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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.
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). PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to ensure that optimal images are acquired for our patients and that these images would be acceptable and interpretable by any clinician in another hospital. This is essential for the management of patients who have the right to have their health care provided in any hospital they chose. Common standards will help promote the use of PET/CT imaging and increase the value of publications and their contribution to evidence-based medicine and potentially enable the role of semi-quantitative and quantitative image interpretation since the numeric values should be consistent between platforms and institutes that acquire the data. FDG PET/CT is being used increasingly to evaluate tumour response in addition to diagnosis and staging of tumours. Increasingly, research is being performed in radiotherapy planning and it will be important that areas such as edge detection of tumours have a translatable measurement.
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 in carrying out, interpret and document quantitative FDG PET/CT examinations, but will concentrate on the optimisation of diagnostic quality and quantitative information. Note, that in this guideline quantification of FDG PET and PET/CT is defined as quantification using standardised uptake values (SUV), as it represents the most commonly used (semi-)quantitative parameter for analysis of oncology FDG PET studies. However, other (full) quantitative measures, which require more complex data-collection procedures, are being used as well, but they are beyond the scope of the present guideline. In this guideline, areas of information will provide a minimum standard for FDG PET and PET/CT data acquisition, quality control, and quality assurance.
The Procedure Guidelines for Tumour Imaging with FDG PET/CT 1.0 of the Society of Nuclear Medicine (SNM)1 , the German Guidelines for FDG-PET/CT in Oncology2 , the quality control/assurance procedures used in the UK for lymphoma/head and neck cancer studies and the Netherlands protocol for standardisation of quantitative whole-body FDG PET/CT  studies have been integrated in the present guideline. An overview of other and previously published guidelines [1, 2, 4–14] or recommendations can be found in the supplement issue of the Journal of Nuclear Medicine 2009 .
Positron emission tomography (PET) is a tomographic technique that computes the three-dimensional distribution of radioactivity based on the annihilation photons that are emitted by positron emitter labelled radiotracers. PET allows non-invasive quantitative assessment of biochemical and functional processes. The most commonly used tracer at present is the glucose analogue FDG. FDG accumulation in tissue is proportional to the amount of glucose utilisation. Increased consumption of glucose is a characteristic of most cancers and is in part related to over-expression of the GLUT-1 glucose transporters and increased hexokinase activity. Given the kinetics of FDG adequate static images are most frequently acquired approximately 60 min after administration. It is recognized, however, that the uptake period is highly variable, FDG concentration not reaching a plateau for up to 4–6 h in some tumours . Moreover, not all cancers are FDG avid. Variable uptake is likely related to biological features of individual cancers, as is observed in broncho-alveolar carcinomas, renal, thyroid cancers, several subtypes of malignant lymphoma, carcinoids but also most prostate carcinomas. The reason and prognostic relevance of this biological heterogeneity is not always clear. However, in the majority of cases, FDG PET is a sensitive imaging modality for the detection, staging, re-staging as well as for assessment of therapy response in oncology [6, 17–25].
In contrast to PET, computed tomography (CT) uses an x-ray beam to generate tomographic images. CT allows the visualisation of morphological and anatomic structures with a high anatomical resolution. Anatomical and morphological information derived from CT can be used to increase the precision of localisation, extent, and characterisation of lesions detected by FDG PET.
FDG PET and CT are established imaging modalities that have been extensively validated in routine clinical practice. Integrated PET/CT combines PET and CT in a single imaging device and allows morphological and functional imaging to be carried out in a single imaging procedure. Integrated PET/CT has been shown to be more accurate for lesion localisation and characterisation than PET and CT alone or the results obtained from PET and CT separately and interpreted side by side or following software based fusion of the PET and CT datasets. PET/CT gains more and more importance in oncology imaging. At the same time, there is greater awareness that the quantitative features of PET may have a major impact in oncology trials and clinical practice. Therefore this guideline focuses on the use of FDG PET/CT in oncology.
