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This study aims to develop an experimentally validated computational fluid dynamics (CFD) model to estimate hemodynamic characteristics in cerebral aneurysms (CAs) using non-Newtonian blood analogues. Blood viscosities varying with shear rates were measured under four temperatures first, which serves as the reference for the generation of blood analogues. Using the blood analogue, particle image velocimetry (PIV) measurements were conducted to quantify flow characteristics in a CA model. Then, using the identical blood properties in the experiment, CFD simulations were executed to quantify the flow patterns, which were used to compare with the PIV counterpart. Additionally, hemodynamic characteristics in the simplified Newtonian and non-Newtonian models were quantified and compared using the experimentally validated CFD model. Results showed the proposed non-Newtonian viscosity model can predict blood shear-thinning properties accurately under varying temperatures and shear rates. Another developed viscosity model based on the blood analogue can well represent blood rheological properties. The comparisons in flow characteristics show good agreements between PIV and CFD, demonstrating the developed CFD model is qualified to investigate hemodynamic factors within CAs. Furthermore, results show the differences of absolute values were insignificant between Newtonian and non-Newtonian fluids in the distributions of wall shear stress (WSS) and oscillatory shear index (OSI) on arterial walls. However, not only does the simplified Newtonian model underestimate WSS and OSI in most regions of the aneurysmal sac, but it also makes mistakes in identifying the high OSI regions on the sac surface, which may mislead the hemodynamic assessment on the pathophysiology of CAs.

Objective Educate providers about the clinical presentation and consequences of delaying diagnosis of traumatic vertebral artery dissection with thromboembolic ischemic strokes in the pediatric population. Vertebral artery dissection is often difficult to diagnose and can be a potentially devastating cause of ischemic stroke. Methods Review of the chart, peer review/discussion, and imaging interpretation. Results A 16-year-old boy was admitted with confusion after a head and neck trauma was sustained while wrestling. (Glasgow Coma Scale=15, NIHSS = 0). Investigations including computed tomography (CT) head and cervical spine were normal. He then developed severe nausea, vomiting, dizziness, and headaches and was admitted for symptoms of concussion. Ten hours later, patient declined (hypertensive and unresponsive) and was noted to have decerebrate posturing. After emergent intubation, he was transferred to the pediatric intensive care unit. Repeat CT head showed an acute left cerebellar infarct with associated cerebellar edema resulting in effacement of the fourth ventricle/basilar cisterns and acute hydrocephalus. The CT angiography and magnetic resonance imaging of brain confirmed arterial dissection and near occlusion of the left vertebral artery at the C2 level. Extensive infarct was seen in the left cerebellum, brainstem, and right cerebellum. During a prolonged hospital stay, the family opted to continue care, and he was transferred to an inpatient rehabilitation facility because of limited brainstem activity, being nonverbal, and not demonstrating purposeful spontaneous movements. Conclusions Detailed history and thorough neurological examination in conjunction with appropriate imaging are necessary to distinguish between brainstem/cerebellar ischemia from vertebral artery dissection and concussion.

The aim of this work was to use a multiscale modeling to study the influence of stent deployment, with generic stents, on flow distributions within the vascular network and the hemodynamic alterations within the cerebral aneurysms pre- and post-stenting. To achieve this goal, two image-based anatomical cerebral aneurysm models were reconstructed along with the respective aneurysms post-stenting models after deploying a 16- or 24-wire stent. The investigation results revealed that the stent may increase the local pressure resistance resulting in flow alterations. The hemodynamic parameters demonstrated stent placement can reduce the intra-aneurysmal pressure, decrease wall shear stress (WSS) at the neck region, and increase blood turnover time for aneurysm case I (sidewall aneurysm). These findings are consistent with the trends of hemodynamic changes reported previously. However, aneurysm case II (bifurcation aneurysm) showed gradually increased intra-aneurysmal pressure and the pressure at the neck region, decreased WSS over the sac surface, and enhanced flow vortices within the aneurysm. When simulating the hemodynamics of pre- and post-stenting aneurysms for a patient using measured flow waveforms, the flow alteration induced by the stent deployment may affect the hemodynamic predictions for the post-stenting aneurysm. Thus, the remeasurement of boundary conditions once the morphology of the aneurysm is deformed is needed in follow-up studies with a focus on aneurysm growth and stent deployment.

