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Background: [ 18 F]FDG PET denoising by SubtlePET™ using deep learning artificial intelligence (AI) was previously found to induce slight modifications in lesion and reference organs' quantification and in lesion detection. As a next step, we aimed to evaluate its clinical impact on [ 18 F]FDG PET solid tumour treatment response assessments, while comparing "standard PET" to "AI denoised half-duration PET" ("AI PET") during follow-up., Results: 110 patients referred for baseline and follow-up standard digital [ 18 F]FDG PET/CT were prospectively included. "Standard" EORTC and, if applicable, PERCIST response classifications by 2 readers between baseline standard PET1 and follow-up standard PET2 as a "gold standard" were compared to "mixed" classifications between standard PET1 and AI PET2 (group 1; n = 64), or between AI PET1 and standard PET2 (group 2; n = 46). Separate classifications were established using either standardized uptake values from ultra-high definition PET with or without AI denoising (simplified to "UHD") or EANM research limited v2 (EARL2)-compliant values (by Gaussian filtering in standard PET and using the same filter in AI PET). Overall, pooling both study groups, in 11/110 (10%) patients at least one EORTC UHD or EARL2 or PERCIST UHD or EARL2 mixed vs. standard classification was discordant, with 369/397 (93%) concordant classifications, unweighted Cohen's kappa = 0.86 (95% CI: 0.78-0.94). These modified mixed vs. standard classifications could have impacted management in 2% of patients., Conclusions: Although comparing similar PET images is preferable for therapy response assessment, the comparison between a standard [ 18 F]FDG PET and an AI denoised half-duration PET is feasible and seems clinically satisfactory., (© 2024. The Author(s).)

Importance: Whether F18-choline (FCH) positron emission tomographic (PET)/computed tomographic (CT) scan can replace Tc99m-sestaMIBI (MIBI) single-photon emission (SPE)CT/CT as a first-line imaging technique for preoperative localization of parathyroid adenomas (PTA) in patients with primary hyperparathyroidism (PHPT) is unclear., Objective: To compare first-line FCH PET/CT vs MIBI SPECT/CT for optimal care in patients with PHPT needing parathyroidectomy and to compare the proportions of patients in whom the first-line imaging method resulted in successful minimally invasive parathyroidectomy (MIP) and normalization of calcemia 1 month after surgery., Design, Setting, and Participants: A French multicenter randomized open diagnostic intervention phase 3 trial was conducted. Patients were enrolled from November 2019 to May 2022 and participated up to 6 months after surgery. The study included adults with PHPT and an indication for surgical treatment. Patients with previous parathyroid surgery or multiple endocrine neoplasia type 1 (MEN1) were ineligible., Interventions: Patients were assigned in a 1:1 ratio to receive first-line FCH PET/CT (FCH1) or MIBI SPECT/CT (MIBI1). In the event of negative or inconclusive first-line imaging, they received second-line FCH PET/CT (FCH2) after MIBI1 or MIBI SPECT/CT (MIBI2) after FCH1. All patients underwent surgery under general anesthesia within 12 weeks following the last imaging. Clinical and biologic (serum calcemia and parathyroid hormone levels) assessments were performed 1 and 6 months after surgery., Main Outcomes and Measures: The primary outcome was a true-positive first-line imaging-guided MIP combined with uncorrected serum calcium levels of 2.55 mmol/l or less 1 month after surgery, corresponding to the local upper limit of normality., Results: Overall, 57 patients received FCH1 (n = 29) or MIBI1 (n = 28). The mean (SD) age of patients was 62.8 (12.5) years with 15 male (26%) and 42 female (74%) patients. Baseline patient characteristics were similar between groups. Normocalcemia at 1 month after positive first-line imaging-guided MIP was observed in 23 of 27 patients (85%) in the FCH1 group and 14 of 25 patients (56%) in the MIBI1 group. Sensitivity was 82% (95% CI, 62%-93%) and 63% (95% CI, 42%-80%) for FCH1 and MIBI1, respectively. Follow-up at 6 months with biochemical measures was available in 43 patients, confirming that all patients with normocalcemia at 1 month after surgery still had it at 6 months. No adverse events related to imaging and 4 adverse events related to surgery were reported., Conclusions: This randomized clinical trial found that first-line FCH PET/CT is a suitable and safe replacement for MIBI SPECT/CT. FCH PET/CT leads more patients with PHPT to correct imaging-guided MIP and normocalcemia than MIBI SPECT/CT thanks to its superior sensitivity., Trial Registration: ClinicalTrials.gov Identifier: NCT04040946.

Background: Exploring the value of baseline and early 18 F-FDG PET/CT evaluations in prediction PFS in ER+/HER2- metastatic breast cancer patients treated with a cyclin-dependent kinase inhibitor in combination with an endocrine therapy., Methods: Sixty-six consecutive breast cancer patients who underwent a pre-therapeutic 18 F-FDG PET/CT and a second PET/CT within the first 6 months of treatment were retrospectively included. Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) and D max , which represents tumour dissemination and is defined as the distance between the two most distant lesions, were computed. The variation in these parameters between baseline and early evaluation PET as well as therapeutic evaluation using PERCIST were assessed as prognosticators of PFS at 18 months., Results: The median follow-up was equal to 22.5 months. Thirty progressions occurred (45.4%). The average time to event was 17.8 ± 10.4 months. At baseline, D max was the only predictive metabolic parameter. Patients with a baseline D max ≤ 18.10 cm had a significantly better 18 m-PFS survival than the others: 69.2% (7.7%) versus 36.7% (8.8%), p = 0.017. There was no association between PERCIST evaluation and 18 m-PFS status (p = 0.149) and there was no difference in 18 m-PFS status between patients classified as complete, partial metabolic responders or having stable metabolic disease., Conclusion: Disease spread at baseline PET, as assessed by D max , is predictive of an event occurring within 18 months. In the absence of early metabolic progression, which occurs in 15% of patients, treatment should be continued regardless of the quality of the initial response to treatment., (© 2024. The Author(s).)

Background: Small-animal PET imaging is an important tool in preclinical oncology. This study evaluated the ability of a clinical SiPM-PET camera to image several rats simultaneously and to perform quantification data analysis., Methods: Intrinsic spatial resolution was measured using 18F line sources, and image quality was assessed using a NEMA NU 4-2018 phantom. Quantification was evaluated using a fillable micro-hollow sphere phantom containing 4 spheres of different sizes (ranging from 3.95 to 7.86 mm). Recovery coefficients were computed for the maximum (Amax) and the mean (A50) pixel values measured on a 50% isocontour drawn on each sphere. Measurements were performed first with the phantom placed in the centre of the field of view and then in the off-centre position with the presence of three scattering sources to simulate the acquisition of four animals simultaneously. Quantification accuracy was finally validated using four 3D-printed phantoms mimicking rats with four subcutaneous tumours each. All experiments were performed for both 18F and 68Ga radionuclides., Results: Radial spatial resolutions measured using the PSF reconstruction algorithm were 1.80 mm and 1.78 mm for centred and off-centred acquisitions, respectively. Spill-overs in air and water and uniformity computed with the NEMA phantom centred in the FOV were 0.05, 0.1 and 5.55% for 18F and 0.08, 0.12 and 2.81% for 68Ga, respectively. Recovery coefficients calculated with the 18F-filled micro-hollow sphere phantom for each sphere varied from 0.51 to 1.43 for Amax and from 0.40 to 1.01 for A50. These values decreased from 0.28 to 0.92 for Amax and from 0.22 to 0.66 for A50 for 68 Ga acquisition. The results were not significantly different when imaging phantoms in the off-centre position with 3 scattering sources. Measurements performed with the four 3D-printed phantoms showed a good correlation between theoretical and measured activity in simulated tumours, with r 2 values of 0.99 and 0.97 obtained for 18F and 68Ga, respectively., Conclusion: We found that the clinical SiPM-based PET system was close to that obtained with a dedicated small-animal PET device. This study showed the ability of such a system to image four rats simultaneously and to perform quantification analysis for radionuclides commonly used in oncology., (© 2023. Springer Nature Switzerland AG.)

Given the constant pressure to increase patient throughput while respecting radiation protection, global body PET image quality (IQ) is not satisfactory in all patients. We first studied the association between IQ and other variables, in particular body habitus, on a digital PET/CT. Second, to improve and homogenize IQ, we evaluated a deep learning PET denoising solution (Subtle PET TM ) using convolutional neural networks. We analysed retrospectively in 113 patients visual IQ (by a 5-point Likert score in two readers) and semi-quantitative IQ (by the coefficient of variation in the liver, CV liv ) as well as lesion detection and quantification in native and denoised PET. In native PET, visual and semi-quantitative IQ were lower in patients with larger body habitus ( p < 0.0001 for both) and in men vs. women ( p ≤ 0.03 for CV liv ). After PET denoising, visual IQ scores increased and became more homogeneous between patients (4.8 ± 0.3 in denoised vs. 3.6 ± 0.6 in native PET; p < 0.0001). CV liv were lower in denoised PET than in native PET, 6.9 ± 0.9% vs. 12.2 ± 1.6%; p < 0.0001. The slope calculated by linear regression of CV liv according to weight was significantly lower in denoised than in native PET ( p = 0.0002), demonstrating more uniform CV liv . Lesion concordance rate between both PET series was 369/371 (99.5%), with two lesions exclusively detected in native PET. SUV max and SUV peak of up to the five most intense native PET lesions per patient were lower in denoised PET ( p < 0.001), with an average relative bias of -7.7% and -2.8%, respectively. DL-based PET denoising by Subtle PET TM allowed [ 18 F]FDG PET global image quality to be improved and homogenized, while maintaining satisfactory lesion detection and quantification. DL-based denoising may render body habitus adaptive PET protocols unnecessary, and pave the way for the improvement and homogenization of PET modalities.

