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Background Immediate and accurate detection of intracranial hemorrhages (ICHs) is essential to provide a good clinical outcome for patients with ICH. Artificial intelligence has the potential to provide this, but the assessment of these methods needs to be investigated in depth. This study aimed to assess the ability of Canon's AUTOStroke Solution ICH detection algorithm to accurately identify patients both with and without ICHs present. Methods Data from 200 ICH and 102 non-ICH patients who presented with stroke-like symptoms between August 2016 and December 2019 were collected retrospectively. Patients with ICH had at least one of the following hemorrhage types: intraparenchymal (n = 181), intraventricular (n = 45), subdural (n = 13), or subarachnoid (n = 19). Noncontrast computed tomography scans were analyzed for each patient using Canon's AUTOStroke Solution ICH algorithm to determine which slices contained hemorrhage. The algorithm's ability to detect ICHs was assessed using sensitivity, specificity, positive predictive value, and negative predictive value. Percentages of cases correctly identified as ICH positive and negative were additionally calculated. Results Automated analysis demonstrated the following metrics for identifying hemorrhage slices within all 200 patients with ICH (95% confidence intervals): sensitivity = 0.93 ± 0.03, specificity = 0.93 ± 0.01, positive predictive value = 0.85 ± 0.02, and negative predictive value = 0.98 ± 0.01. A total of 95% (245 of 258) of ICH volumes were correctly triaged, whereas 88.2% (90 of 102) of non-ICH cases were correctly classified as ICH negative. Conclusions Canon's AUTOStroke Solution ICH detection algorithm was able to accurately detect intraparenchymal, intraventricular, subdural, and subarachnoid hemorrhages in addition to accurately determine when an ICH was not present. Having this automated ICH detection method could drastically improve treatment times for patients with ICH.

Rapid and accurate diagnosis of large vessel occlusions (LVOs) in acute ischemic stroke (AIS) patients using automated software could improve clinical workflow in determining thrombectomy in eligible patients. Artificial intelligence-based methods could accomplish this; however, their performance in various clinical scenarios, relative to clinical experts, must be thoroughly investigated. We aimed to assess the ability of Canon’s AUTOStroke Solution LVO application in properly detecting and locating LVOs in AIS patients. Data from 202 LVO and 101 non-LVO AIS patients who presented with stroke-like symptoms between March 2019 and February 2020 were collected retrospectively. LVO patients had either an internal carotid artery (ICA) ( n = 59), M1 middle cerebral artery (MCA) ( n = 82) or M2 MCA ( n = 61) occlusion. Computed tomography angiography (CTA) scans from each patient were pushed to the automation platform and analyzed. The algorithm’s ability to detect LVOs was assessed using accuracy, sensitivity and Matthews correlation coefficients (MCCs) for each occlusion type. The following results were calculated for each occlusion type in the study (accuracy, sensitivity, MCC): ICA = (0.95, 0.90, 0.89), M1 MCA = (0.89, 0.77, 0.78) and M2 MCA = (0.80, 0.51, 0.59). For the non-LVO cohort, 98% (99/101) of cases were correctly predicted as LVO negative. Processing time for each case was 69.8 ± 1.1 seconds (95% confidence interval). Canon’s AUTOStroke Solution LVO application was able to accurately identify ICA and M1 MCA occlusions in addition to almost perfectly assessing when an LVO was not present. M2 MCA occlusion detection needs further improvement based on the sensitivity results displayed by the LVO detection algorithm.

Computed tomography perfusion (CTP) is crucial for acute ischemic stroke (AIS) patient diagnosis. To improve infarct prediction, enhanced image processing and automated parameter selection have been implemented in Vital Images’ new CTP+ software. We compared CTP+ with its previous version, commercially available software (RAPID and Sphere), and follow-up diffusion-weighted imaging (DWI). Data from 191 AIS patients between March 2019 and January 2020 was retrospectively collected and allocated into endovascular intervention ( n = 81) and conservative treatment ( n = 110) cohorts. Intervention patients were treated for large vessel occlusion, underwent mechanical thrombectomy, and achieved successful reperfusion of thrombolysis in cerebral infarction 2b/2c/3. Conservative treatment patients suffered large or small vessel occlusion and did not receive intravenous thrombolysis or mechanical thrombectomy. Infarct and penumbra were assessed using intervention and conservative treatment patients, respectively. Infarct and penumbra volumes were segmented from CTP+ and compared with 24-h DWI along with RAPID, Sphere, and Vitrea. Mean infarct differences (95% confidence intervals) and Spearman correlation coefficients (SCCs) between DWI and each CTP software product for intervention patients are: CTP+ = (5.8 ± 5.9 ml, 0.62), RAPID = (10.0 ± 5.2 ml, 0.73), Sphere = (3.0 ± 6.0 ml, 0.56), Vitrea = (7.2 ± 4.9 ml, 0.66). For conservative treatment patients, mean infarct differences and SCCs are: CTP+ = (–8.0 ± 5.4 ml, 0.64), RAPID = (–25.6 ± 11.5 ml, 0.60), Sphere = (–25.6 ± 8.0 ml, 0.66), Vitrea = (1.3 ± 4.0 ml, 0.72). CTP+ performed similarly to RAPID and Sphere in addition to its semi-automated predecessor, Vitrea, when assessing intervention patient infarct volumes. For conservative treatment patients, CTP+ outperformed RAPID and Sphere in assessing penumbra. Semi-automated Vitrea remains the most accurate in assessing penumbra, but CTP+ provides an improved workflow from its predecessor.

BackgroundCT perfusion (CTP) infarct and penumbra estimations determine the eligibility of patients with acute ischemic stroke (AIS) for endovascular intervention. This study aimed to determine volumetric and spatial agreement of predicted RAPID, Vitrea, and Sphere CTP infarct with follow-up fluid attenuation inversion recovery (FLAIR) MRI infarct.Methods108 consecutive patients with AIS and large vessel occlusion were included in the study between April 2019 and January 2020 . Patients were divided into two groups: endovascular intervention (n=58) and conservative treatment (n=50). Intervention patients were treated with mechanical thrombectomy and achieved successful reperfusion (Thrombolysis in Cerebral Infarction 2b/2 c/3) while patients in the conservative treatment group did not receive mechanical thrombectomy or intravenous thrombolysis. Intervention and conservative treatment patients were included to assess infarct and penumbra estimations, respectively. It was assumed that in all patients treated conservatively, penumbra converted to infarct. CTP infarct and penumbra volumes were segmented from RAPID, Vitrea, and Sphere to assess volumetric and spatial agreement with follow-up FLAIR MRI.ResultsMean infarct differences (95% CIs) between each CTP software and FLAIR MRI for each cohort were: intervention cohort: RAPID=9.0±7.7 mL, Sphere=−0.2±8.7 mL, Vitrea=−7.9±8.9 mL; conservative treatment cohort: RAPID=−31.9±21.6 mL, Sphere=−26.8±17.4 mL, Vitrea=−15.3±13.7 mL. Overlap and Dice coefficients for predicted infarct were (overlap, Dice): intervention cohort: RAPID=(0.57, 0.44), Sphere=(0.68, 0.60), Vitrea=(0.70, 0.60); conservative treatment cohort: RAPID=(0.71, 0.56), Sphere=(0.73, 0.60), Vitrea=(0.72, 0.64).ConclusionsSphere proved the most accurate in patients who had intervention infarct assessment as Vitrea and RAPID overestimated and underestimated infarct, respectively. Vitrea proved the most accurate in penumbra assessment for patients treated conservatively although all software overestimated penumbra.