PET is a rapidly ‘evolving’ field at both the national and international level, with sometimes striking differences between individual countries. The summary below is therefore subjective in nature and based on a combination of expert experience and scientific literature [6, 17, 18, 20–26]. An excellent overview is given in , but these indications are constantly changing and require updating with time.
The main purpose of the patient preparation is the reduction of tracer uptake in normal tissue (kidneys, bladder, skeletal muscle, myocardium, brown fat) while maintaining and optimizing tracer uptake in the target structures (tumour tissue). In the following, a generally applicable protocol is outlined:
The following recommendations apply to patients with diabetes mellitus:
It is good practice to check the blood glucose level of the patient on arrival at the imaging centre to ensure the patients’ sugar is not too low or high, since this may obviate an unnecessary wait.
In the case of patients on continuous insulin infusion, the PET study should if possible be scheduled early in the morning. The insulin pump is kept on the “night setting” until after the PET study. The patient can have breakfast after the PET study.
See Society of Nuclear Medicine Procedure Guidelines for General Imaging Version 3
When using systems with a high count rate capability (LSO, LYSO, and GSO-based cameras with or without time of flight), the administered FDG activity and scan duration for each bed position must be adjusted so that the product of the FDG activity and scan duration +10% is equal to or greater than the specifications set out below. Therefore, one may decide to apply a higher activity and reduce the duration of the scan or, preferably, use reduced activity and increase scan duration, thereby keeping ALARA principles in mind as well.
The PET emission data must be corrected for geometrical response and detector efficiency (normalisation), system dead time, random coincidences, scatter, and attenuation. Some of these corrections (for example attenuation correction) can be directly implemented in the reconstruction process. In all cases, all corrections needed to obtain quantitative image data should be applied during the reconstruction process. Data acquired in the 3D mode can be reconstructed directly using a 3D-reconstruction algorithm or rebinned in 2D data and subsequently be reconstructed with a 2D-reconstruction algorithm. Iterative reconstruction algorithms represent the current standard for clinical routine and have meanwhile replaced filtered backprojection algorithms for PET reconstruction. It is good clinical practice to perform reconstructions with and without attenuation correction to tackle potential reconstruction artefacts caused by a CT-based attenuation correction. For clinical cases, reading the reconstructed 3D volume data set is visualized in transaxial, coronal, and sagittal slices, but also the maximum intensity projections should be available.
Further standardisation of reconstruction settings is necessary in order to obtain comparable resolutions and SUV recoveries and make SUVs interchangeable, i.e. reconstructions are chosen such to achieve convergence and resolution matching across various PET and PET/CT systems and sites, especially within a multi-centre setting [15, 30, 33]. However, also for clinical practice, strict standardisation is needed to provide the same quality of care across sites and to allow for exchange and use of quantitative PET information elsewhere. Some indicative reconstruction settings are suggested in Appendix II. However, most importantly, reconstructions should be chosen so that they meet the multi-centre QC specifications for both calibration QC and image quality/SUV recovery QC, as described in “Quality control and inter-institution cross-calibration”.
Various new types of cameras are coming into the market. It is not yet possible to specify rational dosage, acquisition, and reconstruction specifications for them. Moreover, default reconstruction settings may change over time. Therefore, institutions may deviate from the recommended/prescribed dosage and acquisition protocol if it can be demonstrated that the alternative protocol provides equivalent data. The convergence and overall final image resolution must also match this study protocol QC specification. Compliance with these requirements must be demonstrated by means of the tests described under Quality Control and inter-institution cross-calibration in “Quality control and inter-institution cross-calibration”. Calibration and activity recovery coefficients may not deviate from multi-centre standard specifications by more than 10%. These specifications are given in “Quality control and inter-institution cross-calibration”. In other words: any combination of acquisition and reconstruction protocol and/or settings which meets the multi-centre QC specifications given later and especially those for the (absolute) activity (or SUV) recovery coefficients is allowed.
