@article{longest_kleinstreuer_deanda_2005, title={Numerical simulation of wall shear stress and particle-based hemodynamic parameters in pre-cuffed and streamlined end-to-side anastomoses}, volume={33}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-005-7784-2}, abstractNote={A number of research studies have related multiple hemodynamic parameters to the formation of distal anastomotic intimal hyperplasia (IH) at the sub-cellular, cellular, and tissue levels. Focusing on mitigating WSS-based parameters alone, several studies have suggested geometrically modified end-to-side anastomoses with the intent of improving synthetic graft patency rates. However, recent clinical trials of commercially available versions of these grafts indicate persistently high rates of failure. Furthermore, recent evidence suggests that platelet-wall interactions may play a significant role in the formation of IH, which is not captured by WSS-based parameters alone. In this study, numerical simulations have been conducted to assess the potential for IH formation in conventional and geometrically modified anastomoses based on both wall shear stress (WSS) conditions and platelet-wall interactions. Sites of significant particle-wall interactions, including elevated concentrations and stasis, were identified by a near-wall residence time model, which includes factors for platelet activation and surface reactivity. Conventional, pre-cuffed, and streamlined distal end-to-side anastomoses were considered with proximal and distal arterial outflow. It was found that a pre-cuffed anastomosis, similar to the Distaflo configuration, does not offer a hemodynamic advantage over the conventional design considered with respect to the magnitude of the WSS field and the potential for platelet interactions with the vessel surface. Streamlined configurations largely consistent with venous confluences resulted in an advantageous reduction of wall shear stress gradient values; however, particle-wall interactions remained significant throughout the anastomosis. Results of this study are not intended to be directly extrapolated to surgical recommendations. However, these results highlight the difficulty associated with designing an end-to-side distal anastomosis with two-way outflow that is capable of simultaneously reducing multiple hemodynamic parameters. Further testing will be necessary to determine if the observed elevated particle-wall interactions in a pre-cuffed anastomosis provide the stimulus responsible for the reported high failure rates of these grafts.}, number={12}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Longest, PW and Kleinstreuer, C and Deanda, A}, year={2005}, month={Dec}, pages={1752–1766} }
 @article{longest_kleinstreuer_2004, title={Interacting effects of uniform flow, plane shear, and near-wall proximity on the heat and mass transfer of respiratory aerosols}, volume={47}, ISSN={["1879-2189"]}, DOI={10.1016/j.ijheatmasstransfer.2004.05.029}, abstractNote={Individual and interacting effects of uniform flow, plane shear, and near-wall proximity on spherical droplet heat and mass transfer have been assessed for low Reynolds number conditions beyond the creeping flow regime. Validated resolved volume simulations were used to compute heat and mass transfer surface gradients of two-dimensional axisymmetric droplets and three-dimensional spherical droplets near planar wall boundaries for conditions consistent with inhalable aerosols (5 ⩽ d ⩽ 300 μm) in the upper respiratory tract. Results indicate that planar shear significantly impacts droplet heat and mass transfer for shear-based Reynolds numbers greater than 1, which occur for near-wall respiratory aerosols with diameters in excess of 50 μm. Wall proximity is shown to significantly enhance heat and mass transfer due to conduction and diffusion at separation distances less than five particle diameters and for small Reynolds numbers. For the Reynolds number conditions of interest, significant non-linear effects arise due to the concurrent interaction of uniform flow and shear such that linear superposition of Sherwood or Nusselt number terms is not allowable. Based on the validated numeric simulations, multivariable Sherwood and Nusselt number correlations are provided to account for individual flow characteristics and concurrent non-linear interactions of uniform flow, planar shear, and near-wall proximity. These heat and mass transfer correlations can be applied to effectively compute condensation and evaporation rates of potentially toxic or therapeutic aerosols in the upper respiratory tract, where non-uniform flow and wall proximity are expected to significantly affect droplet transport, deposition, and vapor formation.}, number={22}, journal={INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER}, author={Longest, PW and Kleinstreuer, C}, year={2004}, month={Oct}, pages={4745–4759} }
