Current generation time-of-flight 18F-FDG PET/CT provides higher SUVs for normal adrenal glands, while maintaining an accurate characterization of benign and malignant glands

OBJECTIVE: Modern PET/CT scanners have significantly improved detectors and fast time-of-flight (TOF) performance and this may improve clinical performance. The aim of this study was to analyze the impact of a current generation TOF PET/CT scanner on standardized uptake values (SUV), lesion-background contrast and characterization of the adrenal glands in patients with suspected lung cancer, in comparison with literature data and commonly used SUV cut-off levels. METHODS: We included 149 adrenal glands from 88 patients with suspected lung cancer, who underwent (18)F-FDG PET/CT. We measured the SUV(max) in the adrenal gland and compared this with liver SUV(mean) to calculate the adrenal-to-liver ratio (AL ratio). Results were compared with literature derived with older scanners, with SUV(max) values of 1.0 and 1.8 for normal glands [1, 2]. Final diagnosis was based on histological proof or follow-up imaging. We proposed cut-off values for optimal separation of benign from malignant glands. RESULTS: In 127 benign and 22 malignant adrenal glands, SUV(max) values were 2.3 ± 0.7 (mean ± SD) and 7.8 ± 3.2 respectively (p < 0.01). Corresponding AL ratios were 1.0 ± 0.3 and 3.5 ± 1.4 respectively (p < 0.01). With a SUV(max) cut-off value of 3.7, 96 % sensitivity and 96 % specificity was reached. An AL ratio cut-off value of 1.8 resulted in 91 % sensitivity and 97 % specificity. The ability of both SUV(max) and AL ratio to separate benign from malignant glands was similar (AUC 0.989 vs. 0.993, p = 0.22). CONCLUSIONS: Compared with literature based on the previous generation of PET scanners, current generation TOF (18)F-FDG PET/CT imaging provides higher SUVs for benign adrenal glands, while it maintains a highly accurate distinction between benign and malignant glands. Clinical implementation of current generation TOF PET/CT requires not only the use of higher cut-off levels but also visual adaptation by PET readers

Development and evaluation of digital twins for district-level heating energy demand simulation.

To achieve the aim of a CO2 neutral built environment in 2050, a large part of the existing housing stock will have to be energetically retrofitted. It has been noted that a neighbourhood-oriented approach will be necessary for the feasibility, affordability and timeliness of this aim. Considering that many different stakeholders are involved in renovations at the neighbourhood level, and that multiple neighbourhoods will have to be retrofitted at the same time, efficient working methods are imperative. To facilitate the design, construction and operation of the new energy infrastructure, a prototype for a digital environment (digital twin) is developed for four Dutch pilot neighbourhoods. In this contribution, the authors will describe a procedure to convert publicly available geo-information to a CityGML model, which is used to simulate the monthly and annual space heating energy demand using SimStadt. To assess model fidelity, the simulation results are compared with publicly available aggregated energy use data. A procedure will be described to split the measured natural gas use into gas usage for space heating, domestic hot water and cooking. It is found that the simulation tends to overestimate the energy demand for space heating by 4 - 125%. This difference is largely explained by the manner in which the thermal properties of the buildings are estimated. In addition, the homogeneity of the neighbourhood in terms of the different building functions present has an impact on the accuracy of the simulation. Finally, possible invalid assumptions concerning setpoint temperatures and internal heating loads are of interest. It is concluded that more accurate simulation results will be obtained through the use of current input data. Most importantly: (i) reliable information on the buildings’ current thermal properties through e.g. energy audits, and (ii) reliable information on the buildings’ setpoint temperatures and internal heating loads through on-board monitoring systems

Increasing the etanercept dose in a treat-to-target approach in juvenile idiopathic arthritis:does it help to reach the target? A post-hoc analysis of the BeSt for Kids randomised clinical trial

