Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a functional imaging modality that capitalizes on the fact that pathologic processes are generally highly metabolically active and accumulate more glucose (and FDG) than normal tissue. However, sites of normal metabolic activity can also demonstrate intense FDG uptake and can sometimes be difficult to distinguish from disease activity.
Fusion imaging modalities that acquire both functional and correlative anatomic imaging provide an important advantage over PET alone because they allow the accurate anatomic localization of sites of increased FDG activity (1–5). In this chapter, normal sites of FDG activ- ity are correlated with computed tomography (CT) anatomy in images obtained during PET-CT scanning. Examples of pathologic FDG activ- ity are included to illustrate the unique value of this fusion imaging modality in distinguishing normal from pathologic activity.
Head and Neck
Identifying normal FDG activity in the head and neck, as elsewhere in the body, is aided by its bilaterally symmetric distribution. Because the brain is exclusively dependent on glucose metabolism, it accumulates intense FDG activity. Accumulation is greatest in the cerebral cortex, basal ganglia, thalamus, and cerebellum (Figs. 29.1 and 29.2). Intense activity is sometimes present, not only in the brain, but also in the ocular muscles and optic nerves (Fig. 29.2). Because FDG is known to accu- mulate in saliva (6,7), minimal to moderate activity may be present in the salivary and parotid glands (Fig. 29.3). Fluorodeoxyglucose uptake also occurs in the lymphatic tissues of the pharynx, specifically within the Waldeyer ring, which consists of the nasopharyngeal, palatine, and lingual tonsils (Fig. 29.3). In patients who are tense, FDG activity may be very prominent in the neck muscles secondary to contraction- induced metabolic activity. Fluorodeoxyglucose activity in the normal thyroid gland is usually absent or minimal but can be prominent. Intrin- sic laryngeal muscles of phonation can exhibit intense FDG activity
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Figure 29.2. A,B: Axial PET-CT images show FDG activity in normal optic nerves (arrowheads), tem- poral lobes (straight arrows), and cerebellum (curved arrows).
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Figure 29.1. A,B: Axial positron emission tomography–computed tomography (PET-CT) images show fluorodeoxyglucose (FDG) activity in normal cerebral cortex (arrows), head of caudate (curved arrows), and thalami (arrowheads).
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Figure 29.3. A,B: Axial PET-CT images show FDG uptake in a normal Waldeyer ring (arrowheads) and normal parotid glands (arrows).
especially in patients who engage in speech activity immediately before or after the injection of FDG (Fig. 29.4) (7–9). To reduce such activity, patients should be encouraged to remain silent beginning 15 minutes prior to radioisotope injection until the imaging session is complete.
Chest
Intense FDG activity is often present within brown adipose tissue in the supraclavicular regions, axilla, and paraspinal regions of the pos- terior mediastinum. The primary function of brown adipose tissue is
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Figure 29.4. A,B: Axial PET-CT images show normal FDG activity in the perilaryngeal tissues (arrows) often seen in patients who have engaged in speech after FDG injection.
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the production of heat. Brown fat differs from other tissues by the presence of an uncoupling protein within its mitochondria. This protein leads to a markedly reduced production of adenosine triphos- phate (ATP) while increasing the oxidation of fatty acids to a maximal rate, resulting in the production of heat. During stimulated thermoge- nesis, glucose prevents this highly metabolic brown fat from becoming ATP-deprived by providing ATP through anaerobic glycolysis (10).
Thermogenesis, therefore, leads to an accumulation of glucose and FDG within brown fat. Brown fat is known to be particularly metabol- ically active in pediatric patients, females, and persons with a low body mass index (10–12). Positron emission tomography–CT is especially useful in localizing sites of intense FDG activity in the supraclavicular regions because the CT will demonstrate either the absence (in the case of brown fat) or the presence of a soft tissue mass in the area of increased activity (Figs. 29.5 and 29.6).
