The number of clinical applications for positron emission tomography (PET) continues to increase, particularly in the field of oncology. In parallel with this is growth in the number of centers that are able to provide a clinical PET or PET/computed tomography (CT) service. As with any imaging technique, including radiography, ultrasound, CT, magnetic resonance imaging (MRI), and conventional single photon nuclear medicine imaging, there are a large number of normal variants, imaging artifacts, and causes of false-positive results that need to be recognized to avoid misinterpretation. It is particularly important to be aware of potential pitfalls while PET is establishing its place in medical imaging so that the confidence of clinical colleagues and patients is maintained. In addition, the advent of combined PET/CT scanners in clinical imaging practice has brought its own specific pitfalls and artifacts.
The most commonly used PET radiopharmaceutical in clinical practice is 18F-fluorodeoxyglucose (FDG). As it has a half-life of nearly 2 h, it can be transported to sites without a cyclotron, and in view of this and the fact that there is a wealth of clinical data and experience with this compound, it is likely to remain the mainstay of clinical PET for the immediate future.
Mechanisms of Uptake of
18
F-Fluorodeoxyglucose
FDG, as an analogue of glucose, is a tracer of energy sub- strate metabolism, and although it has been known for many years that malignant tumors show increased gly- colysis compared to normal tissues, its accumulation is not specific to malignant tissue. FDG is transported into tumor cells by a number of membrane transporter pro- teins that may be overexpressed in many tumors. FDG is converted to FDG-6-phosphate intracellularly by hexoki- nase, but unlike glucose does not undergo significant en- zymatic reactions and, because of its negative charge, remains effectively trapped in tissue. Glucose-6-phos-
phatase-mediated dephosphorylation of FDG occurs only slowly in most tumors, normal myocardium, and brain, and hence the uptake of this tracer is proportional to gly- colytic rate. Rarely, tumors may have higher glucose-6- phosphatase activity resulting in relatively low uptake, a feature that has been described in hepatocellular carci- noma (1). Similarly, some tissues have relatively high glucose-6-phosphatase activity, including liver, kidney, intestine, and resting skeletal muscle, and show only low uptake. Conversely, hypoxia, a feature common in ma- lignant tumors, is a factor that may increase FDG uptake, probably through activation of the glycolytic pathway (2).
Hyperglycemia may impair tumor uptake of FDG because of competition with glucose (3), although it appears that chronic hyperglycemia, as seen in diabetic patients, only minimally reduces tumor uptake (4). To op- timize tumor uptake, patients are usually asked to fast for 4 to 6 h before injection to minimize insulin levels. This practice has also been shown to reduce uptake of FDG into background tissues including bowel, skeletal muscle, and myocardium (5). In contrast, insulin-induced hypo- glycemia may actually impair tumor identification by re- ducing tumor uptake and increasing background muscle and fat activity (6).
In addition to malignant tissue, FDG uptake may be seen in activated inflammatory cells (7, 8), and its use has even been advocated in the detection of inflammation (9).
An area where benign inflammatory uptake of FDG may limit specificity is in the assessment of response to radio- therapy (10). Here, uptake of FDG has been reported in rectal tumors and in the brain in relation to macrophage and inflammatory cell activity (11–13), which may make it difficult to differentiate persistent tumor from inflamma- tory activity for a number of months following radio- therapy in some tumors. Nonspecific, inflammatory, and reactive uptake has also been recorded following chemotherapy in some tumors (14, 15), and there is no clear consensus on the optimal time to study patients fol- lowing this form of therapy.
63
5
Artifacts and Normal Variants in Whole-Body PET and PET/CT Imaging
Gary J.R. Cook
Normal Distribution of FDG
The normal distribution of FDG is summarized in Table 5.1. The brain typically shows high uptake of FDG in the cortex, thalamus, and basal ganglia. Cortical activity may be reduced in patients who require sedation or a general anaesthetic, a feature that might limit the sensitivity of de- tection of areas of reduced uptake as in the investigation of epilepsy. It is not usually possible to differentiate low- grade uptake of FDG in white matter from the adjacent ventricular system (Figure 5.1).
In the neck, it is common to see moderate symmetrical activity in tonsillar tissue. This area may be more difficult to recognize as normal tissue if there has been previous surgery or radiotherapy that may distort the anatomy, re- sulting in asymmetrical activity or even unilateral uptake on the unaffected side. Adenoidal tissue is not usually no- ticeable in adults but may show marked uptake in chil- dren. Another area of lymphoid activity that is commonly seen in children is the thymus. This gland usually has a characteristic shape (an inverted V) and is therefore not usually mistaken for anterior mediastinal tumor (Figure 5.2). Clinical reports vary as to the incidence of diffuse uptake of FDG in the thyroid (16–18). This uptake may be a geographic phenomenon, since its presence is more likely in women and has been correlated with the presence of thyroid autoantibodies and chronic thyroiditis (18).
