Preamble
Introduction
Goals
Definitions
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An integrated or multimodality PET/CT system is a combination of a PET and a CT system with a single, conjoined patient handling system (table).
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PET/CT allows sequential acquisition of PET and CT portions of the examination with the patient in the same position for both examinations. Both datasets are intrinsically coregistered.
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An FDG PET/CT examination may cover various coaxial imaging ranges; these ranges are described as follows, with different denominations depending on European standard (GL 1.0) or US standard (defined in Current Procedural Terminology 2005):
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Whole-body imaging: From the top of the head through the feet (standard for both Europe and the US).
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Torso imaging: Base of the skull to mid-thigh. Covers most of the relevant portions of the body in many oncological diseases (standard for both Europe and the US). If indicated, cranially extended torso imaging may also cover the brain in the same scan (from the top of the head to mid-thigh).
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Limited-area tumour imaging: For the evaluation of tumour-related changes in a limited portion of the body.
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Whole-body or torso imaging combined with dedicated brain imaging: Dedicated brain imaging combined with whole-body or torso imaging from base of skull.
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In PET/CT studies attenuation correction and scatter correction are performed using the CT transmission data.
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A PET/CT examination can include different types of CT scan depending on the CT characteristics, the dose and the use (or not) of oral and/or intravenous contrast agents:
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Low-dose CT scan: CT scan that is performed only for attenuation correction (CT-AC) and anatomical correlation of PET findings (with reduced voltage and/or current of the X-ray tube settings), i.e. a low-dose CT is not intended a priori for a dedicated radiological interpretation.
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Diagnostic CT scan: CT scan with or without intravenous and/or oral contrast agents, commonly using higher X-ray doses than low-dose scans. Diagnostic CT scan should be performed according to applicable local or national protocols and guidelines.
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Common clinical indications
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Differentiation of benign from malignant lesions
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Searching for an unknown primary tumour when metastatic disease is discovered as the first manifestation of cancer or when the patient presents with a paraneoplastic syndrome.
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Staging patients with known malignancies.
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Monitoring the effect of therapy on known malignancies.
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Determining whether residual abnormalities detected on physical examination or on other imaging studies following treatment represent tumour or posttreatment fibrosis or necrosis.
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Detecting tumour recurrence, especially in the presence of elevated tumour markers.
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Selection of the region of tumour most likely to yield diagnostic information for biopsy.
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Guiding radiation therapy planning.
Regulatory issues
Qualifications and responsibilities of personnel
Procedure/specification of the examination
Request
Review of the medical history
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Tumour type (if known) and known tumour sites.
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Oncological history and relevant comorbidity (especially infection/inflammation and diabetes mellitus).
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Neurological or psychiatric clinical presentations, including suspected neurological paraneoplastic syndromes.
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Height and body weight (these must be determined precisely in the case of SUV measurements, see below). Weight must be measured directly prior to each FDG PET/CT examination (also in the case of longitudinal studies) because body weight often changes during the course of disease.
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Serum glucose, date, time.
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Full overview of current and recently used medication, especially (but not limited to) antidiabetic medication, corticosteroids, growth factors and sedatives. In the case of therapy evaluation: type and date of last therapeutic intervention.
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Results of other imaging tests (especially CT, MRI and previous PET/CT), including dates of acquisition, full reports and, if possible, DICOM data of the referred studies for comparison.
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Other examinations performed earlier on the same day as the PET/CT is scheduled. If intravenous contrast agent has been used or specific preparation followed in the 24 – 48 h prior to the FDG PET/CT examination, the situation should be evaluated and noted; if possible such circumstances should be avoided in patient scheduling.
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Allergy to contrast agents. If an FDG PET/CT examination with intravenous CT contrast agent is strictly necessary the referring physician must indicate the premedication protocol to prepare the patient.
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Renal function. Creatinine and/or glomerular filtration should be evaluated, according to national guidelines, if intravenous contrast agent is to be used. If renal function is suboptimal and an FDG PET/CT examination with intravenous CT contrast agent is necessary, then the referring physician can initiate the protocol for prevention of nephrotoxicity (hydrate the patient and repeat the blood test, and if necessary prescribe medication for prevention of nephrotoxicity).
Patient preparation and precautions
Pregnancy (suspected or confirmed)
Breastfeeding
Instructions to patients
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Adequate prehydration is important to ensure a sufficiently low concentration of FDG in the urine (fewer artefacts) and for radiation safety reasons. For example, consumption of 1 L of water during the 2 h prior to injection is suggested. Where necessary, account for the volume of water in oral contrast agent if it is to be given for a diagnostic CT scan.
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Coffee or caffeinated beverages are not recommended because even if “sugarless” they may contain traces of simple carbohydrates and have the potential to induce excitant effects; this may also be the case for “sugar-free” beverages.
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Parenteral nutrition and intravenous fluids containing glucose should be discontinued at least 4 h before the time of FDG injection. In addition, the infusion used to administer intravenous prehydration must not contain glucose.
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During the injection of FDG and the subsequent uptake phase, the patient should remain seated or recumbent and silent (this is particularly true for head and neck cancer patients) to minimise FDG uptake in muscles. The patient should be kept warm starting 30 – 60 min before the injection of FDG and continuing throughout the subsequent uptake period and examination to minimise FDG accumulation in brown fat (especially relevant in winter or if the room is air-conditioned).
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Patients must avoid strenuous exercise for at least 6 h before the FDG PET/CT study, and preferably for 24 h.
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Patients should void immediately prior to the PET/CT examination to reduce bladder activity.
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The patient should be able to lie still in the PET/CT system for the duration of the examination (20 – 45 min). A specific inquiry about claustrophobia at the time the patient is scheduled for the study may decrease the number of nondiagnostic studies and cancellations, and allow premedication planning.
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If possible, the patient should put his/her arms above the head; proper support devices (e.g. foam pallets) provided by the manufacturers should be employed whenever feasible.
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When a diagnostic contrast-enhanced CT examination with intravenous contrast agent is to be performed, specific indications must be followed (see later in these guidelines).
Serum glucose level before FDG administration
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If the plasma glucose level is lower than 11 mmol/L (about 200 mg/dL), the FDG PET/CT study can be performed.
