EANM/EARL harmonization strategies in PET quantification: from daily practice to multicentre oncological studies

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

Feasibility of state of the art PET/CT systems performance harmonisation

Purpose The objective of this study was to explore the feasibility of harmonising performance for PET/CT systems equipped with time-of-flight (ToF) and resolution modelling/point spread function (PSF) technologies. A second aim was producing a working prototype of new harmonising criteria with higher contrast recoveries than current EARL standards using various SUV metrics. Methods Four PET/CT systems with both ToF and PSF capabilities from three major vendors were used to acquire and reconstruct images of the NEMA NU2-2007 body phantom filled conforming EANM EARL guidelines. A total of 15 reconstruction parameter sets of varying pixel size, post filtering and reconstruction type, with three different acquisition durations were used to compare the quantitative performance of the systems. A target range for recovery curves was established such that it would accommodate the highest matching recoveries from all investigated systems. These updated criteria were validated on 18 additional scanners from 16 sites in order to demonstrate the scanners' ability to meet the new target range. Results Each of the four systems was found to be capable of producing harmonising reconstructions with similar recovery curves. The five reconstruction parameter sets producing harmonising results significantly increased SUVmean (25%) and SUVmax (26%) contrast recoveries compared with current EARL specifications. Additional prospective validation performed on 18 scanners from 16 EARL accredited sites demonstrated the feasibility of updated harmonising specifications. SUVpeak was found to significantly reduce the variability in quantitative results while producing lower recoveries in smaller (<= 17 mm diameter) sphere sizes. Conclusions Harmonising PET/CT systems with ToF and PSF technologies from different vendors was found to be feasible. The harmonisation of such systems would require an update to the current multicentre accreditation program EARL in order to accommodate higher recoveries. SUVpeak should be further investigated as a noise resistant alternative quantitative metric to SUVmax

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

Purpose From 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. Methods To 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. Results SUV 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. Conclusions Regardless 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

Feasibility of PET/CT system performance harmonisation for quantitative multicentre Zr-89 studies

PurposeThe aim of this study was to investigate the variability in quantitative performance and feasibility of quantitative harmonisation in Zr-89 PET/CT imaging.MethodsEight EANM EARL-accredited (Kaalep A et al., Eur J Nucl Med Mol Imaging 45:412-22, 2018) PET/CT systems were investigated using phantom acquisitions of uniform and NEMA NU2-2007 body phantoms. The phantoms were filled according to EANM EARL guidelines for [F-18]FDG, but [F-18]FDG solution was replaced by a Zr-89 calibration mixture. For each system, standard uptake value (SUV) accuracy and recovery coefficients (RC) using SUVmean, SUVmax and SUVpeak metrics were determined.ResultsAll eight investigated systems demonstrated similarly shaped RC curves, and five of them exhibited closely aligning recoveries when SUV bias correction was applied. From the evaluated metrics, SUVpeak was found to be least sensitive to noise and reconstruction differences among different systems.ConclusionsHarmonisation of PET/CT scanners for quantitative Zr-89 studies is feasible when proper scanner-dose calibrator cross-calibration and harmonised image reconstruction procedures are followed. An accreditation programme for PET/CT scanners would facilitate multicentre Zr-89 quantitative studies