A one-dimensional (1D) numerical model has been previously developed to investigate the hemodynamics of blood flow in the entire human vascular network. In the current work, an experimental study of water–glycerin mixture flow in a 3D-printed silicone model of an anatomically accurate, complete circle of Willis (CoW) was conducted to investigate the flow characteristics in comparison with the simulated results by the 1D numerical model. In the experiment, the transient flow and pressure waveforms were measured at 13 selected segments within the flow network for comparisons. In the 1D simulation, the initial parameters of the vessel network were obtained by a direct measurement of the tubes in the experimental setup. The results verified that the 1D numerical model is able to capture the main features of the experimental pressure and flow waveforms with good reliability. The mean flow rates measurement results agree with the predictions of the 1D model with an overall difference of less than 1%. Further experiment might be needed to validate the 1D model in capturing pressure waveforms.

One-dimensional (1D) simulation of the complete vascular network, so called THINkS (Total Human Intravascular Network Simulation) is developed to investigate changes of blood flow characteristics caused by the variation of CoW. THINkS contains 158 major veins, 85 major arteries, and 77 venous and 43 arterial junctions. THINkS is validated with available in vivo blood flow waveform data. The overall trends of flow rates in variations of the CoW, such as the missing anterior cerebral artery (missing-A1) or missing posterior cerebral artery (missing-P1), are confirmed by in vivo experimental data. It is demonstrated that the CoW has the ability to shunt blood flow to different areas in the brain. Flow rates in efferent arteries remain unaffected under the variation of CoW, while the flow rates in afferent vessels can be subject to substantial changes. The redistribution of blood flow can cause particular vessels to undergo extra flow rate and hemodynamic stresses.

Objective: To study the hemodynamics of an anatomic internal carotid artery aneurysm derived from a patient-specific model and then manipulate into two phantom morphologies: one growing uniformly by size and the other changing shape unevenly. Methods: The computational model of the saccular, internal carotid artery, aneurysm was constructed from 3D rotational, digitally subtracted, catheter angiography images. Computational fluid dynamics simulations were performed under pulsatile cardiac flow conditions. Velocity vectors, streamlines, pressure, and wall shear stress (WSS) and its variance distributions were quantitatively visualized. Results: The maximum pressure and WSS from the time-averaged distribution on the inside saccular surface of the original case are 415.38 and 17.61 Pa. In contrast, the bi-lobed shape gives rise to higher peak values of pressure (461.00 Pa) and WSS (33.20 Pa) on the saccular dome. Conversely, the evenly enlarged aneurysm actually results in a slightly lower peak pressure (399.58 Pa) and drastically decreased WSS (9.81 Pa). Conclusions: The current study indicates that the size of the aneurysm should not be the only determining factor for the rupture risk consideration, the irregularity of the aneurysm shape and the corresponding aberrant hemodynamics might be a more important factor to consider for risk assessment.

Detailed blood velocity map in the vascular system can be obtained by applying the optical flow method (OFM) in processing fluoroscopic digital subtracted catheter angiographic images; however, there are still challenges with the accuracy of this method. In the present study, a divergence compensatory optical flow method (DC-OFM), in which a nonzero divergence of velocity is assumed due to the finite resolution of the image, was explored and applied to the digital subtraction angiography (DSA) images of blood flow. The objective of this study is to examine the applicability and evaluate the accuracy of DC-OFM in assessing the blood flow velocity in vessels. First, an Oseen vortex flow was simulated on the standard particle image to generate an image pair. Then, the DC-OFM was applied on the particle image pair to recover the velocity field for validation. Second, DSA images of intracranial arteries were used to examine the accuracy of the current method. For each set of images, the first image is the in vivo DSA image, and the second image is generated by superimposing a given flow field. The recovered velocity map by DC-OFM agrees well with the exact velocity for both the particle images and the angiographic images. In comparison with the traditional OFM, the present method can provide more accurate velocity estimation. The accuracy of the velocity estimation can also be improved by implementing preprocess techniques including image intensification, Gaussian filtering, and “image-shift.”