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If the plasma glucose level is higher than or equal to 11 mmol/L (about 200 mg/dL), the FDG PET/CT study should be rescheduled or the patient excluded depending on the patient’s circumstances and the trial being conducted.
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The recommended upper plasma glucose levels may range between 7 and 8.3 mmol/L (126 mg/dL and 150 mg/dL) [30]; the upper threshold should be specified in the study protocol. Patients who fall outside the specified range of serum glucose levels are often excluded from the study, but reference should be made to the specific study protocol in reaching this decision.
Diabetes
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The FDG PET/CT study should preferably be performed in the late morning.
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Patients must comply with the fasting rules indicated above.
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Patients continue to take oral medication to control their blood sugar. If intravenous contrast agent is going to be administered, metformin should be discontinued at the time of the procedure and withheld for 48 h after the procedure (see below).
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Ideally, an attempt should be made to achieve normal glycaemic values prior to the FDG PET/CT study, in consultation with the patient and his/her attending medical doctor.
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There are three options for scheduling the FDG PET/CT study:1.It can be scheduled for late morning or midday. The patient should eat a normal breakfast by early morning (around 7.00 a.m.) and inject the normal amount of insulin. Thereafter the patient should not consume any more food or fluids, apart from the prescribed amount of water. FDG should be injected no sooner than 4 h after subcutaneous injection of rapid-acting insulin or 6 h after subcutaneous injection of short-acting insulin. FDG administration is not recommended on the same day after injection of intermediate-acting and/or long-acting insulin.2.It can be scheduled for early morning. The presence of intermediate-acting insulin administered the evening before should not interfere with the PET/CT study and glycaemia will probably still be under control. If long-acting insulin has been used the evening before, there could be a slight interference with the PET/CT study. Thus, if this is the preferred schedule, intermediate-acting (instead of long-acting) insulin is recommended. The patient should eat a normal breakfast after the PET/CT study and inject the normal amount of insulin.3.In patients on continuous insulin infusion, if possible the FDG PET/CT study should be scheduled for early in the morning. The insulin pump should be switched off for at least 4 h prior to FDG administration. The patient can have breakfast after the FDG PET/CT study and switch on continuous insulin infusion.
Kidney failure
Recommendations for image optimisation in specific circumstances, and extra notes
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There is no reason for routine administration of sedatives (e.g. short-acting benzodiazepines) in adult patients. Sedatives may be considered in the case of tumours in the head and neck region to reduce muscle uptake or in claustrophobic patients. A number of agents have been tried and are being tested to reduce brown fat uptake (e.g. 5 mg of intravenous diazepam, administered 10 min prior to FDG [34], or 80 mg of propranolol given orally 2 h before FDG administration [35]), but conflicting results have been reported [36]. Patients should be instructed not to drive a car and to travel home accompanied after sedation.
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When the patient is referred for the evaluation of a lesion in the heart or very close to the myocardium, additional dietary recommendations can be helpful. While there are many options for decreasing normal glucose uptake by the myocardium, common recommendations may include instructions for the patient to follow a low carbohydrate diet for 24 h prior to the PET/CT study, or at least a low carbohydrate meal before starting the 6 h period of fasting before the study [37, 38]. The low carbohydrate diet helps switch the myocardium from using glucose as an energy source to using fatty acids, reducing the uptake of glucose by the myocardium.
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Clinical value may be added to a whole-body or torso FDG PET/CT scan by adding a dedicated brain FDG PET/CT scan, which may be done on the same injected dose and in a single session before the whole-body or torso scan. This can be achieved in a short 5 mm single field of view (FOV) head acquisition following the guidelines for acquisition and reconstruction of brain FDG PET/CT images [39]. The technical qualities of the brain scan as part of a whole-body FDG PET/CT scan are not sufficiently high for detailed diagnostic purposes. This pertains to resolution, voxel dimensions, signal to noise ratio, head fixation issues and possibly reconstruction algorithms. Thus, a dedicated brain FDG PET/CT scan may be added. The indications include primarily neurological or psychiatric clinical presentations, and suspected paraneoplastic disease (including limbic encephalitis). Many of these patients have a negative whole-body or torso FDG PET/CT scan, and the brain FDG PET/CT scan adds value by documenting the existence and extent of functional damage or abnormalities (regional inflammatory or epileptiform activity, defects following inflammation or from other conditions). The brain FDG PET/CT scan may help the differential diagnosis in patients in whom a tumour cannot be identified (neurodegeneration, toxic encephalopathy, primary neuroinfection). Further, this strategy allows simultaneous treatment monitoring of activity in the tumour and paraneoplastic effects in the brain in tumour-positive patients.
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Clinical experience suggests that proper hydration prevents urinary activity from causing problems in image interpretation of abdominal/pelvic tumours. If patients are properly hydrated before imaging, delayed imaging or furosemide intervention is very rarely necessary. It is noted that some centres use transurethral catheterisation in this circumstance but the possible risk of urinary tract infection needs to be carefully weighed against the potential benefits of better image quality. In addition, if the pelvis is a site of particular concern, the CT examination may be performed first from the head to the pelvis followed by the emission acquisition in the opposite direction. This protocol minimises the time delay between the CT and FDG imaging of the pelvis, and thus there is only minimal change in bladder volume between the two scans.
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When a diagnostic CT scan with intravenous contrast agent enhancement is to be performed as part of the FDG PET/CT study, indications, contraindications and restrictions have to be assessed by a qualified physician.
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Medication that interacts with intravenous contrast agent (e.g. metformin for the treatment of diabetes) and relevant medical history (e.g. compromised renal function) should be taken into consideration:
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Renal function should be checked prior to contrast agent administration in all patients considered at risk of contrast agent nephrotoxicity. Routine creatinine testing prior to contrast agent administration is not necessary in all patients; the major indications are age over 60 years, history of preexisting renal disease or impairment (including dialysis, kidney transplant, single kidney, renal cancer and renal surgery), history of diabetes mellitus, history of hypertension requiring medical therapy or use of metformin/metformin-containing drug combinations. Patients who do not have one of the above risk factors do not require a baseline serum creatinine determination before intravenous iodinated contrast agent administration. Estimated glomerular filtration rate is a better predictor of renal dysfunction than creatinine level alone. Patients with a high risk of nephrotoxicity are those with creatinine >13 mmol/L (1.5 mg/dL) and/or glomerular filtration <60 mL/min. If renal function assessment is required, a creatinine level and estimated glomerular filtration rate within the preceding 4 weeks is sufficient in most clinical settings, although it seems prudent to shorten this interval for inpatients and those with a new or heightened risk factor of renal dysfunction [40, 41].
