Microsphere Transport Research Articles

High-Speed Imaging of Microsphere Transport by Cavitation Activity in a Tissue-Mimicking Phantom.

Ultrasound-mediated cavitation has been harnessed to improve the delivery of various therapeutics, including the extravasation of small molecule drugs and nanoparticles (<1 µm) into soft tissue. This study investigated whether cavitation could also enhance the extravasation of larger (>10 µm) therapeutic particles, representative of radio- or chemo-embolic particles, in a tissue-mimicking phantom. High-speed (103-106 frames/s) optical imaging was used to observe the motion of glass microspheres with diameters of 15-32 or 105-107 µm in an agar phantom under exposure to high-intensity focused ultrasound (0.5 MHz) at a range of peak negative pressures (1.9-2.8 MPa) in the presence of SonoVue microbubbles. In contrast to the microstreaming reported to be responsible for nanoparticle transport, the formation and translation of bubble clouds were found to be primarily responsible for the motion of glass microspheres. The bubble clouds were seen both to create channels in the phantom and to travel along them under the action of primary acoustic radiation force, either propelling or entraining microspheres with them. Collisions between microspheres were also seen to promote cloud formation and cavitation activity. Ultrasound-mediated cavitation can promote the transport of solid microparticles in tissue-mimicking material. Further work is needed to understand the influence of tissue mechanical properties and ultrasound exposure parameters on the extent and uniformity of particle distribution that can be achieved.

Computational Study of the Microsphere Concentration in Blood during Radioembolization

Computational fluid dynamics techniques are increasingly used to computer simulate radioembolization, a transcatheter intraarterial treatment for patients with inoperable tumors, and analyze the influence of treatment parameters on the microsphere distribution. Ongoing clinical research studies are exploring the influence of the microsphere density in tumors on the treatment outcome. In this preliminary study, we computationally analyzed the influence of the microsphere concentration in the vial on the microsphere concentration in the blood. A patient-specific case was used to simulate the blood flow and the microsphere transport during three radioembolization procedures in which the only parameter varied was the concentration of microspheres in the vial and the span of injection, resulting in three simulations with the same number of microspheres injected. Results showed that a time-varying microsphere concentration in the blood at the outlets of the computational domain can be analyzed using CFD, and also showed that there was a direct relationship between the variation of microsphere concentration in the vial and the variation of microsphere concentration in the blood. Future research will focus on elucidating the relationship between the microsphere concentration in the vial, the microsphere concentration in the blood, and the final microsphere distribution in the tissue.

Effects of BNO 1016 on ciliary transport velocity and cell culture surface liquid height of sinonasal epithelial cultures

BackgroundBNO 1016 is an ethanolic extract of a mixture of five herbs that has been sold in different formulations for decades in the European market and more recently, in the United States market as an over-the-counter treatment for rhinosinusitis. Previous studies indicated activation of chloride secretion and increase in ciliary beat frequency by BNO 1016 but the functional consequences on mucociliary transport velocity and airway surface liquid homeostasis are unknown. This study intends to examine the effects of BNO 1016 on these properties in vitro.ResultsHuman sinonasal epithelial cells were grown at an air-liquid interface, with addition of BNO 1016 basolaterally in each experiment. Polystyrene fluorescent microspheres were added to the apical surface of the culture, and distance traveled across the surface of the culture over a fixed time period was measured using live imaging. BNO 1016 concentrations of 50 μg/ml and 500 μg/ml were tested. Basolateral application of compound resulted in a non-dose-dependent increase in culture surface liquid height compared to controls at 30 min, and this effect persisted through the one-hour duration of the experiment (p < 0.01). Basolateral application of BNO 1016 also resulted in a non-dose-dependent increase in microsphere transport velocity at 45 and 60 min following compound application (p < 0.01).ConclusionsBasolateral application of BNO 1016 at a concentration mimicking post-ingestion serum levels appears to elicit increases in cell culture surface liquid height and mucociliary clearance, as assessed by microsphere transport velocity. These properties can potentially be leveraged for therapeutic efficacy in diseases affecting mucus production and mucociliary transport.