Introduction: The yield per elution of a 68 Ge/ 68 Ga generator decreases during its lifespan. This affects the number of patients injected per elution or the injected dose per patient, thereby negatively affecting the cost of examinations and the quality of PET images due to increased image noise. We aimed to investigate whether AI-based PET denoising can offset this decrease in image quality parameters., Methods: All patients addressed to our PET unit for a 68 Ga-DOTATOC PET/CT from April 2020 to February 2021 were enrolled. Forty-four patients underwent their PET scans according to Protocol&#95;FixedDose (150 MBq) and 32 according to Protocol&#95;WeightDose (1.5 MBq/kg). Protocol&#95;WeightDose examinations were processed using the Subtle PET software (Protocol&#95;WeightDose AI ). Liver and vascular SUV mean were recorded as well as SUVmax, SUVmean and metabolic tumour volume (MTV) of the most intense tumoural lesion and its background SUVmean. Liver and vascular coefficients of variation (CV), tumour-to-background and tumour-to-liver ratios were calculated., Results: The mean injected dose of 2.1 (0.4) MBq/kg per patient was significantly higher in the Protocol&#95;FixedDose group as compared to 1.5 (0.1) MBq/kg for the Protocol&#95;WeightDose group. Protocol&#95;WeightDose led to noisier images than Protocol&#95;FixedDose with higher CVs for liver (15.57% ± 4.32 vs. 13.04% ± 3.51, p = 0.018) and blood-pool (28.67% ± 8.65 vs. 22.25% ± 10.37, p = 0.0003). Protocol&#95;WeightDose AI led to less noisy images than Protocol&#95;WeightDose with lower liver CVs (11.42% ± 3.05 vs. 15.57% ± 4.32, p < 0.0001) and vascular CVs (16.62% ± 6.40 vs. 28.67% ± 8.65, p < 0.0001). Tumour-to-background and tumour-to-liver ratios were lower for protocol&#95;WeightDose AI : 6.78 ± 3.49 vs. 7.57 ± 4.73 ( p = 0.01) and 5.96 ± 5.43 vs. 6.77 ± 6.19 ( p < 0.0001), respectively. MTVs were higher after denoising whereas tumour SUVmax were lower: the mean% differences in MTV and SUVmax were + 11.14% (95% CI = 4.84-17.43) and -3.92% (95% CI = -6.25 to -1.59)., Conclusion: The degradation of PET image quality due to a reduction in injected dose at the end of the 68 Ge/ 68 Ga generator lifespan can be effectively counterbalanced by using AI-based PET denoising., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Quak, Weyts, Jaudet, Prigent, Foucras and Lasnon.)

Purpose: Single-photon emission computed tomography has found an important place in preclinical cancer research. Nevertheless, the cameras dedicated to small animals are not widely available. The present study aimed to assess the feasibility of imaging small animals by a newly released 360° cadmium zinc telluride camera (VERITON, Spectrum Dynamics, Israel) dedicated to human patients., Procedures: A cylindrical phantom containing hot spheres was used to evaluate the intrinsic performance of the camera first without the presence of background activity and then with two contrasts between background and hot spheres (1/4 and 1/10). Acquisitions were repeated with different scan durations (10 and 20 min), two tested radioisotopes (Tc-99 m and I-123), and a set of reconstruction parameters (10 iterations [i] 8 subsets [s], 10i16s, 10i32s). A 3D-printed phantom mimicking a rat with four subcutaneous tumours was then used to test the camera under preclinical conditions., Results: The results obtained from the micro-hollow sphere phantom showed that it was possible to visualize spheres with an inner diameter of 3.95 mm without background activity. Moreover, spheres with diameters of 4.95 mm can be seen in the condition of high contrast between background and spheres (1/10) and 7.86 mm with lower contrast (1/4). The rat-sized phantom acquisitions showed that 10- and 8-mm subcutaneous tumours were visible with a good contrast obtained for the two radioisotopes tested in this study. Both Tc-99 m and I-123 measurements demonstrated that a 10-min acquisition reconstructed with an ordered subset expectation maximization algorithm applying 10i32s was optimal to obtain sufficient image quality in terms of noise, resolution, and contrast., Conclusion: Phantom results showed the ability of the system to detect sub-centimetre lesions for various radioisotopes. It seemed feasible to image small animals using a 360° cadmium zinc telluride gamma camera for preclinical cancer research purposes., (© 2022. The Author(s), under exclusive licence to World Molecular Imaging Society.)

This study aimed to investigate if combining clinical characteristics with pre-therapeutic 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET) radiomics could predict the presence of molecular alteration(s) in key molecular targets in lung adenocarcinoma. This non-interventional monocentric study included patients with newly diagnosed lung adenocarcinoma referred for baseline PET who had tumour molecular analyses. The data were randomly split into training and test datasets. LASSO regression with 100-fold cross-validation was performed, including sex, age, smoking history, AJCC cancer stage and 31 PET variables. In total, 109 patients were analysed, and it was found that 63 (57.8%) patients had at least one molecular alteration. Using the training dataset (n = 87), the model included 10 variables, namely age, sex, smoking history, AJCC stage, excessKustosis&#95;HISTO, sphericity&#95;SHAPE, variance&#95;GLCM, correlation&#95;GLCM, LZE&#95;GLZLM, and GLNU&#95;GLZLM. The ROC analysis for molecular alteration prediction using this model found an AUC equal to 0.866 (p < 0.0001). A cut-off value set to 0.48 led to a sensitivity of 90.6% and a positive likelihood ratio (LR+) value equal to 2.4. After application of this cut-off value in the unseen test dataset of patients (n = 22), the test presented a sensitivity equal to 90.0% and an LR+ value of 1.35. A clinico-metabolic 18 F-FDG PET phenotype allows the detection of key molecular target alterations with high sensitivity and negative predictive value. Hence, it opens the way to the selection of patients for molecular analysis.

Purpose: We investigated whether artificial intelligence (AI)-based denoising halves PET acquisition time in digital PET/CT., Methods: One hundred ninety-five patients referred for [ 18 F]FDG PET/CT were prospectively included. Body PET acquisitions were performed in list mode. Original "PET90" (90 s/bed position) was compared to reconstructed ½-duration PET (45 s/bed position) with and without AI-denoising, "PET45AI and PET45". Denoising was performed by SubtlePET™ using deep convolutional neural networks. Visual global image quality (IQ) 3-point scores and lesion detectability were evaluated. Lesion maximal and peak standardized uptake values using lean body mass (SUL max and SUL peak ), metabolic volumes (MV), and liver SUL mean were measured, including both standard and EARL 1 (European Association of Nuclear Medicine Research Ltd) compliant SUL. Lesion-to-liver SUL ratios (LLR) and liver coefficients of variation (CV liv ) were calculated., Results: PET45 showed mediocre IQ (scored poor in 8% and moderate in 68%) and lesion concordance rate with PET90 (88.7%). In PET45AI, IQ scores were similar to PET90 (P = 0.80), good in 92% and moderate in 8% for both. The lesion concordance rate between PET90 and PET45AI was 836/856 (97.7%), with 7 lesions (0.8%) only detected in PET90 and 13 (1.5%) exclusively in PET45AI. Lesion EARL 1 SUL peak was not significantly different between both PET (P = 0.09). Lesion standard SUL peak , standard and EARL1 SUL max , LLR and CV liv were lower in PET45AI than in PET90 (P < 0.0001), while lesion MV and liver SUL mean were higher (P < 0.0001). Good to excellent intraclass correlation coefficients (ICC) between PET90 and PET45AI were observed for lesion SUL and MV (ICC ≥ 0.97) and for liver SUL mean (ICC ≥ 0.87)., Conclusion: AI allows [ 18 F]FDG PET duration in digital PET/CT to be halved, while restoring degraded ½-duration PET image quality. Future multicentric studies, including other PET radiopharmaceuticals, are warranted., (© 2022. The Author(s).)

Despite the feminization of the medical workforce, women do not have the same career perspectives as men. In nuclear medicine, little information is available on the sex gap regarding prominent author positions in scientific articles. Therefore, the purpose of this study was to evaluate recent trends in the sex distribution of first and last authorship of articles published in nuclear medicine journals. Methods: We conducted a bibliometric analysis of first and last author sex of articles published from 2014 to 2020 in 15 nuclear medicine journals. Manuscript title, article type, journal impact factor, date of publication, and first and last name and country of provenance of first and last authors were noted. The Gender API software was used to determine author sex. All statistics were descriptive. Results: Women represented 32.8% of first authors and 19.6% of last authors. Female authorship increased from 28.2% (428 of 1,518 articles) in 2014 to 35.5% (735 of 2,069 articles; relative increase, 72%) in 2020 ( P < 0.001) for first authors and from 15.6% (237 of 1,518 articles) in 2014 to 20.5% (424 of 2,069 articles; relative increase, 79%) in 2020 ( P < 0.001) for last authors. Parity was forecast for 2035 for first authors and 2052 for last authors. Female authorship increased in Europe for first authors ( P = 0.014) and last authors ( P < 0.001), in high-ranking journals for first authors ( P = 0.004) and last authors ( P < 0.001), and in other journal ranks for last authors ( P = 0.01). Female first and last authorship rose for original articles ( P = 0.02 and P = 0.01, respectively) and case reports ( P < 0.001 and P = 0.002, respectively). Regarding collaborations, the proportion of articles produced by male first and last authors decreased from 62.2% in 2014 to 52.9% in 2020 in favor of female first and last authors (odds ratio, 1.07; P < 0.001), male first and female last authors (odds ratio, 1.05; P < 0.001), and female first and male last authors (odds ratio, 1.03; P < 0.001). Conclusion: Female first and last authorship in nuclear medicine journals increased substantially from 2014 to 2020, in particular in high-ranking journals, in Europe, and for original articles and case reports. Male-to-male collaborations decreased by 10% in favor of all other collaborations. Parity can be foreseen in a few decades., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