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Metformin is an oral hypoglycaemic agent. If intravenous contrast agent is going to be administered, metformin should be discontinued at the time of the procedure and withheld for 48 h after the procedure. If the risk of nephrotoxicity is high, metformin can be reinstituted only after renal function has been reevaluated and found to be normal. If the risk of nephrotoxicity is low, metformin can be reinstituted without the need for renal function assessment. An alternative glucose-controlling drug should be considered during this time [40‐42].
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The risk factors for contrast agent-induced nephropathy must be considered. The more important ones include: preexisting renal insufficiency, diabetes mellitus, dehydration or volume depletion, concurrent nephrotoxic drugs, high dose of contrast agent, age greater than 70 years and cardiovascular disease. Patients with normal renal function are at very low risk of contrast agent-induced nephropathy. Recommendations for preventing contrast agent-induced nephropathy in patients at risk include: adequate hydration, administration of N-acetylcysteine, waiting at least 72 h between studies with contrast agent and use of iso-osmolar contrast agent. Discontinuing diuretics, nonsteroidal antiinflammatory agents and aminoglycosides may also decrease the risk of contrast agent-induced renal failure [40, 41].
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Risk factors for adverse reactions to contrast agent must be assessed. A previous reaction to contrast agent is the most important of all the risk factors. Adverse reactions are classified as either idiosyncratic (anaphylactoid) or nonidiosyncratic. Life-threatening reactions are rare. Premedication reduces the risk of recurrent anaphylaxis, but in patients with a history of a severe reaction, an unenhanced CT examination is preferred [40, 41, 43].
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For CT imaging of the abdomen or pelvis, an intraluminal gastrointestinal contrast agent may be administered to improve visualisation of the gastrointestinal tract on CT (unless it is not necessary for the clinical indication or it is medically contraindicated). Contrast agents must only be used in accordance with the recommendations given in section VII. Nowadays, water or water-based contrast agents are often used as an intraluminal contrast agent that provides improved image quality with reduced artefact [44]. Water can be an effective contrast agent allowing better or equal distention in the bowel and better or equal diagnostic clarity compared with routine barium contrast agent.
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Some patients have difficulties such as claustrophobia, dyspnoea or inability to lie still for the duration of the scan. These patients should be carefully evaluated and an effort made to solve the problem with minimum consequences for the patient and the quality of the scan; sometimes, however, a solution cannot be found even if the study is repeated or rescheduled for another day. Occasionally sedatives can be of help in patients suffering claustrophobia. These issues should be noted in order to avoid potential pitfalls and to facilitate interpretation of suboptimal scans.
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Radiopharmaceutical
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Product: 18F-fluoro-2-deoxyglucose (FDG)
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Nuclide: Fluorine-18
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Dosage/activity: Dependent on the system, time per bed position and the patient’s weight
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Administration: Intravenous
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Synthesis and quality control: Conform to the European Pharmacopoeia in Europe or the US Pharmacopeia in the US
Recommendations for FDG dose and administered activity
Recommendations for FDG administered activity
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An exploratory further optimisation is presently being evaluated by EARL [46, 47]. This procedure would allow lowering the administered FDG activity for PET/CT systems with higher sensitivity or improved performance using new enhanced technology (e.g. better time-of-flight performance, continuous bed motion or extended axial FOV, i.e. length of bed position). A prerequisite is that imaging sites first obtain EARL accreditation for that system and subsequently follow the instructions provided by the standard operating procedure (SOP) “EARL procedure for assessing PET/CT system specific patient FDG activity preparations for quantitative FDG PET/CT studies” [47].
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For patients weighing more than 90 kg, increasing the emission acquisition time per bed position rather than increasing the administered FDG activity is recommended to improve image quality. Literature suggests that FDG activities higher than 530 MBq for patients above 90 kg should not be applied for L(Y)SO systems [50].
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A maximum administered FDG activity may be imposed by national law. If this is the case, increasing the emission acquisition time should be pursued to keep administered FDG activity within legal limits.
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If the PET acquisition duration for each bed position can be set separately, then the acquisition duration per bed position may be further reduced by up to 50 % for bed positions outside the thorax and abdomen (i.e. at the level of the head, neck and legs) because overall attenuation in these body regions is lower. The FDG activity must still be calculated assuming the acquisition duration per bed position as used for bed positions at the level of the thorax and abdomen. Systems with continuous motion functionality may increase motion speed twofold outside the thoracic and abdominal regions.
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In all cases the administered FDG activity should not result in activities within the FOV that exceed the peak count rate capability of the PET/CT system in use. The emission acquisition duration should then be increased to keep image quality within acceptable limits.
Materials for preparation and administration of FDG and contrast agent
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Weighing scales that are accredited and checked at least annually. Scales should be accurate to within 1 kg.
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Equipment for measuring height, which should be accurate (to within 0.5 cm) and maintained regularly.
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Bedside glucose meter to check serum glucose. Note that many bedside methods do not have sufficient precision to be used for SUV glucose correction [29].
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A three-way valve system for administering FDG and flushing with physiological saline is usually used. However, if automated bedside administration systems are used, then other types of lines may be required to obtain the same flushing and administration results.
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A programmable fluid injector with at least two fluid containers for intravenous administration of contrast agent. Only if a fluid injector is not available may intravenous contrast agent be injected manually, although two-phase contrast agent protocols cannot be carried out.
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First-line emergency drugs and equipment should be in the examination room when a diagnostic CT scan with intravenous contrast agent is to be performed [43]. Emergency devices and drugs are to be available according to national and hospital procedures.
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In the case of manual administration:
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An indwelling intravenous device is used to administer the FDG once the blood glucose has been determined. Make sure that if there is a needle on the syringe it is free of FDG.
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Flush and rinse out the administration syringe with at least 10 mL of normal saline (NaCl 0.9 %) – or solutions without glucose – using the three-way valve.
