DOI: 10.1148/rg.245035725
RadioGraphics 2004;24:1411-1431
© RSNA, 2004
PET-CT Fusion Imaging in Differentiating Physiologic from Pathologic FDG Uptake1
Lale Kostakoglu, MD,
Ruth Hardoff, MD,
Rosna Mirtcheva, MD and
Stanley J. Goldsmith, MD
1 From the Division of Nuclear Medicine, Department of Radiology, New York Presbyterian Hospital, Weill Medical College of Cornell University, 525 E 68th St, Starr No 221, New York, NY 10021 (L.K., R.M., S.J.G.); and the Department of Nuclear Medicine, Rabin Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel (R.H.). Received October 6, 2003; revision requested November 25 and received January 24, 2004; accepted January 30. All authors have no financial relationships to disclose. Address correspondence to L.K. (e-mail: lak2005@med.cornell.edu).
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Abstract
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Interpretation of positron emission tomographic (PET) scans in the absence of correlative anatomic information can be challenging. PET–computed tomography (CT) fusion imaging is a novel multimodality technology that allows the correlation of findings from two concurrent imaging modalities in a comprehensive examination. CT demonstrates exquisite anatomic detail but does not provide functional information, whereas 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG) PET reveals aspects of tumor function and allows metabolic measurements. Subtle findings at FDG PET that might otherwise be disregarded or interpreted as physiologic variants may lead to detection of a malignant process after being correlated with simultaneously acquired CT findings. Alternatively, equivocal CT findings, which could represent malignant tumor, reactive changes, or fibrosis, can be clarified with the help of the additional metabolic information provided by concurrent FDG PET. Accurate interpretation of FDG PET scans requires a thorough knowledge of the normal physiologic distribution of FDG and of normal variants that may reduce the accuracy of PET studies, thereby significantly affecting patient treatment. Although in rare instances PET-CT cannot help resolve the diagnostic dilemma, it is enjoying widespread acceptance in the medical imaging community, usually allowing differentiation of physiologic variants from juxtaposed or mimetic neoplastic lesions and more accurate tumor localization.
© RSNA, 2004
Index Terms: Computed tomography (CT), **.12112 • Computed tomography (CT), utilization • Fluorine, radioactive • Positron emission tomography (PET), **.12163 • Radionuclide imaging, in diagnosis of neoplasms, **.12163
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LEARNING OBJECTIVES FOR TEST 5
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After reading this article and taking the test, the reader will be able to:
- Describe the physiologic uptake patterns that can mimic disease at FDG PET.
- Discuss the advantages and limitations of PET-CT fusion imaging in differentiating normal from pathologic findings.
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Introduction
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Accurate evaluation of disease extent prior to therapy and of response to therapy have a significant impact on the clinical management of oncologic disorders. Positron emission tomography (PET) with 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG) provides valuable metabolic information and has recently become an essential diagnostic modality in the staging and restaging of various cancers. Increased FDG accumulation in neoplastic tissues is a function of increased expression and activity of glucose transporter proteins and of the glucose phosphorylating enzyme hexokinase, which result from increased anaerobic metabolism in cancer cells as well as metabolic trapping of FDG within the tumor cells due to the lack of further metabolic pathways for FDG (1). Nevertheless, FDG is not specific for neoplastic processes; it accumulates physiologically in various normal organs, including the brain, muscles, salivary glands, myocardium, gastrointestinal tract, urinary tract, brown adipose tissue, thyroid gland, and gonadal tissues (2–4).
FDG PET is a strictly functional modality and lacks anatomic landmarks for precise morphologic orientation. Unless anatomic correlation is available to delineate normal structures, pathologic sites of FDG accumulation can easily be confused with normal physiologic uptake, leading to false-positive or false-negative findings. This is an important shortcoming in the determination of active disease sites, particularly for small lesions and lesions located near sites of physiologic uptake. Coregistration of PET scans (functional and morphologic information) with computed tomographic (CT) scans (anatomic information) using a combined PET-CT scanner improves the overall sensitivity and specificity of information provided by PET or CT alone (4,5). The unique advantage of PET-CT fusion imaging is the ability to correlate findings at two complementary imaging modalities in a comprehensive examination. Hence, PET-CT provides more precise anatomic definition for both the physiologic and pathologic uptake seen at FDG PET. In particular, in the posttherapy period, subtle metabolic findings at FDG PET that might otherwise be overlooked may allow detection of residual disease after correlation with the simultaneously acquired CT data. Conversely, equivocal CT findings can be better evaluated with the help of the additional functional information provided by FDG PET.
