Fred J. Verzijlbergen

FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0

The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about [18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out, interpret, and document quantitative FDG PET/CT examinations, but will concentrate on the optimisation of diagnostic quality and quantitative information.

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.

The Netherlands protocol for standardisation and quantification of FDG whole body PET studies in multi-centre trials.

IntroductionSeveral studies have shown the usefulness of positron emission tomography (PET) quantification using standardised uptake values (SUV) for diagnosis and staging, prognosis and response monitoring. Many factors affect SUV, such as patient preparation procedures, scan acquisition, image reconstruction and data analysis settings, and the variability in methodology across centres prohibits exchange of SUV data. Therefore, standardisation of 2-[18F] fluoro-2-deoxy-D-glucose (FDG) PET whole body procedures is required in multi-centre trials.MethodsA protocol for standardisation of quantitative FDG whole body PET studies in the Netherlands (NL) was defined. This protocol is based on standardisation of: (1) patient preparation; (2) matching of scan statistics by prescribing dosage as function of patient weight, scan time per bed position, percentage of bed overlap and image acquisition mode (2D or 3D); (3) matching of image resolution by prescribing reconstruction settings for each type of scanner; (4) matching of data analysis procedure by defining volume of interest methods and SUV calculations and; (5) finally, a multi-centre QC procedure is defined using a 20-cm diameter phantom for verification of scanner calibration and the NEMA NU 2 2001 Image Quality phantom for verification of activity concentration recoveries (i.e., verification of image resolution and reconstruction convergence).DiscussionThis paper describes a protocol for standardization of quantitative FDG whole body multi-centre PET studies.ConclusionThe protocol was successfully implemented in the Netherlands and has been approved by the Netherlands Society of Nuclear Medicine.

(18)F-FDG PET patterns and BAL cell profiles in pulmonary sarcoidosis.

PurposeBronchoalveolar lavage (BAL) and 18F-fluorodeoxyglucose (18F-FDG) PET can both demonstrate sarcoid activity. To assess whether metabolic activity imaged by 18F-FDG PET represents signs of disease activity as reflected by BAL, 18F-FDG PET patterns were compared with BAL cell profiles.MethodsIn this retrospective analysis, 77 newly diagnosed pulmonary sarcoidosis patients underwent BAL and 18F-FDG PET. Based on 18F-FDG PET, patients were diagnosed with exclusively mediastinal/hilar activity (group A) and activity in the lung parenchyma (group B). Per group, BAL lymphocytes (%), CD4/CD8 ratio, CD103+CD4+/CD4+ ratio and neutrophils (%) were compared with the extent of metabolic activity expressed as the maximum standardized uptake value (SUVmax). Additionally, SUVmax and BAL parameters per radiographic stage were analysed.ResultsOverall, the SUVmax in the lung parenchyma correlated with neutrophils and SUVmax of the mediastinum/hila correlated with the CD4/CD8 ratio. In both groups, a significant, negative correlation between the SUVmax of the mediastinum/hila and the CD103+CD4+/CD4+ ratio was found. In group B, the SUVmax of the mediastinum/hila correlated with the CD4/CD8 ratio, while the SUVmax in the lung parenchyma correlated with the CD103+CD4+/CD4+ ratio and neutrophils. Significant differences were found in the SUVmax, CD4/CD8 ratio, CD103+CD4+/CD4+ ratio and neutrophils between the radiographic stages. The SUVmax of the lung parenchyma was positively related to the radiographic stage, while the SUVmax of the mediastinum/hila and CD4/CD8 ratio were inversely related.Conclusion18F-FDG PET correlates with the CD4/CD8 ratio and neutrophils, suggesting that 18F-FDG PET represents this specific cell profile in BAL. High SUVmax values of the lung parenchyma may therefore correlate with more severe parenchymal involvement, particularly when accompanied by a low SUVmax of the mediastinum/hila.

