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BACKGROUND: Positron emission tomography (PET) traditionally uses coincident annihilation photons emitted from a positron interacting with an electron to localize cancer within the body. The formation of positronium (Ps), a bonded electron-positron pair, has not been utilized in clinical applications of PET due to the need to detect either the emission of a prompt gamma ray or the decay of higher-order coincident events. Assessment of the lifetime of the formed Ps, however, can potentially yield additional diagnostic information of the surrounding tissue because Ps properties vary due to void size and molecular composition. To assess the feasibility of measuring Ps lifetimes with a PET scanner, experiments were performed in a Biograph Vision Quadra (Siemens Healthineers). Quadra is a long-axial field-of-view (LA-FOV) PET scanner capable of producing list-mode data from single interaction events. RESULTS: Ortho-Ps (o-Ps) lifetimes were measured for quartz-glass and polycarbonate samples using a 22 Na positron source. Results produced o-Ps lifetimes of 1.538 ± 0.036 ns for the quartz glass and 1.927 ± 0.042 ns for the polycarbonate. Both o-Ps lifetimes were determined using a double-exponential fit to the time-difference distribution between the emission of a prompt gamma ray and the annihilation of the correlated positron. The measured values match within a single standard deviation of previously published results. The quartz-glass samples were additional measured with 82 Rb , 68 Ga and 124 I to validate the lifetime using clinically available sources. A double-exponential fit was initially chosen as a similar methodology to previously published works, however, an exponentially-modified Gaussian distribution fit to each lifetime more-accurately models the data. A Bayesian method was used to estimate the variables of the fit and o-Ps lifetime results are reported using this methodology for the three clinical isotopes: 1.59 ± 0.03 ns for 82 Rb , 1.58 ± 0.07 ns for 68 Ga and 1.62 ± 0.01 ns for 124 I . The impact of scatter and attenuation on the o-Ps lifetime was also assessed by analyzing a water-filled uniform cylinder (20 ϕ × 30 cm 3 ) with an added 82 Rb solution. Lifetimes were extracted for various regions of the cylinder and while there is a shape difference in the lifetime due to scatter, the extracted o-Ps lifetime of the water, 1.815 ± 0.013 ns, agrees with previously published results. CONCLUSION: Overall, the methodology presented in this manuscript demonstrates the repeatability of Ps lifetime measurements with clinically available isotopes in a commercially-available LA-FOV PET scanner. This validation work lays the foundation for future in-vivo patient scans with Quadra.

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BACKGROUND AND OBJECTIVE: Treatment planning through the diagnostic dimension of theranostics provides insights into predicting the absorbed dose of RPT, with the potential to individualize radiation doses for enhancing treatment efficacy. However, existing studies focusing on dose prediction from diagnostic data often rely on organ-level estimations, overlooking intra-organ variations. This study aims to characterize the intra-organ theranostic heterogeneity and utilize artificial intelligence techniques to localize them, i.e. to predict voxel-wise absorbed dose map based on pre-therapy PET. METHODS: 23 patients with metastatic castration-resistant prostate cancer treated with [177Lu]Lu-PSMA I&T RPT were retrospectively included. 48 treatment cycles with pre-treatment PET imaging and at least 3 post-therapeutic SPECT/CT imaging were selected. The distribution of PET tracer and RPT dose was compared for kidney, liver and spleen, characterizing intra-organ heterogeneity differences. Pharmacokinetic simulations were performed to enhance the understanding of the correlation. Two strategies were explored for pre-therapy voxel-wise dosimetry prediction: (1) organ-dose guided direct projection; (2) deep learning (DL)-based distribution prediction. Physical metrics, dose volume histogram (DVH) analysis, and identity plots were applied to investigate the predicted absorbed dose map. RESULTS: Inconsistent intra-organ patterns emerged between PET imaging and dose map, with moderate correlations existing in the kidney (r = 0.77), liver (r = 0.5), and spleen (r = 0.58) (P < 0.025). Simulation results indicated the intra-organ pharmacokinetic heterogeneity might explain this inconsistency. The DL-based method achieved a lower average voxel-wise normalized root mean squared error of 0.79 ± 0.27%, regarding to ground-truth dose map, outperforming the organ-dose guided projection (1.11 ± 0.57%) (P < 0.05). DVH analysis demonstrated good prediction accuracy (R2 = 0.92 for kidney). The DL model improved the mean slope of fitting lines in identity plots (199% for liver), when compared to the theoretical optimal results of the organ-dose approach. CONCLUSION: Our results demonstrated the intra-organ heterogeneity of pharmacokinetics may complicate pre-therapy dosimetry prediction. DL has the potential to bridge this gap for pre-therapy prediction of voxel-wise heterogeneous dose map.

