Woven EndoBridge (WEB) shape modification (WSM) is a frequently observed phenomenon after aneurysm embolization.
To test our hypothesis that WSM is associated with worse aneurysm occlusion on ...short-term angiographic follow-up images.
Patients with short-term follow-up digital subtraction angiography (DSA) available were included. Baseline patient characteristics, aneurysm morphometrics, and WEB dimensions ("conventional" parameters) and height and width WSM ("WSM" parameters) in the initial and the follow-up examination were analyzed. For ordinal regression analyses, aneurysm occlusion was graded according to the Bicêtre Occlusion Scale Score (BOSS; grades 0, 0', 1, 2, 3, and 1 + 3). Receiver operating characteristic curve analysis was used to distinguish adequately (BOSS 0, 0', and 1) from incompletely (BOSS 2, 3, and 1 + 3) occluded aneurysms.
We included 93 patients with 96 aneurysms. Adequate occlusion was observed in 72 cases (75.0%). In univariate ordinal regression analysis, width WSM in anteroposterior DSA (odds ratio = 0.96, 95% CI: 0.94-0.99, P = .010) and in lateral DSA (odds ratio = 0.98, 95% CI: 0.97-0.99, P = .049) were significantly associated with the BOSS after 6 months. In multivariate regression analysis, WSM was not independently associated with aneurysm occlusion. Based on receiver operating characteristic curve analysis, the area under the curve (AUC) of the "conventional" model (AUC = 0.83, 95% CI 0.74-0.90) was higher than the AUC of the "WSM" model (WSM; AUC = 0.70, 95% CI 0.60-0.79).
WSM was not independently associated with angiographic aneurysm occlusion status after 6 months. However, the "conventional" parameters including sex, rupture state, WEB type, WEB width, aneurysm width, height, and volume were associated with partial aneurysm recanalization in WEB-treated patients at the short-term follow-up.
Endovascular treatment is a highly effective therapy for acute ischemic stroke due to large vessel occlusion and has recently revolutionized stroke care. Oftentimes, ischemic core extent on baseline ...imaging is used to determine endovascular treatment-eligibility. There are, however, 3 fundamental issues with the core conceptFirst, computed tomography and magnetic resonance imaging, which are mostly used in the acute stroke setting, are not able to precisely determine whether and to what extent brain tissue is infarcted (core) or still viable, due to variability in tissue vulnerability, the phenomenon of selective neuronal loss and lack of a reliable gold standard. Second, treatment decision-making in acute stroke is multifactorial, and as such, the relative importance of single variables, including imaging factors, is reduced. Third, there are often discrepancies between core volume and clinical outcome. This review will address the uncertainty in terminology and proposes a direction towards more clarity. This theoretical exercise needs empirical data that clarify the definitions further and prove its value.
Metastatic seeding is driven by cell-intrinsic and environmental cues, yet the contribution of biomechanics is poorly known. We aim to elucidate the impact of blood flow on the arrest and the ...extravasation of circulating tumor cells (CTCs) in vivo. Using the zebrafish embryo, we show that arrest of CTCs occurs in vessels with favorable flow profiles where flow forces control the adhesion efficacy of CTCs to the endothelium. We biophysically identified the threshold values of flow and adhesion forces allowing successful arrest of CTCs. In addition, flow forces fine-tune tumor cell extravasation by impairing the remodeling properties of the endothelium. Importantly, we also observe endothelial remodeling at arrest sites of CTCs in mouse brain capillaries. Finally, we observed that human supratentorial brain metastases preferably develop in areas with low perfusion. These results demonstrate that hemodynamic profiles at metastatic sites regulate key steps of extravasation preceding metastatic outgrowth.
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•Arrest of circulating tumor cells occurs in blood vessels with permissive flow profiles•pN-range adhesion forces favor rapid and stable intravascular adhesion•Flow-mediated endothelial remodeling drives extravasation of tumor cells
Follain et al. demonstrate that blood flow forces tune both the arrest and extravasation of circulating tumor cells in vivo. Permissive flow forces allow stable intravascular arrest of circulating tumor cells. Flow forces drive endothelial remodeling around arrested tumor cells, favoring extravasation preceding metastatic outgrowth.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BACKGROUND AND PURPOSE—In acute ischemic stroke, mechanical thrombectomy allows flow restoration in the majority of cases. In case of an unsuccessful retrieval, little is known about how many ...retrieval attempts should be performed before stopping the procedure. This study assessed the recanalization rate and clinical outcome per retrieval maneuver.
