Biomedical subjects

David A Steinman

Publications and source records attributed to David A Steinman.

At least 19 recordsLinked to original sources

PubMed2006

Hemodynamics in the mouse aortic arch as assessed by MRI, ultrasound, and numerical modeling.

Mice are widely used to study arterial disease in humans, and the pathogenesis of arterial diseases is known to be strongly influenced by hemodynamic factors. It is, therefore, of interest to characterize the hemodynamic environment in the mouse arterial tree. Previous measurements have suggested that many relevant hemodynamic variables are similar between the mouse and the human. Here we use a combination of Doppler ultrasound and MRI measurements, coupled with numerical modeling techniques, to characterize the hemodynamic environment in the mouse aortic arch at high spatial resolution. We find that the hemodynamically induced stresses on arterial endothelial cells are much larger in magnitude and more spatially uniform in the mouse than in the human, an effect that can be explained by fluid mechanical scaling principles. This surprising finding seems to be at variance with currently accepted models of the role of hemodynamics in atherogenesis and the known distribution of atheromatous lesions in mice.

Animals↗

PubMed2006

Inlet conditions for image-based CFD models of the carotid bifurcation: is it reasonable to assume fully developed flow?

BACKGROUND: Computational fluid dynamics tools are useful for their ability to model patient specific data relevant to the genesis and progression of atherosclerosis, but unavailable to measurement tools. The sensitivity of the physiologically relevant parameters of wall shear stress (WSS) and the oscillatory shear index (OSI) to secondary flow in the inlet velocity profiles was investigated in three realistic models of the carotid bifurcation. METHOD OF APPROACH: Secondary flow profiles were generated using sufficiently long entrance lengths, to which curvature and helical pitch were added. The differences observed were contextualized with respect to effect of the uncertainty of the models' geometry on the same parameters. RESULTS: The effects of secondary velocities in the inlet profile on WSS and OSI break down within a few diameters of the inlet. Overall, the effect of secondary inlet flow on these models was on average more than 3.5 times smaller than the effect of geometric variability, with 13% and 48% WSS variability induced by inlet secondary flow and geometric differences, respectively. CONCLUSIONS: The degree of variation is demonstrated to be within the range of the other computational assumptions, and we conclude that given a sufficient entrance length of realistic geometry, simplification to fully developed axial (i.e., Womersley) flow may be made without penalty. Thus, given a choice between measuring three components of inlet velocity or a greater geometric extent, we recommend effort be given to more accurate and detailed geometric reconstructions, as being of primary influence on physiologically significant indicators.

Blood Flow Velocity↗

PubMed2005

Variation in the carotid bifurcation geometry of young versus older adults: implications for geometric risk of atherosclerosis.

BACKGROUND AND PURPOSE: Retrospective analysis of clinical data has demonstrated major variations in carotid bifurcation geometry, in support of the notion that an individual's vascular anatomy or local hemodynamics may influence the development of atherosclerosis. On the other hand, anecdotal evidence suggests that vessel geometry is more homogenous in youth, which would tend to undermine this geometric risk hypothesis. The purpose of our study was to test whether the latter is indeed the case. METHODS: Cross-sectional images of the carotid bifurcations of 25 young adults (24+/-4 years) and a control group of 25 older subjects (63+/-10 years) were acquired via MRI. Robust and objective techniques were developed to automatically characterize the 3D geometry of the bifurcation and the relative dimensions of the internal, external, and common carotid arteries (ICA, ECA, and CCA, respectively). RESULTS: Young vessels exhibited significantly less interindividual variation in the following geometric parameters: bifurcation angle (48.5+/-6.3 degrees versus 63.6+/-15.4 degrees); ICA angle (21.6+/-6.7 degrees versus 29.2+/-11.3 degrees); CCA tortuosity (0.010+/-0.003 versus 0.014+/-0.011); ICA tortuosity (0.025+/-0.013 versus 0.086+/-0.105); ECA/CCA diameter ratio (0.81+/-0.06 versus 0.75+/-0.13), ICA/CCA (0.81+/-0.06 versus 0.77+/-0.12) diameter ratio, and bifurcation area ratio (1.32+/-0.15 versus 1.19+/-0.35). CONCLUSIONS: The finding of more modest interindividual variations in young adults suggests that, if there is a geometric risk for atherosclerosis, its early detection may prove challenging. Taken together with the major interindividual variations seen in older vessels, it suggests a more complex interrelationship between vascular geometry, local hemodynamics, vascular aging, and atherosclerosis, the elucidation of which now calls for prospective studies.