The CT data that are acquired during the PET/CT scanning session are usually reconstructed by use of filtered back projection or a similar algorithm. Depending on the CT-protocol and the diagnostic question separate CT reconstructions for the PET attenuation correction and for the diagnostic CT are performed. The reconstructions differ in their slice thickness, slice overlap, filter, etc. In addition to the reconstruction kernel that modulates the image characteristics within the slices (i.e. spatial resolution, edge enhancement and noise texture), a longitudinal filter in the z-dimension is used to optimise the resolution in the z-direction and to modify the slice-sensitivity profiles. The measured attenuation values are normalized to the density of water in order to assign a device-independent numeric value in the framework of the reconstruction.
This procedure additionally reduces the dependency of the attenuation values from the radiation energy. In modern CT-tomographs, the spatial resolution in the z-dimension is almost as high as the transaxial resolution and almost isotropic allowing image visualisation in coronal and sagittal views in a high quality. Additionally, post-processing like volume rendering or maximum intensity projections (MIPs) benefit from the high quality of the raw data.
The reconstructed PET and CT images are assessed from a computer screen. The software packages for current PET/CT systems enable visualisation of PET, CT, and PET+CT fusion images in the axial, coronal, and sagittal planes as well as maximum intensity projections in a 3D cine mode. FDG PET images can be displayed with and without attenuation correction. On all slices (of the attenuation corrected data) quantitative information with respect to size and FDG uptake can be derived. Images must be evaluated using software and monitors approved for clinical use in radiology and nuclear medicine. Characteristics of monitor and settings should be in line with published standards (e.g. the Medical Electrical Safety Standards (IEC 60601-1/EN 60601-1), the Medical ECM Standards (IEC 60601-1-2, EN 60601-1-2) or national guidelines). Moreover, environment conditions (background light) must be at appropriate levels to ensure adequate image inspection.
The presence or absence of abnormal FDG accumulation in the PET images, especially focal accumulation, in combination with their size and intensity are evaluated. Absence of such accumulation is particularly significant if other tests have revealed findings such as anatomical abnormalities. Where necessary, the report correlates these findings to other diagnostic tests and interprets them in that context (in consultation with a radiologist where necessary) and considers them in relation to the clinical data. For response assessment, the images should be viewed over the same dynamic grey scale or colour scale range, i.e. a fixed colour scale e.g. from SUV=0 to 10 is recommended.
Both uncorrected and attenuation-corrected images need to be assessed in order to identify any artefacts caused by contrast agents, metal implants and/or patient motion.
Criteria for visual analysis must be defined for each study protocol.
Standardized uptake values are increasingly used in clinical studies in addition to visual assessments. SUV is a measurement of the uptake in a tumour normalized on the basis of a distribution volume. It is calculated as follows:
The following calculation is applied in the case of plasma glucose correction
In these calculations, Actvoi is the activity measured in the volume of interest (see “Definitions for volumes of interest (VOI) and regions of interest (ROI)”), Actadministered is the administered activity corrected for the physical decay of FDG to the start of acquisition, and BW is body weight. Patient height, weight, and gender should be reported to allow for other SUV normalisations (LBM, BSA). The latter is of importance to meet EORTC recommendations  and, for response assessment studies, when large changes in body weight occur during the course of the treatment. As stated earlier, it is recommended to measure plasma glucose levels using validated methodology and calculate SUV with and without plasma glucose correction in all response monitoring assessment studies (“Patient preparation”, extra notes). Note that the measured glucose content (Glucplasma) is normalised for an overall population average of 5.0 mmol/l so that the SUVs with (SUVglu) and without (SUV) correction of glucose content are numerically practically identical (on average) .
For further reading, also see the Society of Nuclear Medicine Procedure Guidelines for General Imaging.
Both physiological and physical factors influence the accuracy and reproducibility of ‘standard uptake values’ (SUV) in oncology FDG PET studies. Variations in PET camera calibration, image reconstruction, and data analysis and/or settings can have more than a 50% effect on the measured SUV . The use of SUV in multi-centre oncology PET studies therefore requires an inter-institution calibration procedure in order to facilitate the exchangeability of SUVs between institutions. It is also important that all participating institutions use methodology that is as similar as possible. In order to ensure the exchangeability of SUVs, a minimum set of quality-control procedures must be carried out, such as:
Note that these QC measures do NOT replace any QC measures required by national law or legislation or those recommended by local nuclear medicine societies. A brief summary of PET and PET/CT quality-control procedures, specifically recommended here to ensure accurate SUV quantification, is given below.