METHODS—In this analysis, 330 patients with acute large vessel occlusion treated exclusively with stentrieval devices were included. Successful recanalization was defined as Thrombolysis in Cerebral Infarction 2b-3, a good clinical outcome was defined as modified Rankin Scale at 90 days of ≤2.
RESULTS—The median number of retrieval attempts was 1 (interquartile range, 1–2, maximum 8). Recanalization rates per retrieval attempt were highest for the first retrieval (46.8%) and lowest for the fifth retrieval (22.7%). After 3 retrieval attempts, 67.9% of patients were successfully recanalized. Patients with 1 to 3 retrieval attempts had higher rates of good clinical outcome (28.9% versus 7.4%; P=0.018). The number of passes was an independent negative predictor of good clinical outcome (adjusted odds ratio, 0.65; 95% CI, 0.435–0.970; P=0.035).
CONCLUSIONS—Two-thirds of occlusions were successfully recanalized with up to 3 retrieval attempts. Further attempts had good recanalization rates, but the rate of favorable clinical outcome did not improve.
The fast and accurate assessment of cerebral perfusion is fundamental for the diagnosis and successful treatment of stroke patients. Magnetic particle imaging (MPI) is a new radiation-free ...tomographic imaging method with a superior temporal resolution, compared to other conventional imaging methods. In addition, MPI scanners can be built as prehospital mobile devices, which require less complex infrastructure than computed tomography (CT) and magnetic resonance imaging (MRI). With these advantages, MPI could accelerate the stroke diagnosis and treatment, thereby improving outcomes. Our objective was to investigate the capabilities of MPI to detect perfusion deficits in a murine model of ischemic stroke. Cerebral ischemia was induced by inserting of a microfilament in the internal carotid artery in C57BL/6 mice, thereby blocking the blood flow into the medial cerebral artery. After the injection of a contrast agent (superparamagnetic iron oxide nanoparticles) specifically tailored for MPI, cerebral perfusion and vascular anatomy were assessed by the MPI scanner within seconds. To validate and compare our MPI data, we performed perfusion imaging with a small animal MRI scanner. MPI detected the perfusion deficits in the ischemic brain, which were comparable to those with MRI but in real-time. For the first time, we showed that MPI could be used as a diagnostic tool for relevant diseases in vivo, such as an ischemic stroke. Due to its shorter image acquisition times and increased temporal resolution compared to that of MRI or CT, we expect that MPI offers the potential to improve stroke imaging and treatment.
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IJS, KILJ, NUK, PNG, UL, UM
Following acute ischemic stroke, isolated subcortical lesions induce gray matter atrophy in anatomically connected, yet distant cortical brain regions. We expand on previous studies by analyzing ...cortical thinning in contralesional, homologous regions indirectly linked to primary stroke lesions via ipsilesional cortical areas. For this purpose, stroke patients were serially studied by magnetic resonance imaging (diffusion tensor imaging and high-resolution anatomical imaging) in the acute (days 3–5) and late chronic stage one year after stroke. We analyzed changes of gray and white matter integrity in 18 stroke patients (median age 68 years) with subcortical stroke. We applied probabilistic fiber tractography to identify brain regions connected to stroke lesions and contralesional homologous areas. Cortical thickness was quantified by semi-automatic measurements, and fractional anisotropy was analyzed. One year after stroke, significant decrease of cortical thickness was detected in areas connected to ischemic lesions (mean −0.15 mm; 95% CI −0.23 to −0.07 mm) as well as homologous contralateral brain regions (mean −0.13 mm; 95% CI −0.07 to −0.19 mm). We detected reduced white matter integrity of inter- and intrahemispheric fiber tracts. There were no significant associations with clinical recovery. Our results indicate that impact of subcortical lesions extends to homologous brain areas via transcallosal diaschisis.