Adult↗

PubMed2005

Characterization of volumetric flow rate waveforms in the normal internal carotid and vertebral arteries.

Knowledge of normal cerebrovascular volumetric flow rate (VFR) dynamics is of interest for establishing baselines, and for providing input data to cerebrovascular model studies. Retrospectively gated phase contrast magnetic resonance imaging was used to measure time-resolved VFR waveforms from the two internal carotid arteries (ICA) and two vertebral arteries (VA) of 17 young, normal volunteers (16M:1F) at rest in a supine posture. After normalizing each waveform to its respective cycle-averaged VFR, the timing and amplitude of feature points from the individual waveforms were averaged together to produce archetypal ICA and VA waveform shapes. Despite significant inter-individual differences in cycle-averaged VFR within the ICA compared to VA (275+/-52 versus 91+/-18 mL min-1), the respective waveform shapes were qualitatively similar overall. The VA waveform shape did, however, exhibit significantly higher amplitudes (e.g., peak:average VFR of 1.78+/-0.30 versus 1.66+/-0.16; p<0.05) and significantly higher variability both between and within subjects. A significant correlation was observed between peak and cycle-averaged VFR, suggesting that the representative waveform shapes presented here-when scaled by an individual's cycle-averaged VFR-may be used to characterize normal ICA and VA flow rate dynamics. This capability may be of particular utility for studies where cerebrovascular flow dynamics are required, but only average flow rates are available.

Adult↗

PubMed2005

Anthropometric data for magnetic resonance imaging of the carotid bifurcation.

PURPOSE: To provide anthropometric data applicable to the design of protocols for high-resolution magnetic resonance imaging (MRI) of the carotid bifurcation, particularly those aimed at elucidating the role of local factors in carotid atherogenesis. MATERIALS AND METHODS: Axial black-blood MR images of the carotid bifurcation were acquired from 25 young, healthy volunteers and 25 older, asymptomatic patients, from which were measured a variety of quantities related to the orientation and placement of the bifurcation within the neck. RESULTS: Descriptive statistics were obtained for the following quantities: separation of the bifurcation apices within (57.8+/-6.7 mm) and between (4.9+/-4.1 mm) axial slices; orientation of the bifurcation within the axial plane (31.7+/-26.9 degrees ), and of the common carotid artery (CCA) relative to the sagittal (7.5+/-7.1 degrees ) and coronal (7.9+/-7.8 degrees ) planes; depth of the bifurcation from the skin surface (29.5+/-7.2 mm); and neck width (125.9+/-14.4 mm). CONCLUSION: In most cases, both carotid arteries may be captured, without aliasing, within a 12-cm field-of-view axial image; however, the two apices will rarely be captured within the same axial slice. The CCA is significantly oblique to the body axis, but at angles sufficiently acute to permit the use of axial slices. Finally, a significant linear relationship between neck width and carotid depth may be used to inform radio frequency (RF) coil selection prior to scanning a subject, and hence facilitate optimal imaging in light of the wide anatomic variations observed.

Adult↗

PubMed2005

Flow imaging and computing: large artery hemodynamics.

The objective of our session at the International Bio-Fluid Mechanics Symposium and Workshop was at the International Bio-Fluid Mechanics Symposium and Workshop to review the state-of-the-art in, and identify future directions for, imaging and computational modeling of blood flow in the large arteries and the microcirculation. Naturally, talks in other sessions of the workshop overlapped this broad topic, and so here we summarize progress within the last decade in terms of the technical development and application of flow imaging and computing, rather than the knowledge derived from specific studies. We then briefly discuss ways in these tools may be extended, and their application broadened, in the next decade. Furthermore, owing to the conceptual division between the hemodynamics of large arteries, and those within the microcirculation, we review these regimes separately: The former here by Steinman and Taylor; and the latter in a separate paper by Cristini.