Personalized Dosimetry for Liver Cancer Y-90 Radioembolization Using Computational Fluid Dynamics and Monte Carlo Simulation.

Yttrium-90 (Y-90) transarterial radioembolization uses radioactive microspheres injected into the hepatic artery to irradiate liver tumors internally. One of the major challenges is the lack of reliable dosimetry methods for dose prediction and dose verification. We present a patient-specific dosimetry approach for personalized treatment planning based on computational fluid dynamics (CFD) simulations of the microsphere transport combined with Y-90 physics modeling called CFDose. The ultimate goal is the development of a software to optimize the amount of activity and injection point for optimal tumor targeting. We present the proof-of-concept of a CFD dosimetry tool based on a patient's angiogram performed in standard-of-care planning. The hepatic arterial tree of the patient was segmented from the cone-beam CT (CBCT) to predict the microsphere transport using multiscale CFD modeling. To calculate the dose distribution, the predicted microsphere distribution was convolved with a Y-90 dose point kernel. Vessels as small as 0.45mm were segmented, themicrosphere distribution between the liver segments using flow analysis was predicted,the volumetric microsphere and resulting dose distribution in the liver volume were computed. The patient was imaged with positron emission tomography (PET) 2h after radioembolization to evaluate the Y-90 distribution. The dose distribution was found to be consistent with the Y-90 PET images. These results demonstrate the feasibility of developing a complete framework for personalized Y-90 microsphere simulation and dosimetry using patient-specific input parameters.

Collagen sponge scaffolds containing growth factors for the functional regeneration of tracheal epithelium

Tracheal epithelia have barrier and mucociliary clearance functions that prevent invasion of extraneous particles and infectious materials. Hence, following tracheal reconstructions, functional and morphological regeneration of epithelia is required to prevent respiratory declines and infectious diseases. Although growth factors (GFs) promote the regeneration of tracheal epithelial morphologies, it remains unclear whether tracheal grafts containing GFs are beneficial for regeneration of tracheal epithelial functions. Thus, we fabricated collagen sponge scaffolds containing insulin-like GF-1 (IGF-1) and the basic fibroblast, hepatocyte, and epidermal GFs (bFGFs, HGFs, and EGFs, respectively), and we evaluated the effects of the grafts on the functional regeneration of tracheal epithelia. Partial tracheal defects were imposed surgically, and collagen sponges containing IGF-1, bFGF, HGF, or EGF were then transplanted to defect sites. Subsequent immunofluorescence studies suggested that EGF and bFGF contribute to regular distributions of tight junction molecules, and tracer permeability assays suggested that EGF and bFGF promote regeneration of barrier function. Increased ciliogenesis was also observed using scanning electron microscopy in reconstructed regions treated with EGF- and bFGF-supplemented collagen sponges. However, bFGF-supplemented collagen sponges led to greater microsphere transport than did EGF-supplemented sponges. The present data suggested that collagen sponge scaffold containing bFGF promotes functional regeneration of tracheal epithelial tissues.

Laminar/turbulent airflow and microsphere deposition in a patient-specific airway geometry using an open-source solver

Using the open-source software OpenFOAM as the solver, airflow and microsphere transport have been simulated in a patient-specific lung-airway model. A suitable transitional turbulence model was validated and implemented to accurately simulate airflow fields, as the laryngeal jet occurring in the throat region may induce turbulence immediately downstream. Furthermore, a modified eddy interaction model with a generalised near-wall correction factor is presented that more accurately simulates the particle trajectories and subsequent deposition phenomena which are especially affected by near-wall velocity fluctuations. Particle depositions in the realistic lung-airway configuration are compared with those in an idealised upper airway model. The results indicate that for microsphere deposition in turbulent airflow regions, selection of an appropriate near-wall correction factor can reduce the problem of subject variability for different lung-airway configurations. Open-source solvers for lung-aerosol dynamics simulations, such as OpenFOAM, are predictive tools which are basically cost-free, flexible, largely user-friendly, and portable.