In this article, we discuss and illustrate normal physiologic patterns of FDG uptake and pathologic patterns of uptake at PET in various anatomic locations (head and neck, chest, abdomen and pelvis). We also discuss the utility of PET-CT in differentiating malignant processes from physiologic uptake, since in some cases such differentiation cannot be made with certainty with FDG PET alone.
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Sites of Physiologic FDG Uptake
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There are several sites of normal physiologic accumulation of FDG (Fig 1). FDG accumulation is most intense in the cerebral cortex, basal ganglia, thalamus, and cerebellum, since the brain is exclusively dependent on glucose metabolism. The myocardium expresses insulin-sensitive glucose transporters, which facilitate the transport of glucose into muscle. Although the myocardium uses free fatty acids as its primary substrate, in the nonfasting state the antilipolytic effect of insulin reduces the delivery of free fatty acids, and the heart relies more on glycolytic metabolism. A recent meal often causes intense myocardial FDG uptake because of the associated elevated serum insulin levels. Fasting for 4–6 hours before FDG administration decreases the availability of both glucose and insulin in the circulation, which usually leads to decreased accumulation of FDG within the myocardium.
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Figure 1a. Normal distribution of FDG. Coronal CT (a), PET (b), and PET-CT fusion (c) images demonstrate the physiologic accumulation of FDG in the cerebral-cerebellar cortex at the base of the skull and in the myocardium, liver, kidneys, renal pelvis, bone marrow, and urinary bladder. Note also the minimal uptake in the mediastinum and bilaterally in the lower cervical and psoas muscles.
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Figure 1b. Normal distribution of FDG. Coronal CT (a), PET (b), and PET-CT fusion (c) images demonstrate the physiologic accumulation of FDG in the cerebral-cerebellar cortex at the base of the skull and in the myocardium, liver, kidneys, renal pelvis, bone marrow, and urinary bladder. Note also the minimal uptake in the mediastinum and bilaterally in the lower cervical and psoas muscles.
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Figure 1c. Normal distribution of FDG. Coronal CT (a), PET (b), and PET-CT fusion (c) images demonstrate the physiologic accumulation of FDG in the cerebral-cerebellar cortex at the base of the skull and in the myocardium, liver, kidneys, renal pelvis, bone marrow, and urinary bladder. Note also the minimal uptake in the mediastinum and bilaterally in the lower cervical and psoas muscles.
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Because FDG appears in the glomerular filtrate and, unlike glucose, is not reabsorbed in the tubules, intense FDG activity is seen in the intrarenal collecting systems, ureters, and bladder. Less intense radiotracer activity is present in the liver, spleen, bone marrow, and renal cortex. At 1 hour after radiotracer injection, blood pool activity results in moderate background activity in the mediastinum, whereas lung activity is low.
Significant muscle uptake is observed in the skeletal muscles with exercise, in the breathing muscles with hyperventilation, in the cervical muscles with tension, and in the laryngeal muscles with vocalization. Uptake in lymphatic tissues and salivary glands may also be seen as a normal variant. Uptake in the gastrointestinal tract is variable. Normal stomach, small intestine, and colon may demonstrate increased FDG uptake due to a combination of factors, including smooth muscle contraction and metabolically active mucosa (2). FDG uptake in bone marrow is normally modest. Patients undergoing treatment with granulocyte-stimulating factors have diffuse intense FDG uptake in the bone marrow (6).
