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•Circle of Willis (CoW) artery diameters are larger in men compared to women.•CoW anatomical variants differ between men and women.•CoW bifurcation angles are comparable between men and women. Anatomical variations in the circle of Willis (CoW) arteries are common and can affect hemodynamic stress, thereby influencing the risk of cerebrovascular pathology. Previous studies have suggested sex differences in CoW anatomy, but findings vary due to limited study population size and different measurement methods. This study aims to investigate sex differences in artery diameters, anatomical variants and bifurcation angles of the CoW using a large population cohort and semi-automatic measurements. Sex-specific CoW anatomical variations were assessed using Magnetic Resonance Angiography (MRA) scans of 1,052 individuals without intracranial vascular abnormalities. Diameters and bifurcation angles of large CoW arteries (>1.2 mm) were measured with a semi-automatic tool. Diameters of smaller anterior communicating artery (Acom) and posterior communicating arteries (Pcoms) and the anatomical variants of the CoW were determined manually. Generalized Linear Models (GLMs) and logistic regression models with adjustments for covariates were used to compare anatomical variations between sexes. Men exhibited larger diameters in all semi-automatically measured CoW arteries. A complete anterior CoW was more prevalent in men than women, while there was no difference for the posterior CoW. Aplasia/hypoplasia of the Acom was more prevalent in women. Aplasia/hypoplasia of one Pcom was more common in women, while aplasia/hypoplasia of both Pcoms was more common in men. No sex differences were found in CoW bifurcation angles and in the occurrence of fetal-type posterior cerebral arteries. This study identified significant CoW differences in artery diameters and anatomical variants between sexes, while bifurcation angles between arteries were comparable. Future research should investigate the association between these sex-specific CoW variations and cerebrovascular pathology. [Display omitted]

ObjectivesRecently, hippocampal calcification as observed on brain CT examinations was identified in over 20% of people over 50 years of age and a relation between hippocampal calcification and cognitive decline was shown. We determined the prevalence and investigated the vascular risk factors of hippocampal calcification in patients with cerebrovascular disease.MethodsHippocampal calcification was scored bilaterally on presence and severity on CT examinations in a cohort of 1130 patients with (suspected) acute ischaemic stroke. Multivariable logistic regression analysis, adjusting for age and gender as well as adjusting for multiple cardiovascular disease risk factors, was used to determine risk factors for hippocampal calcification.ResultsHippocampal calcification was present in 381 (34%) patients. Prevalence increased with age from 8% below 40 to 45% at 80 years and older. In multivariable logistic regression analysis, age per decile (OR 1.41 [95% CI 1.26–1.57], p < 0.01), hypertension (OR 0.74 [95% CI 0.56–0.99], p = 0.049), diabetes mellitus (OR 1.57 [95% CI 1.10–2.25], p = 0.01) and hyperlipidaemia (OR 1.63 [95% CI 1.20–2.22], p < 0.01) were significantly associated with hippocampal calcification.ConclusionsHippocampal calcification was a frequent finding on CT in this cohort of stroke patients and was independently positively associated with hyperlipidaemia and diabetes mellitus, suggesting an atherosclerotic origin.Key Points• Hippocampal calcification is prevalent in over 30% of cerebrovascular disease patients.• Prevalence increases from 8% below 40 to 45% over 80 years.• Hippocampal calcification is associated with cardiovascular risk factors hyperlipidaemia and diabetes mellitus.

