Single additive mechanism predicts lateral interactions effects-computational model.

The mechanism underlying the lateral interactions (LI) phenomenon is still an enigma. Over the years, several groups have tried to explain the phenomenon and suggested models to predict its psychophysical results. Most of these models comprise both inhibitory and facilitatory mechanisms for describing the LI phenomenon. Their studies' assumption that a significant inhibition mechanism exists is based on the classical interpretation of the threshold elevation perceived in psychophysical experiments. In this work, we suggest a different interpretation of the threshold elevation obtained experimentally. Our model proposes and demonstrates how a facilitatory additive mechanism can solely predict both the facilitation and "inhibition" aspects of the phenomenon, without the need for an additional inhibitory mechanism, at least for the two flankers' configurations. Though the model is simple it succeeds to predict the LI effect under a large variety of stimuli configurations and parameters. The model is in agreement with both classical and recent psychophysical and neurophysiological results. We suggest that the LI mechanism plays a role in creating an educated guess to form a continuation of gratings and textures based on the surrounding visual stimuli.

Thromboresistance comparison of the HeartMate II ventricular assist device with the device thrombogenicity emulation- optimized HeartAssist 5 VAD.

Approximately 7.5 × 106 patients in the US currently suffer from end-stage heart failure. The FDA has recently approved the designations of the Thoratec HeartMate II ventricular assist device (VAD) for both bridge-to-transplant and destination therapy (DT) due to its mechanical durability and improved hemodynamics. However, incidence of pump thrombosis and thromboembolic events remains high, and the life-long complex pharmacological regimens are mandatory in its VAD recipients. We have previously successfully applied our device thrombogenicity emulation (DTE) methodology for optimizing device thromboresistance to the Micromed Debakey VAD, and demonstrated that optimizing device features implicated in exposing blood to elevated shear stresses and exposure times significantly reduces shear-induced platelet activation and significantly improves the device thromboresistance. In the present study, we compared the thrombogenicity of the FDA-approved HeartMate II VAD with the DTE-optimized Debakey VAD (now labeled HeartAssist 5). With quantitative probability density functions of the stress accumulation along large number of platelet trajectories within each device which were extracted from numerical flow simulations in each device, and through measurements of platelet activation rates in recirculation flow loops, we specifically show that: (a) Platelets flowing through the HeartAssist 5 are exposed to significantly lower stress accumulation that lead to platelet activation than the HeartMate II, especially at the impeller-shroud gap regions (b) Thrombus formation patterns observed in the HeartMate II are absent in the HeartAssist 5 (c) Platelet activation rates (PAR) measured in vitro with the VADs mounted in recirculation flow-loops show a 2.5-fold significantly higher PAR value for the HeartMate II. This head to head thrombogenic performance comparative study of the two VADs, one optimized with the DTE methodology and one FDA-approved, demonstrates the efficacy of the DTE methodology for drastically reducing the device thrombogenic potential, validating the need for a robust in silico/in vitro optimization methodology for improving cardiovascular devices thromboresistance.

Intracoronary monocyte chemoattractant protein 1 and vascular endothelial growth factor levels are associated with necrotic core, calcium and fibrous tissue atherosclerotic plaque components: an intracoronary ultrasound radiofrequency study.