Background: There are multiple clinical and radiographic factors that influence outcomes after endovascular reperfusion therapy (ERT) in acute ischemic stroke (AIS). We sought to derive and validate an outcome prediction score for AIS patients undergoing ERT based on readily available pretreatment and posttreatment factors. Methods: The derivation cohort included 511 patients with anterior circulation AIS treated with ERT at 10 centers between September 2009 and July 2011. The prospective validation cohort included 223 patients with anterior circulation AIS treated in the North American Solitaire Acute Stroke registry. Multivariable logistic regression identified predictors of good outcome (modified Rankin score ≤2 at 3 months) in the derivation cohort; model β coefficients were used to assign points and calculate a risk score. Discrimination was tested using C statistics with 95% confidence intervals (CIs) in the derivation and validation cohorts. Calibration was assessed using the Hosmer-Lemeshow test and plots of observed to expected outcomes. We assessed the net reclassification improvement for the derived score compared to the Totaled Health Risks in Vascular Events (THRIVE) score. Subgroup analysis in patients with pretreatment Alberta Stroke Program Early CT Score (ASPECTS) and posttreatment final infarct volume measurements was also performed to identify whether these radiographic predictors improved the model compared to simpler models. Results: Good outcome was noted in 186 (36.4%) and 100 patients (44.8%) in the derivation and validation cohorts, respectively. Combining readily available pretreatment and posttreatment variables, we created a score (acronym: SNARL) based on the following parameters: symptomatic hemorrhage [2 points: none, hemorrhagic infarction (HI)1-2 or parenchymal hematoma (PH) type 1; 0 points: PH2], baseline National Institutes of Health Stroke Scale score (3 points: 0-10; 1 point: 11-20; 0 points: >20), age (2 points: 79 years), reperfusion (3 points: Thrombolysis In Cerebral Ischemia score 2b or 3) and location of clot (1 point: M2; 0 points: M1 or internal carotid artery). The SNARL score demonstrated good discrimination in the derivation (C statistic 0.79, 95% CI 0.75-0.83) and validation cohorts (C statistic 0.74, 95% CI 0.68-0.81) and was superior to the THRIVE score (derivation cohort: C statistic 0.65, 95% CI 0.60-0.70; validation cohort: C-statistic 0.59, 95% CI 0.52-0.67; p < 0.01 in both cohorts) but was inferior to a score that included age, ASPECTS, reperfusion status and final infarct volume (C statistic 0.86, 95% CI 0.82-0.91; p = 0.04). Compared with the THRIVE score, the SNARL score resulted in a net reclassification improvement of 34.8%. Conclusions: Among AIS patients treated with ERT, pretreatment scores such as the THRIVE score provide only fair prognostic information. Inclusion of posttreatment variables such as reperfusion and symptomatic hemorrhage greatly influences outcome and results in improved outcome prediction.

Purpose Advanced neuroimaging techniques may improve patient selection for endovascular stroke treatment but may also delay time to reperfusion. We studied the effect of advanced modality imaging with CT perfusion (CTP) or MRI compared with non-contrast CT (NCT) in a multicenter cohort. Materials and methods This is a retrospective study of 10 stroke centers who select patients for endovascular treatment using institutional protocols. Approval was obtained from each institution9s review board as only de-identified information was used. We collected demographic and radiographic data, selected time intervals, and outcome data. ANOVA was used to compare the groups (NCT vs CTP vs MRI). Binary logistic regression analysis was performed to determine factors associated with a good clinical outcome. Results 556 patients were analyzed. Mean age was 66±15 years and median National Institutes of Health Stroke Scale score was 18 (IQR 14–22). NCT was used in 286 (51%) patients, CTP in 190 (34%) patients, and MRI in 80 (14%) patients. NCT patients had significantly lower median times to groin puncture (61 min, IQR (40–117)) compared with CTP (114 min, IQR (81–152)) or MRI (124 min, IQR (87–165)). There were no differences in clinical outcomes, hemorrhage rates, or final infarct volumes among the groups. Conclusions The current retrospective study shows that multimodal imaging may be associated with delays in treatment without reducing hemorrhage rates or improving clinical outcomes. This exploratory analysis suggests that prospective randomised studies are warranted to support the hypothesis that advanced modality imaging is superior to NCT in improving clinical outcomes.