Table 5.1. Normal distribution of 18F-fluorodeoxyglucose (FDG).
Organ/system Pattern
Central nervous system High uptake in cortex, basal ganglia, thalami, cerebellum, brainstem.
Low uptake into white matter and cerebrospinal fluid.
Cardiovascular system Variable but homogeneous uptake into left ventricular myocardium. Usually no discernible activity in right ventricle and atria.
Gastrointestinal system Variable uptake into stomach, small intestine, colon, and rectum.
Reticuloendothelial and lymphatic Liver and spleen show low-grade diffuse activity.
No uptake in normal lymph nodes but moderate activity seen in tonsillar tissue.
Age-related uptake is seen in thymic and adenoidal tissue.
Genitourinary system Urinary excretion can cause variable appearances of the urinary tract.
Age-related testicular uptake is seen.
Skeletal muscle Low activity at rest
Bone marrow Normal marrow shows uptake that is usually less than liver.
Lung Low activity (regional variation) Source: From Valk PE, Bailey DL, Townsend DW, Maisey MN. Positron Emission Tomography: Basic Science and Clinical Practice. Springer-Verlag London Ltd 2003, p. 496.
In the chest, it has been recognized that there is varia- tion in regional lung activity, this being greater in the in- ferior and posterior segments, and it has been suggested that this might reduce sensitivity in lesion detection in these regions (19). In the abdomen, homogeneous low- grade accumulation is seen in the liver and to a lesser extent in the spleen. Small and large bowel activity is quite variable, and, unlike glucose, FDG is excreted in the urine, leading to variable appearances of the urinary tract, both of which are discussed further here. Resting skeletal muscle is usually associated with low-grade activity, but active skeletal muscle may show marked uptake of FDG in a variety of patterns that are discussed further next.
Myocardial activity may also be quite variable. Normal myocardial metabolism depends on both glucose and free fatty acids (FFA). For oncologic scans, it is usual to try to reduce activity in the myocardium so as to obtain clear images of the mediastinum and adjacent lung. Although most centers fast patients for at least 4 to 6 h before FDG injection, reducing insulin levels and encouraging FFA acid metabolism in preference to glucose, myocardial activity may still be quite marked and varies among patients. Another possible intervention that has not been quantified or validated as yet is to administer caffeine to the patient to encourage FFA metabolism.
For cardiac viability studies it is necessary to achieve high uptake of FDG into the myocardium. Patients may receive a glucose load to encourage glucose (and hence FDG) rather than FFA metabolism, and it may also be necessary to administer insulin to enhance myocardial uptake, particularly in diabetic patients (20–22). The hy-
perinsulinemic euglycemic clamping method may further improve myocardial uptake but is technically more difficult (23–26); this allows maximum insulin adminis- tration without rendering the patient hypoglycaemic. An alternative method is to encourage myocardial glucose
Slc 33 Z = –138 170++ + Slc 34 Z = –137 670++ + Slc 35 Z = –137 170++ + Slc 36 Z = –136 670++ +
Slc 33 Z = –138 170++ + Slc 34 Z = –137 670++ + Slc 35 Z = –137 170++ + Slc 36 Z = –136 670++ +
Oblique slice (2)+ Oblique slice (2)+ Oblique slice + Oblique slice +
Figure 5.2. Transaxial (a) and coronal (b) FDG images in a child showing
normal thymic activity. b
a
metabolism by reducing FFA levels pharmacologically.
Improved cardiac uptake of FDG has been described fol- lowing oral nicotinic acid derivatives such as acipimox, a simple and safe measure that may also be effective in dia- betic patients (27).
Variants That May Mimic or Obscure Pathology
A number of physiologic variations in uptake of FDG have been recognized, some of which may mimic pathology (16, 28–30) (Table 5.2).
Skeletal muscle uptake is probably the commonest cause of interpretative difficulty. Increased aerobic glycolysis as- sociated with muscle activation, either after exercise or as a result of involuntary tension, leads to increased accumula- tion of FDG that may mimic or obscure pathology. Exercise should be prohibited before injection of FDG and during the uptake period to minimize muscle uptake.
A pattern of symmetrical activity commonly encoun- tered in the neck, supraclavicular, and paraspinal regions (Figure 5.3) was initially assumed to be caused by invol-
Table 5.2. Variants that may mimic or obscure pathology.