AIMS: To investigate the relationship between various serum biomarkers and coronary atherosclerotic plaque composition obtained by intravascular ultrasound virtual histology (IVUS-VH). METHODS: Using ELISA, we measured the serum levels of CD40 ligand, C-reactive protein, monocyte chemoattractant protein 1 (MCP-1), metalloproteinase 9, P-selectin and vascular endothelial growth factor (VEGF) in 40 patients with manifested coronary artery disease. RESULTS: Correlation analysis between biomarkers levels, IVUS grayscale parameters and VH-defined necrotic core (NC), calcium, fibrous and fibrofatty components was performed. MCP-1 and VEGF levels correlated with the severity of area stenosis (r = 0.35, p = 0.03 and r = 0.38, p = 0.017, respectively) and inversely correlated with the remodeling index (r = -0.35, p = 0.03 and r = 0.35, p = 0.02, respectively). Higher levels of MCP-1 were associated with increased calcium (r = 0.47, p = 0.004), NC (r = 0.38, p = 0.02) and less fibrous tissue components (r = -0.34, p = 0.03), whereas VEGF had an inverse correlation with both calcium components (r = -0.37, p = 0.02) and NC (r = -0.34, p = 0.036) but was strongly associated with increased fibrous components (r = 0.47, p = 0.003). No significant correlation was noted for any of the other biomarkers. CONCLUSIONS: MCP-1 and VEGF serum levels in patients with ischemic heart disease are correlated with coronary artery plaque burden and composition.

A predictive multiscale model for simulating flow-induced platelet activation: Correlating in silico results with in vitro results.

Flow-induced platelet activation prompts complex filopodial formation. Continuum methods fail to capture such molecular-scale mechanisms. A multiscale numerical model was developed to simulate this activation process, where a Dissipative Particle Dynamics (DPD) model of viscous blood flow is interfaced with a Coarse Grained Molecular Dynamics (CGMD) platelet model. Embedded in DPD blood flow, the macroscopic dynamic stresses are interactively transferred to the CGMD model, inducing intra-platelet associated events. The platelets activate by a biomechanical transductive linkage chain and dynamically change their shape in response. The models are fully coupled via a hybrid-potential interface and multiple time-stepping (MTS) schemes for handling the disparity between the spatiotemporal scales. Cumulative hemodynamic stresses that may lead to platelet activation are mapped on the surface membrane and simultaneously transmitted to the cytoplasm and cytoskeleton. Upon activation, the flowing platelets lose their quiescent discoid shape and evolve by forming filopodia. The model predictions were validated by a set of in vitro experiments, Platelets were exposed to various combinations of shear stresses and durations in our programmable hemodynamic shearing device (HSD). Their shape change was measured at multiple time points using scanning electron microscopy (SEM). The CGMD model parameters were fine-tuned by interrogating a parameter space established in these experiments. Segmentation of the SEM imaging streams was conducted by a deep machine learning system. This model can be further employed to simulate shear mediated platelet activation thrombosis initiation and to study the effects of modulating platelet properties to enhance their shear resistance via mechanotransduction pathways.

Nonlinear multiscale analysis of coronary atherosclerotic vulnerable plaque artery: fluid-structural modeling with micromechanics.

A unique three-dimensional (3D) computational multiscale modeling approach is proposed to investigate the influence of presence of microcalcification particles on the stress field distribution in the thin cap layer of a coronary atherosclerotic vulnerable plaque system. A nested 3D modeling analysis framework spanning the multiscale nature of a coronary atherosclerotic vulnerable plaque is presented. At the microscale level, a micromechanical modeling approach, which is based on computational finite-element (FE) representative unit cell, is applied to obtain the homogenized nonlinear response of the calcified tissue. This equivalent response effectively allows the integration of extremely small microcalcification inclusions in a global biomechanical FE model. Next, at the macroscale level, a 3D patient-based fluid-structure interaction FE model, reconstructing a refined coronary artery geometry with calcified plaque lesion, is generated to study the mechanical behavior of such multi-component biomechanical system. It is shown that the proposed multiscale modeling approach can generate a higher resolution of stress and strain field distributions within the coronary atherosclerotic vulnerable plaque system and allow the assessment of the local concentration stress around the microcalcifications in plaque cap layers. A comparison of stress field distributions within cap layers with and without inclusion of microcalcifications is also presented.

Preparedness for anthrax attack: the effect of knowledge on the willingness to treat patients.