Technological advances have helped to improve the efficiency of treating patients with large vessel occlusion in acute ischemic stroke. Unfortunately, the sequence of events prior to reperfusion may lead to significant treatment delays. This study sought to determine if high-volume (HV) centers were efficient at delivery of endovascular treatment approaches.A retrospective review was performed of nine centers to assess a series of time points from obtaining a CT scan to the end of the endovascular procedure. Demographic, radiographic and angiographic variables were assessed by multivariate analysis to determine if HV centers were more efficient at delivery of care.A total of 442 consecutive patients of mean age 66 ± 14 years and median NIH Stroke Scale score of 18 were studied. HV centers were more likely to treat patients after intravenous administration of tissue plasminogen activator and those transferred from outside hospitals. After adjusting for appropriate variables, HV centers had significantly lower times from CT acquisition to groin puncture (OR 0.991, 95% CI 0.989 to 0.997, p=0.001) and total procedure times (OR 0.991, 95% CI 0.986 to 0.996, p=0.001). Additionally, patients treated at HV centers were more likely to have a good clinical outcome (OR 1.86, 95% CI 1.11 to 3.10, p0.018) and successful reperfusion (OR 1.82, 95% CI 1.16 to 2.86, p0.008).Significant delays occur in treating patients with endovascular therapy in acute ischemic stroke, offering opportunities for improvements in systems of care. Ongoing prospective clinical trials can help to assess if HV centers are achieving better clinical outcomes and higher reperfusion rates.

A 1-dimensional (1D)-3-dimensional (3D) multiscale model for the human vascular network was proposed by combining a low-fidelity 1D modeling of blood circulation to account for the global hemodynamics with a detailed 3D simulation of a zonal vascular segment. The coupling approach involves a direct exchange of flow and pressure information at interfaces between the 1D and 3D models and thus enables patient-specific morphological models to be inserted into flow network with minimum computational efforts. The proposed method was validated with good agreements against 3 simplified test cases where experimental data and/or full 3D numerical solution were available. The application of the method in aneurysm and stenosis studies indicated that the deformation of the geometry caused by the diseases may change local pressure loss and as a consequence lead to an alteration of flow rate to the vessel segment.

Age-associated alterations in cardiovascular structure and function induce cardiovascular disease in elderly subjects. To investigate the effects of normal vascular aging (NVA) and early vascular aging (EVA) on hemodynamic characteristics in the circle of Willis (CoW), a closed-loop one-dimensional computational model was developed based on fluid mechanics in the vascular system. The numerical simulations revealed that higher central pulse pressure and augmentation index (AIx) appear in the EVA subjects due to early arrival of reflected waves, resulted in the increase of cardiac afterload compared with the NVA subjects. Moreover, the hemodynamic characteristics in the CoW show that the EVA subjects in an older age display a higher blood pressure than that of the NVA with a complete CoW. Herein, the increased blood pressure and flow rate coexist in the subjects with an incomplete CoW. In conclusion, the hemodynamic characteristics in the aortic tree and CoW related to aging appear to play an important role in causing cardiovascular and intravascular disease.

Background: Age is a strong predictor of outcomes following acute ischemic stroke (AIS). Conflicting data exist on whether endovascular reperfusion therapy (ERT) should be offered to patients over 80 years of age. We compared the safety and efficacy of ERT in elderly (> 80 years) compared to non-elderly (< 80 years) patients with AIS. Methods: We collected data from a large multi-center prospective registry of AIS patients treated with ERT. Data were available on demographics, initial severity, angiographic results, hemorrhagic complications using the ECASS criteria, and 3-month functional outcomes using the modified Rankin Scale (mRS). The thrombolysis in myocardial infarction (TIMI) score was used to grade reperfusion. We compared baseline factors, procedural results, and clinical outcomes in those over > 80 years versus those < 80 years. P-value < 0.05 was considered significant. Results: Among 1077 patients with anterior circulation AIS, 223 (20.7%) were > 80 years. Elderly patients were more likely to have atrial fibrillation (54.3% vs. 31.4%, P < 0.001) but less likely to have diabetes (16.1% vs. 24.6%; P=0.046) or smoking (13.2% vs. 32.6%, P 80 vs. 70.7% in those < 80 (P=0.080). Rates of symptomatic hemorrhage and any intracranial hemorrhage were not different between groups. Good outcome at 3 months (mRS 0-2) was noted in 16.5% of elderly compared to 41.5% of non-elderly patients (P 20. Conclusions: Patients > 80 years account for over one-fifth of those treated with ERT in this large registry and had worse outcomes compared with those < 80 years despite similar initial severity, time to treatment, and procedural results. Other factors such as increased baseline disability, more rapid time to completed infarction, and reduced neural plasticity may be contributing to these findings.