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Accurate measurements of photonuclear reaction cross sections are crucial for a number of applications, including radiation shielding design, absorbed dose calculations, reactor physics and engineering, nuclear safeguard and inspection, astrophysics, and nuclear medicine. Primarily motivated by the study of the production of selected radionuclides with high-energy photon beams (mainly 225Ac, 47Sc, and 67Cu), we have established a methodology for the measurement of photonuclear reaction cross sections with the microtron accelerator available at the Swiss Federal Institute of Metrology (METAS). The proposed methodology is based on the measurement of the produced activity with a High Purity Germanium (HPGe) spectrometer and on the knowledge of the photon fluence spectrum through Monte Carlo simulations. The data analysis is performed by applying a Bayesian fitting procedure to the experimental data and by assuming a functional trend of the cross section, in our case a Breit-Wigner function. We validated the entire methodology by measuring a well-established photonuclear cross section, namely the 197Au(γ, n)196Au reaction. The results are consistent with those reported in the literature.

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PURPOSE: Evaluation of 90Y liver radioembolization post-treatment clinical data using a whole-body Biograph Vision Quadra PET/CT to investigate the potential of protocol optimization in terms of scan time and dosimetry. METHODS: 17 patients with hepatocellular carcinoma with median (IQR) injected activity 2393 (1348-3298) MBq were included. Pre-treatment dosimetry plan was based on 99mTc-MAA SPECT/CT with Simplicit90Y™ and post-treatment validation with Quadra using Simplicit90Y™ and HERMIA independently. Regarding the image analysis, mean and peak SNR, the coefficient of variation (COV) and lesion-to-background ratio (LBR) were evaluated. For the post-treatment dosimetry validation, the mean tumor, whole liver and lung absorbed dose evaluation was performed using Simplicit90Y and HERMES. Images were reconstructed with 20-, 15-, 10-, 5- and 1- min sinograms with 2, 4, 6 and 8 iterations. Wilcoxon signed rank test was used to show statistical significance (p < 0.05). RESULTS: There was no difference of statistical significance between 20- and 5- min reconstructed times for the peak SNR, COV and LBR. In addition, there was no difference of statistical significance between 20- and 1- min reconstructed times for all dosimetry metrics. Lung dosimetry showed consistently lower values than the expected. Tumor absorbed dose based on Simplicit90Y™ was similar to the expected while HERMES consistently underestimated significantly the measured tumor absorbed dose. Finally, there was no difference of statistical significance between expected and measured tumor, whole liver and lung dose for all reconstruction times. CONCLUSION: In this study we evaluated, in terms of image quality and dosimetry, whole-body PET clinical images of patients after having been treated with 90Y microspheres radioembolization for liver cancer. Compared to the 20-min standard scan, the simulated 5-min reconstructed images provided equal image peak SNR and noise behavior, while performing also similarly for post-treatment dosimetry of tumor, whole liver and lung absorbed doses.