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Physiologic versus Pathologic FDG Uptake
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Head and Neck
Although muscle uptake anywhere in the body may make the interpretation of FDG PET scans difficult, the abundance of small muscle groups in the neck constitutes a diagnostic dilemma, particularly in patients with head and neck neoplasms. Differentiation of physiologic muscle uptake from pathologic uptake is even more critical in the posttherapy follow-up period. Moderate to high FDG uptake is noticeable in the muscles, including the ocular muscles, and may be a potential source of false-positive findings in patients with malignant head and neck tumors and central nervous system tumors. Even without the help of CT, the origin of such FDG uptake is usually obvious due to the symmetric uptake pattern and the typical anatomic location. Contraction-induced FDG uptake in cervical muscles in tense patients can be confused with lymph node metastasis or, alternatively, may lead to false-negative findings of disease in the underlying lymph nodes (Fig 2), which constitutes a serious problem in patients with asymmetric muscle uptake due to prior neck dissection (Fig 3).
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Figure 2a. Contraction-induced FDG uptake in a 50-year-old woman with advanced non-small cell lung cancer who was referred for presurgical evaluation. (a) Axial FDG PET scans demonstrate multiple hypermetabolic foci in the anterior cervical region. Intense symmetric and superficial uptake in the anterior neck (arrowheads) suggests tense sternocleidomastoid muscle uptake. An additional asymmetric focus of uptake posterior to the right sternocleidomastoid muscle (arrows) suggests cervical lymph node metastasis, which represents a more advanced disease stage and renders the patient ineligible for surgery until after neoadjuvant chemotherapy. (b, c) Axial CT (b) and PET-CT fusion (c) images demonstrate that the unilateral uptake in the right cervical region corresponds to the anterior scalene muscle (long arrow) and that the superficially located symmetric FDG uptake corresponds to the sternocleidomastoid muscles (short arrows). Evaluation with PET-CT excluded the possibility of a false-positive finding (ie, metastatic disease in the neck), which would subject the patient to unnecessary chemotherapy.
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Figure 2b. Contraction-induced FDG uptake in a 50-year-old woman with advanced non-small cell lung cancer who was referred for presurgical evaluation. (a) Axial FDG PET scans demonstrate multiple hypermetabolic foci in the anterior cervical region. Intense symmetric and superficial uptake in the anterior neck (arrowheads) suggests tense sternocleidomastoid muscle uptake. An additional asymmetric focus of uptake posterior to the right sternocleidomastoid muscle (arrows) suggests cervical lymph node metastasis, which represents a more advanced disease stage and renders the patient ineligible for surgery until after neoadjuvant chemotherapy. (b, c) Axial CT (b) and PET-CT fusion (c) images demonstrate that the unilateral uptake in the right cervical region corresponds to the anterior scalene muscle (long arrow) and that the superficially located symmetric FDG uptake corresponds to the sternocleidomastoid muscles (short arrows). Evaluation with PET-CT excluded the possibility of a false-positive finding (ie, metastatic disease in the neck), which would subject the patient to unnecessary chemotherapy.
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Figure 2c. Contraction-induced FDG uptake in a 50-year-old woman with advanced non-small cell lung cancer who was referred for presurgical evaluation. (a) Axial FDG PET scans demonstrate multiple hypermetabolic foci in the anterior cervical region. Intense symmetric and superficial uptake in the anterior neck (arrowheads) suggests tense sternocleidomastoid muscle uptake. An additional asymmetric focus of uptake posterior to the right sternocleidomastoid muscle (arrows) suggests cervical lymph node metastasis, which represents a more advanced disease stage and renders the patient ineligible for surgery until after neoadjuvant chemotherapy. (b, c) Axial CT (b) and PET-CT fusion (c) images demonstrate that the unilateral uptake in the right cervical region corresponds to the anterior scalene muscle (long arrow) and that the superficially located symmetric FDG uptake corresponds to the sternocleidomastoid muscles (short arrows). Evaluation with PET-CT excluded the possibility of a false-positive finding (ie, metastatic disease in the neck), which would subject the patient to unnecessary chemotherapy.