OBJECTIVE. The objective of this study was to compare image quality and clinically significant lesion detection on deep learning reconstruction (DLR) and iterative reconstruction (IR) images of submillisievert chest and abdominopelvic CT. MATERIALS AND METHODS. Our prospective multiinstitutional study included 59 adult patients (33 women, 26 men; mean age ± SD, 65 ± 12 years old; mean body mass index [weight in kilograms divided by the square of height in meters] = 27 ± 5) who underwent routine chest (n = 22; 16 women, six men) and abdominopelvic (n = 37; 17 women, 20 men) CT on a 640-MDCT scanner (Aquilion ONE, Canon Medical Systems). All patients gave written informed consent for the acquisition of low-dose (LD) CT (LDCT) after a clinically indicated standard-dose (SD) CT (SDCT). The SDCT series (120 kVp, 164-644 mA) were reconstructed with interactive reconstruction (IR) (adaptive iterative dose reduction [AIDR] 3D, Canon Medical Systems), and the LDCT (100 kVp, 120 kVp; 30-50 mA) were reconstructed with filtered back-projection (FBP), IR (AIDR 3D and forward-projected model-based iterative reconstruction solution [FIRST], Canon Medical Systems), and deep learning reconstruction (DLR) (Advanced Intelligent Clear-IQ Engine [AiCE], Canon Medical Systems). Four subspecialty-trained radiologists first read all LD image sets and then compared them side-by-side with SD AIDR 3D images in an independent, randomized, and blinded fashion. Subspecialty radiologists assessed image quality of LDCT images on a 3-point scale (1 = unacceptable, 2 = suboptimal, 3 = optimal). Descriptive statistics were obtained, and the Wilcoxon sign rank test was performed. RESULTS. Mean volume CT dose index and dose-length product for LDCT (2.1 ± 0.8 mGy, 49 ± 13mGy·cm) were lower than those for SDCT (13 ± 4.4 mGy, 567 ± 249 mGy·cm) (p < 0.0001). All 31 clinically significant abdominal lesions were seen on SD AIDR 3D and LD DLR images. Twenty-five, 18, and seven lesions were detected on LD AIDR 3D, LD FIRST, and LD FBP images, respectively. All 39 pulmonary nodules detected on SD AIDR 3D images were also noted on LD DLR images. LD DLR images were deemed acceptable for interpretation in 97% (35/37) of abdominal and 95-100% (21-22/22) of chest LDCT studies (p = 0.2-0.99). The LD FIRST, LD AIDR 3D, and LD FBP images had inferior image quality compared with SD AIDR 3D images (p < 0.0001). CONCLUSION. At submillisievert chest and abdominopelvic CT doses, DLR enables image quality and lesion detection superior to commercial IR and FBP images.

Supplemental material, sj-pdf-1-neu-10.1177_1971400921998952 for Validation of an artificial intelligence-driven large vessel occlusion detection algorithm for acute ischemic stroke patients by Ryan A Rava, Blake A Peterson, Samantha E Seymour, Kenneth V Snyder, Maxim Mokin, Muhammad Waqas, Yiemeng Hoi, Jason M Davies, Elad I Levy, Adnan H Siddiqui and Ciprian N Ionita in The Neuroradiology Journal

Introduction/Purpose Computed tomography perfusion (CTP) is a common imaging modality utilized to assess acute ischemic stroke (AIS) patient eligibility for mechanical thrombectomy. This assessment is done using an ischemic tissue ratio (penumbra to infarct) which is required to be greater than 1 for patients to be eligible for thrombectomy. Since various CTP software utilize different perfusion parameters and thresholds, there are known to be discrepancies in the amount of ischemic tissue quantified for each and therefore conflicting decisions regarding thrombectomy eligibility across software. This study aimed to assess the volumetric agreement of infarct between CTP and 24-hour follow-up fluid-attenuation inversion recovery (FLAIR) magnetic resonance imaging (MRI) along with the number of patients who would be misdiagnosed as ineligible for thrombectomy based on penumbra to infarct ratios by each CTP software. Materials and Methods Eighty-one emergent large vessel occlusion AIS patients who underwent successful reperfusion (thrombolysis in cerebral infarction 2b/2c/3) were included in this study. Predicted infarct and penumbra volumes were quantified within RAPID, Sphere, and Vitrea CTP software and compared with infarct measurements from FLAIR MRI. The following CTP parameters and thresholds were used to quantify ischemic tissue through comparison with contralateral hemispheres: RAPID: infarct=30% reduction of cerebral blood flow (CBF), penumbra=6 second increase in time to reach maximal residue function; Sphere: infarct=25% reduction of CBF (and 5 second increase of time-to-peak (TTP)), penumbra=5 second increase in TTP; Vitrea: infarct=38% reduction in cerebral blood volume (and 5.3 second increase in TTP or 55% reduction in mean-transit-time), penumbra=5.3 second increase in TTP or 5.8 second increase in delay time or 58% reduction in CBF. Penumbra to infarct ratios were calculated utilizing each software. Results Mean infarct differences, represented as 95% confidence intervals, between each software and FLAIR MRI are as follows: RAPID=6.96±4.93 mL, Sphere=-0.07±6.11 mL, Vitrea=4.13±4.73 mL. Mean absolute errors for each CTP software compared with FLAIR MRI are: RAPID=14.48 mL, Sphere=15.43 mL, Vitrea=11.44 mL. Mean penumbra to infarct ratios for each CTP software are: RAPID=70.93; Sphere=32.72; Vitrea=12.33. Total number of patients misdiagnosed as ineligible for thrombectomy (penumbra to infarct ratio less than 1 but successful reperfusion was conducted) for each software: RAPID=1.23% (1/81), Sphere=6.17% (5/81), Vitrea=25.93% (21/81). Conclusions Sphere provided the most accurate results regarding the closest predicted CTP infarct volume to the true FLAIR MRI infarct volume, although with slightly higher error in its measurements compared to RAPID and Vitrea. Penumbra to infarct ratio analysis indicated RAPID and Sphere to provide the most accurate assessment regarding patient eligibility for thrombectomy. However, it appears sacrificing ischemic tissue measurement precision is required for more accurate inclusion of patients as thrombectomy eligible. This is seen by the significantly high mean penumbra to infarct ratio for RAPID which may suggest a caution overestimation of penumbra to label as many patients as possible as thrombectomy eligible for the purpose of regaining lost neurological function. Disclosures R. Rava: None. M. Mokin: 1; C; NIH grant support R21NS109575. 2; C; Canon Medical Systems Corporation, Cerebrotech, Imperative care. M. Waqas: None. J. Davies: 1; C; National Center for Advancing Translational Sciences of the National Institutes of Health under award number KL2TR001413. 3; C; Penumbra. 4; C; RIST Neurovascular. E. Levy: 2; C; Claret Medical, GLG Consulting, Guidepoint Global, Imperative Care, Medtronic, Rebound, StimMed. 4; C; NeXtGen Biologics, RAPID Medical, Claret Medical, Cognition Medical, Imperative Care (formerly the Stroke Project), Rebound Therapeutics, StimMed, Three Rivers Medical. Y. Hoi: 5; C; Canon Medical Systems Inc. A. Siddiqui: 2; C; Amnis Therapeutics, Boston Scientific, Canon Medical Systems USA Inc, Cerebrotech Medical Systems Inc, Cerenovus, Corindus Inc, Endostream Medical Ltd, Guidepoint Global Consulting, Imperative Care, Integra LifeSciences Corp, Medtronic, MicroVention, Northwest University–DSMB Chair for HEAT Trial, Penumbra, Q’Apel Medical Inc, Rapid Medical, Rebound Therapeutics Corp, Serenity Medical Inc, Silk Road Medical, StimMed, Stryker, Three Rivers Medical, Inc., VasSol, W.L. Gore & Associates. 4; C; Amnis Therapeutics, Apama Medical, Blink TBI Inc, Buffalo Technology Partners Inc, Cardinal Consultants, Cerebrotech Medical Systems, Inc, Cognition Medical, Endostream Medical Ltd, Imperative Care, International Medical Distribution Partners, Neurovascular Diagnostics Inc, Q’Apel Medical Inc, Rebound Therapeutics Corp, Rist Neurovascular Inc, Serenity Medical Inc, Silk Road Medical, StimMed, Synchron, Three Rivers Medical Inc, Viseon Spine Inc. C. Ionita: 1; C; Equipment grant from Canon Medical Systems, Cummings Foundation support. K. Snyder: 2; C; Canon Medical Systems Corporation, Penumbra Inc, Medtronic, Jacobs Institute.