Little is known about the factors that may impact on the willingness of physicians and nurses to treat patients during a bioterrorism attack. This survey was conducted among 76 randomly selected nurses and physicians in the emergency rooms of three public hospitals in order to analyse the relationship between knowledge, profession and the willingness to treat anthrax. The study finds that the willingness of physicians and nurses to come to work is 50% greater among the group with the highest knowledge about anthrax (P < 0.0001). Within that group, the willingness to treat patients suspected of being infected with anthrax was 37% greater (P < 0.0001) and the willingness to treat patients diagnosed with anthrax was 28% greater (P = 0.004) than in the other groups. These results imply that enhancement of knowledge among health care workers may improve their willingness to come to work and treat patients infected with anthrax during a bioterrorism attack.

New Insights into Valve Hemodynamics.

Heart valve diseases are common disorders with five million annual diagnoses being made in the United States alone. All heart valve disorders alter cardiac hemodynamic performance; therefore, treatments aim to restore normal flow. This paper reviews the state-of-the-art clinical and engineering advancements in heart valve treatments with a focus on hemodynamics. We review engineering studies and clinical literature on the experience with devices for aortic valve treatment, as well as the latest advancements in mitral valve treatments and the pulmonic and tricuspid valves on the right side of the heart. Upcoming innovations will potentially revolutionize treatment of heart valve disorders. These advancements, and more gradual enhancements in the procedural techniques and imaging modalities, could improve the quality of life of patients suffering from valvular disease who currently cannot be treated.

Shear stress-induced transcriptional regulation via hybrid promoters as a potential tool for promoting angiogenesis.

Among the key effects of fluid shear stress on vascular endothelial cells is modulation of gene expression. Promoter sequences termed shear stress response elements (SSREs) mediate the responsiveness of endothelial genes to shear stress. While previous studies showed that shear stress responsiveness is mediated by a single SSRE, these endogenous promoters often encode for multiple SSREs. Moreover, hybrid promoters encoding a single SSRE rarely respond to shear stress at the same magnitude as the endogenous promoter. Thus, to better understand the interplay between the various SSREs, and between SSREs and endothelial-specific sequences (ESS), we generated a series of constructs regulated by SSREs cassettes alone, or in combination with ESS, and tested their response to shear stress and endothelial specific expression. Among these constructs, the most responsive promoter (NR1/2) encoded a combination of two GAGACC/SSREs, the Sp1/Egr1 sequence, as well as a TPA response element (TRE). This construct was four- to five-fold more responsive to shear stress than a promoter encoding a single SSRE. The expression of constructs containing other SSRE combinations was unaffected or suppressed by shear stress. Addition of ESS derived from the Tie2 promoter, either 5' or 3' to NR1/2 resulted in shear stress transcriptional suppression, yet retained endothelial specific expression. Thus, the combination and localization order of the various SSREs in a single promoter is crucial in determining the pattern and degree of shear stress responsiveness. These shear stress responsive cassettes may prove beneficial in our attempt to time the expression of an endothelial transgene in the vasculature.

Does the chromatic Mach bands effect exist?

The achromatic Mach bands effect is a well-known visual illusion, discovered over a hundred years ago. This effect has been investigated thoroughly, mainly for its brightness aspect. The existence of Chromatic Mach bands, however, has been disputed. In recent years it has been reported that Chromatic Mach bands are not perceived under controlled iso-luminance conditions. However, here we show that a variety of Chromatic Mach bands, consisting of chromatic and achromatic regions, separated by a saturation ramp, can be clearly perceived under iso-luminance and iso-brightness conditions. In this study, observers' eye movements were recorded under iso-brightness conditions. Several observers were tested for their ability to perceive the Chromatic Mach bands effect and its magnitude, across different cardinal and non-cardinal Chromatic Mach bands stimuli. A computational model of color adaptation, which predicted color induction and color constancy, successfully predicts this variation of Chromatic Mach bands. This has been tested by measuring the distance of the data points from the "achromatic point" and by calculating the shift of the data points from predicted complementary lines. The results suggest that the Chromatic Mach bands effect is a specific chromatic induction effect.