A Lagrangian Approach for Calculating Microsphere Deposition in a One-Dimensional Lung-Airway Model.

Using the open-source software openfoam as the solver, a novel approach to calculate microsphere transport and deposition in a 1D human lung-equivalent trumpet model (TM) is presented. Specifically, for particle deposition in a nonlinear trumpetlike configuration a new radial force has been developed which, along with the regular drag force, generates particle trajectories toward the wall. The new semi-empirical force is a function of any given inlet volumetric flow rate, micron-particle diameter, and lung volume. Particle-deposition fractions (DFs) in the size range from 2 μm to 10 μm are in agreement with experimental datasets for different laminar and turbulent inhalation flow rates as well as total volumes. Typical run times on a single processor workstation to obtain actual total deposition results at comparable accuracy are 200 times less than that for an idealized whole-lung geometry (i.e., a 3D-1D model with airways up to 23rd generation in single-path only).

Computationally Efficient Fluid-Particle Dynamics Simulations of Arterial Systems

AbstractRealistic and accurate computer simulations of the particle-hemodynamics in arterial systems can be a valuable tool for numerous biomedical applications. Examples include optimal by-pass grafting and optimal drug-delivery, as well as best medical management concerning the cardio-vascular system. However, such numerical analyses require large computer resources which may become prohibitive for extended sets of arterial bifurcations. A remedy is to develop a hybrid model where the first few generations of the bifurcating arteries of interest are simulated in full 3-D, while a 1-D model is then coupled for subsequent bifurcations. Alternatively, a 1-D computer model can be directly employed to simulate fluid-particle transport in complex bifurcating networks.Relying on a representative axial velocity profile, a physiological 1-D model has been developed and validated, which is capable of predicting with reasonable accuracy arterial flow, pressure field and elastic wall interaction as well as particle transport. The usefulness of the novel 1-D simulation approach is demonstrated via a comparison to 3-D blood flow and microsphere transport in a hepatic artery system, featuring as outlets one major branch and four small daughter vessels. Compared to the 3-D simulation, the 1-D analysis requires only about 1% of computational time. The hybrid modeling approach would be also applicable to the human respiratory tract to evaluate the fate of inhaled aerosols.A simple and cost-effective way to simulate particle-hemodynamics is using a 1-D model for simulating arterial pressures and flow rates as well as microsphere transport, based on assumptions involving the use of a simple algebraic pressure-area relation, an exponential elasticity model for the vessels, and considering only unidirectional flow with a representative skewed velocity profile. In summary, the novel contributions are:• Particle tracking in arteries via 1-D fluid modeling and selection of an averaged, skewed velocity profile based on 3-D simulation results to provide more realistic friction and inertia term values for modeling a flow system with bifurcations.• The 1-D model can be coupled to a 3-D model so that simulations can be run for larger regions of vascular or lung-airway systems.

A hepatic dose-toxicity model opening the way toward individualized radioembolization planning.

The 50% normal-tissue complication probability (NTCP) after lobar irradiation of the liver results in highly variable biologic effective doses depending on the modality used: a biologic effective dose for 50% (BED50) of 115, 93, and 250 Gy for external-beam radiotherapy, resin microsphere radioembolization, and glass microsphere radioembolization, respectively. This misunderstood property has made it difficult to predict the maximal tolerable dose as a function of microsphere activity and targeted liver volume. The evolution toward more selective catheterization techniques, resulting in more variable targeted volumes, makes it urgent to solve this issue. We computed by Monte Carlo simulations the microsphere distribution in the portal triads based on microsphere transport dynamics through a synthetically grown hepatic arterial tree. Afterward, the microscale dose distribution was computed using a dose deposition kernel. We showed that the equivalent uniform dose cannot handle microscale dosimetry and fails to solve the discordance between the BED50 values. Consequently, we developed a new radiobiologic model to compute the liver NTCP from the microscale dose distribution. The new model explains all the observed BED50 values and provides a way to compute the hepatic dose-toxicity relationship as a function of microsphere activity and targeted liver volume. The NTCP obtained is in agreement with the data reported from clinical radioembolization studies. The results should encourage interventional radiologists to fine-tune the delivered dose to the liver as a function of the targeted volume. The present model could be used as the backbone of the treatment planning, allowing optimization of the absorbed dose to the tumors.

