Background: Transarterial therapies are routinely used for the locoregional treatment of unresectable hepatocellular carcinoma (HCC). However, the impact of clinical parameters (i.e. injection location, particle size, particle density etc.) and patient-specific conditions (i.e. hepatic geometry, cancer burden) on the intrahepatic particle distribution (PD) after transarterial injection of embolizing microparticles is still unclear. Computational fluid dynamics (CFD) may help to better understand this impact.Methods: Using CFD, both the blood flow and microparticle mass transport were modeled throughout the 3D-reconstructed arterial vasculature of a patient-specific healthy and cirrhotic liver. An experimental feasibility study was performed to simulate the PD in a 3D-printed phantom of the cirrhotic arterial network.Results: Axial and in-plane injection locations were shown to be effective parameters to steer particles towards tumor tissue in both geometries. Increasing particle size or density made it more difficult for particles to exit the domain. As cancer burden increased, the catheter tip location mattered less. The in vitro study and numerical results confirmed that PD largely mimics flow distribution, but that significant differences are still possible.Conclusions: Our findings highlight that optimal parameter choice can lead to selective targeting of tumor tissue, but that targeting potential highly depends on patient-specific conditions. KEY WORDS: biofluid mechanics; computational fluid dynamics; hepatocellular carcinoma; locoregional drug delivery; personalized medicine; transarterial therapy. ARTICLE HIGHLIGHTS * Computational fluid dynamics (CFD) is a powerful numerical technique that allows simulating blood and drug particle flow in patient-specific liver vasculatures. CFD can increase our understanding of key factors influencing fluid flow and drug delivery, and can play a role in pre-operative procedure planning.* The targeting potentialthe dependency of particle behavior on controllable injection parametersvaries between the two patients considered in this study, but also varies for different regions within the vasculature of one patient, and for the specific injection parameter considered. This underlines the potency of targeting potential as a relevant metric to evaluate the possible optimization of clinical procedures pre-operatively.* The focus should be shifted to personalized modelling of particle behavior in patient-specific hepatic arterial geometries, rather than literature-based or simplified patient-inspired geometries.* Particle destination is clearly correlated with injection location, affirming results from previous studies. However, it should be noted that the possibility to steer particles towards specific outlets depends highly on the possibility to accurately control the catheter tip within the bloodstream, which has not yet proven to be technically feasible up to date. * In vitro validation showed that flow distribution throughout the hepatic arterial tree is not a perfect sur...

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. At its intermediate, unresectable stage, HCC is typically treated by local injection of embolizing microspheres in the hepatic arteries to selectively damage tumor tissue. Interestingly, computational fluid dynamics (CFD) has been applied increasingly to elucidate the impact of clinically variable parameters, such as injection location, on the downstream particle distribution. This study aims to reduce the computational cost of such CFD approaches by introducing a novel truncation algorithm to simplify hepatic arterial trees, and a hybrid particle-flow modeling approach which only models particles in the first few bifurcations. A patient-specific hepatic arterial geometry was pruned at three different levels, resulting in three trees: Geometry 1 (48 outlets), Geometry 2 (38 outlets), and Geometry 3 (17 outlets). In each geometry, 1 planar injection and 3 catheter injections (each with different tip locations) were performed. For the truncated geometries, it was assumed that, downstream of the truncated outlets, particles distributed themselves proportional to the blood flow. This allowed to compare the particle distribution in all 48 “outlets” for each geometry. For the planar injections, the median difference in outlet-specific particle distribution between Geometry 1 and 3 was 0.21%; while the median difference between outlet-specific flow and particle distribution in Geometry 1 was 0.40%. Comparing catheter injections, the maximum median difference in particle distribution between Geometry 1 and 3 was 0.24%, while the maximum median difference between particle and flow distribution was 0.62%. The results suggest that the hepatic arterial tree might be reliably truncated to estimate the particle distribution in the full-complexity tree. In the resulting hybrid particle-flow model, explicit particle modeling was only deemed necessary in the first few bifurcations of the arterial tree. Interestingly, using flow distribution as a surrogate for particle distribution in the entire tree was considerably less accurate than using the hybrid model, although the difference was much higher for catheter injections than for planar injections. Future work should focus on replicating and experimentally validating these results in more patient-specific geometries.

Objectives: To assess the ability of four-dimensional (4D) flow MRI to measure hepatic arterial hemodynamics by determining the effects of spatial resolution and respiratory motion suppression in vitro and its applicability in vivo with comparison to two-dimensional (2D) phase-contrast MRI.Methods: A dynamic hepatic artery phantom and 20 consecutive volunteers were scanned. The accuracies of Cartesian 4D flow sequences with k-space reordering and navigator gating at four spatial resolutions (0.5-to 1-mm isotropic) and navigator acceptance windows (± 8 to ± 2 mm) and one 2D phase-contrast sequence (0.5-mm in-plane) were assessed in vitro at 3T. Two sequences centered on gastroduodenal and hepatic artery branches were assessed for intra-and interobserver agreement and compared to 2D phase-contrast. Results:In vitro, higher spatial resolution led to a greater decrease in error than narrower navigator window (30.5 to -4.67% vs -6.64 to -4.67% for flow). In vivo, hepatic and gastroduodenal arteries were overall more often visualized with the higher resolution sequence (90 vs 71%). Despite similar interobserver agreement (κ = 0.660 and 0.704), the higher resolution sequence had lower variability for area (CV = 20.04 vs 30.67%), flow (CV = 34.92 vs 51.99%) and average velocity (CV = 26.47 vs 44.76%). 4D flow had lower differences between inflow and outflow at the hepatic artery bifurcation (11.03 ± 5.05% and 15.69 ± 6.14%) than 2D phase-contrast (28.77 ± 21.01%). Conclusion:High-resolution 4D flow can assess hepatic artery anatomy and hemodynamics with improved accuracy, greater vessel visibility, better interobserver reliability and internal consistency.