Comparative accuracy and cost-effectiveness of dynamic contrast-enhanced CT and positron emission tomography in the characterisation of solitary pulmonary nodules.

INTRODUCTION: Dynamic contrast-enhanced CT (DCE-CT) and positron emission tomography/CT (PET/CT) have a high reported accuracy for the diagnosis of malignancy in solitary pulmonary nodules (SPNs). The aim of this study was to compare the accuracy and cost-effectiveness of these. METHODS: In this prospective multicentre trial, 380 participants with an SPN (8-30 mm) and no recent history of malignancy underwent DCE-CT and PET/CT. All patients underwent either biopsy with histological diagnosis or completed CT follow-up. Primary outcome measures were sensitivity, specificity and overall diagnostic accuracy for PET/CT and DCE-CT. Costs and cost-effectiveness were estimated from a healthcare provider perspective using a decision-model. RESULTS: 312 participants (47% female, 68.1±9.0 years) completed the study, with 61% rate of malignancy at 2 years. The sensitivity, specificity, positive predictive value and negative predictive values for DCE-CT were 95.3% (95% CI 91.3 to 97.5), 29.8% (95% CI 22.3 to 38.4), 68.2% (95% CI 62.4% to 73.5%) and 80.0% (95% CI 66.2 to 89.1), respectively, and for PET/CT were 79.1% (95% CI 72.7 to 84.2), 81.8% (95% CI 74.0 to 87.7), 87.3% (95% CI 81.5 to 91.5) and 71.2% (95% CI 63.2 to 78.1). The area under the receiver operator characteristic curve (AUROC) for DCE-CT and PET/CT was 0.62 (95% CI 0.58 to 0.67) and 0.80 (95% CI 0.76 to 0.85), respectively (p<0.001). Combined results significantly increased diagnostic accuracy over PET/CT alone (AUROC=0.90 (95% CI 0.86 to 0.93), p<0.001). DCE-CT was preferred when the willingness to pay per incremental cost per correctly treated malignancy was below £9000. Above £15 500 a combined approach was preferred. CONCLUSIONS: PET/CT has a superior diagnostic accuracy to DCE-CT for the diagnosis of SPNs. Combining both techniques improves the diagnostic accuracy over either test alone and could be cost-effective. TRIAL REGISTRATION NUMBER: NCT02013063.

FDG PET-CT imaging in head and neck paragangliomas: A centre experience.

Head and neck paragangliomas (HNPGLs) are rare tumours with ~ 30% genetic mutations, mainly in succinate dehydrogenase (SDHx) genes. The utility of FDG PET-CT in HNPGLs is questioned by recent developments in novel radiotracers. We therefore performed a retrospective study in a single tertiary referral centre to address the utility of FDG PET/CT in HNPGLs. METHODS: Clinical data on genetic testing and follow-up were collected for patients who had FDG PET-CT scans from 2004 to 2016. Receiver operator characteristic (ROC) analysis was used to compare standardized uptake values (SUVs), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) between lesions in patients who had a clinically related event: event (+) and those who did not: event (-). Similarly, we compared PET parameters between SDHx+ patients and a control group with low probability of mutation. RESULTS: Of 153 HNPGL patients, 73 (29 SDHx+) with 93 FDG-positive lesions were identified: 53.8% of lesions were assessed in a pre-therapeutic setting. In comparison with a reference extracted from clinicoradiological database, FDG PET-CT showed good performance to detect HNPGLs (96.6% accuracy). In this study population, 16 disease progression, 1 recurrence and 1 death were recorded and event (+) patients had lesions with higher SUVmax (p = .03 and p = .02, respectively). Conversely, there were no differences in PET parameters between lesions in SDHx+ patients and controls with low probability of SDHx+ mutations. CONCLUSIONS: FDG PET-CT has clinical utility in HNPGLs, mostly before local treatment. There were no significant differences in PET parameters between SDHx patients and a sporadic HNPGL population. However, regardless of SDHx mutation status, a high SUVmax was associated with more clinical events and prompts to a closer follow-up.

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.

Association between hypoxic volume and underlying hypoxia-induced gene expression in oropharyngeal squamous cell carcinoma.

