Computationally efficient particle release map determination for direct tumor-targeting in a representative hepatic artery system.

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.

A new catheter for tumor targeting with radioactive microspheres in representative hepatic artery systems. Part I: impact of catheter presence on local blood flow and microsphere delivery.

Building on previous studies in which the transport and targeting of (90)Y microspheres for liver tumor treatment were numerically analyzed based on medical data sets, this two-part paper discusses the influence of an anchored, radially adjustable catheter on local blood flow and microsphere delivery in an idealized hepatic artery system (Part I). In Part II a patient-inspired case study with necessary conditions for optimal targeting of radioactive microspheres (i.e., yttrium 90) onto liver tumors is presented. A new concept of optimal catheter positioning is introduced for selective targeting of two daughter-vessel exits potentially connected to liver tumors. Assuming laminar flow in rigid blood vessels with an anchored catheter in three controlled positions, the transient three-dimensional (3D) transport phenomena were simulated employing user-enhanced engineering software. The catheter position as well as injection speed and delivery function may influence fluid flow and particle transport. Although the local influences of the catheter may not be negligible, unique cross-sectional particle release zones exist, with which selectively the new controlled targeting methodology would allow optimal microsphere delivery. The insight gained from this analysis paves the way for improved design and testing of a smart microcatheter (SMC) system as well as new investigations leading to even more successful treatment with (90)Y microspheres or combined internal radiation and chemotherapy.

A new catheter for tumor-targeting with radioactive microspheres in representative hepatic artery systems--part II: solid tumor-targeting in a patient-inspired hepatic artery system.

In this second part, the methodology for optimal tumor-targeting is further explored, employing a patient-inspired hepatic artery system which differs significantly from the idealized configuration discussed in Part I. Furthermore, the fluid dynamics of a microsphere supply apparatus is also analyzed. The best radial catheter positions and particle-release intervals for tumor targeting were determined for both the idealized and patient-inspired configurations. This was accomplished by numerically analyzing generated particle release maps (PRMs) for ten equally spaced intervals throughout the pulse. As in Part I, the effects of introducing a catheter were also investigated. In addition to the determination of micro-catheter positioning and, hence, optimal microsphere release, a microsphere-supply apparatus (MSA) was analyzed, which transports the particles to the catheter-nozzle, considering different axial particle injection functions, i.e., step, ramp, and S-curve. A refined targeting methodology was developed which demonstrates how the optimal injection region and interval can be determined with the presence of a catheter for any geometric configuration. Additionally, the less abrupt injection functions (i.e., ramp and S-curve) were shown to provide a more compact particle stream, making them better choices for targeting. The results of this study aid in designing the smart micro-catheter (SMC) in conjunction with the MSA, bringing this innovative treatment procedure one step closer to implementation in clinical practice.