Automated grading of cerebral vasospasm to standardize computed tomography angiography examinations after subarachnoid hemorrhage

Background: Computed tomography angiography (CTA) is frequently used with computed tomography perfusion imaging (CTP) to evaluate whether endovascular vasospasm treatment is indicated for subarachnoid hemorrhage patients with delayed cerebral ischemia. However, objective parameters for CTA evaluation are lacking. In this study, we used an automated, investigator-independent, digital method to detect vasospasm, and we evaluated whether the method could predict the need for subsequent endovascular vasospasm treatment.Methods: We retrospectively reviewed the charts and analyzed imaging data for 40 consecutive patients with subarachnoid hemorrhages. The cerebrovascular trees were digitally reconstructed from CTA data, and vessel volume and the length of the arteries of the circle of Willis and their peripheral branches were determined. Receiver operating characteristic curve analysis based on a comparison with digital subtraction angiographies was used to determine volumetric thresholds that indicated severe vasospasm for each vessel segment. Results: The automated threshold-based volumetric evaluation of CTA data was able to detect severe vasospasm with high sensitivity and negative predictive value for predicting cerebral hypoperfusion on CTP, although the specificity and positive predictive value were low. Combining the automated detection of vasospasm on CTA and cerebral hypoperfusion on CTP was superior to CTP or CTA alone in predicting endovascular vasospasm treatment within 24 h after the examination. Conclusions: This digital volumetric analysis of the cerebrovascular tree allowed the objective, investigator-independent detection and quantification of vasospasms. This method could be used to standardize diagnostics and the selection of subarachnoid hemorrhage patients with delayed cerebral ischemia for endovascular diagnostics and possible interventions

Neutrophils mediate early cerebral cortical hypoperfusion in a murine model of subarachnoid haemorrhage

Cerebral hypoperfusion in the first hours after subarachnoid haemorrhage (SAH) is a major determinant of poor neurological outcome. However, the underlying pathophysiology is only partly understood. Here we induced neutropenia in C57BL/6N mice by anti-Ly6G antibody injection, induced SAH by endovascular filament perforation, and analysed cerebral cortical perfusion with laser SPECKLE contrast imaging to investigate the role of neutrophils in mediating cerebral hypoperfusion during the first 24 h post-SAH. SAH induction significantly increased the intracranial pressure (ICP), and significantly reduced the cerebral perfusion pressure (CPP). At 3 h after SAH, ICP had returned to baseline and CPP was similar between SAH and sham mice. However, in SAH mice with normal neutrophil counts cortical hypoperfusion persisted. Conversely, despite similar CPP, cortical perfusion was significantly higher at 3 h after SAH in mice with neutropenia. The levels of 8-iso-prostaglandin-F2α in the subarachnoid haematoma increased significantly at 3 h after SAH in animals with normal neutrophil counts indicating oxidative stress, which was not the case in neutropenic SAH animals. These results suggest that neutrophils are important mediators of cortical hypoperfusion and oxidative stress early after SAH. Targeting neutrophil function and neutrophil-induced oxidative stress could be a promising new approach to mitigate cerebral hypoperfusion early after SAH

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Die Ausdauerleistungsfähigkeit als Prädiktor der kognitiven Leistung: Ergebnisse der SMART-Studie.

Schwarz S, Fleckenstein J, Engeroff T, et al. Die Ausdauerleistungsfähigkeit als Prädiktor der kognitiven Leistung: Ergebnisse der SMART-Studie. Deutsche Zeitschrift für Sportmedizin. 2015;66:174-219

Improved Detection of Circulating Tumor Cells in Metastatic Colorectal Cancer by the Combination of the CellSearch® System and the AdnaTest®.

Colorectal cancer (CRC) is one of the major causes of cancer-related death and reliable blood-based prognostic biomarkers are urgently needed. The enumeration and molecular characterization of circulating tumor cells (CTCs) has gained increasing interest in clinical practice. CTC detection by CellSearch® has already been correlated to an unfavorable outcome in metastatic CRC. However, the CTC detection rate in mCRC disease is low compared to other tumor entities. Thus, the use of alternative (or supplementary) assays might help to itemize the prognostic use of CTCs as blood-based biomarkers. In this study, blood samples from 47 mCRC patients were screened for CTCs using the FDA-cleared CellSearch® technology and / or the AdnaTest®. 38 samples could be processed in parallel. We demonstrate that a combined analysis of CellSearch® and the AdnaTest® leads to an improved detection of CTCs in our mCRC patient cohort (positivity rate CellSearch® 33%, AdnaTest® 30%, combined 50%). While CTCs detected with the CellSearch® system were significantly associated with progression-free survival (p = 0.046), a significant correlation regarding overall survival could be only seen when both assays were combined (p = 0.013). These findings could help to establish improved tools to detect CTCs as on-treatment biomarkers for clinical routine in future studies

Lifespan Physical Activity Profile, Cognitive Function And Brain Metabolism In Old Age

Engeroff T, Vogt L, Fleckenstein J, et al. Lifespan Physical Activity Profile, Cognitive Function And Brain Metabolism In Old Age. Presented at the 64th Annual Meeting of the American College of Sports Medicine, Denver, USA

A segmentation-based volumetric approach to localize and quantify cerebral vasospasm based on tomographic imaging data

Introduction Quantification of cerebral vasospasm after subarachnoid hemorrhage (SAH) is crucial in animal studies as well as clinical routine. We have developed a method for computer-based volumetric assessment of intracranial blood vessels from cross-sectional imaging data. Here we demonstrate the quantification of vasospasm from micro computed tomography (micro-CT) data in a rodent SAH model and the transferability of the volumetric approach to clinical data. Methods We obtained rodent data by performing an ex vivo micro-CT of murine brains after sham surgery or SAH by endovascular filament perforation on day 3 post hemorrhage. Clinical CT angiography (CTA) was performed for diagnostic reasons unrelated to this study. We digitally reconstructed and segmented intracranial vascular trees, followed by calculating volumes of defined vessel segments by standardized protocols using Amira® software. Results SAH animals demonstrated significantly smaller vessel diameters compared with sham (MCA: 134.4±26.9μm vs.165.0±18.7μm, p<0.05). We could highlight this difference by analyzing vessel volumes of a defined MCA-ICA segment (SAH: 0.044±0.017μl vs. sham: 0.07±0.006μl, p<0.001). Analysis of clinical CTA data allowed us to detect and volumetrically quantify vasospasm in a series of 5 SAH patients. Vessel diameters from digital reconstructions correlated well with those measured microscopically (rodent data, correlation coefficient 0.8, p<0.001), or angiographically (clinical data, 0.9, p<0.001). Conclusions Our methodological approach provides accurate anatomical reconstructions of intracranial vessels from cross-sectional imaging data. It allows volumetric assessment of entire vessel segments, hereby highlighting vasospasm-induced changes objectively in a murine SAH model. This method could also be a helpful tool for analysis of clinical CTA