Background: Etanercept has been studied in doses up to 0.8 mg/kg/week (max 50 mg/week) in juvenile idiopathic arthritis (JIA) patients. In clinical practice higher doses are used off-label, but evidence regarding the relation with outcomes is lacking. We describe the clinical course of JIA-patients receiving high-dose etanercept (1.6 mg/kg/week; max 50 mg/week) in the BeSt for Kids trial. Methods: 92 patients with oligoarticular JIA, RF-negative polyarticular JIA or juvenile psoriatic arthritis were randomised across three treat-to-target arms: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination-therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX + etanercept. In any treatment-arm, patients could eventually escalate to high-dose etanercept alongside MTX 10mg/m2/week. Results: 32 patients received high-dose etanercept (69% female, median age 6 years (IQR 4–10), median 10 months (7–16) from baseline). Median follow-up was 24.6 months. Most clinical parameters improved within 3 months after dose-increase: median JADAS10 from 7.2 to 2.8 (p = 0.008), VAS-physician from 12 to 4 (p = 0.022), VAS-patient/parent from 38.5 to 13 (p = 0.003), number of active joints from 2 to 0.5 (p = 0.12) and VAS-pain from 35.5 to 15 (p = 0.030). Functional impairments (CHAQ-score) improved more gradually and ESR remained stable. A comparable pattern was observed in 11 patients (73% girls, median age 8 (IQR 6–9)) who did not receive high-dose etanercept despite eligibility (comparison group). In both groups, 56% reached inactive disease at 6 months. No severe adverse events (SAEs) occurred after etanercept dose-increase. In the comparison group, 2 SAEs consisting of hospital admission occurred. Rates of non-severe AEs per subsequent patient year follow-up were 2.27 in the high-dose and 1.43 in the comparison group. Conclusions: Escalation to high-dose etanercept in JIA-patients who were treated to target was generally followed by meaningful clinical improvement. However, similar improvements were observed in a smaller comparison group who did not escalate to high-dose etanercept. No SAEs were seen after escalation to high-dose etanercept. The division into the high-dose and comparison groups was not randomised, which is a potential source of bias. We advocate larger, randomised studies of high versus regular dose etanercept to provide high level evidence on efficacy and safety. Trial registration: Dutch Trial Register; NTR1574; 3 December 2008; https://onderzoekmetmensen.nl/en/trial/26585.</p

Significant pain decrease in children with non-systemic Juvenile Idiopathic Arthritis treated to target:results over 24 months of follow up

Background: The aim of this study was to compare pain-scores in three targeted treatment-strategies in JIA-patients and to identify characteristics predicting persistent pain. Methods: In the BeSt-for-Kids-study 92 DMARD-naïve JIA-patients were randomized in 3 treatment-strategies: 1) initial sequential DMARD-monotherapy 2) initial methotrexate (MTX)/prednisolone-bridging or 3) initial MTX/etanercept. Potential differences in VAS pain scores (0-100 mm) over time between treatment-strategies were compared using linear mixed models with visits clustered within patients. A multivariable model was used to assess the ability of baseline characteristics to predict the chance of high pain-scores during follow-up. Results: Pain-scores over time reduced from mean 55.3 (SD 21.7) to 19.5 (SD 25.3) mm after 24 months. On average, pain-scores decreased significantly with β -1.37 mm (95% CI -1.726; -1.022) per month. No significant difference was found between treatment-strategies (interaction term treatment arm*time (months) β (95% CI) arm 1: 0.13 (-0.36; 0.62) and arm 2: 0.37 (-0.12; 0.86) compared to arm 3). Correction for sex and symptom duration yielded similar results. Several baseline characteristics were predictive for pain over time. Higher VAS pain [β 0.44 (95% CI 0.25; 0.65)] and higher active joint count [0.77 (0.19; 1.34)] were predictive of higher pain over time, whereas, low VAS physician [-0.34 (-0.55; -0.06)], CHQ Physical [-0.42 (-0.72; -0.11)] and Psychosocial summary Score [-0.42 (-0.77; -0.06)] were predictive of lower pain. Conclusions: Treatment-to-target seems effective in pain-reduction in non-systemic JIA-patients irrespective of initial treatment-strategy. Several baseline-predictors for pain over time were found, which could help to identify patients with a high risk for development of chronic pain. Trial registration: Dutch Trial Registry number 1574.</p

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Small lesion detection with new PET technology

