EANM Research Ltd. Research Articles

Clinical Performance Comparison of a Long Versus a Short Axial Field-of-View PET/CT Using EARL-Compliant Reconstructions

PurposeTo ensure comparable PET/CT image quality between or within centres, clinical inter-system performance comparisons following European Association of Nuclear Medicine Research Ltd. (EARL) guidelines is required. In this work the performance of the long axial field-of-view Biograph Vision Quadra is compared to its predecessor, the short axial field-of-view Biograph Vision.ProceduresTo this aim, patients with suspected tumour lesions received a single weight-based (3 MBq/kg) 2-deoxy-2-[18F]fluoro-D-glucose injection and underwent routine clinical (∼\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\sim$$\\end{document} 15 min) scans on the Vision and 3-min scans on the Quadra in listmode in balanced order. Image quality (IQ), image noise (IN), and tumour demarcation (TD) were assessed visually by four nuclear medicine physicians using a 5-point Likert scale and semiquantitative analysis was performed using standardised uptake values (SUVs). Inter-reader agreement was tested using Wilcoxon’s signed rank test and the SUVs were statistically compared using a paired t-test.ResultsTwenty patients (mean age, 60 years ± 8.8 [standard deviation], 16 male) were enrolled. Inter-reader agreement ranged from good to very good for IQ and IN (0.62 ≤ W ≤ 0.81), and fair for TD (0.29 ≤ W ≤ 0.39). Furthermore, a significant difference was found for TD (p = 0.015) between the systems, showing improved TD for the Quadra.ConclusionThis study demonstrates that the Quadra can be used in routine clinical practice with multiple PET/CT systems or in multicentre studies. This system provides comparable diagnostic image quality and semiquantitative accuracy, improved TD, and has the advantage of shorter scan durations.

Quantitative and clinical implications of the EARL2 versus EARL1 [18F]FDG PET-CT performance standards in head and neck squamous cell carcinoma

BackgroundThe EANM Research Ltd. (EARL) guidelines give recommendations for harmonization of [18F]FDG PET-CT image acquisition and reconstruction, aiming to ensure reproducibility of quantitative data between PET scanners. Recent technological advancements in PET-CT imaging resulted in an updated version of the EARL guidelines (EARL2). The aim of this study is to compare quantitative [18F]FDG uptake metrics of the primary tumor and lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC) on EARL2 versus EARL1 reconstructed images and to describe clinical implications for nodal staging and treatment.MethodsForty-nine consecutive patients with HNSCC were included. For all, both EARL1 and EARL2 images were reconstructed from a singular [18F]FDG PET-CT scan. Primary tumors and non-necrotic lymph nodes ≥ 5 mm were delineated on CT-scan. In the quantitative analysis, maximum standardized uptake values (SUVmax) and standardized uptake ratios (SURmax, i.e., SUVmax normalized to cervical spinal cord uptake) were calculated for all lesions on EARL1 and EARL2 reconstructions. Metabolic tumor volume (MTV) and total lesion glycolysis were compared between EARL1 and EARL2 using different segmentation methods (adaptive threshold; SUV2.5/3.5/4.5; SUR2.5/3.5/4.5; MAX40%/50%). In the qualitative analysis, each lymph node was scored independently by two nuclear medicine physicians on both EARL1 and EARL2 images on different occasions using a 4-point scale.ResultsThere was a significant increase in SUVmax (16.5%) and SURmax (9.6%) of primary tumor and lymph nodes on EARL2 versus EARL1 imaging (p < 0.001). The proportional difference of both SUVmax and SURmax between EARL2 and EARL1 decreased with increasing tumor volume (p < 0.001). Absolute differences in MTVs between both reconstructions were small (< 1.0 cm3), independent of the segmentation method. MTVs decreased on EARL2 using relative threshold methods (adaptive threshold; MAX40%/50%) and increased using static SUV or SUR thresholds. With visual scoring of lymph nodes 38% (11/29) of nodes with score 2 on EARL1 were upstaged to score 3 on EARL2, which resulted in an alteration of nodal stage in 18% (6/33) of the patients.ConclusionsUsing the EARL2 method for PET image reconstruction resulted in higher SUVmax and SURmax compared to EARL1, with nodal upstaging in a significant number of patients.

Optimal clinical protocols for total-body 18F-FDG PET/CT examination under different activity administration plans