BACKGROUND: Hypoxia imaging is a promising tool for targeted therapy but the links between imaging features and underlying molecular characteristics of the tumour have not been investigated. The aim of this study was to compare hypoxia biomarkers and gene expression in oropharyngeal squamous cell carcinoma (OPSCC) diagnostic biopsies with hypoxia imaged with 64Cu-ATSM PET/CT. METHODS: 64Cu-ATSM imaging, molecular and clinical data were obtained for 15 patients. Primary tumour SUVmax, tumour to muscle ratio (TMR) and hypoxic volume were tested for association with reported hypoxia gene signatures in diagnostic biopsies. A putative gene signature for hypoxia in OPSCCs (hypoxic volume-associated gene signature (HVS)) was derived. RESULTS: Hypoxic volume was significantly associated with a reported hypoxia gene signature (rho=0.57, P=0.045), but SUVmax and TMR were not. Immunohistochemical staining with the hypoxia marker carbonic anhydrase 9 (CA9) was associated with a gene expression hypoxia response (rho=0.63, P=0.01). Sixteen genes were positively and five genes negatively associated with hypoxic volume (adjusted P<0.1; eight genes had adjusted P<0.05; HVS). This signature was associated with inferior 3-year progression-free survival (HR=1.5 (1.0-2.2), P=0.047) in an independent patient cohort. CONCLUSIONS: 64Cu-ATSM-defined hypoxic volume was associated with underlying hypoxia gene expression response. A 21-gene signature derived from hypoxic volume from patients with OPSCCs in our study may be linked to progression-free survival.

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.

Interobserver variability in interim PET assessment in Hodgkin lymphoma-reasons and solutions.

INTRODUCTION: Interim PET (iPET) assessment is important for response adaptation in Hodgkin lymphoma (HL). The current standard for iPET assessment is the Deauville score (DS). The aim of our study was to evaluate the causes of interobserver variability in assigning the DS for iPET in HL patients and to make suggestions for improvement. METHODS: All evaluable iPET scans from the RAPID study were re-read by two nuclear physicians, blinded to the results and patient outcomes in the RAPID trial. The iPET scans were assessed visually according to the DS and, thereafter, quantified using the qPET method. All discrepancies of more than one DS level were re-evaluated by both readers to find the reason for the discordant result. RESULTS: In 249/441 iPET scans (56%) a concordant visual DS result was achieved. A "minor discrepancy" of one DS level occurred in 144 scans (33%) and a "major discrepancy" of more than one DS level in 48 scans (11%). The main causes for major discrepancies were 1) different interpretation of PET-positive lymph nodes-malignant vs. inflammatory; 2) lesions missed by one reader and 3) different assessment of lesions in activated brown fat tissue. In 51% of the minor discrepancy scans with residual lymphoma uptake, additional quantification resulted in a concordant quantitative DS result. CONCLUSION: Discordant visual DS assessment occurred in 44% of all iPET scans. The main reason for major discrepancies was the different interpretation of PET positive lymph nodes as malignant or inflammatory. Disagreements in evaluation of the hottest residual lymphoma lesion can be solved by the use of semi-quantitative assessment.

EFOMP's protocol quality controls in PET/CT and PET/MR.

This article presents the protocol on Quality Controls in PET/CT and PET/MRI published online in May 2022 by the European Federation of Organisations for Medical Physics (EFOMP), which was developed by the Working group for PET/CT and PET/MRI Quality Control (QC) protocol. The main objective of this protocol was to comprehensively provide simple and practical procedures that may be integrated into clinical practice to identify changes in the PET/CT/MRI system's performance and avoid short- and long-term quality deterioration. The protocol describes the quality control procedures on radionuclide calibrators, weighing scales, PET, CT and MRI systems using selected and measurable parameters that are directly linked to clinical images quality. It helps to detect problems before they can impact clinical studies in terms of safety, image quality, quantification accuracy and patient radiation dose. CT and MRI QCs are described only in the context of their use for PET (attenuation correction and anatomical localization) imaging. Detailed step-by-step instructions have been provided, limiting any misinterpretations or interpersonal variations as much as possible. This paper presents the main characteristics of the protocol illustrated together with a brief summary of the content of each chapter. A regular QC based on the proposed protocol would guarantee that PET/CT and PET/MRI systems operate under optimal conditions, resulting in the best performance for routine clinical tasks.

Quality control in PET/CT and PET/MRI: Results of a survey amongst European countries.