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In the case of automated administration:
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Make sure that the automated system is able to administer a net FDG activity within 3 % accuracy (this must be ensured by the manufacturer and verified by the user), i.e. the actual administered activity may not deviate by more than 3 % from that indicated by the device. Follow the instructions provided by the manufacturer.
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Procedure for preparation and administration of FDG and contrast agent
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Report any problems with FDG administration and image the injection area if extravasation is suspected.
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The administration system and/or administration lines and intravenous access can be removed after tracer administration (unless CT contrast agent is to be administered subsequently by intravenous injection).
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Residual activity in administration lines and intravenous access should be measured in order to derive net administered FDG activity; procedures and recommendations are detailed in the UPICT oncology FDG-PET CT protocol [30].
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Ambient conditions of the waiting room should help create a stress-free environment and a warm temperature. Give the patient extra blankets if necessary.
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Ask patients to lie or sit as calmly as they can, and not to talk. Provide comfortable beds or chairs. They may go to the toilet while waiting, preferably more than 30 min after injection. Ask patients to use the bathroom to empty their bladder 5 min before the start of the FDG PET/CT study.
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When dedicated brain imaging is indicated, additional preparation is necessary [39]. Patients should be positioned comfortably in a quiet, dimly lit room several minutes before FDG administration and during the uptake phase of FDG (at least 20 min). They should be instructed not to speak, read or be otherwise active. If possible, they should keep their eyes closed during the uptake phase of FDG. It is desirable to have the cannula for intravenous administration in place 10 min before FDG administration.
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Intense bladder or ureter activity can impair the interpretation of lesions in the pelvis and retroperitoneum. Therefore, during the waiting period patients may be asked to drink another 500 mL of water. If a patient is unable to hydrate orally, this amount can be given in the form of normal saline intravenously, provided such a fluid load is not medically contraindicated, e.g. due to impaired renal function or poor cardiac function. Loop diuretics (e.g. intravenous furosemide) can occasionally be given, although this is rarely necessary.
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The recommended interval between FDG administration and the start of acquisition is 60 min. However, for clinical trials this may differ depending on the disease and the aims of the study. Any such variation should be clearly stated in the study protocol. The actual interval should be recorded, i.e. the time between FDG injection and imaging should be reported. Be aware that this is usually not equal to the FDG activity assay or calibration time. Note that consistency of SUV measurements (in-house and when compared to the literature) depends on strict observance of the uptake time, and therefore a 60 min interval is recommended with an acceptable range of 55 – 75 min [30]. When repeating an FDG PET/CT study in the same patient, especially in the context of therapy response assessment, it is essential to apply the same uptake interval to within 10 min [30]. In addition, the use of the same PET/CT system and identical acquisition and reconstruction settings should be applied when making multiple examinations in the same patient.
Protocol/image acquisition
PET acquisition protocol
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Axial anatomical scan coverage: For most oncology indications covering the range from the base of the skull to the mid-thigh is sufficient. A longer scanning trajectory of the whole body may be used if appropriate. Extended whole-body examinations are performed in patients with tumours that show a high probability of metastases in the head, skull, brain and lower extremities. In patients with tumours with a high risk of head and brain metastasis but not metastasis in the lower extremities (e.g. lung cancer), it may be appropriate to perform an extended torso FDG PET/CT scan including the brain in the same scan [53]. Limited-view tumour imaging can be considered for follow-up examinations if the disease is restricted to a defined region (e.g. solitary pulmonary nodule, suspicion of lung cancer, examination of hilar lymph nodes, head and neck tumours, assessment of therapy response). If limited-view imaging is performed in the setting of a longitudinal study, the uptake time of the lesion being studied should be the same (to within 5 min) across all longitudinal imaging studies in the same patient.
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Generally, the patient should be positioned with the arms elevated and supported above the head to avoid beam-hardening artefacts in the abdominal and pelvic regions as well as artefacts caused by truncation of the measured FOV. If the patient is not able to keep the arms elevated above the head, one arm can be kept above the head with the other positioned alongside the body, or both arms can be positioned alongside and close to the body. Either way, every attempt should be made to avoid CT truncation. When using systems with extended CT FOVs, the arms may be positioned alongside the body to enhance patient comfort provided CT truncation is avoided.
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For examination of head and neck tumours a two-step protocol may be helpful [54]:1.Head and neck portion with the arms down, then2.Apex of the lung through the mid-thigh with the arms up.
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If the FDG PET/CT data are used for radiation planning, the examination should be performed in the position used for radiotherapy treatment, employing the same dedicated positioning devices as are used in the radiotherapy department (e.g. the same radiotherapy table top, laser alignment, immobilisation devices and measures) [15]. These guidelines consider static acquisitions only. Radiotherapy planning may increasingly require respiratory gating, too, but this is not covered in the present guidelines.
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When dedicated brain imaging is indicated [39]:
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Patient preparation should be as for brain scan [39]
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Arms down, head fixed in a head holder
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CT topogram of head, followed by
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Low-dose CT scan, followed by
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Single FOV PET acquisition
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5 min acquisition 45 – 50 min after injection with injected doses of 300 – 400 MBq. If the suspected underlying indication for the brain scan is probably not cancer-related (dementia, etc.), the emission scan can be acquired earlier, up to 30 min after injection. However, identical time frames must be used for the same indications to render the results comparable.
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Arms down followed by one of the protocols described in the next section (CT protocols for the FDG PET/CT study).
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Brain image reconstruction performed independently for body scan following guidelines.
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In general, FDG PET/CT is performed using a protocol comprising a scanogram/scout scan/topogram and a low-dose CT scan for attenuation correction (CT-AC) and anatomical correlation.
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The CT-AC scan should be performed while the patient continues tidal or shallow breathing. In the case of CT systems with six or fewer rings, a protocol using breath hold in normal expiration should be considered for the duration of scanning the thorax and upper abdomen.
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A standard diagnostic CT scan with intravenous contrast agent may, if appropriate, be performed. Several strategies for performing PET/CT studies that include diagnostic CT imaging are provided in detail below.
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Images should be reviewed before the patient leaves the department to ensure that the examination is technically satisfactory (i.e. that the clinical question can be addressed properly) and to assess any need for additional imaging or urgent contact with the referring physician.