BackgroundHighly sensitive digital total-body PET/CT scanners (uEXPLORER) have great potential for clinical applications and fundamental research. Given their increasing sensitivity, low-dose scanning or snapshot imaging is now possible in clinics. However, a standardized total-body 18F-FDG PET/CT protocol is still lacking. Establishing a standard clinical protocol for total-body 18F-FDG PET/CT examination under different activity administration plans can help provide a theoretical reference for nuclear radiologists.MethodsThe NEMA image quality (IQ) phantom was used to evaluate the biases of various total-body 18F-FDG PET/CT protocols related to the administered activity, scan duration, and iterations. Several objective metrics, including contrast recovery (CR), background variability (BV), and contrast-to-noise ratio (CNR), were measured from different protocols. In line with the European Association of Nuclear Medicine Research Ltd. (EARL) guidelines, optimized protocols were suggested and evaluated for total-body 18F-FDG PET/CT imaging for three different injected activities.ResultsOur NEMA IQ phantom evaluation resulted in total-body PET/CT images with excellent contrast and low noise, suggesting great potential for reducing administered activity or shortening the scan duration. Different to the iteration number, prolonging the scan duration was the first choice for achieving higher image quality regardless of the activity administered. In light of image quality, tolerance of oncological patients, and the risk of ionizing radiation damage, the 3-min acquisition and 2-iteration (CNR = 7.54), 10-min acquisition and 3-iteration (CNR = 7.01), and 10-min acquisition and 2-iteration (CNR = 5.49) protocols were recommended for full-dose (3.70 MBq/kg), half-dose (1.95 MBq/kg), and quarter-dose (0.98 MBq/kg) activity injection schemes, respectively. Those protocols were applied in clinical practices, and no significant differences were observed for the SUVmax of large/small lesions or the SUVmean of different healthy organs/tissues.ConclusionThese findings support that digital total-body PET/CT scanners can generate PET images with a high CNR and low-noise background, even with a short acquisition time and low administered activity. The proposed protocols for different administered activities were determined to be valid for clinical examination and can maximize the value of this imaging type.

Shortened duration whole body 18F-FDG PET Patlak imaging on the Biograph Vision Quadra PET/CT using a population-averaged input function

BackgroundExcellent performance characteristics of the Vision Quadra PET/CT, e.g. a substantial increase in sensitivity, allow for precise measurements of image-derived input functions (IDIF) and tissue time activity curves. Previously we have proposed a method for a reduced 30 min (as opposed to 60 min) whole body 18F-FDG Patlak PET imaging procedure using a previously published population-averaged input function (PIF) scaled to IDIF values at 30–60 min post-injection (p.i.). The aim of the present study was to apply this method using the Vision Quadra PET/CT, including the use of a PIF to allow for shortened scan durations.MethodsTwelve patients with suspected lung malignancy were included and received a weight-based injection of 18F-FDG. Patients underwent a 65-min dynamic PET acquisition which were reconstructed using European Association of Nuclear Medicine Research Ltd. (EARL) standards 2 reconstruction settings. A volume of interest (VOI) was placed in the ascending aorta (AA) to obtain the IDIF. An external PIF was scaled to IDIF values at 30–60, 40–60, and 50–60 min p.i., respectively, and parametric 18F-FDG influx rate constant (Ki) images were generated using a t* of 30, 40 or 50 min, respectively. Herein, tumour lesions as well as healthy tissues, i.e. liver, muscle tissue, spleen and grey matter, were segmented.ResultsGood agreement between the IDIF and corresponding PIF scaled to 30–60 min p.i. and 40–60 min p.i. was obtained with 7.38% deviation in Ki. Bland–Altman plots showed excellent agreement in Ki obtained using the PIF scaled to the IDIF at 30–60 min p.i. and at 40–60 min p.i. as all data points were within the limits of agreement (LOA) (− 0.004–0.002, bias: − 0.001); for the 50–60 min p.i. Ki, all except one data point fell in between the LOA (− 0.021–0.012, bias: − 0.005).ConclusionsParametric whole body 18F-FDG Patlak Ki images can be generated non-invasively on a Vision Quadra PET/CT system. In addition, using a scaled PIF allows for a substantial (factor 2 to 3) reduction in scan time without substantial loss of accuracy (7.38% bias) and precision (image quality and noise interference).

EARL compliance and imaging optimisation on the Biograph Vision Quadra PET/CT using phantom and clinical data

PurposeCurrent European Association of Nuclear Medicine (EANM) Research Ltd. (EARL) guidelines for the standardisation of PET imaging developed for conventional systems have not yet been adjusted for long axial field-of-view (LAFOV) systems. In order to use the LAFOV Siemens Biograph Vision Quadra PET/CT (Siemens Healthineers, Knoxville, TN, USA) in multicentre research and harmonised clinical use, compliance to EARL specifications for 18F-FDG tumour imaging was explored in the current study. Additional tests at various locations throughout the LAFOV and the use of shorter scan durations were included. Furthermore, clinical data were collected to further explore and validate the effects of reducing scan duration on semi-quantitative PET image biomarker accuracy and precision when using EARL-compliant reconstruction settings.MethodsEARL compliance phantom measurements were performed using the NEMA image quality phantom both in the centre and at various locations throughout the LAFOV. PET data (maximum ring difference (MRD) = 85) were reconstructed using various reconstruction parameters and reprocessed to obtain images at shorter scan durations. Maximum, mean and peak activity concentration recovery coefficients (RC) were obtained for each sphere and compared to EARL standards specifications.Additionally, PET data (MRD = 85) of 10 oncological patients were acquired and reconstructed using various reconstruction settings and reprocessed from 10 min listmode acquisition into shorter scan durations. Per dataset, SUVs were derived from tumour lesions and healthy tissues. ANOVA repeated measures were performed to explore differences in lesion SUVmax and SUVpeak. Wilcoxon signed-rank tests were performed to evaluate differences in background SUVpeak and SUVmean between scan durations. The coefficient of variation (COV) was calculated to characterise noise.ResultsPhantom measurements showed EARL compliance for all positions throughout the LAFOV for all scan durations. Regarding patient data, EARL-compliant images showed no clinically meaningful significant differences in lesion SUVmax and SUVpeak or background SUVmean and SUVpeak between scan durations. Here, COV only varied slightly.ConclusionImages obtained using the Vision Quadra PET/CT comply with EARL specifications. Scan duration and/or activity administration can be reduced up to a factor tenfold without the interference of increased noise.

