Hybrid PET/CT Neoplasm Imaging

Brain

The gray matter of the brain (cortex, basal ganglia, and thalami) is always high in ¹⁸ F-FDG uptake because the cells of gray matter have a high metabolic rate and use glucose as their primary substrate. When acquiring scans of the face and neck, it is important to exclude the brain from the acquisition to be able to see abnormalities that do not have as much activity as gray matter.

Vocal Cords

In the neck, activity near the vocal cords is seen if the patient was talking at the time of injection ( Fig. 11.2 ). The activity can be minimized by having the patient remain silent during injection and during the early uptake of ¹⁸ F-FDG. Speaking during the uptake period may also increase ¹⁸ F-FDG activity in the tongue. After lingual or laryngeal surgery, asymmetric activity can often be seen in the residual intact musculature and be difficult to differentiate from residual or recurrent tumor. An intense ¹⁸ F-FDG focus in the lower neck just lateral to the midline may be caused by compensatory activation of an intact laryngeal muscle when the contralateral vocal cord is paralyzed due to any cause, including mediastinal tumor involvement of the recurrent laryngeal nerve.

Tonsils, Salivary Glands, and Thyroid

The tonsils (especially the palatine tonsils), lymphoid tissue at Waldeyer ring, and the parotid and submandibular glands can normally accumulate ¹⁸ F-FDG. This activity usually decreases with patient age and should be symmetric. Thyroid activity is normally not seen. However, mild diffuse activity can occasionally be seen in normal glands. Significantly increased activity can occur with thyroiditis or Graves disease ( Fig. 11.3 ). An enlarged inhomogeneous gland should raise the possibility of a nodular goiter. An unexpected intense focal area raises the possibility of thyroid malignancy (20% to 45%), and further evaluation should be performed.

Thymus

Thymic activity can be seen normally in children but also occasionally in young adults up to the age of about 30 years. It is very uncommon in adults older than 30 years. Increased activity can be seen as a result of thymic rebound after chemotherapy in children and young adults but also occasionally in older adults ( Fig. 11.4 ).

Muscle and Brown Fat

In the resting skeletal muscle, ¹⁸ F-FDG uptake is usually low. Increased activity is often seen in the shoulder girdle (especially teres minor) and upper back if the patient was tense at the time of injection or within 30 minutes after injection. Muscle relaxants or antianxiety medications may be helpful in some patients, especially when imaging the neck, where the strap muscles often demonstrate increased activity. Heavy exercise within the 24 hours before the examination can increase muscle uptake, as can elevated insulin levels ( Fig. 11.5 ).

Activity can also be seen normally in the diaphragmatic crura, intercostal muscles, psoas muscles, thoracic paravertebral muscles, forearms, and muscles of mastication. In patients with severe dyspnea, there is often increased activity in intercostal muscles as a result of the increased work of breathing (see Fig. 11.2 ). At any location, symmetry and a diffuse or typical linear configuration are often helpful to distinguish normal muscle activity from pathology.

Activity in the supraclavicular region is typically a result of one of three causes: muscle activity, activity in lymph nodes resulting from pathology, or accumulation in brown fat. Muscle activity is seen in about 5% of patients and is usually linear and bilateral. Activity in brown fat occurs in about 2% to 5% of patients (mostly female) and in about 15% of children. Uptake in brown fat is typically bilateral, symmetric, and more often focal than linear wherever it occurs ( Fig. 11.6 ). Standardized uptake values (SUVs) can range from 2 to 20, with the mean often about 7 or more (well above the threshold value worrisome for malignancy) and thus, if not recognized as benign, may be the cause of false-positive interpretations. Uptake appears to be related in part to sympathetic stimulation during periods of anxiety or shivering in response to ambient temperature and is seen more often with an acute lowering of temperature in the winter months or even in a cold, air-conditioned room. In patients with activity in neck fat, about one-third will also show focal activity in mediastinal, paravertebral, axillary, supraclavicular, posterior intercostal, and abdominal (especially perinephric, perihepatic, and para-aortic) locations ( Fig. 11.7 ). Several interventions have been suggested to prevent uptake of FDG in brown fat, including a warmer study environment or premedication with benzodiazepine or propranolol. However, with coregistered PET/CT images localizing this activity to fat in typical symmetric patterns, these interventions are usually unnecessary.

Heart

Left ventricular ¹⁸ F-FDG activity is usually faint, but can be intense under certain conditions. Although the myocardium uses fatty acids as its primary substrate, it will switch to glucose if high levels are available or if the patient has been exercising. A large amount of cardiac activity often means that the patient did not fast in preparation for the examination, and the heart is actively using readily available glucose (see Fig. 11.1 ). Intense cardiac activity is usually not a problem but can interfere with a diagnosis of pathology located adjacent to the heart.

After 12 hours of fasting, the heart switches from glucose to fatty acid metabolism, and the activity becomes the same as the background blood pool. The switch from intense activity to faint activity is often not uniform, and the base of the heart tends to be the last section to convert from glucose metabolism. It is important not to interpret lack of activity near the left ventricular apex as an infarct without additional information. It is also important not to mistake isolated activity at the base of the heart for pathology such as abnormal mediastinal lymph nodes. The right ventricle usually has faint activity when compared with that of the left ventricle, unless there is right ventricular hypertrophy. Atrial activity is not infrequently noted, especially in the right atrium. This can be spotty and, again, should not be mistaken for abnormal lymph nodes.

