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1.
Ann Neurol ; 85(5): 752-764, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30840312

RESUMO

OBJECTIVE: To investigate whether hemodynamic features of symptomatic intracranial atherosclerotic stenosis (sICAS) might correlate with the risk of stroke relapse, using a computational fluid dynamics (CFD) model. METHODS: In a cohort study, we recruited patients with acute ischemic stroke attributed to 50 to 99% ICAS confirmed by computed tomographic angiography (CTA). With CTA-based CFD models, translesional pressure ratio (PR = pressurepoststenotic /pressureprestenotic ) and translesional wall shear stress ratio (WSSR = WSSstenotic - throat /WSSprestenotic ) were obtained in each sICAS lesion. Translesional PR ≤ median was defined as low PR and WSSR ≥4th quartile as high WSSR. All patients received standard medical treatment. The primary outcome was recurrent ischemic stroke in the same territory (SIT) within 1 year. RESULTS: Overall, 245 patients (median age = 61 years, 63.7% males) were analyzed. Median translesional PR was 0.94 (interquartile range [IQR] = 0.87-0.97); median translesional WSSR was 13.3 (IQR = 7.0-26.7). SIT occurred in 20 (8.2%) patients, mostly with multiple infarcts in the border zone and/or cortical regions. In multivariate Cox regression, low PR (adjusted hazard ratio [HR] = 3.16, p = 0.026) and high WSSR (adjusted HR = 3.05, p = 0.014) were independently associated with SIT. Patients with both low PR and high WSSR had significantly higher risk of SIT than those with normal PR and WSSR (risk = 17.5% vs 3.0%, adjusted HR = 7.52, p = 0.004). INTERPRETATION: This work represents a step forward in utilizing computational flow simulation techniques in studying intracranial atherosclerotic disease. It reveals a hemodynamic pattern of sICAS that is more prone to stroke relapse, and supports hypoperfusion and artery-to-artery embolism as common mechanisms of ischemic stroke in such patients. Ann Neurol 2019;85:752-764.

2.
J Neurol Neurosurg Psychiatry ; 90(4): 428-435, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30554138

RESUMO

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs), which predict future intracerebral haemorrhage (ICH), may guide anticoagulant decisions for atrial fibrillation (AF). We aimed to evaluate the risk of warfarin-associated ICH in Chinese patients with AF with CMBs. METHODS: In this prospective, observational, multicentre study, we recruited Chinese patients with AF who were on or intended to start anticoagulation with warfarin from six hospitals in Hong Kong. CMBs were evaluated with 3T MRI brain at baseline. Primary outcome was clinical ICH at 2-year follow-up. Secondary outcomes were ischaemic stroke, systemic embolism, mortality of all causes and modified Rankin Scale ≥3. Outcome events were compared between patients with and without CMBs. RESULTS: A total of 290 patients were recruited; 53 patients were excluded by predefined criteria. Among the 237 patients included in the final analysis, CMBs were observed in 84 (35.4%) patients, and 11 had ≥5 CMBs. The mean follow-up period was 22.4±10.3 months. Compared with patients without CMBs, patients with CMBs had numerically higher rate of ICH (3.6% vs 0.7%, p=0.129). The rate of ICH was lower than ischaemic stroke for patients with 0 to 4 CMBs, but higher for those with ≥5 CMBs. CMB count (C-index 0.82) was more sensitive than HAS-BLED (C-index 0.55) and CHA2DS2-VASc (C-index 0.63) scores in predicting ICH. CONCLUSIONS: In Chinese patients with AF on warfarin, presence of multiple CMBs may be associated with higher rate of ICH than ischaemic stroke. Larger studies through international collaboration are needed to determine the risk:benefit ratio of oral anticoagulants in patients with AF of different ethnic origins.

