[Article] A proof‑of‑concept Study of the In‑vivo Validation of a Computational Fluid Dynamics Model of Personalized Radioembolization

A proof‑of‑concept study of the in‑vivo validation of a computational fluid dynamics model of personalized radioembolization

Raúl Antón^1,2, Javier Antoñana¹, Jorge Aramburu¹, Ana Ezponda^2,3, Elena Prieto^2,4, Asier Andonegui¹, Julio Ortega^1,8, Isabel Vivas^2,3, Lidia Sancho^2,5, Bruno Sangro^2,6,7, José Ignacio Bilbao^2,3 & Macarena Rodríguez‑Fraile^2,4,*

 1 Universidad de Navarra, TECNUN Escuela de Ingeniería, 20018 Donostia-San Sebastián, Spain.
2  IdiSNA, Instituto de Investigación Sanitaria de Navarra, 31008 Pamplona, Spain.
3 Department of Radiology, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
4 Department of Nuclear Medicine, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
5 Department of Nuclear Medicine, Clínica Universidad de Navarra, 28027 Madrid, Spain.
6 Department of Hepatology, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
7 CIBEREHD, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas Y Digestivas, 28029 Madrid, Spain.
8 Present address: Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile.
*email: mrodriguez@unav.es

ABSTRACT
Introduction: Radioembolization (RE) with yttrium-90 (90Y) microspheres is a transcatheter intraarterial therapy that has emerged as a safe and effective treatment option for patients with primary or secondary liver cancer, such as hepatocellular carcinoma (HCC). RE consists of the intraarterial infusion of 90Y-loaded microspheres that are transported to the tumoral bed, where they emit tumor-killing doses of  radiation. Currently, a simulation of the RE procedure is performed with the intraarterial administration of 99mTc-Macroaggregated of Albumin (99mTc-MAA) on the assumption that the distribution of 99mTc-MAA and 90Y-microspheres are similar. Nevertheless, systematic errors (e.g. differences in catheter position, injection techniques) or hemodynamic changes during both procedures can result in a poor correlation between 99mTc-MAA and 90Y-microspheres  distribution3. There have been in vitro studies where the density, flow dynamics and the embolization effect of several types of par-ticles are experimentally  analyzed.

Material and methods: Three-dimensional (3D) simulation of hemodynamics and microsphere transport using computational fluid dynamics (CFD) has been designed to improve RE. These in silico (performed on computer) simulations allow the flow patterns of a fluid and the trajectories of some particles (in this case microspheres) to be predicted in a certain region of space, or computational domain, over time. This in silico approach has been success-fully evaluated experimentally using a scaled model of a generalized hepatic  artery7. Numerous investigations based on CFD models have analyzed the influence that local 3D parameter modifications (e.g., type of catheter, catheter-tip location, microsphere infusion velocity, etc.) have on the final distribution of the  microspheres8–14. This information may contribute to enhance antitumor efficacy and minimize complications due to radiation of nontarget tissues. These simulations could also complement the conventional planning with 99mTc-MAA by defining the ideal injection speed and catheter placement in standard scenarios. If the information provided by CFD models could be calculated for individual patients, it would enable the development of more efficient and personalized RE procedures. However, the results from CFD simulations have not yet been compared to the actual microsphere distribution in real patients to assess to what extent the model represents the real-life hepatic artery hemodynamics during RE.

Results: In RE, 90Y PET/CT is commonly used to assess microsphere distribution. This imaging modality has been shown to be a reliable tool to assess activity deposition, to accurately quantify the total activity  delivered16 and to estimate the absorbed  doses.

Conclusion: The aim of this study was to assess the ability of personalized CFD models to predict the microsphere distri-bution observed in the 90Y PET/CT study performed in each patient after the RE procedure. The average activity (estimation of the number of 90Y-microspheres) that the computational simulation study predicted would reach the liver irrigated by the artery in which the 90Y-microspheres were injected was compared with the real average activity obtained in the 90Y PET/CT study after RE.