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Cerebral small vessel disease (CSVD) is a common cause of morbidity and cognitive decline in the elderly population. However, characterizing the disease pathophysiology and its association with ...potential clinical sequelae in early stages is less well explored. We applied fixel-based analysis (FBA), a novel framework of investigating microstructural white matter integrity by diffusion-weighted imaging, to data of 921 participants of the Hamburg City Health Study, comprising middle-aged individuals with increased cerebrovascular risk in early stages of CSVD. In individuals in the highest quartile of white matter hyperintensity loads (n = 232, median age 63 years; IQR 15.3 years), FBA detected significantly reduced axonal density and increased atrophy of transcallosal fiber tracts, the bilateral superior longitudinal fasciculus, and corticospinal tracts compared to participants in the lowest quartile of white matter hyperintensities (n = 228, mean age 55 years; IQR 10 years). Analysis of all participants (N = 921) demonstrated a significant association between reduced fiber density and worse executive functions operationalized by the Trail Making Test. Findings were confirmed by complementary analysis of diffusion tensor metrics.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Net water uptake (NWU) is a quantitative imaging biomarker used to assess cerebral edema resulting from ischemia via Computed Tomography (CT)-densitometry. It serves as a strong predictor of clinical ...outcome. Nevertheless, NWU measurements on follow-up CT scans after mechanical thrombectomy (MT) can be affected by contrast staining. To improve the accuracy of edema estimation, virtual non-contrast images (VNC-I) from dual-energy CT scans (DECT) were compared to conventional polychromatic CT images (CP-I) in this study. We examined NWU measurements derived from VNC-I and CP-I to assess their agreement and predictive value in clinical outcome. 88 consecutive patients who received DECT as follow-up after MT were included. NWU was quantified on CP-I (cNWU) and VNC-I (vNWU). The clinical endpoint was functional independence at discharge. cNWU and vNWU were highly correlated (r = 0.71, p < 0.0001). The median difference between cNWU and vNWU was 8.7% (IQR: 4.5-14.1%), associated with successful vessel recanalization (mTICI2b-3) (ß: 11.6%, 95% CI 2.9-23.0%, p = 0.04), and age (ß: 4.2%, 95% CI 1.3-7.0%, p = 0.005). The diagnostic accuracy to classify outcome between cNWU and vNWU was similar (AUC:0.78 versus 0.77). Although there was an 8.7% median difference, indicating potential edema underestimation on CP-I, it did not have short-term clinical implications.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Atypical brain connectivity is a major contributor to the pathophysiology of neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASDs). TAOK2 is one of several genes in the ...16p11.2 microdeletion region, but whether it contributes to NDDs is unknown. We performed behavioral analysis on Taok2 heterozygous (Het) and knockout (KO) mice and found gene dosage-dependent impairments in cognition, anxiety, and social interaction. Taok2 Het and KO mice also have dosage-dependent abnormalities in brain size and neural connectivity in multiple regions, deficits in cortical layering, dendrite and synapse formation, and reduced excitatory neurotransmission. Whole-genome and -exome sequencing of ASD families identified three de novo mutations in TAOK2 and functional analysis in mice and human cells revealed that all the mutations impair protein stability, but they differentially impact kinase activity, dendrite growth, and spine/synapse development. Mechanistically, loss of Taok2 activity causes a reduction in RhoA activation, and pharmacological enhancement of RhoA activity rescues synaptic phenotypes. Together, these data provide evidence that TAOK2 is a neurodevelopmental disorder risk gene and identify RhoA signaling as a mediator of TAOK2-dependent synaptic development.
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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
Thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke aims to restore compromised blood flow and prevent further neuronal damage. Despite the proven clinical efficacy of ...this treatment, little is known about the short-term effects of systemic thrombolysis on structural brain connectivity. In this secondary analysis of the WAKE-UP trial, we used MRI-derived measures of infarct size and estimated structural network disruption to establish that thrombolysis is associated not only with less infarct growth, but also with reduced loss of large-scale connectivity between grey-matter areas after stroke. In a causal mediation analysis, infarct growth mediated a non-significant 8.3% (CI
-8.0, 32.6%) of the clinical effect of thrombolysis on functional outcome. The proportion mediated jointly through infarct growth and change of structural connectivity, especially in the border zone around the infarct core, however, was as high as 33.4% (CI
8.8, 77.4%). Preservation of structural connectivity is thus an important determinant of treatment success and favourable functional outcome in addition to lesion volume. It might, in the future, serve as an imaging endpoint in clinical trials or as a target for therapeutic interventions.
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