Investigation and optimization of PET-guided SPECT reconstructions for improved radionuclide therapy dosimetry estimates

IntroductionTo investigate and optimize the SPECTRE (Single Photon Emission Computed Theranostic REconstruction) reconstruction approach, using the hybrid kernelised expectation maximization (HKEM) algorithm implemented in the software for tomographic image reconstruction (STIR) software library, and to demonstrate the feasibility of performing algorithm exploration and optimization in 2D. Optimal SPECTRE parameters were investigated for the purpose of improving SPECT-based radionuclide therapy (RNT) dosimetry estimates.Materials and MethodsUsing the NEMA IEC body phantom as the test object, SPECT data were simulated to model an early and late imaging time point following a typical therapeutic dose of 8 GBq of 177Lu. A theranostic 68Ga PET-prior was simulated for the SPECTRE reconstructions. The HKEM algorithm parameter space was investigated for SPECT-unique and PET-SPECT mutual features to characterize optimal SPECTRE parameters for the simulated data. Mean and maximum bias, coefficient of variation (COV %), recovery, SNR and root-mean-square error (RMSE) were used to facilitate comparisons between SPECTRE reconstructions and OSEM reconstructions with resolution modelling (OSEM_RM). 2D reconstructions were compared to those performed in 3D in order to evaluate the utility of accelerated algorithm optimization in 2D. Segmentation accuracy was evaluated using a 42% fixed threshold (FT) on the 3D reconstructed data.ResultsSPECTRE parameters that demonstrated improved image quality and quantitative accuracy were determined through investigation of the HKEM algorithm parameter space. OSEM_RM and SPECTRE reconstructions performed in 2D and 3D were qualitatively and quantitatively similar, with SPECTRE showing an average reduction in background COV % by a factor of 2.7 and 3.3 for the 2D case and 3D case respectively. The 42% FT analysis produced an average % volume difference from ground truth of 158% and 26%, for the OSEM_RM and SPECTRE reconstructions, respectively.ConclusionsThe SPECTRE reconstruction approach demonstrates significant potential for improved SPECT image quality, leading to more accurate RNT dosimetry estimates when conventional segmentation methods are used. Exploration and optimization of SPECTRE benefited from both fast reconstruction times afforded by first considering the 2D case. This is the first in-depth exploration of the SPECTRE reconstruction approach, and as such, it reveals several insights for reconstructing SPECT data using PET side information

A multicentre comparison of quantitative 90Y PET/CT for dosimetric purposes after radioembolization with resin microspheres

Purpose: To investigate and compare the quantitative accuracy of Y-90 imaging across different generation PET/CT scanners, for the purpose of dosimetry after radioembolization with resin microspheres. Methods: A strict experimental and imaging protocol was followed by 47 international sites using the NEMA 2007/IEC 2008 PET body phantom with an 8-to-1 sphere-to-background ratio of Y-90 solution. The phantom was imaged over a 7-day period (activity ranging from 0.5 to 3.0 GBq) and all reconstructed data were analysed at a core laboratory for consistent processing. Quantitative accuracy was assessed through measures of total phantom activity, activity concentration in background and hot spheres, misplaced counts in a nonradioactive insert, and background variability. Results: Of the 69 scanners assessed, 37 had both time-of-flight (ToF) and resolution recovery (RR) capability. These current generation scanners from GE, Philips and Siemens could reconstruct background concentration measures to within 10 % of true values over the evaluated range, with greater deviations on the Philips systems at low count rates, and demonstrated typical partial volume effects on hot sphere recovery, which dominated spheres of diameter 20 mm in diameter, activity concentrations were consistently underestimated by about 20 %. Non-ToF scanners from GE Healthcare and Siemens were capable of producing accurate measures, but with inferior quantitative recovery compared with ToF systems. Conclusion: Current generation ToF scanners can consistently reconstruct Y-90 activity concentrations, but they underestimate activity concentrations in small structures (a parts per thousand currency sign37 mm diameter) within a warm background due to partial volume effects and constraints of the reconstruction algorithm. At the highest count rates investigated, measures of background concentration (about 300 kBq/ml) could be estimated on average to within 1 %, 5 % and 2 % for GE Healthcare (all-pass filter, RR + ToF), Philips (4i8s ToF) and Siemens (2i21s all-pass filter, RR + ToF) ToF systems, respectively. Over the range of activities investigated, comparable performance between GE Healthcare and Siemens ToF systems suggests suitability for quantitative analysis in a scenario analogous to that of postradioembolization imaging for treatment of liver cancer