FDG-PET/CT imaging plays an important role in the diagnostic evaluation of cancer. However, this technique has two major limitations: a low spatial resolution and a limited system sensitivity. Consequently, the detection of small lesions (<20 mm) is limited and PET images have a relatively low signal-to-noise ratio. Since the clinical introduction of whole-body PET 20 years ago, several techniques were introduced, such as new reconstruction methods and digital detectors, to improve the image quality and diagnostic performance of PET. The aim of this thesis was to evaluate the impact of these new PET techniques on the detection of small lesions in cancer imaging. We studied the influence of conventional TOF-PET scanners and small-voxel reconstructions on small lesion detectability in lung and breast cancer. Furthermore, we studied digital TOF-PET scanners and determined their impact on semi-quantitative uptake measurements, image quality and lesion detectability in patients with cancer. Moreover, we evaluated the impact of conventional and digital PET scanners on European guidelines and procedure standards (EARL) for PET imaging using two different radionuclides. We performed three retrospective and two prospective studies in patients with cancer. We found that the use of smaller voxels and digital PET technology resulted in an improved detection of small lesions with higher standardized uptake values, higher signal-to-noise ratio’s, improved visual image quality and disease upstaging in some cases. We also demonstrated that images acquired with state-of-the-art PET scanners provided higher uptake values for both benign and malignant lesions. Therefore, PET readers should adapt their reference standards to distinguish benign from malignant when evaluating PET images acquired on such modern PET systems. Meanwhile, we also demonstrated that when using standardised EARL protocols and following European guidelines, conventional and digital PET systems can be used interchangeably

Impact of image processing in the detection of ischaemia using CZT-SPECT/CT

Background:\ud The new multipinhole cardiac single photon emission computed tomography/computed tomography (SPECT/CT) cameras with cadmium–zinc–telluride (CZT) detectors are highly sensitive and produce images of high quality but rely on complex dedicated reconstruction algorithms. The aim of this study was to determine the impact of various processing steps on image formation and in the detection of ischaemia in CZT-SPECT/CT both with and without attenuation correction (AC).\ud \ud Materials and methods:\ud Data on 20 consecutive patients who underwent a 1-day protocol stress–rest SPECT/CT using 99mTc-tetrofosmin were processed twice by three experienced operators, yielding 120 AC and 120 noncorrected (NC) data sets. Processing steps included selection and determination of myocardial axes, manual SPECT/CT coregistration for AC and myocardial masking. Using the 17-segment cardiac model, differences between stress and rest segmental uptake (%) were calculated for NC and AC image sets. Both interoperator and intraoperator variations were considered significant for the diagnosis of ischaemia when greater than 5%.\ud \ud Results:\ud The mean interoperator variations were 2.4±1.4% (NC) and 3.8±1.9% (AC) (P<0.01). In 6% (NC) and 23% (AC) of the 120 processed cases, operator variation was larger than 5% and therefore potentially clinically interfering with the diagnosis of ischaemia. Differences between interoperator and intraoperator variations were nonsignificant.\ud \ud Conclusion:\ud Operator variations in the processing of myocardial perfusion image data using CZT-SPECT/CT are significant and may influence the diagnosis of ischaemia, especially when AC is applied. Clearer guidelines for image processing are necessary to improve the reproducibility of the studies and to obtain a more reliable diagnosis of ischaemia

Improving the detection of small lesions using a state-of-the-art time-of-flight PET/CT system and small-voxel reconstructions