We related composition of cerebral thrombi to stroke subtype and attenuation on non-contrast CT (NCCT) to gain more insight in etiopathogenesis and to validate thrombus attenuation as a new imaging biomarker for acute stroke. We histopathologically investigated 22 thrombi retrieved after mechanical thrombectomy in acute stroke patients. First, thrombi were classified as fresh, lytic or organized. Second, percentages of red blood cells (RBCs), platelets and fibrin and number of red, white (respectively RBCs or platelets outnumbering other components with ≥ 15%) or mixed thrombi were compared between large artery atherosclerosis (LAA), cardioembolism, dissection and unknown subtype. Third, correlation between attenuation and RBCs, platelets and fibrin was calculated using Pearson's correlation coefficients (r). Thrombi were fresh in 73% (n = 16), lytic in 18% (n = 4) and organized in 9% (n = 2). The stroke cause was LAA in eight (36%), cardioembolism in six (27%), dissection in three (14%), and unknown in five (23%) patients. LAA thrombi showed the highest percentage RBCs (median 50 (range 35-90)), followed by dissection (35 (20-40), p = 0.05), cardioembolism (35 (5-45), p = 0.013) and unknown subtype (25 (2-40), p = 0.006). No differences in platelets (p = 0.16) and fibrin (p = 0.52) between subtypes were found. LAA thrombi were classified as red or mixed (both n = 4), cardioembolisms as mixed (n = 5) or white (n = 1) and dissection as mixed (n = 3). There was a moderate positive correlation between attenuation and RBCs (r = 0.401, p = 0.049), and weak negative correlations with platelets (r = -0.368, p = 0.09) and fibrin (r = -0.073, p = 0.75). The majority of cerebral thrombi is fresh. There are no differences in age of thrombi between subtypes. LAA thrombi have highest percentages RBCs, cardioembolism and unknown subtype lowest. No relationship exists between subtype and platelets or fibrin percentages. We found a correlation between the RBC-component and thrombus attenuation, which improves validation of thrombus attenuation on NCCT as an imaging biomarker for stroke management.

Objectives To investigate whether iterative reconstruction (IR) in cerebral CT perfusion (CTP) allows for 50 % dose reduction while maintaining image quality (IQ). Methods A total of 48 CTP examinations were reconstructed into a standard dose (150 mAs) with filtered back projection (FBP) and half-dose (75 mAs) with two strengths of IR (middle and high). Objective IQ (quantitative perfusion values, contrast-to-noise ratio (CNR), penumbra, infarct area and penumbra/infarct (P/I) index) and subjective IQ (diagnostic IQ on a four-point Likert scale and overall IQ binomial) were compared among the reconstructions. Results Half-dose CTP with high IR level had, compared with standard dose with FBP, similar objective (grey matter cerebral blood volume (CBV) 4.4 versus 4.3 mL/100 g, CNR 1.59 versus 1.64 and P/I index 0.74 versus 0.73, respectively) and subjective diagnostic IQ (mean Likert scale 1.42 versus 1.49, respectively). The overall IQ in half-dose with high IR level was scored lower in 26–31 %. Half-dose with FBP and with the middle IR level were inferior to standard dose with FBP. Conclusion With the use of IR in CTP imaging it is possible to examine patients with a half dose without significantly altering the objective and diagnostic IQ. The standard dose with FBP is still preferable in terms of subjective overall IQ in about one quarter of patients. Key points • Computed tomography perfusion (CTP) is increasingly important in ischaemia imaging. • Radiation exposure of CTP is a drawback. • Iterative reconstruction (IR) allows reduction of radiation dose in unenhanced head CT. • CTP IR enables 50 % dose reduction without altering objective and diagnostic quality.

Delayed cerebral ischemia (DCI) is at presentation a diagnosis per exclusionem, and can only be confirmed with follow-up imaging. For treatment of DCI a diagnostic tool is needed. We performed a systematic review to evaluate the value of CT perfusion (CTP) in the prediction and diagnosis of DCI. We searched PubMed, Embase, and Cochrane databases to identify studies on the relationship between CTP and DCI. Eleven studies totaling 570 patients were included. On admission, cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time-to-peak (TTP) did not differ between patients who did and did not develop DCI. In the DCI time-window (4 to 14 days after subarachnoid hemorrhage (SAH)), DCI was associated with a decreased CBF (pooled mean difference −11.9 mL/100 g per minute (95% confidence interval (CI): −15.2 to −8.6)) and an increased MTT (pooled mean difference 1.5 seconds (0.9–2.2)). Cerebral blood volume did not differ and TTP was rarely reported. Perfusion thresholds reported in studies were comparable, although the corresponding test characteristics were moderate and differed between studies. We conclude that CTP can be used in the diagnosis but not in the prediction of DCI. A need exists to standardize the method for measuring perfusion with CTP after SAH, and optimize and validate perfusion thresholds.