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Online random correction should be based on the ‘delayed coincidence time window’ technique or random correction using a model based on (block) singles count rates.
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During patient registration with the PET/CT system, users should carefully enter all information into the PET/CT console correctly. This includes, but may not be limited to, patient height and body weight, radiopharmaceutical and the net activity administered. Also the assay activity (i.e. FDG activity) and assay time (i.e. activity calibration time) should be noted and reported. In addition, the time of injection (usually not equal to the assay time or activity calibration time) should be noted and reported. If this information cannot be entered into the PET/CT system, it should be reported in the patient or scan report file.
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Decay correction must be ‘on’ (see also section PET image reconstruction).
CT protocols for the FDG PET/CT study
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CT imaging within the framework of FDG PET/CT studies typically consists of a topogram and a single or multiple helical CT scans.
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CT acquisition parameters (e.g. tube current, voltage, slice thickness, rotation time and pitch) should be chosen with regard to the objective of the CT examination (e.g. attenuation and scatter correction, colocalisation of radiologically equivalent interpretation). Specific local or national dose limits may apply for these types of CT examinations and should always be adhered to. Overall, CT scan parameters should be chosen such that patient exposure is minimised yet dose is adequate to obtain the necessary diagnostic information.
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Ultra low-dose CT scans are now being introduced on some PET/CT systems, often in combination with iterative reconstruction methods (as discussed below), which may be applied to further reduce CT radiation dose.
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For a diagnostic contrast-enhanced CT scan, standard CT settings as suggested by related guidelines and the supervising radiologist or responsible physician should be employed. Modulation of the tube current is encouraged in the absence of metallic implants (e.g. orthopaedic braces) in the coaxial imaging range to lower patient exposure. Depending on the clinical question, intravenous and/or oral contrast agents may be employed. It might be appropriate to perform a diagnostic CT scan for particular regions of the body, followed by a low-dose CT scan of the rest of the body for CT attenuation correction and colocalisation. In some instances, it might be preferable to begin with a low-dose CT scan of the body and then decide to add a diagnostic CT scan of a particular region, as the findings on the low-dose CT scan may influence the need for a contrast-enhanced or higher resolution regional view.
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High intravenous or intestinal concentrations of contrast agent may cause artefacts in the reconstructed PET images following CT attenuation correction and thus affect quantification. The impact of intravenous contrast agents on the accuracy of attenuation correction is considered acceptable when CT data are collected in the equilibrium or venous phase (i.e. delayed acquisition) and in some centres a contrast-enhanced CT scan only is performed, although uptake in reference regions such as the mediastinum and liver may be affected.
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Arterial phase CT acquisitions should be avoided. In FDG PET/CT studies without the need for advanced quantification, intravenous contrast agents may be used directly (i.e. the CT scan can also be used for attenuation correction) during the FDG PET/CT study because the impact on visual image quality and interpretation is modest. However, deep inspiration for chest CT acquisition will cause a large degree of misregistration and may introduce unacceptable artefacts if the low-dose CT scan (with normal breathing) is replaced by such a diagnostic deep inspiration CT scan.
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Deep inspiration chest CT scans should not be used for attenuation correction when PET quantification is required or intended. Therefore, for attenuation correction, the PET study ideally should be combined with a low-dose CT scan obtained during tidal or shallow breathing or with a contrast-enhanced CT scan obtained during tidal or shallow breathing (as described below).
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The presence of a positive contrast agent (intravenous or oral) may minimally affect the CT attenuation map and, therefore, affects SUV quantification [55]. If this were the only aspect to be taken into consideration, the ideal would be to prohibit CT contrast agent administration. However, in some clinical situations (depending upon tumour type, tumour behaviour or level of anatomical interest), the benefit of CT contrast agents may outweigh the small errors induced in SUV measurement, which may include increased SUV variability. Each protocol should specify the desired approach for the given study. Most importantly, in the same subject, the same approach should be followed at all subsequent imaging time points. In the case of longitudinal studies in which a diagnostic contrast-enhanced CT scan may not be indicated in all PET/CT examinations, strategies 1, 2a and 2b, as indicated below, should be followed.
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If the FDG PET/CT study is performed with the purpose of quantitatively assessing FDG uptake and a diagnostic CT scan is required, the following PET and CT acquisition sequences or strategies should be followed, as indicated in the UPICT Oncology FDG PET/CT protocol [30] and the FDG PET/CT QIBA profile [56]:
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Strategy 1: When CT is used for attenuation correction and localisation only (not intended as a clinically diagnostic CT scan):
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CT topogram, followed by
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Low-dose CT scan, followed by
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PET acquisition
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Strategy 2: When a contrast-enhanced diagnostic CT scan is also needed, one of the following options must be used:
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Strategy 2a (recommended as it avoids any, albeit possibly minimal, impact of intravenous contrast enhancement on attenuation correction and therefore SUV determination):
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Follow strategy 1
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Acquire an additional intravenous contrast-enhanced diagnostic CT scan with breathing instructions, if needed
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Strategy 2b:
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Perform an intravenous contrast-enhanced diagnostic CT scan with breathing instruction if needed
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Follow strategy 1 with a delay of at least 60 s to allow contrast agent to dilute over the body/blood pool
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In the case of protocols or scanning strategies that can be used in clinical practice, i.e. when there is no need for or intention to perform SUV-based quantification, the diagnostic CT scan with intravenous contrast agent may be used for attenuation correction. If contrast-enhanced CT is used for attenuation correction it may alter SUV quantification (<10 % on average). Therefore, the strategies below are for image interpretation based on visual (uptake) assessment only. FDG PET/CT studies performed with the intention of assessing FDG uptake quantitatively should follow the recommendations given above (strategy 1, 2a or 2b). A deep-inspiration thoracic CT scan with a 20 s delay from the beginning of contrast agent infusion can be included as it will provide additional information. However, this CT scan is used neither for attenuation correction nor for PET/CT image fusion, but rather to assess the lung parenchyma with thinner slices (2.5 mm), which is very useful for comparison with previous and/or future studies, and also allows evaluation of thoracic vessels.