A possible role of 18F-FDG positron-emission tomography scanning in the early detection of rituximab-induced pneumonitis in patients with non-Hodgkin’s lymphoma

Rituximab is safe and effective in the treatment of patients with non-Hodgkin’s lymphoma (NHL). Rituximab is generally well-tolerated. Its major adverse effects are infusion related and include fever, chills, dyspnea and hypotension. Dyspnea is a frequent complaint in NHL patients, and is often

Small field-of-view dedicated cardiac SPECT systems: impact of projection truncation

PurposeSmall field-of-view (FOV) dedicated cardiac SPECT systems suffer from truncated projection data. This results in (1) neglect of liver activity that otherwise could be used to estimate (and subsequently correct) the amount of scatter in the myocardium by model-based scatter correction, and (2) distorted attenuation maps. In this study, we investigated to what extent truncation impacts attenuation correction and model-based scatter correction in the cases of 99mTc, 201Tl, and simultaneous 99mTc/201Tl studies. In addition, we evaluated a simple correction method to mitigate the effects of truncation.MethodsDigital thorax phantoms of different sizes were used to simulate the full FOV SPECT projections for 99mTc, 201Tl, and simultaneous 99mTc/201Tl studies. Small FOV projections were obtained by artificially truncating the full FOV projections. Deviations from ideal heart positioning were simulated by axially shifting projections resulting in more severe liver truncation. Effects of truncation on SPECT images were tested for ordered subset (OS) expectation maximization reconstruction with (1) attenuation correction and detector response modelling (OS-AD), and (2) with additional Monte-Carlo-based scatter correction (OS-ADS). To correct truncation-induced artefacts, we axially extended truncated projections on both sides by duplicating pixel values on the projection edge.ResultsFor both 99mTc and 201Tl, differences in the reconstructed myocardium between full FOV and small FOV projections were negligible. In the nine myocardial segments, the maximum deviations of the average pixel values were 1.3% for OS-AD and 3.5% for OS-ADS. For the simultaneous 99mTc/201Tl studies, reconstructed 201Tl SPECT images from full FOV and small FOV projections showed clearly different image profiles due to truncation. The maximum deviation in defected segments was found to be 49% in the worst-case scenario. However, artificially extending projections reduced deviations in defected segments to a few percent.ConclusionOur results indicate that, for single isotope studies, using small FOV systems has little impact on attenuation correction and model-based scatter correction. For simultaneous 99mTc/201Tl studies, artificial projection extension almost fully eliminates the adverse effects of projection truncation.

Radiopharmaceuticals are special, but is this recognized? The possible impact of the new Clinical Trials Regulation on the preparation of radiopharmaceuticals

Dear Sir, Nuclear medicine techniques are in the forefront of molecular imaging, thereby translating discoveries in molecular biology, genetics, pharmacology and many other disciplines into imaging diseases for the patient’s benefit. Awide variety of radiopharmaceuticals for many different targets are available and many others are continually being developed for oncology, neurology, cardiology and other clinical settings. Over the past decade the major hurdle in translating this radiopharmaceutical development into the clinic has been an excessive and ever tightening regulatory framework for pharmaceuticals in general, which does not take into account the special nature of radiopharmaceuticals. In particular, novel radiopharmaceuticals are to a great extent developed at universities and hospitals and are prepared on a small scale in a non-industrial setting. This is due to their relatively short shelf life, which typically requires preparation on an extemporaneous basis for individual patients. As radiopharmaceuticals are medicinal products according to Directive 2001/83 [1], radiopharmaceuticals used within clinical trials are regarded almost exclusively as investigational medicinal products (IMPs) [2]. With the release of the “Clinical Trials Regulation”, i.e. Directive 2001/20 [3], the last decade was characterized by great regulatory changes [4], especially for the preparation of IMPs. In particular, the introduction of pharmaceutical Good Manufacturing Practice (GMP) as a requirement with subsequent release of specific guidelines (Annex 13, [5]), has shown its full impact in recent years in many European countries. The impact is manifold: GMP requires dedicated clean room facilities and as most radiopharmaceuticals have to be prepared aseptically, this requires the application of the highest clean room classifications. In many European countries millions of euros have been invested to build new or adapt old facilities to meet these standards. Additionally, GMP and the Clinical Trials Regulation also imposed the need for authorization and the