The thymus is located in the anterior mediastinum and extends from the thoracic inlet to the heart. Normal thymic FDG activity is homogeneous and may be minimal, moderate, or more intense than the mediastinal blood pool (Fig. 29.7). On CT the thymus has a quadrilateral-shaped configuration with homogeneous density. In
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Figure 29.5. A: Maximum intensity projection (MIP) image showing intense, symmetric activity in the supraclavicular regions (arrow). B,C: Axial PET-CT images allow localization of this activity to supra- clavicular brown fat (arrows). This finding is common in pediatric patients.
Figure 29.6. A 26-year-old woman with non-Hodgkin’s lymphoma. A,B: Axial PET-CT images show FDG activity in both supraclavicular brown fat (arrows) and pathologic supraclavicular nodes (arrow- heads). This example illustrates the value of PET-CT in identifying adenopathy that may be difficult to distinguish from physiologic brown fat activity on PET alone.
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Figure 29.7. A: MIP anterior PET image shows normal thymic contour and FDG activity (arrow) in a 3-year-old girl. B,C: Axial PET-CT images allow localization of activity to the thymus (arrows).
early childhood, the lateral margins are slightly convex outward until adolescence when the thymus begins to involute and becomes more triangular in appearance. The normal thymus should have smooth margins and should never be nodular or lobulated (13).
At about 1 hour after injection of FDG, blood pool activity in the mediastinum is moderate whereas lung activity is low. The heart has variable FDG avidity, usually with intense activity seen in the left ventricular myocardium (Fig. 29.8). Activity in the myocardium is dependent on serum insulin levels. When insulin levels are high, such as following a meal, the myocardium shifts from the metabolism of free-fatty acids to the glycolytic pathway, resulting in intense myocardial FDG activity (14,15). Fasting for 4 to 6 hours before the administration of FDG reduces both serum glucose and insulin availability, leading to decreased myocardial FDG activity. Minimal to moderate FDG activity may be present within the distal esopha- gus due to gastroesophageal reflux, muscle contraction, or inflam- mation (8,15).
Abdomen and Pelvis
Fusion imaging is especially helpful in the abdomen and pelvis because sites of FDG activity can be difficult to localize accurately on PET alone, and sites that demonstrate abnormal FDG uptake may be overlooked on CT alone when the abnormality is subtle or unexpected (Fig. 29.9).
In the upper abdomen, the cruces of the diaphragms and accessory muscles of respiration may demonstrate intense FDG activity, particu- larly in patients with increased work of breathing (Fig. 29.10) (8). There may be intense activity in the region of the adrenal glands within normal retroperitoneal brown fat. Liver activity is usually patchy but uniform in distribution without focal areas of intense activity. Splenic Figure 29.8. A,B: Axial PET-CT images show typical intense FDG activity in a normal left ventricular myocardium (arrows).
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Figure 29.9. A,B: Axial PET-CT images show intense FDG activity within a metastatic deposit in the pancreas (arrows) of a 10-year-old girl with widely metastatic rhabdomyosarcoma. This pancreatic deposit was not clinically suspected and was overlooked on a CT scan performed 2 days earlier.
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Figure 29.10. A,B: Axial PET-CT images show normal FDG activity in the crus of the left diaphragm (straight arrows) and normal, homogeneous FDG uptake within the liver (curved arrows) and spleen (arrowheads). The spleen usually shows activity that is equal to or less than that of the liver.
uptake is generally uniform and equal to or less than that of the liver (Figs. 29.10, 29.11, and 29.12).
Fluorodeoxyglucose activity in the bowel is commonly seen but poorly understood. Postulated causes of bowel activity include smooth muscle contraction, metabolically active mucosa, uptake in lymphoid tissue, swallowed secretions containing FDG, and colonic microbial uptake (15–17). The stomach usually shows minimal to moderate activ- ity within the fundus, although occasionally intense activity is seen
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Figure 29.11. A,B: Axial PET-CT images show a focal area of abnormal activity that localizes to the liver (arrows). This was proven by biopsy to be metastatic Hodgkin’s lymphoma in this 12-year-old girl with ataxia-telangiectasia and Hodgkin’s lymphoma.