F18-FDG PET/CT imaging early predicts pathologic complete response to induction chemoimmunotherapy of locally advanced head and neck cancer: preliminary single-center analysis of the checkrad-cd8 trial

AimIn the CheckRad-CD8 trial patients with locally advanced head and neck squamous cell cancer are treated with a single cycle of induction chemo-immunotherapy (ICIT). Patients with pathological complete response (pCR) in the re-biopsy enter radioimmunotherapy. Our goal was to study the value of F-18-FDG PET/CT in the prediction of pCR after induction therapy.MethodsPatients treated within the CheckRad-CD8 trial that additionally received FDG- PET/CT imaging at the following two time points were included: 3–14 days before (pre-ICIT) and 21–28 days after (post-ICIT) receiving ICIT. Tracer uptake in primary tumors (PT) and suspicious cervical lymph nodes (LN +) was measured using different quantitative parameters on EANM Research Ltd (EARL) accredited PET reconstructions. In addition, mean FDG uptake levels in lymphatic and hematopoietic organs were examined. Percent decrease (Δ) in FDG uptake was calculated for all parameters. Biopsy of the PT post-ICIT acquired after FDG-PET/CT served as reference. The cohort was divided in patients with pCR and residual tumor (ReTu).ResultsThirty-one patients were included. In ROC analysis, ΔSUVmax PT performed best (AUC = 0.89) in predicting pCR (n = 17), with a decline of at least 60% (sensitivity, 0.77; specificity, 0.93). Residual SUVmax PT post-ICIT performed best in predicting ReTu (n = 14), at a cutpoint of 6.0 (AUC = 0.91; sensitivity, 0.86; specificity, 0.88). Combining two quantitative parameters (ΔSUVmax ≥ 50% and SUVmax PT post-ICIT ≤ 6.0) conferred a sensitivity of 0.81 and a specificity of 0.93 for determining pCR. Background activity in lymphatic organs or uptake in suspected cervical lymph node metastases lacked significant predictive value.ConclusionFDG-PET/CT can identify patients with pCR after ICIT via residual FDG uptake levels in primary tumors and the related changes compared to baseline. FDG-uptake in LN + had no predictive value.Trial registryClinicalTrials.gov identifier: NCT03426657.

EARL compliance measurements on the biograph vision Quadra PET/CT system with a long axial field of view

BackgroundOur aim was to determine sets of reconstruction parameters for the Biograph Vision Quadra (Siemens Healthineers) PET/CT system that result in quantitative images compliant with the European Association of Nuclear Medicine Research Ltd. (EARL) criteria. Using the Biograph Vision 600 (Siemens Healthineers) PET/CT technology but extending the axial field of view to 106 cm, gives the Vision Quadra currently an around fivefold higher sensitivity over the Vision 600 with otherwise comparable spatial resolution. Therefore, we also investigated how the number of incident positron decays—i.e., exposure—affects EARL compliance. This will allow estimating a minimal acquisition time or a minimal applied dose in clinical scans while retaining data comparability.MethodsWe measured activity recovery curves on a NEMA IEC body phantom filled with an aqueous 18F solution and a sphere to background ratio of 10–1 according to the latest EARL guidelines. Reconstructing 3570 image sets with varying OSEM PSF iterations, post-reconstruction Gaussian filter full width at half maximum (FWHM), and varying exposure from 59 kDecays/ml (= 3 s frame duration) to 59.2 MDecays/ml (= 1 h), allowed us to determine sets of parameters to achieve compliance with the current EARL 1 and EARL 2 standards. Recovery coefficients (RCs) were calculated for the metrics RCmax, RCmean, and RCpeak, and the respective recovery curves were analyzed for monotonicity. The background’s coefficient of variation (COV) was also calculated.ResultsUsing 6 iterations, 5 subsets and 7.8 mm Gauss filtering resulted in optimal EARL1 compliance and recovery curve monotonicity in all analyzed frames, except in the 3 s frames. Most robust EARL2 compliance and monotonicity were achieved with 2 iterations, 5 subsets, and 3.6 mm Gauss FWHM in frames with durations between 30 s and 10 min. RCpeak only impeded EARL2 compliance in the 10 s and 3 s frames.ConclusionsWhile EARL1 compliance was robust over most exposure ranges, EARL2 compliance required exposures between 1.2 MDecays/ml to 11.5 MDecays/ml. The Biograph Vision Quadra’s high sensitivity makes frames as short as 10 s feasible for comparable quantitative images. Lowering EARL2 RCmax limits closer to unity would possibly even permit shorter frames.

