| To improve the treatment of unresectable tumors, a direct tumor-targeting methodology has been proposed in which precise catheter positioning, particle velocity, and infusion interval allows for the injected therapeutic particles to be transported by the blood flow to the target site. Specifically, tens-of-thousands of particles are randomly infused over the entire injection plane of the truncated arterial system and tracked through the system. Via a method of backtracking along the particle trajectories, a patient-specific particle release map (PRM) is generated, which visually links particle injection regions with associated exit branches, some potentially connected to tumors. Such PRMs then determine radial catheter positions to achieve optimal targeting. Continuing the work of previous investigations, this study sought to further validate the feasibility of this new drug-delivery methodology under more realistic, i.e., physiological as well as computationally most efficient conditions. Specifically, the overall goal is to further develop the Computational Medical Management Program (CMMP) which has been proposed to implement this targeting methodology with a smart micro-catheter system in the clinic. Thus, new tasks included the determination of the injection protocol; the influence of blood flow pulsatility, an analysis of two-way fluid-particle coupling and arterial wall motion; and assessments of optimal microsphere delivery as well as direct multifunctional nanoparticle targeting. In the execution of these tasks, a method for incorporating the catheter presence without including additional mesh elements was proposed; a technique for comparing PRMs was presented; a nonlinear material model for the hepatic arterial walls was estimated; and Windkessel boundary conditions were implemented. Key findings of this study include confirmation of the feasibility of direct tumor-targeting of micron particles in transient pulsatile flow with flexible arterial walls; comparisons of steady and transient PRMs for efficient CMMP implementation, establishment of the semi-steady diastolic phase as the best interval for targeting; observations of the influence of the catheter and two-way fluid-particle coupling; determination of a technique for predicting PRM changes due to downstream occlusions using the ratio of the flow rate after occlusions to the flow rate before occlusions; and initial confirmation of direct nanoparticle targeting. |