Pore-scale investigation of micron-size polyacrylamide elastic microspheres (MPEMs) transport and retention in saturated porous media.

Knowledge of micrometer-size polyacrylamide elastic microsphere (MPEM) transport and retention mechanisms in porous media is essential for the application of MPEMs as a smart sweep improvement and profile modification agent in improving oil recovery. A transparent micromodel packed with translucent quartz sand was constructed and used to investigate the pore-scale transport, surface deposition-release, and plugging deposition-remigration mechanisms of MPEMs in porous media. The results indicate that the combination of colloidal and hydrodynamic forces controls the deposition and release of MPEMs on pore-surfaces; the reduction of fluid salinity and the increase of Darcy velocity are beneficial to the MPEM release from pore-surfaces; the hydrodynamic forces also influence the remigration of MPEMs in pore-throats. MPEMs can plug pore-throats through the mechanisms of capture-plugging, superposition-plugging, and bridge-plugging, which produces resistance to water flow; the interception with MPEM particulate filters occurring in the interior of porous media can enhance the plugging effect of MPEMs; while the interception with MPEM particulate filters occurring at the surface of low-permeability layer can prevent the low-permeability layer from being damaged by MPEMs. MPEMs can remigrate in pore-throats depending on their elasticity through four steps of capture-plugging, elastic deformation, steady migration, and deformation recovery.

The Low Hepatic Toxicity per Gray of 90Y Glass Microspheres Is Linked to Their Transport in the Arterial Tree Favoring a Nonuniform Trapping as Observed in Posttherapy PET Imaging

(90)Y resin and glass microsphere liver radioembolizations delivering lobar doses of 70 and 120 Gy, respectively, display hepatic toxicity similar to 40-Gy fractionated external-beam radiotherapy. We investigated how the lower number of glass microspheres could induce a sufficiently nonuniform dose distribution explaining this paradox. Microscale dosimetry was assessed in the realistic liver model developed by Gulec et al. but using the Russell's dose deposition kernel. A lattice of hexagonal prisms represented the hepatic lobules. Two hepatic arterial tree models-that is, a fixed-length and a variable-branches length-were used for the microsphere transport. Equal or asymmetric microsphere relative-spreading probability between 2 daughter vessels was assumed. Several 120-Gy liver simulations were performed: periodic simulations, where 1 or 6 glass microspheres were trapped in all and in only 1 of 6 portal tracts, respectively, and random simulations, where glass microsphere trapping assumed an equal probability for all the portal tracts or a variable probability depending on the successions of artery connections leading to the portal tract, both for the 2 arterial tree models. For the 2 uniform simulations, all hepatic structures received at least 100 Gy. The fast decrease of the (90)Y kernel as the inverse of the square of the distance r is counterbalanced by the number of contributing lobules containing microspheres that increases as r(2). The random simulation with equal-spreading probability gave for the less irradiated tissue a lobule dose distribution centered around 103 Gy (full width at half maximum, 20 Gy). The distribution became significantly asymmetric with the 60%-40% relative-spreading probability, with a shift of the maximum from 103 down to 50 Gy, and about 17% of the lobules got a dose lower than 40 Gy to their different structures. The large nonuniform trapping produced by the microsphere transport in the arterial tree jointly with the low number of injected glass microspheres begins to explain their lower hepatic toxicity per Gray. In addition, the nonuniform trapping supports the fact that the granular aspect of (90)Y PET imaging observed in patients could represent some reality and not only statistical noise.