Standardisation of conventional and advanced iterative reconstruction methods for Gallium-68 multi-centre PET-CT trials

PurposeTo assess the applicability of the Fluorine-18 performance specifications defined by EANM Research Ltd (EARL), in Gallium-68 multi-centre PET-CT trials using conventional (ordered subset expectation maximisation, OSEM) and advanced iterative reconstructions which include the systems’ point spread function (PSF) and a Bayesian penalised likelihood algorithm (BPL) commercially known as Q.CLEAR. The possibility of standardising the two advanced reconstruction methods was examined.MethodsThe NEMA image quality phantom was filled with Gallium-68 and scanned on a GE PET-CT system. PSF and BPL with varying post-reconstruction Gaussian filter width (2–6.4 mm) and penalisation factor (200–1200), respectively, were applied. The average peak-to-valley ratio from six profiles across each sphere was estimated to inspect any edge artefacts. Image noise was assessed using background variability and image roughness. Six GE and Siemens PET-CT scanners provided Gallium-68 images of the NEMA phantom using both conventional and advanced reconstructions from which the maximum, mean and peak recoveries were drawn. Fourteen patients underwent 68Ga-PSMA PET-CT imaging. BPL (200-1200) reconstructions of the data were compared against PSF smoothed with a 6.4-mm Gaussian filter.ResultsA Gaussian filter width of approximately 6 mm for PSF and a penalisation factor of 800 for BPL were needed to suppress the edge artefacts. In addition, those reconstructions provided the closest agreement between the two advanced iterative reconstructions and low noise levels with the background variability and the image roughness being lower than 7.5% and 11.5%, respectively. The recoveries for all methods generally performed at the lower limits of the EARL specifications, especially for the 13- and 10-mm spheres for which up to 27% (conventional) and 41% (advanced reconstructions) lower limits are suggested. The lesion standardised uptake values from the clinical data were significantly different between BPL and PSF smoothed with a Gaussian filter of 6.4 mm wide for all penalisation factors except for 800 and 1000.ConclusionIt is possible to standardise the advanced reconstruction methods with the reconstruction parameters being also sufficient for minimising the edge artefacts and noise in the images. For both conventional and advanced reconstructions, Gallium-68 specific recovery coefficient limits were required, especially for the smallest phantom spheres.

1050 Normal imaging findings after aortic valve implantation on 18f-fluorodeoxyglucose positron emission tomography with computed tomography and computed tomography angiography

Abstract Purpose Although 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET) with computed tomography (CT) and cardiac computed tomography angiography (CTA) are essential tools in diagnosing prosthetic heart valve (PHV) endocarditis, the normal imaging findings in the first year after PHV implantation on 18F-FDG-PET/CT and CTA have not been studied prospectively. We prospectively assessed the perivalvular FDG uptake at different time points after aortic PHV implantation and assessed the normal imaging findings on CTA. Materials and methods Patients who had undergone uncomplicated aortic PHV implantation were included and underwent 18F-FDG PET/CT and CTA at 5(±1) weeks (group 1), 12(±2) weeks (group 2) or 52(±8) weeks (group 3) after implantation. After a preparatory diet to suppress normal myocardial glucose uptake, FDG uptake in the myocardium as well as around the PHV was scored using the Qualification Visual Score for Hypermetabolism (QVSH) as "none" (&amp;lt; mediastinum), "low" (&amp;gt; mediastinum but &amp;lt; liver), "intermediate" (&amp;gt; liver), or "high" (intense uptake) and quantitative analysis was performed with maximum Standardized Uptake Value (SUVmax) and target to background ratio (SUVratio) on standardized European Association of Nuclear Medicine Research Ltd. (EARL) reconstructions by an experienced nuclear medicine physician. CTA was analysed for image quality, artefacts and stranding of the peri-aortic fat by a cardiac radiologist. Results In total 37 patients (group 1: n = 12, group 2: n = 12, group 3: n = 13) (age 66 ± 8 years) were included. Myocardial FDG uptake was intermediate or less in 29/37 scans (78%). QVSH around the PHV was 8/12(67%) low and 4/12(33%) intermediate in group 1, 7/12(58%) low and 5/12(42%) intermediate in group 2 and 8/13(62%) low and 5/13(38%) intermediate in group 3 (p = 0.91). No scan was scored as "none" or "high". EARL SUVmax was 3.48 ± 0.57, 3.50 ± 0.59 and 3.34 ± 0.55 (mean ± SD, p = 0.77) and EARL SUVratio was 2.00 ± 0.29, 1.96 ± 0.41 and 1.71 ± 0.26 (mean ± SD, p = 0.07) for groups 1, 2 and 3, respectively. One patient in group 3 refused to undergo the additional CTA and one CTA in group 3 could not be analysed for image quality and artefacts due to techniqual difficulties. Overall CTA image quality was "good" or "excellent" with an artefact score of "virtually none" or "mild" in most cases (n = 33, 94%). Stranding of peri-aortic fat was seen in 27/35 (77%) of these patients (group 1: n = 11; group 2: n = 9; group 3: n = 7) with no signs of FDG uptake on PET/CT scan. Conclusion Baseline FDG uptake around aortic PHV at 5, 12 and 52 weeks after implantation is similar and mild in the majority of cases with an overall mean SUVmax and SUVratio of 3.44 ± 0.56 and 1.89 ± 0.34 respectively. CTA revealed baseline post-surgical findings in the first year after PHV implantation.