Controlling cardiac transport and plaque formation.

Macro-particles transported in the bloodstream, such as LDL particles and macrophages, are considered to be one of the initiating factors of atherosclerotic plaque development. LDL infiltration from the bloodstream into a blood vessel's wall, whether the coronary, peripheral, or carotid arteries, is considered a major inflammatory factor, recruiting macrophages from the blood flow and leading to the formation of vulnerable atherosclerotic plaques. Infiltration sites are influenced by patterns of blood flow, as regions of lower shear stresses and high oscillations may give rise to higher infiltration rates through the endothelium, exacerbating the growth of a plaque and its tendency to rupture. Previous studies demonstrated a high prevalence of rupture sites proximal to the minimum lumen area, which raised the question of whether the existence of two distinct adjacent plaques, in which the distal plaque is more severe, can give rise to hemodynamic forces that can push the non-stenotic plaque to rupture. Models of the coronary arteries with one and two eccentric and concentric stenotic narrowings were built into a closed flow loop. The single stenosis model had a 75% area reduction narrowing (representing the vunerable atherosclerotic plaque) with relevant elastic properties. The double stenosis model included an additional distal 84% area reduction narrowing. The flow in the area between the two stenoses was recorded and analyzed using continuous doppler particle image velocimetry (CDPIV), together with the hydrostatic pressure acting on the proximal plaque. Results indicated that the combined shear rates and pressure effects in a model with a significant distal stenosis can contribute to the increase in plaque instability by LDL and enhanced macrophage uptake. The highly oscillatory nature of the disturbed flow near the shoulder of the vulnerable atherosclerotic plaque enriches its lipid soft core, and the high hydrostatic pressures acting on the same lesion in this geometry induce high internal maximal stresses that can trigger the rupture of the plaque.

Influence of microcalcifications on vulnerable plaque mechanics using FSI modeling.

Sudden heart attacks remain one of the primary causes of premature death in the developed world. Asymptomatic vulnerable plaques that rupture are believed to prompt such fatal heart attacks and strokes. The role of microcalcifications in the vulnerable plaque rupture mechanics is still debated. Recent studies suggest the microcalcifications increase the plaque vulnerability. In this manuscript we present a numerical study of the role of microcalcifications in plaque vulnerability in an eccentric stenosis model using a transient fluid-structure interaction (FSI) analysis. Two cases are being compared (i) in the absence of a microcalcification (ii) with a microcalcification spot fully embedded in the fibrous cap. Critical plaque stress/strain conditions were affected considerably by the presence of a calcified spot, and were dependent on the timing (phase) during the flow cycle. The vulnerable plaque with the embedded calcification spot presented higher wall stress concentration region in the fibrous cap a bit upstream to the calcified spot, with stress propagating to the deformable parts of the structure around the calcified spot. Following previous studies, this finding supports the hypothesis that microcalcifications increase the plaque vulnerability. Further studies in which the effect of additional microcalcifications and parametric studies of critical plaque cap thickness based on plaque properties and thickness, will help to establish the mechanism by which microcalcifications weaken the plaque and may lead to its rupture.

Brightness contrast-contrast induction model predicts assimilation and inverted assimilation effects.

In classical assimilation effects, intermediate luminance patches appear lighter when their immediate surround is comprised of white patches and appear darker when their immediate surround is comprised of dark patches. With patches either darker or lighter than both inducing patches, the direction of the brightness effect is reversed and termed as "inverted assimilation effect." Several explanations and models have been suggested, some are relevant to specific stimulus geometry, anchoring theory, and models that involve high level cortical processing (such as scission, etc.). None of these studies predicted the various types of assimilation effects and their inverted effects. We suggest here a compound brightness model, which is based on contrast-contrast induction (second-order adaptation mechanism). The suggested model predicts the various types of brightness assimilation effects and their inverted effects. The model is composed of three main stages: (1) composing post-retinal second-order opponent receptive fields, (2) calculations of local and remote contrast, and (3) adaptation of the second-order (contrast-contrast induction). We also utilize a variation of the Jacobi iteration process to enable elegant edge integration in order to evaluate the model is performance.