This article reviews the current evolution and future directions in PET/CT technology focusing on three areas: time of flight, image reconstruction, and data-driven gating. Image reconstruction is considered with advances in point spread function modelling, Bayesian penalised likelihood reconstruction, and artificial intelligence approaches. Data-driven gating is examined with reference to respiratory motion, cardiac motion, and head motion. For each of these technological advancements, theory will be briefly discussed, benefits of their use in routine practice will be detailed and potential future developments will be discussed. Representative clinical cases will be presented, demonstrating the huge opportunities given to the PET community by hardware and software advances in PET technology when it comes to lesion detection, disease characterization, accurate quantitation and quicker scans. Through this review, hospitals are encouraged to embrace, evaluate and appropriately implement the wide range of new PET technologies that are available now or in the near future, for the improvement of patient care., Competing Interests: Conflict of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

At present, 18 F-fluorodesoxyglucose ( 18 FDG) positron emission tomography (PET)/computed tomography (CT) cannot be used to omit a bone marrow biopsy (BMB) among initial staging procedures in follicular lymphoma (FL). The additional diagnostic value of skeletal textural features on baseline 18 FDG-PET/CT in diffuse large B-cell lymphoma (DLBCL) patients has given promising results. The aim of this study is to evaluate the value of 18 FDG-PET/CT radiomics for the diagnosis of bone marrow involvement (BMI) in FL patients. This retrospective bicentric study enrolled newly diagnosed FL patients addressed for baseline 18 FDG PET/CT. For visual assessment, examinations were considered positive in cases of obvious bone focal uptakes. For textural analysis, the skeleton volumes of interest (VOIs) were automatically extracted from segmented CT images and analysed using LifeX software. BMB and visual assessment were taken as the gold standard: BMB -/PET - patients were considered as bone- NEGATIVE patients, whereas BMB +/PET -, BMB -/PET + and BMB +/PET + patients were considered bone- POSITIVE patients. A LASSO regression algorithm was used to select features of interest and to build a prediction model. Sixty-six consecutive patients were included: 36 bone- NEGATIVE (54.5%) and 30 bone- POSITIVE (45.5%). The LASSO regression found variance &#95;GLCM , correlation &#95;GLCM , joint entropy &#95;GLCM and busyness &#95;NGLDM to have nonzero regression coefficients. Based on ROC analysis, a cut-off equal to - 0.190 was found to be optimal for the diagnosis of BMI using PET pred.score. The corresponding sensitivity, specificity, PPV and NPV values were equal to 70.0%, 83.3%, 77.8% and 76.9%, respectively. When comparing the ROC AUCs with using BMB alone, visual PET assessment or PET pred.score, a significant difference was found between BMB versus visual PET assessments (p = 0.010) but not between BMB and PET pred.score assessments (p = 0.097). Skeleton texture analysis is worth exploring to improve the performance of 18 FDG-PET/CT for the diagnosis of BMI at baseline in FL patients., (© 2021. The Author(s).)

In DLBCL, the Deauville scoring system (DS) is the standard for PET/CT response assessment. An alternative system, based on the semi-quantitative change in standardized uptake values, namely ΔSUVmax, has been reported to be more objective than the DS. We aimed to compare ΔSUVmax and DS for risk stratification of DLBCL patients on end-of-treatment (EoT) PET. 108 consecutive patients were included. 2-year EFS Kaplan-Meier survival analyses and Cox regression models were performed. 2-year EFS was significantly different between favorable ΔSUVmax (favΔ < -86.5%) and unfavorable ΔSUVmax (unfavΔ ≥ -86.5%) patients: 100.0% ± 0.0 versus 58.3% ± 14.2 ( p  = 0.001). On Cox multivariable regression, ΔSUVmax status was the only independent predictor of 2-year EFS, outperforming DS. Therefore, ΔSUVmax should be computed for non-responder patients, especially DS4, as the 2-year EFS is not different between responders and non-responders in the case of favΔ. Further studies are needed in order to confirm this hypothesis.

Aim: To perform a comprehensive analysis of discordances between contrast-enhanced CT (ceCT) and 18 F-FDG PET/CT in the evaluation of the extra-cerebral treatment monitoring in patients with stage IV melanoma., Materials and Methods: We conducted a retrospective monocentric observational study over a 3-year period in patients referred for 18 F-FDG PET/CT and ceCT in the framework of therapy monitoring of immune checkpoint (ICIs) as of January 2017. Imaging reports were analyzed by two physicians in consensus. The anatomical site responsible for discordances, as well as induced changes in treatment were noted., Results: Eighty patients were included and 195 pairs of scans analyzed. Overall, discordances occurred in 65 cases (33%). Eighty percent of the discordances (52/65) were due to 18 F-FDG PET/CT scans upstaging the patient. Amongst these discordances, 17/52 (33%) led to change in patient's management, the most frequent being radiotherapy of a progressing site. ceCT represented 13/65 (20%) of discordances and induced changes in patients' management in 2/13 cases (15%). The most frequent anatomical site involved was subcutaneous for 18 F-FDG PET/CT findings and lung or liver for ceCT., Conclusions: Treatment monitoring with 18 F-FDG PET/CT is more efficient than ceCT and has a greater impact in patient's management.

Background: Immune checkpoint inhibitors (ICIs) have significantly improved survival in advanced melanoma. There is a need for robust biomarkers to identify patients who do not respond. We analysed 14 baseline 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) metrics and their evolution to assess their correlation with patient outcome, compared with 7 established biological markers and 7 clinical variables., Methods: We conducted a retrospective monocentric observational study of 29 patients with advanced melanoma who underwent baseline 18 F-FDG PET/CT, followed by an early monitoring PET/CT (iPET) scan after 1 month of treatment and follow-up studies at 3rd (M3PET) and 6th month (M6PET). 18 F-FDG uptake in immune organs (spleen, bone marrow, ileocecal valve) and derived spleen-to-liver (SLR) and bone-to-liver (BLR) ratios were reviewed by two PET readers for reproducibility analysis purposes including 14 PET variables. The most reproducible indexes were used for evaluation as predictors of overall survival (OS) in comparison with PET response using imPERCIST5, whole-body metabolic active tumour volume (WB-MATV) and biological parameters (lactate dehydrogenases (LDH), reactive protein c (CRP), white blood count (WBC), absolute lymphocyte count (ALC), neutrophil to lymphocyte ratio (NLR) and derived neutrophils to lymphocyte ratio)., Results: Strong reproducibility's (intraclass coefficients of correlation (ICC) > 0.90) were observed for spleen anterior SUV peak , spleen MV, spleen TLG, spleen length and BLR mean . ICC for SLR mean and ileocecal SUV mean were 0.86 and 0.65, respectively. In the 1-year OS 1 group, SLR mean tended to increase at each time point to reach a significant difference at M6-PET (p = 0.019). The same trends were observed with spleen SUV peak anterior and spleen length. In the 1-year OS 0 group, a significative increase of spleen length was found at iPET, as compared with baseline PET (p = 0.014) and M3-PET (p = 0.0239). Univariable Kaplan-Meier survival analysis found that i%var spleen length, M3%var SLR mean , baseline LDH, i%var NLR and response at M6PET were all predictors of 1-year OS., Conclusions: SLR mean is recommended as a prognosticator in melanoma patients under immunotherapy: its increase greater than 25% at 3 months, compared with baseline, was associated with poor outcome after ICIs.

Background Early reports show the unequal effect the COVID-19 pandemic might have on men versus women engaged in medical research. Purpose To investigate whether the COVID-19 pandemic has had an impact on scientific publishing by female physicians in medical imaging. Materials and Methods The authors conducted a descriptive bibliometric analysis of the gender of the first and last authors of manuscripts submitted to the top 50 medical imaging journals from March to May 2020 ( n = 2480) compared with the same period of the year in 2018 ( n = 2238) and 2019 ( n = 2355). Manuscript title, date of submission, first and last names of the first and last authors, journal impact factor, and author country of provenance were recorded. The Gender-API software was used to determine author gender. Statistical analysis comprised χ 2 tests and multivariable logistic regression. Results Percentages of women listed as first and last authors were 31.6% (1172 of 3711 articles) and 19.3% (717 of 3711 articles), respectively, in 2018-2019 versus 32.3% (725 of 2248 articles) and 20.7% (465 of 2248 articles) in 2020 ( P = .61 and P = .21, respectively). For COVID-19-related articles, 35.2% (89 of 253 articles) of first authors and 20.6% (52 of 253 articles) of last authors were women. No associations were found between first- and last-author gender, year of publication, and region of provenance. First and last authorship of high-ranking articles was not in favor of North American women whatever the year (odds ratio [OR], 0.79 [ P = .05] and 0.72 [ P = .02], respectively). Higher rates of female last authorship of high-ranking articles were observed in Europe ( P = .003) and of female first authorship of low-ranking publications in Asia in 2020 (OR, 1.38; 95% CI: 0.98, 1.92; P = .06). Female first and last authorship of COVID-19-related articles was overrepresented for lowest-rank publications ( P = .02 and P = .01, respectively). Conclusion One in three first authors and one in five last authors were women in 2018-2019 and 2020, respectively. Although the first 2020 lockdown did not diminish the quantity of women-authored publications, the impact on the quality was variable. ©RSNA, 2021 See also the editorial by Robbins and Khosa in this issue.