 @article{hyun_kleinstreuer_longest_chen_2004, title={Particle-hemodynamics simulations and design options for surgical reconstruction of diseased carotid artery bifurcations}, volume={126}, ISSN={["1528-8951"]}, DOI={10.1115/1.1688777}, abstractNote={Based on the hypothesis that aggravating hemodynamic factors play a key role in the onset of arterial diseases, the methodology of “virtual prototyping” of branching blood vessels was applied to diseased external carotid artery (ECA) segments. The goals were to understand the underlying particle-hemodynamics and to provide various geometric design options for improved surgical reconstruction based on the minimization of critical hemodynamic wall parameters (HWPs). First, a representative carotid artery bifurcation (CAB) and then CABs with stenosed ECAs, i.e., a distally occluded ECA and an ECA stump, were analyzed based on transient three-dimensional blood flow solutions, employing a user-enhanced commercial finite volume code. Specifically, the HWPs, i.e., oscillatory shear index, wall shear stress angle gradient, near-wall residence time of monocytes, and near-wall helicity angle difference were evaluated to compare the merits of each design option, including a reconstructed near-optimal junction which generates the lowest HWP-values. The results provide physical insight to the biofluid dynamics of branching blood vessels and guide vascular surgeons as well as stent manufacturers towards interventions leading to high sustained patency rates.}, number={2}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Hyun, S and Kleinstreuer, C and Longest, PW and Chen, C}, year={2004}, month={Apr}, pages={188–195} }
 @article{longest_kleinstreuer_2003, title={Comparison of blood particle deposition models for non-parallel flow domains}, volume={36}, ISSN={["1873-2380"]}, DOI={10.1016/S0021-9290(02)00434-7}, abstractNote={Adhesions of monocytes and platelets to a vascular surface, particularly in regions of flow stagnation, recirculation, and reattachment, are a significant initial event in a broad spectrum of particle–wall interactions that significantly influence the formation of stenotic lesions and mural thrombi. A number of approximations are available for the simulation of both monocyte and platelet interactions with the vascular surface. For the simulation of blood particle adhesion, this study hypothesizes that: (a) the discrete element approach, which accounts for finite particle size and inertia, is advantageous in the context of non-parallel flow domains including stagnation, recirculation, and reattachment; and (b) the likelihood for particle deposition may be effectively approximated as being non-linearly proportional to local particle concentration, residence time, and wall proximity. Models such as wall shear stress correlations, the multicomponent mixture approach, and Lagrangian particle tracking with and without hydrodynamic particle–wall interactions were evaluated. Quantitative performance of the selected models was established by comparisons to available experimental data sets for non-parallel axisymmetric suspension flows of monocytes and platelets. Factors including the convective-diffusive transport of particles, finite particle size and inertia, as well as near-wall hydrodynamic interactions were found to significantly influence blood particle deposition. Of the models studied, the near-wall residence time approach was found to be a particularly effective indicator for the deposition of monocytes (r2=0.74) and platelets (r2=0.57), given that nano-scale physical and biochemical effects must be greatly approximated in computational simulations involving relatively large-scale geometries and complex flow fields.}, number={3}, journal={JOURNAL OF BIOMECHANICS}, author={Longest, PW and Kleinstreuer, C}, year={2003}, month={Mar}, pages={421–430} }
