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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 R*2. The current 166Ho quantification method does not take regional differences in baseline R*2 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 R*2 distributions between tumor tissue and healthy tissue and assess the feasibility and accuracy of voxelwise subtraction-based ΔR*2 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 R*2 distributions between tumor tissue and healthy tissue were characterized. Same-day pre- and post-treatment R*2 maps were aligned using a deformable registration algorithm and subsequently subtracted to generate voxelwise R*2 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 R*2 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 subtractionbased 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 subtractionbased 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 R*2 differences, and appears to correspond better with SPECT-based dosimetry compared to the currently implemented mean subtraction method. [ABSTRACT FROM AUTHOR]

Ho-166 is a combined beta-gamma emitter of which the betas can be used therapeutically. From the 81 keV gammas of Ho-166, SPECT images can be obtained, which give opportunities to guide Ho-166 therapy. Accurate reconstruction of Ho-166 images is currently hampered by photopeak-scatter in the patient, down-scatter in the detector, collimator and patient caused by the 1.4 MeV photons and by bremsstrahlung. We developed and validated a method for quantitative SPECT of Ho-166 that involves correction for both types of scatter plus non-uniform attenuation correction using attenuation maps. Photopeak-scatter (S) is compensated for by a rapid 3D Monte Carlo (MC) method that is incorporated in ordered subset (OS) reconstruction of the emission data, together with simultaneous correction for attenuation (A) and detector response (D); this method is referred to as OS-ADS. Additionally, for correction of down-scatter, we use a 14 keV wide energy window centred at 118 keV (OS-ADSS). Due to a limited number of available energy windows, the same 118 keV energy window was used for down-scatter correction of the simultaneously acquired Gd-153 transmission data. Validations were performed using physical phantom experiments carried out on a dual-head SPECT system; Gd-153 transmission line sources were used for acquiring attenuation maps. For quantitative comparison of OS-ADS and OS-ADSS, bottles filled with Ho-166 were placed in both a cylindrical phantom and an anthropomorphic thorax phantom. Both OS-ADS and OS-ADSS were compared with an ordered subset reconstruction without any scatter correction (OS-AD). Underestimations of about 20% in the attenuation map were reduced to a few per cent after down-scatter correction. The average deviation from the true activity contained in the bottles was +72% with OS-AD. Using OS-ADS, this average overestimation was reduced to +28% and with OS-ADSS the deviation was further reduced to 16%. With OS-AD and OS-ADS, these numbers were more sensitive to the choice of volumes of interest than with OS-ADSS. For the reconstructed activity distributions, erroneous background activity found with OS-AD was reduced by a factor of approximately 2 by applying OS-ADS and reduced by a factor of approximately 4 by applying OS-ADSS. The combined attenuation, photopeak-scatter and down-scatter correction framework proposed here greatly enhanced the quantitative accuracy of Ho-166 imaging, which is of the uppermost importance for image-guided therapies. It is expected that the method, with adapted window settings, also can be applied to other isotopes with high energy peaks that contaminate the photopeak data, such as I-131 or In-111.