Introduction/Purpose Utilization of computed tomography perfusion (CTP) to quantify infarct core and penumbra is commonly conducted to determine acute ischemic stroke patient (AIS) eligibility for endovascular intervention procedures. Accurate estimations of infarct and penumbra spatial location are essential as they provide information regarding the location of the vessel occlusion and regions where infarct will advance to. Discrepancies have been known to occur between various CTP software regarding volumetric calculations and spatial location of ischemic tissue due to different perfusion parameters and thresholds being used across software. This study aimed to assess the spatial and volumetric accuracy of RAPID, Sphere, and Vitrea CTP software predicted infarct and penumbra in comparison with final infarct from fluid-attenuation inversion recovery (FLAIR) magnetic resonance imaging (MRI). Materials and Methods Sixty emergent large vessel occlusion AIS patients treated at a single comprehensive stroke center were included in this study. All patients were required to have undergone initial CTP imaging and 24-hour follow-up FLAIR MRI. Thirty endovascular intervention and 30 medical management patients were included to assess infarct and penumbra tissue, respectively. Endovascular intervention patients were required to have achieved complete successful reperfusion defined as thrombolysis in cerebral infarction 2c/3 to assure all penumbra was salvaged. For medical management patients, it is assumed that all estimated penumbra has converted to infarct on follow-up FLAIR MRI. Within RAPID, Sphere, and Vitrea CTP software, infarct and penumbra tissue was quantified and segmented. Volumetric assessment of CTP infarct and penumbra volumes were conducted using mean infarct differences and mean absolute error (MAE). Spatial accuracy of segmented ischemic tissue was assessed using Dice coefficients, overlap coefficients, sensitivity, specificity, and accuracy metrics. Results Mean infarct differences, represented as 95% confidence intervals, between FLAIR MRI and each CTP software for each patient cohort are: Intervention patients- RAPID=4.9±6.4 mL, Sphere=-4.5±6.6 mL, Vitrea=3.5±4.9 mL; Medical management patients- RAPID=-40.0±23.3 mL, Sphere=-21.4±17.4 mL, Vitrea=7.4±10.3 mL. MAEs for predicted infarct from each software compared to FLAIR MRI infarct are: Intervention patients- RAPID=13.7 mL, Sphere=12.8 mL, Vitrea=7.3 mL; Medical management patients: RAPID=52.5 mL, Sphere=34.3 mL, Vitrea=18.9 mL. Spatial assessment metrics for ischemic tissue for each patient group and for each software are indicated in table 1. Conclusions Volumetric results indicate RAPID, Sphere, and Vitrea CTP software all perform similarly in assessing volumetric agreement with final FLAIR MRI infarct for endovascular intervention patients. However, spatial agreement metrics indicate Vitrea performs the best in locating infarct for endovascular intervention patients. For medical management patients, Vitrea software appears the most accurate in assessing penumbra based on volumetric measurements in addition to overlap coefficients. Disclosures R. Rava: None. M. Mokin: 1; C; NIH grant R21NS109575. 2; C; Canon Medical Systems Corporation, Cerebrotech, Imperative Care. M. Waqas: None. J. Davies: 1; C; National Center for Advancing Translational Sciences of the National Institutes of Health under award number KL2TR001413. 3; C; Penumbra. 4; C; RIST Neurovascular. A. Siddiqui: 2; C; Amnis Therapeutics, Boston Scientific, Canon Medical Systems USA Inc, Cerebrotech Medical Systems Inc, Cerenovus, Corindus Inc, Endostream Medical Ltd., Guidepoint Global Consulting, Imperative Care, Integra LifeSciences Corp, Medtronic, MicroVention, Northwest University–DSMB Chair for HEAT Trial, Penumbra, Q’Apel Medical Inc, Rapid Medical, Rebound Therapeutics Corp, Serenity Medical Inc, Silk Road Medical, StimMed, Stryker, Three Rivers Medical, Inc, VasSol, W.L. Gore & Associates. 4; C; Amnis Therapeutics, Apama Medical, Blink TBI Inc., Buffalo Technology Partner Inc., Cardinal Consultants, Cerebrochtech Medical Systems Inc., Cognition Medical, Endostream Medical Ltd, Imperative Care, International Medical Distribution Partners, Neurovascular Diagnostics Inc., Q’Apel Medical Inc, Rebound Therapeutics Corp, Rist Neurovascular Inc, Serenity Medical Inc, Silk Road Medical, StimMed, Synchron, Three Rivers Medical Inc., Viseon Spine Inc. E. Levy: 2; C; Claret Medical, GLG Consulting, Guidepoint Global, Imperative Care, Medtronic, Rebound, StimMed. 4; C; NeXtGen Biologics, RAPID Medical, Claret Medical, Cognition Medical, Imperative Care (formerly the Stroke Project), Rebound Therapeutics, StimMed, Three Rivers Medical. Y. Hoi: 5; C; Canon Medical Systems Inc. C. Ionita: 1; C; Equipment grant from Canon Medical Systems, Cummings Foundation support. K. Snyder: 2; C; Canon Medical Systems Corporation, Penumbra Inc, Medtronic, Jacobs Institute.

BACKGROUND AND PURPOSE: Brain CTP is used to estimate infarct and penumbra volumes to determine endovascular treatment eligibility for patients with acute ischemic stroke. We aimed to assess the accuracy of a Bayesian CTP algorithm in determining penumbra and final infarct volumes. MATERIALS AND METHODS: Data were retrospectively collected for 105 patients with acute ischemic stroke (55 patients with successful recanalization [TICI 2b/2c/3] and large-vessel occlusions and 50 patients without interventions). Final infarct volumes were calculated using DWI and FLAIR 24 hours following CTP imaging. RAPID and the Vitrea Bayesian CTP algorithm (with 3 different settings) predicted infarct and penumbra volumes for comparison with final infarct volumes to assess software performance. Vitrea settings used different combinations of perfusion maps (MTT, TTP, CBV, CBF, delay time) for infarct and penumbra quantification. Patients with and without interventions were included for assessment of predicted infarct and penumbra volumes, respectively. RESULTS: RAPID and Vitrea default setting had the most accurate final infarct volume prediction in patients with interventions ([Spearman correlation coefficient, mean infarct difference] default versus FLAIR: [0.77, 4.1 mL], default versus DWI: [0.72, 4.7 mL], RAPID versus FLAIR: [0.75, 7.5 mL], RAPID versus DWI: [0.75, 6.9 mL]). Default Vitrea and RAPID were the most and least accurate in determining final infarct volume for patients without an intervention, respectively (default versus FLAIR: [0.76, –0.4 mL], default versus DWI: [0.71, –2.6 mL], RAPID versus FLAIR: [0.68, −49.3 mL], RAPID versus DWI: [0.65, –51.5 mL]). CONCLUSIONS: Compared with RAPID, the Vitrea default setting was noninferior for patients with interventions and superior in penumbra estimation for patients without interventions as indicated by mean infarct differences and correlations with final infarct volumes.

