Francis Loth

Hydrodynamic Modeling of Cerebrospinal Fluid Motion Within the Spinal Cavity

The fluid that resides within cranial and spinal cavities, cerebrospinal fluid (CSF), moves in a pulsatile fashion to and from the cranial cavity. This motion can be measured hy magnetic resonance imaging (MRI) and may he of clinical importance in the diagnosis of several brain and spinal cord disorders such as hydrocephalus, Chiari malformation, and syringomyelia. In the present work, a geometric and hydrodynamic characterization of an anatomically relevant spinal canal model is presented. We found that inertial effects dominate the flow field under normal physiological flow rates. Along the length of the spinal canal, hydraulic diameter was found to vary significantly from 5 to 15 mm. The instantaneous Reynolds number at peak flow rate ranged from 150 to 450, and the Womersle number ranged from 5 to 17. Pulsatile flow calculations are presented for an idealized geometric representation of the spinal cavity. A linearized Navier-Stokes model of the pulsatile CSF flow was constructed based on MRI flow rate measurements taken on a healthy volunteer. The numerical model was employed to investigate effects of cross-sectional geometry and spinal cord motion on unsteady velocity, shear stress, and pressure gradientfields. The velocity field was shown to be blunt, due to the inertial character of the flow, with velocity peaks located near the boundaries of the spinal canal rather than at the midpoint between boundaries. The pressure gradient waveform was found to be almost exclusively dependent on the flow waveform and cross-sectional area. Characterization of the CSF dynamics in normal and diseased states may be important in understanding the pathophysiology of CSF related disorders. Flow models coupled with MRI flow measurements mnay become a noninvasive tool to explain the abnormal dynamics of CSF in related brain disorders as well as to determine concentration and local distribution of drugs delivered into the CSF space.

PIV-Measured Versus CFD-Predicted Flow Dynamics in Anatomically Realistic Cerebral Aneurysm Models

Computational fluid dynamics (CFD) modeling of nominally patient-specific cerebral aneurysms is increasingly being used as a research tool to further understand the development, prognosis, and treatment of brain aneurysms. We have previously developed virtual angiography to indirectly validate CFD-predicted gross flow dynamics against the routinely acquired digital subtraction angiograms. Toward a more direct validation, here we compare detailed, CFD-predicted velocity fields against those measured using particle imaging velocimetry (PIV). Two anatomically realistic flow-through phantoms, one a giant internal carotid artery (ICA) aneurysm and the other a basilar artery (BA) tip aneurysm, were constructed of a clear silicone elastomer. The phantoms were placed within a computer-controlled flow loop, programed with representative flow rate waveforms. PIV images were collected on several anterior-posterior (AP) and lateral (LAT) planes. CFD simulations were then carried out using a well-validated, in-house solver, based on micro-CT reconstructions of the geometries of the flow-through phantoms and inlet/outlet boundary conditions derived from flow rates measured during the PIV experiments. PIV and CFD results from the central AP plane of the ICA aneurysm showed a large stable vortex throughout the cardiac cycle. Complex vortex dynamics, captured by PIV and CFD, persisted throughout the cardiac cycle on the central LAT plane. Velocity vector fields showed good overall agreement. For the BA, aneurysm agreement was more compelling, with both PIV and CFD similarly resolving the dynamics of counter-rotating vortices on both AP and LAT planes. Despite the imposition of periodic flow boundary conditions for the CFD simulations, cycle-to-cycle fluctuations were evident in the BA aneurysm simulations, which agreed well, in terms of both amplitudes and spatial distributions, with cycle-to-cycle fluctuations measured by PIV in the same geometry. The overall good agreement between PIV and CFD suggests that CFD can reliably predict the details of the intra-aneurysmal flow dynamics observed in anatomically realistic in vitro models. Nevertheless, given the various modeling assumptions, this does not prove that they are mimicking the actual in vivo hemodynamics, and so validations against in vivo data are encouraged whenever possible.

Improved phase-contrast flow quantification by three-dimensional vessel localization

In this paper, a method of three-dimensional (3D) vessel localization is presented to allow the identification of a vessel of interest, the selection of a vessel segment, and the determination of a slice orientation to improve the accuracy of phase-contrast magnetic resonance (PCMR) angiography. A marching-cube surface-rendering algorithm was used to reconstruct the 3D vasculature. Surface-rendering was obtained using an iso-surface value determined from a maximum intensity projection (MIP) image. This 3D vasculature was used to find a vessel of interest, select a vessel segment, and to determine the slice orientation perpendicular to the vessel axis. Volumetric flow rate (VFR) was obtained in a phantom model and in vivo using 3D localization with double oblique cine PCMR scanning. PCMR flow measurements in the phantom showed 5. 2% maximum error and a standard deviation of 9 mL/min during steady flow, 7.9% maximum error and a standard deviation of 13 mL/min during pulsatile flow compared with measurements using an ultrasonic transit-time flowmeter. PCMR VFR measurement error increased with misalignment at 10, 20, and 30 degrees oblique to the perpendicular slice in vitro and in vivo. The 3D localization technique allowed precise localization of the vessel of interest and optimal placement of the slice orientation for minimum error in flow measurements.