Improving the Mechanical Rigidity of Hyaluronic Acid by Integration of a Supramolecular Peptide Matrix.

Hyaluronic acid (HA), a major component of the extracellular matrix, is an attractive material for various medical applications. Yet, its low mechanical rigidity and fast in vivo degradation hinder its utilization. Here, we demonstrate the reinforcement of HA by its integration with a low-molecular-weight peptide hydrogelator to produce a composite hydrogel. The formulation of HA with the fluorenylmethoxycarbonyl diphenylalanine (FmocFF) peptide, one of the most studied self-assembling hydrogel-forming building blocks, showing notable mechanical properties, resulted in the formation of stable, homogeneous hydrogels. Electron microscopy analysis demonstrated a uniform distribution of the two matrices in the composite forms. The composite hydrogels showed improved mechanical properties and stability to enzymatic degradation while maintaining their biocompatibility. Moreover, the storage modulus of the FmocFF/HA composite hydrogels reached up to 25 kPa. The composite hydrogels allowed sustained release of curcumin, a hydrophobic polyphenol showing antioxidant, anti-inflammatory, and antitumor activities. Importantly, the rate of curcumin release was modulated as a function of the concentration of the FmocFF peptide within the hydrogel matrix. This work provides a new approach for conferring mechanical rigidity and stability to HA without the need of cross-linking, thus potentially facilitating its utilization in different clinical applications, such as sustained drug release.

Quantitative T2 mapping for detection and quantification of thrombophlebitis in a rabbit model.

Short peripheral catheter thrombophlebitis (SPCT), a sterile inflammation of the vein wall, is the most common complication associated with short peripheral catheters (SPCs) and affects up to 80% of hospitalized patients receiving IV therapy. Extensive research efforts have been devoted for improvement and optimization of the catheter material, but means for examination of any novel design are limited, inaccurate and require costly comprehensive pre-clinical and clinical trials. Therefore, there is a conclusive need for a reliable quantitative method for evaluation of SPCT, in particular for research purposes examining the thrombophlebitis-related symptoms of any novel catheter design. In this study, we developed for the first time a quantitative MRI based tool for evaluation of SPCT. The extent and severity of SPCT caused by two different commercially available SPCs with known predisposition for thrombophlebitis, were studied in a rabbit model. MRI analysis was consistent with the standardized pathology evaluation and showed remarkable difference in the percent of edema between the experimental groups. These differences were in line with previous studies and provide evidence that this type of analysis may be useful for future assessment of SPCT in vivo. As a non-invasive method, it may constitute a cost effective solution for examination of new catheters and other medical devices, thereby reducing the need for animal sacrifice.

The effect of pathologic venous valve on neighboring valves: fluid-structure interactions modeling.

Understanding the hemodynamics surrounding the venous valve environment is of a great importance for prosthetic valves design. The present study aims to evaluate the effect of leaflets' stiffening process on the venous valve hemodynamics, valve's failure on the next proximal valve hemodynamics and valve's failure in a secondary daughter vein on the healthy valve hemodynamics in the main vein when both of these valves are distal to a venous junction. Fully coupled, two-way fluid-structure interaction computational models were developed and employed. The sinus pocket region experiences the lowest fluid shear stress, and the base region of the sinus side of the leaflet experiences the highest tissue stress. The leaflets' stiffening increases the tissue stress the valve is experiencing in a very low fluid shear region. A similar effect occurs with the proximal healthy valve as a consequence of the distal valve's failure and with the mother vein valve as a consequence of daughter vein valve's failure. Understanding the described mechanisms may be helpful for elucidating the venous valve stiffness-function relationship in nature, the reasons for a retrograde development of reflux and the relationship between venous valves located near venous junctions, and for designing better prosthetic valves and for improving their positioning.