Image Quality and Activity Optimization in Oncologic 18F-FDG PET Using the Digital Biograph Vision PET/CT System.

The first Biograph Vision PET/CT system (Siemens Healthineers) was installed at the University Medical Center Groningen. Improved performance of this system could allow for a reduction in activity administration or scan duration. This study evaluated the effects of reduced scan duration in oncologic 18F-FDG PET imaging on quantitative and subjective imaging parameters and its influence on clinical image interpretation. Methods: Patients referred for a clinical PET/CT scan were enrolled in this study, received a weight-based 18F-FDG injected activity, and underwent list-mode PET acquisition at 180 s per bed position (s/bp). Acquired PET data were reconstructed using the vendor-recommended clinical reconstruction protocol (hereafter referred to as "clinical"), using the clinical protocol with additional 2-mm gaussian filtering (hereafter referred to as "clinical+G2"), and-in conformance with European Association of Nuclear Medicine Research Ltd. (EARL) specifications-using different scan durations per bed position (180, 120, 60, 30, and 10 s). Reconstructed images were quantitatively assessed for comparison of SUVs and noise. In addition, clinically reconstructed images were qualitatively evaluated by 3 nuclear medicine physicians. Results: In total, 30 oncologic patients (22 men, 8 women; age: 48-88 y [range], 67 ± 9.6 y [mean ± SD]) received a single weight-based (3 MBq/kg) 18F-FDG injected activity (weight: 45-123 kg [range], 81 ± 15 kg [mean ± SD]; activity: 135-380 MBq [range], 241 ± 47.3 MBq [mean ± SD]). Significant differences in lesion SUVmax were found between the 180-s/bp images and the 30- and 10-s/bp images reconstructed using the clinical protocols, whereas no differences were found in lesion SUVpeak EARL-compliant images did not show differences in lesion SUVmax or SUVpeak between scan durations. Quantitative parameters showed minimal deviation (∼5%) in the 60-s/bp images. Therefore, further subjective image quality assessment was conducted using the 60-s/bp images. Qualitative assessment revealed the influence of personal preference on physicians' willingness to adopt the 60-s/bp images in clinical practice. Although quantitative PET parameters differed minimally, an increase in noise was observed. Conclusion: With the Biograph Vision PET/CT system for oncologic 18F-FDG imaging, scan duration or activity administration could be reduced by a factor of 3 or more with the use of the clinical+G2 or the EARL-compliant reconstruction protocol.

Experimental Multicenter and Multivendor Evaluation of the Performance of PET Radiomic Features Using 3-Dimensionally Printed Phantom Inserts.

The sensitivity of radiomic features to several confounding factors, such as reconstruction settings, makes clinical use challenging. To investigate the impact of harmonized image reconstructions on feature consistency, a multicenter phantom study was performed using 3-dimensionally printed phantom inserts reflecting realistic tumor shapes and heterogeneity uptakes. Methods: Tumors extracted from real PET/CT scans of patients with non-small cell lung cancer served as model for three 3-dimensionally printed inserts. Different heterogeneity pattern were realized by printing separate compartments that could be filled with different activity solutions. The inserts were placed in the National Electrical Manufacturers Association image-quality phantom and scanned various times. First, a list-mode scan was acquired and 5 statistically equal replicates were reconstructed. Second, the phantom was scanned 4 times on the same scanner. Third, the phantom was scanned on 6 PET/CT systems. All images were reconstructed using EANM Research Ltd. (EARL)-compliant and locally clinically preferred reconstructions. EARL-compliant reconstructions were performed without (EARL1) or with (EARL2) point-spread function. Images were analyzed with and without resampling to 2-mm cubic voxels. Images were discretized with a fixed bin width (FBW) of 0.25 and a fixed bin number (FBN) of 64. The intraclass correlation coefficient (ICC) of each scan setup was calculated and compared across reconstruction settings. An ICC above 0.75 was regarded as high. Results: The percentage of features yielding a high ICC was largest for the statistically equal replicates (70%-91% for FBN; 90%-96% for FBW discretization). For scans acquired on the same system, the percentage decreased, but most features still resulted in a high ICC (FBN, 52%-63%; FBW, 75%-85%). The percentage of features yielding a high ICC decreased more in the multicenter setting. In this case, the percentage of features yielding a high ICC was larger for images reconstructed with EARL-compliant reconstructions: for example, 40% for EARL1 and 60% for EARL2 versus 21% for the clinically preferred setting for FBW discretization. When discretized with FBW and resampled to isotropic voxels, this benefit was more pronounced. Conclusion: EARL-compliant reconstructions harmonize a wide range of radiomic features. FBW discretization and a sampling to isotropic voxels enhances the benefits of EARL-compliant reconstructions.