The circle of Willis (CoW) is a circular arrangement of arteries in the human brain, exhibiting significant anatomical variability. The CoW is extensively studied in relation to neurovascular pathologies, with certain anatomical variants previously linked to ischemic stroke and intracranial aneurysms. In an individual CoW, arteries might be absent (aplasia) or underdeveloped (hypoplasia, diameter < 1 mm). As the assessment of such variations is time-consuming and susceptible to subjectivity, robust automatic extraction of personalized CoW topology from time-of-flight magnetic resonance angiography (TOF-MRA) images would highly benefit large-scale clinical investigations. Previous work has sought to extract CoW topology from voxel-based semantic segmentation masks. However, hypoplastic arteries are challenging to recover in voxel-based segmentation. Instead, we propose using a complete CoW as an anatomical prior for extracting all possible CoW arteries as shortest paths between automatically identified anatomical landmarks, guided by automatically determined artery orientation vector fields. These fields are obtained using a scale-invariant and rotation-equivariant mesh-CNN-based model (SIRE). For a 3D TOF-MRA volume, a potentially overcomplete graph of the CoW is thus extracted in which each edge represents an artery. Subsequently, a binary Random Forest classifier labels each artery as normal or hypo-/aplastic. The model was optimized and validated using a data set of 351 3D TOF-MRA scans in a cross-validation setup. We showed that using a shortest path algorithm with a cost function based on local artery orientations results in continuous artery paths, even in hypoplastic cases. We tracked the correct path in the posterior communicating arteries in 70–74% of the cases, an artery that is known to pose challenges in voxel-based segmentation models. Our downstream artery path classifier obtained an average F1 score of 0.91, demonstrating the potential of our proposed framework to extract personalized CoW topology automatically.

Introduction Vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is thought to cause ischemia. To evaluate the contribution of vasospasm to delayed cerebral ischemia (DCI), we investigated the effect of vasospasm on cerebral perfusion and the relationship of vasospasm with DCI. Methods We studied 37 consecutive SAH patients with CT angiography (CTA) and CT perfusion (CTP) on admission and within 14 days after admission or at time of clinical deterioration. CTP values (cerebral blood volume, cerebral blood flow (CBF) and mean transit time), degree of vasospasm on CTA, and occurrence of DCI were recorded. Vasospasm was categorized as follows: no spasm (0–25% decrease in vessel diameter), moderate spasm (25–50% decrease), and severe spasm (>50% decrease). The correspondence of the flow territory of the most spastic vessel with the least perfused region was evaluated, and differences in perfusion values and occurrence of DCI between degrees of vasospasm were calculated with 95% confidence intervals (95% CI). Results Fourteen patients had no vasospasm, 16 were moderate, and seven were severe. In 65% of patients with spasm, the flow territory of the most spastic vessel corresponded with the least perfused region. There was significant CBF (milliliters per 100 g per minute) difference (−21.3; 95% CI, −37 ↔ −5.3) between flow territories of severe and no vasospasm. Four of seven patients with severe, six of 16 with moderate, and three of 14 patients with no vasospasm had DCI. Conclusion Vasospasm decreases cerebral perfusion, but corresponds with the least perfused region in only two thirds of our patients. Furthermore, almost half of patients with severe vasospasm do not have DCI. Thus, although severe vasospasm can decrease perfusion, it may not result in DCI.