Is quantitative analysis superior to visual analysis of planar thallium 201 myocardial exercise scintigraphy in the evaluation of coronary artery disease ? Analysis of a prospective clinical study

Quantitative analysis of myocardial exercise scintigraphy has been previously reported to be superior to visual image interpretation for detection of the presence and extent of coronary artery disease. Computer analysis of perfusion defects and washout rate of thallium 201 was performed on scintigrams from a group of 131 consecutive patients (prospective group), using criteria defined from a previous group of 72 patients (initial group), and compared with visual interpretation of scintigrams for detection and evaluation of coronary artery disease. The sensitivity of the quantitative technique with regard to overall detection of coronary artery disease was not significantly different from the visual method (69% and 74%, respectively), whereas the specificity was higher (86% and 68%). Quantitative analysis did not increase the sensitivity of thallium imaging over the visual method in the left anterior descending artery (46% vs 65%) and the right coronary artery (51% vs 72%) but did increase sensitivity in the left circumflex artery (75% vs 47%). Whereas in the initial group quantitative analysis resulted in a better identification of multivessel disease (sensitivity 81 % vs 57%), in the prospective group sensitivity decreased (54% vs 67%) without significant loss of specificity. The initial group had a 40% incidence of three-vessel disease and the prospective group, 22% (P < 0.05). One-vessel disease was higher in the prospective group (32% vs 11%,P < 0.05). Thus, assessing the quantitative technique in a larger prospective patient population, there was no improvement of detection of the presence and extent of coronary artery disease when compared with visual interpretation.

18F-fluorodeoxyglucose positron emission/computed tomography and computed tomography angiography in prosthetic heart valve endocarditis: from guidelines to clinical practice

The timely diagnosis of prosthetic heart valve endocarditis remains challenging yet of utmost importance. 18F-fluorodeoxyglucose (18 F-FDG) positron emission/computed tomography (PET/CT) and cardiac computed tomography angiography (CTA) were recently introduced as additional diagnostic tools in the most recent ESC guidelines on infective endocarditis. However, how to interpret PET/CT findings with regard to what is to be considered abnormal, what the potential confounders may be, as well as which patients benefit most from these additional imaging techniques and how to best perform them in these often-complex patients, remains unclear. This review focusses on factors regarding patient selection and image acquisition that need to be taken into account when employing 18F-FDG PET/CT and CTA in daily clinical practice, and the importance of a multidisciplinary Endocarditis Team herein. Furthermore, it emphasizes the need for standardized acquisition protocols and image interpretation, especially now that these techniques are starting to be widely embraced by the cardiovascular society.

Quantitative thallium-201 scintigraphy after dipyridamole infusion combined with low level exercise in healthy volunteers

To establish test specific normal limits for quantitative analysis of uptake and washout of 201Tl after dipyridamole infusion combined with low level exercise, 20 healthy volunteers were studied with low likelihood of coronary artery disease (CAD) assessed by a stepwise probability analysis based on age, sex, symptoms, resting electrocardiogram, and exercise electrocardiography. Likelihood of CAD in these volunteers was calculated as ≦1%. After dipyridamole infusion combined with low level exercise, one volunteer complained of headache; no other side effects were observed. There were no chest pain complaints. Maximal hemodynamic changes were achieved during the 6th and 7th min of the test. No ST segment depression was recorded. Visual analysis of the 201Tl scintigrams was normal in all volunteers. Mean regional washout at 4 h was 44.37%±2.11%. The regional washout in the 70° LAO view (46.65%±1.10%) was significantly higher than in the anterior and 30° LAO views (43.44%±1.50% and 43.02%±1.45%, respectively). Profiles of uptake and washout of 201Tl were different after dipyridamole infusion combined with low level exercise as compared to maximal exercise. Thus, in quantitative analysis of 201Tl scintigraphy after dipyridamole infusion in conjunction with low level exercise as applied in the present study, it is mandatory to use normal limits of uptake and washout of 201Tl derived from healthy volunteers who underwent the same combined protocol.