Organ/system Variant
Skeletal muscle High uptake after exercise or resulting from tension, including eye movement, vocalization, swallowing, chewing gum, hyperventilation.
Adipose tissue Uptake in brown fat may be seen particularly in winter months in patients with low body mass index.
Myocardium Variable (may depend on or be manipulated by diet and drugs).
Endocrine Testes, breast (cyclic, lactation, hormone replacement therapy), follicular ovarian cysts, thyroid.
Gastrointestinal Bowel activity is variable and may simulate tumor activity.
Genitourinary Small areas of ureteric stasis may simulate paraaortic or pelvic lymphadenopathy.
Source: From Valk PE, Bailey DL, Townsend DW, Maisey MN. Positron Emission Tomography: Basic Science and Clinical Practice. Springer-Verlag London Ltd 2003, p. 498.
Figure 5.3. Coronal sections from a FDG study. Symmetrical brown fat activity is seen in the neck (a) and paraspinal (b) regions. Although this is a recognizable pattern, it can be appreciated that metastatic lymphadenopathy may be obscured, especially in the neck. PET/CT is helpful for the differentiation.
a b
untary muscle tension but with the advent of PET/CT it has become obvious that this activity originates in brown fat, a vestigial organ of thermogenesis that is sympatheti- cally innervated and driven. To support this hypothesis, it has been noted that this pattern is commoner in winter months and in patients with lower body mass index (31).
It appears that benzodiazepines are able to reduce the in- cidence of this potentially confusing appearance, possibly by a generalized reduction in sympathetic drive.
Even apparently innocent activities such as talking or chewing gum may lead to muscle uptake that simulates malignant tissue (Figures 5.4, 5.5). In patients being as- sessed for head and neck malignancies, it is therefore im- portant that they maintain silence and refrain from chewing during the uptake period. In addition, anxious or breathless patients may hyperventilate, producing in- creased intercostal and diaphragmatic activity, and invol- untary muscle spasm such as that seen with torticollis may lead to a pattern that is recognizable but may obscure diseased lymph nodes.
The symmetrical nature of most muscle uptake usually alerts the interpreter to the most likely cause, but occa- sionally unilateral muscle uptake may be seen when there is a nerve palsy on the contralateral side and may be mis- taken for an abnormal tumor focus. This appearance has been described in recurrent laryngeal nerve palsy and in VIth cranial nerve palsy (30). Diffusely increased uptake
of FDG may also be seen in dermatomyositis complicating malignancy, a factor that may reduce image contrast and tumor detectability.
Uptake in the gastrointestinal system is quite variable and is most commonly seen in the stomach (Figure 5.6) and large bowel (Figure 5.7) and to a lesser extent in loops of small bowel. It is probable that activity in bowel is related to smooth muscle uptake as well as activity in in- traluminal contents (32, 33). If it is important to reduce intestinal physiologic activity, pharmacologic methods to reduce peristalsis as well as bowel lavage could be useful.
This procedure is too invasive and is unnecessary for routine patient preparation, and in most situations it is possible to differentiate physiologic uptake within bowel from abdominal tumor foci by the pattern of uptake, the former usually being curvilinear and the latter being focal (Figure 5.8). Some centers use a mild laxative as a routine in any patient requiring abdominal imaging, but improve- ment in interpretation has not been demonstrated.
Unlike glucose, FDG is not totally reabsorbed in the renal tubules, and urinary activity is seen in all patients and may be present in all parts of the urinary tract. This activity may interfere with a study of renal or pelvic tumors, either by obscuring local tumors or by causing re- construction artifacts that reduce the visibility of abnor- malities adjacent to areas of high urinary activity. Using iterative reconstruction algorithms rather than filtered
Figure 5.4. FDG uptake seen in laryngeal muscles in a patient who was talking during the uptake period.
back-projection can reduce this problem. Catheterization and drainage of urinary activity may reduce bladder ac- tivity that may obscure perivesical or intravesical tumors.
However, this may still leave small pockets of concen- trated activity that may resemble lymphadenopathy, causing even greater problems in interpretation. Bladder irrigation may help to some extent but is associated with increased radiation dose to staff and may introduce infection.
We have found it beneficial to hydrate the patient and administer a diuretic. This approach leads to a full bladder with dilute urine, making it easier to differentiate normal urinary activity from perivesical tumor activity and allowing the bladder to be used as an anatomic land- mark. By diluting vesical FDG activity, reconstruction ar- tifacts from filtered back-projection algorithms are also reduced. It is often helpful to perform image registration with either CT or MRI in the pelvis. Here it may be helpful
Figure 5.5. Symmetrical FDG uptake in the masseter muscles in a patient chewing gum, resembling bilateral lymphadenopathy.