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Strategy 3 (low-dose CT scan):
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CT topogram, followed by
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A deep-inspiration thoracic CT scan with a 20 s delay from the beginning of the contrast agent infusion (this CT scan is used neither for attenuation correction nor for PET/CT image fusion), followed by
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A whole-body low-dose CT scan (with shallow or tidal breathing) with a 45 s delay after the thoracic CT scan (equilibrium or venous phase) if the thoracic CT scan was performed or with a 60 s delay after the beginning of contrast agent infusion if the thoracic CT was not performed, followed by
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PET acquisition
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Strategy 4 (diagnostic CT scan):
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CT topogram, followed by
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A deep-inspiration thoracic CT scan with a 20 s delay from the beginning of contrast agent infusion (this CT scan is used neither for attenuation correction nor for PET/CT image fusion), followed by
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A whole-body diagnostic CT scan (with shallow breathing) with a 45 s delay after the thoracic CT scan (equilibrium or venous phase) if the thoracic CT scan was performed, or with a 60 s delay after the beginning of contrast agent infusion if the thoracic CT scan was not performed, followed by
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PET acquisition
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Other specific protocols can be applied depending on the tumour type and the clinical indication.
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Intravenous contrast agent is ideally administered with a programmable fluid injector at a speed of 2.5 ml/s for a catheter of 20G × 1.16″ if located in the elbow. If the catheter is placed in other locations, the diameter of the catheter and/or the speed of infusion and delay may need to be adjusted.
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Oral contrast agents allow better delineation of the gastrointestinal tract. A positive contrast agent (for example diluted barium) as well as a negative or water-based contrast agent (for example water or locust bean gum) can be used [44]. High intraluminal concentrations of barium or iodinated contrast agents can cause an attenuation correction artefact in PET images, resulting in an overestimation of FDG accumulation at those sites. These artefacts can be avoided by using a negative contrast agent. However, administration of water only as a negative intraluminal contrast agent itself is associated with fast reabsorption and can cause increased nonspecific FDG accumulation in the bowel [57]. If quantification of the FDG PET/CT studies is required, the use of diluted positive contrast agents only is recommended. The concentration of diluted positive contrast agents should be low enough to guarantee absence of attenuation correction artefacts, and this should be verified for each combination of PET/CT system, PET/CT image reconstruction software and contrast agent being used.
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It should be ensured that the patient is lying within the CT-AC FOV and in the same position as during the PET acquisition. If the system is equipped with extended FOV capabilities this option should preferably be used to avoid CT truncation.
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Metal implants can cause severe artefacts in the CT image. Metal artefact reduction techniques may be used to minimise these artefacts. When the CT data are used for attenuation correction of the PET data, it should be considered that even when using metal artefact reduction techniques, metal implants will likely result in reduced PET image quality and will prevent proper quantification (at and near the metal implant). FDG uptake should be confirmed by inspecting the PET images without attenuation correction.
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-
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In most PET/CT systems today, the measured FOV of the CT scanner is smaller than that of the PET scanner. Truncating the CT images causes reconstruction artefacts and thus inaccurate quantification of the PET study. When available, truncation correction algorithms may be applied during image reconstruction (and/or during processing of the CT data used for attenuation correction). As the amount of truncation may vary across studies and subjects, it will be difficult to ensure proper quantification across studies and subjects. It is, therefore, strongly recommended that any truncation of the CT images is avoided. If available, the use of extended CT and PET FOVs is recommended. It should be noted that truncation of the CT images may occasionally seriously affect scatter correction scaling as well, and may lead to inaccurate quantitative results.
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Make sure that all clocks (including the dose calibrators – the one at the hospital and the one at the external laboratory dispensing the FDG – and the PET/CT system) are synchronised and that this is regularly checked. Consult the local service engineer when needed. Clocks should be synchronised with the official local time to within 1 min (in the case of studies using 18F).
Image reconstruction
PET image reconstruction
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All the corrections necessary to obtain quantitative image data should be applied during the reconstruction process.
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When available, time-of-flight information should be used during reconstruction.
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Resolution modelling during reconstruction or other new reconstruction or image processing methods may be applied. In the case of multicentre studies or when quantification is required, the use of these methods typically entails additional filtering during or after image reconstruction in order to meet the standardised/harmonised quantitative PET/CT system performance specifications, as detailed below. When these multicentre standards cannot be met, these reconstruction methods and settings should not be used for quantification of FDG uptake.
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Spatial filters applied during or after reconstruction should not exceed a full-width at half-maximum of 7 mm, not even to mitigate Gibbs artefacts when using resolution modelling. In these cases the use of reconstructed images generated without resolution modelling should be considered.
CT image reconstruction
Image analysis and interpretation
Image analysis and SUV calculations
Physiological FDG distribution and interpretation criteria
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Due to the high physiological FDG uptake in the brain, FDG PET/CT is of limited value for detection of brain metastases. Consequently, FDG PET/CT is generally not used for the primary detection or exclusion of brain metastases.
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Increased FDG uptake is observed in many neoplastic lesions, granulation tissue (e.g. wound healing), infections and other inflammatory processes. A detailed description of pitfalls and situations that can lead to false-positive (benign processes that can show FDG uptake) or false-negative FDG PET/CT interpretation has been published [67].
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Patterns of FDG uptake, established CT morphological criteria and correlation with patient history, physical examination and other imaging modalities may be helpful for differentiation between malignant and benign lesions.
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There is no single lower limit of the intensity of FDG uptake for the detection of abnormal uptake within lesions as it depends on the degree of contrast between the tumour and its immediate surroundings. This contrast is related to several pathophysiological factors, the most significant of which are histology (FDG avidity of the type of tumour), volume of vital tumour cells, movement during static acquisition (e.g. blurred signals in the case of pulmonary foci) and physiological high uptake in adjacent background. Furthermore, the sensitivity of FDG PET/CT may be reduced in diabetic patients with elevated glucose levels [72].
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Although there are no conclusive data on the optimum interval between chemotherapy and FDG PET/CT, an interval of at least 10 days between the last treatment and the FDG PET/CT examination is generally considered adequate for measurement of response [20]. This is because of the balance between any possible effects on tumour metabolism (such as macrophage impairment) and systemic effects (such as bone marrow activation following bone marrow depression, which may or may not be caused by growth factors). If an interval of 10 days is not possible, FDG PET/CT should be delayed as long as possible after the previous chemotherapy administration (i.e. until as close as possible to the next treatment cycle).
