Image Quality and Lesion Detection on Deep Learning Reconstruction and Iterative Reconstruction of Submillisievert Chest and Abdominal CT.

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.

Variability of computational fluid dynamics solutions for pressure and flow in a giant aneurysm: the ASME 2012 Summer Bioengineering Conference CFD Challenge.

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.

Assessment of an Artificial Intelligence Algorithm for Detection of Intracranial Hemorrhage.

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.

Validation of an artificial intelligence-driven large vessel occlusion detection algorithm for acute ischemic stroke patients.

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.

Assessment of computed tomography perfusion software in predicting spatial location and volume of infarct in acute ischemic stroke patients: a comparison of Sphere, Vitrea, and RAPID.

BACKGROUND: CT 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. METHODS: 108 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. RESULTS: Mean 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). CONCLUSIONS: Sphere 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.

Enhancing performance of a computed tomography perfusion software for improved prediction of final infarct volume in acute ischemic stroke patients.

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.

Effect of common carotid artery inlet length on normal carotid bifurcation hemodynamics.

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.

Carotid bifurcation hemodynamics in older adults: effect of measured versus assumed flow waveform.

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.

Can fully iterative reconstruction technique enable routine abdominal CT at less than 1 mSv?

OBJECTIVE: We assessed the effect of the forward projected model-based reconstruction technique (FIRST) on lesion detection of routine abdomen CT at <1 mSv. MATERIALS AND METHODS: Thirty-seven adult patients gave written informed consent for acquisition of low-dose CT (LDCT) immediately after their clinically-indicated, standard of care dose (SDCT), routine abdomen CT on a 640-slice MDCT (Aquillion One, Canon Medical System). The LDCT series were reconstructed with FIRST (at STD (Standard) and STR (Strong) levels), and SDCT series with filtered back projection (FBP). Two radiologists assessed lesions in LD-FBP and FIRST images followed by SDCT images. Then, SDCT and LDCT were compared for presence of artifacts in a randomized and blinded fashion. Patient demographics, size and radiation dose descriptors (CTDIvol, DLP) were recorded. Descriptive statistics and inter-observer variability were calculated for data analysis. RESULTS: Mean CTDIvol for SDCT and LDCT were 13 ± 4.7 mGy and 2.2 ± 0.8 mGy, respectively. There were 46 true positive lesions detected on SDCT. Radiologists detected 38/46 lesions on LD-FIRST-STD compared to 26/46 lesions on LD-FIRST-STR. The eight lesions (liver and kidney cysts, pancreatic lesions, sub-cm peritoneal lymph node) missed on LD-FIRST-STD were seen in patients with BMI > 25.8 kg/m2. Diagnostic confidence for lesion assessment was optimal in LD-FIRST-STD setting in most patients regardless of their size. The inter-observer agreement (kappa-value) for overall image quality were 0.98 and 0.84 for LD-FIRST-STD and STR levels, respectively. CONCLUSION: FIRST enabled optimal lesion detection in routine abdomen CT at less than 1 mSv radiation dose in patients with body mass less than ≤25.8 kg/m2.

Nascent aneurysm formation at the basilar terminus induced by hemodynamics.

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. CONCLUSIONS: 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.

In vivo assessment of rapid cerebrovascular morphological adaptation following acute blood flow increase.

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.

Complex hemodynamics at the apex of an arterial bifurcation induces vascular remodeling resembling cerebral aneurysm initiation.

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.

Effects of arterial geometry on aneurysm growth: three-dimensional computational fluid dynamics study.

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.

Automatic neck plane detection and 3D geometric characterization of aneurysmal sacs.

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.

Correlation between local hemodynamics and lesion distribution in a novel aortic regurgitation murine model of atherosclerosis.

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.

On the shape of the common carotid artery with implications for blood velocity profiles.

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. Toward elucidating the influence of mild vascular curvatures on blood flow patterns and atherosclerosis, this study aimed to characterize the three-dimensional shape of the human CCA. The left and right carotid arteries of 28 participants (63 ± 12 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 a 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° and rotated close to 90° 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 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 to axisymmetry, 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.

Mapping vascular response to in vivo hemodynamics: application to increased flow at the basilar terminus.

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.

Characterization of volumetric flow rate waveforms at the carotid bifurcations of older adults.

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.

Molecular alterations associated with aneurysmal remodeling are localized in the high hemodynamic stress region of a created carotid bifurcation.

OBJECTIVE: Although elevated hemodynamics has been speculated to play a key role in intracranial aneurysm (IA) initiation, little is known about the specific hemodynamic microenvironment that triggers aneurysmal vascular degradation. We previously demonstrated maladaptive remodeling characteristic of IA initiation occurring in hemodynamic regions of combined high wall shear stress (WSS) and high WSS gradient near the apex of an experimentally created carotid bifurcation. This study examines whether this remodeling recapitulates the molecular changes found in IAs and whether molecular changes also correspond to specific hemodynamic environments. METHODS: De novo bifurcations were surgically created using both native common carotid arteries in each of 6 dogs. Bifurcations were imaged 2 weeks or 2 months after surgery by high-resolution 3-dimensional angiography, from which flow fields were obtained by computational fluid dynamics simulations. Subsequently, harvested tissues, demonstrating early aneurysmal changes near the apex, were immunostained for interleukin-1beta, endothelial and inducible nitric oxide synthases, nitrotyrosine, and matrix metalloproteinase-2 and -9. Spatial distributions of these molecules were comapped with computational fluid dynamics results. RESULTS: The aneurysmal wall showed decreased endothelial nitric oxide synthase expression compared with surrounding segments, the feeding artery, and native controls, whereas all other markers increased. Anti-CD68 staining indicated the absence of inflammatory cells in the aneurysmal wall. Comapping molecular marker distributions with flow fields revealed confinement of these molecular changes within the hemodynamic region of high WSS and high, positive WSS gradient. CONCLUSION: Aneurysm-initiating remodeling induced by combined high WSS and high, positive WSS gradient is associated with molecular changes implicated in IAs.

Validation of CFD simulations of cerebral aneurysms with implication of geometric variations.

BACKGROUND: Computational fluid dynamics (CFD) simulations using medical-image-based anatomical vascular geometry are now gaining clinical relevance. This study aimed at validating the CFD methodology for studying cerebral aneurysms by using particle image velocimetry (PIV) measurements, with a focus on the effects of small geometric variations in aneurysm models on the flow dynamics obtained with CFD. METHOD OF APPROACH: An experimental phantom was fabricated out of silicone elastomer to best mimic a spherical aneurysm model. PIV measurements were obtained from the phantom and compared with the CFD results from an ideal spherical aneurysm model (S1). These measurements were also compared with CFD results, based on the geometry reconstructed from three-dimensional images of the experimental phantom. We further performed CFD analysis on two geometric variations, S2 and S3, of the phantom to investigate the effects of small geometric variations on the aneurysmal flow field. Results. We found poor agreement between the CFD results from the ideal spherical aneurysm model and the PIV measurements from the phantom, including inconsistent secondary flow patterns. The CFD results based on the actual phantom geometry, however, matched well with the PIV measurements. CFD of models S2 and S3 produced qualitatively similar flow fields to that of the phantom but quantitatively significant changes in key hemodynamic parameters such as vorticity, positive circulation, and wall shear stress. CONCLUSION: CFD simulation results can closely match experimental measurements as long as both are performed on the same model geometry. Small geometric variations on the aneurysm model can significantly alter the flow-field and key hemodynamic parameters. Since medical images are subjected to geometric uncertainties, image-based patient-specific CFD results must be carefully scrutinized before providing clinical feedback.