Aim: To evaluate the use of digital 18 F-FDG PET/CT with small-voxels reconstruction for detecting in-transit metastases in melanoma patients with primary lesion located on the upper or lower limbs, in comparison with standard reconstruction and European Association of Nuclear Medicine Research limited (EARL)-compliant reconstruction mimicking former generation PET systems., Methods: Forty-six PET examinations acquired in list mode on a Vereos digital PET/CT system were reconstructed with (1) the standard reconstruction [2 iterations, 10 subsets (2i10s), point-spread function (PSF) modelling and time-of-flight enabled, no post-filtering and voxel size of 2 mm], (2) a small-voxel reconstruction using 1 mm voxels otherwise using the same parameters, (3) an EARL-compliant reconstruction mimicking a former generation system. Comparison of results across these reconstructions was made for a blind randomized review using a 3-point scale for the presence of in-transit metastases and image quality as well as for tumour-to-background (T/B) ratios and noise level in reference organs., Results: Seven of the thirty-two EARL-compliant images classified as negative moved to positive on 1mm PSF images, and 5 of the 6 EARL-compliant images classified as indeterminate moved to positive on 1mm PSF images (P = 0.01). Amongst a total of 20 PET examinations classified as positive using the 1mm PSF reconstruction, fifteen were considered true positive, five false positive results occurred. Twenty-four patients with 1 mm PSF images were classified as negative, none of those under active surveillance experienced in-transit metastases during the 17 months following their PET examination. The positive likelihood ratio for the 1 mm reconstruction was much higher than that observed for EARL-compliant images (14.7 vs 7.82). Importantly, negative likelihood ratios for the 1 mm and 1mm PSF reconstruction were almost perfect. Compared to EARL-compliant data, T/B ratios extracted from the 1mm PSF showed a 2.84-fold increase (P < 0.001). A similar pattern of statistically significant increase was observed for noise level in organs of reference. Image quality for the torso was found to be significantly lower for 1mm PSF reconstruction (P = 0.03). Image quality for the limbs was found to be better for 1mm PSF (P < 0.001)., Conclusion: Digital PET with small-voxel reconstruction brings an additional value for the detection of in-transit metastases by reducing the number of indeterminate findings and making up for falsely negative scans using former generation PET systems. An acquisition encompassing lower or upper limbs as appropriate should be performed.

Purpose: Until now, results evaluating the expression of PSMA in ovarian cancer were sparse and contradictory. The aim was to reinvestigate the feasibility of a PSMA targeted theranostic approach in epithelial ovarian cancers with data from the tumour bank of a referring cancer centre., Materials and Methods: The OvaRessources Biological Resources Center database was screened from January 2004 to December 2017 to seek patients referred for the initial management of a serous epithelial ovarian cancer and for whom peritoneal histological samples were available in the tumour bank. Immunodetection of PSMA was performed to assess its cellular and neovascular expression. Slides were controlled by a certified pathologist, recorded as tiled tiff images and processed to compute the proportion of DAB stained surface., Results: Of the 51 patients identified by the database screening, 32 patients were included resulting in 57 samples (32 pre-chemotherapy and 25 post-chemotherapy histological samples). Nine patients were chemo-sensitive, 10 were partially chemo-sensitive and 13 were chemo-resistant/refractory. In the entire dataset, the expression of PSMA was quasi-inexistent: %DAB PSMA  = 0.04 (± 0.12) %. There was no significant difference in the %DAB PSMA of sensitive, partially sensitive and resistant/refractory patients. There was also no significant difference in %DAB PSMA in tumours before and after chemotherapy in the 25 patients for whom both samples were available., Conclusion: The present work demonstrates that PSMA expression is negligible and a fortiori non-sufficient to ensure its usefulness as a prognosticator or a target for a theranostic strategy in ovarian cancers.

Introduction: We aimed to investigate whether 18 F-FDG PET metabolic heterogeneity reflects the heterogeneity of estrogen receptor (ER) and progesterone receptor (PR) expressions within luminal non-metastatic breast tumors and if it could help in identifying patients with worst event-free survival (EFS)., Materials and Methods: On 38 PET high-resolution breast bed positions, a single physician drew volumes of interest encompassing the breast tumors to extract SUV max , histogram parameters and textural features. High-resolution immunochemistry (IHC) scans were analyzed to extract Haralick parameters and descriptors of the distribution shape. Correlation between IHC and PET parameters were explored using Spearman tests. Variables of interest to predict the EFS status at 8 years (EFS-8y) were sought by means of a random forest classification. EFS-8y analyses were then performed using univariable Kaplan-Meier analyses and Cox regression analysis. When appropriate, Mann-Whitney tests and Spearman correlations were used to explore the relationship between clinical data and tumoral PET heterogeneity variables., Results: For ER expression, correlations were mainly observed with 18 F-FDG histogram parameters, whereas for PR expression correlations were mainly observed with gray-level co-occurrence matrix (GLCM) parameters. The strongest correlations were observed between skewness&#95; ER and uniformity&#95; HISTO (ρ = -0.386, p = 0.017) and correlation&#95; PR and entropy&#95; GLCM (ρ = 0.540, p = 0.001), respectively. The median follow-up was 6.5 years and the 8y-EFS was 71.0%. Random forest classification found age, clinical stage, SUV max , skewness&#95; ER , kurtosis&#95; ER , entropy&#95; HISTO , and uniformity&#95; HISTO to be variables of importance to predict the 8y-EFS. Univariable Kaplan-Meier survival analyses showed that skewness&#95; ER was a predictor of 8y-EFS (66.7 ± 27.2 versus 19.1 ± 15.2, p = 0.018 with a cut-off value set to 0.163) whereas other IHC and PET parameters were not. On multivariable analysis including age, clinical stage and skewness&#95; ER , none of the parameters were independent predictors. Indeed, skewness&#95; ER was significantly higher in youngest patients (ρ = -0.351, p = 0.031) and in clinical stage III tumors (p = 0.023)., Conclusion: A heterogeneous distribution of ER within the tumor in IHC appeared as an EFS-8y prognosticator in luminal non-metastatic breast cancers. Interestingly, it appeared to be correlated with PET histogram parameters which could therefore become potential non-invasive prognosticator tools, provided these results are confirmed by further larger and prospective studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Aide, Elie, Blanc-Fournier, Levy, Salomon and Lasnon.)

Background: The common endocrine disorder primary hyperparathyroidism (PHPT) can be cured by surgery. Preoperative localization of parathyroid adenoma (PTA) by imaging is a prerequisite for outpatient minimally invasive parathyroidectomy (MIP). Compared to inpatient bilateral cervical exploration (BCE) which is performed if imaging is inconclusive, MIP is superior in terms of cure and complication rates and less costly. The imaging procedure F18-choline (FCH) PET/CT outperforms Tc99m-sestaMIBI (MIBI) SPECT/CT for PTA localization, but it is much costlier. The aim of this study is to identify the most efficient first-line imaging modality for optimal patient care in PHPT without added cost to society., Methods: We will conduct a multicenter open diagnostic intervention randomized phase III trial comparing two diagnostic strategies in patients with PHPT: upfront FCH PET/CT versus MIBI SPECT/CT. The primary endpoint is the proportion of patients in whom the first-line imaging method results in successful MIP and cure. Follow-up including biological tests will be performed 1 and 6 months after surgery. The main secondary endpoint is the social cost of both strategies. Other secondary endpoints are as follows: FCH PET/CT and MIBI SPECT/CT diagnostic performance, performance of surgical procedure and complication rate, FCH PET/CT inter- and intra-observer variability and optimization of FCH PET/CT procedure. Fifty-eight patients will be enrolled and randomized 1:1., Discussion: FCH PET/CT is a highly efficient but expensive imaging test for preoperative PTA localization and costs three to four times more than MIBI SPECT/CT. Whether FCH PET/CT improves patient outcomes compared to the reference standard MIBI SPECT/CT is unknown. To justify its added cost, FCH PET/CT-guided parathyroid surgery should lead to improved patient management, resulting in higher cure rates and fewer BCEs and surgical complications. In the previous phase II APACH1 study, we showed that second-line FCH PET/CT led to a cure in 88% of patients with negative or inconclusive MIBI SPECT/CT. BCE could be avoided in 75% of patients and surgical complication rates were low. We therefore hypothesize that upfront FCH PET/CT would improve patient care in PHPT and that the reduction in clinical costs would offset the increase in imaging costs., Trial Registration: NCT04040946 , registered August 1, 2019.  Protocol version Version 2.1 dated from 2020/04/23.

