Background
The presence of metabolically viable brain tissue that may be salvageable with rapid cerebral blood flow restoration is the fundament rationale for reperfusion therapy in patients with ...large vessel occlusion stroke. The effect of endovascular treatment (EVT) on functional outcome largely depends on the degree of recanalization. However, the relationship of recanalization degree and penumbra salvage has not yet been investigated. We hypothesized that penumbra salvage volume mediates the effect of thrombectomy on functional outcome.
Methods
99 acute anterior circulation stroke patients who received multimodal CT and underwent thrombectomy with resulting partial to complete reperfusion (modified thrombolysis in cerebral infarction scale (mTICI) ≥ 2a) were retrospectively analyzed. Penumbra volume was quantified on CT perfusion and penumbra salvage volume (PSV) was calculated as difference of penumbra and net infarct growth from admission to follow-up imaging.
Results
In patients with complete reperfusion (mTICI ≥ 2c), the median PSV was significantly higher than the median PSV in patients with partial or incomplete (mTICI 2a–2b) reperfusion (median 224 mL, IQR: 168–303 versus 158 mL, IQR: 129–225;
p
< 0.01). A higher degree of recanalization was associated with increased PSV (+ 63 mL per grade, 95% CI: 17–110;
p
< 0.01). Higher PSV was also associated with improved functional outcome (OR/mRS shift: 0.89; 95% CI: 0.85–0.95,
p
< 0.0001).
Conclusions
PSV may be an important mediator between functional outcome and recanalization degree in EVT patients and could serve as a more accurate instrument to compare treatment effects than infarct volumes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The link between metabolic syndrome (MetS) and neurodegenerative as well as cerebrovascular conditions holds substantial implications for brain health in at-risk populations. This study elucidates ...the complex relationship between MetS and brain health by conducting a comprehensive examination of cardiometabolic risk factors, brain morphology, and cognitive function in 40,087 individuals. Multivariate, data-driven statistics identified a latent dimension linking more severe MetS to widespread brain morphological abnormalities, accounting for up to 71% of shared variance in the data. This dimension was replicable across sub-samples. In a mediation analysis, we could demonstrate that MetS-related brain morphological abnormalities mediated the link between MetS severity and cognitive performance in multiple domains. Employing imaging transcriptomics and connectomics, our results also suggest that MetS-related morphological abnormalities are linked to the regional cellular composition and macroscopic brain network organization. By leveraging extensive, multi-domain data combined with a dimensional stratification approach, our analysis provides profound insights into the association of MetS and brain health. These findings can inform effective therapeutic and risk mitigation strategies aimed at maintaining brain integrity.
Imbalance between positive and negative outcomes, a so-called class imbalance, is a problem generally found in medical data. Imbalanced data hinder the performance of conventional classification ...methods which aim to improve the overall accuracy of the model without accounting for uneven distribution of the classes. To rectify this, the data can be resampled by oversampling the positive (minority) class until the classes are approximately equally represented. After that, a prediction model such as gradient boosting algorithm can be fitted with greater confidence. This classification method allows for non-linear relationships and deep interactive effects while focusing on difficult areas by iterative shifting towards problematic observations. In this study, we demonstrate application of these methods to medical data and develop a practical framework for evaluation of features contributing into the probability of stroke.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Computed-tomography perfusion (CTP) is frequently used to screen acute ischemic stroke (AIS) patients for endovascular treatment (EVT), despite known problems with ischemic "core" overestimation. ...This potentially leads to the unfair exclusion of patients from EVT. We propose that net water uptake (NWU) can be used in addition to CTP to more accurately assess the extent and/or stage of tissue infarction. Patients treated for AIS between 06/2015 and 07/2020 were retrospectively analyzed. Baseline CTP-derived core volume (pCore) and NWU were determined. Logistic regression tested the relationship between baseline clinical and imaging variables and core-overestimation (primary outcome). The secondary outcomes comprised 90-day functional independence (modified Rankin score) and lesion growth. 284 patients were included. Median NWU was 7.2% (IQR 2.6-12.8). ASPECTS (RR 1.28, 95% CI 1.09-1.51), NWU (RR 0.94, 95% CI 0.89-0.98), onset to recanalization (RR 1.00, 95% CI 0.99-1.00) and imaging (RR 1.00, 95% CI 1.00-1.00) times, and pCore (RR 1.02, 95% CI 1.01-1.02) were significantly associated with core overestimation. Core-overestimation was more likely to occur in patients with large pCores and low NWU at baseline. NWU was significantly correlated with lesion growth. We conclude that NWU can be used as a supplemental tool to CTP during admission imaging to more accurately assess the extent of ischemia, particularly relevant for patients with large CTP-defined cores who would otherwise be excluded from treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
RATIONALE:Blood–brain–barrier (BBB) breakdown and cerebral edema result from postischemic inflammation and contribute to mortality and morbidity after ischemic stroke. A functional role for the ...carcinoembryonic antigen–related cell adhesion molecule 1 (CEACAM1) in the regulation of reperfusion injury has not yet been demonstrated.