Stimulated by a recent controversy regarding pressure drops predicted in a giant aneurysm with a proximal stenosis, the present study sought to assess variability in the prediction of pressures and flow by a wide variety of research groups. In phase I, lumen geometry, flow rates, and fluid properties were specified, leaving each research group to choose their solver, discretization, and solution strategies. Variability was assessed by having each group interpolate their results onto a standardized mesh and centerline. For phase II, a physical model of the geometry was constructed, from which pressure and flow rates were measured. Groups repeated their simulations using a geometry reconstructed from a micro-computed tomography (CT) scan of the physical model with the measured flow rates and fluid properties. Phase I results from 25 groups demonstrated remarkable consistency in the pressure patterns, with the majority predicting peak systolic pressure drops within 8% of each other. Aneurysm sac flow patterns were more variable with only a few groups reporting peak systolic flow instabilities owing to their use of high temporal resolutions. Variability for phase II was comparable, and the median predicted pressure drops were within a few millimeters of mercury of the measured values but only after accounting for submillimeter errors in the reconstruction of the life-sized flow model from micro-CT. In summary, pressure can be predicted with consistency by CFD across a wide range of solvers and solution strategies, but this may not hold true for specific flow patterns or derived quantities. Future challenges are needed and should focus on hemodynamic quantities thought to be of clinical interest.

BACKGROUND AND PURPOSE: Ulceration in carotid plaque is a risk indicator for ischemic stroke. Our aim was to compare plaque ulcer detection by standard TOF and CE-MRA techniques and to identify factors that influence its detection. MATERIALS AND METHODS: Carotid MR imaging scans were acquired on 2066 participants in the ARIC study. We studied the 600 thickest plaques. TOF-MRA, CE-MRA, and black-blood MR images were analyzed together to define ulcer presence (plaque surface niche ≥2 mm in depth). Sixty ulcerated arteries were detected. These arteries were randomly assigned, along with 40 nonulcerated plaques from the remaining 540, for evaluation of ulcer presence by 2 neuroradiologists. Associations between ulcer detection and ulcer characteristics, including orientation, location, and size, were determined and explored by CFD modeling. RESULTS: One CE-MRA and 3 TOF-MRAs were noninterpretable and excluded. Of 71 ulcers in 56 arteries, readers detected an average of 39 (55%) on both TOF-MRA and CE-MRA, 26.5 (37.5%) only on CE-MRA, and 1 (1.5%) only on TOF-MRA, missing 4.5 (6%) ulcers by both methods. Ulcer detection by TOF-MRA was associated with its orientation (distally pointing versus perpendicular: OR = 5.57 [95% CI, 1.08–28.65]; proximally pointing versus perpendicular: OR = 0.21 [95% CI, 0.14–0.29]); location relative to point of maximum stenosis (distal versus isolevel: OR = 5.17 [95% CI, 2.10–12.70]); and neck-to-depth ratio (OR = 1.96 [95% CI, 1.11–3.45]) after controlling for stenosis and ulcer volume. CONCLUSIONS: CE-MRA detects more ulcers than TOF-MRA in carotid plaques. Missed ulcers on TOF-MRA are influenced by ulcer orientation, location relative to point of maximum stenosis, and neck-to-depth ratio.

Object Pathological extremes in cerebrovascular remodeling may contribute to basilar artery (BA) dolichoectasia and fusiform aneurysm development. Factors regulating cerebrovascular remodeling are poorly understood. To better understand hemodynamic influences on cerebrovascular remodeling, we examined BA remodeling following common carotid artery (CCA) ligation in an animal model. Methods Rabbits were subjected to sham surgery (3 animals), unilateral CCA ligation (3 animals), or bilateral CCA ligation (5 animals). Transcranial Doppler ultrasonography and rotational angiography were used to compute BA flow, diameter, wall shear stress (WSS), and a tortuosity index on Days 0, 1, 4, 7, 14, 28, 56, and 84. Basilar artery tissues were stained and analyzed at Day 84. Statistical analysis was performed using orthogonal contrast analysis, repeated measures analysis of variance, or mixed regression analysis of repeated measures. Statistical significance was defined as a probability value < 0.05. Results Basilar artery flow and diameter increased significantly after the procedure in both ligation groups, but only the bilateral CCA ligation group demonstrated significant differences between groups. Wall shear stress significantly increased only in animals in the bilateral CCA ligation group and returned to baseline by Day 28, with 52% of WSS correction occurring by Day 7. Only the bilateral CCA ligation group developed significant BA tortuosity, occurring within 7 days postligation. Unlike the animals in the sham and unilateral CCA ligation groups, the animals in the bilateral CCA ligation group had histological staining results showing a substantial internal elastic lamina fragmentation. Conclusions Increased BA flow results in adaptive BA remodeling until WSS returns to physiological baseline levels. Morphological changes occur rapidly following flow alteration and do not require chronic insult to affect substantial and significant structural transformation. Additionally, it appears that there exists a flow-increase threshold that, when surpassed, results in significant tortuosity.

Background and Purpose— Hemodynamic insults at arterial bifurcations are hypothesized to play a key role in intracranial aneurysm formation. This study investigates aneurysm-initiating vascular responses at the rabbit basilar terminus subsequent to common carotid artery ligation. Methods— Nine adult female New Zealand white rabbits were subjected to sham, unilateral, or bilateral common carotid artery ligation to produce varying degrees of compensatory basilar artery flow increase. Basilar artery flow velocity and geometry were monitored by transcranial Doppler and rotational angiography, respectively, for 12 weeks after surgery. Bifurcation tissues were harvested at 12 weeks and examined histologically. From the histological sections, we quantified the destructive structural changes at the basilar terminus and correlated them with the basilar artery flow rate increase. Results— Subsequent to common carotid artery ligation, basilar artery flow rate increased by 105% to 900% at the maximum. All common carotid artery-ligated rabbits presented nascent aneurysm formation characterized by a bulge with thinned media and absent internal elastic lamina near the basilar terminus. We defined a nascent aneurysm index based on a multiplicative combination of the local destructive remodeling lengths measured at the nascent aneurysm. The nascent aneurysm index strongly correlated with the increase in basilar artery flow rate with R 2 =0.91. Conclusion— Without other known predisposition, flow increase alone at the basilar bifurcation can lead to a nascent aneurysm. This nascent aneurysm formation is dose-dependent on basilar artery flow increase.

Background and Purpose— Arterial bifurcation apices are common sites for cerebral aneurysms, raising the possibility that the unique hemodynamic conditions associated with flow dividers predispose the apical vessel wall to aneurysm formation. This study sought to identify the specific hemodynamic insults that lead to maladaptive vascular remodeling associated with aneurysm development and to identify early remodeling events at the tissue and cellular levels. Methods— We surgically created new branch points in the carotid vasculature of 6 female adult dogs. In vivo angiographic imaging and computational fluid dynamics simulations revealed the detailed hemodynamic microenvironment for each bifurcation, which were then spatially correlated with histologic features showing specific tissue responses. Results— We observed 2 distinct patterns of vessel wall remodeling: (1) hyperplasia that formed an intimal pad at the bifurcation apex and (2) destructive remodeling in the adjacent region of flow acceleration that resembled the initiation of an intracranial aneurysm, characterized by disruption of the internal elastic lamina, loss of medial smooth muscle cells, reduced proliferation of smooth muscle cells, and loss of fibronectin. Conclusions— Strong localization of aneurysm-type remodeling to the region of accelerating flow suggests that a combination of high wall shear stress and a high gradient in wall shear stress represents a “dangerous” hemodynamic condition that predisposes the apical vessel wall to aneurysm formation.