Impact of kaolinite clay particles on the filtration of Cryptosporidium-sized microspheres

Granular filtration remains a key barrier for Cryptosporidium removal in water treatment plants without UV irradiation. To assess the impact of clay particles in source water on Cryptosporidium removal efficiency by granular filtration, this study investigated the co-transport of Cryptosporidium-sized microspheres and kaolinite particles in sand columns. To investigate the influence of clay load on microsphere transport and deposition, varying influent kaolinite concentrations (0–106particles/mL) and microsphere concentrations (102–106microspheres/mL) were tested. The spatial distribution of retained microspheres was examined subsequent to experiments via filter coring. Results demonstrate that increasing the influent microsphere concentration impaired filter performance due to a blocking mechanism whereby previously retained particles repel incoming particles. In contrast, when the particulate load was dominated by kaolinite (for an equivalent particulate load), filter performance improved as a result of filter ripening whereby previously deposited particles act as additional collectors. Thus, microsphere-kaolinite interactions proved to be favorable although both particles possessed negative zeta potentials in the tested conditions. This study demonstrates that granular filter performance is vulnerable to peak events of microbial contamination. Conversely, Cryptosporidium-sized microsphere removal by granular filtration is enhanced in the presence of kaolinite in source water.

Comparison of enhanced microsphere transport in an iron-oxide-coated porous medium by pre-adsorbed and co-depositing organic matter

The effects of two types of organic matter (OM) (humic acid and protein) on colloid transport in porous media were investigated with column experiments and numerical modeling. Colloid deposition was explored in double-pulse experiments (DPEs) by injecting a pulse of OM to allow its pre-adsorption to iron-oxide-coated sand, followed by a pulse of latex microspheres. These experiments were compared with single-pulse experiments (SPEs), where one mixed pulse of OM and microspheres was introduced to the column. The experimental results show that pre-adsorbed and co-depositing OM may, respectively, limit initial and transient colloid deposition. The DPE results can be interpreted with an existing colloid transport model (random sequential adsorption: RSA). SPE results were interpreted with an extended RSA model (RSAE) that couples the process of OM co-deposition and blocking to colloid transport by introducing a conversion factor (Kconv) that reflects the blocking efficiency of OM. The calculations with the verified model suggest a comparable site blocking capacity of pre-adsorbed and co-depositing OM with a blocking capacity that differs for different sources of OM. Traditionally described as a modification of the chemistry of the overall deposition surface for the suspended particles, OM adsorption can also be interpreted as blocking local colloid attachment sites by the OM. This second interpretation may be more useful in describing nanoparticle deposition where the particle size is comparable to the length scale where a molecule of OM modifies the deposition surface.

Virus and virus‐sized microsphere transport in a dolomite rock fracture

Key Points Bacteriophage and microsphere transport studied in dolomite fracture Bacteriophage and microsphere transport are quite different Two site kinetic model used to model transport

Colloid Transport in Dolomite Rock Fractures: Effects of Fracture Characteristics, Specific Discharge, and Ionic Strength

The effects of fracture characteristics, specific discharge, and ionic strength on microsphere transport in variable-aperture dolomite rock fractures were studied in a laboratory-scale system. Fractures with different aperture distributions and mineral compositions were artificially created in two dolomite rock blocks. Transport tests were conducted with bromide and carboxylate-modified latex microspheres (20, 200, and 500 nm diameter). Under overall unfavorable attachment conditions, there was significant retention of the 20 nm microsphere and minimal retention of the 500 nm microsphere for all conditions examined. Aperture variability produced significant spatial variation in colloid transport. Flushing with low ionic strength solution (1 mM) following microsphere transport at 12 mM ionic strength solution produced a spike in effluent microsphere concentrations, consistent with retention of colloids in secondary energy minima. Surface roughness and charge heterogeneity effects may have also contributed to the effect of microsphere size on retention. Matrix diffusion influenced bromide transport but was not a dominant factor in transport for any microsphere size. Calibrated one-dimensional, two-site kinetic model parameters for colloid transport in fractured dolomite were sensitive to the physical and chemical properties of both the fractured dolomite and the colloids, indicating the need for mechanistic modeling for accurate prediction.