OBJECTIVE:We sought to identify and characterize the relevance of CEACAM1-expressing inflammatory cells in BBB breakdown and outcome after ischemic stroke in Ceacam1 and wild-type mice.
METHODS AND RESULTS:Focal ischemia was induced by temporary occlusion of the middle cerebral artery with a microfilament. Using MRI and Evans blue permeability assays, we observed increased stroke volumes, BBB breakdown and edema formation, reduction of cerebral perfusion, and brain atrophy in Ceacam1 mice. This translated into poor performance in neurological scoring and high poststroke-associated mortality. Elevated neutrophil influx, hyperproduction, and release of neutrophil-related matrix metalloproteinase-9 in Ceacam1 mice were confirmed by immune fluorescence, flow cytometry, zymography, and stimulation of neutrophils. Importantly, neutralization of matrix metalloproteinase-9 activity in Ceacam1 mice was sufficient to alleviate stroke sizes and improve survival to the level of CEACAM1-competent animals. Immune histochemistry of murine and human poststroke autoptic brains congruently identified abundance of CEACAM1matrix metalloproteinase-9 neutrophils in the ischemic hemispheres.
CONCLUSIONS:CEACAM1 controls matrix metalloproteinase-9 secretion by neutrophils in postischemic inflammation at the BBB after stroke. We propose CEACAM1 as an important inhibitory regulator of neutrophil-mediated tissue damage and BBB breakdown in focal cerebral ischemia.
Purpose
Evaluating the extent of cerebral ischemic infarction is essential for treatment decisions and assessment of possible complications in patients with acute ischemic stroke. Patients are often ...triaged according to image-based early signs of infarction, defined by Alberta Stroke Program Early CT Score (ASPECTS). Our aim was to evaluate interrater reliability in a large group of readers.
Methods
We retrospectively analyzed 100 investigators who independently evaluated 20 non-contrast computed tomography (NCCT) scans as part of their qualification program for the TENSION study. Test cases were chosen by four neuroradiologists who had previously scored NCCT scans with ASPECTS between 0 and 8 and high interrater agreement. Percent and interrater agreements were calculated for total ASPECTS, as well as for each ASPECTS region.
Results
Percent agreements for ASPECTS ratings was 28%, with interrater agreement of 0.13 (95% confidence interval, CI 0.09–0.16), at zero tolerance allowance and 66%, with interrater agreement of 0.32 (95% CI: 0.21–0.44), at tolerance allowance set by TENSION inclusion criteria. ASPECTS region with highest level of agreement was the insular cortex (percent agreement = 96%, interrater agreement = 0.96 (95% CI: 0.94–0.97)) and with lowest level of agreement the M3 region (percent agreement = 68%, interrater agreement = 0.39 95% CI: 0.17–0.61).
Conclusion
Interrater agreement reliability for total ASPECTS and study enrollment was relatively low but seems sufficient for practical application. Individual region analysis suggests that some are particularly difficult to evaluate, with varying levels of reliability. Potential impairment of the supraganglionic region must be examined carefully, particularly with respect to the decision whether or not to perform mechanical thrombectomy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Determining the optimal transportation for each stroke patient is critically important to achieve the best possible outcomes. In border regions the next comprehensive stroke center may be just across ...an international border, but bureaucratic and financial hurdles may prevent a simple transfer to the next stroke center. We hypothesized that in regions close to international borders, patients may benefit from an "open border, closed transfer scenario", meaning that patients in whom a large vessel occlusion (LVO) is detected in the primary stroke center will benefit from a transfer to the nearest stroke center offering endovascular thrombectomy-even if this may be across a national border. We used the Swiss-German-French trinational region as an example for a region with several international borders within close proximity to one another, and compared two feasible scenarios; (a) a "closed borders, open transfer" scenario, where the patient is transported to any center in the same country, (b) an "open border, closed transfer" scenario, where patients are always transported to the nearby primary stroke center first and then to the nearest comprehensive stroke center in either the same or a neighboring country and (c) and "open borders, open transfer" scenario. The outcome of interest was the predicted probability of acute ischemic stroke patients to achieve a good outcome using a conditional probability model which predicts the likelihood of excellent outcome (modified Rankin scale score of 0-1 at 90 days post-stroke) for patients with suspected LVO. Results were modeled in a virtual map from which the ideal transport concept emerged. For an exemplary LVO stroke patient in Germany, the probability of a good outcome was higher in an open border, closed transfer scenario than with closed borders, open transfer (33.1 vs. 30.1%). Moreover, time to EVT would decrease from 232 min in the first scenario to 169 min in an open border, closed transfer scenario. The catchment area of the University Hospital Basel was almost double the size in an open border, closed transfer scenario compared to closed borders (1674 km
vs. 2897 km
