Transarterial drug delivery for liver cancer: numerical simulations and experimental validation of particle distribution in patient-specific livers

Abstract

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...

CFD Simulations of Radioembolization: A Proof-of-Concept Study on the Impact of the Hepatic Artery Tree Truncation

“…Regarding the fraction of injected microspheres that do not exit the baseline computational domain, these values are 13.8%, 18.4%, 17.3%, and 9.7% for Patient 1, Patient 2a, Patient 2b, and Patient 3, respectively. These values are similar to those reported by Bomberna et al [9]. In the truncated geometries, the fraction of non-exiting microspheres reduces to 13.8%, 0%, 6.2%, and 7.6% for Patient 1, Patient 2a, Patient 2b, and Patient 3, respectively.…”

“…The first observation is that the imposed blood flow split differs from the predicted or calculated microsphere distribution (see Figures 5,7,9 and 11). This finding is not novel, it is indeed observed in previous studies that used a microcatheter to inject the microspheres [8] or the studies that used the particle release maps [7,9,26] as a research tool-particle release maps correlate each point in the injection cross-sectional plane with the computational domain outlet from which microspheres would exit. Even if a blood flow split-matching microsphere distribution can be achieved [5], this cannot be assumed as a general rule.…”

“…Some studies have focused on the type of microcatheter (e.g., standard end-hole microcatheter, antireflux catheter, angled-tip microcatheter) [4][5][6], and others have focused on the influence of various treatment and patient parameters (e.g., injection velocity, microcatheter location, hepatic artery geometry, etc.) on the microsphere distribution [7][8][9]. The ultimate goal of these studies is to provide the multidisciplinary team (interventional radiologists, hepatologists, nuclear oncologists, nuclear medicine physicians, etc.)…”

Computational Fluid Dynamics Modeling of Liver Radioembolization: A Review

“…In order to use CFD simulations as a reliable research tool, these simulation results must be validated, meaning that the results must be compared with reality (i.e., in vivo), or at least with an experiment (i.e., in vitro). In this regard, both in vitro validations [ 23 , 44 ] and an in vivo validation have been performed [ 10 ]. The model in vivo validated consists of injecting microspheres during one cardiac cycle and simulating additional cardiac cycles so that most of the injected microspheres exit the flow domain.…”

“…Second, the injection position (especially if near a bifurcation) is of utmost importance in predicting the microsphere distribution (Fig. 2 A) [ 16 , 22 , 23 ]. Injection velocity can also be important if that is much greater than that of the surrounding blood flow [ 29 ].…”