Impact of SPECT corrections on 3D-dosimetry for liver transarterial radioembolization using the patient relative calibration methodology.

PURPOSE: Many centers aim to plan liver transarterial radioembolization (TARE) with dosimetry, even without CT-based attenuation correction (AC), or with unoptimized scatter correction (SC) methods. This work investigates the impact of presence vs absence of such corrections, and limited spatial resolution, on 3D dosimetry for TARE. METHODS: Three voxelized phantoms were derived from CT images of real patients with different body sizes. Simulations of (99m)Tc-SPECT projections were performed with the SIMIND code, assuming three activity distributions in the liver: uniform, inside a "liver's segment," or distributing multiple uptaking nodules ("nonuniform liver"), with a tumoral liver/healthy parenchyma ratio of 5:1. Projection data were reconstructed by a commercial workstation, with OSEM protocol not specifically optimized for dosimetry (spatial resolution of 12.6 mm), with/without SC (optimized, or with parameters predefined by the manufacturer; dual energy window), and with/without AC. Activity in voxels was calculated by a relative calibration, assuming identical microspheres and (99m)Tc-SPECT counts spatial distribution. 3D dose distributions were calculated by convolution with (90)Y voxel S-values, assuming permanent trapping of microspheres. Cumulative dose-volume histograms in lesions and healthy parenchyma from different reconstructions were compared with those obtained from the reference biodistribution (the "gold standard," GS), assessing differences for D95%, D70%, and D50% (i.e., minimum value of the absorbed dose to a percentage of the irradiated volume). γ tool analysis with tolerance of 3%/13 mm was used to evaluate the agreement between GS and simulated cases. The influence of deep-breathing was studied, blurring the reference biodistributions with a 3D anisotropic gaussian kernel, and performing the simulations once again. RESULTS: Differences of the dosimetric indicators were noticeable in some cases, always negative for lesions and distributed around zero for parenchyma. Application of AC and SC reduced systematically the differences for lesions by 5%-14% for a liver segment, and by 7%-12% for a nonuniform liver. For parenchyma, the data trend was less clear, but the overall range of variability passed from -10%/40% for a liver segment, and -10%/20% for a nonuniform liver, to -13%/6% in both cases. Applying AC, SC with preset parameters gave similar results to optimized SC, as confirmed by γ tool analysis. Moreover, γ analysis confirmed that solely AC and SC are not sufficient to obtain accurate 3D dose distribution. With breathing, the accuracy worsened severely for all dosimetric indicators, above all for lesions: with AC and optimized SC, -38%/-13% in liver's segment, -61%/-40% in the nonuniform liver. For parenchyma, D50% resulted always less sensitive to breathing and sub-optimal correction methods (difference overall range: -7%/13%). CONCLUSIONS: Reconstruction protocol optimization, AC, SC, PVE and respiratory motion corrections should be implemented to obtain the best possible dosimetric accuracy. On the other side, thanks to the relative calibration, D50% inaccuracy for the healthy parenchyma from absence of AC was less than expected, while the optimization of SC was scarcely influent. The relative calibration therefore allows to perform TARE planning, basing on D50% for the healthy parenchyma, even without AC or with suboptimal corrections, rather than rely on nondosimetric methods.

Differences in 3D dose distributions due to calculation method of voxel S-values and the influence of image blurring in SPECT.

