, opacification of the vessel and device lumen, as well as the degree of aneurysm occlusion. RESULTS: Corresponding ia DSA and iv ACT images were scored identically in all patients regarding the stent deployment, wall apposition and neck coverage, as well as the degree of aneurysm occlusion and patency status of the device and parent artery. Opacification of the parent vessel lumen and perfused parts of the aneurysm was considered slightly inferior for iv ACT in comparison with ia DSA (seven of 36 cases), without impact on diagnosis. CONCLUSIONS: We demonstrated the feasibility and diagnostic value of iv ACT in follow-up imaging of intracranial flow diverting devices. Due to its high spatial resolution and non-invasive character, this novel technique might become a valuable imaging modality in these patients.

Intravenous flat detector CT angiography for non-invasive visualisation of intracranial flow diverter: technical feasibility.

OBJECTIVE: To demonstrate the feasibility of intravenous Flat Detector CT Angiography (FD-CTA) for visualisation of intracranial Flow Diverting Devices. Flow Diverting Devices are used increasingly for treatment of intracranial aneurysms. A close follow up is necessary because it becomes obvious that a significant proportion of aneurysms treated with these devices remain patent. A minimally invasive method is highly desirable. METHODS: In two patients treated with flow diverters a Flat Detector CT (FD-CT) with intravenous contrast medium application was performed. Post-processing was performed using commercially available software. RESULTS: In both patients the lumen of the device and the lumen of the aneurysm could be clearly evaluated. Some beam hardening artefacts due to the marker wires of the device were obvious. CONCLUSION: Flat Detector CT with intravenous contrast material application to evaluate flow-diverting devices seems to be feasible. Further studies are necessary to perform comparative evaluation of FD-CTA with angiography and other techniques like MRA or conventional CT angiography.

Flat-detector computed tomography in the assessment of intracranial stents: comparison with multi detector CT and conventional angiography in a new animal model.

OBJECTIVE: Careful follow up is necessary after intracranial stenting because in-stent restenosis (ISR) or residual stenosis (RS) is not rare. A minimally invasive follow-up imaging technique is desirable. The objective was to compare the visualisation of stents in Flat Detector-CT Angiography (FD-CTA) after intravenous contrast medium injection (i.v.) with Multi Detector Computed Tomography Angiography (MD-CTA) and Digital Subtracted Angiography (DSA) in an animal model. METHODS: Stents were implanted in the carotid artery of 12 rabbits. In 6 a residual stenosis (RS) was surgically created. Imaging was performed using FD-CTA, MD-CTA and DSA. Measurements of the inner and outer diameter and cross-section area of the stents were performed. Stenosis grade was calculated. RESULTS: In subjective evaluation FD-CTA was superior to MD-CTA. FD-CTA was more accurate compared with DSA than MD-CTA. Cross-sectional area of the stent lumen was significantly larger (p < 0.05) in FD-CTA in comparison to MD-CTA. Accurate evaluation of stenosis was impossible in MD-CTA. There was no statistically significant difference in the stenosis grade of DSA and FD-CTA. CONCLUSION: Our results show that visualisation of stent and stenosis using intravenous FD-CTA compares favourably with DSA and may replace DSA in the follow-up of patients treated with intracranial stents.

Optimized intravenous Flat Detector CT for non-invasive visualization of intracranial stents: first results.

OBJECTIVE: As stents for treating intracranial atherosclerotic stenosis may develop in-stent re-stenosis (ISR) in up to 30%, follow-up imaging is mandatory. Residual stenosis (RS) is not rare. We evaluated an optimised Flat Detector CT protocol with intravenous contrast material application (i.v. FD-CTA) for non-invasive follow-up. METHODS: In 12 patients with intracranial stents, follow-up imaging was performed using i.v. FD-CTA. MPR, subtracted MIP and VRT reconstructions were used to correlate to intra-arterial angiography (DSA). Two neuroradiologists evaluated the images in anonymous consensus reading and calculated the ISR or RS. Correlation coefficients and a Wilcoxon test were used for statistical analysis. RESULTS: In 4 patients, no stenosis was detected. In 6 patients RS and in two cases ISR by intima hyperplasia perfectly visible on MPR reconstructions of i.v. FD-CTA were detected. Wilcoxon's test showed no significant differences between the methods (p > 0.05). We found a high correlation with coefficients of the pairs DSA/ FD-CT MIP r = 0.91, DSA/ FD-CT MPR r = 0.82 and FD-CT MIP/ FD-CT MPR r = 0.8. CONCLUSION: Intravenous FD-CTA could clearly visualise the stent and the lumen, allowing ISR or RS to be recognised. FD-CTA provides a non-invasive depiction of intracranial stents and might replace DSA for non-invasive follow-up imaging.