Quantitative implications of the updated EARL 2019 PET-CT performance standards

Purpose Recently, updated EARL specifications (EARL2) have been developed and announced. This study aims at investigating the impact of the EARL2 specifications on the quantitative reads of clinical PET-CT studies and testing a method to enable the use of the EARL2 standards whilst still generating quantitative reads compliant with current EARL standards (EARL1). Methods Thirteen non-small cell lung cancer (NSCLC) and seventeen lymphoma PET-CT studies were used to derive four image datasets-the first dataset complying with EARL1 specifications and the second reconstructed using parameters as described in EARL2. For the third (EARL2F6) and fourth (EARL2F7) dataset in EARL2, respectively, 6 mm and 7 mm Gaussian post-filtering was applied. We compared the results of quantitative metrics (MATV, SUVmax, SUVpeak, SUVmean, TLG, and tumor-to-liver and tumor-to-blood pool ratios) obtained with these 4 datasets in 55 suspected malignant lesions using three commonly used segmentation/volume of interest (VOI) methods (MAX41, A50P, SUV4). Results We found that with EARL2 MAX41 VOI method, MATV decreases by 22%, TLG remains unchanged and SUV values increase by 23-30% depending on the specific metric used. The EARL2F7 dataset produced quantitative metrics best aligning with EARL1, with no significant differences between most of the datasets (p>0.05). Different VOI methods performed similarly with regard to SUV metrics but differences in MATV as well as TLG were observed. No significant difference between NSCLC and lymphoma cancer types was observed. Conclusions Application of EARL2 standards can result in higher SUVs, reduced MATV and slightly changed TLG values relative to EARL1. Applying a Gaussian filter to PET images reconstructed using EARL2 parameters successfully yielded EARL1 compliant data

Radiation Safety and Accidental Radiation Exposures in Nuclear Medicine

Medical radiation accidents and unintended events may lead to accidental or unintended medical exposure of patients and exposure of staff or the public. Most unintended exposures in nuclear medicine will lead to a small increase in risk; nevertheless, these require investigation and a clinical and dosimetric assessment. Nuclear medicine staff are exposed to radiation emitted directly by radiopharmaceuticals and by patients after administration of radiopharmaceuticals. This is particularly relevant in PET, due to the penetrating 511 keV γ-rays. Dose constraints should be set for planning the exposure of individuals. Staff body doses of 1-25 µSv/GBq are reported for PET imaging, the largest component being from the injection. The preparation and administration of radiopharmaceuticals can lead to high doses to the hands, challenging dose limits for radionuclides such as 90Y and even 18F. The risks of contamination can be minimized by basic precautions, such as carrying out manipulations in purpose-built facilities, wearing protective clothing, especially gloves, and removing contaminated gloves or any skin contamination as quickly as possible. Airborne contamination is a potential problem when handling radioisotopes of iodine or administering radioaerosols. Manipulating radiopharmaceuticals in laminar air flow cabinets, and appropriate premises ventilation are necessary to improve safety levels. Ensuring patient safety and minimizing the risk of incidents require efficient overall quality management. Critical aspects include: the booking process, particularly if qualified medical supervision is not present; administration of radiopharmaceuticals to patients, with the risk of misadministration or extravasation; management of patients' data and images by information technology systems, considering the possibility of misalignment between patient personal data and clinical information. Prevention of possible mistakes in patient identification or in the management of patients with similar names requires particular attention. Appropriate management of pregnant or breast-feeding patients is another important aspect of radiation safety. In radiopharmacy activities, strict quality assurance should be implemented at all operational levels, in addition to adherence to national and international regulations and guidelines. This includes not only administrative aspects, like checking the request/prescription, patient's data and the details of the requested procedure, but also quantitative tests according to national/international pharmacopoeias, and measuring the dispensed activity with a calibrated activity meter prior to administration. In therapy with radionuclides, skin tissue reactions can occur following extravasation, which can result in localized doses of tens of Grays. Other relevant incidents include confusion of products for patients administered at the same time or malfunction of administration devices. Furthermore, errors in internal radiation dosimetry calculations for treatment planning may lead to under or over-treatment. According to literature, proper instructions are fundamental to keep effective dose to caregivers and family members after patient discharge below the Dose constraints. The IAEA Basic Safety Standards require measures to minimize the likelihood of any unintended or accidental medical exposures and reporting any radiation incident. The relative complexity of nuclear medicine practice presents many possibilities for errors. It is therefore important that all activities are performed according to well established procedures, and that all actions are supported by regular quality assurance/QC procedures. © 2021 Elsevier Inc