Aorta

¹⁸ F-FDG activity is seen in the aortic wall of about 60% to 70% of older adults. The uptake can be focal or bandlike and is usually more intense in the lower descending thoracic aorta than in the ascending portion or arch. Thoracic aortic uptake appears to be more common in women and patients with hyperlipidemia. The degree of activity appears to be unrelated to calcium deposition but has been shown to correlate with macrophage content in the atherosclerotic plaques, possibly reflecting the metabolic activity of atherosclerotic change. Infected vascular grafts often demonstrate increased activity, conforming to the shape of the grafts. However, aortofemoral bypass grafts routinely have some mild diffuse increased activity for years even if not infected.

Lungs

The lungs have relatively low uptake, appearing photopenic on attenuation-corrected images. However, on images that are not attenuation corrected, they will appear to have increased activity. Pleural effusions from congestive failure will not accumulate activity, but empyemas and malignant effusions often do.

Breast

Breast activity slightly above that in the blood pool is normal and is more common in young women and in postmenopausal women on hormone replacement therapy. The ¹⁸ F-FDG activity in the breast is related to the glandular volume and density. As expected, fatty breasts have less activity than do dense breasts. However, even in dense breasts, the SUV is almost always less than 1.5 (much below the 2.5 value that may suggest malignant tissue). Breast activity is notably greater in lactating females ( Fig. 11.8 ), but the activity is in the breast tissue and not in the milk. It is not necessary to discontinue breastfeeding in these patients. However, there may be significant dose concerns to the baby from direct radiation emission from the mother, and as a result, some authors recommend that breastfeeding be suspended for 8 to 12 hours after the injection. Thus an infant feeding just before patient injection may be advised.

Gastrointestinal Tract

Activity in the bowel is exceedingly variable in terms of both intensity and location. The ¹⁸ F-FDG activity in the bowel is located in the mucosa and not in the luminal contents. The FDG is not excreted by the liver and biliary system into the bowel. Low-level activity is sometimes seen in the normal esophagus and should be uniform throughout its length. Fusiform or focal esophageal activity should raise the possibility of pathology, including neoplasm, although esophagitis or inflammation related to gastroesophageal reflux can produce a similar appearance.

Activity in the stomach is often greater than that in the liver, and a contracted normal stomach or hiatal hernia can appear very intense, causing difficulties in evaluation of esophagogastric junction and gastric neoplasms. Focal activity in the stomach should prompt a search for a gastric mass on the CT. Small-bowel activity is usually less than that seen in the colon and is commonly located in the lower abdomen or pelvis. Activity in the small bowel tends to be faint, but activity in the colon can normally be quite intense. It is often helpful to view the rotating three-dimensional display (maximum intensity projection [MIP] image) to be able to distinguish normal colonic activity from pathology. The pattern of uptake in the colon may be diffuse, segmental, or nodular. It is usually highest in the cecum and ascending colon ( Fig. 11.9 ) presumably because of the higher concentration of lymphocytes in this region. Diffuse activity is most often nonpathologic, whereas segmental uptake may imply inflammation. Nodular focal intense uptake is seen in about 1% of patients having studies for nongastrointestinal reasons. This has a positive predictive value of 70% to 85% because of lesions such as polyps, villous adenomas, and carcinoma. Approximately 30% of such findings will prove to be malignant, and the majority of the remainder will be premalignant. Metformin is known to be a cause of increased small and large bowel activity, which may interfere with evaluation of known or suspected lesions in these regions.

The liver typically has more activity than the background blood pool. The gallbladder is not usually seen, and if there is activity in this area, it should not be assumed to be normal or a normal variant. The pancreas is not normally seen.

Genitourinary Tract

Activity is almost always seen in the urinary tract because about 40% of the administered activity is excreted via the kidneys in the first 2 hours. The upper pole calyces, renal pelvis, and ureters are easily visualized on ¹⁸ F-FDG PET scans ( Fig. 11.10 ). Ureteral activity can be discontinuous because of peristalsis and can mimic pathologic foci. Bladder activity is usually intense. On a contrast PET/CT scan, the heavier iodine contrast is usually dependent with the FDG layered anteriorly. In patients with suspected pelvic pathology, catheterization may be warranted to minimize or eliminate interfering bladder activity, but in practice, this is usually not necessary. Activity can be present in the normal uterus (especially early in menstruation). Activity is also usually seen in the testes and, to a lesser extent, in the penis.

Bone Marrow, Lymph Nodes, and Spleen

Bone marrow activity is usually seen at an intensity slightly higher than the blood pool and about the same as the liver. Bone marrow activity can be increased in anemic patients or those who have had stimulation therapy (e.g., granulocyte colony-stimulating factor [G-CSF]) ( Fig. 11.11 ). Increased marrow activity is usually highest after the cessation of chemotherapy and rapidly declines over 2 to 4 weeks. This may obscure marrow metastases in some cases. Marrow activity will be decreased regionally in the treated area after radiation therapy.

Normal lymph nodes have minimal activity. However, if an injection of the radiopharmaceutical into an arm vein was infiltrated, there may be activity in the axillary or supraclavicular nodes on the side of injection owing to lymphatic drainage to these nodes. Splenic activity is usually low but can be increased in anemic patients or those treated with G-CSF.