Hemodynamic Patterns in Two Models of End-to-Side Vascular Graft Anastomoses: Effects of Pulsatility, Flow Division, Reynolds Number, and Hood Length

Flow behavior in models of end-to-side vascular graft anastomoses was studied under steady and pulsatile flow conditions. Models were constructed to simulate geometries employed in experimental studies on intimal thickening in a canine model. Reynolds numbers, division of flow in the outflow tracts and the pulsatile waveform employed were taken from measurements obtained in the canine model. Flows in the scaled-up, transparent models were visualized with white, neutrally buoyant particles which were photographed under laser illumination and also recorded on video tape under bright incandescent light. Strong, three-dimensional helical patterns which formed in the anastomotic junction were prominent features of the flow fields. Regions of low wall shear, oscillatory wall shear and long particle residence time were identified from the flow visualization experiments. Comparisons with the limited qualitative data available on intimal thickening in vascular graft anastomoses suggest a relation between localization of vascular intimal thickening and those surfaces experiencing low shear and long particle residence time.

DIRECT NUMERICAL SIMULATION OF TRANSITIONAL FLOW IN A STENOSED CAROTID BIFURCATION

The blood flow dynamics of a stenosed, subject-specific, carotid bifurcation were numerically simulated using the spectral element method. Pulsatile inlet conditions were based on in vivo color Doppler ultrasound measurements of blood velocity. The results demonstrated the transitional or weakly turbulent state of the blood flow, which featured rapid velocity and pressure fluctuations in the post-stenotic region of the internal carotid artery (ICA) during systole and laminar flow during diastole. High-frequency vortex shedding was greatest downstream of the stenosis during the deceleration phase of systole. Velocity fluctuations had a frequency within the audible range of 100-300Hz. Instantaneous wall shear stress (WSS) within the stenosis was relatively high during systole ( approximately 25-45Pa) compared to that in a healthy carotid. In addition, high spatial gradients of WSS were present due to flow separation on the inner wall. Oscillatory flow reversal and low pressure were observed distal to the stenosis in the ICA. This study predicts the complex flow field, the turbulence levels and the distribution of the biomechanical stresses present in vivo within a stenosed carotid artery.

Relative Contribution of Wall Shear Stress and Injury in Experimental Intimal Thickening at PTFE End-to-Side Arterial Anastomoses

BACKGROUND Intimal hyperplastic thickening (IHT) is a frequent cause of prosthetic bypass graft failure. Induction and progression of IHT is thought to involve a number of mechanisms related to variation in the flow field, injury and the prosthetic nature of the conduit. This study was designed to examine the relative contribution of wall shear stress and injury to the induction of IHT at defined regions of experimental end-to-side prosthetic anastomoses. METHODS AND RESULTS The distribution of IHT was determined at the distal end-to-side anastomosis of seven canine Iliofemoral PTFE grafts after 12 weeks of implantation. An upscaled transparent model was constructed using the in vivo anastomotic geometry, and wall shear stress was determined at 24 axial locations from laser Doppler anemometry measurements of the near wall velocity under conditions of pulsatile flow similar to that present in vivo. The distribution of IHT at the end-to-side PTFE graft was determined using computer assisted morphometry. IHT involving the native artery ranged from 0.0+/-0.1 mm to 0.05+/-0.03 mm. A greater amount of IHT was found on the graft hood (PTFE) and ranged from 0.09+/-0.06 to 0.24+/-0.06 mm. Nonlinear multivariable logistic analysis was used to model IHT as a function of the reciprocal of wall shear stress, distance from the suture line, and vascular conduit type (i.e. PTFE versus host artery). Vascular conduit type and distance from the suture line independently contributed to IHT. An inverse correlation between wall shear stress and IHT was found only for those regions located on the juxta-anastomotic PTFE graft. CONCLUSIONS The data are consistent with a model of intimal thickening in which the intimal hyperplastic pannus migrating from the suture line was enhanced by reduced levels of wall shear stress at the PTFE graft/host artery interface. Such hemodynamic modulation of injury induced IHT was absent at the neighboring artery wall.