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Figure 3a. Asymmetric muscle uptake in a 62-year-old woman with squamous cell carcinoma of the tongue who had undergone neck dissection. (a) Axial FDG PET scans demonstrate multiple hypermetabolic foci in the right anterolateral cervical region. Asymmetric and superficial uptake in the right anterior portion of the neck (arrowheads) suggests tense sternocleidomastoid muscle uptake. An additional asymmetric focus of uptake is noted posterior to the right sternocleidomastoid muscle (long arrow) and suggests cervical lymph node metastasis, although unilateral cervical muscle uptake cannot be excluded (cf Fig 4). Symmetric foci seen within the larynx (short arrows) probably represent the intrinsic laryngeal muscles. (b, c) Axial CT (b) and PET-CT fusion (c) images help confirm that the superficial asymmetric FDG uptake in the anterior cervical region corresponds to the right sternocleidomastoid muscle (arrowhead). The absence of contralateral muscle uptake is due to prior neck dissection. The unilateral focus of uptake posterior to the right sternocleidomastoid muscle (long arrow) corresponds to a cervical lymph node, and symmetric foci within the larynx (short arrows) correspond to the intrinsic laryngeal muscles and cricoarytenoid muscles posteriorly. The results of simultaneous evaluation with PET and CT confirmed the diagnosis of (advanced) metastatic disease in the neck and had a significant impact on clinical management. The patient was started on therapy on the basis of the PET-CT findings.
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Figure 3b. Asymmetric muscle uptake in a 62-year-old woman with squamous cell carcinoma of the tongue who had undergone neck dissection. (a) Axial FDG PET scans demonstrate multiple hypermetabolic foci in the right anterolateral cervical region. Asymmetric and superficial uptake in the right anterior portion of the neck (arrowheads) suggests tense sternocleidomastoid muscle uptake. An additional asymmetric focus of uptake is noted posterior to the right sternocleidomastoid muscle (long arrow) and suggests cervical lymph node metastasis, although unilateral cervical muscle uptake cannot be excluded (cf Fig 4). Symmetric foci seen within the larynx (short arrows) probably represent the intrinsic laryngeal muscles. (b, c) Axial CT (b) and PET-CT fusion (c) images help confirm that the superficial asymmetric FDG uptake in the anterior cervical region corresponds to the right sternocleidomastoid muscle (arrowhead). The absence of contralateral muscle uptake is due to prior neck dissection. The unilateral focus of uptake posterior to the right sternocleidomastoid muscle (long arrow) corresponds to a cervical lymph node, and symmetric foci within the larynx (short arrows) correspond to the intrinsic laryngeal muscles and cricoarytenoid muscles posteriorly. The results of simultaneous evaluation with PET and CT confirmed the diagnosis of (advanced) metastatic disease in the neck and had a significant impact on clinical management. The patient was started on therapy on the basis of the PET-CT findings.
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Figure 3c. Asymmetric muscle uptake in a 62-year-old woman with squamous cell carcinoma of the tongue who had undergone neck dissection. (a) Axial FDG PET scans demonstrate multiple hypermetabolic foci in the right anterolateral cervical region. Asymmetric and superficial uptake in the right anterior portion of the neck (arrowheads) suggests tense sternocleidomastoid muscle uptake. An additional asymmetric focus of uptake is noted posterior to the right sternocleidomastoid muscle (long arrow) and suggests cervical lymph node metastasis, although unilateral cervical muscle uptake cannot be excluded (cf Fig 4). Symmetric foci seen within the larynx (short arrows) probably represent the intrinsic laryngeal muscles. (b, c) Axial CT (b) and PET-CT fusion (c) images help confirm that the superficial asymmetric FDG uptake in the anterior cervical region corresponds to the right sternocleidomastoid muscle (arrowhead). The absence of contralateral muscle uptake is due to prior neck dissection. The unilateral focus of uptake posterior to the right sternocleidomastoid muscle (long arrow) corresponds to a cervical lymph node, and symmetric foci within the larynx (short arrows) correspond to the intrinsic laryngeal muscles and cricoarytenoid muscles posteriorly. The results of simultaneous evaluation with PET and CT confirmed the diagnosis of (advanced) metastatic disease in the neck and had a significant impact on clinical management. The patient was started on therapy on the basis of the PET-CT findings.
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Physiologic FDG uptake in the normal thyroid gland is usually absent or minimal, whereas in adenomas, uptake can be as high as that which is observed in malignant processes (7). In the absence of correlative imaging with an anatomic modality, focal uptake in the thyroid gland can be falsely interpreted as metastatic disease in the lower cervical lymph node stations (Figs 4, 5).