Figure 5.6. Physiologic uptake of FDG is seen in the stomach wall (arrows). Moderate myocardial activity is also seen.
Figure 5.7. Moderate physiologic uptake that is seen in the region of the cecum and ascending colon in a patient with a primary lung cancer.
to administer a small amount of 18F-fluoride ion in addi- tion to FDG, to allow easy identification of bony land- marks for registration purposes. Although excreted FDG may be seen in any part of the urinary tract, it is impor- tant to gain a history of any previous urinary diversion procedures, because these may cause areas of high activity outside the normal renal tract and may result in errors of interpretation unless this is appreciated.
Glandular breast tissue often demonstrates moderate FDG activity in premenopausal women and post- menopausal women taking estrogens for hormone re- placement therapy. The pattern of uptake is usually symmetrical and easily identified as being physiologic, but there is the potential for lesions to be obscured by this normal activity. Breast-feeding mothers show intense uptake of FDG bilaterally (Figure 5.9). Similarly in males,
uptake of FDG may be seen in normal testes and appears to be greater in young men than in old (34).
Artifacts
Image reconstruction of PET images without attenuation correction may lead to higher apparent activity in superficial structures that may obscure lesions such as cu- taneous melanoma metastases (28). A common artifact arising from this phenomenon is caused by the axillary skin fold, where lymphadenopathy may be mimicked in coronal image sections. However, the linear distribution of activity can be appreciated on transaxial or sagittal slices, which should prevent misinterpretation. Another
Figure 5.8. (a) Transaxial FDG slice through the upper abdomen and (b) corresponding CT slice in a patient with a history of seminoma and previous paraaortic lymph node dissec- tion but rising tumor markers. The linear area of low-grade FDG activity can be seen to correspond to a barium-filled loop of bowel, but the more-focal area of high uptake (arrow on each part) corresponds to a small density located adjacent to the previous surgical clips, indicating recurrent disease at this site. The case demonstrates how normal bowel activity can be differentiated from tumor foci.
Figure 5.9. Transaxial FDG scan of a breast-feeding mother in whom intense symmetrical breast activity can be seen.
major difference between attenuation corrected and non- corrected images is an apparent increase in lung activity in the latter caused by to relatively low attenuation by the air-containing lung (Table 5.3).
Filtered back-projection reconstruction leads to streak artifacts and may obscure lesions adjacent to areas of high activity. Many of these artifacts can be overcome by using iterative reconstruction techniques (Figure 5.10).
Patient movement may compromise image quality. In brain imaging it is possible to split the acquisition into a number of frames, so that if movement occurs in one frame then this can be discarded before summation of the data (35). When performing whole-body scans, unusual appearances may result if the patient moves between bed scan positions; this most commonly occurs when the upper part of the arm is visible in higher scanning posi- tions but the lower part disappears when moved out of the field of view on lower subsequent scanning positions.
Table 5.3. Artifacts.
Attenuation correction related Apparent superficial increase in activity and lung activity if no correction applied.
Injection related Lymph node uptake following tissued injection.
Reconstruction artifacts due to tissued activity.
Inaccuracies in standard uptake value calculation.
Attenuating material Coins, medallions, prostheses.
Patient movement Poor image quality.
Artifacts on applying attenuation correction.
Source: From Valk PE, Bailey DL, Townsend DW, Maisey MN. Positron Emission Tomography: Basic Science and Clinical Practice. Springer-Verlag London Ltd 2003, p. 502.
Figure 5.10. Transaxial, sagittal, and coronal abdominal FDG images from iterative reconstruction (a) and filtered back-projection (b) demonstrate the improved image quality and reduction in streak artifacts possible with the former.
a b
Special care is required in injecting FDG because soft tissue injection may cause reconstruction artifacts across the trunk and may even cause a low-count study or inac- curacies in standardized uptake value (SUV) measure- ments. Axillary lymph nodes, draining the region of tracer extravasation, may also accumulate activity following ex- travasated injections. The site of administration should be chosen carefully so as to minimize the risk of false- positive interpretation should extravasation occur.
Artifacts caused by prostheses are usually readily recog- nizable. Photon-deficient regions may result from metallic joint prostheses or other metallic objects carried by the patient. Ring artifacts may occur if there is misregistra- tion between transmission and emission scans because of patient movement and are particularly apparent at borders where there are sudden changes in activity concentrations, for example, at a metal prosthesis.
Misregistration artifacts between emission and transmis- sion scans have become less frequent now that interleaved or even simultaneous emission/transmission scans are being performed.