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The effects of growth factors (G-CSF and GM-CSF) on FDG biodistribution (due to enhanced bone marrow uptake) generally last for more than 2 weeks after the final administration [20].
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It is assumed that the (side) effects of radiotherapy are longer-lasting; investigation of patients with head and neck carcinoma treated with radiation have shown that radiation-induced inflammation can be seen on the FDG PET/CT images for 2 – 3 months after the end of treatment [73, 74]. Waiting 2 or 3 months following completion of radiation therapy before obtaining a PET/CT scan is clinically appropriate as patients rarely develop clinical problems in the first 3 months after treatment.
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In patients who have undergone surgery, uptake depends on the extent of surgery, the presence of infection/inflammation in the wound, and how long after surgery images are acquired. For example, there are few visible signs of a mediastinoscopy after 10 days but sternotomy signs will remain visible for months. Following surgery, it is recommended to delay the FDG PET/CT for at least 6 weeks due to postsurgical inflammation if the scan is primarily being done to assess the surgical field.
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FDG PET/CT for diagnostic purposes is generally assessed using visual criteria, looking for focally increased uptake that may represent malignancy in the appropriate clinical context. It is unclear how SUV can contribute to patient assessment, partly because of the considerable variability in the methodology used. However, this document and several others propose harmonised quantitative FDG PET/CT imaging procedures in multicentre studies and harmonised quantitative interpretation criteria to assess treatment response [30].
Documentation and reporting
Direct communication
Written communication
Contents of the report
Study identification
Clinical information
Procedure description
Description of the findings
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Quality of the FDG PET/CT study, e.g. limited due to motion artefacts, abnormal biodistribution of tracer (FDG accumulation in muscles and/or brown fat), infiltration of tracer at the injection site or hyperglycaemia. CT-related artefacts should also be mentioned such as metallic artefacts and other information on large patient body habitus when the quality of the study is affected.
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Description of the location, the extent and the intensity (SUV and/or SUL) of pathological FDG accumulation related to normal tissue.
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Description of relevant findings on CT and their relationship to pathological FDG accumulation. FDG uptake may be reported as mild, moderate or intense and compared to the background uptake in, for example, the liver parenchyma (mean SUV 2.0 – 3.0, maximum SUV 3.0 – 4.0). However, criteria for visual interpretation need to be defined for each study protocol and may vary according to the type of cancer and for different tumour locations. Some criteria have already been proposed [78, 79]. Incidental FDG PET and CT findings should be included in the report, particularly if they are of clinical relevance.
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The CT part of the FDG PET/CT report must describe all relevant anatomical findings (some of which may be FDG PET-negative).
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Limitations: If necessary, confounding factors that might influence the sensitivity or specificity of the FDG PET/CT study may be mentioned such as small lesions (partial volume effect), inflammatory changes, muscle activity, high blood glucose levels at the time of injection, paravascular infiltration of FDG or tissue injections.
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Clinical context: In the body of the report it can occasionally be helpful to address the findings of the study with respect to the clinical questions asked. However, this is more commonly done in the report Summary/Impression. Any interpretation or summary in the body of the report should also be repeated in the report Summary/Impression.
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Complementary information: Comparison with previous examinations should be part of the FDG PET/CT report. FDG PET/CT studies are more valuable if they are interpreted in the context of other imaging examinations (CT, PET/CT, MRI etc.) and clinical data.
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Assessment of response to therapy: If an FDG PET/CT study is performed in the context of the assessment of response to therapy, the extent and the intensity of the FDG uptake should be documented and compared to prior measurements, if available. Examples of criteria for therapy response with FDG as a metabolic biomarker have been suggested by The European Organisation for Research and Treatment of Cancer [68]. In 2009, Wahl et al. suggested the so-called PERCIST criteria for assessing solid tumour response [61]. Further, a five-point scale has been proposed for assessment of lymphoma therapy response [80]. Reporting of the change in intensity of the FDG uptake using semiquantitative parameters – expressed as absolute or relative change – can be used for specific dedicated clinical questions. At present, relative changes in SUV during therapy represent the most robust parameters. The reliability of the results reported will depend on having comparable patient preparation, injection and scanning protocols, as well as comparable data analysis.
Summary and diagnosis/impression
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Clearly identify the study as normal or abnormal.
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The question asked in the study requisition should be directly addressed.
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If possible, a definite diagnosis should be stated. Whenever possible this should provide a staging assessment (TNM or other) stating whether there are categories of uncertainty. Alternatively, a qualitative estimate of the likelihood of a diagnosis and the differential diagnoses should be given.
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If appropriate, repeat examinations and/or additional examinations should be recommended to clarify or confirm findings.
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For therapy evaluation, serial studies should be compared, using visual and/or semiquantitative assessment as appropriate.
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Document the communication of urgent or emergency findings to referring physicians or their deputy.
Additional notes
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Limitations of staging: Every diagnostic test has a threshold. The threshold used may vary depending on the implications for treatment (to optimise diagnostic accuracy or according to treatment intent).
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Indeterminate lesions and management of uncertainty: Indeterminate lesions should be the point of clinical–radiological discussion and/or multidisciplinary review, if better characterisation of the lesion will further affect patient management. The options for resolving uncertainties are discussion, further investigation, intervention and active monitoring (watch and wait).
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Multidisciplinary team meetings: Multidisciplinary team meetings allow a team approach to patient management to take into account and evaluate all aspects of the disease prior to individualised therapy planning. It should be possible to review all relevant examinations in a multidisciplinary meeting, especially when there is discrepancy between clinical and imaging findings or other diagnostic uncertainty. During the meetings, the results of the discussions should be recorded, and discrepancies noted and, if necessary, reported as an addendum to the imaging report. If additional tests are needed, these should be scheduled as soon as possible. The presence of a reporting radiologist or nuclear medicine specialist is essential [72].
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Imaging the treated patient or follow-up studies: The format of the report should mirror the one at baseline. Reports of follow-up studies must include clear statements regarding the detection of new disease as this implies metabolic progression of disease. Also, descriptions on the direction of change, indeterminate lesions and mixed responses and findings at variance with one another that may reflect different pathologies should be stated [30].