The aim of daily quality control is to determine whether the PET or PET/CT camera is functioning well; in other words, to establish detector failure and/or electronic drift. Most commercial systems are equipped with an automatic or semi-automatic procedure for performing daily quality controls. For some PET and PET/CT systems, the daily quality control includes tuning of hardware and/or settings. Thus both the procedure and its name may be different between various PET and PET/CT systems. In all cases, all daily quality-control measures and/or daily setup/tuning measurements should be performed according to the manufacturer’s specifications. Users should check whether the daily quality control meets the specifications or passed the test correctly.
When available, a daily PET or PET/CT scan of a cylindrical phantom filled with a Ge-68 solution may be collected. Inspection of uniformity and quantitative accuracy of the reconstructed image may help to identify technical failures that were not detected using the routine daily QC procedures. In addition, sinogram data may be visually inspected to check detector failures.
The aim of calibration and cross-calibration is to determine the correct and direct calibration of a PET or PET/CT camera with the institution’s own dose calibrator or against another one which is used to determine patient-specific FDG activities . If these FDG activities are ordered directly from and supplied by a pharmaceutical company, cross-calibration of the PET camera should be carried out using a calibration sample supplied by that company (i.e. the customer should order an FDG activity of about 70 MBq, see below, as if it concerns an FDG activity needed for a clinical study). Remember that cross-calibration must not be confused with normal calibration. Cross-calibration is a direct, relative calibration between the used (or institution’s own) calibrator and the PET camera, and therefore provides information about possible calibration discrepancies between the PET camera and the dose calibrator, which is more essential for correct SUV quantification than the individual calibrations themselves. Differences of up to 15% in the cross-calibration between PET camera and dose calibrator have been observed  due to the fact that individual calibrations of the dose calibrator and the PET camera (usually carried out by the manufacturer) are performed using different calibration sources and procedures, and by different companies and/or persons. This explains the importance of a direct cross-calibration between the dose calibrator and PET camera used.
In short, the procedure is as follows: A syringe is filled with approximately 70±10 MBq of FDG solution and is re-measured in a calibrated dose calibrator (or the syringe is ordered from the pharmaceutical company). The FDG is then introduced into a calibration phantom with an exact known volume (<1%) filled with water, which results in a solution containing an exactly known activity concentration (Bq/ml). Homogenisation of the FDG in the phantom should be achieved by leaving an air bubble of approximately 10–20 ml within the phantom and subsequently shaking/mixing the phantom for a short period of time (10 min). If the institution has a calibrated well counter, three samples of approximately 0.5 ml should be taken from the calibration phantom solution using a pipette. The exact weight/volume of the samples should be determined before placing the samples in the well counter. Emission scans of the calibration phantom are performed with the PET or PET/CT camera using the recommended whole-body acquisition protocol/procedure (including multi-bed acquisitions, see Appendix III). Once the activity has decayed (after an interval of 10 h or more), a transmission scan is performed without moving the phantom from its position in the PET or PET/CT system. For PET/CT cameras on which attenuation correction is performed using a low-dose CT-scan (CT-AC), the CT-AC scan can be carried out either directly before or after the emission scan.
Emission scans are reconstructed in accordance with the recommended reconstruction parameters as described in “Image reconstruction” on image reconstruction and Appendix II. VOI analysis is performed in order to determine the average volumetric concentration of activity within the phantom as measured by the PET camera. Cross-calibration factors between the PET or PET/CT camera and dose calibrator and well counters can then be derived directly. Once the cross-calibration procedure has been completed, conversion factors will be known with which the counts/measurements for different equipment can be synchronised. N.B.: The cross-calibration factor between the PET camera and dose calibrator should be equal to 1.0 (<10%). A ‘standard operating procedure’ (SOP) is described in Appendix III.1 (Software and/or processing programs for (automated) analysis of the QC calibration experiments are available on request as research tool, email@example.com).