The use of a proposed updated EARL harmonization of 18F-FDG PET-CT in patients with lymphoma yields significant differences in Deauville score compared with current EARL recommendations

BackgroundThe Deauville score (DS) is a clinical tool, based on the comparison between lesion and reference organ uptake of 18F-fluorodeoxyglucose (FDG), used to stratify patients with lymphoma into categories reflecting their disease status. With a plethora of positron emission tomography with computed tomography (PET-CT) hard- and software algorithms, standard uptake value (SUV) in lesions and reference organs may differ which affects DS classification and therefore medical treatment. The EANM Research Ltd. (EARL) harmonization program from the European Association of Nuclear Medicine (EANM) partly mitigates this issue, but local preferences are common in clinical practice. We have investigated the discordance in DS calculated from patients with lymphoma referred for 18F-FDG PET-CT reconstructed with three different algorithms: the newly introduced block-sequential regularization expectation-maximization algorithm commercially sold as Q. Clear (QC, GE Healthcare, Milwaukee, WI, USA), compliant with the newly proposed updated EARL recommendations, and two settings compliant with the current EARL recommendations (EARLlower and EARLupper, representing the lower and upper limit of the EARL recommendations).MethodsFifty-two patients with non-Hodgkin and Hodgkin lymphoma were included (18 females and 34 males). Segmentation of mediastinal blood pool and liver were semi-automatically performed, whereas segmentation of lesions was done manually. From these segmentations, SUVmax and SUVpeak were obtained and DS calculated.ResultsThere was a significant difference in DS between the QC algorithm and EARLlower/EARLupper (p < 0.0001 for both) but not between EARLlower and EARLupper (p = 0.102) when SUVmax was used. For SUVpeak, there was a significant difference between QC and EARLlower (p = 0.001), but not for QC vs EARLupper (p = 0.071) or EARLlower vs EARLupper (p = 0.102). Five non-responders (DS 4–5) for QC were classified as responders (DS 1–3) when EARLlower/EARLupper was used, both when SUVmax and SUVpeak were investigated.ConclusionUsing the proposed updated EARL recommendations compared with the current recommendations will significantly change DS classification. In select cases, the discordance would affect the choice of medical treatment. Specifically, the current EARL recommendations were more often prone to classify patients as responders.

Repeatability of [18F]FDG PET/CT total metabolic active tumour volume and total tumour burden in NSCLC patients

BackgroundTotal metabolic active tumour volume (TMATV) and total tumour burden (TTB) are increasingly studied as prognostic and predictive factors in non-small cell lung cancer (NSCLC) patients. In this study, we investigated the repeatability of TMATV and TTB as function of uptake interval, positron emission tomography/computed tomography (PET/CT) image reconstruction settings, and lesion delineation method. We used six lesion delineation methods, four direct PET image-derived delineations and two based on a majority vote approach, i.e. intersection between two or more delineations (MV2) and between three or more delineations (MV3). To evaluate the accuracy of those methods, they were compared with a reference delineation obtained from the consensus of the segmentations performed by three experienced observers. Ten NSCLC patients underwent two baseline whole-body [18F]2-Fluoro-2-deoxy-2-D-glucose ([18F]FDG) PET/CT studies on separate days, within 3 days. Two scans were obtained on each day at 60 and 90 min post-injection to assess the influence of tracer uptake interval. PET/CT images were reconstructed following the European Association of Nuclear Medicine Research Ltd. (EARL) compliant settings and with point-spread-function (PSF) modelling. Repeatability between the measurements of each day was determined and the influence of uptake interval, reconstruction settings, and lesion delineation method was assessed using the generalized estimating equations model.ResultsBased on the Jaccard index with the reference delineation, the MV2 lesion delineation method was the most successful method for automated lesion segmentation. The best overall repeatability (lowest repeatability coefficient, RC) was found for TTB from 90 min of tracer uptake scans reconstructed with EARL compliant settings and delineated with 41% of lesion’s maximum SUV method (RC = 11%). In most cases, TMATV and TTB repeatability were not significantly affected by changes in tracer uptake time or reconstruction settings. However, some lesion delineation methods had significantly different repeatability when applied to the same images.ConclusionsThis study suggests that under some circumstances TMATV and TTB repeatability are significantly affected by the lesion delineation method used. Performing the delineation with a majority vote approach improves reliability and does not hamper repeatability, regardless of acquisition and reconstruction settings. It is therefore concluded that by using a majority vote based tumour segmentation approach, TMATV and TTB in NSCLC patients can be measured with high reliability and precision.

Performance Characteristics of the Digital Biograph Vision PET/CT System.