Benign Causes of FDG Uptake
Uptake of FDG is not specific to malignant tissue, and it is well recognized that inflammation may lead to accumula- tion in macrophages and other activated inflammatory cells (7, 8). In oncologic imaging, this inflammatory uptake may lead to decrease in specificity. For example, it may be difficult to differentiate benign postradiotherapy changes from recurrent tumor in the brain unless the study is opti- mally timed or unless alternative tracers such as 11C-me- thionine are used. Apical lung activity may be seen following radiotherapy for breast cancer, and moderate uptake may follow radiotherapy for lung cancer (36). It may also be difficult to differentiate radiation changes from recurrent tumor in patients who have undergone radio- therapy for rectal cancer within 6 months of the study (12).
Pancreatic imaging with FDG may be problematic. In some cases, uptake into mass-forming pancreatitis may be comparable in degree to uptake in pancreatic cancer.
Conversely, false-negative results have been described in diabetic patients with pancreatic cancer. However, if dia- betic patients and those with raised inflammatory markers are excluded, then FDG-PET may still be an accu- rate test to differentiate benign from malignant pancreatic masses (37).
A number of granulomatous disorders have been de- scribed as leading to increased uptake of FDG, including tuberculosis (38) and sarcoidosis (39) (Figure 5.11). It is often necessary to be cautious in ascribing FDG lesions to cancer in patients who are known to be immunocompro- mised. It is these patients who often have the unusual infec- tions that may lead to uptake that cannot be differentiated from malignancy. PET remains useful in these patients,
despite a lower specificity, as it is often able to locate areas of disease that have not been identified by other means and that may be more amenable to biopsy (40).
A more-comprehensive list of benign causes of abnor- mal FDG uptake is displayed in Table 5.4.
Specific Problems Related to PET/CT
One of the most exciting technologic advances in recent years is the clinical application of combined PET/CT scan- ners. However, this new technology has come with its own particular set of artifacts and pitfalls.
One of the biggest problems with PET/CT imaging in a dedicated combined scanner is related to differences in breathing patterns between the CT and the PET acquisi- tions. CT scans can be acquired during a breath-hold but PET acquisitions are taken during tidal breathing and rep- resent an average position of the thoracic cage over 30 min or more. This difference may result in misregistration of pulmonary nodules between the two modalities, particu- larly in the peripheries and at the bases of the lungs where differences in position may approach 15 mm (41).
Misregistration may be reduced by performing the CT scan while the breath is held in normal expiration (42, 43). It has been noted that deep inspiration during the CT acquisition can lead to deterioration of the CT attenuation-corrected PET image with the appearance of cold artifacts (Figure 5.12) and can even lead to the mispositioning of abdominal activity into the thorax (44). CT acquisition during normal expiration minimizes the incidence of such artifacts and also optimizes coregistration of abdominal organs.
High-density contrast agents, for example, oral contrast, or metallic objects (Figure 5.13) can lead to an artifactual overestimation of activity if CT data are used for attenua- tion correction (45–51). Such artifacts may be recognized by studying the uncorrected image data. Low-density oral contrast agents can be used without significant artifacts (52, 53), or the problem may be avoided by using water as a negative bowel contrast agent. Algorithms have been de- veloped to account for the overestimation of activity when using CT-based attenuation correction that may minimize these effects in the future (53).
The use of intravenous contrast during CT acquisition may be a more-difficult problem. Similarly, the concen- trated bolus of contrast in the large vessels may lead to overcorrection for attenuation, particularly because the concentrated column of contrast has largely dissipated by the time the PET emission scan is acquired. Artifactual hot spots in the attenuation-corrected image (48) or quan- titative overestimation of FDG activity may result. When intravenous contrast is considered essential for a study, the diagnostic aspect of the CT scan is best performed as a third study with the patient in the same position, after, first, a low-current CT scan for attenuation correction purposes and, second, the PET emission scan.
Although many centers have found low-current CT ac- quisitions to be adequate for attenuation correction and image fusion (54), it may be necessary to increase CT tube current in larger patients to minimize beam-hardening ar- tifacts on the CT scan that may translate through to incor- rect attenuation correction of the PET emission data (49).
This effect can be caused by the patient’s arms being in the field of view and may be minimized by placing the arms above the head for imaging. Differences in the field- of-view diameter between the larger PET and smaller CT
parts of combined scanners can lead to truncation arti- facts at the edge of the CT image, but these are generally small and can be minimized by the use of iterative image reconstruction methods (53).