Analysis of matrix effects critical to microbial transport in organic waste‐affected soils across laboratory and field scales

Organic waste applications to soil (manure, various wastewaters, and biosolids) are among the most significant sources of bacterial contamination in surface and groundwater. Transport of bacteria through the vadose zone depends on flow path geometry and stability and is mitigated by interaction between soil, soil solution, air‐water interfaces, and characteristics of microbial surfaces. After initial entry, the transport through soil depends on continued entrainment of bacteria and resuspension of those retained in the porous structure. We evaluated the retention of bacteria‐sized artificial microspheres, varying in diameter and surface charge and applied in different suspending solutions, by a range of sieved soils contained in minicolumns, the transport of hydrophobic bacteria‐sized microspheres through undisturbed soil columns as affected by waste type under simulated rainfall, and the field‐scale transport of Enterococcus spp. to an unconfined sandy aquifer after the application of liquid manure. Microsphere retention reflected microsphere properties. The soil type and suspending solution affected retention of hydrophilic but not hydrophobic particles. Retention was not necessarily facilitated by manure‐microsphere‐soil interactions but by manure‐soil interactions. Undisturbed column studies confirmed the governing role of waste type on vadose‐zone microsphere transport. Filtration theory applied as an integrated analysis of transport across length scales showed that effective collision efficiency depended on the distance of travel. It followed a power law behavior with the power coefficient varying from ∼0.4 over short distances to &gt;0.9 over 1 m (i.e., very little filtration for a finite fraction of biocolloids), consistent with reduced influence of soil solution and biocolloid properties at longer travel distances.

Enhanced Microsphere Transport in Capillary by Conditioned Cells of Green Paramecia Used as Living Micromachines Controlled by Electric Stimuli

Some researchers have described the cells of Paramecium species as “swimming sensory cells” or “swimming neurons” applicable to micro-biorobotics and biological micro-electromechanical systems (BioMEMS). Paramecium species including green paramecia (Paramecium bursaria) migrate towards the anodic electrode when exposed to an electric field. This type of cellular movement is known as galvanotaxis. Because the ideal micromachines designed for microparticle transport must have a capacity for loading certain numbers of particles, P. bursaria was chosen as a model organism. In this study, we show enhanced microparticle transport by overcoming (i) the particle size limitation for the cell-mediated transport of microspheres of up to ca. 10 μm size (doubling the size of particles ever reported) and (ii) the limit of cellular migration distance manifested by galvanotactically stimulated cells.

Computational Fluid Dynamics Modeling of 90Y Microspheres in Human Hepatic Tumors

