Cognitive impairment in asymptomatic carotid artery stenosis is associated with abnormal segments in the Circle of Willis.

OBJECTIVE: Our group has previously demonstrated that patients with asymptomatic carotid artery stenosis (ACAS) demonstrate cognitive impairment. One proposed mechanism for cognitive impairment in patients with ACAS is cerebral hypoperfusion due to flow-restriction. We tested whether the combination of a high-grade carotid stenosis and inadequate cross-collateralization in the Circle of Willis (CoW) resulted in worsened cognitive impairment. METHODS: Twenty-four patients with high-grade (≥70% diameter-reducing) ACAS underwent carotid duplex ultrasound, cognitive assessment, and 3D time-of-flight magnetic resonance angiography. The cognitive battery consisted of nine neuropsychological tests assessing four cognitive domains: learning and recall, attention and working memory, motor and processing speed, and executive function. Raw cognitive scores were converted into standardized T-scores. A structured interpretation of the magnetic resonance angiography images was performed with each segment of the CoW categorized as being either normal or abnormal. Abnormal segments of the CoW were defined as segments characterized as narrowed or occluded due to congenital aplasia or hypoplasia, or acquired atherosclerotic stenosis or occlusion. Linear regression was used to estimate the association between the number of abnormal segments in the CoW, and individual cognitive domain scores. Significance was set to P < .05. RESULTS: The mean age of the patients was 66.1 ± 9.6 years, and 79.2% (n = 19) were male. A significant negative association was found between the number of abnormal segments in the CoW and cognitive scores in the learning and recall (ß = -6.5; P = .01), and attention and working memory (ß = -7.0; P = .02) domains. There was a trend suggesting a negative association in the motor and processing speed (ß = -2.4; P = .35) and executive function (ß = -4.5; P = .06) domains that did not reach significance. CONCLUSIONS: In patients with high-grade ACAS, the concomitant presence of increasing occlusive disease in the CoW correlates with worse cognitive function. This association was significant in the learning and recall and attention and working memory domains. Although motor and processing speed and executive function also declined numerically with increasing abnormal segments in the CoW, the relationship was not significant. Since flow restriction at a carotid stenosis compounded by inadequate collateral compensation across a diseased CoW worsens cerebral perfusion, our findings support the hypothesis that cerebral hypoperfusion underlies the observed cognitive impairment in patients with ACAS.

Ophthalmic artery reversal predicts contralateral body weakness symptoms better than carotid Doppler velocity-preliminary results.

Background: The measurement of blood velocity in the carotid artery has been the most popular noninvasive method of identifying and classifying carotid stenosis for half a century. Carotid stenosis is an indicator of elevated risk of stroke; anatomic revascularization reduces the chance of stroke by more than half. Controversy persists on how patients with severe carotid stenosis should be selected for anatomic revascularization. Patients with a connected circle of Willis (coW) might not benefit from anatomic revascularization; patients with two segments missing in the coW are most likely to benefit from revascularization. Methods: Based on this analysis of data from carotid duplex examinations and transcranial Doppler examinations including ophthalmic artery (OA) direction in 28 patients, a refined carotid examination protocol is proposed. This refinement includes Doppler measurement of OA flow direction and documentation of internal carotid artery (ICA) bruit in addition to the adoption of an ICA peak systolic velocity (PSV) criterion exceeding 350 cm/s for identification of the patient most likely to benefit from carotid stenosis treatment. Results: Sensitivity and specificity of OA direction or carotid bruit are 84.6%±5.4%, 71.4%±2.1% and for PSV >350 cm/s are 84.6%±5.4%, 59.5%±2.3% for predicting contralateral body weakness. Conclusions: The proposed examination can be performed with the same duplex scanner and scan head currently used for carotid examinations with little additional time.

D. Eugene Strandness, Jr., MD, vascular surgeon of persistent curiosity.

As a junior colleague of Dr. D. E. Strandness, Jr., for almost 30 years, I had the unique professional opportunity to witness the development of duplex ultrasonography at the University of Washington. "Gene" as he liked to be called, was a surgeon with a persistent curiosity about vascular disease. He led the multidisciplinary team that developed the technique of duplex ultrasound, measured its diagnostic accuracy, and performed research studies to reduce stroke due to carotid bifurcation atherosclerosis. My reflections on the legacy of Dr. Strandness are offered with gratitude for the curiosity "bug" he nurtured in me, which continues today.