A multicentre comparison of quantitative ⁹⁰Y PET/CT for dosimetric purposes after radioembolization with resin microspheres: The QUEST Phantom Study

PURPOSE: To investigate and compare the quantitative accuracy of (90)Y imaging across different generation PET/CT scanners, for the purpose of dosimetry after radioembolization with resin microspheres. METHODS: A strict experimental and imaging protocol was followed by 47 international sites using the NEMA 2007/IEC 2008 PET body phantom with an 8-to-1 sphere-to-background ratio of (90)Y solution. The phantom was imaged over a 7-day period (activity ranging from 0.5 to 3.0 GBq) and all reconstructed data were analysed at a core laboratory for consistent processing. Quantitative accuracy was assessed through measures of total phantom activity, activity concentration in background and hot spheres, misplaced counts in a nonradioactive insert, and background variability. RESULTS: Of the 69 scanners assessed, 37 had both time-of-flight (ToF) and resolution recovery (RR) capability. These current generation scanners from GE, Philips and Siemens could reconstruct background concentration measures to within 10 % of true values over the evaluated range, with greater deviations on the Philips systems at low count rates, and demonstrated typical partial volume effects on hot sphere recovery, which dominated spheres of diameter <20 mm. For spheres >20 mm in diameter, activity concentrations were consistently underestimated by about 20 %. Non-ToF scanners from GE Healthcare and Siemens were capable of producing accurate measures, but with inferior quantitative recovery compared with ToF systems. CONCLUSION: Current generation ToF scanners can consistently reconstruct (90)Y activity concentrations, but they underestimate activity concentrations in small structures (≤37 mm diameter) within a warm background due to partial volume effects and constraints of the reconstruction algorithm. At the highest count rates investigated, measures of background concentration (about 300 kBq/ml) could be estimated on average to within 1 %, 5 % and 2 % for GE Healthcare (all-pass filter, RR + ToF), Philips (4i8s ToF) and Siemens (2i21s all-pass filter, RR + ToF) ToF systems, respectively. Over the range of activities investigated, comparable performance between GE Healthcare and Siemens ToF systems suggests suitability for quantitative analysis in a scenario analogous to that of postradioembolization imaging for treatment of liver cancer

A multicentre comparison of quantitative 90Y PET/CT for dosimetric purposes after radioembolization with resin microspheres

Purpose: To investigate and compare the quantitative accuracy of 90Y imaging across different generation PET/CT scanners, for the purpose of dosimetry after radioembolization with resin microspheres. Methods: A strict experimental and imaging protocol was followed by 47 international sites using the NEMA 2007/IEC 2008 PET body phantom with an 8-to-1 sphere-to-background ratio of 90Y solution. The phantom was imaged over a 7-day period (activity ranging from 0.5 to 3.0 GBq) and all reconstructed data were analysed at a core laboratory for consistent processing. Quantitative accuracy was assessed through measures of total phantom activity, activity concentration in background and hot spheres, misplaced counts in a nonradioactive insert, and background variability. Results: Of the 69 scanners assessed, 37 had both time-of-flight (ToF) and resolution recovery (RR) capability. These current generation scanners from GE, Philips and Siemens could reconstruct background concentration measures to within 10 % of true values over the evaluated range, with greater deviations on the Philips systems at low count rates, and demonstrated typical partial volume effects on hot sphere recovery, which dominated spheres of diameter 20 mm in diameter, activity concentrations were consistently underestimated by about 20 %. Non-ToF scanners from GE Healthcare and Siemens were capable of producing accurate measures, but with inferior quantitative recovery compared with ToF systems. Conclusion: Current generation ToF scanners can consistently reconstruct 90Y activity concentrations, but they underestimate activity concentrations in small structures (≤37 mm diameter) within a warm background due to partial volume effects and constraints of the reconstruction algorithm. At the highest count rates investigated, measures of background concentration (about 300 kBq/ml) could be estimated on average to within 1 %, 5 % and 2 % for GE Healthcare (all-pass filter, RR + ToF), Philips (4i8s ToF) and Siemens (2i21s all-pass filter, RR + ToF) ToF systems, respectively. Over the range of activities investigated, comparable performance between GE Healthcare and Siemens ToF systems suggests suitability for quantitative analysis in a scenario analogous to that of postradioembolization imaging for treatment of liver cancer

