Cerebral haemodynamics in symptomatic intracranial atherosclerotic disease: a narrative review of the assessment methods and clinical implications.

Intracranial atherosclerotic disease (ICAD) is a common cause of ischaemic stroke and transient ischaemic attack (TIA) with a high recurrence rate. It is often referred to as intracranial atherosclerotic stenosis (ICAS), when the plaque has caused significant narrowing of the vessel lumen. The lesion is usually considered 'symptomatic ICAD/ICAS' (sICAD/sICAS) when it has caused an ischaemic stroke or TIA. The severity of luminal stenosis has long been established as a prognostic factor for stroke relapse in sICAS. Yet, accumulating studies have also reported the important roles of plaque vulnerability, cerebral haemodynamics, collateral circulation, cerebral autoregulation and other factors in altering the stroke risks across patients with sICAS. In this review article, we focus on cerebral haemodynamics in sICAS. We reviewed imaging modalities/methods in assessing cerebral haemodynamics, the haemodynamic metrics provided by these methods and application of these methods in research and clinical practice. More importantly, we reviewed the significance of these haemodynamic features in governing the risk of stroke recurrence in sICAS. We also discussed other clinical implications of these haemodynamic features in sICAS, such as the associations with collateral recruitment and evolution of the lesion under medical treatment, and indications for more individualised blood pressure management for secondary stroke prevention. We then put forward some knowledge gaps and future directions on these topics.

Small vessel disease burden may not portend unfavorable outcome after thrombectomy for acute large vessel occlusion.

OBJECTIVES: We aimed to investigate the correlation between an overall cerebral small vessel disease (CSVD) burden and outcomes after endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). METHODS: In a multicenter registry study, we enrolled patients with EVT for anterior-circulation LVO-stroke. In 3.0-T MR imaging, we assessed 4 CSVD imaging markers, lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces, each assigned a score of 0 or 1 and summed up to an overall CSVD burden score of 0-4. We dichotomized the overall CSVD severity as none to mild (score 0-2) and moderate to severe (3-4). Primary outcome was 90-day functional dependence or death (modified Rankin Scale (mRS) 3-6). Secondary outcomes included increase in NIH Stroke Scale ≥ 4 within 24 h (early neurological deterioration (END)) and within 7 days, symptomatic intracranial hemorrhage, 90-day mRS 2-6, and 90-day mortality. RESULTS: Among 311 patients (63.0% male; mean age 65.1 ± 12.7 years), 260 (83.6%) had none-to-mild and 51 (16.4%) had moderate-to-severe overall CSVD burden. Moderate-to-severe CSVD burden was not significantly associated with the primary outcome (47.1% versus 45.4%; p > 0.05 in univariate and multivariate logistic regression), or the secondary outcomes except for a higher risk of END (11.8% versus 3.1%; p < 0.05 in multivariate analyses). Sensitivity analyses with 0-1 versus 2-4 of the CSVD burden score, and the score as an ordinal variable, showed similar results. CONCLUSIONS: An overall moderate-to-severe CSVD burden was not associated with 90-day functional dependence or death, after EVT for anterior-circulation LVO. TRIAL REGISTRATION: ChiCTR1900022154 KEY POINTS: • Moderate-to-severe cerebral small vessel disease burden on MRI should not be an exclusion indicator in determining the eligibility of an acute ischemic stroke patient for endovascular treatment.

Post-Stroke Cognitive Impairment: Epidemiology, Risk Factors, and Management.

Stroke, characterized as a neurological deficit of cerebrovascular cause, is very common in older adults. Increasing evidence suggests stroke contributes to the risk and severity of cognitive impairment. People with cognitive impairment following stroke often face with quality-of-life issues and require ongoing support, which have a profound effect on caregivers and society. The high morbidity of post-stroke cognitive impairment (PSCI) demands effective management strategies, in which preventive strategies are more appealing, especially those targeting towards modifiable risk factors. In this review article, we attempt to summarize existing evidence and knowledge gaps on PSCI: elaborating on the heterogeneity in current definitions, reporting the inconsistent findings in PSCI prevalence in the literature, exploring established or less established predictors, outlining prevention and treatment strategies potentially effective or currently being tested, and proposing promising directions for future research.

Stability of unruptured intracranial aneurysms in the anterior circulation: nomogram models for risk assessment.

