Anne van den Brekel, Kirsten de Vries, Veerle A Lantinga, Tess J Snoeijink, Arja Gerritsen, Milou Boswinkel, Joey Roosen, Alexandra G Arranja, Marius C van den Heuvel, Cyril Moers, Jurgen J Fütterer, Koert P de Jong, Vincent E de Meijer, Simeon J S Ruiter, J Frank W Nijsen
Purpose: To investigate dose heterogeneity in liver tumors and non-tumor target liver following transarterial radioembolization (TARE) by developing an experimental magnetic resonance imaging (MRI)-compatible ex vivo perfusion model based on human tumor-bearing livers, and to validate the observed heterogeneity patterns against in vivo data.
Materials and methods: Fractionated TARE was performed under MRI in four machine-perfused human tumor-bearing liver explants using fluorescent holmium microspheres. Dose heterogeneity was quantified by calculating the homogeneity index (HI) from MRI-based dose maps (voxel size <2.5 mm). These results were validated against HI values from two TARE-treated patients. Fluorescence microscopy was used to assess the microscopic distribution of four distinct microsphere fractions.
Results: MRI-based dose maps revealed lower heterogeneity in liver tumors (mean HI 2.41, range 0.72-4.43) compared to non-tumor target liver (mean HI 2.95, range 1.58-5.94), but this difference was not significant (p = 0.06) and was primarily driven by higher microsphere concentrations in tumors, which were associated with reduced heterogeneity (ρ = -0.88, p < 0.001). Microspheres administered in consecutive fractions decreased the HI while mostly preserving the spatial distribution pattern of earlier fractions, as confirmed by fluorescence microscopy.
Conclusion: TARE induces heterogeneous dose distributions in both liver tumors and non-tumor target liver at a scale below the resolution of nuclear imaging. While these findings provide insight into microsphere distribution and dose heterogeneity, the clinical significance of fine-scale dose heterogeneity and its potential impact on treatment outcomes remains uncertain and warrants further investigation.