PURPOSE: An EFOMP Working Group (WG) was created in 2020 to establish recommendations for PET/CT/MRI Quality Control (QC). The WG's intention was to create a document containing a set of measurements suitable for routine practice. In order to map the current situation in PET facilities, the WG prepared a survey addressed to European Medical Physics Experts (MPE). METHODS: The survey was conducted using an electronic questionnaire with 10 sections, for a total of 43 multiple choice or open questions. Data regarding general information, model of installed scanners, contract of maintenance and phantoms available were collected. The focal part of the questionnaire concerned the QC protocol adopted and accreditation programs. RESULTS: 123 answers from 24 countries were collected. 90.2% of the respondents are affiliated as staff MPEs; 45% have non-digital TOF PET/CT scanners with a contract of maintenance (97.6%). In 98.4% and 86.8% of responding centres a sealed source for daily QC and the NEMA Image Quality Phantom were present. 94.3% of respondents perform daily QC according to manufacturer recommendations, while NEMA Tests are not performed routinely (51.2%). 56.1% of the respondents have scanners accredited by a national or international organization. 56% of the centres perform annual CT tests, while more than 90% do not perform any MRI QCs. CONCLUSIONS: The results of the survey show that there is a lack of harmonization in the PET QC procedures across Europe. The information obtained will guide the WG in proposing a guideline containing a set of measurements suitable for the clinical routine.

Role of 3'-Deoxy-3'-[18F] Fluorothymidine Positron Emission Tomography-Computed Tomography as a Predictive Biomarker in Argininosuccinate Synthetase 1-Deficient Thoracic Cancers Treated With Pegargiminase.

Introduction: Pegargiminase (ADI-PEG 20I) degrades arginine in patients with argininosuccinate synthetase 1-deficient malignant pleural mesothelioma (MPM) and NSCLC. Imaging with proliferation biomarker 3'-deoxy-3'-[18F] fluorothymidine (18F-FLT) positron emission tomography (PET)-computed tomography (CT) was performed in a phase 1 study of pegargiminase with pemetrexed and cisplatin (ADIPemCis). The aim was to determine whether FLT PET-CT predicts treatment response earlier than CT. Methods: A total of 18 patients with thoracic malignancies (10 MPM; eight NSCLC) underwent imaging. FLT PET-CT was performed at baseline (PET1), 24 hours post-pegargiminase monotherapy (PET2), post one cycle of ADIPemCis (PET3), and at end of treatment (EOT, PET4). CT was performed at baseline (CT1) and EOT (CT4). CT4 (modified) Response Evaluation Criteria in Solid Tumors (RECIST) response was compared with treatment response on PET (changes in maximum standardized uptake value [SUVmax] on European Organisation for Research and Treatment of Cancer-based criteria). Categorical responses (progression, partial response, and stable disease) for PET2, PET3, and PET4 were compared against CT using Cohen's kappa. Results: ADIPemCis treatment response resulted in 22% mean decrease in size between CT1 and CT4 and 37% mean decrease in SUVmax between PET1 and PET4. PET2 agreed with CT4 response in 62% (8 of 13) of patients (p = 0.043), although decrease in proliferation (SUVmax) did not precede decrease in size (RECIST). Partial responses on FLT PET-CT were detected in 20% (3 of 15) of participants at PET2 and 69% (9 of 13) at PET4 with good agreement between modalities in MPM at EOT. Conclusions: Early FLT imaging (PET2) agrees with EOT CT results in nearly two-thirds of patients. Both early and late FLT PET-CT provide evidence of response to ADIPemCis therapy in MPM and NSCLC. We provide first-in-human FLT PET-CT data in MPM, indicating it is comparable with modified RECIST.

Dynamic contrast-enhanced CT compared with positron emission tomography CT to characterise solitary pulmonary nodules: the SPUtNIk diagnostic accuracy study and economic modelling.