Acute ischemic stroke diagnosis using brain tissue pulsations.

Healthy brain tissue pulsates with the cardiac cycle, but whether brain tissue pulsations (BTPs) are impaired by tissue ischemia due to ischemic stroke is currently unclear. This study is the first to explore the clinical potential of measuring BTPs using ultrasound in acute ischemic stroke patients. BTPs were measured in 24 healthy volunteers (aged 52-82 years) and 14 acute ischemic stroke patients (aged 51-86 years) using a novel Transcranial Tissue Doppler (TCTD) method. Measurements were quick to perform and were well tolerated by all subjects. A mixed-methods approach was used for blinded analysis of recordings. This identified qualitative disruption of BTPs in acute stroke patients, which were used to create an analysis checklist. Blinded BTP analysis by novices using the checklist resulted in high sensitivity but low specificity for stroke detection. Quantitative analysis also identified differences between stroke and healthy participants, including weaker BTPs in stroke patients. This first study reporting BTP characteristics in acute ischemic stroke revealed weaker brain tissue pulsations and waveform disruption in acute stroke patients. However, further clinical evaluation using a larger sample size is required to confirm these findings and to explore whether TCTD monitoring might be beneficial for clinical neuromonitoring.

Brain Tissue Pulsation in Healthy Volunteers.

It is well known that the brain pulses with each cardiac cycle, but interest in measuring cardiac-induced brain tissue pulsations (BTPs) is relatively recent. This study was aimed at generating BTP reference data from healthy patients for future clinical comparisons and modelling. BTPs were measured through the forehead and temporal positions as a function of age, sex, heart rate, mean arterial pressure and pulse pressure. A multivariate regression model was developed based on transcranial tissue Doppler BTP measurements from 107 healthy adults (56 male) aged from 20-81 y. A subset of 5 participants (aged 20-49 y) underwent a brain magnetic resonance imaging scan to relate the position of the ultrasound beam to anatomy. BTP amplitudes were found to vary widely between patients (from ∼4 to ∼150 µm) and were strongly associated with pulse pressure. Comparison with magnetic resonance images confirmed regional variations in BTP with depth and probe position.

Venous hemodynamic changes in lower limb venous disease: the UIP consensus according to scientific evidence.

There are excellent guidelines for clinicians to manage venous diseases but few reviews to assess their hemodynamic background. Hemodynamic concepts that evolved in the past have largely remained unchallenged in recent decades, perhaps due to their often complicated nature and in part due to emergence of new diagnostic techniques. Duplex ultrasound scanning and other imaging techniques which evolved in the latter part of the 20th century have dominated investigation. They have greatly improved our understanding of the anatomical patterns of venous reflux and obstruction. However, they do not provide the physiological basis for understanding the hemodynamics of flow, pressure, compliance and resistance. Hemodynamic investigations appear to provide a better correlation with post-treatment clinical outcome and quality of life than ultrasound findings. There is a far better prospect for understanding the complete picture of the patient's disability and response to management by combining ultrasound with hemodynamic studies. Accordingly, at the instigation of Dr Angelo Scuderi, the Union Internationale de Phlebologie (UIP) executive board commissioned a large number of experts to assess all aspects of management for venous disease by evidence-based principles. These included experts from various member societies including the European Venous Forum (EVF), American Venous Forum (AVF), American College of Phlebology (ACP) and Cardiovascular Disease Educational and Research Trust (CDERT). Their aim was to confirm or dispel long-held hemodynamic principles and to provide a comprehensive review of venous hemodynamic concepts underlying the pathophysiology of lower limb venous disorders, their usefulness for investigating patients and the relevant hemodynamic changes associated with various forms of treatment. Chapter 1 is devoted to basic hemodynamic concepts and normal venous physiology. Chapter 2 presents the mechanism and magnitude of hemodynamic changes in acute deep vein thrombosis indicating their pathophysiological and clinical significance. Chapter 3 describes the hemodynamic changes that occur in different classes of chronic venous disease and their relation to the anatomic extent of disease in the macrocirculation and microcirculation. The next four chapters (Chapters 4-7) describe the hemodynamic changes resulting from treatmen by compression using different materials, intermittent compression devices, pharmacological agents and finally surgical or endovenous ablation. Chapter 8 discusses the unique hemodynamic features associated with alternative treatment techniques used by the CHIVA and ASVAL. Chapter 9 describes the hemodynamic effects following treatment to relieve pelvic reflux and obstruction. Finally, Chapter 10 demonstrates that contrary to general belief there is a moderate to good correlation between certain hemodynamic measurements and clinical severity of chronic venous disease. The authors believe that this document will be a timely asset to both clinicians and researchers alike. It is directed towards surgeons and physicians who are anxious to incorporate the conclusions of research into their daily practice. It is also directed to postgraduate trainees, vascular technologists and bioengineers, particularly to help them understand the hemodynamic background to pathophysiology, investigations and treatment of patients with venous disorders. Hopefully it will be a platform for those who would like to embark on new research in the field of venous disease.