Although a correct cross-calibration is guaranteed using the quality-control procedure described above, differences in SUV quantification may still occur between centres as a result of differences in the reconstruction and data analysis methodology used. In particular, differences in the final image reconstruction (i.e. following reconstruction, including all effects due to filters and pixel size settings, etc.) have, depending on the shape of the tumour, a significant effect on the SUV result for smaller (<5 cm diameter) tumours. It is therefore important to determine the accuracy of the SUV using a standardized ‘anthropomorphic’ phantom containing spheres (tumours) of varying sizes. Phantoms such as these enable to verify SUV quantification under clinically relevant conditions. The aim of the IQRC quality-control procedure is:
The IQRC quality-control procedure is carried out closely in accordance with the ‘image quality, accuracy of attenuation and scatter corrections’ procedure described in the NEMA Standards Publication NU 2-2001, “Performance measurements of positron emission tomographs”. VOIs are defined manually according to this procedure. However, it is known that automatic definition of 3D volumes of interest (VOI) based on isocontours using fixed percentages results in a higher SUV accuracy and precision than those determined using manually defined ROIs or VOIs (2,3,6). Therefore, 3D-VOIs are also determined using an automatic VOI method such as described in “Definitions for volumes of interest (VOI) and regions of interest (ROI)”:
The procedure for making this VOI is as follows: Firstly, the location of the pixel with the maximum SUV in the tumour must be determined (manually or semi-automatically). Secondly, a 3D-VOI is generated automatically based on the maximum SUV/pixel value and its location with a 3D ‘region growing’ algorithm in which all pixels/voxels above the defined threshold limit are included. Once a VOI has been generated for each sphere, the average concentration of activity (or SUV) for the sphere can also be determined. The average VOI activity concentration value measured is then normalized with the actual concentration of activity in the spheres, which indicates the ‘activity concentration recovery coefficient’ per sphere (i.e. the ratio of the measured and actual concentration of activity as a function of sphere size). The ‘recovery coefficient’ is finally defined as a function of sphere size and VOI definition. A standard operating procedure is presented in Appendix III.2. (Software and/or processing programs for (automated) analysis of the QC image quality/recovery experiments are available on request as research tool, firstname.lastname@example.org).
The measured activity concentration recovery coefficients must meet the specifications given below. These specifications are based on recovery coefficients measured according to this protocol on various PET and PET/CT systems of different vendors .
Specifications for activity concentration recovery coefficients (RC) measured according the Image Quality QC SOP (Appendix III.2). Specifications are given for recovery coefficients obtained using A50 VOI and the maximum pixel value only.
The review contributions of the EANM Dosimetry Committee and the EANM Radiopharmacy committee are highly appreciated. Moreover, the authors would like to thank the European Society of Radiology (ESR) experts for reviewing the CT dosimetry section. In addition, the reviews by the EANM National Society delegates are highly appreciated.
Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
Calculation of FDG activity to be administered, example 1:
Calculation of FDG activity to be administered, example 2:
Note: the scanner brands are solely given as examples. The key factors in determining the FDG activity are the mode of acquisition (2D or 3D), the time per bed position (time/bed) and the degree of bed overlap and, finally, the patient’s weight.
In order to simplify implementation in a routine clinical setting, a Table in 10-kg steps may be used such as published by Boellaard et al. . Note however that in the present guideline, a maximum FDG activity of 529 MBq for patients above 90 kg is recommended. Moreover, a maximum allowed FDG activity may be applicable by national law. In the latter case, i.e. for obese patients, increase of scanning time should be applied to obtain sufficient image quality and/or to remain within (national) legal limits.