BACKGROUND: Current pathways recommend positron emission tomography-computerised tomography for the characterisation of solitary pulmonary nodules. Dynamic contrast-enhanced computerised tomography may be a more cost-effective approach. OBJECTIVES: To determine the diagnostic performances of dynamic contrast-enhanced computerised tomography and positron emission tomography-computerised tomography in the NHS for solitary pulmonary nodules. Systematic reviews and a health economic evaluation contributed to the decision-analytic modelling to assess the likely costs and health outcomes resulting from incorporation of dynamic contrast-enhanced computerised tomography into management strategies. DESIGN: Multicentre comparative accuracy trial. SETTING: Secondary or tertiary outpatient settings at 16 hospitals in the UK. PARTICIPANTS: Participants with solitary pulmonary nodules of ≥ 8 mm and of ≤ 30 mm in size with no malignancy in the previous 2 years were included. INTERVENTIONS: Baseline positron emission tomography-computerised tomography and dynamic contrast-enhanced computer tomography with 2 years' follow-up. MAIN OUTCOME MEASURES: Primary outcome measures were sensitivity, specificity and diagnostic accuracy for positron emission tomography-computerised tomography and dynamic contrast-enhanced computerised tomography. Incremental cost-effectiveness ratios compared management strategies that used dynamic contrast-enhanced computerised tomography with management strategies that did not use dynamic contrast-enhanced computerised tomography. RESULTS: A total of 380 patients were recruited (median age 69 years). Of 312 patients with matched dynamic contrast-enhanced computer tomography and positron emission tomography-computerised tomography examinations, 191 (61%) were cancer patients. The sensitivity, specificity and diagnostic accuracy for positron emission tomography-computerised tomography and dynamic contrast-enhanced computer tomography were 72.8% (95% confidence interval 66.1% to 78.6%), 81.8% (95% confidence interval 74.0% to 87.7%), 76.3% (95% confidence interval 71.3% to 80.7%) and 95.3% (95% confidence interval 91.3% to 97.5%), 29.8% (95% confidence interval 22.3% to 38.4%) and 69.9% (95% confidence interval 64.6% to 74.7%), respectively. Exploratory modelling showed that maximum standardised uptake values had the best diagnostic accuracy, with an area under the curve of 0.87, which increased to 0.90 if combined with dynamic contrast-enhanced computerised tomography peak enhancement. The economic analysis showed that, over 24 months, dynamic contrast-enhanced computerised tomography was less costly (£3305, 95% confidence interval £2952 to £3746) than positron emission tomography-computerised tomography (£4013, 95% confidence interval £3673 to £4498) or a strategy combining the two tests (£4058, 95% confidence interval £3702 to £4547). Positron emission tomography-computerised tomography led to more patients with malignant nodules being correctly managed, 0.44 on average (95% confidence interval 0.39 to 0.49), compared with 0.40 (95% confidence interval 0.35 to 0.45); using both tests further increased this (0.47, 95% confidence interval 0.42 to 0.51). LIMITATIONS: The high prevalence of malignancy in nodules observed in this trial, compared with that observed in nodules identified within screening programmes, limits the generalisation of the current results to nodules identified by screening. CONCLUSIONS: Findings from this research indicate that positron emission tomography-computerised tomography is more accurate than dynamic contrast-enhanced computerised tomography for the characterisation of solitary pulmonary nodules. A combination of maximum standardised uptake value and peak enhancement had the highest accuracy with a small increase in costs. Findings from this research also indicate that a combined positron emission tomography-dynamic contrast-enhanced computerised tomography approach with a slightly higher willingness to pay to avoid missing small cancers or to avoid a 'watch and wait' policy may be an approach to consider. FUTURE WORK: Integration of the dynamic contrast-enhanced component into the positron emission tomography-computerised tomography examination and the feasibility of dynamic contrast-enhanced computerised tomography at lung screening for the characterisation of solitary pulmonary nodules should be explored, together with a lower radiation dose protocol. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018112215 and CRD42019124299, and the trial is registered as ISRCTN30784948 and ClinicalTrials.gov NCT02013063. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 17. See the NIHR Journals Library website for further project information.