Quest for the Vulnerable Atheroma: Carotid Stenosis and Diametric Strain--A Feasibility Study.

The Bernoulli effect may result in eruption of a vulnerable carotid atheroma, causing a stroke. We measured electrocardiography (ECG)-registered QRS intra-stenotic blood velocity and atheroma strain dynamics in carotid artery walls using ultrasonic tissue Doppler methods, providing displacement and time resolutions of 0.1 µm and 3.7 ms. Of 22 arteries, 1 had a peak systolic velocity (PSV) >280 cm/s, 4 had PSVs between 165 and 280 cm/s and 17 had PSVs <165 cm/s. Eight arteries with PSVs <65 cm/s and 4 of 9 with PSVs between 65 and 165 cm/s had normal systolic diametric expansion (0% and 7%) and corresponding systolic wall thinning. The remaining 10 arteries had abnormal systolic strain dynamics, 2 with diametric reduction (>-0.05 mm), 2 with extreme wall expansion (>0.1 mm), 2 with extreme wall thinning (>-0.1 mm) and 4 with combinations. Decreases in systolic diameter and/or extreme systolic arterial wall thickening may indicate imminent atheroma rupture.

Effects of wall distensibility in hemodynamic simulations of an arteriovenous fistula.

Arteriovenous fistulae are created surgically to provide adequate access for dialysis patients suffering from end-stage renal disease. It has long been hypothesized that the rapid blood vessel remodeling occurring after fistula creation is in part a process to restore the mechanical stresses to some preferred level, i.e., mechanical homeostasis. The current study presents fluid-structure interaction (FSI) simulations of a patient-specific model of a mature arteriovenous fistula reconstructed from 3D ultrasound scans. The FSI results are compared with previously published data of the same model but with rigid walls. Ultrasound-derived wall motion measurements are also used to validate the FSI simulations of the wall motion. Very large time-averaged shear stresses, 10-15 Pa, are calculated at the fistula anastomosis in the FSI simulations, values which are much larger than what is typically thought to be the normal homeostatic shear stress in the peripheral vasculature. Although this result is systematically lower by as much as 50% compared to the analogous rigid-walled simulations, the inclusion of distensible vessel walls in hemodynamic simulations does not reduce the high anastomotic shear stresses to "normal" values. Therefore, rigid-walled analyses may be acceptable for identifying high shear regions of arteriovenous fistulae.

Agreement between site-reported and ultrasound core laboratory results for duplex ultrasound velocity measurements in the Carotid Revascularization Endarterectomy versus Stenting Trial.