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Figure 4a. Thyroid carcinoma in a 45-year-old woman with a history of breast cancer who was referred for posttherapy evaluation. Axial PET scan (b) reveals a hypermetabolic focus in a cervical lymph node in the left side of the neck (arrowhead) that is highly suspicious for metastatic disease. (a, c) Axial CT (a) and PET-CT fusion (c) images demonstrate that the focus (arrowhead) corresponds to the left thyroid lobe and is consistent with a thyroid nodule. Subsequent ultrasonography demonstrated a multinodular gland with a dominant nodule in the left lower pole. Further investigation with needle biopsy revealed follicular carcinoma of the thyroid gland. PET-CT findings confirmed that the patient had thyroid disease (adenoma or carcinoma) rather than lymph node metastasis; however, the nodule could not be characterized on the basis of PET-CT findings alone.
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Figure 4b. Thyroid carcinoma in a 45-year-old woman with a history of breast cancer who was referred for posttherapy evaluation. Axial PET scan (b) reveals a hypermetabolic focus in a cervical lymph node in the left side of the neck (arrowhead) that is highly suspicious for metastatic disease. (a, c) Axial CT (a) and PET-CT fusion (c) images demonstrate that the focus (arrowhead) corresponds to the left thyroid lobe and is consistent with a thyroid nodule. Subsequent ultrasonography demonstrated a multinodular gland with a dominant nodule in the left lower pole. Further investigation with needle biopsy revealed follicular carcinoma of the thyroid gland. PET-CT findings confirmed that the patient had thyroid disease (adenoma or carcinoma) rather than lymph node metastasis; however, the nodule could not be characterized on the basis of PET-CT findings alone.
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Figure 4c. Thyroid carcinoma in a 45-year-old woman with a history of breast cancer who was referred for posttherapy evaluation. Axial PET scan (b) reveals a hypermetabolic focus in a cervical lymph node in the left side of the neck (arrowhead) that is highly suspicious for metastatic disease. (a, c) Axial CT (a) and PET-CT fusion (c) images demonstrate that the focus (arrowhead) corresponds to the left thyroid lobe and is consistent with a thyroid nodule. Subsequent ultrasonography demonstrated a multinodular gland with a dominant nodule in the left lower pole. Further investigation with needle biopsy revealed follicular carcinoma of the thyroid gland. PET-CT findings confirmed that the patient had thyroid disease (adenoma or carcinoma) rather than lymph node metastasis; however, the nodule could not be characterized on the basis of PET-CT findings alone.
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Figure 5a. Thyroid nodule in a 51-year-old man with a history of squamous cell carcinoma of the tonsil who was referred for postsurgical evaluation. Axial PET scan (b) reveals a hypermetabolic focus in the right side of the neck (arrow) that is highly suspicious for metastatic disease. (a, c) Axial CT (a) and PET-CT fusion (c) images demonstrate that the focus (arrow) corresponds to the right thyroid lobe and is consistent with a thyroid nodule, a finding that was confirmed with subsequent ultrasonography. PET-CT findings confirmed that the patient did not have lymph node metastasis; however, a thyroid nodule requires further investigation with biopsy to rule out a malignant cause within the thyroid gland.
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Figure 5b. Thyroid nodule in a 51-year-old man with a history of squamous cell carcinoma of the tonsil who was referred for postsurgical evaluation. Axial PET scan (b) reveals a hypermetabolic focus in the right side of the neck (arrow) that is highly suspicious for metastatic disease. (a, c) Axial CT (a) and PET-CT fusion (c) images demonstrate that the focus (arrow) corresponds to the right thyroid lobe and is consistent with a thyroid nodule, a finding that was confirmed with subsequent ultrasonography. PET-CT findings confirmed that the patient did not have lymph node metastasis; however, a thyroid nodule requires further investigation with biopsy to rule out a malignant cause within the thyroid gland.
