@article{childress_kleinstreuer_2014, title={Computationally Efficient Particle Release Map Determination for Direct Tumor-Targeting in a Representative Hepatic Artery System}, volume={136}, ISSN={["1528-8951"]}, DOI={10.1115/1.4025881}, abstractNote={Implementation of a novel direct tumor-targeting technique requires a computer modeling stage to generate particle release maps (PRMs) which allow for optimal catheter positioning and selection of best injection intervals for drug-particles. This simulation task for a patient-specific PRM may require excessive computational resources and a relatively long turn-around time for a fully transient analysis. Hence, steady-state conditions were sought which generates PRMs equivalent to the pulsatile arterial flow environment. Fluid-particle transport in a representative hepatic artery system was simulated under fully transient and steady-state flow conditions and their corresponding PRMs were analyzed and compared. Comparisons of the transient PRMs from ten equal intervals of the cardiac pulse revealed that the diastolic phase produced relatively constant PRMs due to its semisteady flow conditions. Furthermore, steady-state PRMs, which best matched the transient particle release maps, were found for each interval and over the entire cardiac pulse. From these comparisons, the flow rate and outlet pressure differences proved to be important parameters for estimating the PRMs. The computational times of the fully transient and steady simulations differed greatly, i.e., about 10 days versus 0.5 to 1 h, respectively. The time-averaged scenario may provide the best steady conditions for estimating the transient particle release maps. However, given the considerable changes in the PRMs due to the accelerating and decelerating phases of the cardiac cycle, it may be better to model several steady scenarios, which encompass the wide range of flows and pressures experienced by the arterial system in order to observe how the PRMs may change throughout the pulse. While adding more computation time, this method is still significantly faster than running the full transient case. Finally, while the best steady PRMs provide a qualitative guide for best catheter placement, the final injection position could be adjusted in vivo using biodegradable mock-spheres to ensure that patient-specific optimal tumor-targeting is achieved. In general, the methodology described could generate computationally very efficient and sufficiently accurate solutions for the transient fluid-particle dynamics problem. However, future work should test this methodology in patient-specific geometries subject to various flow waveforms.}, number={1}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Childress, E. M. and Kleinstreuer, C.}, year={2014}, month={Jan} }
 @article{childress_kleinstreuer_2014, title={Impact of Fluid-Structure Interaction on Direct Tumor-Targeting in a Representative Hepatic Artery System}, volume={42}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-013-0910-7}, abstractNote={Direct targeting of solid tumors with chemotherapeutic drugs and/or radioactive microspheres can be a treatment option which minimizes side-effects and reduces cost. Briefly, computational analysis generates particle release maps (PRMs) which visually link upstream particle injection regions in the main artery with associated exit branches, some connected to tumors. The overall goal is to compute patient-specific PRMs realistically, accurately, and cost-effectively, which determines the suitable radial placement of a micro-catheter for optimal particle injection. Focusing in this paper on new steps towards realism and accuracy, the impact of fluid-structure interaction on direct drug-targeting is evaluated, using a representative hepatic artery system with liver tumor as a test bed. Specifically, the effect of arterial wall motion was demonstrated by modeling a two-way fluid-structure interaction analysis with Lagrangian particle tracking in the bifurcating arterial system. Clearly, rapid computational evaluation of optimal catheter location for tumor-targeting in a clinical application is very important. Hence, rigid-wall cases were also compared to the flexible scenario to establish whether PRMs generated when based on simplifying assumptions could provide adequate guidance towards ideal catheter placement. It was found that the best rigid (i.e., time-averaged) geometry is the physiological one that occurs during the diastolic targeting interval.}, number={3}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Childress, Emily M. and Kleinstreuer, Clement}, year={2014}, month={Mar}, pages={461–474} }
 @article{richards_kleinstreuer_kennedy_childress_buckner_2012, title={Experimental Microsphere Targeting in a Representative Hepatic Artery System}, volume={59}, ISSN={["1558-2531"]}, DOI={10.1109/tbme.2011.2170195}, abstractNote={Recent work employing the computational fluid-particle modeling of the hepatic arteries has identified a correlation between particle release position and downstream branch distribution for direct tumor-targeting in radioembolization procedures. An experimental model has been constructed to evaluate the underlying simulation theory and determine its feasibility for future clinical use. A scaled model of a generalized hepatic system with a single inlet and five outlet branches was fabricated to replicate the fluid dynamics in the hepatic arteries of diseased livers. Assuming steady flow, neutrally buoyant microspheres were released from controlled locations within the inlet of the model and the resulting output distributions were recorded. Fluid and particle transport simulations were conducted with identical parameters. The resulting experimentally and simulation-derived microsphere distributions were compared. The experimental microsphere distribution exhibited a clear dependence on injection location that correlated very strongly with the computationally predicted results. Individual branch targeting was possible for each of the five outputs. The experimental results validate the simulation methodology for achieving targeted microsphere distributions in a known geometry under constant flow conditions.}, number={1}, journal={IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING}, author={Richards, Andrew L. and Kleinstreuer, Clement and Kennedy, Andrew S. and Childress, Emily and Buckner, Gregory D.}, year={2012}, month={Jan}, pages={198–204} }
 @article{basciano_kleinstreuer_kennedy_dezarn_childress_2010, title={Computer Modeling of Controlled Microsphere Release and Targeting in a Representative Hepatic Artery System}, volume={38}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-010-9955-z}, abstractNote={Combating liver tumors via yttrium-90 ((90)Y) radioembolization is a viable treatment option of nonresectable liver tumors. Employing clinical (90)Y microparticles (i.e., SIR-Spheres and TheraSpheres) in a computational model of a representative hepatic artery system, laminar transient 3D particle-hemodynamics were simulated. Specifically, optimal particle release positions in the right hepatic (parent) artery as well as the best temporal release window were determined for the microspheres to exit specific outlet daughter vessels, potentially connected to liver tumors. The results illustrate the influence of a curved geometry on the velocity field and the particle trajectory dependence on the spatial and temporal particle injection conditions. The differing physical particle characteristics of the SIR-Spheres and the TheraSpheres had a subtle impact on particle trajectories in the decelerating portion of the arterial pulse, i.e., when the inertial forces on the particles are weaker. Conversely, particle characteristics and inelastic wall collisions had little effect on particles released during the accelerating phase of the arterial pulse, i.e., both types of microspheres followed organized paths to predetermined outlets. Such results begin paving the way towards directing 100% of the released microspheres to specific daughter vessels (e.g., those connected to tumors) under transient flow conditions in realistic geometries via a novel drug-particle targeting methodology.}, number={5}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Basciano, Christopher A. and Kleinstreuer, Clement and Kennedy, Andrew S. and Dezarn, William A. and Childress, Emily}, year={2010}, month={May}, pages={1862–1879} }