The number of patients afflicted with liver tumors continues to rise being a major concern of international healthcare. Yttrium-90 microsphere radioembolization can be an effective and safe treatment of unresectable primary and secondary liver tumors, and has the potential to be a forefront treatment option for tumor-afflicted patients. Computational fluid-particle dynamics is a powerful research tool that can be used to understand the underlying physics of Yttrium-90 microsphere transport and deposition, leading to improved clinical strategies and ultimately to a better treatment of tumor-afflicted patients. Two representative, patient-inspired three-dimensional geometries of the hepatic arterial system with assumed connections to liver tumors have been considered. Experimentallyvalidated computational fluid-particle dynamics modeling results have shown the significant influence of vessel morphology, downstream resistance to flow, catheter radial and axial location associated with microsphere injection time interval, and injection velocity on microsphere transport through the hepatic arterial system. Moreover, the computational investigations have identified the ability to preferentially deliver microspheres to a specific arterial vessel outlet, presumably connected to a tumor, by selecting appropriate temporal and spatial parameters of the microsphere injection. As the computational findings are extended to additional experiments as well as nextgeneration smart micro-catheters, clinicians can implement a refined set of treatment strategies that utilize the aforementioned physical phenomena. Computational fluid-particle dynamics models have thus provided valuable physical insight as well as suggestions for the improvement of current Yttrium-90 microsphere radioembolization treatment. Additional computational investigations are needed to create more encompassing conclusions from a large collection of patient-specific analyses plus the design, prototyping, and testing of a new smart micro-catheter and high-resolution imaging devices that give radiation and interventional oncologists new degrees of control and precision when administering Yttrium-90 microsphere radioembolization.

Foam, a promising vehicle to deliver nanoparticles for vadose zone remediation

Foam delivery of remedial amendments for in situ immobilization of deep vadose zone contaminants can overcome the intrinsic problems associated with solution-based delivery, such as preferential flow and contaminant mobilization. In this work, the feasibility of using foam to deliver nanoparticles in unsaturated porous media was investigated. Carboxyl-modified polystyrene latex microspheres were used as surrogates for nanoparticles of remediation purposes. Foams generated from the solutions of six commonly available surfactants all had excellent abilities to carry the microspheres. The presence of the microspheres did not reduce the stabilities of the foams. When microsphere-laden foam was injected through the unsaturated columns, the fractions of microspheres exiting the column were much higher than that when the microsphere water suspensions were injected through the columns. The enhanced microsphere transport implies that foam delivery could significantly increase the radius of influence of injected nanoparticles of remediation purposes. Reduced tension at air–water interfaces by the surfactant and increased driving forces imparted on the microspheres at the interfaces by the flowing foam bubbles may have both contributed to the enhanced transport. Preliminary tests also demonstrated that foam can carry significant fractions of zero valent iron nanoparticles at concentrations relevant to field remediation conditions (up to 5.3gL−1). As such, this study demonstrates that surfactant foam is potentially a promising vehicle to deliver nanoparticles for vadose zone remediation.

Computer Modeling of Yttrium-90–Microsphere Transport in the Hepatic Arterial Tree to Improve Clinical Outcomes

Radioembolization (RE) via yttrium-90 ((90)Y) microspheres is an effective and safe treatment for unresectable liver malignancies. However, no data are available regarding the impact of local blood flow dynamics on (90)Y-microsphere transport and distribution in the human hepatic arterial system. A three-dimensional (3-D) computer model was developed to analyze and simulate blood-microsphere flow dynamics in the hepatic arterial system with tumor. Supplemental geometric and flow data sets from patients undergoing RE were also available to validate the accuracy of the computer simulation model. Specifically, vessel diameters, curvatures, and branching patterns, as well as blood flow velocities/pressures and microsphere characteristics (i.e., diameter and specific gravity), were measured. Three-dimensional computer-aided design software was used to create the vessel geometries. Initial trials, with 10,000 noninteracting microspheres released into the hepatic artery, used resin spheres 32-microm in diameter with a density twice that of blood. Simulations of blood flow subject to different branch-outlet pressures as well as blood-microsphere transport were successfully carried out, allowing testing of two types of microsphere release distributions in the inlet plane of the main hepatic artery. If the inlet distribution of microspheres was uniform (evenly spaced particles), a greater percentage would exit into the vessel branch feeding the tumor. Conversely, a parabolic inlet distribution of microspheres (more particles around the vessel center) showed a high percentage of microspheres exiting the branch vessel leading to the normal liver. Computer simulations of both blood flow patterns and microsphere dynamics have the potential to provide valuable insight on how to optimize (90)Y-microsphere implantation into hepatic tumors while sparing normal tissue.