) and would receive transfers from 3 primary stroke centers in other countries (2 in Germany and 1 in France). Stroke patients showed a higher likelihood of good outcome in the "open border" scenarios without transfer restrictions to a specific healthcare system. This probably has implications for stroke treatment in all border regions where EVT eligible stroke patients may benefit from transport to the closest EVT capable center whenever possible, regardless of whether this hospital is located in the same or a neighboring country/jurisdiction.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Cerebral small vessel disease (CSVD) is a widespread condition associated to stroke, dementia and depression. To shed light on its opaque pathophysiology, we conducted a neuroimaging study aiming to ...assess the location of CSVD-induced damage in the human brain network. Structural connectomes of 930 subjects of the Hamburg City Health Study were reconstructed from diffusion weighted imaging. The connectome edges were partitioned into groups according to specific schemes: (1) connection to grey matter regions, (2) course and length of underlying streamlines. Peak-width of skeletonised mean diffusivity (PSMD) - a surrogate marker for CSVD - was related to each edge group's connectivity in a linear regression analysis allowing localisation of CSVD-induced effects. PSMD was associated with statistically significant decreases in connectivity of most investigated edge groups except those involved in connecting limbic, insular, temporal or cerebellar regions. Connectivity of interhemispheric and long intrahemispheric edges as well as edges connecting subcortical and frontal brain regions decreased most severely with increasing PSMD. In conclusion, MRI findings of CSVD are associated with widespread impairment of structural brain network connectivity, which supports the understanding of CSVD as a global brain disease. The pattern of regional preference might provide a link to clinical phenotypes of CSVD.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The aim of this study was to investigate if ischemic stroke final infarction volume and location can be used to predict the associated functional outcome using a multi-class support vector machine ...(SVM).
Sixty-eight follow-up MR FLAIR datasets of ischemic stroke patients with known modified Rankin Scale (mRS) functional outcome after 30 days were used. The infarct regions were segmented and used to calculate the percentage of lesioned voxels in the predefined MNI, Harvard-Oxford cortical and subcortical atlas regions as well as using four problem-specific VOIs, which were identified from the database using voxel-based lesion symptom mapping. An overall of 12 SVM classification models for predicting the corresponding mRS score were generated using the lesion overlap values from the different brain region definitions, stroke laterality information, and the optional parameters infarct volume, admission NIHSS, and patient age.
Leave-one-out cross validations revealed that including information about the stroke location in terms of lesion overlap measurements led to improved mRS prediction results compared to classification models not utilizing the stroke location information. Furthermore, integration of the optional features led to improved mRS prediction results in all cases tested. The problem-specific brain regions and additional integration of the optional features led to the best mRS predictions with a precise multi-value mRS prediction accuracy of 56%, sliding window multi-value mRS prediction accuracy (mRS±1) of 82%, and binary mRS (0-2 vs. 3-5) prediction accuracy of 85%.
Therefore, a graded SVM-based functional stroke outcome prediction using the problem-specific brain regions for lesion overlap quantification leads to promising results but needs to be further validated using an independent database to rule out a potential methodical bias and overfitting effects. The prediction of the graded mRS functional outcome could be a valuable tool if combined with voxel-wise tissue outcome predictions based on multi-parametric datasets acquired at the acute phase.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PurposeThe increased demand for training of mechanical thrombectomy in ischemic stroke and development of new recanalization devices urges the creation of new simulation models both for training and ...device assessment. Clots properties have shown to play a role in procedural planning and thrombectomy device effectiveness. In this study, we analyzed the characteristics and applicability of completely synthetic, animal-free clots in the setting of an in-vitro model of mechanical thrombectomy for training and device assessment.MethodsSynthetic clots based on agarose (n = 12) and silicone (n = 11) were evaluated in an in-vitro neurointervention simulation of mechanical thrombectomy with clot extraction devices. Calcified clots of mixed nature were simulated with addition of 3D printed structures. 9 clots were excluded due to insufficient vessel occlusion and failure to integrate with clot extraction device. Synthetic thrombi were characterized and compared using a categorical score-system on vessel occlusion, elasticity, fragmentation, adherence and device integration.ResultsBoth agarose-based and silicone-based clots demonstrated relevant flow arrest and a good integration with the clot extraction device. Silicone-based clots scored higher on adherence to the vessel wall and elasticity.ConclusionSelected synthetic clots can successfully be implemented in an in-vitro training environment of mechanical thrombectomy. The clots' different properties might serve to mimic fibrin-rich and red blood cell-rich human thrombi.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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