3.
J Stroke Cerebrovasc Dis ; 27(1): 44-52, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29107636

RESUMO

BACKGROUND: Computational fluid dynamics (CFD) allows noninvasive fractional flow (FF) computation in intracranial arterial stenosis. Removal of small artery branches is necessary in CFD simulation. The consequent effects on FF value needs to be judged. METHODS: An idealized vascular model was built with 70% focal luminal stenosis. A branch with one third or one half of the radius of the parent vessel was added at a distance of 5, 10, 15 and 20 mm to the lesion. With pressure and flow rate applied as inlet and outlet boundary conditions, CFD simulations were performed. Flow distribution at bifurcations followed Murray's law. By including or removing side branches, five patient-specific intracranial artery models were simulated. Transient simulation was performed on a patient-specific model, with a larger branch for validation. Branching effect was considered trivial if the FF difference between paired models (branches included or removed) was within 5%. RESULTS: Compared with the control model without a branch, in all idealized models the relative differences of FF was within 2%. In five pairs of cerebral arteries (branches included/removed), FFs were 0.876 and 0.877, 0.853 and 0.858, 0.874 and 0.869, 0.865 and 0.858, 0.952 and 0.948. The relative difference in each pair was less than 1%. In transient model, the relative difference of FF was 3.5%. CONCLUSION: The impact of removing side branches with radius less than 50% of the parent vessel on FF measurement accuracy is negligible in static CFD simulations, and minor in transient CFD simulation.


Assuntos
Artérias Cerebrais/fisiopatologia , Circulação Cerebrovascular , Doenças Arteriais Intracranianas/fisiopatologia , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Velocidade do Fluxo Sanguíneo , Angiografia Cerebral/métodos , Artérias Cerebrais/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Constrição Patológica , Humanos , Hidrodinâmica , Doenças Arteriais Intracranianas/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador , Fluxo Sanguíneo Regional
4.
J Neuroimaging ; 26(3): 331-8, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26598796

RESUMO

OBJECTIVE: Success in clinical trials of intracranial atherosclerosis (ICAS) is related to accurate identification of high-risk patients. Noninvasive computational fluid dynamics (CFD) of stenotic lesions may enhance therapeutic decision-making. We determined whether physiologic parameters change downstream cerebral hemodynamics in patients with ICAS. METHODS: Consecutive ICAS patients who underwent both CT angiography (CTA) and digital subtraction angiography were enrolled. CFD models were made using CTA source images. Inlet boundary conditions were defined using three ranges of systolic blood pressure (BP) (109.2, 158, and 225 mmHg) and hematocrit (27.3, 40.2, and 48.8). Ratios of pressure, shear strain rates (SSR), and flow velocity across the lesion were calculated using CFD simulations. A linear mixed model was used for the statistical analysis of repeated simulations. RESULTS: Among the 56 patients, 32 had moderate stenosis (50-69%) and 24 had severe stenosis (70-99%). A linear mixed model revealed that the ratio of pressure was predicted by systolic BP and stenosis group interaction (P = .036). These pressure decreases were associated with systolic BP (P < .001) and stenosis group (P < .001), but not with hematocrit (P = .337). Post-hoc analysis revealed that pressure decreases were more profound in the severe stenosis than the moderate stenosis group when comparing high and low systolic BP (P = .0108). Ratios of SSR and velocity were only associated in the stenosis group. CONCLUSIONS: Our study showed that systolic BP along with the degree of stenosis was associated with pressure decreases across stenotic lesions. Physiologic conditions may superimpose further changes in post-stenotic or downstream blood flow.


Assuntos
Pressão Sanguínea/fisiologia , Simulação por Computador , Hematócrito , Hemodinâmica/fisiologia , Hidrodinâmica , Arteriosclerose Intracraniana/fisiopatologia , Software , Idoso , Idoso de 80 Anos ou mais , Angiografia Digital , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/fisiopatologia
5.
Interv Neurol ; 2(3): 105-17, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-25187786