Purpose: To seek for the minimal duration per bed position with a digital PET system without compromising image quality and lesion detection in patients requiring fast 18 F-FDG PET imaging., Materials and Methods: 19 cancer patients experiencing pain or dyspnea and 9 pediatric patients were scanned on a Vereos system. List mode data were reconstructed with decreasing time frame down to 10 s per bed position. Noise was evaluated in the liver, blood pool and muscle, and using target-to-background ratios. Five PET readers recorded image quality, number of clinically relevant foci and of involved anatomical sites in reconstructions ranging from 60 to 10 s per bed position, compared to the standard 90 s reconstruction., Results: The following reconstructions, which harboured a noise not significantly higher than that of the standard reconstruction, were selected for clinical evaluation: 1iterations/10 subsets/20 sec (1i10 s20 sec ), 1i10 s30 sec , and 2i10 sPSF60 sec. Only the 60 s per bed acquisition displayed similar target-to-background ratios compared to the standard reconstruction, but mean ratios were still higher than 2.0 for the 30 s reconstruction. Inter-rater agreement for the number of involved anatomical sites and detected lesion was good or almost perfect (Kappa: 0.64-0.91) for all acquisitions. In particular, kappa for the 30 s per bed acquisition was 0.78 and 0.91 for lesion and anatomical sites number, respectively. Intra-rater agreement was also excellent for the 30 s reconstruction (kappa = 0.72). Median estimated total PET acquisition time for the 1i10 s30 sec , and the standard reconstruction were 4 and 12 min, respectively., Conclusions: Fast imaging is feasible with state-of-the-art PET systems. Acquisitions of 30 s per bed position are feasible with the Vereos system, requiring optimization of reconstruction parameters., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To explore the prognostic value of positron emission tomography (PET) radiomic features in the field of diffuse large B cell lymphoma (DLBCL) treated with a first-line immunochemotherapy., Methods: One-hundred thirty-two patients newly diagnosed with DLBCL were retrospectively included. PET studies were reconstructed using an ordered subset expectation maximisation algorithm with point spread function modelling. The total metabolic tumour volume (MTV) was recorded for each patient, and the volume of interest structure of the largest target lesion was used to compute 18 F-FDG textural parameters. Data was randomly split into training and validation datasets. Optimal cutoff values were determined by means of 2-year event-free survival (EFS) ROC analyses. Two-year EFS analyses were performed using Kaplan-Meier survival analyses and univariable and multivariable Cox regression models., Results: The median follow-up was 27 months, and the 2-year event-free survival (2y-EFS) was 77.3% in the entire population. ROC analyses for the 2y-EFS reached statistical significance for total MTV as well as four second-order metrics (homogeneity, contrast, correlation, dissimilarity) and five third-order metrics (LZE (Long-Zone Emphasis), LZLGE (Long-Zone Low-Grey Level Emphasis), LZHGE (Long-Zone High-Grey Level Emphasis), GLNU (Grey-Level Non-Uniformity) and ZP (Zone Percentage)). LZHGE displayed the highest ROC analysis accuracy (acc. = 0.76) and the best discriminant value on univariable Kaplan-Meier analysis (p < 0.0001, HR = 4.54). On multivariable analysis, including IPIaa, total MTV and LZHGE, LZHGE was the only independent predictor of 2y-EFS. These results were confirmed on the validation dataset., Conclusions: Baseline 18 F-FDG PET heterogeneity of the largest lymphoma lesion is a promising predictor of 2y-EFS in newly diagnosed DLBCL treated with immunochemotherapy., Key Points: • 18 F-FDG metabolic heterogeneity emerges as a new tool for survival prognostication of patients and has been explored in many solid tumours with promising results. • Baseline 18 F-FDG PET heterogeneity of the largest lymphoma lesion is an independent predictor of 2y-EFS in newly diagnosed DLBCL treated with immunochemotherapy. • DLBCL patients presenting with a heterogeneous tumour displayed a worse prognosis.

Background: Anal cancer is a relatively rare tumor of which incidence increases in developed countries. 18 F-FDG PET has been increasingly used for its post radio-chemotherapy evaluation. However, several authors have reported the risk of local false-positive findings leading to low specificity and positive predictive values. These false-positive results could be due to post-radiotherapy inflammation or infection but certainly also to physiological anal canal uptake that is observed on a regular basis in clinical practice. The purpose of this prospective study (NCT03506529; HYPHYCA) was therefore to seek predictive factors of physiological anal canal hypermetabolism., Materials and Methods: Over a 2-month period, patients aged 18 years old and more, referred for 18 F-FDG PET-CT at two EARL-accredited PET centers were included, after obtaining their informed and written consent. They were asked to fill in a questionnaire including seven closed questions about usual intestinal transit, ongoing medications relative to intestinal transit, history of digestive, and anal and/or pelvic diseases. Age, gender, and body mass index (BMI) were recorded. A single nuclear medicine physician visually and quantitatively analyzed anal canal uptake (SUV max&#95;EARL ) and assessed visual rectal content (air, feces, or both) and the largest rectal diameter (mm)., Results: Six hundred and thirteen patients were included (sex ratio F/M = 0.99) and 545 (89%) questionnaires were entirely completed. Significantly more males presented anal canal hypermetabolism (sex ratio (M/F) = 1.18 versus 0.85, p = 0.048). Moreover, patients with anal canal hypermetabolism had higher BMI (27.6 (5.7) kg/m 2 versus 23.9 (4.5) kg/m 2 , p < 0.0001), higher rate of hemorrhoid history (43% versus 27%, p = 0.016), and higher rate of rectum filled with only feces (21% versus 12%, p = 0.019) as compared to patients with no anal canal uptake. On logistic regression, all these variables were found to be independent predictors of the occurrence of an anal canal hypermetabolism. Odds ratio were 1.16 (1.12-1.20) per unit of BMI (kg/m 2 ) (p < 0.0001), 1.48 (1.04-2.11) for males (p = 0.030), 1.64 (1.10-2.45) for hemorrhoids history (p = 0.016), and 1.94 (1.147-3.22) for the rectum filled with only feces (p = 0.010)., Conclusion: According to our study, the predictive factors of physiological anal canal hypermetabolism are high BMI, male gender, hemorrhoid history, and rectum filled with only feces. This may pave the way to a more specific interpretation of post radio-chemotherapy PET evaluations of anal canal cancer, provided that other studies are conducted in this specific population., Trial Registration: This prospective study was registered at Clinicaltrial.gov: NCT03506529; HYPHYCA on April 24, 2018.

Aims: (1) To perform a comprehensive analysis of the time elapsed between the last G-CSF injection and the PET/CT examination on the biodistribution of 18 F-FDG, with emphasis on liver, spleen, and bone marrow uptake, and (2) to investigate whether an inversion of the liver to spleen ratio affects the Deauville scoring., Materials and Methods: Retrospectively included were 74 consecutive diffuse large B cell lymphoma (DLBCL) patients referred for baseline and interim examinations and receiving immunochemotherapy with various G-CSF regimens. A comprehensive evaluation considering baseline metabolic active tumour volume (MATV), factors affecting liver uptake, the type of G-CSF, and the time elapsed between chemotherapy/G-CSF and interim PET/CTs was performed., Results: Mean (± SD) percentage variations between baseline and interim PET/CTs (i-PET/CT) for bone marrow (%Variation&#95; BONE ), liver (%Variation&#95; LIVER ) and spleen (%Variation&#95; SPLEEN ) were equal to 32.0 ± 46.9%, 16.1 ± 42.8%, and 10.6 ± 51.1 %, respectively. %Variation&#95; LIVER and %Variation&#95; SPLEEN were higher in patients using lenograstim, but this was linked to lower uptakes at baseline and was therefore likely not due to G-CSF itself. The mean delay between G-CSF injection and i-PET/CT acquisition was not an independent explanatory variable for %Variation&#95; BONE , %Variation&#95; LIVER , and %Variation&#95; SPLEEN . On the contrary, %Variation&#95; BONE and %Variation&#95; SPLEEN were negatively correlated to the time-lapse between the end of chemotherapy and i-PET/CT: ρ = - 0.342 (p = 0.010) and ρ = - 0.529 (p < 0.0001), respectively. Patients with a time-lapse since the last injection of chemotherapy < 17 days displayed higher bone and spleen SUVmax EARL . %Variation&#95; LIVER was positively correlated to baseline MATV: ρ = 0.243 (p = 0.039). Patients displaying a high baseline MATV ≥ 177 cc had significantly lower liver SUVmax EARL at baseline. This difference was no longer observed at i-PET/CT, after tumours had shrunk., Conclusions: Neither the type of G-CSF used nor the time elapsed between its last injection and i-PET/CT examination independently influences bone, hepatic, or splenic uptakes at i-PET/CT. The major determinant for the occurrence of a bone or spleen hypermetabolism on i-PET/CT is the time elapsed between the chemotherapy and the examination, which should be maintained above 15 days. Inversion of the liver to spleen ratio appeared to be due to increased spleen hypermetabolism on i-PET/CT, making unlikely an impact on the Deauville scoring.

An error occurred in the labelling of Fig. 3, where math symbols for SUV thresholds were inverted in panel b when the EARL threshold was applied to the PSF dataset and vice versa. This figure should read as follows: Fig. 3: Prognostic value of tumour SUVmax.

Background: To determine EARL-compliant prognostic SUV thresholds in a mature cohort of patients with locally advanced NSCLC, and to demonstrate how detrimental it is to use a threshold determined on an older-generation PET system with a newer PET/CT machine, and vice versa, or to use such a threshold with non-harmonized multicentre pooled data., Materials and Methods: This was a single-centre retrospective study including 139 consecutive stage IIIA-IIIB patients. PET data were acquired as per the EANM guidelines and reconstructed with unfiltered point spread function (PSF) reconstruction. Subsequently, a 6.3 mm Gaussian filter was applied using the EQ.PET (Siemens Healthineers) methodology to meet the EANM/EARL harmonizing standards (PSF EARL ). A multicentre study including non-EARL-compliant systems was simulated by randomly creating four groups of patients whose images were reconstructed with unfiltered PSF and PSF with Gaussian post-filtering of 3, 5, and 10 mm. Identification of optimal SUV thresholds was based on a two-fold cross-validation process that partitioned the overall sample into learning and validation subsamples. Proportional Cox hazards models were used to estimate age-adjusted and multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals. Kaplan-Meier curves were compared using the log rank test., Results: Median follow-up was 28 months (1-104 months). For the whole population, the estimated overall survival rate at 36 months was 0.39 [0.31-0.47]. The optimal SUV max cutoff value was 25.43 (95% CI: 23.41-26.31) and 8.47 (95% CI: 7.23-9.31) for the PSF and for the EARL-compliant dataset respectively. These SUV max cutoff values were both significantly and independently associated with lung cancer mortality; HRs were 1.73 (1.05-2.84) and 1.92 (1.16-3.19) for the PSF and the EARL-compliant dataset respectively. When (i) applying the optimal PSF SUV max cutoff on an EARL-compliant dataset and the optimal EARL SUV max cutoff on a PSF dataset or (ii) applying the optimal EARL compliant SUV max cutoff to a simulated multicentre dataset, the tumour SUV max was no longer significantly associated with lung cancer mortality., Conclusion: The present study provides the PET community with an EARL-compliant SUV max as an independent prognosticator for advanced NSCLC that should be confirmed in a larger cohort, ideally at other EARL accredited centres, and highlights the need to harmonize PET quantitative metrics when using them for risk stratification of patients.