Animals↗

PubMed2005

Template-based finite-element mesh generation from medical images.

The finite-element (FE) method is commonly used in biomedical engineering to simulate the behaviour of biological structures because of its ability to model complex shapes in a subject-specific manner. However, generating FE meshes from medical images remains a bottleneck. We present a template-based technique for semi-automatically generating FE meshes which is applicable to prospective studies of individual patients in which FE meshes must be generated from scans of the same structure taken at different points in time to study the effects of disease progression/regression. In this "template-based" meshing approach, the baseline FE (tetrahedral) volume mesh is first manually aligned with the follow-up images. The triangulated surface of the mesh is then automatically deformed to fit the imaged organ boundary. The deformed surface nodes are then smoothed using a Laplacian smoothing algorithm to correct triangle (surface nodes) distortion and thus preserve triangle quality. Finally, the internal mesh nodes are smoothed to correct distorted tetrahedral elements and thus preserve tetrahedral element quality. This template-based approach is shown to be as accurate and precise as the previous technique used by our group, while preserving element quality and volume.

Algorithms↗

PubMed2005

Real-time numerical simulation of Doppler ultrasound in the presence of nonaxial flow.

Numerical simulations of Doppler ultrasound (DUS) relying on computational fluid dynamics (CFD) models of nonaxial flow have traditionally employed detailed (but computationally intensive) models of the DUS physics, or have sacrificed much of the physics in the interest of computational or conceptual simplicity. In this paper, we present a compromise between these extremes, with the objective of simulating the essential characteristics of DUS spectrograms in a real-time manner. Specifically, a precomputed pulsatile CFD velocity field is interrogated at some number, N, of discrete points distributed spatially within a sample volume of prescribed geometry and power distribution and temporally within a prescribed sampling window. Intrinsic spectral broadening is accounted for by convolving each of the point velocities with a semiempirical broadening function. Real-time performance is facilitated through the use of an efficient algorithm for interpolating the unstructured CFD data. A spherical sample volume with Gaussian power distribution, N = 1000 sampling points, and quadratic broadening function are shown to be adequate for simulating, at frame rates of 86 Hz on a 1.5 GHz desktop workstation, realistic-looking spectrograms at representative locations within a stenosed carotid bifurcation model. Via qualitative comparisons with matched in vitro data, these simulated spectrograms are shown to mimic the distinctive spectral envelopes, broadening and power characteristics associated with common carotid, stenotic jet and poststenotic recirculating flows. We conclude that the complex interaction between Doppler ultrasound and complicated clinically relevant blood flow dynamics can be simulated in real time via this relatively straightforward semiempirical approach.

Algorithms↗

PubMed2005

Virtual angiography for visualization and validation of computational models of aneurysm hemodynamics.

It has recently become possible to simulate aneurysmal blood flow dynamics in a patient-specific manner via the coupling of three-dimensional (3-D) X-ray angiography and cmputational fluid dynamics (CFD). Before such image-based CFD models can be used in a predictive capacity, however, it must be shown that they indeed reproduce the in vivo hemodynamic environment. Motivated by the fact that there are currently no techniques for adequately measuring complex blood velocity fields in vivo, in this paper we describe how cine X-ray angiograms may be simulated for the purpose of indirectly validating patient-sperific CFD models. Mimicking the radiological procedure, a virtual angiogram is constructed by first simulating the time-varying injection of contrast agent into a precomputed, patient-specific CFD model. A time-series of images is then constructed by simulating the attenuation of X-rays through the computed 3-D contrast-agent flow dynamics. Virtual angiographic images and residence time maps, here derived from an image-based CFD model of a giant aneurysm, are shown to be in excellent agreement wiith the corresponding clinical images and residence time maps, but only when the interaction between the quasisteady contrast agent injection and the pulsatile flow are properly accounted for. These virtual angiographic techniques pave the way for validating image-based CFD models against routinely available clinical data, and provide a means of visualizing complex, 3-D blood flow dynamics in a clinically relevant manner. They also clearly show how the contrast agent injection perturbs the noraml blood flow patterns, further highlighting the potential utility of image-based CFD as a window into the true aneurysmal hemodynamics.