Definitions of volumes of interest
Recommended tumour uptake metrics
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The maximum SUL or SUV (SULmax, SUVmax) is required for each lesion as specified in the study protocol and/or as considered clinically relevant for routine clinical studies. The SULmax and SUVmax are measures of the single whole voxel in a particular lesion with highest/maximum uptake. The maximum uptake should be defined on original reconstructed PET images, i.e. no additional rebinning, resampling, smoothing or any other manipulation by the user is allowed.
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Use of a 3D peak VOI (providing SUVpeak and SULpeak) may be determined (when possible) using a 3D 1.2 cm diameter (and 1.0 mL volume) spherical VOI [61] positioned such that the average value across all positions within the lesion is maximised. Often this coincides with the location (not value) of SUVmax and SULmax, but this may not necessarily be the case in all situations.
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The TLG and MTV are of increasing interest and these parameters or their change may have prognostic and/or predictive value. These parameters should therefore be reported, if available. These metrics requires a 3D delineation or segmentation of the FDG-avid lesions. 3D VOIs based on percentage of SUVmax or SULmax thresholds are frequently used [48, 81] and most widely available. It is recommended, when possible, to include the following 3D region isocontour-based VOIs for reporting TLG and MTV [48, 81, 82]:
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3D isocontour at 41 % of the maximum pixel value (VOI41)
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3D isocontour at 50 % of the maximum pixel value (VOI50)
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The MTV represents the volume of the above given VOI. MTV41 is derived using VOI41 and MTV50 is derived using VOI50. TLG is the product of the VOI average SUV or SUL (SUVmean, SULmean) multiplied by the corresponding MTV. TLG41 is derived using VOI41 and TLG50 using VOI50.
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In a longitudinal setting the quantitative metrics described above should be derived using the same VOI approach for all FDG PET/CT examinations in the same patient. Changes in SUL, TLG and MTV should be evaluated using the same VOI approach for all PET/CT studies in the same patient.
Some considerations with respect to semiautomated percentage threshold-based delineation methods
Liver uptake assessment
Mediastinal uptake assessment
Quality control and interinstitution PET/CT system performance harmonisation
PET/CT system quality control
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Daily QC (both the PET and the CT component of the PET/CT system)
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Calibration QC and cross-calibration of PET/CT system with the institution’s own dose calibrator or against a dose calibrator (e.g. that of an FDG provider) which is generally used to determine patient-specific FDG activities
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Image quality and recovery coefficients (IQRC)
Daily QC
Calibration QC and cross-calibration of PET/CT systems
Image quality and recovery coefficient harmonisation
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To determine/check the correctness of a calibration and quantification using a noncylindrical (calibration) phantom containing a set of high-contrast spherical objects.
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To measure standardised ‘activity concentration or SUV recovery coefficients’ as a function of sphere (tumour) size.
Minimum frequency of PET/CT system QC procedures
Procedure | Frequency |
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Daily QC (outlined above) | Daily |
Cross-calibration | Quarterly and always immediately following software and hardware revisions/upgrades and immediately following new set-ups/normalisations |
IQRC | Annually and always following reconstruction/system software adjustments, especially adjustments to the reconstruction and/or data analysis (region of interest) software/hardware, and following relevant system hardware changes |
CT quality control (CT-QC)
Additional QC measures
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Alignment of PET and CT images on a PET/CT system should be checked according to the procedure and frequency recommended by the manufacturer.
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Set-up and normalisation for both PET and CT systems should be performed according to the procedure and frequency recommended by the manufacturer.
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All devices involved (PET/CT systems, dose calibrators, well counters, clocks, scales) should be maintained according to the manufacturers’ recommendations or following national guidelines [99]. This includes preventive and corrective maintenance required to ensure correct and accurate functioning of the devices.
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Calibration should always be performed or correct (cross-)calibration should be verified (by means of QC) after maintenance and software upgrades.
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The accuracy of scales used to measure height and to weigh patients should be checked at installation and after maintenance and/or according to the procedure and frequency recommended by the manufacturer.
Radiation exposure to the patient
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The radiation dose with FDG PET/CT is the combination of the radiation exposure from the radiopharmaceutical (Table 1) and the CT study. The radiation dose of diagnostic CT is a matter of concern, particularly for paediatric examinations. The mean dose for a CT scan depends on applications, protocols and CT systems. Especially in children but also in adults it is important to optimise the radiation exposure with respect to the diagnostic question. Recent advances in technology have allowed the radiation doses to be significantly reduced relative to a conventional CT or PET examination.Table 1Radiation dosimetry for FDGAdult15 years10 years5 years1 yearRecommended administered activity at nominal weight (MBq) [51]See section VII30218912070Nominal weight (kg)–55321910Organ receiving highest dose [25]BladderBladderBladderBladderBladderAbsorbed dose per unit activity at voiding interval (mGy/MBq) [25]1.3 × 10−11.6 × 10−12.5 × 10−13.4 × 10−14.7 × 10−1Voiding interval (h) [25]3.53.53.53.02.0Effective dose (mSv/MBq) [25]1.9 × 10−22.4 × 10−23.7 × 10−25.6 × 10−29.5 × 10−2
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The coefficient for effective dose from FDG in adults is 1.9 × 10−2 mSv/MBq according to ICRP publication 106 [25], i.e. about 3.5 mSv for an administered activity of 185 MBq. The radiation exposure related to a CT scan carried out as part of an FDG PET/CT study depends on the intended use of the CT study and may differ from patient to patient: the CT scan can be a very low-dose scan (with lower tube voltage and current) for attenuation correction only, or as a low-dose or intermediate-dose scan for attenuation correction and localisation of PET lesions, or additionally a diagnostic CT scan can be indicated (in most cases with intravenous contrast agent administration and deep inspiration for chest CT) for a full diagnostic CT examination. The effective CT dose ranges from 1 to 20 mSv and may be even higher for a static high-resolution diagnostic CT examination. Given the variety of CT systems and protocols, the radiation exposure for a FDG PET/CT study should be estimated specifically for a given imaging system and protocol. Guidelines provided by European radiological societies should be consulted regarding effective dose from the CT examination.1
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The choice of imaging protocol strongly depends on the clinical question and must be considered for every single case. Paediatric studies require special attention. For the optimisation of FDG PET/CT studies, dose reduction techniques should be considered.