OBJECTIVE: The probable stability of the lesion is critical in guiding treatment decisions in unruptured intracranial aneurysms (IAs). The authors aimed to develop multidimensional predictive models for the stability of unruptured IAs. METHODS: Patients with unruptured IAs in the anterior circulation were prospectively enrolled and regularly followed up. Clinical data were collected, IA morphological features were assessed, and adjacent hemodynamic features were quantified with patient-specific computational fluid dynamics modeling. Based on multivariate logistic regression analyses, nomograms incorporating these factors were developed in a primary cohort (patients enrolled between January 2017 and February 2018) to predict aneurysm rupture or growth within 2 years. The predictive accuracies of the nomograms were compared with the population, hypertension, age, size, earlier rupture, and site (PHASES) and earlier subarachnoid hemorrhage, location, age, population, size, and shape (ELAPSS) scores and validated in the validation cohort (patients enrolled between March and October 2018). RESULTS: Among 231 patients with 272 unruptured IAs in the primary cohort, hypertension, aneurysm location, irregular shape, size ratio, normalized wall shear stress average, and relative resident time were independently related to the 2-year stability of unruptured IAs. The nomogram including clinical, morphological, and hemodynamic features (C+M+H nomogram) had the highest predictive accuracy (c-statistic 0.94), followed by the nomogram including clinical and morphological features (C+M nomogram; c-statistic 0.89), PHASES score (c-statistic 0.68), and ELAPSS score (c-statistic 0.58). Similarly, the C+M+H nomogram had the highest predictive accuracy (c-statistic 0.94) in the validation cohort (85 patients with 97 unruptured IAs). CONCLUSIONS: Hemodynamics have predictive values for 2-year stability of unruptured IAs treated conservatively. Multidimensional nomograms have significantly higher predictive accuracies than conventional risk prediction scores.

A Data-Driven Approach to Transfer Function Analysis for Superior Discriminative Power: Optimized Assessment of Dynamic Cerebral Autoregulation.

Transfer function analysis (TFA) is extensively used to assess human physiological functions. However, extracting parameters from TFA is not usually optimized for detecting impaired function. In this study, we propose to use data-driven approaches to improve the performance of TFA in assessing blood flow control in the brain (dynamic cerebral autoregulation, dCA). Data were collected from two distinct groups of subjects deemed to have normal and impaired dCA. Continuous arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) were simultaneously recorded for approximately 10 mins in 82 subjects (including 41 healthy controls) to give 328 labeled samples of the TFA variables. The recordings were further divided into 4,294 short data segments to generate 17,176 unlabeled samples of the TFA variables. We optimized TFA post-processing with a generic semi-supervised learning strategy and a novel semi-supervised stacked ensemble learning (SSEL) strategy for classification into normal and impaired dCA. The generic strategy led to a performance with no significant difference to that of the conventional dCA analysis methods, whereas the proposed new strategy boosted the performance of TFA to an accuracy of 93.3%. To our knowledge, this is the best dCA discrimination performance obtained to date and the first attempt at optimizing TFA through machine learning techniques. Equivalent methods can potentially also be applied to assessing a wide spectrum of other human physiological functions.

Functional assessment of cerebral artery stenosis: A pilot study based on computational fluid dynamics.

The fractional pressure ratio is introduced to quantitatively assess the hemodynamic significance of severe intracranial stenosis. A computational fluid dynamics-based method is proposed to non-invasively compute the FPRCFD and compared against fractional pressure ratio measured by an invasive technique. Eleven patients with severe intracranial stenosis considered for endovascular intervention were recruited and an invasive procedure was performed to measure the distal and the aortic pressure ( Pd and Pa). The fractional pressure ratio was calculated as [Formula: see text]. The computed tomography angiography was used to reconstruct three-dimensional (3D) arteries for each patient. Cerebral hemodynamics was then computed for the arteries using a mathematical model governed by Navier-Stokes equations and with the outflow conditions imposed by a model of distal resistance and compliance. The non-invasive [Formula: see text], [Formula: see text], and FPRCFD were then obtained from the computational fluid dynamics calculation using a 16-core parallel computer. The invasive and non-invasive parameters were tested by statistical analysis. For this group of patients, the computational fluid dynamics method achieved comparable results with the invasive measurements. The fractional pressure ratio and FPRCFD are very close and highly correlated, but not linearly proportional, with the percentage of stenosis. The proposed computational fluid dynamics method can potentially be useful in assessing the functional alteration of cerebral stenosis.

Fractional Flow Assessment for the Evaluation of Intracranial Atherosclerosis: A Feasibility Study.

PURPOSE: Current studies on endovascular intervention for intracranial atherosclerosis select patients based on luminal stenosis. Coronary studies demonstrated that fractional flow measurements assess ischemia better than anatomical stenosis and can guide patient selection for intervention. We similarly postulated that fractional flow can be used to assess ischemic stroke risk. METHODS: This was a feasibility study to assess the technical use and safety of applying a pressure guidewire to measure fractional flow across intracranial stenoses. Twenty patients with severe intracranial stenosis were recruited. The percentage of luminal stenosis, distal to proximal pressure ratios (fractional flow) and the fractional flow gradients across the stenosis were measured. Procedural success rate and safety outcomes were documented. RESULTS: All 20 patients had successful crossing of stenosis by the pressure guidewire. Ten patients underwent angioplasty, and 5 had stenting performed. There was one perforator stroke, but not related to the use of the pressure wire. For the 13 patients with complete pre- and postintervention data, the mean preintervention stenosis, fractional flow and translesional pressure gradient were 76.2%, 0.66 and 29.9 mm Hg, whilst the corresponding postintervention measurements were 24.7%, 0.88 and 10.9 mm Hg, respectively. Fractional flow (r = -0.530, p = 0.001) and the translesional pressure gradient (r = 0.501, p = 0.002) only had a modest correlation with the luminal stenosis. CONCLUSION: Fractional flow measurement by floating a pressure guidewire across the intracranial stenosis was technically feasible and safe in this study. Further studies are needed to validate its use for ischemic stroke risk assessment.