Object. Few researchers have quantified the role of arterial geometry in the pathogenesis of saccular cerebral aneurysms. The authors investigated the effects of parent artery geometry on aneurysm hemodynamics and assessed the implications relative to aneurysm growth and treatment effectiveness. Methods. The hemodynamics of three-dimensional saccular aneurysms arising from the lateral wall of arteries with varying arterial curves (starting with a straight vessel model) and neck sizes were studied using a computational fluid dynamics analysis. The effects of these geometric parameters on hemodynamic parameters, including flow velocity, aneurysm wall shear stress (WSS), and area of elevated WSS during the cardiac cycle (time-dependent impact zone), were quantified. Unlike simulations involving aneurysms located on straight arteries, blood flow inertia (centrifugal effects) rather than viscous diffusion was the predominant force driving blood into aneurysm sacs on curved arteries. As the degree of arterial curvature increased, flow impingement on the distal side of the neck intensified, leading to elevations in the WSS and enlargement of the impact zone at the distal side of the aneurysm neck. Conclusions. Based on these simulations the authors postulate that lateral saccular aneurysms located on more curved arteries are subjected to higher hemodynamic stresses. Saccular aneurysms with wider necks have larger impact zones. The large impact zone at the distal side of the aneurysm neck correlates well with other findings, implicating this zone as the most likely site of aneurysm growth or regrowth of treated lesions. To protect against high hemodynamic stresses, protection of the distal side of the aneurysm neck from flow impingement is critical.

Flexible graphite is effective for electronic applications, specifically electro-magnetic interference (EMI) gasketing, resistive heating, thermoelectric-energy generation, and heat dissipation. It is comparable to or better than conductive-filled silicone materials for EMI gasketing. The shielding effectiveness reaches 125 dB. Flexible graphite as a heating element provides temperatures up to 980°C, response half-time down to 4 sec, and heat output at 60 sec up to 5600 J. The through-thickness, absolute thermoelectric power of flexible graphite is -2.6 µV/°C. Flexible graphite is effective as a thermal-interface material if the thickness is low (0.13 mm), the density is low (1.1 g/cm3), and the contact pressure is high (11.1 MPa). These applications make use of the flexibility and compliance of flexible graphite, in addition to its electronic and thermal behavior. Compliance is particularly important for the use of flexible graphite as interface materials, whether the interface is electromagnetic, thermoelectric, or thermal.

Stimulated by a recent controversy regarding pressure drops predicted in a giant aneurysm with a proximal stenosis, the present study sought to assess variability in the prediction of pressures and flow by a wide variety of research groups. In phase I, lumen geometry, flow rates, and fluid properties were specified, leaving each research group to choose their solver, discretization, and solution strategies. Variability was assessed by having each group interpolate their results onto a standardized mesh and centerline. For phase II, a physical model of the geometry was constructed, from which pressure and flow rates were measured. Groups repeated their simulations using a geometry reconstructed from a micro-computed tomography (CT) scan of the physical model with the measured flow rates and fluid properties. Phase I results from 25 groups demonstrated remarkable consistency in the pressure patterns, with the majority predicting peak systolic pressure drops within 8% of each other. Aneurysm sac flow patterns were more variable with only a few groups reporting peak systolic flow instabilities owing to their use of high temporal resolutions. Variability for phase II was comparable, and the median predicted pressure drops were within a few millimeters of mercury of the measured values but only after accounting for submillimeter errors in the reconstruction of the life-sized flow model from micro-CT. In summary, pressure can be predicted with consistency by CFD across a wide range of solvers and solution strategies, but this may not hold true for specific flow patterns or derived quantities. Future challenges are needed and should focus on hemodynamic quantities thought to be of clinical interest.

Briefly, this Challenge aims to test the sensitivity of steady and pulsatile pressure drops as predicted by different CFD solvers or groups, and ultimately against in vitro pressure measurements. The current study focuses on the Phase I of the Challenge. We simulated steady state and pulsatile pressure drops based on the nominal surface geometry and specific inlet flow rates on a giant cerebral aneurysm with proximal stenosis.Copyright © 2012 by ASME

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Clinical and engineering studies typically assume that the common carotid artery (CCA) is straight enough to assume fully developed flow, yet recent studies have demonstrated the presence of skewed velocity profiles. Towards elucidating the influence of mild vascular curvatures on blood flow patterns and atherosclerosis, the present study aimed to characterize the three-dimensional shape of the human CCA. The left and right carotid arteries of 28 participants (62±13 years) in the VALIDATE (Vascular Aging – The Link that Bridges Age to Atherosclerosis) study were digitally segmented from 3D contrast-enhanced magnetic resonance angiograms, from the aortic arch to the carotid bifurcation. Each CCA was divided into nominal cervical and thoracic segments, for which curvatures were estimated by least squares fitting of the respective centerlines to planar arcs. The cervical CCA had mean radius of curvature of 127 mm, corresponding to a mean lumen:curvature radius ratio of 1:50. The thoracic CCA was significantly more curved at 1:16, with the plane of curvature tilted by a mean angle of 25 degrees and rotated close to 90 degrees with respect to that of the cervical CCA. The left CCA was significantly longer and slightly more curved than the right CCA, and there was a weak but significant increase in CCA curvature with age. Computational fluid dynamic (CFD) simulations carried out for idealized CCA geometries derived from these and other measured geometric parameters demonstrated that mild cervical curvature is sufficient to prevent flow from fully developing, independent of the degree of thoracic curvature. These findings reinforce the idea that fully-developed flow may be the exception rather than the rule for the CCA, and perhaps other nominally long and straight vessels.

An asymmetric stent with low porosity patch across the intracranial aneurysm neck and high porosity elsewhere is designed to modify the flow to result in thrombogenesis and occlusion of the aneurysm and yet to reduce the possibility of also occluding adjacent perforator vessels. The purposes of this study are to evaluate the flow field induced by an asymmetric stent using both numerical and digital subtraction angiography (DSA) methods and to quantify the flow dynamics of an asymmetric stent in an in vivo aneurysm model. We created a vein-pouch aneurysm model on the canine carotid artery. An asymmetric stent was implanted at the aneurysm, with 25% porosity across the aneurysm neck and 80% porosity elsewhere. The aneurysm geometry, before and after stent implantation, was acquired using cone beam CT and reconstructed for computational fluid dynamics (CFD) analysis. Both steady-state and pulsatile flow conditions using the measured waveforms from the aneurysm model were studied. To reduce computational costs, we modeled the asymmetric stent effect by specifying a pressure drop over the layer across the aneurysm orifice where the low porosity patch was located. From the CFD results, we found the asymmetric stent reduced the inflow into the aneurysm by 51%, and appeared to create a stasis-like environment which favors thrombus formation. The DSA sequences also showed substantial flow reduction into the aneurysm. Asymmetric stents may be a viable image guided intervention for treating intracranial aneurysms with desired flow modification features.