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(Fig. 29.13). In these instances, correlating with CT imaging is useful in excluding obvious abnormalities within the stomach wall or to local- ize the activity to adjacent soft tissue abnormalities, such as adenopa- thy or pancreatic neoplasms. The degree of FDG activity in the small bowel and colon may be minimal, moderate, or intense and can be focal or diffuse (Fig. 29.14). Fluorodeoxyglucose activity in the small bowel and colon is often increased in patients who have fasted and is often most pronounced in the region of the cecum and right colon (15). The value of PET imaging in colorectal cancer is well established; however,
Figure 29.12. A 17-year-old boy with stage IV Hodgkin’s disease. A,B: Axial PET-CT images show abnormal FDG activity in the spleen and nodes in the splenic hilum (straight arrows) and porta hepatis (curved arrows), consistent with lymphomatous involvement. Note that splenic activity is greater than the normal liver.
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Figure 29.13. A,B: Axial PET-CT images show moderate FDG activity in the wall of a normal stomach (arrows). Normal gastric FDG activity can vary from minimal to intense.
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without correlative CT imaging, the findings of bowel activity on PET alone can be misleading. Computed tomography is useful in localizing the activity to the bowel and may demonstrate underlying bowel pathology such as a focal mass or an apple core lesion (Fig. 29.15). Even so, evaluation of the bowel by CT performed as part of a standard PET- CT scan may be limited by the lack of oral or intravenous contrast material. If bowel pathology is a specific concern, the use of contrast agents may enhance lesion conspicuity.
Fluorodeoxyglucose also accumulates in the glomerular filtrate but, unlike glucose, it is not resorbed in the renal tubules. This results in the intense accumulation of FDG in the renal collecting systems, ureters, and bladder (Fig. 29.16). The value of PET in evaluating the
Figure 29.14. MIP anterior image show- ing normal colonic activity (arrows).
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Figure 29.15. This example illustrates the value of PET-CT in localizing abnormal bowel activity. A:
MIP anterior image shows a small focus of intense activity in the left abdomen (arrow) in this 19-year- old man with previously treated neuroendocrine tumor. B,C: Axial PET-CT images localize the activ- ity to a small colonic filling defect that was biopsied and found to be an adenomatous polyp.
Figure 29.16. MIP anterior image of the abdomen shows the normal distribution of FDG activity in the kidneys (arrow), ureters (arrow), and urinary bladder (arrow).
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Figure 29.17. A,B: Axial PET-CT images show the normally intense activity seen in the kidneys (arrows) due to the accumulation of FDG in the glomerular filtrate.
kidneys is limited by the intense activity normally present within the renal collecting systems, which may obscure underlying abnormalities (Fig. 29.17). However, correlative PET-CT imaging may improve lesion conspicuity and localization of renal tumors. Intense FDG activity within the ureters is a common finding due to pooling of the radiotracer in the recumbent patient (8). Correlation with CT imaging allows distinction of the normal ureter from abnormal adjacent structures.
Within the female pelvis, intense FDG activity may be present in normal ovaries and uteri, depending on the phase of the patient’s men- strual cycle (18). Positron emission tomography–CT is extremely useful in localizing FDG activity to these structures (Fig. 29.18). Activity within normal ovaries may not be bilaterally symmetric because the
Figure 29.18. A,B: Axial PET-CT images show FDG activity within normal ovaries (arrows) in this 17- year-old girl who was in remission from stage IIA Hodgkin’s disease. The degree of FDG uptake in the ovaries and uterus varies with menstrual phase. Normal ovarian activity may be asymmetric, as in this case.
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Figure 29.19. A,B: Axial PET-CT images show bilaterally symmetric and intense activity in normal testes in this 19-year-old boy. The degree of FDG activity in normal testes can vary from minimal to intense but should be symmetric.
ovary containing the dominant follicle may be more physiologically active than the contralateral ovary. Correlation with the patients’ clin- ical history is useful in ruling out malignancy as an underlying cause of FDG uptake in the uterus and ovaries. In equivocal cases, follow-up PET-CT should show resolution or a diminution of FDG activity when the etiology is physiologic in nature (18). Within the male pelvis, activ- ity in the normal testes can vary from minimal to intense, but should be bilaterally symmetric (Fig. 29.19).
