Dose Heterogeneity in Transarterial Radioembolization after Fractional Administration of Holmium Microspheres: A Study in Perfused Human Tumor-Bearing Liver Explants under MR Imaging

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PURPOSE: To investigate dose heterogeneity in liver tumors and nontumor target liver (NTTL) following transarterial radioembolization (TARE) by developing an experimental magnetic resonance (MR) imaging-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 MR imaging in 4 machine-perfused human tumor-bearing liver explants using fluorescent holmium microspheres. Dose heterogeneity was quantified by calculating the homogeneity index (HI) from MR imaging-based dose maps (voxel size, <2.5 mm). These results were validated against HI values from 2 TARE-treated patients. Fluorescence microscopy was used to assess the microscopic distribution of 4 distinct microsphere fractions. RESULTS: MR imaging-based dose maps revealed lower heterogeneity in liver tumors (mean HI, 2.41; range, 0.72-4.43) than in nontumor target liver (mean HI, 2.95; range, 1.58-5.94); however, this difference was not significant (P = .06) and was primarily driven by higher microsphere concentrations in tumors, which were associated with reduced heterogeneity (ρ = -0.88, P < .001). Microspheres administered in consecutive fractions decreased the HI while mostly preserving the spatial distribution pattern of earlier fractions, as confirmed by fluorescence microscopy. CONCLUSIONS: TARE induces heterogeneous dose distributions in both liver tumors and nontumor target liver at a scale below the resolution of nuclear imaging. Although 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.

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