Geometric indices defined on intracranial aneurysms have been widely used in rupture risk assessment and surgical planning. However, most indices employed in clinical settings are currently evaluated based on two-dimensional images that inevitably fail to capture the three-dimensional nature of complex aneurysmal shapes. In addition, since measurements are performed manually, they can suffer from poor inter and intra operator repeatability. The purpose of the current work is to introduce objective and robust techniques for the 3D characterization of intracranial aneurysms, while preserving a close connection to the way aneurysms are currently characterized in clinical settings. Techniques for automatically identifying the neck plane, key aneurysm dimensions, shape factors, and orientations relative to the parent vessel are demonstrated in a population of 15 sidewall and 15 terminal aneurysms whose surface has been obtained by two trained operators using both level-set segmentation and thresholding, the latter reflecting typical clinical practice. Automatically-identified neck planes are shown to be in concordance with those manually positioned by an expert neurosurgeon, and automatically-derived geometric indices are shown to be largely insensitive to segmentation method or operator. By capturing the 3D nature of aneurysmal sacs and by minimizing observer variability, our approach allows large retrospective and prospective studies on aneurysm geometric risk factors to be performed using routinely acquired clinical images.

Previously, Zhou et al. [1] presented a novel mouse model of aortic valve regurgitation (AR) to explore the effect of altered hemodynamics on atherogenesis. In these ldlr−/− mice with AR, extensive atherosclerotic plaque was found along the naturally lesion-free descending thoracic (DTAo) and abdominal aorta (AbAo), with distinct spatial distributions suggestive of a strong local hemodynamic influence (Fig. 1, top). Doppler ultrasound measurement showed that both DTAo and AbAo of the AR mice experienced an oscillatory flow pattern induced by the diastolic retrograde flow, as opposed to the consistent antegrade flow found in the non-AR mice. The study also suggested that the fraction of the DTAo surface covered by lesions tends to increase with the absolute diastolic retrograde Time-Velocity Integral (TVI) as measured from the Doppler ultrasound.

Controversy exists regarding the suitability of fully developed versus measured inlet velocity profiles for image-based computational fluid dynamics (CFD) studies of carotid bifurcation hemodynamics. Here, we attempt to resolve this by investigating the impact of the reconstructed common carotid artery (CCA) inlet length on computed metrics of “disturbed” flow. Twelve normal carotid bifurcation geometries were reconstructed from contrast-enhanced angiograms acquired as part of the Vascular Aging—The Link That Bridges Age to Atherosclerosis study (VALIDATE). The right carotid artery lumen geometry was reconstructed from its brachiocephalic origin to well above the bifurcation, and the CCA was truncated objectively at locations one, three, five, and seven diameters proximal to where it flares into the bifurcation. Relative to the simulations carried out using the full CCA, models truncated at one CCA diameter strongly overestimated the amount of disturbed flow. Substantial improvement was offered by using three CCA diameters, with only minor further improvement using five CCA diameters. With seven CCA diameters, the amounts of disturbed flow agreed unambiguously with those predicted by the corresponding full-length models. Based on these findings, we recommend that image-based CFD models of the carotid bifurcation should incorporate at least three diameters of CCA length if fully developed velocity profiles are to be imposed at the inlet. The need for imposing measured inlet velocity profiles would seem to be relevant only for those cases where the CCA is severely truncated.

Following surgical induction of aortic valve regurgitation (AR), extensive atherosclerotic plaque development along the descending thoracic and abdominal aorta of Ldlr⁻/⁻ mice has been reported, with distinct spatial distributions suggestive of a strong local hemodynamic influence. The objective of this study was to test, using image-based computational fluid dynamics (CFD), whether this is indeed the case. The lumen geometry was reconstructed from micro-CT scanning of a control Ldlr⁻/⁻ mouse, and CFD simulations were carried out for both AR and control flow conditions derived from Doppler ultrasound measurements and literature data. Maps of time-averaged wall shear stress magnitude (TAWSS), oscillatory shear index (OSI) and relative residence time (RRT) were compared against the spatial distributions of plaque stained with oil red O, previously acquired in a group of AR and control mice. Maps of OSI and RRT were found to be consistent with plaque distributions in the AR mice and the absence of plaque in the control mice. TAWSS was uniformly lower under control vs. AR flow conditions, suggesting that levels (> 100 dyn/cm²) exceeded those required to alone induce a pro-atherogenic response. Simulations of a straightened CFD model confirmed the importance of anatomical curvature for explaining the spatial distribution of lesions in the AR mice. In summary, oscillatory and retrograde flow induced in the AR mice, without concomitant low shear, may exacerbate or accelerate lesion formation, but the distinct anatomical curvature of the mouse aorta is responsible for the spatial distribution of lesions.

Clinical and engineering studies of carotid artery disease typically assume that the common carotid artery (CCA), proximal to the bifurcation, is relatively straight, at least enough to assume the velocity profile is fully-developed (i.e., Poiseuille or Womersley profile) or at least axisymmetric. However, a recent study from our group has shown the surprising presence, in vivo, of strongly skewed velocity profiles in what appeared to be only mildly curved CCAs [1]. A computational fluid dynamics (CFD) study from our group also demonstrated strong velocity profile skewing in an idealized geometry possessing subtle wiggles similar to those observed in the CCA [2].Copyright © 2010 by ASME

Recent work has illuminated differences in carotid artery blood flow rate dynamics of older versus young adults. To what degree flow waveform shape, and indeed the use of measured versus assumed flow rates, affects the simulated hemodynamics of older adult carotid bifurcations has not been elucidated. Image-based computational fluid dynamics models of N=9 normal, older adult carotid bifurcations were reconstructed from magnetic resonance angiography. Subject-specific hemodynamics were computed by imposing each individual’s inlet and outlet flow rates measured by cine phase-contrast magnetic resonance imaging or by imposing characteristic young and older adult flow waveform shapes adjusted to cycle-averaged flow rates measured or allometrically scaled to the inlet and outlet areas. Despite appreciable differences in the measured versus assumed flow conditions, the locations and extents of low wall shear stress and elevated relative residence time were broadly consistent; however, the extent of elevated oscillatory shear index was substantially underestimated, more by the use of assumed cycle-averaged flow rates than the assumed flow waveform shape. For studies of individual vessels, use of a characteristic flow waveform shape is likely sufficient, with some benefit offered by scaling to measured cycle-averaged flow rates. For larger-scale studies of many vessels, ranking of cases according to presumed hemodynamic or geometric risk is robust to the assumed flow conditions.

Human studies of haemodynamic factors in the pathogenesis of cerebral aneurysms require knowledge of the pre-aneurysmal vasculature. This paper presents an objective and automated technique to digitally remove an aneurysm and reconstruct the parent artery, based on lumen geometries segmented from angiographic images. Relying on robust computational geometry concepts, notably Voronoi diagrams of the digitised lumen surface, the aneurysm attachment region is first defined objectively using lumen centrelines. Centrelines within this region are replaced by smooth interpolations, which then guide the interpolation of Voronoi points within the attachment region. Combined with Voronoi points from outside the attachment region, the parent artery lumen, without the aneurysm, can be reconstructed. Plausible reconstructions were obtained, automatically, for a set of 10 side-wall or terminal aneurysms, of various sizes and shapes, from the ANEURISK project data set. Application of image-based computational fluid dynamics analysis to a five side-wall aneurysm cases data set revealed an association between the recently proposed gradient oscillatory number (GON) and the site of aneurysm formation in four of five cases; however, elevated GON was also evident at non-aneurysmal sites. A potential application to the automated delineation of aneurysms for morphological characterisations is also suggested. The proposed approach may serve as a broad platform for investigating haemodynamic and morphological factors in aneurysm initiation, rupture and therapy in a way amenable to large-scale clinical studies or routine clinical use. Nevertheless, while the parent artery reconstructions are plausible, it remains to be proven that they are faithful representations of the pre-aneurysmal artery.