Feasibility and accuracy of single time point imaging for renal dosimetry following 177Lu-DOTATATE (‘Lutate’) therapy

Abstract Background This study aims to assess both feasibility and accuracy of renal dosimetry imaging protocols in patients receiving Lutate therapy for neuroendocrine tumours (NETs), when data acquisition over multiple days is not possible on all cycles. Method Patients who had received a full 4 cycles of Lutate therapy with complete imaging at each cycle were included. Imaging consisted of quantitative SPECT/CT of the kidneys at 4, 24 and 96–120 h post injection. Renal absorbed dose was calculated for each data set, and in addition, five alternative methods were explored for comparison. Method 1: a patient average clearance time (t 1/2 average) derived from the first half of contributing patient data was used to estimate absorbed dose for subsequent patients based on 4 h imaging alone; method 2: t 1/2 average was applied to subsequent patients on 24 h imaging alone; method 3: a patient-specific clearance rate (t 1/2 patient) was determined from complete image data of cycle 1 and applied subsequently to remaining cycles using 4 h image data alone; method 4: t 1/2 patient was applied to 24 h imaging alone in subsequent cycles; method 5: the 120 h data was estimated on subsequent cycles based on the cycle 1 fraction of injected activity (%IA) at 24 and 120 h. Results Twenty treatments from 18 patients, resulting in 80 cycles of therapy, were analysed. The measured average renal absorbed dose per cycle of treatment was 0.38 ± 0.19 Gy/GBq when derived from full imaging data. The use of t 1/2 average applied to a single time point led to large deviations of dose estimates from true values (on average 59% and 30%, when using 4 h data and 24 h data, respectively). The use of complete image data on cycle 1 and the derivation of t 1/2 patient led to improved dose estimates, with an average deviation from true values of 13% and 2% when using 4 h data only and 24 h data only, respectively. The use of a 120 h %IA derived from cycle 1 led to an average deviation from true dose estimates of 14%. Conclusion In instances where demands on both patients and facilities make multiple time point data acquisition impractical, renal dosimetry is best derived through complete imaging at cycle 1 only followed by a single 24 h imaging time point on subsequent cycles, assuming no significant changes in renal function during the time course of therapy

Comparison of radiobiological parameters for 90Y radionuclide therapy (RNT) and external beam radiotherapy (EBRT) in vitro