OBJECTIVE: Patients in the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) had duplex ultrasound (DU) scans prior to treatment and during follow-up to document the severity of carotid disease and the anatomic outcome of carotid endarterectomy (CEA) or carotid artery stenting (CAS). An ultrasound core laboratory (UCL) reviewed DU data from the clinical sites. This analysis was done to determine the agreement between site-reported and UCL-verified DU velocity measurements. METHODS: Clinical site DU worksheets, B-mode images, and Doppler velocity waveforms for the treated carotid arteries were reviewed at the UCL. The highest internal carotid artery peak systolic velocity (PSV) and associated Doppler angle were verified. If the angle was misaligned by >3 degrees, it was remeasured at the UCL and the PSV was recalculated. Agreement for PSV was defined as site-reported PSV within ± 5% of UCL-verified PSV. Transcription errors were corrected by the UCL but were not considered as disagreements. Follow-up analysis was limited to patients who received the assigned treatment. RESULTS: The UCL reviewed 1702 prior-to-treatment and 1743 12-month follow-up DU scans (873 CEA, 870 CAS) from 111 clinical sites. Site-reported and UCL-verified PSV agreed in 1124 (66%) of the prior-to-treatment scans and 1200 (69%) of the follow-up scans. In those cases with a disagreement, Doppler angle accounted for disagreement in 339 (59%) of the prior-to-treatment scans and 277 (51%) of the follow-up scans. Based on a threshold PSV for ≥ 70% stenosis of ≥ 230 cm/s on the prior-to-treatment scans and ≥ 300 cm/s on the follow-up scans, UCL review resulted in reclassification of stenosis severity in 75 (4.4%) of the prior-to-treatment scans and 13 (0.75%) of the follow-up scans. There is evidence that the proportion of reclassification at follow-up was greater for CAS (10 scans; 1.2%) than for CEA (three scans; 0.34%) (P = .057). CONCLUSIONS: There was a high rate of agreement between site-reported and UCL-verified DU results in CREST, and UCL review was associated with a low rate of stenosis reclassification. However, angle alignment errors were quite common and prompted recalculation of velocity in 20% of prior-to-treatment scans and 18% of follow-up scans. The use of a UCL provides a uniform process for DU interpretation and can identify sources of error and suggest technical improvements for future studies.

Incomplete restoration of homeostatic shear stress within arteriovenous fistulae.

Arteriovenous fistulae are surgically created to provide adequate access for dialysis patients suffering from end-stage renal disease. It has long been hypothesized that the rapid blood vessel remodeling occurring after fistula creation is, in part, a process to restore the mechanical stresses to some preferred level, i.e., mechanical homeostasis. We present computational hemodynamic simulations in four patient-specific models of mature arteriovenous fistulae reconstructed from 3D ultrasound scans. Our results suggest that these mature fistulae have remodeled to return to ''normal'' shear stresses away from the anastomoses: about 1.0 Pa in the outflow veins and about 2.5 Pa in the inflow arteries. Large parts of the anastomoses were found to be under very high shear stresses >15 Pa, over most of the cardiac cycle. These results suggest that the remodeling process works toward restoring mechanical homeostasis in the fistulae, but that the process is limited or incomplete, even in mature fistulae, as evidenced by the elevated shear at or near the anastomoses. Based on the long term clinical viability of these dialysis accesses, we hypothesize that the elevated nonhomeostatic shear stresses in some portions of the vessels were not detrimental to fistula patency.

Three-dimensional ultrasonography measurements after endovascular aneurysm repair.

BACKGROUND: Ultrasonographic (US) assessment of abdominal aortic aneurysms is typically performed by measuring maximal aneurysm diameter from two-dimensional images. These measurements are prone to inaccuracies owing to image planes and interobserver variability. The purpose of this study was to compare the variability in diameter, cross-sectional area (CSA), and volume measurements of abdominal aortic aneurysms obtained using a three-dimensional (3D) US imaging system with those obtained using computed tomographic (CT) angiography, and to determine the reliability of these measures. METHODS: Seven patients in whom endovascular aneurysm repairs were performed underwent CT angiography in addition to a 3D US scan. Measurements computed using 3D surface reconstructions of CT and 3D US scans included maximum diameter, CSA, and aneurysm volume. The seven matched CT and 3D US scans were compared at baseline and 6 to 8 weeks later. RESULTS: The average aneurysm measured 57.2 mm on CT and 56.2 mm on US (P = 0.14). Correlation coefficients for diameter, CSA, and volume were 0.88, 0.90, and 0.93, respectively (all P values < 0.001). A Bland-Altman analysis demonstrated a strong agreement between 92% of the diameter, 96.4% of the CSA, and 100% of the volume measurements. The interrater reliability was remarkably high comparing the modalities (CT vs. US), and ranged from 0.934 to 0.997 for single measurements and 0.965 to 0.998 for all measurements together; moreover, there was a strong reliability when the tests were reviewed 6 to 8 weeks later, with a reliability of 0.962 to 0.998 for single measurements and 0.992 to 0.999 for all tests (all P values < 0.001). CONCLUSIONS: The 3D US is an accurate and noninvasive method of determining aneurysm size and geometry that is reproducible. Volumetric measurements may represent a significant advancement in long-term follow-up after endovascular aneurysm repair.

Restenosis after carotid artery stenting and endarterectomy: a secondary analysis of CREST, a randomised controlled trial.