 @article{longest_kleinstreuer_buchanan_2004, title={Efficient computation of micro-particle dynamics including wall effects}, volume={33}, ISSN={["0045-7930"]}, DOI={10.1016/j.compfluid.2003.06.002}, abstractNote={This study describes an effective method for one-way coupled Eulerian–Lagrangian simulations of spherical micro-size particles, including particle–wall interactions and the quantification of near-wall stasis at possibly elevated concentrations. The focus is on particle-hemodynamics simulations where particle suspensions are composed of critical blood cells, such as monocytes, and the carrier fluid is non-Newtonian. Issues regarding adaptive time-step integration of the particle motion equation, relevant point-force model terms, and adaptation of surface-induced particle forces to arbitrary three-dimensional geometries are outlined. By comparison to available experimental trajectories, it is shown that fluid-element pathlines may be used to simulate non-interacting blood particles removed from wall boundaries under dilute transient conditions. However, when particle–wall interactions are significant, an extended form of the particle trajectory equation is required which includes terms for Stokes drag, near-wall drag modifications, or lubrication forces, pressure gradients, and near-wall particle lift. Still, additional physical and/or biochemical wall forces in the nano-meter range cannot be readily calculated; hence the near-wall residence time (NWRT) model indicating the probability of blood particle deposition is presented. The theory is applied to a virtual model of a femoral bypass end-to-side anastomosis, where profiles of the Lagrangian-based NWRT parameter are illustrated and convergence is verified. In order to effectively compute the large number of particle trajectories required to resolve regions of particle stasis, the proposed particle tracking algorithm stores all transient velocity field solution data on a shared memory architecture (SGI Origin 2400) and computes particle trajectories using an adaptive parallel approach. Compared to commercially available particle tracking packages, the algorithm presented is capable of reducing computational time by an order of magnitude for typical transient one-way coupled blood particle simulations in complex cyclical flow domains.}, number={4}, journal={COMPUTERS & FLUIDS}, author={Longest, PW and Kleinstreuer, C and Buchanan, JR}, year={2004}, month={May}, pages={577–601} }
 @article{longest_kleinstreuer_2003, title={Numerical simulation of wall shear stress conditions and platelet localization in realistic end-to-side arterial anastomoses}, volume={125}, ISSN={["1528-8951"]}, DOI={10.1115/1.1613298}, abstractNote={Research studies over the last three decades have established that hemodynamic interactions with the vascular surface as well as surgical injury are inciting mechanisms capable of eliciting distal anastomotic intimal hyperplasia (IH) and ultimate bypass graft failure. While abnormal wall shear stress (WSS) conditions have been widely shown to affect vascular biology and arterial wall self-regulation, the near-wall localization of critical blood particles by convection and diffusion may also play a significant role in IH development. It is hypothesized that locations of elevated platelet interactions with reactive or activated vascular surfaces, due to injury or endothelial dysfunction, are highly susceptible to IH initialization and progression. In an effort to assess the potential role of platelet-wall interactions, experimentally validated particle-hemodynamic simulations have been conducted for two commonly implemented end-to-side anastomotic configurations, with and without proximal outflow. Specifically, sites of significant particle interactions with the vascular surface have been identified by a novel near-wall residence time (NWRT) model for platelets, which includes shear stress-based factors for platelet activation as well as endothelial cell expression of thrombogenic and anti-thrombogenic compounds. Results indicate that the composite NWRT model for platelet-wall interactions effectively captures a reported shift in significant IH formation from the arterial floor of a relatively high-angle (30 deg) graft with no proximal outflow to the graft hood of a low-angle graft (10 deg) with 20% proximal outflow. In contrast, other WSS-based hemodynamic parameters did not identify the observed system-dependent shift in IH formation. However, large variations in WSS-vector magnitude and direction, as encapsulated by the WSS-gradient and WSS-angle-gradient parameters, were consistently observed along the IH-prone suture-line region. Of the multiple hemodynamic factors capable of eliciting a hyperplastic response at the cellular level, results of this study indicate the potential significance of platelet-wall interactions coinciding with regions of low WSS in the development of IH.}, number={5}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Longest, PW and Kleinstreuer, C}, year={2003}, month={Oct}, pages={671–681} }