Algorithms↗

PubMed2004

Sex differences in carotid plaque and stenosis.

BACKGROUND AND PURPOSE: Women are relatively protected from cardiovascular events; they are 3 times as likely as men to survive to age 90 years. Although clinical trials show an excess of thrombotic events with estrogen/progestin hormone replacement therapy, much experimental and epidemiological evidence suggests that estrogen may have beneficial effects on endothelial function and atherosclerosis, raising the possibility of sex differences in arterial remodeling. We studied sex differences in carotid plaque and stenosis in relation to survival free of stroke, death, and myocardial infarction. METHODS: A total of 1686 patients from an atherosclerosis prevention clinic were followed annually for up to 5 years (mean, 2.5+/-1.3 years) with baseline and follow-up measurements; there were 45 strokes, 94 myocardial infarctions, and 41 deaths. RESULTS: Carotid stenosis and plaque increased with age. Women had greater stenosis compared with men (P=0.001), whereas men had greater plaque area than did women at all ages (P<0.0001). Stroke, myocardial infarction, and death combined were predicted significantly by plaque area (P=0.004) but not by stenosis (P=0.042). CONCLUSIONS: Women have more stenosis but less plaque than men, suggesting that differences in sex hormones may affect remodeling of atherosclerosis. Plaque area was a stronger predictor of outcomes than was stenosis.

Age Distribution↗

PubMed2004

Robust and objective decomposition and mapping of bifurcating vessels.

Computational modeling of human arteries has been broadly employed to investigate the relationships between geometry, hemodynamics and vascular disease. Recent developments in modeling techniques have made it possible to perform such analyses on realistic geometries acquired noninvasively and, thus, have opened up the possibility to extend the investigation to populations of subjects. However, for this to be feasible, novel methods for the comparison of the data obtained from large numbers of realistic models in the presence of anatomic variability must be developed. In this paper, we present an automatic technique for the objective comparison of distributions of geometric and hemodynamic quantities over the surface of bifurcating vessels. The method is based on centerlines and consists of robustly decomposing the surface into its constituent branches and mapping each branch onto a template parametric plane. The application of the technique to realistic data demonstrates how similar results are obtained over similar geometries, allowing for proper model-to-model comparison. Thanks to the computational and differential geometry criteria adopted, the method does not depend on user-defined parameters or user interaction, it is flexible with respect to the bifurcation geometry and it is readily extendible to more complex configurations of interconnecting vessels.

Algorithms↗

PubMed2004

Finite-element modeling of the hemodynamics of stented aneurysms.

BACKGROUND: Computational fluid dynamics (CFD) simulations are used to analyze the wall shear stress distribution and flow streamlines near the throat of a stented basilar side-wall aneurysm. Previous studies of stented aneurysm flows used low mesh resolution, did not include mesh convergence analyses, and depended upon conformal meshing techniques that apply only to very artificial stent geometries. METHOD OF APPROACH: We utilize general-purpose computer assisted design and unstructured mesh generation tools that apply in principle to stents and vasculature of arbitrary complexity. A mesh convergence analysis for stented steady flow is performed, varying node spacing near the stent. Physiologically realistic pulsatile simulations are then performed using the converged mesh. RESULTS: Artifact-free resolution of the wall shear stress field on stent wires requires a node spacing of approximately 1/3 wire radius. Large-scale flow features tied to the velocity field are, however, captured at coarser resolution (nodes spaced by about one wire radius or more). CONCLUSIONS: Results are consistent with previous work, but our methods yield more detailed insights into the complex flow dynamics. However, routine applications of CFD to anatomically realistic cases still depend upon further development of dedicated algorithms, most crucially to handle geometry definition and mesh generation for complicated stent deployments.

