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

PURPOSE: To 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. METHODS: The 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. RESULTS: A 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. CONCLUSION: It 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.

Automated Segmentation of Baseline Metabolic Total Tumor Burden in Diffuse Large B-Cell Lymphoma: Which Method Is Most Successful? A Study on Behalf of the PETRA Consortium.

Metabolic tumor volume (MTV) is a promising biomarker of pretreatment risk in diffuse large B-cell lymphoma (DLBCL). Different segmentation methods can be used that predict prognosis equally well but give different optimal cutoffs for risk stratification. Segmentation can be cumbersome; a fast, easy, and robust method is needed. Our aims were to evaluate the best automated MTV workflow in DLBCL; determine whether uptake time, compliance or noncompliance with standardized recommendations for 18F-FDG scanning, and subsequent disease progression influence the success of segmentation; and assess differences in MTVs and discriminatory power of segmentation methods. Methods: One hundred forty baseline 18F-FDG PET/CT scans were selected from U.K. and Dutch studies on DLBCL to provide a balance between scans at 60 and 90 min of uptake, parameters compliant and noncompliant with standardized recommendations for scanning, and patients with and without progression. An automated tool was applied for segmentation using an SUV of 2.5 (SUV2.5), an SUV of 4.0 (SUV4.0), adaptive thresholding (A50P), 41% of SUVmax (41%), a majority vote including voxels detected by at least 2 methods (MV2), and a majority vote including voxels detected by at least 3 methods (MV3). Two independent observers rated the success of the tool to delineate MTV. Scans that required minimal interaction were rated as a success; scans that missed more than 50% of the tumor or required more than 2 editing steps were rated as a failure. Results: One hundred thirty-eight scans were evaluable, with significant differences in success and failure ratings among methods. The best performing was SUV4.0, with higher success and lower failure rates than any other method except MV2, which also performed well. SUV4.0 gave a good approximation of MTV in 105 (76%) scans, with simple editing for a satisfactory result in additionally 20% of cases. MTV was significantly different for all methods between patients with and without progression. The 41% segmentation method performed slightly worse, with longer uptake times; otherwise, scanning conditions and patient outcome did not influence the tool's performance. The discriminative power was similar among methods, but MTVs were significantly greater using SUV4.0 and MV2 than using other thresholds, except for SUV2.5. Conclusion: SUV4.0 and MV2 are recommended for further evaluation. Automated estimation of MTV is feasible.

Guidance on the use of PET for treatment planning in radiotherapy clinical trials.

The aim of this article is to propose meaningful guidance covering the practical and technical issues involved when planning or conducting clinical trials involving positron emission tomography (PET)-guided radiotherapy. The complexity of imaging requirements will depend on the study aims, design and PET methods used. Where PET is used to adapt radiotherapy, a high level of accuracy and reproducibility is required to ensure effective and safe treatment delivery. The guidance in this document is intended to assist researchers designing clinical trials involving PET-guided radiotherapy to provide sufficient information about the appropriate methods to complete PET-CT imaging to a consistent standard at participating centres. The guidance is divided into six categories: application of PET in radiotherapy, resource requirements, quality assurance, imaging protocol design, data management and image processing. Each section provides an overview of the recent literature to support the specific recommendations. This guidance builds on previous recommendations from the National Cancer Research Institute PET Research Network and has been produced in collaboration with the National Radiotherapy Trials Quality Assurance Group.

PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study.

International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice.

FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0.

The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.

Positron emission tomography oncology research in the UK: a comparison with USA and Europe.

PET imaging with 18F-fluorodeoxyglucose (FDG) has become a valuable procedure in oncology patient management and drug development. The availability of non-FDG radiotracers to study different aspects of cancer biology presents new opportunities to improve healthcare outcomes and develop new therapeutics. An investigation has been carried out to determine the extent of the use of non-FDG tracers in the UK, assess overall oncology PET research activity and document current UK PET infrastructure. There has been significant recent investment in PET facilities, increasing the UK's capacity to undertake PET research. Nevertheless, the UK still has a lower level of PET equipment compared with Europe and the USA. Despite the increase in PET imaging capacity in UK research centres, there has not been an increase in non-FDG research, with most studies utilizing FDG at multiple sites. Most non-FDG trials are single-centre studies at well established centres. High tracer prices, a limited range of non-FDG tracers and restricted geographical availability make multicentre trials with non-FDG radiotracers difficult. Several solutions have been identified: formation of purchasing consortia for 18F-labelled radiotracers, production of radiotracers with longer half-lives and establishment of production at regional supply centres.