BACKGROUND: In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite primary endpoint of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke thereafter did not differ between carotid artery stenting and carotid endarterectomy for symptomatic or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to compare the composite endpoint of restenosis or occlusion. METHODS: Patients with stenosis of the carotid artery who were asymptomatic or had had a transient ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000, and July 18, 2008. In this secondary analysis, the main endpoint was a composite of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a reduction in diameter of the target artery of at least 70%, diagnosed by a peak systolic velocity of at least 3·0 m/s. Studies were done in CREST-certified laboratories and interpreted at the Ultrasound Core Laboratory (University of Washington). The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. We used proportional hazards models to assess the association between baseline characteristics and risk of restenosis. Analyses were per protocol. CREST is registered with ClinicalTrials.gov, number NCT00004732. FINDINGS: 2191 patients received their assigned treatment within 30 days of randomisation and had eligible ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting (Kaplan-Meier rate 6·0%) and 62 who had carotid endarterectomy (6·3%) had restenosis or occlusion (hazard ratio [HR] 0·90, 95% CI 0·63-1·29; p=0·58). Female sex (1·79, 1·25-2·56), diabetes (2·31, 1·61-3·31), and dyslipidaemia (2·07, 1·01-4·26) were independent predictors of restenosis or occlusion after the two procedures. Smoking predicted an increased rate of restenosis after carotid endarterectomy (2·26, 1·34-3·77) but not after carotid artery stenting (0·77, 0·41-1·42). INTERPRETATION: Restenosis and occlusion were infrequent and rates were similar up to 2 years after carotid endarterectomy and carotid artery stenting. Subsets of patients could benefit from early and frequent monitoring after revascularisation. FUNDING: National Institute of Neurological Disorders and Stroke and Abbott Vascular Solutions.

Carotid Doppler velocity measurements and anatomic stenosis: correlation is futile.

BACKGROUND: Duplex ultrasound with Doppler velocimetry is widely used to evaluate the presence and severity of internal carotid artery stenosis; however, a variety of velocity criteria are currently being applied to classify stenosis severity. The purpose of this study is to compare published Doppler velocity measurements to the severity of internal carotid artery stenosis as assessed by x-ray angiography in order to clarify the relationship between these 2 widely used approaches to assess carotid artery disease. METHODS: Scatter diagrams or "scattergrams" of correlations between Doppler velocity measurements and stenosis severity as assessed by x-ray contrast angiography were obtained from published articles for native and stented internal carotid arteries. The scattergrams were graphically digitized, combined, and segmented into categories bounded by 50% and 70% diameter reduction. These data were combined and divided into 3 sets representing different velocity parameters: (1) peak systolic velocity, (2) end-diastolic velocity, and (3) the internal carotid artery to common carotid artery peak systolic velocity ratio. The horizontal axis of each scattergram was transformed to form a cumulative distribution function, and thresholds were established for the stenosis categories to assess data variability. RESULTS: Nineteen publications with 22 data sets were identified and included in this analysis. Wide variability was apparent between all 3 velocity parameters and angiographic percent stenosis. The optimal peak systolic velocity thresholds for stenosis in stented carotid arteries were higher than those for native carotid arteries. Within each category of stenosis, the variability of all 3 velocity parameters was significantly lower in stented arteries than in native arteries. CONCLUSION: Although Doppler velocity criteria have been successfully used to classify the severity of stenosis in both native and stented carotid arteries, the relationship to angiographic stenosis contains significant variability. This analysis of published studies suggests that further refinements in Doppler velocity criteria will not lead to improved correlation with carotid stenosis as demonstrated by angiography.

Hemodynamic conditions in a failing peripheral artery bypass graft.

OBJECTIVE: The mechanisms of restenosis in autogenous vein bypass grafts placed for peripheral artery disease are not completely understood. We investigated the role of hemodynamic stress in a case study of a revised bypass graft that failed due to restenosis. METHODS: The morphology of the lumen was reconstructed from a custom three-dimensional ultrasound system. Scans were taken at 1, 6, and 16 months after a patch angioplasty procedure. Computational hemodynamic simulations of the patient-specific model provided the blood flow features and the hemodynamic stresses on the vessel wall at the three times studied. RESULTS: The vessel was initially free of any detectable lesions, but a 60% diameter-reducing stenosis developed during the 16-month study interval. As determined from the simulations, chaotic and recirculating flow occurred downstream of the stenosis due to the sudden widening of the lumen at the patch location. Curvature and a sudden increase in the lumen cross-sectional area induced these flow features that are hypothesized to be conducive to intimal hyperplasia. Favorable agreement was found between simulation results and in vivo Doppler ultrasound velocity measurements. CONCLUSIONS: Transitional and chaotic flow occurs at the site of the revision, inducing a complex pattern of wall shear as computed with the hemodynamic simulations. This supports the hypothesis that the hemodynamic stresses in the revised segment, produced by the coupling of vessel geometry and chaotic flow, led to the intimal hyperplasia and restenosis of the graft.