RESUMO

Recent advances in ischemic stroke enable a seamless transition of the patient flow from the prehospital setting to definitive reperfusion, without the arbitrary separation of therapeutic phases of ischemia based on time alone. In 2013, the framework to understand and directly address the pathophysiology of cerebral blood flow that determines the timeline or evolution of ischemia in an individual case is given. This continuum of flow and the homeostasis of brain perfusion balanced by collaterals may be captured with serial imaging. Ongoing imaging core laboratory activities permit large-scale measurement of angiographic and tissue biomarkers of ischemia. Prehospital neuroprotection has become a reality and may be combined with revascularization therapies. Recent studies confirm that image-guided thrombolysis may be achieved without restrictive time windows. Baseline imaging patterns may be used to predict response to therapy and serial imaging may discern recanalization and reperfusion. Advanced techniques, such as arterial spin-labeled MRI, may also report hyperperfusion associated with hemorrhagic transformation. Endovascular therapies, including novel stent retriever devices, may augment revascularization and angiographic core laboratories may define optimal reperfusion. Serial evaluation of collaterals and reperfusion may identify definitive reperfusion linked with good clinical outcome rather than imposing arbitrary definitions of effective recanalization. Reperfusion injury and hemorrhagic transformation of various types may be detailed to explain clinical outcomes. Similar approaches may be used in intracranial atherosclerosis where flow, and not the degree of luminal stenosis, is paramount. Fractional flow may now be measured with computational fluid dynamics to identify high-risk lesions that require revascularization to restore the equilibrium of antegrade and collateral perfusion. Serial perfusion imaging of such cases may also illustrate inadequate cerebral blood volume gradients that may be more informative than blood flow delay alone. In sum, the growing understanding of collateral perfusion throughout all stages of ischemic stroke provides a framework for the future of ischemic stroke.

6.
PLoS One ; 9(5): e97531, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24818753

RESUMO

BACKGROUND: Patients with symptomatic intracranial atherosclerosis (ICAS) of ≥ 70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset. METHODS: Patients with a symptomatic ICAS lesion of 70-99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year. RESULTS: Overall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (-2.46-0.79), 4.5 (2.2-20.6), and 7.4 (5.2-12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004-1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002-1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594-0.903; P = 0.014) and 0.776 (95% CI, 0.594-0.903; P = 0.002) in receiver operating characteristic analysis. CONCLUSIONS: Hemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70-99% luminal stenosis.


Assuntos
Simulação por Computador , Hidrodinâmica , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/fisiopatologia , Acidente Vascular Cerebral/complicações , Idoso , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Recidiva , Estudos Retrospectivos , Medição de Risco
7.
J Stroke Cerebrovasc Dis ; 22(8): e615-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24075586

RESUMO

BACKGROUND: Changes of signal intensities (SIs) across intracranial atherosclerosis (ICAS) on magnetic resonance angiography (MRA) may reflect hemodynamic impact of the lesion. We evaluated the interobserver reproducibility of an index termed signal intensity ratio (SIR), developed in a previous study to represent the changes of SIs across ICAS on MRA. METHODS: Symptomatic ICAS on MRA were retrospectively recruited. Two observers respectively evaluated the images and calculated the SIR as follows, blinded to each other's readings: SIR=(mean poststenotic SI-mean background SI)/(mean prestenotic SI-mean background SI). Statistical analyses were performed to evaluate the interobserver reproducibility of this index. RESULTS: A total of 102 symptomatic ICASs were enrolled, with 36 (35.3%) lesions of 50%-69% MRA stenoses and others being 70%-99% stenoses or flow void on MRA. Overall, mean SIRs were not significantly different between the 2 observers (.92±.17 versus .93±.17; mean difference -.006±.09; P=.496 for paired t test). Pearson correlation coefficients were >.80 for all analyses, indicating strong linear correlations between SIRs by the 2 observers. Bland-Altman analysis for SIRs of all cases showed no systematic bias between the 2 observers. For different cut-points ranging from .75 to 1.00, the kappa statistics were mostly greater than .6 and interobserver agreements were all greater than 80%, implying substantial agreement between observers. CONCLUSIONS: SIR was demonstrated to be highly reproducible between observers in the present study. Future studies are warranted to further explore the role of this index in comprehensive evaluation and risk stratification of symptomatic ICAS.


Assuntos
Artéria Basilar/fisiopatologia , Artéria Carótida Interna/fisiopatologia , Circulação Cerebrovascular , Hemodinâmica , Arteriosclerose Intracraniana/diagnóstico , Angiografia por Ressonância Magnética , Artéria Cerebral Média/fisiopatologia , China , Constrição Patológica , Humanos , Arteriosclerose Intracraniana/fisiopatologia , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos
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