Background: Tools to predict outcome after endovascular reperfusion therapy (ERT) for acute ischemic stroke (AIS) have previously included only pre-treatment variables. We sought to derive and validate an outcome prediction score based on readily available pre-treatment and treatment factors. Methods: The derivation cohort consisted of 516 patients with anterior circulation AIS from 9 centers from September 2009-July 2011. The validation cohort consisted of 110 patients with anterior circulation AIS from the Penumbra Pivotal Trial. Multivariable logistic regression identified predictors of good outcome, defined as a modified Rankin Score (mRS) of < 2, in the derivation sample; model beta coefficients were used to assign point scores. Discrimination was tested using C-statistics. We then validated the score in the Penumbra cohort and performed calibration (predicted versus observed good outcome) in both cohorts. Results: Good outcome at 3 months was noted in 189 (36.8%) patients in the derivation cohort. The independent predictors of good outcome were A ge (2 pts: 79), N IHSS score (4 pts: 0-10; 2 pts: 11-20; 0 pts: > 20), L ocation of clot (2 pts: M2; 1 pt: M1; 0 pts: ICA), R ecanalization (5 pts: TICI 2 or 3), and S ymptomatic hemorrhage (2 pts: none, HT1-2, or PH1; 0 pts: PH2). The outcome (SNARL) score demonstrated good discrimination in the derivation cohort (C-statistic 0.78, 95% CI 0.72-0.78) and validation cohort (C-statistic 0.74, 95% CI 0.64-0.84). There was excellent calibration in each cohort (Figure). Conclusions: The SNARL score is a validated tool to determine the probability of functional recovery among AIS treated with endovascular reperfusion strategies. Unlike previous scores that did not include treatment factors such as successful recanalization or hemorrhagic complications, our score can be applied to patients after treatment and may provide guidance to physicians, patients, and families about expected functional outcome.

Background: Advanced modality imaging with CT perfusion (CTP) is frequently employed to optimize patient selection for endovascular reperfusion treatment in stroke. Although acquisition of images can be obtained rapidly, delays in decision making may occur. Time delays may be balanced by the data obtained with regards to core infarct. The current study examines if CTP aids in selecting patients best suited for endovascular stroke interventions by assessing clinical outcomes, hemorrhage rates and final infarct volume. Methods: We retrospectively reviewed patients from seven institutions who utilize endovascular reperfusion therapies for acute ischemic stroke. Patients with anterior circulation strokes treated less than 8 hours from symptoms onset were included. Patients were selected with a non-contrast head CT or CTP based on institutional protocols. We reviewed demographic, radiographic, and angiographic information to compare CTP and CT. Outcomes were dichotomized to good (mRS 0–2) or poor (mRS>2). Hemorrhages were classified using the ECASS definition with a parenchymal hematoma (PH) type 2 classified as symptomatic hemorrhage. Infarct volumes were measured on diffusion weighted MRI imaging using summation of regions of interest. A univariate analysis was performed using the Fisher’s exact test for categorical variables and student’s t-test for continuous variables to determine the characteristics of patients undergoing CTP compared to non-contrast CT only. A binary logistic regression model was constructed using variables with a p-value < 0.20 in univariate analysis to determine if patients selected with CTP had longer times to treatment or differences in outcomes. Results: A total of 338 patients with a mean age of 67±14 years and mean NIHSS of 18±5 were included. There were no differences in baseline demographics including age, site of vascular occlusion, and pre-treatment NIHSS in patients selected with CTP compared to non-contrast. There was no difference in rates of symptomatic hemorrhage in patients imaged with CTP compared to CT (6.8% vs. 6.6%, p3 vs. 88±62 cm 3 , p Conclusion: There were no differences in hemorrhage rates or clinical outcomes in patients selected based on non-contrast head CT and CTP. Acquisition of CTP may lead to delays in initiating endovascular procedures. This analysis may be limited in power, but a future prospective study is being designed to determine if non contrast CT is not inferior to CTP in selecting patients for endovascular therapies in acute ischemic stroke.