This study compares 3D dose distributions obtained with voxel S values (VSVs) for soft tissue, calculated by several methods at their current state-of-the-art, varying the degree of image blurring. The methods were: 1) convolution of Dose Point Kernel (DPK) for water, using a scaling factor method; 2) an analytical model (AM), fitting the deposited energy as a function of the source-target distance; 3) a rescaling method (RSM) based on a set of high-resolution VSVs for each isotope; 4) local energy deposition (LED). VSVs calculated by direct Monte Carlo simulations were assumed as reference. Dose distributions were calculated considering spheroidal clusters with various sizes (251, 1237 and 4139 voxels of 3 mm size), uniformly filled with (131)I, (177)Lu, (188)Re or (90)Y. The activity distributions were blurred with Gaussian filters of various widths (6, 8 and 12 mm). Moreover, 3D-dosimetry was performed for 10 treatments with (90)Y derivatives. Cumulative Dose Volume Histograms (cDVHs) were compared, studying the differences in D95%, D50% or Dmax (ΔD95%, ΔD50% and ΔDmax) and dose profiles.For unblurred spheroidal clusters, ΔD95%, ΔD50% and ΔDmax were mostly within some percents, slightly higher for (177)Lu with DPK (8%) and RSM (12%) and considerably higher for LED (ΔD95% up to 59%). Increasing the blurring, differences decreased and also LED yielded very similar results, but D95% and D50% underestimations between 30-60% and 15-50%, respectively (with respect to 3D-dosimetry with unblurred distributions), were evidenced. Also for clinical images (affected by blurring as well), cDVHs differences for most methods were within few percents, except for slightly higher differences with LED, and almost systematic for dose profiles with DPK (-1.2%), AM (-3.0%) and RSM (4.5%), whereas showed an oscillating trend with LED.The major concern for 3D-dosimetry on clinical SPECT images is more strongly represented by image blurring than by differences among the VSVs calculation methods. For volume sizes about 2-fold the spatial resolution, D95% and D50% underestimations up to about 60 and 50% could result, so the usefulness of 3D-dosimetry is highly questionable for small tumors, unless adequate corrections for partial volume effects are adopted.

Improving the dose-myelotoxicity correlation in radiometabolic therapy of bone metastases with 153Sm-EDTMP.

PURPOSE: (153)Sm-ethylene diamine tetramethylene phosphonic acid ((153)Sm-EDTMP) is widely used to palliate pain from bone metastases, and is being studied for combination therapy beyond palliation. Conceptually, red marrow (RM) dosimetry allows myelotoxicity to be predicted, but the correlation is poor due to dosimetric uncertainty, individual sensitivity and biological effects from previous treatments. According to EANM guidelines, basic dosimetric procedures have been studied to improve the correlation between dosimetry and myelotoxicity in (153)Sm-EDTMP therapy. METHODS: RM dosimetry for 33 treatments of bone metastases from breast, prostate and lung tumours was performed prospectively (with (99m)Tc-MDP) and retrospectively, acquiring whole-body scans early and late after injection. The (153)Sm-EDTMP activity was calculated by prospective dosimetry based on measured skeletal uptake and full physical retention, with the RM absorbed dose not exceeding 3.8 Gy. Patient-specific RM mass was evaluated by scaling in terms of body weight (BW), lean body mass (LBM) and trabecular volume (TV) estimated from CT scans of the L2­L4 vertebrae. Correlations with toxicity were determined in a selected subgroup of 27 patients, in which a better correlation between dosimetry and myelotoxicity was expected. RESULTS: Skeletal uptakes of (99m)Tc and (153)Sm (Tc% and Sm%) were well correlated. The median Sm% was higher in prostate cancer (75.3 %) than in lung (60.5%, p = 0.005) or breast (60.8%, p = 0.008). PLT and WBC nadirs were not correlated with administered activity, but were weakly correlated with uncorrected RM absorbed doses, and the correlation improved after rescaling in terms of BW, LBM and TV. Most patients showed transient toxicity (grade 1­3), which completely and spontaneously recovered over a few days. Using TV, RM absorbed dose was in the range 2­5 Gy, with a median of 312 cGy for PLT in patients with toxicity and 247 cGy in those with no toxicity (p = 0.019), and 312 cGy for WBC in those with toxicity and 232 cGy in those with no toxicity (p = 0.019). ROC curves confirmed the correlations, yielding toxicity absorbed dose thresholds of 265 cGy for PLT and 232 cGy for WBC. CONCLUSION: The best predictor of myelotoxicity and blood cells nadir was obtained scaling the RM absorbed dose in terms of the estimated TV. It seems clear that the increase in skeletal uptake due to the presence of bone metastases and the assumption of full physical retention cause an overestimation of the RM absorbed dose. Nevertheless, an improvement of the dose­toxicity correlation is easily achievable by simple methods, also leading to possible improvement in multifactorial analyses of myelotoxicity.