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PURPOSE: Long axial field-of-view (LAFOV) positron emission tomography (PET) systems allow to image all major organs with one bed position, which is particularly useful for acquiring whole-body dynamic data using short-lived radioisotopes like 82Rb. METHODS: We determined the absorbed dose in target organs of three subjects (29, 40, and 57 years old) using two different methods, i.e., MIRD and voxel dosimetry. The subjects were injected with 407.0 to 419.61 MBq of [82Rb]Cl and were scanned dynamically for 7 min with a LAFOV PET/CT scanner. RESULTS: Using the MIRD formalism and voxel dosimetry, the absorbed dose ranged from 1.84 to 2.78 µGy/MBq (1.57 to 3.92 µGy/MBq for voxel dosimetry) for the heart wall, 2.76 to 5.73 µGy/MBq (3.22 to 5.37 µGy/MBq for voxel dosimetry) for the kidneys, and 0.94 to 1.88 µGy/MBq (0.98 to 1.92 µGy/MBq for voxel dosimetry) for the lungs. The total body effective dose lied between 0.50 and 0.76 µSv/MBq. CONCLUSION: Our study suggests that the radiation dose associated with [82Rb]Cl PET/CT can be assessed by means of dynamic LAFOV PET and that it is lower compared to literature values.

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The use of artificial intelligence systems in clinical routine is still hampered by the necessity of a medical device certification and/or by the difficulty of implementing these systems in a clinic's quality management system. In this context, the key questions for a user are how to ensure robust model predictions and how to appraise the quality of a model's results on a regular basis. In this paper we discuss some conceptual foundation for a clinical implementation of a machine learning system and argue that both vendors and users should take certain responsibilities, as is already common practice for high-risk medical equipment. We propose the methodology from AAPM Task Group 100 report No. 283 as a conceptual framework for developing risk-driven a quality management program for a clinical process that encompasses a machine learning system. This is illustrated with an example of a clinical workflow. Our analysis shows how the risk evaluation in this framework can accommodate artificial intelligence based systems independently of their robustness evaluation or the user's in-house expertise. In particular, we highlight how the degree of interpretability of a machine learning system can be systematically accounted for within the risk evaluation and in the development of a quality management system.

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PURPOSE: The physical properties of yttrium-90 (90Y) allow for imaging with positron emission tomography/computed tomography (PET/CT). The increased sensitivity of long axial field-of-view (LAFOV) PET/CT scanners possibly allows to overcome the small branching ratio for positron production from 90Y decays and to improve for the post-treatment dosimetry of 90Y of selective internal radiation therapy. METHODS: For the challenging case of an image quality body phantom, we compare a full Monte Carlo (MC) dose calculation with the results from the two commercial software packages Simplicit90Y and Hermes. The voxel dosimetry module of Hermes relies on the 90Y images taken with a LAFOV PET/CT, while the MC and Simplicit90Y dose calculations are image independent. RESULTS: The resulting doses from the MC calculation and Simplicit90Y agree well within the error margins. The image-based dose calculation with Hermes, however, consistently underestimates the dose. This is due to the mismatch of the activity distribution in the PET images and the size of the volume of interest. We found that only for the smallest phantom sphere there is a statistically significant dependence of the Hermes dose on the image reconstruction parameters and scan time. CONCLUSION: Our study shows that Simplicit90Y's local deposition model can provide a reliable dose estimate. On the other hand, the image based dose calculation suffers from the suboptimal reconstruction of the 90Y distribution in small structures.

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We report the dosimetric evaluation of prostate-specific membrane antigen-based radioligand therapy (RLT) for metastatic prostate cancer in a patient with autosomal-dominant polycystic kidney disease. Methods: The patient received hemodialysis during each of 6 RLT cycles while staying as an inpatient. We used voxel dosimetry and blood sampling for the dose calculation. Results: The patient responded well to the RLT, as indicated by the prostate-specific antigen level decreasing from 298 to 7.1 ng/mL. The doses per cycle ranged from 0.19 to 0.4 Gy/GBq for the parotid gland, 0.14 to 0.28 Gy/GBq for the submandibular gland, 0.03 to 0.11 Gy/GBq per kidney, and 0.10 to 0.15 Gy/GBq for the red bone marrow. Conclusion: This case suggests that [177Lu]Lu-PSMA-based RLT can be applied successfully and safely to a patient with chronic kidney disease undergoing hemodialysis.