A nodule found on a lung scan can cause concern as it may be a sign of cancer. Finding lung cancer nodules when they are small (i.e. < 3 cm) is very important. Most nodules are not cancerous. Computerised tomography (cross-sectional images created from multiple X-rays) and positron emission tomography­computerised tomography (a technique that uses a radioactive tracer combined with computerised tomography) are used to see whether or not a nodule is cancerous; although they perform well, improvements are required. This study compared dynamic contrast-enhanced computerised tomography with positron emission tomography­computerised tomography scans to find out which test is best. Dynamic contrast-enhanced computerised tomography involves injection of a special dye into the bloodstream, followed by repeated scans of the nodule over several minutes. We assessed the costs to the NHS of undertaking the different scans, relative to their benefits, to judge which option was the best value for money. We recruited 380 patients from 16 hospitals across England and Scotland, of whom 312 had both dynamic contrast-enhanced computerised tomography and positron emission tomography­computerised tomography scans. We found that current positron emission tomography­computerised tomography is more accurate, providing a correct diagnosis in 76% of cases, than the new dynamic contrast-enhanced computerised tomography, which provides a correct diagnosis in 70% of cases. Although dynamic contrast-enhanced computerised tomography cannot replace positron emission tomography­computerised tomography, it may represent good-value use of NHS resources, especially if it is performed before positron emission tomography­computerised tomography and they are used in combination. Although more research is required, it may be possible in the future to perform dynamic contrast-enhanced computerised tomography at the same time as positron emission tomography­computerised tomography in patients with suspected lung cancer or if a lung nodule is found on a lung screening programme at the time of the computerised tomography examination. This may reduce the need for some people to have positron emission tomography­computerised tomography.

Optimisation of CT protocols in PET-CT across different scanner models using different automatic exposure control methods and iterative reconstruction algorithms.

BACKGROUND: A significant proportion of the radiation dose from a PET-CT examination is dependent on the CT protocol, which should be optimised for clinical purposes. Matching protocols on different scanners within an imaging centre is important for the consistency of image quality and dose. This paper describes our experience translating low-dose CT protocols between scanner models utilising different automatic exposure control (AEC) methods and reconstruction algorithms. METHODS: The scanners investigated were a newly installed Siemens Biograph mCT PET with 64-slice SOMATOM Definition AS CT using sinogram affirmed iterative reconstruction (SAFIRE) and two GE Discovery 710 PET scanners with 128-slice Optima 660 CT using adaptive statistical reconstruction (ASiR). Following exploratory phantom work, 33 adult patients of various sizes were scanned using the Siemens scanner and matched to patients scanned using our established GE protocol to give 33 patient pairs. A comparison of volumetric CT dose index (CTDIvol) and image noise within these patient pairs informed optimisation, specifically for obese patients. Another matched patient study containing 27 patient pairs was used to confirm protocol matching. Size-specific dose estimates (SSDEs) were calculated for patients in the second cohort. With the acquisition protocol for the Siemens scanner determined, clinicians visually graded the images to identify optimal reconstruction parameters. RESULTS: In the first matched patient study, the mean percentage difference in CTDIvol for Siemens compared to GE was - 10.7% (range - 41.7 to 50.1%), and the mean percentage difference in noise measured in the patients' liver was 7.6% (range - 31.0 to 76.8%). In the second matched patient study, the mean percentage difference in CTDIvol for Siemens compared to GE was - 20.5% (range - 43.1 to 1.9%), and the mean percentage difference in noise was 19.8% (range - 27.0 to 146.8%). For these patients, the mean SSDEs for patients scanned on the Siemens and GE scanners were 3.27 (range 2.83 to 4.22) mGy and 4.09 (range 2.81 to 4.82) mGy, respectively. The analysis of the visual grading study indicated no preference for any of the SAFIRE strengths. CONCLUSIONS: Given the different implementations of acquisition parameters and reconstruction algorithms between vendors, careful consideration is required to ensure optimisation and standardisation of protocols.

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.

Quantitative assessment of interim PET in Hodgkin lymphoma: An evaluation of the qPET method in adult patients in the RAPID trial.