 @article{longest_kleinstreuer_archie_2003, title={Particle hemodynamics analysis of Miller cuff arterial anastomosis}, volume={38}, ISSN={["0741-5214"]}, DOI={10.1016/S0741-5214(03)00950-9}, abstractNote={ObjectiveStudies of animal and human below-knee anastomoses with Miller cuffs indicate that improved graft patency results from redistribution of intimal hyperplasia away from areas critical to flow delivery, such as the arterial toe. We hypothesize that particle hemodynamic conditions are a biophysical mechanism potentially responsible for the clinically observed shift in intimal hyperplasia localization associated with better patency of the Miller configuration.MethodsComputational fluid dynamics analysis of vortical flow patterns, wall shear stress fields, and potential for platelet interaction with the vascular surface was performed for realistic three-dimensional conventional and Miller cuff distal end-to-side anastomoses. Sites of significant platelet-wall interaction, including elevated near-wall particle concentrations and stasis, were identified with a validated near-wall residence time model, which includes shear stress–based factors for particle activation and surface reactivity.ResultsParticle hemodynamics largely coincide with the observed redistribution of intimal hyperplasia away from the critical arterial toe region. Detrimental changes in wall shear stress vector magnitude and direction are significantly reduced along the arterial suture line of the Miller cuff, largely as a result of increased anastomotic area available for flow redirection. However, because of strong particle-wall interaction, resulting high near-wall residence time contours indicate significant intimal hyperplasia along the graft-vein suture line and in the vicinity of the arterial heel.ConclusionsWhile a number of interacting mechanical, biophysical, and technical factors may be responsible for improved Miller cuff patency, our results imply that particle hemodynamics conditions engendered by Miller cuff geometry provide a mechanism that may account for redistribution of intimal hyperplasia. In particular, it appears that a focal region of significant particle-wall interaction at the arterial toe is substantially reduced with the Miller cuff configuration.}, number={6}, journal={JOURNAL OF VASCULAR SURGERY}, author={Longest, PW and Kleinstreuer, C and Archie, JP}, year={2003}, month={Dec}, pages={1353–1362} }
 @article{longest_kleinstreuer_2003, title={Particle-hemodynamics modeling of the distal end-to-side femoral bypass: effects of graft caliber and graft-end cut}, volume={25}, ISSN={["1873-4030"]}, DOI={10.1016/S1350-4533(03)00124-3}, abstractNote={Late-stage occlusions of peripheral synthetic bypass grafts are frequently due to intimal hyperplasia and/or thrombosis at the distal anastomosis, resulting in unacceptably high failure rates. It has been widely established that hemodynamic and blood particle interactions with the vascular surface as well as surgical injury and compliance mismatch are inciting mechanisms capable of eliciting various cellular level responses associated with distal anastomotic intimal hyperplasia (IH) formation. Primary geometric factors influencing anastomotic hemodynamics include the graft-to-artery diameter ratio and graft-hood shape, which are determined by the graft caliber and initial graft-end cut selected by the vascular surgeon. In this study, the particle-hemodynamic effects of graft-end cuts (straight, curved, and S-shaped) and graft-to-artery diameter ratios (2:1 vs. 1.5:1) have been numerically assessed in four common unexpanded anastomotic configurations with respect to vortical flow patterns, wall shear stress based parameters, and platelet interactions with the vascular surface. Sites of significant platelet-wall interactions have been identified by a novel near-wall residence time (NWRT) model, which includes shear stress based factors for platelet activation and endothelial cell expression of anti-thrombogenic compounds. Of the configurations evaluated, straight and curved graft-end cuts with a graft-to-artery diameter ratio of 1.5:1 were found to reduce the particle-hemodynamic potential for IH development at locations critical to flow delivery. Nevertheless, the potential for significant IH occurrence via platelet and/or endothelial response pathways was highly evident in all conventional anastomoses considered, such that a decisively superior configuration was not determined. These results illustrate the need for alternative anastomotic designs with the intent of reducing critical hemodynamic wall parameters and mitigating regions of significant particle-wall interactions.}, number={10}, journal={MEDICAL ENGINEERING & PHYSICS}, author={Longest, PW and Kleinstreuer, C}, year={2003}, month={Dec}, pages={843–858} }