Spectral Element Methods for Transitional Flows in Complex Geometries

We describe the development and implementation of an efficient spectral element code for simulating transitional flows in complex three-dimensional domains. Critical to this effort is the use of geometrically nonconforming elements that allow localized refinement in regions of interest, coupled with a stabilized high-order time-split formulation of the semi-discrete Navier–Stokes equations. Simulations of transition in a model of an arteriovenous graft illustrate the potential of this approach in biomechanical applications.

Pulsatile Flow in an End-to-Side Vascular Graft Model: Comparison of Computations With Experimental Data

Various hemodynamic factors have been implicated in vascular graft intimal hyperplasia, the major mechanism contributing to chronic failure of small-diameter grafts. However, a thorough knowledge of the graft flow field is needed in order to determine the role of hemodynamics and how these factors affect the underlying biological processes. Computational fluid dynamics offers much more versatility and resolution than in vitro or in vivo methods, yet computations must be validated by careful comparison with experimental data. Whereas numerous numerical and in vitro simulations of arterial geometries have been reported, direct point-by-point comparisons of the two techniques are rare in the literature. We have conducted finite element computational analyses for a model of an end-to-side vascular graft and compared the results with experimental data obtained using laser-Doppler velocimetry. Agreement for velocity profiles is found to be good, with some clear differences near the recirculation zones during the deceleration and reverse-flow segments of the flow waveform. Wall shear stresses are determined from velocity gradients, whether by computational or experimental methods, and hence the agreement for this quantity, while still good, is less consistent than for velocity itself from the wall shear stress numerical results, we computed four variables that have been cited in the development of intiimal hyperplasia-the time-averaged wall shear stress, an oscillating shear index, and spatial and temporal wall shear stress gradients in order to illustrate the versatility of numerical methods. We conclude that the computational approach is a valid alternative to the experimental approach for quantitative hemodynamic studies. Where differences in velocity were found by the two methods, it was generally attributed to the inability of the numerical method to model the fluid dynamics when flow conditions are destabilizing. Differences in wall shear, in the absence of destabilizing phenomena, were more likely to be caused by difficulties in calculating wall shear from relatively low resolution in vitro data.

Transitional Flow at the Venous Anastomosis of an Arteriovenous Graft: Potential Activation of the ERK1/2 Mechanotransduction Pathway

We present experimental and computational results that describe the level, distribution, and importance of velocity fluctuations within the venous anastomosis of an arteriovenous graft. The motivation of this work is to understand better the importance of biomechanical forces in the development of intimal hyperplasia within these grafts. Steady-flow in vitro studies (Re = 1060 and 1820) were conducted within a graft model that represents the venous anastomosis to measure velocity by means of laser Doppler anemometry. Numerical simulations with the same geometry and flow conditions were conducted by employing the spectral element technique. As flow enters the vein from the graft, the velocity field exhibits flow separation and coherent structures (weak turbulence) that originate from the separation shear layer. We also report results of a porcine animal study in which the distribution and magnitude of vein-wall vibration on the venous anastomosis were measured at the time of graft construction. Preliminary molecular biology studies indicate elevated activity levels of the extracellular regulatory kinase ERK1/2, a mitogen-activated protein kinase involved in mechanotransduction, at regions of increased vein-wall vibration. These findings suggest a potential relationship between the associated turbulence-induced vein-wall vibration and the development of intimal hyperplasia in arteriovenous grafts. Further research is necessary, however, in order to determine if a correlation exists and to differentiate the vibration effect from that of flow related effects.

Measurements of Velocity and Wall Shear Stress Inside a PTFE Vascular Graft Model Under Steady Flow Conditions

The flow field inside a model of a polytetrafluorethylene (PTFE) canine artery end-to-side bypass graft was studied under steady flow conditions using laser-Doppler anemometry. The anatomically realistic in vitro model was constructed to incorporate the major geometric features of the in vivo canine anastomosis geometry, most notably a larger graft than host artery diameter. The velocity measurements at Reynolds number 208, based on the host artery diameter, show the flow field to be three dimensional in nature. The wall shear stress distribution, computed from the near-wall velocity gradients, reveals a relatively low wall shear stress region on the wall opposite to the graft near the stagnation point approximately one artery diameter in axial length at the midplane. This low wall shear stress region extends to the sidewalls, suture lines, and along the PTFE graft where its axial length at the midplane is more than two artery diameters. The velocity distribution inside the graft model presented here provides a data set well suited for validation of numerical solutions on a model of this type.