Background: The aim of this study is to determine if the choice of the 18 F-FDG-PET protocol, especially matrix size and reconstruction algorithm, is of importance to discriminate between immunohistochemical subtypes (luminal versus non-luminal) in breast cancer with textural features (TFs)., Procedures: Forty-seven patients referred for breast cancer staging in the framework of a prospective study were reviewed as part of an ancillary study. In addition to standard PET imaging (PSF WholeBody ), a high-resolution breast acquisition was performed and reconstructed with OSEM and PSF (OSEM breast /PSF breast ). PET standard metrics and TFs were extracted. For each reconstruction protocol, a prediction model for tumour classification was built using a random forests method. Spearman coefficients were used to seek correlation between PET metrics., Results: PSF WholeBody showed lower numbers of voxels within VOIs than OSEM breast and PSF breast with median (interquartile range) equal to 130 (43-271), 316 (167-1042), 367 (107-1221), respectively (p < 0.0001). Therefore, using LifeX software, 28 (59%), 46 (98%) and 42 (89%) patients were exploitable with PSF WholeBody , OSEM breast and PSF breast , respectively. On matched comparisons, PSF breast reconstruction presented better abilities than PSF wholeBody and OSEM breast for the classification of luminal versus non-luminal breast tumours with an accuracy reaching 85.7% as compared to 67.8% for PSF wholeBody and 73.8% for OSEM breast . PSF breast accuracy, sensitivity, specificity, PPV and NPV were equal to 85.7%, 94.3%, 42.9%, 89.2%, 60.0%, respectively. Coarseness and ZLNU were found to be main variables of importance, appearing in all three prediction models. Coarseness was correlated with SUV max on PSF wholeBody images (ρ = - 0.526, p = 0.005), whereas it was not on OSEM breast (ρ = - 0.183, p = 0.244) and PSF breast (ρ = - 0.244, p = 0.119) images. Moreover, the range of its values was higher on PSF breast images as compared to OSEM breast , especially in small lesions (MTV < 3 ml)., Conclusions: High-resolution breast PET acquisitions, applying both small-voxel matrix and PSF modelling, appeared to improve the characterisation of breast tumours.

When evaluating 18 F-FDG PET images with the Deauville score (DS), the quantification of tumor and reference organs limits the problem of optical misinterpretation. Compared with conventional reconstruction algorithms, point-spread function (PSF) modeling increases SUVs significantly in tumors but only moderately in the liver, which could affect the DS. We investigated whether the choice of the reconstruction algorithm affects the DS and whether discordance affects the capability of 18 F-FDG PET to stratify lymphoma patients. Methods: Overall, 126 patients with diffuse large B-cell lymphoma were included (56 female and 70 male; median age, 65 y; range, 20-88 y). PET data were reconstructed with the unfiltered PSF method. Additionally, a 6-mm filter was applied to PSF images to meet the requirements of the EANM Research Ltd. (EARL) harmonization program from the European Association of Nuclear Medicine (EANM) (PSF EARL ). One hundred interim PET (i-PET) and 95 end-of-treatment PET (EoT-PET) studies were analyzed. SUV max in the liver and aorta was determined using automatic volumes of interest and compared with SUV max in the residual mass with the highest 18 F-FDG uptake. Results: For i-PET, using PSF and PSF EARL , we classified patients as responders and nonresponders in 60 and 40 cases versus 63 and 37 cases, respectively. Five cases of major discordance (5.0%) occurred (i.e., changes from responder to nonresponder). For Eot-PET, patients were classified using PSF and PSF EARL as responders and nonresponders in 69 and 26 cases versus 72 and 23 cases, respectively. Three cases of major discordance (3.2%) occurred. Concordance (Cohen unweighted κ) between the PSF and the PSF EARL DS was 0.82 (95% confidence interval, 0.73-0.91) for i-PET and 0.89 (95% confidence interval, 0.81-0.96) for EoT-PET. The median follow-up periods were 28.4 and 27.4 mo for i-PET and EoT-PET, respectively. Kaplan-Meier analysis showed statistically significant differences in progression-free survival and overall survival among responders and nonresponders no matter which reconstruction was used for i-PET and EoT-PET. Conclusion: Neither DS nor risk stratification of diffuse large B-cell lymphoma patients is affected by the choice of PET reconstruction. Specifically, the use of PSF is not an issue in routine clinical processes or in multicenter trials. These findings have to be confirmed in escalation and deescalation procedures based on early i-PET., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Aim: Our aim was (1) to evaluate the prevalence of steatosis in lymphoma patients and its evolution during treatment; (2) to evaluate the impact of hepatic steatosis on 18 F-FDG liver uptake; and (3) to study how hepatic steatosis affects the Deauville score (DS) for discriminating between responders and non-responders., Methods: Over a 1-year period, 358 PET scans from 227 patients [122 diffuse large B cell lymphoma (DLBCL), 57 Hodgkin lymphoma (HL) and 48 Follicular lymphoma (FL)] referred for baseline (n = 143), interim (n = 79) and end-of-treatment (EoT, n = 136) PET scans were reviewed. Steatosis was diagnosed on the unenhanced CT part of PET/CT examinations using a cut-off value of 42 Hounsfield units (HU). EARL-compliant SUL max were recorded on the liver and the tumour target lesion. DS were then computed., Results: Prevalence of steatosis at baseline, interim and EoT PET was 15/143 (10.5%), 6/79 (7.6%) and 16/136 (11.8%), respectively (p = 0.62).Ten out of 27 steatotic patients (37.0%) displayed a steatotic liver on all examinations. Six patients (22.2%) had a disappearance of hepatic steatosis during their time-course of treatment. Only one patient developed steatosis during his course of treatment. Liver SUL max values were significantly lower in the steatosis versus non-steatotic groups of patients for interim (1.66 ± 0.36 versus 2.15 ± 0.27) and EoT (1.67 ± 0.29 versus 2.17 ± 0.30) PET. CT density was found to be an independent factor that correlated with liver SUL max , while BMI, blood glucose level and the type of chemotherapy regimen were not. Using a method based on this correlation to correct liver SUL max , all DS4 steatotic patients on interim (n = 1) and EoT (n = 2) PET moved to DS3., Conclusions: Steatosis is actually a theoretical but not practical issue in most patients but should be recognised and corrected in appropriate cases, namely, for those patients scored DS4 with a percentage difference between the target lesion and the liver background lower than 30%.

Purpose: Our purpose was to evaluate the diagnostic and prognostic value of skeletal textural features (TFs) on baseline FDG PET in diffuse large B cell lymphoma (DLBCL) patients., Methods: Eighty-two patients with DLBCL who underwent a bone marrow biopsy (BMB) and a PET scan between December 2008 and December 2015 were included. Two readers blinded to the BMB results visually assessed PET images for bone marrow involvement (BMI) in consensus, and a third observer drew a volume of interest (VOI) encompassing the axial skeleton and the pelvis, which was used to assess skeletal TFs. ROC analysis was used to determine the best TF able to diagnose BMI among four first-order, six second-order and 11 third-order metrics, which was then compared for diagnosis and prognosis in disease-free patients (BMB-/PET-) versus patients considered to have BMI (BMB+/PET-, BMB-/PET+, and BMB+/PET+)., Results: Twenty-two out of 82 patients (26.8%) had BMI: 13 BMB-/PET+, eight BMB+/PET+ and one BMB+/PET-. Among the nine BMB+ patients, one had discordant BMI identified by both visual and TF PET assessment. ROC analysis showed that SkewnessH, a first-order metric, was the best parameter for identifying BMI with sensitivity and specificity of 81.8% and 81.7%, respectively. SkewnessH demonstrated better discriminative power over BMB and PET visual analysis for patient stratification: hazard ratios (HR), 3.78 (P = 0.02) versus 2.81 (P = 0.06) for overall survival (OS) and HR, 3.17 (P = 0.03) versus 1.26 (P = 0.70) for progression-free survival (PFS). In multivariate analysis accounting for IPI score, bulky status, haemoglobin and SkewnessH, the only independent predictor of OS was the IPI score, while the only independent predictor of PFS was SkewnessH., Conclusion: The better discriminative power of skeletal heterogeneity for risk stratification compared to BMB and PET visual analysis in the overall population, and more specifically in BMB-/PET- patients, suggests that it can be useful to identify diagnostically overlooked BMI.

The formulae for Dice and Jaccard indices used to assess volumes concordance should read as follows.

Background: The clinical validation of the EARL harmonization program for standardised uptake value (SUV) metrics is well documented; however, its potential for defining metabolic active tumour volume (MATV) has not yet been investigated. We aimed to compare delineation of MATV on images reconstructed using conventional ordered subset expectation maximisation (OSEM) with those reconstructed using point spread function modelling (PSF-reconstructed images), and either optimised for diagnostic potential (PSF) or filtered to meet the EANM/EARL harmonising standards (PSF 7 )., Methods: Images from 18 stage IIIA-IIIB lung cancer patients were reconstructed using all the three methods. MATVs were then delineated using both a 40% isocontour and a gradient-based method. MATVs were compared by means of Bland-Altman analyses, and Dice coefficients and concordance indices based on the unions and intersections between each pair of reconstructions (PSF vs OSEM, PSF 7 vs PSF and PSF 7 vs OSEM)., Results: Using the 40% isocontour method and taking the MATVs delineated on OSEM images as a reference standard, the use of PSF 7 images led to significantly higher Dice coefficients (median value = 0.96 vs 0.77; P < 0.0001) and concordance indices (median value = 0.92 vs 0.64; P < 0.0001) than those obtained using PSF images. The gradient-based methodology was less sensitive to reconstruction variability than the 40% isocontour method; Dice coefficients and concordance indices were superior to 0.8 for both PSF reconstruction methods. However, the use of PSF 7 images led to narrower interquartile ranges and significantly higher Dice coefficients (median value = 0.96 vs 0.94; P = 0.01) and concordance indices (median value = 0.89 vs 0.85; P = 0.003) than those obtained with PSF images., Conclusion: This study demonstrates that automatic contouring of lung tumours on EARL-compliant PSF images using the widely adopted automatic isocontour methodology is an accurate means of overcoming reconstruction variability in MATV delineation. Although gradient-based methodology appears to be less sensitive to reconstruction variability, the use of EARL-compliant PSF images significantly improved the Dice coefficients and concordance indices, demonstrating the importance of harmonised-images, even when more advanced contouring algorithms are used.