 @article{longest_kleinstreuer_truskey_buchanan_2003, title={Relation between near-wall residence times of monocytes and early lesion growth in the rabbit aorto-celiac junction}, volume={31}, ISSN={["0090-6964"]}, DOI={10.1114/1.1531635}, abstractNote={Transient particle-hemodynamic simulations were conducted in a model of the rabbit aorto-celiac junction to investigate mechanisms responsible for localized monocyte attachment and subsequent lesion formation. We hypothesized that the probability for monocyte deposition is related to discrete near-wall particle stasis and/or elevated concentrations, as encapsulated by a new near-wall residence time (NWRT) parameter. A low wall shear stress (WSS) condition accounted for factors such as endothelial cell expression of adhesive molecules as well as a reduced probability of monocyte rolling and detachment. To accurately simulate particle transport, terms for the near-wall drag modification and lift were included. Low WSS and high oscillatory shear index parameters proved ineffective compared to localized in vivo results of monocyte accumulation and lesion initialization. The NWRT parameter, with a limiting WSS condition, identified the lateral flow divider as most susceptible to monocyte deposition, as observed in vivo. A representative quantitative correlation between monocyte deposition and NWRT occurrence was established (r2 = 0.77 and p<10(-4)) on a highly focal basis for an averaged data set. Results indicate that cell transport and conditions for hemodyamically induced surface reactivity are necessary components in formulating an effective model for monocyte adhesion in complex three-dimensional vessel configurations.}, number={1}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Longest, PW and Kleinstreuer, C and Truskey, GA and Buchanan, JR}, year={2003}, month={Jan}, pages={53–64} }
 @article{kleinstreuer_hyun_buchanan_longest_archie_truskey_2001, title={Hemodynamic parameters and early intimal thickening in branching blood vessels}, volume={29}, DOI={10.1615/critrevbiomedeng.v29.i1.10}, abstractNote={Intimal thickening due to atherosclerotic lesions or intimal hyperplasia in medium to large blood vessels is a major contributor to heart disease, the leading cause of death in the Western World. Balloon angioplasty with stenting, bypass surgery, and endarterectomy (with or without patch reconstruction) are some of the techniques currently applied to occluded blood vessels. On the basis of the preponderance of clinical evidence that disturbed flow patterns play a key role in the onset and progression of atherosclerosis and intimal hyperplasia, it is of interest to analyze suitable hemodynamic wall parameters that indicate susceptible sites of intimal thickening and/or favorable conditions for thrombi formation. These parameters, based on the wall shear stress, wall pressure, or particle deposition, are applied to interpret experimental/clinical observations of intimal thickening. Utilizing the parameters as "indicator" functions, internal branching blood vessel geometries are analyzed and possibly altered for different purposes: early detection of possibly highly stenosed vessel segments, prediction of future disease progression, and vessel redesign to potentially improve long-term patency rates. At the present time, the focus is on the identification of susceptible sites in branching blood vessels and their subsequent redesign, employing hemodynamic wall parameters. Specifically, the time-averaged wall shear stress (WSS), its spatial gradient (WSSG), the oscillatory shear index (OSI), and the wall shear stress angle gradient (WSSAG) are compared with experimental data for an aortoceliac junction. Then, the OSI, wall particle density (WPD), and WSSAG are segmentally averaged for different carotid artery bifurcations and compared with clinical data of intimal thickening. The third branching blood vessel under consideration is the graft-to-vein anastomosis of a vascular access graft. Suggested redesigns reduce several hemodynamic parameters (i.e., the WSSG, WSSAG, and normal pressure gradient [NPG]), thereby reducing the likelihood of restenosis, especially near the critical toe region.}, number={1}, journal={Critical Reviews in Biomedical Engineering}, author={Kleinstreuer, C. and Hyun, S. and Buchanan, J. R. and Longest, P. W. and Archie, J. P. and Truskey, G. A.}, year={2001}, pages={1–64} }