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PURPOSE: The image quality characteristics of two NEMA phantoms with yttrium-90 (90Y) were evaluated on a long axial field-of-view (AFOV) PET/CT. The purpose was to identify the optimized reconstruction setup for the imaging of patients with hepatocellular carcinoma after 90Y radioembolization. METHODS: Two NEMA phantoms were used, where one had a 1:10 sphere to background activity concentration ratio and the second had cold background. Reconstruction parameters used are as follows: iterations 2 to 8, Gaussian filter 2- to 6-mm full-width-at-half-maximum, reconstruction matrices 440 × 440 and 220 × 220, high sensitivity (HS), and ultra-high sensitivity (UHS) modes. 50-, 40-, 30-, 20-, 10-, and 5-min acquisitions were reconstructed. The measurements included recovery coefficients (RC), signal-to-noise ratio (SNR), background variability, and lung error which measures the residual error in the corrections. Patient data were reconstructed with 20-, 10-, 5-, and 1-min time frames and evaluated in terms of SNR. RESULTS: The RC for the hot phantom was 0.36, 0.45, 0.53, 0.63, 0.68, and 0.84 for the spheres with diameters of 10, 13, 17, 22, 28, and 37 mm, respectively, for UHS 2 iterations, a 220 × 220 matrix, and 50-min acquisition. The RC values did not differ with acquisition times down to 20 min. The SNR was the highest for 2 iterations, measured 11.7, 16.6, 17.6, 19.4, 21.9, and 27.7 while the background variability was the lowest (27.59, 27.08, 27.36, 26.44, 30.11, and 33.51%). The lung error was 18%. For the patient dataset, the SNR was 19%, 20%, 24%, and 31% higher for 2 iterations compared to 4 iterations for 20-, 10-, 5-, and 1-min time frames, respectively. CONCLUSIONS: This study evaluates the NEMA image quality of a long AFOV PET/CT scanner with 90Y. It provides high RC for the smallest sphere compared to other standard AFOV scanners at shorter scan times. The maximum patient SNR was for 2 iterations, 20 min, while 5 min delivers images with acceptable SNR.

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The characterization of particle accelerator induced neutron fields is challenging but fundamental for research and industrial activities, including radiation protection, neutron metrology, developments of neutron detectors for nuclear and high-energy physics, decommissioning of nuclear facilities, and studies of neutron damage on materials and electronic components. This work reports on the study of a novel approach to the experimental characterization of neutron spectra at two complex accelerator environments, namely the CERF, a high-energy mixed reference field at CERN in Geneva, and the Bern medical cyclotron laboratory, a facility used for multi-disciplinary research activities, and for commercial radioisotope production for nuclear medicine. Measurements were performed through an innovative active neutron spectrometer called DIAMON, a device developed to provide in real time neutron energy spectra without the need of guess distributions. The intercomparison of DIAMON measurements with reference data, Monte Carlo simulations, and with the well-established neutron monitor Berthold LB 6411, has been found to be highly satisfactory in all conditions. It was demonstrated that DIAMON is an almost unique device able to characterize neutron fields induced by hadrons at 120 GeV/c as well as by protons at 18 MeV colliding with different materials. The accurate measurement of neutron spectra at medical cyclotrons during routine radionuclide production for nuclear medicine applications is of paramount importance for the facility decommissioning. The findings of this work are the basis for establishing a methodology for producing controlled proton-induced neutron beams with medical cyclotrons.

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Traditional simulation techniques such as wave optics methods and Monte Carlo (MC) particle transport cannot model both interference and inelastic scattering phenomena within one framework. Based on the rules of quantum mechanics to calculate probabilities, we propose a new semi-classical MC algorithm for efficient and simultaneous modeling of scattering and interference processes. The similarities to MC particle transport allow the implementation as a flexible c++ object oriented extension of EGSnrc-a well-established MC toolkit. In addition to previously proposed Huygens principle based transport through optics components, new variance reduction techniques for the transport through gratings are presented as transport options to achieve the required improvement in speed and memory costs necessary for an efficient exploration (system design-dose estimations) of the medical implementation of X-ray grating interferometry (GI), an emerging imaging technique currently subject of tremendous efforts towards clinical translation. The feasibility of simulation of interference effects is confirmed in four academic cases and an experimental table-top GI setup. Comparison with conventional MC transport show that deposited energy features of EGSnrc are conserved.