The effect of anesthetic management (general anesthesia [GA], conscious sedation, or local anesthesia) on functional outcome and the role of blood pressure management during endovascular treatment (EVT) for acute ischemic stroke is under debate. We aimed to determine whether hypotension during EVT under GA is associated with functional outcome at 90 days. We retrospectively collected data from patients with a proximal intracranial occlusion of the anterior circulation treated with EVT under GA. The primary outcome was the distribution on the modified Rankin Scale at 90 days. Hypotension was defined using two thresholds: a mean arterial pressure (MAP) of 70 mm Hg and a MAP 30% below baseline MAP. To quantify the extent and duration of hypotension, the area under the threshold (AUT) was calculated using both thresholds. Of the 366 patients included, procedural hypotension was observed in approximately half of them. The occurrence of hypotension was associated with poor functional outcome (MAP <70 mm Hg: adjusted common odds ratio [acOR], 0.57; 95% confidence interval [CI], 0.35-0.94; MAP decrease [greater than or equal to]30%: acOR, 0.76; 95% CI, 0.48-1.21). In addition, an association was found between the number of hypotensive periods and poor functional outcome (MAP <70 mm Hg: acOR, 0.85 per period increase; 95% CI, 0.73-0.99; MAP decrease [greater than or equal to]30%: acOR, 0.90 per period; 95% CI, 0.78-1.04). No association existed between AUT and functional outcome (MAP <70 mm Hg: acOR, 1.000 per 10 mm Hg*min increase; 95% CI, 0.998-1.001; MAP decrease [greater than or equal to]30%: acOR, 1.000 per 10 mm Hg*min; 95% CI, 0.999-1.000). Occurrence of procedural hypotension and an increase in number of procedural hypotensive periods were associated with poor functional outcome, whereas the extent and duration of hypotension were not. Randomized clinical trials are needed to confirm our hypothesis that hypotension during EVT under GA has detrimental effects.

Intracranial aneurysms more often occur in the same arterial territory within families. Several aneurysm locations are associated with specific circle of Willis variations. We investigated whether the same circle of Willis variations are more likely to occur in first-degree relatives than in unrelated individuals. We assessed four circle of Willis variations (classical, A1-asymmetry, incomplete posterior communicating artery and fetal circulation) in two independent groups of families with familial aneurysms and ≥2 first-degree relatives with circle of Willis imaging on MRA/CTA. In each (index) family we determined the proportion of first-degree relatives with the same circle of Willis variation as the proband and compared it to the proportion of first-degree relatives of a randomly selected unrelated (comparison) family who had the same circle of Willis variation as the index family's proband. Concordance in index families and comparison families was compared with a conditional logistic events/trials model. The analysis was simulated 1001 times; we report the median concordances, odds ratios (ORs), and 95% confidence intervals (95%CI). The groups were analysed separately and together by meta-analysis. We found a higher overall concordance in circle of Willis configuration in index families than in comparison families (meta-analysis, 244 families: OR 2.2, 95%CI 1.6-3.0) mostly attributable to a higher concordance in incomplete posterior communicating artery (meta-analysis: OR 2.8, 95%CI 1.8-4.3). No association was found for the other three circle of Willis variations. In two independent groups of families with familial aneurysms, the incomplete PcomA variation occurred more often within than between families suggesting heritability of this circle of Willis variation. Further studies should investigate genetic variants associated with circle of Willis formation.

Good reliability of methods to assess the extent of ischemia in acute stroke is important for implementation in clinical practice, especially between observers with varying experience. Our aim was to determine inter- and intra-observer reliability of the 1/3 middle cerebral artery (MCA) rule and the Alberta Stroke Program Early CT Score (ASPECTS) for different CT modalities in patients suspected of acute ischemic stroke. We prospectively included 105 patients with acute neurological deficit due to suspected acute ischemic stroke within 9 hours after symptom onset. All patients underwent non-contrast CT, CT perfusion and CT angiography on admission. All images were evaluated twice for presence of ischemia, ischemia with >1/3 MCA involvement, and ASPECTS. Four observers evaluated twenty scans twice for intra-observer agreement. We used kappa statistics and intraclass correlation coefficient to calculate agreement. Inter-observer agreement for the 1/3 MCA rule and ASPECTS was fair to good for non-contrast CT, poor to good for CT angiography source images, but excellent for all CT perfusion maps (cerebral blood volume, mean transit time, and predicted penumbra and infarct maps). Intra-observer agreement for the 1/3 MCA rule and ASPECTS was poor to good for non-contrast CT, fair to moderate for CT angiography source images, and good to excellent for all CT perfusion maps. Between observers with a different level of experience, agreement on the radiological diagnosis of cerebral ischemia is much better for CT perfusion than for non-contrast CT and CT angiography source images, and therefore CT perfusion is a very reliable addition to standard stroke imaging.