Background: This study evaluates the consistency of PET evaluation response criteria in solid tumours (PERCIST) and European Organisation for Research and Treatment of Cancer (EORTC) classification across different reconstruction algorithms and whether aligning standardized uptake values (SUVs) to the European Association of Nuclear Medicine acquisition (EANM)/EARL standards provides more consistent response classification., Materials and Methods: Baseline ( PET1 ) and response assessment ( PET2 ) scans in 61 patients with non-small cell lung cancer were acquired in protocols compliant with the EANM guidelines and were reconstructed with point-spread function (PSF) or PSF + time-of-flight (TOF) reconstruction for optimal tumour detection and with a standardized ordered subset expectation maximization (OSEM) reconstruction known to fulfil EANM harmonizing standards. Patients were recruited in three centres. Following reconstruction, EQ.PET, a proprietary software solution was applied to the PSF ± TOF data (PSF ± TOF.EQ) to harmonize SUVs to the EANM standards. The impact of differing reconstructions on PERCIST and EORTC classification was evaluated using standardized uptake values corrected for lean body mass (SUL)., Results: Using OSEM PET1 /OSEM PET2 (standard scenario), responders displayed a reduction of -57.5% ± 23.4 and -63.9% ± 22.4 for SUL max and SUL peak , respectively, while progressing tumours had an increase of +63.4% ± 26.5 and +60.7% ± 19.6 for SUL max and SUL peak respectively. The use of PSF ± TOF reconstruction impacted the classification of tumour response. For example, taking the OSEM PET1 /PSF ± TOF PET2 scenario reduced the apparent reduction in SUL in responding tumours (-39.7% ± 31.3 and -55.5% ± 26.3 for SUL max and SUL peak , respectively) but increased the apparent increase in SUL in progressing tumours (+130.0% ± 50.7 and +91.1% ± 39.6 for SUL max and SUL peak , respectively). Consequently, variation in reconstruction methodology (PSF ± TOF PET1 /OSEM PET2 or OSEM PET1 /PSF ± TOF PET2 ) led, respectively, to 11/61 (18.0%) and 10/61 (16.4%) PERCIST classification discordances and to 17/61 (28.9%) and 19/61 (31.1%) EORTC classification discordances. An agreement was better for these scenarios with application of the propriety filter, with kappa values of 1.00 and 0.95 compared to 0.75 and 0.77 for PERCIST and kappa values of 0.93 and 0.95 compared to 0.61 and 0.55 for EORTC, respectively., Conclusion: PERCIST classification is less sensitive to reconstruction algorithm-dependent variability than EORTC classification but harmonizing SULs within the EARL program is equally effective with either.

Quantitative positron emission tomography/computed tomography (PET/CT) can be used as diagnostic or prognostic tools (i.e. single measurement) or for therapy monitoring (i.e. longitudinal studies) in multicentre studies. Use of quantitative parameters, such as standardized uptake values (SUVs), metabolic active tumor volumes (MATVs) or total lesion glycolysis (TLG), in a multicenter setting requires that these parameters be comparable among patients and sites, regardless of the PET/CT system used. This review describes the motivations and the methodologies for quantitative PET/CT performance harmonization with emphasis on the EANM Research Ltd. (EARL) Fluorodeoxyglucose (FDG) PET/CT accreditation program, one of the international harmonization programs aiming at using FDG PET as a quantitative imaging biomarker. In addition, future accreditation initiatives will be discussed. The validation of the EARL accreditation program to harmonize SUVs and MATVs is described in a wide range of tumor types, with focus on therapy assessment using either the European Organization for Research and Treatment of Cancer (EORTC) criteria or PET Evaluation Response Criteria in Solid Tumors (PERCIST), as well as liver-based scales such as the Deauville score. Finally, also presented in this paper are the results from a survey across 51 EARL-accredited centers reporting how the program was implemented and its impact on daily routine and in clinical trials, harmonization of new metrics such as MATV and heterogeneity features.

Background: Evolutions in hardware and software PET technology, such as point spread function (PSF) reconstruction, have been shown to improve diagnostic performance, but can also lead to important device-dependent and reconstruction-dependent variations in standardized uptake values (SUVs). This may preclude the multicentre use of SUVs as a prognostic or diagnostic tool or as a biomarker of the early response to antineoplastic treatments. This study compared two SUV harmonization strategies using a newer reconstruction algorithm that improves lesion detection while maintaining comparability with older systems: (1) the use of a second reconstruction compliant with harmonization standards and (2) the use of a proprietary software tool (EQ.PET)., Methods: PET data from 50 consecutive non-small cell lung cancer patients were reconstructed with PSF reconstruction for optimal tumor detection and an ordered subset expectation maximization (OSEM3D) reconstruction to mimic a former generation PET. An additional PSF reconstruction was performed with a 7 mm Gaussian filter (PSF 7 , first method), and, post-reconstruction, the EQ filter (same Gaussian filter) was applied to the PSF data (PSF EQ , second method) for harmonization purposes. The 7 mm kernel filter was chosen to comply with the European Association of Nuclear Medicine (EANM) standards. SUVs for all reconstructions were compared with regression analyses and/or Bland-Altman plots., Results: Overall, 171 lesions were analyzed: 55 lung lesions (32.2%), 87 lymph nodes (50.9%), and 29 metastases (16.9%). In these lesions, the mean PSF 7 /OSEM3D ratios for SUV max and SUV peak were 1.02 (95% CI: 0.93-1.11) and 1.04 (95% CI: 0.95-1.14), respectively. The mean PSF EQ /OSEM3D ratios for SUV max and SUV peak were 1.01 (95% CI: 0.91-1.11) and 1.04 (95% CI: 0.94-1.14), respectively. When comparing PSF 7 and PSF EQ , Bland-Altman analysis showed that the mean PSF 7 /PSF EQ ratios for SUV max and SUV peak were 1.01 (95% CI: 0.96-1.06) and 1.01 (95% CI: 0.97-1.04), respectively., Conclusion: The issue of reconstruction dependency in SUV values that hampers the comparison of data between different PET systems can be overcome using two reconstructions for harmonized quantification and optimal diagnosis or using the EQ.PET technology. Both technologies produce similar results, EQ.PET sparing reconstruction and interpretation time. Other manufacturers are encouraged to either emulate this solution or to produce a vendor-neutral approach.

Purpose: Quantification of tumour heterogeneity in PET images has recently gained interest, but has been shown to be dependent on image reconstruction. This study aimed to evaluate the impact of the EANM/EARL accreditation program on selected 18 F-FDG heterogeneity metrics., Methods: To carry out our study, we prospectively analysed 71 tumours in 60 biopsy-proven lung cancer patient acquisitions reconstructed with unfiltered point spread function (PSF) positron emission tomography (PET) images (optimised for diagnostic purposes), PSF-reconstructed images with a 7-mm Gaussian filter (PSF 7 ) chosen to meet European Association of Nuclear Medicine (EANM) 1.0 harmonising standards, and EANM Research Ltd. (EARL)-compliant ordered subset expectation maximisation (OSEM) images. Delineation was performed with fuzzy locally adaptive Bayesian (FLAB) algorithm on PSF images and reported on PSF 7 and OSEM ones, and with a 50 % standardised uptake values (SUV) max threshold (SUV max50% ) applied independently to each image. Robust and repeatable heterogeneity metrics including 1st-order [area under the curve of the cumulative histogram (CH AUC )], 2nd-order (entropy, correlation, and dissimilarity), and 3rd-order [high-intensity larger area emphasis (HILAE) and zone percentage (ZP)] textural features (TF) were statistically compared., Results: Volumes obtained with SUV max50% were significantly smaller than FLAB-derived ones, and were significantly smaller in PSF images compared to OSEM and PSF 7 images. PSF-reconstructed images showed significantly higher SUVmax and SUVmean values, as well as heterogeneity for CH AUC , dissimilarity, correlation, and HILAE, and a wider range of heterogeneity values than OSEM images for most of the metrics considered, especially when analysing larger tumours. Histological subtypes had no impact on TF distribution. No significant difference was observed between any of the considered metrics (SUV or heterogeneity features) that we extracted from OSEM and PSF 7 reconstructions. Furthermore, the distributions of TF for OSEM and PSF 7 reconstructions according to tumour volumes were similar for all ranges of volumes., Conclusion: PSF reconstruction with Gaussian filtering chosen to meet harmonising standards resulted in similar SUV values and heterogeneity information as compared to OSEM images, which validates its use within the harmonisation strategy context. However, unfiltered PSF-reconstructed images also showed higher heterogeneity according to some metrics, as well as a wider range of heterogeneity values than OSEM images for most of the metrics considered, especially when analysing larger tumours. This suggests that, whenever available, unfiltered PSF images should also be exploited to obtain the most discriminative quantitative heterogeneity features.