 @article{longest_kleinstreuer_andreotti_2000, title={Computational analyses and design improvements of graft-to-vein anastomoses}, volume={28}, ISSN={["0278-940X"]}, DOI={10.1615/critrevbiomedeng.v28.i12.240}, abstractNote={For hemodialysis patients, arteriovenous grafts are omnipresent. Unfortunately, a large percentage of such grafts fail within the first year after surgery because of occlusive lesions mainly at the venous anastomotic site. It is textbook knowledge that critical values of certain hemodynamic parameters, such as low (oscillatory) wall shear stresses, large sustained wall shear stress gradients, significant changes in wall shear stress angles, excessive radial pressure gradients, etc., play significant roles in the onset and/or development of vascular diseases. The idea is to geometrically design graft-to-vein configurations such that aggravating flow patterns are reduced, and hence stenotic developments are minimized. Focusing on a new blood rheological model in conjunction with three graft-to-vein anastomotic configurations, that is, a base case, the Bard-IMPRA Venaflo graft, and a new graft-end design, the corresponding transient laminar 3-D hemodynamics are numerically simulated and compared. The design criterion for the best performance of these junction geometries is the most significant reduction in locally disturbed flow as expressed by equally weighted indicator functions for the onset and progression of stenotic developments. As a result of this comparison study, quantitative recommendations for arteriovenous loop graft designs toward increased patency rates are provided. The resulting improved graft design will be scrutinized in clinical trials.}, number={1-2}, journal={CRITICAL REVIEWS IN BIOMEDICAL ENGINEERING}, author={Longest, PW and Kleinstreuer, C and Andreotti, PJ}, year={2000}, pages={141–147} }
 @article{longest_kleinstreuer_2000, title={Computational haemodynamics analysis and comparison study of arterio-venous grafts}, volume={24}, number={3}, journal={Journal of Medical Engineering & Technology}, author={Longest, P. W. and Kleinstreuer, C.}, year={2000}, month={May}, pages={102–110} }
 @article{longest_kleinstreuer_kinsey_2000, title={Turbulent three-dimensional air flow and trace gas distribution in an inhalation test chamber}, volume={122}, ISSN={["0098-2202"]}, DOI={10.1115/1.483270}, abstractNote={Steady incompressible turbulent air flow and transient carbon monoxide transport in an empty Rochester-style human exposure chamber have been numerically simulated and compared with experimental data sets. The system consisted of an inlet duct with a continuous carbon monoxide point source, 45- and 90-degree bends, a round diffuser, a round-to-square transition, a rectangular diffuser, the test chamber, a perforated floor, and again transition pieces from the chamber to an outlet duct. Such a configuration induced highly nonuniform vortical flow patterns in the chamber test area where a pollutant concentration is required to be constant at breathing level for safe and accurate inhalation studies. Presented are validated momentum and mass transfer results for this large-scale system with the main goals of determining the development of tracer gas (CO) distributions in the chamber and analyzing the contributions to CO-mixing. Numerical simulations were conducted employing a k-ε model and the latest available RNG k-ε model for air and CO-mixing. Both models predict similar velocity fields and are in good agreement with measured steady and transient CO-concentrations. It was found that secondary flows in the inlet section and strong vortical flow in the chamber with perforated flooring contributed to effective mixing of the trace gas at breathing levels. Specifically, in the height range of 1.4 m<h<2.0 m above the chamber floor, predicted CO-concentrations rapidly reached a near constant value which agrees well with experimental results. This work can be extended to analyze trace gas mixing as well as aerosol dispersion in occupied test chambers with or without flow redirection devices installed in the upstream section. A complementary application is particle transport and deposition in clean rooms of the electronic, pharmaceutical, and health care industries. [S0098-2202(00)01702-8]}, number={2}, journal={JOURNAL OF FLUIDS ENGINEERING-TRANSACTIONS OF THE ASME}, author={Longest, PW and Kleinstreuer, C and Kinsey, JS}, year={2000}, month={Jun}, pages={403–411} }