This study evaluated the performance of the Biograph Vision digital PET/CT system according to the NEMA NU 2-2012 standard (published by the National Electrical Manufacturers Association [NEMA]) to allow for a reliable, reproducible, and intersystem-comparable performance measurement. Methods: The new digital PET/CT system features silicon photomultiplier-based detectors with 3.2-mm lutetium oxyorthosilicate crystals and full coverage of the scintillator area. The PET components incorporate 8 rings of 38 detector blocks, and each block contains 4 × 2 mini blocks. Each mini block consists of a 5 × 5 lutetium oxyorthosilicate array of 3.2 × 3.2 × 20 mm crystals coupled to a silicon photomultiplier array of 16 × 16 mm, resulting in an axial field of view of 26.1 cm. In this study, PET/CT system performance was evaluated for conformation with the NEMA NU 2-2012 standard, with additional measurements described in the new NEMA NU 2-2018 standard. Spatial resolution, sensitivity, count-rate performance, accuracy of attenuation and scatter correction, image quality, coregistration accuracy, and time-of-flight performance were determined. Measurements were directly compared with results from its predecessor, the Biograph mCT Flow, using existing literature. Moreover, feasibility to comply with the European Association of Nuclear Medicine Research Ltd. (EARL) criteria was evaluated, and some illustrative patient PET images were obtained. Results: The Biograph Vision showed a transverse and axial spatial resolution of 3.6 and 3.5 mm, respectively, in full width at half maximum at a 1-cm offset from the center of the field of view (measured with a 22Na 0.25-mm point source), a NEMA sensitivity of 16.4 kcps/MBq, and a NEMA peak noise-equivalent count-rate of 306 kcps at 32 kBq/mL. Time-of-flight resolution varied from 210 to 215 as count-rate increased up to the peak noise-equivalent count-rate. The overall image contrast seen with the NEMA image quality phantom ranged from 77.2% to 89.8%. Furthermore, the system was able to comply with the current and future EARL performance criteria. Conclusion: The Biograph Vision outperforms the analog Biograph mCT Flow, and the system is able to meet European harmonizing performance standards.

Impact of PET reconstruction protocols on quantification of lesions that fulfil the PERCIST lesion inclusion criteria

BackgroundThe aim of this study was to compare liver and oncologic lesion standardized uptake values (SUV) obtained through two different reconstruction protocols, GE’s newest clinical lesion detection protocol (Q.Clear) and the EANM Research Ltd (EARL) harmonization protocol, and to assess the clinical relevance of potential differences and possible implications for daily clinical practice using the PERCIST lesional inclusion criteria.NEMA phantom recovery coefficients (RC) and SUV normalized for lean body mass (LBM), referred to as SUV normalized for LBM (SUL), of liver and lesion volumes of interest were compared between the two reconstruction protocols. Head-to-toe PET/CT examinations and raw data from 64 patients were retrospectively retrieved. PET image reconstruction was carried out twice: once optimized for quantification, complying with EARL accreditation requirements, and once optimized for lesion detection, according to GE’s Q.Clear reconstruction settings.ResultsThe two reconstruction protocols showed different NEMA phantom RC values for different sphere sizes. Q.Clear values were always highest and exceeded the EARL accreditation maximum for smaller spheres. Comparison of liver SULmean showed a statistically significant but clinically irrelevant difference between both protocols. Comparison of lesion SULpeak and SULmax showed a statistically significant, and clinically relevant, difference of 1.64 and 4.57, respectively.ConclusionsFor treatment response assessment using PERCIST criteria, the harmonization reconstruction protocol should be used as the lesion detection reconstruction protocol using resolution recovery systematically overestimates true SUL values.

SUV Harmonization Between Different Hybrid PET/CT Systems.

Current PET/CT lutetium oxyorthosilicate (LSO) or lutetium-yttrium oxyorthosilicate crystal scanners are equipped with sophisticated softwares including point-spread function (PSF) and time-of-flight (TOF) image reconstruction. These softwares are associated with increased SUVs compared with 3D-OSEM reconstructions associated with older BGO PET/CT scanners. The European Association of Nuclear Medicine (EANM) identified the problem of SUV harmonization since 2010 through the EANM Research Ltd European Association of Nuclear Medicine Research Ltd [EARL] FDG PET/CT accreditation program. This required processing 2 reconstructions, one optimized for maximum spatial lesion detection and one for harmonized quantitation. We investigated an alternative single reconstruction method for both qualitative and quantitative analysis optimized to maximize spatial lesion detectability, followed by an intrinsic postreconstruction algorithm for SUV harmonization. Phantom and "in vivo" patient data analysis were acquired and analyzed on (a) a Siemens Biograph mCT system with LSO crystals and PSF and TOF algorithms, and on (b) a General Electric Discovery STE system with BGO crystals, without PSF and TOF. A dedicated algorithm (EQ.filter) was tested to harmonize SUV between the 2 scanners compared with EANM/EARL specifications. NEMA IQ phantom and a Jaszczak cylindrical phantom equipped with small fillable spheres (lesion to background ratios of 8:1 and 4:1) were used. Phantom data were validated on 7 oncologic patients with 39 hyperactive lesions ranging from 3 mm to 26 mm. The main benefit of PSF + TOF LSO PET/CT systems was increased contrast for small active lesions. Recovery coefficients measured according to NEMA standards exceeded those obtained by 3D-OSEM reconstruction. SUVmax discrepancies between the 2 PET/CT systems were as high as 149%, dropping to below 10% when optimized by EQ.filter. A single reconstruction optimized by EQ.filter for maximum spatial lesion detectability is an easy and precise solution to harmonize SUVs between different PET/CT scanners, avoiding a second reconstruction with an additional smoothing filter as requested by EANM/EARL.

Does PET Reconstruction Method Affect Deauville Score in Lymphoma Patients?

When evaluating 18F-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 18F-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) (PSFEARL). One hundred interim PET (i-PET) and 95 end-of-treatment PET (EoT-PET) studies were analyzed. SUVmax in the liver and aorta was determined using automatic volumes of interest and compared with SUVmax in the residual mass with the highest 18F-FDG uptake. Results: For i-PET, using PSF and PSFEARL, 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 PSFEARL 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 PSFEARL 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.

