Improving MRI-based dosimetry for holmium-166 transarterial radioembolization using a nonrigid image registration for voxelwise ΔR2* calculation

Abstract

Background: Transarterial radioembolization (TARE) is a treatment modality for liver tumors during which radioactive microspheres are injected into the hepatic arterial system. These microspheres distribute throughout the liver as a result of the blood flow until they are trapped in the arterioles because of their size. Holmium-166 (166Ho)-loaded microspheres used for TARE can be visualized and quantified with MRI, as holmium is a paramagnetic metal and locally increases the transverse relaxation rate (Formula presented.). The current 166Ho quantification method does not take regional differences in baseline (Formula presented.) values (such as between tumors and healthy tissue) into account, which intrinsically results in a systematic error in the estimated absorbed dose distribution. As this estimated absorbed dose distribution can be used to predict response to treatment of tumors and potential toxicity in healthy tissue, a high accuracy of absorbed dose estimation is required. Purpose: To evaluate pre-existing differences in (Formula presented.) distributions between tumor tissue and healthy tissue and assess the feasibility and accuracy of voxelwise subtraction-based (Formula presented.) calculation for MRI-based dosimetry of holmium-166 transarterial radioembolization (166Ho TARE). Methods: MRI data obtained in six patients who underwent 166Ho TARE of the liver as part of a clinical study was retrospectively evaluated. Pretreatment differences in (Formula presented.) distributions between tumor tissue and healthy tissue were characterized. Same-day pre- and post-treatment (Formula presented.) maps were aligned using a deformable registration algorithm and subsequently subtracted to generate voxelwise (Formula presented.) maps and resultant absorbed dose maps. Image registration accuracy was quantified using the dice similarity coefficient (DSC), relative overlay (RO), and surface dice (≤4 mm; SDSC). Voxelwise subtraction-based absorbed dose maps were quantitatively (root-mean-square error, RMSE) and visually compared to the current MRI-based mean subtraction method and routinely used SPECT-based dosimetry. Results: Pretreatment (Formula presented.) values were lower in tumors than in healthy liver tissue (mean 36.8 s−1 vs. 55.7 s−1, P = 0.004). Image registration improved the mean DSC of 0.83 (range: 0.70–0.88) to 0.95 (range: 0.92–0.97), mean RO of 0.71 (range 0.53–0.78) to 0.90 (range: 0.86–0.94), and mean SDSC ≤4 mm of 0.47 (range: 0.28–0.67) to 0.97 (range: 0.96–0.98). Voxelwise subtraction-based absorbed dose maps yielded a higher tumor-absorbed dose (median increase of 9.0%) and lower healthy liver-absorbed dose (median decrease of 13.8%) compared to the mean subtraction method. Voxelwise subtraction-based absorbed dose maps corresponded better to SPECT-based absorbed dose maps, reflected by a lower RMSE in three of six patients. Conclusions: Voxelwise subtraction presents a robust alternative method for MRI-based dosimetry of 166Ho microspheres that accounts for pre-existing (Formula presented.) differences, and appears to correspond better with SPECT-based dosimetry compared to the currently implemented mean subtraction method.