Targeted drug delivery during radioembolization in a comprehensive hepatic artery system: A computational study

Abstract

Nonresectable liver tumors can be successfully treated with radioembolization (RE) using yttrium-90 (90Y) microspheres. However, hepatocellular carcinoma's therapeutic methods are hindered primarily by the complex arterial morphology of the liver and its high dependence on arteries' geometry to target the tumors. Thus, this study aims to investigate the particle-fluid dynamics of yttrium-90 (90Y) loaded microspheres injected into the blood flow within a comprehensive hepatic artery system consisting of 17 daughter vessels branches. Also, the effect of particles' characteristics (size and density) with two types of commercially available 90Y microspheres, SIR-Spheres and TheraSpheres, and time infusion intervals (various release phases) were studied leading to a total of 20 investigated cases. The results demonstrated the vital influence of flow dynamics on the particles' preference to deposit in specific daughter vessels. Regardless of phase shift, except GDA, outlet 1 receives the largest portion of CHA inflow with nearly 14.5% which consequently implies the highest value of exit fraction after particles injection, and outlet 11 receives the minimum portion of CHA inflow with 1.97%. The maximum and minimum reductions of mean flow rate through the phase shift from acceleration toward minimum phase are for daughter vessels 17 and 10 with nearly 17.7% and 4.8%, respectively. The maximum percentage of particles that remains in the domain after 4 heart cycle simulation time is for glass microspheres consisting of particles with the diameter of 80μm released at t=0 sec, indicating that 25.4% of the injected particles are unable to discharge the domain. Whereas, the minimum percentage (0.16%) of remaining particles is for resin microspheres with a diameter of 20μm released at t=0 sec. Moreover, regardless of particles type, 7 daughter vessels discharge their maximum number of particles at the time point of injection associated with the minimum velocity of CHA flow rate which highlights the significant importance of minimum phase for those daughter vessels, potentially terminating tumor cells. Results exhibit that for none of the daughter vessels, the acceleration phase and peak phase (except for the GDA outlet) are proper time zones to release the 90Y microspheres, regardless of particles type. Finally, to conduct the released particles to particular vessels which are connected to tumor cells, the best radial position of the micro-catheter at the CHA inlet cross-section was identified by generating particle release maps (PRMs) for each investigated case.