Blood Flow Velocity↗

PubMed2004

Image-based computational fluid dynamics: a new paradigm for monitoring hemodynamics and atherosclerosis.

Complex blood flow dynamics are thought to play a key role in the development and treatment of atherosclerosis; however, the exact nature of this role is incompletely understood owing to the practical difficulties associated with measuring important local hemodynamic factors, notably wall shear stresses, in vivo. Only recently has it become possible to consider mapping these hemodynamic factors in a prospective, patient-specific manner via the coupling of in vivo medical imaging and computational fluid dynamics (CFD) modelling. CFD models derived from intravascular ultrasound have already been used to elucidate the role that hemodynamic forces play in mechanical and pharmacological interventions for coronary atherosclerosis. CFD models derived from magnetic resonance imaging and three-dimensional ultrasound provide a less invasive window into more superficial vessels such as the carotid bifurcation, and thus are promising tools for clarifying the role of, and eventually exploiting, purported local geometric and hemodynamic risk factors for atherosclerosis and its response to therapeutic options. Efforts to improve the ease and robustness with which these models are constructed have led to concomitant improvements in accuracy and precision, data for which are presented to facilitate estimation of sample sizes for future studies. Current limitations and anticipated future directions for these powerful new tools are discussed.

Arteriosclerosis↗

PubMed2004

Extracorporeal femoral to carotid artery perfusion in selective brain cooling for a giant aneurysm. Case report.

Giant partially thrombosed intracranial aneurysms are a challenge to treat surgically, and they are also unsuitable for coil embolization. The current options for treatment include extracranial-intracranial bypass followed by parent artery occlusion or direct surgical occlusion in which deep hypothermic circulatory arrest is used. The authors report the use of another approach in the treatment of a giant anterior circulation aneurysm: selective brain cooling accomplished by extracorporeal perfusion. This facilitated direct surgery on a 4.2-cm, partially thrombosed aneurysm of the middle cerebral artery (MCA). A brain temperature of 22 degrees C was achieved after 20 minutes of perfusion with blood cooled using an extracorporeal technique of femoral-common carotid artery perfusion. This was followed by a 20-minute period of surgical trapping of the MCA, then evacuation and clip occlusion of the aneurysm. During the period of selective brain cooling the patient's core body temperature was maintained above 35 degrees C. This technique of selective brain cooling may be a useful alternative to currently available surgical and endovascular methods of treatment for giant aneurysms.

Aged↗

PubMed2003

Reproducibility of image-based computational fluid dynamics models of the human carotid bifurcation.

Recent studies have demonstrated the ability of magnetic resonance imaging (MRI) to provide anatomically realistic boundary conditions for computational fluid dynamics (CFD) simulations of arterial hemodynamics. To date, however, little is known about the overall reproducibility of such image-based CFD techniques. Towards this end we used serial black blood and cine phase contrast MRI to reconstruct CFD models of the carotid bifurcations of three subjects with early atherosclerosis, each imaged three times at weekly intervals. The lumen geometry was found to be precise on average to within 0.15 mm or 5%, while measured flow and heart rates varied by less than 10%. Spatial patterns of a variety of wall shear stress (WSS) indices were largely preserved among the three repeat models. Time-averaged WSS was reproduced best, on average to within 5 dyn/cm2 or 37%, followed by WSS spatial gradients, angle gradients, and oscillatory shear index. The intrasubject flow rate variations were found to contribute little to the overall WSS variability. Instead, reproducibility was determined largely by the precision of the lumen boundary extraction from the individual MR images, itself shown to be a function of the image quality and proximity to the geometrically complex bifurcation region.

Aged↗

PubMed2003

Path-dependent hemodynamics of the stenosed carotid bifurcation.