Although some new artifacts are introduced by com- bined PET/CT imaging, it is likely that many pitfalls caused by normal variant uptake may be avoided by the ability to correctly attribute FDG activity to a structurally normal organ on the CT scan; this may be particularly evident in the abdomen when physiologic bowel activity
Figure 5.11. Coronal FDG scan demonstrates high uptake in the lungs and spine in a patient with sarcoidosis.
Figure 5.12. Coronal CT attenuation corrected FDG scan demonstrates an apparent loss of activity at the level of the diaphragm (arrows) resulting from differences in breathing patterns between the CT and PET scans.
Figure 5.13. Coronal FDG scan with (a) CT attenuation correction, (b) CT alone, and (c) uncorrected FDG of a patient with a metallic pacemaker placed over the right upper chest demonstrates arti- factual increased uptake on the cor- rected images.
a b c
Table 5.4. Benign causes of FDG uptake.
Organ/type Disease
Brain Postradiotherapy uptake.
Pulmonary Tuberculosis, sarcoidosis, histoplasmosis, atypical mycobacteria, pneumoconiosis, radiotherapy.
Myocardium Heterogeneous left ventricular activity possible after myocardial infarction, increased right ventricular activity in right heart failure
Bone/bone marrow Paget’s disease, osteomyelitis, hyperplastic bone marrow.
Inflammation Wound healing, pyogenic infection, organizing hematoma, esophagitis, inflammatory bowel disease, lymphadenopathy associated with granulomatous disorders, viral and atypical infections, chronic pancreatitis, retroperitoneal fibrosis, radiation fibrosis (early), bursitis.
Endocrine Graves’ disease and chronic thyroiditis, adrenal hyperplasia.
Source: From Valk PE, Bailey DL, Townsend DW, Maisey MN. Positron Emission Tomography: Basic Science and Clinical Practice. Springer-Verlag London Ltd 2003, p. 504.
or ureteric activity can otherwise cause interpretative difficulties. PET/CT also has the potential to limit false- negative interpretations in tumors that are not very FDG avid by recognizing uptake as being related to structurally abnormal tissue and increasing the diagnostic confidence in tumor recognition by the use of the combined struc- tural and functional data. Similarly, it may be possible to detect small lung metastases of a few millimeters on CT lung windows that are beyond the resolution of FDG-PET.
The full use of the combined data, including the corrected and noncorrected PET emission data, and the inspection of soft tissue, lung, and bone windows on the CT data, may also allow the description and correct diagnosis of pertinent FDG-negative lesions, such as liver cysts, and incidental FDG-negative CT abnormalities, such as ab- dominal aortic aneurysm, to provide an integrated inter- pretation of all the available data resulting from this technology.
References
1. Torizuka T, Tamaki N, Inokuma T, et al. In vivo assessment of glucose metabolism in hepatocellular carcinoma with FDG-PET. J Nucl Med 1995;36(10):1811–1817.
2. Minn H, Clavo AC, Wahl RL. Influence of hypoxia on tracer accu- mulation in squamous cell carcinoma: in vitro evaluation for PET imaging. Nucl Med Biol 1996;23:941–946.
3. Wahl RL, Henry CA, Ethier SP. Serum glucose: effects on tumour and normal tissue accumulation of 2-[F-18]-fluoro-2-deoxy-D- glucose in rodents with mammary carcinoma. Radiology 1992;183:643–647.
4. Torizuka T, Clavo AC, Wahl RL. Effect of hyperglycaemia on in vitro tumour uptake of tritiated FDG, thymidine, L-methionine and L-leucine. J Nucl Med 1997;38:382–386.
5. Yasuda S, Kajihara M, Fujii H, Takahashi W, Ide M, Shohtsu A.
Factors influencing high FDG uptake in the intestine, skeletal muscle and myocardium. J Nucl Med 1999;40:140P
6. Torizuka T, Fisher SJ, Wahl RL. Insulin induced hypoglycaemia de- creases uptake of 2-[F-18]fluoro-2-deoxy-D-glucose into experi- mental mammary carcinoma. Radiology 1997;203:169–172.
7. Yamada S, Kubota K, Kubota R, et al. High accumulation of fluorine-18-fluorodeoxyglucose in turpentine-induced inflamma- tory tissue. J Nucl Med 1995;36:1301–1306.
8. Kubota R, Kubota K, Yamada S, et al. Methionine uptake by tumor tissue: a microautoradiographic comparison with FDG. J Nucl Med 1995;36:484–492.
9. Sugawara Y, Braun DK, Kison PV, et al. Rapid detection of human infections with fluorine-18 fluorodeoxyglucose and positron emission tomography: preliminary results. Eur J Nucl Med 1998;25:1238–1243.