Pre-aggregated Aß1-42 peptide increases tau aggregation and hyperphosphorylation after short-term application.

Neuritic amyloid plaques and neurofibrillary tangles, consisting of hyperphosphorylated tau protein, are the hallmarks of Alzheimer disease. It is not clear so far, how both structures are functionally and physiologically connected. We have investigated the role of Aß1-42 on hyperphosphorylation and aggregation of tau in SY5Y cells by transfection and overexpression with two tau constructs, a shortened wildtype tau (2N4R) and a point mutation tau (P301L), found in fronto-temporal dementia. It was found that the tau protein becomes hyperphosphorylated and forms large aggregates inside cells, visualized by immunofluorescence, after short incubation of 90 min with preaggregated Aß1-42. In Addition, Aß1-42 caused a decrease of tau solubility in both tau constructs in this relatively short time period. Taken together, these experiments suggest that pathological preaggregated Aß1-42 in physiological concentrations quickly induces hyperphosphorylation and pathological structural changes of tau protein and thereby directly linking the 'amyloid hypothesis' to tau pathology, observed in Alzheimer disease.

Embolic cerebral insults after transapical aortic valve implantation detected by magnetic resonance imaging.

OBJECTIVES: This study assessed the rate of periprocedural embolic ischemic brain injury during transapical aortic valve replacement in 25 consecutive patients. BACKGROUND: Transcatheter aortic valve implantation is rapidly being established as a new therapeutic approach for aortic valve stenosis. Although initial clinical results are promising, it is unknown whether mobilization and embolization of calcified particles may lead to cerebral ischemia. METHODS: Twenty-five consecutive patients (10 men, 15 women, mean age: 81 ± 5 years, mean log EuroSCORE [European System for Cardiac Operative Risk Evaluation]: 32 ± 10%) scheduled for transapical aortic valve implantation were included. All patients received a baseline cerebral magnetic resonance imaging scan. The scan was repeated approximately 6 days after valve implantation. The magnetic resonance imaging studies included axial diffusion-weighted, T(2)-weighted, fluid attenuated inversion recovery-weighted, and T(2) gradient echo sequences. Standardized assessment of the neurologic status was performed before aortic valve replacement and post-operatively. RESULTS: Transapical aortic valve implantation was successfully performed in all patients. In 17 patients (68%), new cerebral lesions could be detected, whereas 8 patients showed no new cerebral insults. The pattern of distribution and morphology were typical of embolic origin. Despite the high incidence of morphologically detectable lesions, only 5 patients showed clinical neurologic alterations. Out of these patients, only 1 suffered from a permanent stroke. CONCLUSIONS: New embolic ischemic cerebral insults are detected in 68% of patients after transapical valve implantation. Clinical symptoms are rare and usually transitory. Larger trials will need to establish the clinical significance of asymptomatic ischemic lesions as well as the rate of ischemic events in patients undergoing transfemoral valve replacement.

Flat-detector computed tomography with intravenous contrast material application in experimental aneurysms: comparison with multislice CT and conventional angiography.

BACKGROUND: Despite limited soft tissue resolution flat-detector computed tomography (FD-CT) provides substantial superior spatial resolution in comparison with multislice computed tomography (MS-CT). This may add value in the visualization of small vascular structures if intravenous contrast application leads to substantial opacification and visibility of intracranial vessels or aneurysms. PURPOSE: To evaluate the feasibility of visualization of vascular structures by FD-CT angiography (FD-CTA) after intravenous contrast injection compared with MS-CTA and intra-arterial digital subtracted angiography (IADSA) in an animal model. MATERIAL AND METHODS: Aneurysms were created in the right common carotid artery in six New Zealand White Rabbits using the elastase technique. Imaging was performed using FD-CTA, MS-CTA (injection of 1 ml/kg body weight) and IADSA. Anonymized volume rendering reconstruction (VRT), maximum intensity projection (MIP), and multiplanar reconstruction (MPR) images were reconstructed and evaluated by two experienced reviewers for aneurysm geometry and vascular structure anatomy using standard tools of a dedicated workstation. RESULTS: Aneurysms could be successfully created in all animals. Measurements of aneurysm geometry (aneurysm height, width, neck width) and vascular structures (brachiocephalic trunk, carotid artery diameter and plane) were nearly identical in all three modalities. Intra- and inter-observer correlations of the different parameters showed high r values between 0.83 and 0.99. CONCLUSION: Our results show the feasibility of FD-CTA in comparison with MS-CTA and IADSA in an animal model. Despite limited soft tissue resolution, opacification of vascular structures with sufficient contrast to the surrounding structures was possible in all animals. Vascular structures appeared better delineated in FD-CTA than in MS-CTA, probably due to the superior spatial resolution.