Background: Currently, no metric exists for door to arterial puncture time for endovascular treatment in acute ischemic stroke. The aim of this study was to determine the timings of each step of endovascular stroke intervention stratified by the volume of procedures at each center. Methods: We retrospectively reviewed patients from seven institutions undergoing endovascular reperfusion therapies for acute ischemic stroke. Patients with anterior circulation strokes treated less than 8 hours from symptoms onset were included. Demographic, radiographic, angiographic and clinical outcomes were collected. The time interval at each milestone from CT acquisition to reperfusion was recorded. Successful reperfusion was defined as achieving a TICI 2B or 3 score as graded by the operator. Symptomatic hemorrhage was defined as a parenchymal hemorrhage type 2 as defined by ECASScriteria. Centers that performed more than 50 intra-arterial stroke interventions annually were considered high volume (HV) centers. A univariate analysis was performed with the Fisher’s exact test for categorical variables and students t-test for continuous variables to compare HV to lower volume (LV) centers. Variables with a p-value < 0.20 were placed in a binary logistic regression model to determine if there were differences in time to treatment between the two groups. Results: A total of 338 patients with a mean age of 67±14 years and mean NIHSS of 18±5 were included. The mean time from CT imaging to groin puncture was 108±73 minutes. The mean time from groin puncture to the placement of a microcatheter in the thrombus was 41±21 minutes and total procedure time 104±55 minutes. There were no differences in demographics, site of vascular occlusion and hemorrhage rates between high volume and lower volume centers. In univariate analysis, HV centers had a lower time from CT imaging to groin puncture (89±57 minutes vs. 154±84 minutes, p3 vs. 94±106 cm 3 , p Conclusions: Currently there is variability in the time from CT to arterial puncture and total procedure time across institutions, but HV centers appear to have lower times to treatment. Further study is required to determine how to reduce times to treatment and develop a metric for centers to target.

As part of an ongoing survey to identify hormones capable of stimulating growth in Pacific salmon, groups of underyearling coho salmon were injected with bovine (Ultralente) insulin (0.32, 1.0, 3.2, or 10 IU/kg body weight) into the peritoneal cavity either once or twice weekly for 70 days.All doses of insulin, when injected twice weekly, increased the values for specific growth rates and decreased those for food–gain ratios relative to solvent-injected controls, but the differences were not statistically significant. All doses of insulin caused a marked increase in the granulation of the pancreatic B cells. Plasma glucose concentrations in starved coho injected with 10 IU insulin/kg body weight were significantly lower than in solvent-injected controls 4 h after injection.It is concluded that proper evaluation of the effectiveness of insulin as a growth promoter for salmon requires further studies preferably using insulin preparations specific to teleosts.

The physics based optical flow method (OFM) was explored and applied to the blood flow measurement based on the digital subtraction angiography X-ray images. The objective of the present study is to examine the applicability of the physics-based OFM in the biological flow and evaluate the accuracy of OFM in recovering the velocity of blood flow in cerebral arteries. In order to examine the algorithm and conduct the error analysis, simulations are conducted on synthetic grid images (640×480 piexiels and 8 bits), where the intensity profiles across a grid line is Gaussian. The recovered velocity from OFM agrees well with the exact velocity distribution. Then, the improved OFM algorithm was applied on the DSA images of cerebral arteries including the cerebral arterial aneurysm and the parent internal cerebral artery. Again, synthetic parabolic velocity distribution and Oseen vortices were imposed to the vessel image and aneurysm image respectively to examine the accuracy of the current method. Compared to the grid image, the DSA image featured as low-intensity and isotropic distribution challenges the OFM algorithm. Appropriate intensification process combined with Gaussian filtering are applied to improve the accuracy of the OFM estimation. Finally the improved OFM was applied to the in-vivo measurement of the blood flow in the aneurysm to analyze the blood velocity distribution and hemodynamics.