EANM/EARL FDG-PET/CT accreditation - summary results from the first 200 accredited imaging systems

PurposeFrom 2010 until July 2016, the EANM Research Ltd. (EARL) FDG-PET/CT accreditation program has collected over 2500 phantom datasets from approximately 200 systems and 150 imaging sites worldwide. The objective of this study is to report the findings and impact of the accreditation program on the participating PET/CT systems.MethodsTo obtain and maintain EARL accredited status, sites were required to complete and submit two phantom scans - calibration quality control (CalQC), using a uniform cylindrical phantom and image quality control (IQQC), using a NEMA NU2–2007 body phantom. Average volumetric SUV bias and SUV recovery coefficients (RC) were calculated and the data evaluated on the basis of quality control (QC) type, approval status, PET/CT system manufacturer and submission order.ResultsSUV bias in 5% (n = 96) of all CalQC submissions (n = 1816) exceeded 10%. After corrective actions following EARL feedback, sites achieved 100% compliance within EARL specifications. 30% (n = 1381) of SUVmean and 23% (n = 1095) of SUVmax sphere recoveries from IQQC submissions failed to meet EARL accreditation criteria while after accreditation, failure rate decreased to 12% (n = 360) and 9% (n = 254), respectively. Most systems demonstrated longitudinal SUV bias reproducibility within ±5%, while RC values remained stable and generally within ±10% for the four largest and ±20% for the two smallest spheres.ConclusionsRegardless of manufacturer or model, all investigated systems are able to comply with the EARL specifications. Within the EARL accreditation program, gross PET/CT calibration errors are successfully identified and longitudinal variability in PET/CT performances reduced. The program demonstrates that a harmonising accreditation procedure is feasible and achievable.

Quantification and monitoring of PET/CT data in multicentre trials: The Swiss SAKK 56/07 trial experience

AimTo outline the importance of continuous monitoring of quantitative positron emission tomography (PET) data in multicentre trials to minimize quantitative bias in longitudinal intra-patient PET studies in light of the multicentre SAKK 56/07 experience in quantification and monitoring 18F-FDG PET/CT data. Patients and methodsWe collected 64 uniform phantom 18F-FDG PET acquisitions periodically at the enrolling centres (12 European institutions). A core-laboratory analysed them for standard uptake value (SUV) accuracy (desired 1.00±10%) and acceptable image noise was defined by a coefficient of variation (COV) less than 15%. In total, 151 patients 18F-FDG PET acquisitions (baseline and follow-up) were also collected and analysed to verify longitudinal coherence of main acquisition/reconstruction parameters (DICOM tags verification) and patient preparation, in particular the uptake time (desired uptake time [UT]=60±10min). ResultsUniform phantom PET acquisition satisfied the inclusion criteria in 58/64 (89%) examinations. All PET scanner exhibited comparable SUV quantification, but we found large dispersion in terms of noise, with COV ranging 3–15%. Only 1 phantom PET acquisition was out of range with COV=21.5%. Patient data exhibited important variation in uptake time with UT=65±10min (mean±SD), with only 111/151 (74%) patients’ examinations satisfying inclusion criteria while 26% were out of range. ConclusionsRegular monitoring of PET data in multicentre trials is capital to ensure longitudinal intra-patient PET data consistence and minimize quantitative bias while it helps to spread the culture of quality in participating centre. Recent EARL (EANM Research Ltd) standardization and unification of procedures is a welcome step in this direction.

Technical note: how to determine the FDG activity for tumour PET imaging that satisfies European guidelines.

BackgroundFor tumour imaging with PET, the literature proposes to administer a patient-specific FDG activity that depends quadratically on a patient’s body weight. However, a practical approach on how to implement such a protocol in clinical practice is currently lacking. We aimed to provide a practical method to determine a FDG activity formula for whole-body PET examinations that satisfies both the EANM guidelines and this quadratic relation.ResultsWe have developed a methodology that results in a formula describing the patient-specific FDG activity to administer. A PET study using the NEMA NU-2001 image quality phantom forms the basis of our method. This phantom needs to be filled with 2.0 and 20.0 kBq FDG/mL in the background and spheres, respectively. After a PET acquisition of 10 min, a reconstruction has to be performed that results in sphere recovery coefficients (RCs) that are within the specifications as defined by the EANM Research Ltd (EARL). By performing reconstructions based on shorter scan durations, the minimal scan time per bed position (Tmin) needs to be extracted using an image coefficient of variation (COV) of 15 %. At Tmin, the RCs should be within EARL specifications as well. Finally, the FDG activity (in MBq) to administer can be described by A=c cdot {w}^2cdot frac{T_{min }}{t} with c a constant that is typically 0.0533 (MBq/kg2), w the patient’s body weight (in kg), and t the scan time per bed position that is chosen in a clinical setting (in seconds). We successfully demonstrated this methodology using a state-of-the-art PET/CT scanner.ConclusionsWe provide a practical method that results in a formula describing the FDG activity to administer to individual patients for whole-body PET examinations, taking into account both the EANM guidelines and a quadratic relation between FDG activity and patient’s body weight. This formula is generally applicable to any PET system, using a specified image reconstruction and scan time per bed position.