Pre- and posttreatment PET comparative scans should ideally be obtained with identical acquisition and processing, but this is often impractical. The degree to which differing protocols affect PERCIST classification is unclear. This study evaluates the consistency of PERCIST classification across different reconstruction algorithms and whether a proprietary software tool can harmonize SUV estimation sufficiently to provide consistent response classification., Methods: Eighty-six patients with non-small cell lung cancer, colorectal liver metastases, or metastatic melanoma who were scanned for therapy monitoring purposes were prospectively recruited in this multicenter trial. Pre- and posttreatment PET scans were acquired in protocols compliant with the Society of Nuclear Medicine and Molecular Imaging and the European Association of Nuclear Medicine (EANM) acquisition guidelines and were reconstructed with a point spread function (PSF) or PSF + time-of-flight (TOF) for optimal tumor detection and also with standardized ordered-subset expectation maximization (OSEM) known to fulfill EANM harmonizing standards. After reconstruction, a proprietary software solution was applied to the PSF ± TOF data (PSF ± TOF.EQ) to harmonize SUVs with the OSEM values. The impact of differing reconstructions on PERCIST classification was evaluated., Results: For the OSEM PET1 /OSEM PET2 (OSEM reconstruction for pre- and posttherapeutic PET, respectively) scenario, which was taken as the reference standard, the change in SUL was -41% ± 25 and +56% ± 62 in the groups of tumors showing a decrease and an increase in 18 F-FDG uptake, respectively. The use of PSF reconstruction affected classification of tumor response. For example, taking the PSF ± TOF PET1 /OSEM PET2 scenario increased the apparent reduction in SUL in responding tumors (-48% ± 22) but reduced the apparent increase in SUL in progressing tumors (+37% ± 43), as compared with the OSEM PET1 /OSEM PET2 scenario. As a result, variation in reconstruction methodology (PSF ± TOF PET1 /OSEM PET2 or OSEM PET1 /PSF ± TOF PET2 ) led to 13 of 86 (15%) and 17 of 86 (20%) PERCIST classification discordances, respectively. Agreement was better for these scenarios with application of the propriety filter, with κ values of 1 and 0.95 compared with 0.79 and 0.72, respectively., Conclusion: Reconstruction algorithm-dependent variability in PERCIST classification is a significant issue but can be overcome by harmonizing SULs using a proprietary software tool., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Background: Tail vein injection under short anesthesia is the most commonly used route for administering radiopharmaceuticals. However, the small caliber of the vein in rodents may lead to tracer extravasation and thereby compromise quantitative accuracy of PET. We aimed to evaluate a method for correction of interstitial radiotracer leakage in the context of pre-clinical therapeutic response assessment., Methods: In two separate studies involving 16 nude rats, a model of human ovarian cancer was xenografted and each was treated with a Phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor or used as a control. Tracer injections were performed via the tail vein by a single operator. Two observers qualitatively evaluated the resulting images and if appropriate drew a volume of interest (VOI) over the injection site to record extravasated activities. Uncorrected and corrected tumors' mean standardized uptake value (SUV)mean was computed (corrected injected activity = calibrated activity - decay corrected residual syringe activity - decay corrected tail extravasated activity). Molecular analyses were taken as a gold standard. The frequency and magnitude of extravasation were analyzed, as well as the inter-observer agreement and the impact of the correction method on tumor uptake quantification., Results: Extravasation never exceeded 20 % of the injected dose but occurred in more than 50 % of injections. It was independent of groups of animals and protocol time points with p values of 1.00 and 0.61, respectively, in the first experiment and 0.47 and 0.13, respectively, in the second experiment. There was a good inter-observer agreement for qualitative analysis (kappa = 0.72) and a moderate agreement when using quantitative analysis (ρ c = 0.94). In both experiments, there was significant difference between uncorrected and corrected SUVmean. Despite this significant difference, mean percent differences between uncorrected and corrected SUVmean in the first and the second experiments were -3.61 and -1.78, respectively. Concerning therapy assessment, in both experiments, significant differences in median %SUVmean between control and treated groups were observed over all time points with either uncorrected and corrected data (p < 0.05)., Conclusions: Although extravasation is common and can be reproducibly corrected, this is probably not required for validation of response to drugs that induce large SUV changes. However, further studies are required to evaluate the impact of extravasation in situations where less marked metabolic responses are observed or important extravasations occur.

Purpose: We compared conventional filtered back-projection (FBP), two-dimensional-ordered subsets expectation maximization (OSEM) and maximum a posteriori (MAP) NEMA NU 4-optimized reconstructions for therapy assessment., Procedures: Varying reconstruction settings were used to determine the parameters for optimal image quality with two NEMA NU 4 phantom acquisitions. Subsequently, data from two experiments in which nude rats bearing subcutaneous tumors had received a dual PI3K/mTOR inhibitor were reconstructed with the NEMA NU 4-optimized parameters. Mann-Whitney tests were used to compare mean standardized uptake value (SUV(mean)) variations among groups., Results: All NEMA NU 4-optimized reconstructions showed the same 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) kinetic patterns and detected a significant difference in SUV(mean) relative to day 0 between controls and treated groups for all time points with comparable p values., Conclusion: In the framework of therapy assessment in rats bearing subcutaneous tumors, all algorithms available on the Inveon system performed equally.

Purpose: We prospectively evaluated whether a strategy using point spread function (PSF) reconstruction for both diagnostic and quantitative analysis in non-small cell lung cancer (NSCLC) patients meets the European Association of Nuclear Medicine (EANM) guidelines for harmonization of quantitative values., Methods: The NEMA NU-2 phantom was used to determine the optimal filter to apply to PSF-reconstructed images in order to obtain recovery coefficients (RCs) fulfilling the EANM guidelines for tumour positron emission tomography (PET) imaging (PSF(EANM)). PET data of 52 consecutive NSCLC patients were reconstructed with unfiltered PSF reconstruction (PSF(allpass)), PSF(EANM) and with a conventional ordered subset expectation maximization (OSEM) algorithm known to meet EANM guidelines. To mimic a situation in which a patient would undergo pre- and post-therapy PET scans on different generation PET systems, standardized uptake values (SUVs) for OSEM reconstruction were compared to SUVs for PSF(EANM) and PSF(allpass) reconstruction., Results: Overall, in 195 lesions, Bland-Altman analysis demonstrated that the mean ratio between PSF(EANM) and OSEM data was 1.03 [95% confidence interval (CI) 0.94-1.12] and 1.02 (95% CI 0.90-1.14) for SUV(max) and SUV(mean), respectively. No difference was noticed when analysing lesions based on their size and location or on patient body habitus and image noise. Ten patients (84 lesions) underwent two PET scans for response monitoring. Using the European Organization for Research and Treatment of Cancer (EORTC) criteria, there was an almost perfect agreement between OSEM(PET1)/OSEM(PET2) (current standard) and OSEM(PET1)/PSF(EANM-PET2) or PSF(EANM-PET1)/OSEM(PET2) with kappa values of 0.95 (95% CI 0.91-1.00) and 0.99 (95% CI 0.96-1.00), respectively. The use of PSF(allpass) either for pre- or post-treatment (i.e. OSEM(PET1)/PSF(allpass-PET2) or PSF(allpass-PET1)/OSEM(PET2)) showed considerably less agreement with kappa values of 0.75 (95% CI 0.67-0.83) and 0.86 (95% CI 0.78-0.94), respectively., Conclusion: Protocol-optimized images and compliance with EANM guidelines allowed for a reliable pre- and post-therapy evaluation when using different generation PET systems. These data obtained in NSCLC patients could be extrapolated to other solid tumours.

Background: The use of iodinated contrast media in small-animal positron emission tomography (PET)/computed tomography (CT) could improve anatomic referencing and tumor delineation but may introduce inaccuracies in the attenuation correction of the PET images. This study evaluated the diagnostic performance and accuracy of quantitative values in contrast-enhanced small-animal PET/CT (CEPET/CT) as compared to unenhanced small animal PET/CT (UEPET/CT)., Methods: Firstly, a NEMA NU 4-2008 phantom (filled with 18F-FDG or 18F-FDG plus contrast media) and a homemade phantom, mimicking an abdominal tumor surrounded by water or contrast media, were used to evaluate the impact of iodinated contrast media on the image quality parameters and accuracy of quantitative values for a pertinent-sized target. Secondly, two studies in 22 abdominal tumor-bearing mice and rats were performed. The first animal experiment studied the impact of a dual-contrast media protocol, comprising the intravenous injection of a long-lasting contrast agent mixed with 18F-FDG and the intraperitoneal injection of contrast media, on tumor delineation and the accuracy of quantitative values. The second animal experiment compared the diagnostic performance and quantitative values of CEPET/CT versus UEPET/CT by sacrificing the animals after the tracer uptake period and imaging them before and after intraperitoneal injection of contrast media., Results: There was minimal impact on IQ parameters (%SDunif and spillover ratios in air and water) when the NEMA NU 4-2008 phantom was filled with 18F-FDG plus contrast media. In the homemade phantom, measured activity was similar to true activity (-0.02%) and overestimated by 10.30% when vials were surrounded by water or by an iodine solution, respectively. The first animal experiment showed excellent tumor delineation and a good correlation between small-animal (SA)-PET and ex vivo quantification (r2 = 0.87, P < 0.0001). The second animal experiment showed a good correlation between CEPET/CT and UEPET/CT quantitative values (r2 = 0.99, P < 0.0001). Receiver operating characteristic analysis demonstrated better diagnostic accuracy of CEPET/CT versus UEPET/CT (senior researcher, area under the curve (AUC) 0.96 versus 0.77, P = 0.004; junior researcher, AUC 0.78 versus 0.58, P = 0.004)., Conclusions: The use of iodinated contrast media for small-animal PET imaging significantly improves tumor delineation and diagnostic performance, without significant alteration of SA-PET quantitative accuracy and NEMA NU 4-2008 IQ parameters.