Investigation of cerebral hemodynamics and collateralization in asymptomatic carotid stenoses.

Stroke is the second leading cause of death in the world, and one of the major causes of disability. Approximately 30% of ischemic strokes are due to plaque rupture in the carotid arteries. The most popular diagnostic method uses Doppler ultrasound to find the percent stenosis. However, other factors, such as the hemodynamics around the plaque may play a larger role in identifying the risk of plaque rupture. It has been shown previously in simulations that non-collateral flow in the circle of Willis (COW) could cause an increase of the intraluminal velocity around carotid plaque. This added strain may increase the vulnerability of the plaque to rupture. We investigated asymmetries in flow waveforms in the middle cerebral artery (MCA) in asymptomatic patients with carotid artery stenosis. We compared clinical results of velocity waveforms in the MCA, acquired using transcranial Doppler (TCD), with a simple linear simulation model of the intra- and extracranial arterial network to investigate the relationship between contralateral and ipsilateral flow profiles in the MCA for patients with asymptomatic carotid stenosis. In 17 out of 23 patients we found waveforms consistent with those predicted for a collateralized COW, with minimal differences in delay, velocity magnitude and resistivity index. In 6 cases, some unexpected findings were noted, such as large delays for 2 patients ≤ 50% stenosis, and a large velocity difference with low delay for 4 patients. More studies are needed to elucidate the role of incomplete intracranial collateralization on the hemodynamics around carotid plaque and to use imaging of the COW to corroborate our results.

Intracranial collateralization determines hemodynamic forces for carotid plaque disruption.

INTRODUCTION: Percent diameter reduction provides an imperfect assessment of the risk for stroke from carotid atheroembolism. Stroke associated with atherosclerotic carotid stenosis commonly results from plaque disruption brought about by hemodynamic shear stress and Bernoulli forces. The aim of the present study was to predict the effect of incomplete intracranial collateralization through the circle of Willis (COW) on disruptive hemodynamic forces acting on carotid plaques. METHODS: A simple circuit model of the major pathways and collaterals that form and supply the COW was developed. We modeled the intra- and extracranial arterial circuits from standard anatomic references, and the pressure-flow relationships within these conduits from standard fluid mechanics. The pressure drop caused by (laminar and turbulent) flow along the internal carotid artery path was then computed. Carotid circulation to the brain was classified as being with or without collateral connections through the COW, and the extracranial carotid circuit as being with or without severe stenosis. The pressure drop was computed for each scenario. Finally, a linear circuit model was used to compute brain blood flow in the presence/absence of a disconnected COW. RESULTS: Pressure drop across a carotid artery stenosis increased as the flow rate within the carotid conduit increased. Poststenotic turbulence from a sudden expansion distal to the stenosis resulted in an additional pressure drop. Despite the stenosis, mean brain blood flow was sustained at 4.15 mL/s bilaterally. In the presence of an intact (collateralized) COW, this was achieved by enhanced flow in the contralateral (normal) carotid artery. However, in a disconnected COW, this was achieved by sustained systolic and enhanced diastolic flow through the stenosed artery. For a similar degree of stenosis, flow and velocity across the plaque was much higher when the COW was disconnected compared with an intact COW. Furthermore, the pressure drop across a similar stenosis was significantly higher with a disconnected COW compared with an intact COW. CONCLUSIONS: Incomplete intracranial collateralization through the COW results in increased flow rates and velocities, and therefore large pressure drops across a carotid artery stenosis. This exerts large disruptive shear stress on the plaque compared with patients with an intact COW. Percent diameter reduction provides an inaccurate assessment of risk for atheroembolic stroke. An assessment of carotid flow rates, flow velocities, and the intracranial collateral circulation may add independent information to refine the estimation of stroke risk in patients with asymptomatic carotid atherosclerosis.