Liver radioembolizationcomputational particle-hemodynamics studies in a patient-specific hepatic artery under literature-based cancer scenarios

Resumo

Liver radioembolization is a promising treatment for combating primary and metastatic liver tumors. It consists of administering radioactive microspheres via an intraarterially placed microcatheter with the aim of lodging these microspheres, which are driven by the arterial bloodstream, in the tumoral bed. The position of the microcatheter and the microsphere injection velocity are decided during a pretreatment assessment, by which the treatment is mimicked via the infusion of macroaggregated albumin microparticles. It is assumed that the pretreatment microcatheter placement and microsphere injection velocity are reproduced during the treatment. Even though it is a safe and effective treatment, some complications (e.g., radiation-induced hepatitis or pneumonitis, gastrointestinal ulcers, etc.) may arise due to nontarget radiation, which can occur due to differences between pretreatment and treatment injection conditions related to microcatheter placement, the injection itself, and the patient’s bloodstream. In terms of microcatheter placement, there are a number of parameters that can vary from pretreatment to treatment. Of those, the ones that are of special interest in this thesis are the longitudinal and radial position of the microcatheter tip, the microcatheter’s distal direction, the expandable-tip presence (for antireflux catheters only), and the tip orientation (for angled-tip microcatheters only). As for the injection itself, of the parameters that can be modified, this thesis is most concerned with two of them: the quantity and size of the microagent, and the particle injection velocity. With regard to the bloodstream, the arterial blood flow conditions might vary, e.g., due to microsphere-caused embolization of arterioles, leading to a reflux of microspheres. Any alteration in these parameters may be responsible for nontarget radiation and therefore radiation-induced complications. In order to reduce these radiation-induced complications, it has been suggested that the pretreatment injection conditions be matched as closely as possible during treatment. An alternative solution is to modify the design of microcatheters. For instance, it has been reported that using an antireflux catheter has eliminated particle reflux. The aim of this thesis is to analyze the influence of the abovementioned parameters on microsphere distribution via computational fluid–particle dynamics simulations. The thesis is divided into four major studies, each of which follows the same numerical strategy (i.e., the liver radioembolization is simulated in a patient-specific hepatic artery model under literature-based liver cancer scenarios). The first study analyzes the pretreatment as an actual treatment surrogate, the second analyzes the influence of an antireflux catheter, the third investigates the influence of the microcatheter distal direction and the injection point and velocity, and the last one explores the influence of an angled-tip microcatheter. Furthermore, prior to conducting these four studies, a methodology was developed to define realistic boundary conditions for numerical simulations in hepatic arteries. For the study on the pretreatment, results suggest that microcatheter placement is of paramount importance, both in terms of its location in the artery (near a bifurcation or not) and in the longitudinal shifting in microcatheter tip locations between pretreatment and actual treatment. Moreover, the higher the cancer burden, the better the tumor targeting because of the enhanced particle transport power. For the study on antireflux catheter influence, the main conclusion that can be drawn is that injecting from a sufficiently long and tortuous artery branch may ensure a downstream particle distribution that matches flow split, almost regardless of catheter type due to the likely adequate conditions for microsphere redistribution in the bloodstream. With regard to the third study, despite the importance of microcatheter tip position, microcatheter direction and injection velocity seem also to play an important role in particle distribution; results show that unintentional modifications to microcatheter tip and direction and injection velocity during tumor targeting may influence procedure outcome. The final study involving the angled-tip microcatheter shows that the higher the injection velocity the more spread out the particle distribution across cross-sectional areas of artery lumen. Moreover, when only focusing on tip orientation, it is not possible to accurately predict which branch of the bifurcation will take the particles because the complex geometry of hepatic arteries makes the bloodstream take the form of helical and chaotic streamlines. This means that the particle pathlines are not initially intuitive, even though the particle distribution will be similar to flow split.