While it is widely appreciated that volumetric blood flow rate (VFR) dynamics change with age, there has been no detailed characterization of the typical shape of carotid bifurcation VFR waveforms of older adults. Toward this end, retrospectively gated phase contrast magnetic resonance imaging was used to measure time-resolved VFR waveforms proximal and distal to the carotid bifurcations of 94 older adults (age 68 +/- 8 years) with little or no carotid artery disease, recruited from the BLSA cohort of the VALIDATE study of factors in vascular aging. Timings and amplitudes of well-defined feature points from these waveforms were extracted automatically and averaged to produce representative common, internal and external carotid artery (CCA, ICA and ECA) waveform shapes. Relative to young adults, waveforms from older adults were found to exhibit a significantly augmented secondary peak during late systole, resulting in significantly higher resistance index (RI) and flow augmentation index (FAI). Cycle-averaged VFR at the CCA, ICA and ECA were 389 +/- 74, 245 +/- 61 and 125 +/- 49 mL min(-1), respectively, reflecting a significant cycle-averaged outflow deficit of 5%, which peaked at around 10% during systole. A small but significant mean delay of 13 ms between arrivals of ICA versus CCA/ECA peak VFR suggested differential compliance of these vessels. Sex and age differences in waveform shape were also noted. The characteristic waveforms presented here may serve as a convenient baseline for studies of VFR waveform dynamics or as suitable boundary conditions for models of blood flow in the carotid arteries of older adults.

Recent works in neurology have explored ways to obtain a better understanding of blood flow circulation in the brain with the ultimate goal of improving the treatment of cerebrovascular diseases, such as strokes, stenosis, and aneurysms. In this paper, we propose a framework to reconstruct three-dimensional (3D) models of intracerebral vessels from biplane angiograms. The reconstructed vessel geometries are then used to perform simulations of computational fluid dynamic (CFD). A key component of our framework is to perform such a reconstruction by incorporating user interaction to identify the centerline of the vessels in each view. Then the vessel profile is estimated automatically at each point along the centerlines, and an optimization procedure refines the 3D model using epipolar constraints and back-projection in the original angiograms. Finally, the 3D model of the vessels is then used as the domain where the wall shear stress (WSS), and velocity vectors are estimated from a blood flow model that follows Navier-Stokes equations as an incompressible Newtonian fluid. Visualization of hemodynamic parameters are illustrated on two stroke patients.

Approximately 80% to 90% of intracranial aneurysms (IA) are saccular or berry pouches formed at or near bifurcation apices or on the outer curvature of curved vessels in regions of complex hemodynamics (42). IA formation is proposed to result from maladaptive vascular responses to elevated hemodynamic stress at these locations (24, 26, 37). However, the specific causative hemodynamic microenvironments responsible for the biological changes that underlie aneurysm-initiating remodeling have not been elucidated. Recently, we surgically created a Y-shaped bifurcation from 2 native common carotid arteries (CCAs) in dogs (28) and examined how a naive vessel responded to impinging flow at a bifurcation apex from time zero. We found that the periapical wall underwent destructive remodeling characteristic of IA initiation, including degradation of the internal elastic lamina, loss of smooth muscle cells (SMCs) and endothelial cells (ECs), and reduced cell proliferation (29). Using high-resolution in vivo image-based computational fluid dynamics (CFD) to quantify the impinging flow environment and its spatial association with the observed histological changes, we demonstrated that morphological and cellular aneurysmal changes were localized in a flow acceleration region characterized by high wall shear stress (WSS) and high WSS gradient (WSSG) (28, 29). These observations suggest that the aneurysm-initiating remodeling results from maladaptation of the periapical arterial wall to high WSS and high WSSG hemodynamic insult and that this hemodynamic microenvironment constitutes a “danger zone” prone to aneurysm initiation. The current study examines whether the maladaptive remodeling in response to high WSS and high WSSG hemodynamics induces significant molecular up- or down-regulation of specific markers associated with IAs, such as endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS), nitrotyrosine, and matrix metalloproteinase (MMP)-2 and -9 (1, 3, 13, 19, 23, 39). Additionally, we sought to localize these findings to their specific hemodynamic environments.

Although local hemodynamic forces are widely believed to play a role in aneurysm pathogenesis, the hemodynamic mechanisms have not been confirmed in a prospective manner. Ideally, one would identify the patient-specific vessel that is prone to aneurysm formation and follow it longitudinally to investigate the associated aneurysm formation factors or mechanisms. However, such studies are not practical in humans, and so the knowledge to predict aneurysm formation at a specific location, a priori, is not available.Copyright © 2009 by ASME

A recent study demonstrated that certain geometric features of young adult carotid bifurcations are surrogate markers of disturbed flow [1]. However, as the carotid bifurcation ages, the bifurcation and flow waveform changes its geometry and dynamics, respectively [2, 3]. In addition to confounding systemic risk factors, such changes may interrupt homeostasis, potentially altering the likelihood of disturbed flow and atherosclerotic disease in the aging carotid bifurcation. Despite this, disturbed flow in aged bifurcations is typically inferred from image-based computational fluid dynamics (CFD) approaches using representative young and healthy adult flow waveforms.Copyright © 2009 by ASME

Hemodynamic forces play critical roles in vascular pathologies such as atherosclerosis, aneurysms, and stenosis. However, detailed relationships between the specific in vivo hemodynamic microenvironment and vascular responses leading to the triggering or exacerbation of pathological remodeling of the vessel remain elusive. We have developed a hemodynamics-biology co-mapping technique that enables in situ correlation between the in vivo blood flow field and vascular changes secondary to hemodynamic insult. The hemodynamics profile is obtained from computational fluid dynamics simulation within the vascular geometry reconstructed from three-dimensional in vivo images, whereas the vascular response is obtained from histology or immunohistochemistry on harvested vascular tissue. The hemodynamics field is virtually sectioned in the histological slicing planes and digitally co-mapped with the histological images, thereby enabling correlation of the specific local vascular responses with the inciting hemodynamic stresses. We demonstrate application of this technique to rabbit basilar terminus subjected to elevated flow. Morphological changes at the basilar terminus 5 days after the flow increase were co-mapped with the initial wall shear stress and wall shear stress gradient distributions, from which localization of destructive remodeling in a specific hemodynamic zone was noticed. This method paves the way for further investigations to determine the connection between in vivo mechanical stimuli and biological responses, such as initiation of aneurysmal remodeling.

Pathological extremes in cerebrovascular remodeling may contribute to basilar artery (BA) dolichoectasia and fusiform aneurysm development. Factors regulating cerebrovascular remodeling are poorly understood. To better understand hemodynamic influences on cerebrovascular remodeling, we examined BA remodeling following common carotid artery (CCA) ligation in an animal model.Rabbits were subjected to sham surgery (3 animals), unilateral CCA ligation (3 animals), or bilateral CCA ligation (5 animals). Transcranial Doppler ultrasonography and rotational angiography were used to compute BA flow, diameter, wall shear stress (WSS), and a tortuosity index on Days 0, 1, 4, 7, 14, 28, 56, and 84. Basilar artery tissues were stained and analyzed at Day 84. Statistical analysis was performed using orthogonal contrast analysis, repeated measures analysis of variance, or mixed regression analysis of repeated measures. Statistical significance was defined as a probability value0.05.Basilar artery flow and diameter increased significantly after the procedure in both ligation groups, but only the bilateral CCA ligation group demonstrated significant differences between groups. Wall shear stress significantly increased only in animals in the bilateral CCA ligation group and returned to baseline by Day 28, with 52% of WSS correction occurring by Day 7. Only the bilateral CCA ligation group developed significant BA tortuosity, occurring within 7 days postligation. Unlike the animals in the sham and unilateral CCA ligation groups, the animals in the bilateral CCA ligation group had histological staining results showing a substantial internal elastic lamina fragmentation.Increased BA flow results in adaptive BA remodeling until WSS returns to physiological baseline levels. Morphological changes occur rapidly following flow alteration and do not require chronic insult to affect substantial and significant structural transformation. Additionally, it appears that there exists a flow-increase threshold that, when surpassed, results in significant tortuosity.

