Voxel-Wise Dose Heterogeneity Following Yttrium-90 Glass Microsphere Radioembolization In HCC: Association with Pretreatment Tc-99m Maa SPECT/CT Tumor-to-Normal Ratio
Abstract
Purpose
Tumor-to-normal ratio (TNR) derived from pretreatment Tc-99m MAA SPECT/CT is widely used as a surrogate marker of perfusion in yttrium-90 (⁹⁰Y) radioembolization for patients with hepatocellular carcinoma (HCC). Delivered activity is critical for achieving ablative doses that induce cumulative DNA damage and tumor cell death. However, microspheres deposit heterogeneously within tumors, producing hot regions of high absorbed dose and cold regions of low dose, quantified by the heterogeneity index (D5/D95). Cold regions may receive insufficient dose, potentially reducing local tumor control. This study quantifies the relationship between pretreatment TNR and post-treatment dose heterogeneity in HCC patients treated with ⁹⁰Y glass microspheres and evaluates the implications for pretreatment perfusion assessment.
Methods
Ten HCC patients treated with ⁹⁰Y glass microspheres (2018–2022) were retrospectively analyzed. TNR was calculated from pretreatment Tc-99m MAA SPECT/CT. Post-treatment ⁹⁰Y imaging was imported into MIM Software for voxel-based dosimetry. Dose volume histograms (DVHs) were generated to extract D95 and D5, quantifying intratumoral dose heterogeneity. Associations between TNR and heterogeneity indicies were assessed using Pearson correlation, with R² reported to indicate the proportion of variance.
Results
Substantial interpatient variability was observed in TNR and post-treatment dosimetry. Heterogeneity indices ranged from 2.3 to 19.4, indicating highly nonuniform dose distributions despite targeted delivery. No strong correlation was found between TNR and D95 or heterogeneity indices (R² = 0.03), suggesting TNR alone may not capture voxel-level absorbed dose patterns.
Conclusion
This exploratory study demonstrates the feasibility of extracting DVH-based cold-spot metrics from post-treatment ⁹⁰Y dosimetry and quantifies microsphere deposition within tumors. The weak association between TNR and intratumoral dose coverage highlights the limitations of Tc-99m MAA SPECT/CT for predicting voxel-level heterogeneity, underscoring the need for pretreatment measures that more accurately reflect local perfusion. These findings provide a framework for future studies on factors affecting microsphere distribution and dose heterogeneity in HCC.