Previous work using computational simulations and experimental flow visualizations has demonstrated marked differences in local flow patterns between stenosed carotid bifurcation models having the same stenosis severity but different stenosis geometries. Since local blood flow patterns are known to influence thrombosis and atherosclerotic plaque development and rupture, such differences may in turn reflect differences in thromboembolic and atherosclerotic potential, and hence risk of ischemic stroke. Towards testing this hypothesis, we tracked point particles, representing uniformly distributed blood elements, through concentrically and eccentrically stenosed carotid bifurcation models, and computed and compared various path-dependent hemodynamic parameters between the models. Our results suggest that residence time alone is not sensitive to stenosis geometry; however, notable differences between the stenosis models were observed with residence time indicators that incorporate shear-related phenomena, such as the transit times and levels of activation of platelets that exceed a given shear threshold. Specifically, these and other indicators, including the magnitude of platelet shear exposure and the size and density of local platelet and monocyte deposition, were found to be higher in the eccentric model. Experimental work is now required to assess the significance of these differences.

Blood Flow Velocity↗

PubMed2003

Image-based computational simulation of flow dynamics in a giant intracranial aneurysm.

BACKGROUND AND PURPOSE: Blood flow dynamics are thought to play an important role in the pathogenesis and treatment of intracranial aneurysms; however, hemodynamic quantities of interest are difficult to measure in vivo. This study shows that computational fluid dynamics (CFD) combined with computed rotational angiography can provide such hemodynamic information in a patient-specific and prospective manner. METHODS: A 58-year-old woman presented with partial right IIIrd cranial nerve palsy due to a giant carotid-posterior communicating artery aneurysm that was subsequently coiled. Computed rotational angiography provided high resolution volumetric image data from which the lumen geometry was extracted. This and a representative flow rate waveform were provided as boundary conditions for finite element CFD simulation of the 3D pulsatile velocity field. RESULTS: CFD analysis revealed high speed flow entering the aneurysm at the proximal and distal ends of the neck, promoting the formation of both persistent and transient vortices within the aneurysm sac. This produced dynamic patterns of elevated and oscillatory wall shear stresses distal to the neck and along the sidewalls of the aneurysm. These hemodynamic features were consistent with patterns of contrast agent wash-in during cine angiography and with the configuration of coil compaction observed at 6-month follow-up. CONCLUSION: Anatomic realism of lumen geometry and flow pulsatility is essential for elucidating the patient-specific nature of aneurysm hemodynamics. Such image-based CFD analysis may be used to provide key hemodynamic information for prospective studies of aneurysm growth and rupture or to predict the response of an individual aneurysm to therapeutic options.

Blood Flow Velocity↗

PubMed2002

Reconstruction of carotid bifurcation hemodynamics and wall thickness using computational fluid dynamics and MRI.

A thorough understanding of the relationship between local hemodynamics and plaque progression has been hindered by an inability to prospectively monitor these factors in vivo in humans. In this study a novel approach for noninvasively reconstructing artery wall thickness and local hemodynamics at the human carotid bifurcation is presented. Three-dimensional (3D) models of the lumen and wall boundaries, from which wall thickness can be measured, were reconstructed from black-blood magnetic resonance imaging (MRI). Along with time-varying inlet/outlet flow rates measured via phase contrast (PC) MRI, the lumen boundary was used as input for computational fluid dynamic (CFD) simulation of the subject-specific flow patterns and wall shear stresses (WSSs). Results from a 59-year-old subject with early, asymptomatic carotid artery disease show good agreement between simulated and measured velocities, and demonstrate a correspondence between wall thickening and low and oscillating shear at the carotid bulb. High shear at the distal internal carotid artery (ICA) was also colocalized with higher WSS; however, a quantitative general relationship between WSS and wall thickness was not found. Similar results were obtained from a 23-year-old normal subject. These findings represent the first direct comparison of hemodynamic variables and wall thickness at the carotid bifurcation of human subjects. The noninvasive nature of this image-based modeling approach makes it ideal for carrying out future prospective studies of hemodynamics and plaque development or progression in otherwise healthy subjects.

Adult↗