Flow dynamics is a key player in the initiation and progression of vascular diseases such as atherosclerosis and cerebral aneurysms [1–4]. Numerous hemodynamic parameters, such as wall shear stress (WSS), pressure, oscillatory shear index, wall shear stress gradient, impingement size on the arterial wall, and residence time of blood, have been postulated to indicate the tendency for initiation or progression of these vascular pathologies and to evaluate the effectiveness of medical devices in the treatments of such diseases [1–4]. However, in vivo measurements of these hemodynamic parameters for patients are difficult and often cost prohibitive. The combination of noninvasive diagnostic tools (e.g. MRI, CT, or ultrasound) and image-based computational fluid dynamics (CFD) techniques provides an alternative to in vivo measurements to estimate these patient-specific hemodynamic parameters [5–12]. Such image-based CFD analysis has the potential to provide key hemodynamic feedback for prospective studies of vascular diseases and to plan for individual therapeutic options [6,11,13]. Although the application of image-based CFD is rapidly advancing, the ever-present uncertainties in CFD analysis need to be evaluated. In particular, CFD outputs such as WSS or WSS gradients are extremely sensitive to the acquired in vivo geometry. The accuracy and reproducibility of the image-based CFD geometries depend on the orientation of the subject, physiological condition of the subject, variation in vascular structure, contrast-media injection techniques, and operator-dependent decisions in converting the medical images to CFD models [14,15]. Such variations produce poor geometric renditions that can generate as much as 60% variation in hemodynamic parameters obtained using CFD, especially in complex flow regions such as bifurcation apexes, anastomoses, flow separation zones, and aneurysm inflow zones [8,15–17]. Smoothing can reduce poor geometric renditions [16], but the process is somewhat subjective, resulting in an unknown deviation from the true in vivo geometry and subsequent in vitro and CFD models. In addition, the validity of CFD results relies heavily on both temporal and spatial boundary conditions [17–19], which are not routinely available in clinical practice. Significant efforts have been made to improve image-based CFD techniques [8,14,16,20–22], but there have been insufficient efforts to validate the CFD results with experiments. In vitro experimental studies have often been employed to investigate the hemodynamics of vascular diseases and mechanical treatment devices, as well as assisting the development of CFD techniques. Rhee et al. and Imbesi et al. explored the influence of aneurysm geometry and intervention through flow visualization techniques [23,24]. Particle image velocimetry (PIV) and particle tracking velocimetry have been utilized to study the influence of intervention on aneurysmal flow [25–29]. Direct in vivo measurements of blood flow through x-ray imaging, MRI, and ultrasound techniques have also been explored [10,30–33]. MRI and ultrasound allow noninvasive measurement of instantaneous velocities in the 3D domain. Based on the field data, velocity gradients and strain rates are obtained to determine shear stresses and shear stress gradients. However, to date, in vitro studies have been limited to 2D flow fields and scaled-up models that provide optical access. These studies experience significant difficulties in reproducing the in vivo geometries [23] and in vivo biological environments. Direct in vivo measurements pose technical shortcomings, such as inadequate resolutions to derive the flow velocity near the wall, uncertainties in wall positions and insufficient velocity vectors to estimate the derivatives in complex flow regions [10,11,30,31,34–36]. One of the clinical applications of CFD is cerebral vascular diseases such as cerebral aneurysms. Subarachnoid hemorrhage following cerebral aneurysm rupture is often catastrophic, resulting in 12.4% of patient death before patients receive medical attention [37]. Recent studies using aneurysm geometry to predict the risks of aneurysm rupture relied heavily on the imaged aneurysm geometry [38–41]. Prospective patient-specific aneurysm studies that combine medical imaging, CFD analysis, and knowledge of biological responses to hemodynamics forces can provide insight into the hemodynamics of cerebral aneurysms, scientific assessments on therapeutic planning and, ultimately, positive clinical outcomes. However, quantitative validation of image-based CFD analysis against experimental and in vivo data has, to date, not been fully addressed. Following a prior CFD study, which focused on the characteristics of the hemodynamics in an aneurysm located on a curved vessel [42], a PIV validation effort was undertaken in our lab, leading to the investigation of flow sensitivity to aneurysm geometric variations. The goals of this study were to validate our CFD results with PIV experiments using an experimental aneurysm phantom and to quantify the influence of geometric variations on the aneurysmal flow dynamics.

Since the early 1970s, studies of arterial bifurcation morphology have suggested linkage between hemodynamic stresses and vascular remodeling (2, 16). It is generally accepted that blood flow patterns and hemodynamic stresses associated with such morphology contribute to the development of vascular pathologies (4, 5, 11). Cerebral aneurysms are preferentially located near arterial bifurcations or along the outer curvature of arteries on or near the Circle of Willis (10, 15). The local hemodynamics at such sites are complex, presenting impinging flow, regions of high wall shear stress (WSS), gradients in wall shear stress (WSSG), combinations of both, as well as “disturbed flow” (1, 8, 18). Yet, these relationships between hemodynamic conditions at an arterial bifurcation and pathological vascular remodeling leading to aneurysms are not well understood. Recent developments in computational fluid dynamics (CFD) enable detailed characterization of three-dimensional (3-D) flow fields in arteries of humans and larger animals (6). Thus, angiographic imaging and CFD can provide detailed flow fields from which measured hemodynamics can be correlated spatially and temporally with specific tissue responses in local microenvironments. Such hemodynamic-vascular response correlations constitute a model system for studying disease mechanisms that are mediated by altered hemodynamics. In this study, we present a new method for correlating morphological changes in the vascular wall with the local hemodynamics in a surgically created arterial bifurcation in dogs. To study how arterial tissue adapts to the complex hemodynamic environment of impinging flow, we created the bifurcation from native arterial segments and studied how the morphology of the vascular wall changed in response to altered hemodynamics. The major benefit of using a created bifurcation is to establish a cause and effect relationship between the altered hemodynamics (specifically, the flow impingement normally associated with a bifurcation) and remodeling of the vascular wall at the cellular level. Here, the naive vessel wall had never before been exposed to the type of impingement flow. New morphology that develops after the bifurcation has been created can thus be attributed to hemodynamic insult resulting from manipulated exposure of the naive vessel wall to impinging flow. Our observations provide insight into how complex hemodynamic conditions near the apex of an arterial bifurcation (including flow impingement, WSS and spatial variations, or gradients, of WSS) could affect vascular remodeling processes, including those that go awry. The changes observed have important implications concerning the fundamental mechanisms of aneurysm initiation.

The effects of parent vessel curvature on the hemodynamic forces for lateral saccular aneurysms are evaluated by using computational fluid dynamics (CFD). As the vessel curvature increases, flow impinges the distal neck and enters the aneurysm violently, causing both the pressure and shear stress at the distal neck to increase. High-pressure and high wall shear stress zones at the distal neck expand with the increasing of vessel curvature. The location of maximal wall shear stress implies that the growth or rupture of aneurysm may initiate in this region. Moreover, the effects of parent vessel curvature on aneurysm hemodynamics may eventually help to predict the risk of individual aneurysm rupture. Implantation of stents has the dual effect of disrupting the flow into the aneurysm and altering the radius of curvature. The study of the effects of vessel curvature effects on flow thus has new implications for stent design and implantation.