Pressure drop and arterial compliance - Two arterial parameters in one measurement.

Coronary artery pressure-drop and distensibility (compliance) are two major, seemingly unrelated, parameters in the cardiovascular clinical setting, which are indicative of coronary arteries patency and atherosclerosis severity. While pressure drop is related to flow, and therefore serves as a functional indicator of a stenosis severity, the arterial distensibility is indicative of the arterial stiffness, and hence the arterial wall composition. In the present study, we hypothesized that local pressure drops are dependent on the arterial distensibility, and hence can provide information on both indices. The clinical significance is that a single measurement of pressure drop could potentially provide both functional and bio-mechanical metrics of lesions, and thus assist in real-time decision making prior to stenting. The goal of the current study was to set the basis for understanding this relationship, and define the accuracy and sensitivity required from the pressure measurement system. The investigation was performed using numerical fluid-structure interaction (FSI) simulations, validated experimentally using our high accuracy differential pressure measurement system. Simplified silicone mock coronary arteries with zero to intermediate size stenoses were used, and various combinations of arterial distensibility, diameter, and flow rate were simulated. Results of hyperemic flow cases were also compared to fractional flow reserve (FFR). The results indicate the potential clinical superiority of a high accuracy pressure drop-based parameter over FFR, by: (i) being more lesion-specific, (ii) the possibility to circumvent the FFR dependency on pharmacologically-induced hyperemia, and, (iii) by providing both functional and biomechanical lesion-specific information.

Mechanical Compression Effects on the Secretion of vWF and IL-8 by Cultured Human Vein Endothelium.

Short peripheral catheters are ubiquitous in today's healthcare environment enabling effective delivery of fluids and medications directly into a patient's vasculature. However, complications related to their use, such as short peripheral catheter thrombophlebitis (SPCT), affect up to 80% of hospitalized patients. While indwelling within the vein, the catheters exert prolonged constant pressure upon the endothelium which can trigger inflammation processes. We have developed and studied an in-vitro model of cultured endothelial cells subjected to mechanical compression of modular self-designed weights, and explored their inflammatory response by quantification of two key biomarkers- vWF and IL-8. Evaluation was performed by ELISA immunoassay and processing of vWF-labeled immunofluorescence images. We found that application of weights correspond to 272 Pa yielded increased release of vWF and IL-8 up to 150% and 250% respectively, comparing to the exertion of 136 Pa. Analyses of the immunofluorescence images revealed significantly longer and more extracellular vWF-strings as well as higher intensity stained-pixels in cells exposed to elevated pressures. The release of both factors found to be significantly dependent on the extent of the exerted pressure. The research shed a light on the relationship between induced mechanical compression and the pathogenesis of SPCT. Minimizing, let alone eliminating the contact between the catheter and the vein wall will mitigate the pressure acting on the endothelium, thereby reducing the secretion of inflammatory factors and lessen the incidence of SPCT.

Ventricular Assist Device Implantation Configurations Impact Overall Mechanical Circulatory Support System Thrombogenic Potential.