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Figure 5c. Thyroid nodule in a 51-year-old man with a history of squamous cell carcinoma of the tonsil who was referred for postsurgical evaluation. Axial PET scan (b) reveals a hypermetabolic focus in the right side of the neck (arrow) that is highly suspicious for metastatic disease. (a, c) Axial CT (a) and PET-CT fusion (c) images demonstrate that the focus (arrow) corresponds to the right thyroid lobe and is consistent with a thyroid nodule, a finding that was confirmed with subsequent ultrasonography. PET-CT findings confirmed that the patient did not have lymph node metastasis; however, a thyroid nodule requires further investigation with biopsy to rule out a malignant cause within the thyroid gland.
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The intrinsic laryngeal muscles serve both as a sphincter and as an organ of phonation. FDG accumulates in the striated laryngeal muscles in proportion to contractile activity during speech. This phenomenon is a major concern and may lead to false readings in patients with head and neck cancers (Figs 6, 7) (8,9). A rigorous approach to preventing physiologic FDG uptake in the laryngeal muscles should be adopted to avoid false-positive findings. In practice, patients should be encouraged to remain silent beginning 15 minutes prior to injection and continuing until the study is completed.
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Figure 6a. Primary tumor of the larynx in a 45-year-old man with epiglottic carcinoma who was referred for presurgical evaluation. Axial CT (a), PET (b), and PET-CT fusion (c) images show a focus of uptake (arrow) that corresponds to a mass that originates from the larynx and nearly obliterates the lumen on the CT scan. Correlation with CT and PET-CT helped greatly in establishing the diagnosis of primary laryngeal malignancy rather than activated laryngeal muscles. In cases of occult head and neck tumor, differentiation may be difficult without CT correlation. It is essential that the patient remain silent during the period of FDG uptake.
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Figure 6b. Primary tumor of the larynx in a 45-year-old man with epiglottic carcinoma who was referred for presurgical evaluation. Axial CT (a), PET (b), and PET-CT fusion (c) images show a focus of uptake (arrow) that corresponds to a mass that originates from the larynx and nearly obliterates the lumen on the CT scan. Correlation with CT and PET-CT helped greatly in establishing the diagnosis of primary laryngeal malignancy rather than activated laryngeal muscles. In cases of occult head and neck tumor, differentiation may be difficult without CT correlation. It is essential that the patient remain silent during the period of FDG uptake.
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Figure 6c. Primary tumor of the larynx in a 45-year-old man with epiglottic carcinoma who was referred for presurgical evaluation. Axial CT (a), PET (b), and PET-CT fusion (c) images show a focus of uptake (arrow) that corresponds to a mass that originates from the larynx and nearly obliterates the lumen on the CT scan. Correlation with CT and PET-CT helped greatly in establishing the diagnosis of primary laryngeal malignancy rather than activated laryngeal muscles. In cases of occult head and neck tumor, differentiation may be difficult without CT correlation. It is essential that the patient remain silent during the period of FDG uptake.
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Figure 7a. Physiologic laryngeal uptake in a 52-year-old woman with squamous cell carcinoma of the floor of the mouth who had undergone surgery and radiation therapy. Axial CT (a), PET (b), and PET-CT fusion (c) images clearly demonstrate a midline focus of uptake (arrow) that corresponds to the cricoarytenoid muscles located posterior to the thyrocricoid cartilage. Although this site and pattern of uptake are typical for activated vocal cords, CT helps confirm the physiologic nature of the FDG accumulation. Without CT correlation, this focus of uptake may lead to a false-positive finding in patients with malignant processes in this location, particularly in the posttherapy setting.
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Figure 7b. Physiologic laryngeal uptake in a 52-year-old woman with squamous cell carcinoma of the floor of the mouth who had undergone surgery and radiation therapy. Axial CT (a), PET (b), and PET-CT fusion (c) images clearly demonstrate a midline focus of uptake (arrow) that corresponds to the cricoarytenoid muscles located posterior to the thyrocricoid cartilage. Although this site and pattern of uptake are typical for activated vocal cords, CT helps confirm the physiologic nature of the FDG accumulation. Without CT correlation, this focus of uptake may lead to a false-positive finding in patients with malignant processes in this location, particularly in the posttherapy setting.