10. Reinhardt MJ, Kubota K, Yamada S, Iwata R, Yaegashi H.
Assessment of cancer recurrence in residual tumors after fraction- ated radiotherapy: a comparison of fluorodeoxyglucose, L-methio- nine and thymidine. J Nucl Med 1997;38:280–287.
11. Strauss LG. Fluorine-18 deoxyglucose and false-positive results: a major problem in the diagnostics of oncological patients. Eur J Nucl Med 1996;23:1409–1415.
12. Haberkorn U, Strauss LG, Dimitrakopoulou A, et al. PET studies of fluorodeoxyglucose metabolism in patients with recurrent colorec- tal tumors receiving radiotherapy. J Nucl Med 1991;32:1485–1490.
13. Kubota R, Kubota K, Yamada S et al. Methionine uptake by tumour tissue: a microautoradiographic comparison with FDG. J Nucl Med 1995;36:484–492.
14. Nuutinen JM, Leskinen S, Elomaa I, et al. Detection of residual tumours in postchemotherapy testicular cancer by FDG-PET. Eur J Cancer 1997;33:1234–1241.
15. Jones DN, McCowage GB, Sostman HD, et al. Monitoring of neoad- juvant therapy response of soft-tissue and musculoskeletal sarcoma using fluorine-18-FDG PET. J Nucl Med 1996;37:
1438–1444.
16. Shreve PD, Anzai Y, Wahl RL. Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants. Radiographics 1999;19:61–77.
17. Kato T, Tsukamoto E, Suginami Y, et al. Visualization of normal organs in whole-body FDG-PET imaging. Jpn J Nucl Med 1999;36:971–977.
18. Yasuda S, Shohtsu A, Ide M, et al. Chronic thyroiditis: diffuse uptake of FDG at PET. Radiology 1998;207:775–778.
19. Miyauchi T, Wahl RL. Regional 2-[18F]fluoro-2-deoxy-D-glucose uptake varies in normal lung. Eur J Nucl Med 1996; 23:517–523.
20. Kubota K, Kubota R, Yamada S, Tada M, Takahashi T, Iwata R. Re- evaluation of myocardial FDG uptake in hyperglycaemia. J Nucl Med 1996;37:1713–1717.
21. Knuuti MJ, Maki M, Yki-Jarvinen H, et al. The effect of insulin and FFA on myocardial glucose uptake. J Mol Cell Cardiol 1995;27:1359–1367.
22. Choi Y, Brunken RC, Hawkins RA, et al. Factors affecting myocar- dial 2-[F-18]fluoro-2-deoxy-D-glucose uptake in positron emission tomography studies of normal humans. Eur J Nucl Med 1993;
20:308–318.
23. Bax JJ, Visser FC, Raymakers PG, et al. Cardiac 18F-FDG-SPET studies in patients with non-insulin dependent diabetes mellitus during hyperinsulinaemic euglycaemic clamping. Nucl Med Commun 1997;18:200–206.
24. Huitink JM, Visser FC, van Leeuwen GR, et al. Influence of high and low plasma insulin levels on the uptake of fluorine-18 fluorodeoxyglucose in myocardium and femoral muscle assessed by planar imaging. Eur J Nucl Med 1995;22:1141–1148.
25. Locher JT, Frey LD, Seybold K, Jenzer H. Myocardial 18F-FDG-PET.
Experiences with the euglycaemic hyperinsulinaemic clamp tech- nique. Angiology 1995;46:313–320.
26. Ohtake T, Yokoyama I, Watanabe T, et al. Myocardial glucose me- tabolism in noninsulin dependent diabetes mellitus patients evalu- ated by FDG-PET. J Nucl Med 1995;36:456–463.
27. Bax JJ, Veening MA, Visser FC, et al. Optimal metabolic conditions during fluorine-18 fluorodeoxyglucose imaging: a comparative study using different protocols. Eur J Nucl Med 1997;24:35–41.
28. Engel H, Steinert H, Buck A, et al. Whole body PET: physiological and artifactual fluorodeoxyglucose accumulations. J Nucl Med 1996;37:441–446.
29. Cook GJR, Fogelman I, Maisey M. Normal physiological and benign pathological variants of 18-fluoro-2-deoxyglucose positron emission tomography scanning: potential for error in interpreta- tion. Semin Nucl Med 1996;24:308–314.
30. Cook GJR, Maisey MN, Fogelman I. Normal variants, artefacts and interpretative pitfalls in PET imaging with 18-fluoro-2-deoxyglucose and carbon-11 methionine. Eur J Nucl Med 1999;26:1363–1378.
