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 toward 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.

KEYWORDS:

• Biofluid mechanics
• computational fluid dynamics
• hepatocellular carcinoma
• locoregional drug delivery
• personalized medicine
• transarterial therapy

Acknowledgments

We would like to thank Sirtex Medical for the delivery of experimental SIR-Spheres for the in vitro validation study.

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 potential – the dependency of particle behavior on controllable injection parameters – varies 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 surrogate for particle distribution. Hence, it is preferred to model both blood and particle behavior in CFD simulations. Furthermore, the discrepancy between computational and validation results shows that the validation method would benefit from further finetuning.

Author contributions

Tim Bomberna, Ghazal Adeli Koudehi, Charlotte Claerebout and Charlotte Debbaut were involved in study conception and design. Tim Bomberna, Ghazal Adeli Koudehi, and Charlotte Debbaut were involved in analysis and interpretation of the data. Tim Bomberna and Charlotte Debbaut were involved in paper drafting and revision. Geert Maleux and Chris Verslype were involved in data collection, paper revision and provided clinical input. All authors agree to be accountable for all aspects of the work.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The research was supported by the special research fund, Ghent University (grant number BOFSTA201909015). Charlotte Debbaut was partially supported by a postdoctoral fellowship from Research Foundation Flanders (1202418N).