Ventricular assist devices (VADs) became in recent years the standard of care therapy for advanced heart failure with hemodynamic compromise. With the steadily growing population of device recipients, various postimplant complications have been reported, mostly associated with the hypershear generated by VADs that enhance their thrombogenicity by activating platelets. Although VAD design optimization can significantly improve its thromboresistance, the implanted VAD need to be evaluated as part of a system. Several clinical studies indicated that variability in implantation configurations may contribute to the overall system thrombogenicity. Numerical simulations were conducted in the HeartAssist 5 (HA5) and HeartMate II (HMII) VADs in the following implantation configurations: 1) inflow cannula angles: 115° and 140° (HA5); 2) three VAD circumferential orientations: 0°, 30°, and 60° (HA5 and HMII); and 3) 60° and 90° outflow graft anastomotic angles with respect to the ascending aorta (HA5). The stress accumulation of the platelets was calculated along flow trajectories and collapsed into a probability density function, representing the "thrombogenic footprint" of each configuration-a proxy to its thrombogenic potential (TP). The 140° HA5 cannula generated lower TP independent of the circumferential orientation of the VAD. Sixty-degree orientation generated the lowest TP for the HA5 versus 0° for the HMII. An anastomotic angle of 60° resulted in lower TP for HA5. These results demonstrate that optimizing the implantation configuration reduces the overall system TP. Thromboresistance can be enhanced by combining VAD design optimization with the surgical implantation configurations for achieving better clinical outcomes of implanted VADs.

Modelling catheter-vein biomechanical interactions during an intravenous procedure.

A reliable intravenous (IV) access into the upper extremity veins requires the insertion of a temporary short peripheral catheter (SPC). This so common procedure is, however, associated with a risk of developing short peripheral catheter thrombophlebitis (SPCT) which causes distress and potentially prolongs patient hospitalization. We have developed and studied a biomechanical SPC-vein computational model during an IV procedure, and explored the biomechanical effects of repeated IV episodes on onset and reoccurrences of SPCT. The model was used to determine the effects of different insertion techniques as well as inter-patient biological variability on the catheter-vein wall contact pressures and wall deformations. We found that the maximal pressure exerted upon the vein wall was inhomogeneously distributed, and that the bending region was exposed to significantly greater pressures and deformations. The maximal exerted contact pressure on the inner vein's wall was 2938 Pa. The maximal extent of the SPC penetration into the vein wall reached 3.6 µm, which corresponds to approximately 100% of the average height of the inner layer, suggesting local squashing of endothelial cells at the contact site. The modelling describes a potential biomechanical damage pathway that can explain the reoccurrence of SPCT.

Hemodynamic evaluation of embolic trajectory in an arterial bifurcation: an in-vitro experimental model.

BACKGROUND AND PURPOSE: Despite the importance of embolism as a major cause of brain infarction, little is known about the hemodynamic factors governing the path large emboli tend to follow. Our aim was to test in vitro, whether hemodynamic parameters other than flow ratios between bifurcation branches may affect the distribution of embolic particles in a Y-shaped bifurcation model, used as an analogue to an arterial bifurcation. METHODS: In vitro experiments were conducted using suspensions of sphere-shaped particles (0.6, 1.6, and 3.2 mm) in water-glycerin mixture, using steady and pulsatile laminar flow regimes in a Y-shaped bifurcation model (identical branching angles [theta1=theta2=45 degrees] with one daughter branch diameter wider than the other [D1=6 mm, D2=4 mm]; average Reynolds number 500). RESULTS: Experiments using naturally buoyant particles under steady flow conditions and four outlet-flow ratios revealed that small (0.6 mm) and mid-sized (1.6 mm) particles entered into either the narrower or wider bifurcation daughter branch nonpreferentially, proportionally to the flow ratios. Large particles (3.2 mm), however, preferentially entered the wider daughter branch. Moreover, as the flow ratio increases this phenomenon was augmented. Further experiments revealed that the preference of the wider daughter branch for high particle-to-branch diameter-ratios further increases under pulsatile flow and by the density ratio between particles and fluid. CONCLUSIONS: Particles' distribution in a bifurcation is affected, beyond its outlets-flow-ratios, by the particle-to-branch diameter-ratio. The tendency of large particles to preferentially enter the wider bifurcation branch, beyond the flow ratio, is augmented under pulsatile flow conditions and is affected by particle-to-fluid density-ratio. These findings may have important implications for understanding the hemodynamic mechanisms underlying the trajectory of large emboli.