A major disadvantage of 18F-FDG PET involves poor detection of small lesions and lesions with low metabolism, caused by limited spatial resolution and relatively large image voxel size. As spatial resolution and sensitivity are better in new PET systems, it is expected that small-lesion detection could be improved using smaller voxels. The aim of this study was to test this hypothesis using a state-of-the-art time-of-flight PET/CT device. Methods: 18F-FDG PET scans of 2 image-quality phantoms (sphere sizes, 4–37 mm) and 39 consecutive patients with lung cancer were analyzed on a time-of-flight PET/CT system. Images were iteratively reconstructed with standard 4 × 4 × 4 mm voxels and smaller 2 × 2 × 2 mm voxels. For the phantom study, we determined contrast-recovery coefficients and signal-to-noise ratios (SNRs). For the patient study, 18F-FDG PET–positive lesions in the chest and upper abdomen with a volume less than 3.0 mL (diameter, <18 mm) were included. Lesion mean and maximum standardized uptake values (SUVmean and SUVmax, respectively) were determined in both image sets. SNRs were determined by comparing SUVmax and SUVmean with background noise levels. A subanalysis was performed for lesions less than 0.75 mL (diameter, <11 mm). For qualitative analysis of patient data, 3 experienced nuclear medicine physicians gave their preference after visual side-by-side analysis. Results: For phantom spheres 13 mm or less, we found higher contrast-recovery coefficients and SNRs using small-voxel reconstructions. For 66 included 18F-FDG PET–positive lesions, the average increase in SUVmean and SUVmax using the small-voxel images was 17% and 32%, respectively (P < 0.01). For lesions less than 0.75 mL (21 in total), the average increase was 21% and 44%, respectively. Moreover, averaged over all lesions, the mean and maximum SNR increased by 20% and 27%, respectively (P < 0.01). For lesions less than 0.75 mL, these values increased up to 23% and 46%, respectively. The physicians preferred the small-voxel reconstructions in 76% of cases. Conclusion: Supported by a phantom study, there was a visual preference toward 18F-FDG PET images reconstructed with 2 × 2 × 2 mm voxels and a profound increase in standardized uptake value and SNR for small lesions. Hence, it is expected that small-lesion detection improves using small-voxel reconstructions

SUV variability in EARL-accredited conventional and digital PET

Background: A high SUV-reproducibility is crucial when different PET scanners are in use. We evaluated the SUV variability in whole-body FDG-PET scans of patients with suspected or proven cancer using an EARL-accredited conventional and digital PET scanner. In a head-to-head comparison we studied images of 50 patients acquired on a conventional scanner (cPET, Ingenuity TF PET/CT, Philips) and compared them with images acquired on a digital scanner (dPET, Vereos PET/CT, Philips). The PET scanning order was randomised and EARL-compatible reconstructions were applied. We measured SUVmean, SUVpeak, SUVmax and lesion diameter in up to 5 FDG-positive lesions per patient. The relative difference ΔSUV between cPET and dPET was calculated for each SUV-parameter. Furthermore, we calculated repeatability coefficients, reflecting the 95% confidence interval of ΔSUV. Results: We included 128 lesions with an average size of 19 ± 14 mm. Average ΔSUVs were 6-8% with dPET values being higher for all three SUV-parameters (p < 0.001). ΔSUVmax was significantly higher than ΔSUVmean (8% vs. 6%, p = 0.002) and than ΔSUVpeak (8% vs. 7%, p = 0.03). Repeatability coefficients across individual lesions were 27% (ΔSUVmean and ΔSUVpeak) and 33% (ΔSUVmax) (p < 0.001). Conclusions: With EARL-accredited conventional and digital PET, we found a limited SUV variability with average differences up to 8%. Furthermore, only a limited number of lesions showed a SUV difference of more than 30%. These findings indicate that EARL standardisation works. Trial registration: This prospective study was registered on the 31th of October 2017 at ClinicalTrials.cov. URL: https://clinicaltrials.gov/ct2/show/NCT03457506?id=03457506&rank=1

Adverse Events of Diagnostic Radiopharmaceuticals: A Systematic Review

Diagnostic radiopharmaceuticals used in nuclear medicine can cause adverse events. Information on these adverse events is available in case reports and databases but may not be readily accessible to healthcare professionals. This systematic review provides an overview of adverse events of diagnostical radiopharmaceuticals and their characteristics. A median frequency for adverse events in diagnostical radiopharmaceuticals of 1.63 (interquartile range: 1.09-2.29) per 100,000 is reported. Most common are skin and subcutaneous tissue disorders, and general disorders and administration site conditions. Many adverse events reported are minor in severity, although 6.7% can be classified as important. In rare cases, adverse events are serious and potentially life-threatening. With the introduction of new radiopharmaceuticals and the increasing use of positron emission tomography-computed tomography, previously unknown adverse events may be detected in daily practice. Future work should cover the experience of the patient with adverse events from diagnostic radiopharmaceuticals