Musculoskeletal
Increased uptake of glucose into skeletal muscle is known to occur during muscle exercise (19). Likewise, the uptake of glucose, and hence FDG, into skeletal muscle is increased when muscle is electrically stim- ulated to undergo isometric contraction (19,20). The mechanism of glucose uptake into muscle is poorly understood, but it is distinct from the regulation of glucose metabolism by insulin. Increased blood flow and the translocation of glucose from the intracellular pool to the sar- colemmal membrane and activation of the protein carriers GLUT-1 and GLUT-4, in response to calcium released from the sarcoplasmic reticu- lum during muscle stimulation, may be responsible (19). When PET imaging reveals muscle FDG activity that is bilaterally symmetric (Fig.
29.20), it is likely due to increased glucose metabolism secondary to vol- untary muscle contraction. Symmetric uptake of FDG in the neck and paravertebral muscles can be caused merely by patient anxiety. Admin- istration of the muscle relaxant and anxiolytic agent diazepam has been effective in abolishing the high muscle FDG uptake seen in some patients (19). Asymmetric muscle activity can be due to the sequelae of local treatments such as surgery or radiation therapy or can be seen in a recently exercised muscle, even if the activity occurred prior to the
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Figure 29.20. Three-year-old boy with previously treated rhabdomyosarcoma of the left lower leg. A:
MIP anterior image of the body shows symmetric activity in the forearm muscles (arrows). Note also the appearance of the normal bone marrow with increased activity in the growing physes of the prox- imal humeri (arrowhead), knees (curved arrow), and distal tibiae. The distribution of bone marrow activity depends on patient age. Younger children have relatively more metabolically active marrow than older children. Normal marrow activity is generally equal to or less than the liver. B,C: Axial PET- CT images localize the forearm activity to the forearm muscles (arrows). Such activity can be seen in tense patients or may be related to physical activity.
injection of FDG (Fig. 29.21) (15). When FDG muscle activity is not bilat- erally symmetric, the correlative anatomic information provided by CT is extremely useful in elucidating the underlying cause of the abnor- mality particularly when an intra- or perimuscular mass is present.
Interpretation of the PET appearance of normal bone marrow in chil- dren requires knowledge of the age-dependent conversion patterns from hematopoietic to fatty marrow (21–24). Younger children have rel- atively more metabolically active and FDG-avid hematopoietic marrow within long bones than older children whose marrow has undergone fatty conversion. Intense FDG activity may be present in the physes of growing children (Fig. 29.20). Fluorodeoxyglucose uptake in normal bone marrow is generally less than or equal to that of the liver (Fig.
29.20). Diffuse and symmetric increased FDG bone marrow activity is often seen in patients receiving granulocyte colony-stimulating factor (G-CSF) (Fig. 29.22) (25). Occasionally, focal areas of increased FDG activity are present within the vertebral bodies that can be difficult to
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Figure 29.21. A 14-year-old boy with metastatic osteosarcoma. A,B: Axial PET- CT images show increased activity in the thenar muscles of the left hand (arrows) relative to the right (arrowheads). This was felt to be related to the physical activity of this patient, who had exercised the left hand while playing a video game prior to FDG injection.
Figure 29.22. An 18-year-old woman under treat- ment for rhabdomyosarcoma who had recently received granulocyte colony-stimulating factor (G- CSF). MIP anterior image shows marrow activity that is diffusely increased relative to the liver. This pattern of marrow activity is commonly seen in patients receiving G-CSF.
distinguish from a pathologic process. Generally, a repeating pattern of patchy increased activity throughout the spine can be seen on the sagit- tal or coronal images that is characteristic of physiologic uptake. When increased bone marrow activity is solitary or nonuniformly distributed, other causes, such as infection, metastatic disease, or primary bone malignancies, should be considered. Correlative CT imaging, utilizing a bone window, may reveal an underlying destructive process, frac- ture, or other pathology (Fig. 29.23).
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