Abstract Background Dose rate variation is a critical factor affecting radionuclide therapy (RNT) efficacy. Relatively few studies to date have investigated the dose rate effect in RNT. Therefore, the aim of this study was to benchmark 90Y RNT (at different dose rates) against external beam radiotherapy (EBRT) in vitro and compare cell kill responses between the two irradiation processes. Results Three human colorectal carcinoma (CRC) cell lines (HT29, HCT116, SW48) were exposed to 90Y doses in the ranges 1–10.4 and 6.2–62.3 Gy with initial dose rates of 0.013–0.13 Gy/hr (low dose rate, LDR) and 0.077–0.77 Gy/hr (high dose rate, HDR), respectively. Results were compared to a 6-MV photon beam doses in the range from 1–9 Gy with constant dose rate of 277 Gy/hr. The cell survival parameters from the linear quadratic (LQ) model were determined. Additionally, Monte Carlo simulations were performed to calculate the average dose, dose rate and the number of hits in the cell nucleus. For the HT29 cell line, which was the most radioresistant, the α/β ratio was found to be ≈ 31 for HDR–90Y and ≈ 3.5 for EBRT. LDR–90Y resulting in insignificant cell death compared to HDR–90Y and EBRT. Simulation results also showed for LDR–90Y, for doses ≲ 3 Gy, the average number of hits per cell nucleus is ≲ 2 indicating insufficiently delivered lethal dose. For 90Y doses ≳ $\gtrsim$ 3 Gy the number of hits per nucleus decreases rapidly and falls below ≈ 2 after ≈ 5 days of incubation time. Therefore, our results demonstrate that LDR–90Y is radiobiologically less effective than EBRT. However, HDR–90Y at ≈ 56 Gy was found to be radiobiologically as effective as acute ≈ 8 Gy EBRT. Conclusion These results demonstrate that the efficacy of RNT is dependent on the initial dose rate at which radiation is delivered. Therefore, for a relatively long half-life radionuclide such as 90Y, a higher initial activity is required to achieve an outcome as effective as EBRT

(90)Y -PET imaging: Exploring limitations and accuracy under conditions of low counts and high random fraction

International audiencePURPOSE: (90)Y -positron emission tomography (PET) imaging is becoming a recognized modality for postinfusion quantitative assessment following radioembolization therapy. However, the extremely low counts and high random fraction associated with (90)Y -PET may significantly impair both qualitative and quantitative results. The aim of this work was to study image quality and noise level in relation to the quantification and bias performance of two types of Siemens PET scanners when imaging (90)Y and to compare experimental results with clinical data from two types of commercially available (90)Y microspheres.METHODS: Data were acquired on both Siemens Biograph TruePoint [non-time-of-flight (TOF)] and Biograph microcomputed tomography (mCT) (TOF) PET/CT scanners. The study was conducted in three phases. The first aimed to assess quantification and bias for different reconstruction methods according to random fraction and number of true counts in the scan. The NEMA 1994 PET phantom was filled with water with one cylindrical insert left empty (air) and the other filled with a solution of (90)Y . The phantom was scanned for 60 min in the PET/CT scanner every one or two days. The second phase used the NEMA 2001 PET phantom to derive noise and image quality metrics. The spheres and the background were filled with a (90)Y solution in an 8:1 contrast ratio and four 30 min acquisitions were performed over a one week period. Finally, 32 patient data (8 treated with Therasphere(®) and 24 with SIR-Spheres(®)) were retrospectively reconstructed and activity in the whole field of view and the liver was compared to theoretical injected activity.RESULTS: The contribution of both bremsstrahlung and LSO trues was found to be negligible, allowing data to be decay corrected to obtain correct quantification. In general, the recovered activity for all reconstruction methods was stable over the range studied, with a small bias appearing at extremely high random fraction and low counts for iterative algorithms. Point spread function (PSF) correction and TOF reconstruction in general reduce background variability and noise and increase recovered concentration. Results for patient data indicated a good correlation between the expected and PET reconstructed activities. A linear relationship between the expected and the measured activities in the organ of interest was observed for all reconstruction method used: a linearity coefficient of 0.89 ± 0.05 for the Biograph mCT and 0.81 ± 0.05 for the Biograph TruePoint.CONCLUSIONS: Due to the low counts and high random fraction, accurate image quantification of (90)Y during selective internal radionuclide therapy is affected by random coincidence estimation, scatter correction, and any positivity constraint of the algorithm. Nevertheless, phantom and patient studies showed that the impact of number of true and random coincidences on quantitative results was found to be limited as long as ordinary Poisson ordered subsets expectation maximization reconstruction algorithms with random smoothing are used. Adding PSF correction and TOF information to the reconstruction greatly improves the image quality in terms of bias, variability, noise reduction, and detectability. On the patient studies, the total activity in the field of view is in general accurately measured by Biograph mCT and slightly overestimated by the Biograph TruePoint