31. Hany TF, Gharehpapagh E, Kamel EM, et al. Brown adipose tissue:
a factor to consider in symmetrical tracer uptake in the neck and upper chest region. Eur J Nucl Med 2002;29:1393–1398.
32. Bischof Delalove A, Wahl RL. How high a level of FDG abdominal activity is considered normal? J Nucl Med 1995;36:106P.
33. Nakada K, Fisher SJ, Brown RS, Wahl RL. FDG uptake in the gas- trointestinal tract: can it be reduced? J Nucl Med 1999;40:22P–23P.
34. Kosuda S, Fisher S, Kison PV, Wahl RL, Grossman HB. Uptake of 2-deoxy-2-[18F]fluoro-D-glucose in the normal testis: retrospec- tive PET study and animal experiment. Ann Nucl Med 1997;11:195–199.
35. Picard Y, Thompson CJ. Motion correction of PET images using multiple acquisition frames. IEEE Trans Med Imaging 1997;
16:137–144.
36. Nunez RF, Yeung HW, Macapinlac HA, Larson SM. Does post-radi- ation therapy changes in the lung affect the accuracy of FDG PET in the evaluation of tumour recurrence in lung cancer. J Nucl Med 1999;40:234P.
37. Diederichs CG, Staib L, Vogel J et al. Values and limitations of 18F- fluorodeoxyglucose-positron-emission tomography with preoper- ative evaluation of patients with pancreatic masses. Pancreas 2000;20:109–116.
38. Knopp MV, Bischoff HG. Evaluation of pulmonary lesions with positron emission tomography. Radiologe 1994;34:588–591.
39. Lewis PJ, Salama A. Uptake of fluorine-18-fluorodeoxyglucose in sarcoidosis. J Nucl Med 1994;35:1–3.
40. O’Doherty MJ, Barrington SF, Campbell M, et al. PET scanning and the human immunodeficiency virus-positive patient. J Nucl Med 1997;38:1575–1583.
41. Goerres GW, Kamel E, Seifert B, et al. Accuracy of image coregis- tration of pulmonary lesions in patients with non-small cell lung cancer using an integrated PET/CT system. J Nucl Med 2002;43:1469–1475.
42. Goerres GW, Kamel E, Heidelberg TN, et al. PET/CT image co-reg- istration in the thorax: influence of respiration. Eur J Nucl Med 2002;29:351–360.
43. Goerres GW, Burger C, Schwitter MR, et al. PET/CT of the abdomen: optimizing the patient breathing pattern. Eur Radiol 2003;13:734–739.
44. Osman MM, Cohade C, Nakamoto Y, et al. Clinically significant in- accurate localization of lesions with PET/CT: frequency in 300 pa- tients. J Nucl Med 2003;44:240–243.
45. Dizendorf E, Hany TF, Buck A, et al. Cause and magnitude of the error induced by oral CT contrast agent in CT-based attenuation correction of PET emission studies. J Nucl Med 2003;44:732–738.
46. Goerres GW, Hany TF, Kamel E, et al. Head and neck imaging with PET and PET/CT: artefacts from dental metallic implants. Eur J Nucl Med 2003;29:367–370.
47. Kamel EM, Burger C, Buck A, von Schulthess GK, Goerres GW.
Impact of metallic dental implants on CT-based attenuation correc- tion in a combined PET/CT scanner. Eur Radiol 2003;13:724–728.
48. Antoch G, Freudenberg LS, Egelhof T, et al. Focal tracer uptake: a potential artifact in contrast-enhanced dual-modality PET/CT scans. J Nucl Med 2002;43:1339–1342.
49. Cohade C, Wahl RL. Applications of PET/CT image fusion in clini- cal PET: clinical use, interpretation methods, diagnostic improve- ments. Semin Nucl Med 2003;33:228–237.
50. Goerres GW, Ziegler SI, Burger C et al. Artifacts at PET and PET/CT caused by metallic hip prosthetic material. Radiology 2003;226:577–584.
51. Kinahan PE, Hasegawa BH, Beyer T. X-ray based attenuation cor- rection for PET/CT scanners. Semin Nucl Med 2003;33:166–179.
52. Cohade C, Osman M, Nakamoto Y, et al. Initial experience with oral contrast in PET/CT: phantom and clinical studies. J Nucl Med 2003;44:412–416.
53. Dizendorf EV, Treyer V, Von Schulthess GK, et al. Application of oral contrast media in coregistered positron emission tomography- CT. AJR 2002;179:477–481.
54. Hany TF, Steinert HC, Goerres GW, et al. PET diagnostic accuracy:
improvement with in-line PET/CT system: initial results. Radiology 2002;225:575–581.