Here a number of indicative settings are given for different system types. These indicative settings usually provide results that meet closely the QC specifications as defined later in this guideline. In case these reconstructions cannot be set exactly as indicated below, settings may be set as close as possible to the ones listed below. However, note that reconstructions should be set such that they meet the multi-centre QC specifications for both calibration and image quality/SUV recovery as function of sphere size (see “Exceptions/special features”)
General Electric systems:
Philips systems (Gemini, Gemini ToF):
PET or PET CT scan acquisition
Reconstructions should be performed with attenuation, scatter, normalisation, decay, dead time corrections, i.e. all corrections required for quantification. Follow the instructions given in this guideline (“Image reconstruction”).
Determine average activity concentration or SUV within the phantom. Verify that activity concentration and/or SUV are within 10% of expected values.
Stock/solution for spheres:
Filling of background compartment of image quality phantom:
PET or PET/CT Scans
Reconstructions should be performed with attenuation, scatter, normalisation, decay, dead time corrections, i.e. all correction needed for quantification. Reconstructions need to be performed conform specifications given in this guideline. In case such a protocol is not in place, the recommendation for quantitative studies as provided by the vendor should be applied.
Determine recovery coefficient as function of sphere using maximum pixel value and A50 VOI.
If the department has a calibrated well counter available (see calibration procedure), this is the tool of preference with which to determine/verify the exact concentration of activity in the spheres and in the background of the phantom.
1Sections of this document were adapted and reprinted with permission of the Society of Nuclear Medicine, Procedure Guidelines for Tumour Imaging with 18F-FDG PET/CT: Delbeke D (chair), Coleman RE, Guiberteau MJ, Brown ML, Royal HD, Siegel BA, Townsend DW, Berland LL, Parker JA, Hubner K, Stabin MJ, Zubal G, Kachelreiss M, Cronin V, Hoolbrook S. J Nucl Med 2006; 47: 885–895
2Sections of this document were translated and reprinted with permission of the DGN (Deutsche Gesellschaft für Nuklearmedizin): Krause BJ, Beyer T, Bockisch A, Delbeke D, Kotzerke J, Minkov V, Reiser M, Willich N und der Arbeitsausschuss Positronen-Emissions-Tomographie der Deutschen Gessellschaft für Nuklearmedizin. FDG-PET/CT in oncology. German Guideline. Nuklearmedizin 2007; 46: 291–301
3It should be noted that the entity “effective dose” does not necessarily reflect the radiation risk associated with this nuclear medicine examination. The effective dose values given in this guideline are used to compare the exposure due to different medical procedures. If the risk associated with this procedure is to be assessed, it is mandatory to adjust the radiation-associated risk factors at least according to the gender and age distribution of the institution’s patient population.
This guideline is a joint project of the EANM Oncology Committee and the EANM Physics Committee. In addition, this guideline is based on the following three documents:
(1) DGN (Deutsche Gesellschaft für Nuklearmedizin) Leitlinie: “FDG-PET/CT in der Onkologie” by Krause BJ, Beyer T, Bockisch A, Delbeke D, Kotzerke J, Minkov V, Reiser M, Willich N, Arbeitsausschuss Positronenemissionstomographie der Deutschen Gesellschaft für Nuklearmedizin. 2007.
(2) SNM Guidelines: “Procedure Guidelines for tumour imaging with 18F-FDG PET/CT 1.0.” by Delbeke D, Coleman RE, Guiberteau MF, Brown ML, Royal HD, Siegel BA, Townsend DW, Berland LL, Parker JA, Hubner K, Stabin MG, Zubal G, Kachelries M, Cronin V, Holbrook S. 2006.
(3) “Applications of F18-FDG-PET in Oncology and Standardisation for Multi-Centre Studies” by Boellaard R, Oyen WJG, Hoekstra CJ, Hoekstra OS, Visser EP, Willemsen AT, Arends AJ, Verzijlbergen JF, Paans AM, Comans EFI, Lugtenburg E, Stoker J, Schaefer-Prokop C, Zijlstra JM, Pruim J. HOVON Imaging workgroup and the Netherlands Society of Nuclear Medicine. 2007