AIM: qPET is a quantitative method used to assess FDG-PET response in lymphoma. qPET was developed using 898 scans from children with Hodgkin Lymphoma (HL) in the EuroNet-PHL-C1 (C1) trial. The aim of this study was to determine if qPET could be applied as an alternative response method in adults in the RAPID trial. METHODS: PET-CT scans performed after 3 cycles of ABVD in RAPID were re-evaluated by an independent reader, blinded to PET results and outcome in RAPID. All initially involved regions were assessed visually and by qPET. The distribution of qPET measurements was compared for RAPID and C1 patients. Previously published qPET thresholds corresponding to visual DS (vDS) of 1-5 in C1 were used to derive quantitative DS (qDS) for RAPID patients. RESULTS: PET-CT scans were available for 450 patients from RAPID. vDS were 1 (171 scans), 2 (153 scans), 3 (72 scans), 4 (31 scans) and 5 (23 scans) respectively. The distribution of qPET values was similar to C1 patients, with a unimodal 'normal' distribution and a long tail to the right, suggestive of favorable response in the majority and less favorable response in the minority with outlying values. qPET thresholds from C1 applied in RAPID patients gave 86% concordance for vDS and qDS. There was 97% concordance for complete metabolic response (CMR; DS 1-3) vs. no-CMR using the Lugano classification. CONCLUSION: qPET which was developed in pediatric patients receiving more intensive OEPA chemotherapy, was a suitable quantitative method for assessing response in adult patients treated with ABVD in a response-adapted setting in the RAPID trial.

Advanced Sandwich Composite Cores for Patient Support in Advanced Clinical Imaging and Oncology Treatment.

Ongoing advances in both imaging and treatment for oncology purposes have seen a significant rise in the use of not only the individual imaging modalities, but also their combination in single systems such as Positron Emission Tomography combined with Computed Tomography (PET-CT) and PET-MRI (Magnetic Resonance Imaging) when planning for advanced oncology treatment, the most demanding of which is proton therapy. This has identified issues in the availability of suitable materials upon which to support the patient undergoing imaging and treatment owing to the differing requirements for each of the techniques. Sandwich composites are often selected to solve this issue but there is little information regarding optimum materials for their cores. In this paper, we presented a range of materials which are suitable for such purposes and evaluated the performance for use in terms of PET signal attenuation, proton beam stopping, MRI signal shading and X-Ray CT visibility. We found that Extruded Polystyrene offers the best compromise for patient support and positioning structures across all modalities tested, allowing for significant savings in treatment planning time and delivering more efficient treatment with lower margins.

Functional foods and urban agriculture: two responses to climate change-related food insecurity.

Affluent diets have negative effects on the health of the population and the environment. Moreover, the ability of industrialised agricultural ecosystems to continue to supply these diets is threatened by the anticipated consequences of climate change. By challenging the ongoing supply the diets of affluent countries, climate change provides a population and environmental health opportunity. This paper contrasts two strategies for dealing with climate change-related food insecurity. Functional foods are being positioned as one response because they are considered a hyper-efficient mechanism for supplying essential micronutrients. An alternative response is civic and urban agriculture. Rather than emphasising increased economic or nutritional efficiencies, civic agriculture presents a holistic approach to food security that is more directly connected to the economic, environmental and social factors that affect diet and health.

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.

Machine-learned target volume delineation of 18F-FDG PET images after one cycle of induction chemotherapy.

Biological tumour volume (GTVPET) delineation on 18F-FDG PET acquired during induction chemotherapy (ICT) is challenging due to the reduced metabolic uptake and volume of the GTVPET. Automatic segmentation algorithms applied to 18F-FDG PET (PET-AS) imaging have been used for GTVPET delineation on 18F-FDG PET imaging acquired before ICT. However, their role has not been investigated in 18F-FDG PET imaging acquired after ICT. In this study we investigate PET-AS techniques, including ATLAAS a machine learned method, for accurate delineation of the GTVPET after ICT. Twenty patients were enrolled onto a prospective phase I study (FiGaRO). PET/CT imaging was acquired at baseline and 3 weeks following 1 cycle of induction chemotherapy. The GTVPET was manually delineated by a nuclear medicine physician and clinical oncologist. The resulting GTVPET was used as the reference contour. The ATLAAS original statistical model was expanded to include images of reduced metabolic activity and the ATLAAS algorithm was re-trained on the new reference dataset. Estimated GTVPET contours were derived using sixteen PET-AS methods and compared to the GTVPET using the Dice Similarity Coefficient (DSC). The mean DSC for ATLAAS, 60% Peak Thresholding (PT60), Adaptive Thresholding (AT) and Watershed Thresholding (WT) was 0.72, 0.61, 0.63 and 0.60 respectively. The GTVPET generated by ATLAAS compared favourably with manually delineated volumes and in comparison, to other PET-AS methods, was more accurate for GTVPET delineation after ICT. ATLAAS would be a feasible method to reduce inter-observer variability in multi-centre trials.