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Figure 7c. Physiologic laryngeal uptake in a 52-year-old woman with squamous cell carcinoma of the floor of the mouth who had undergone surgery and radiation therapy. Axial CT (a), PET (b), and PET-CT fusion (c) images clearly demonstrate a midline focus of uptake (arrow) that corresponds to the cricoarytenoid muscles located posterior to the thyrocricoid cartilage. Although this site and pattern of uptake are typical for activated vocal cords, CT helps confirm the physiologic nature of the FDG accumulation. Without CT correlation, this focus of uptake may lead to a false-positive finding in patients with malignant processes in this location, particularly in the posttherapy setting.
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Low to moderate FDG uptake occurs in the lymphatic tissues in the pharynx, consisting of the nasopharyngeal, palatine, and lingual tonsils (Waldeyer ring) (Figs 8–10 ) (4). The Waldeyer ring is a common site of head and neck manifestations of extranodal non-Hodgkin lymphoma (Fig 8). Furthermore, primary squamous cell carcinoma of the head and neck may occur within the crypts of the Waldeyer ring (Fig 9). In cases of tonsillar lymphoma, the asymmetric nature of FDG uptake suggests a pathologic process (Fig 10). However, in the absence of CT guidance, malignant processes arising from the lymphatic tissues may be difficult to identify at FDG PET.
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Figure 8a. Extranodal disease in a 33-year-old man with a history of aggressive non-Hodgkin lymphoma who had undergone chemotherapy 1 year earlier. Axial PET scan (b) demonstrates intense FDG uptake in the posterosuperior oral cavity (arrows). (a, c) Axial CT (a) and PET-CT fusion (c) images demonstrate that the uptake (arrows) corresponds to the palatine tonsils, with minimal asymmetry seen at CT. In the tonsillar lymphatic tissues, physiologic uptake cannot be differentiated from extranodal lymphoma, especially in cases of subtle CT findings.
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Figure 8b. Extranodal disease in a 33-year-old man with a history of aggressive non-Hodgkin lymphoma who had undergone chemotherapy 1 year earlier. Axial PET scan (b) demonstrates intense FDG uptake in the posterosuperior oral cavity (arrows). (a, c) Axial CT (a) and PET-CT fusion (c) images demonstrate that the uptake (arrows) corresponds to the palatine tonsils, with minimal asymmetry seen at CT. In the tonsillar lymphatic tissues, physiologic uptake cannot be differentiated from extranodal lymphoma, especially in cases of subtle CT findings.
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Figure 8c. Extranodal disease in a 33-year-old man with a history of aggressive non-Hodgkin lymphoma who had undergone chemotherapy 1 year earlier. Axial PET scan (b) demonstrates intense FDG uptake in the posterosuperior oral cavity (arrows). (a, c) Axial CT (a) and PET-CT fusion (c) images demonstrate that the uptake (arrows) corresponds to the palatine tonsils, with minimal asymmetry seen at CT. In the tonsillar lymphatic tissues, physiologic uptake cannot be differentiated from extranodal lymphoma, especially in cases of subtle CT findings.
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Figure 9a. Lymph node metastasis in a 48-year-old man with newly diagnosed squamous cell cancer of the tonsil. Axial PET scan (b) demonstrates intense FDG uptake in the region of the left tonsil (arrow) and in a left cervical lymph node (arrowhead), findings that are consistent with primary and metastatic disease, respectively. (a, c) Axial CT (a) and PET-CT fusion (c) images help confirm that the uptake corresponds to the left palatine tonsil (arrow) and left jugular lymph node (arrowhead). The asymmetric nature of the tonsillar uptake and the presence of lymph node metastasis allow definitive diagnosis.
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Figure 9b. Lymph node metastasis in a 48-year-old man with newly diagnosed squamous cell cancer of the tonsil. Axial PET scan (b) demonstrates intense FDG uptake in the region of the left tonsil (arrow) and in a left cervical lymph node (arrowhead), findings that are consistent with primary and metastatic disease, respectively. (a, c) Axial CT (a) and PET-CT fusion (c) images help confirm that the uptake corresponds to the left palatine tonsil (arrow) and left jugular lymph node (arrowhead). The asymmetric nature of the tonsillar uptake and the presence of lymph node metastasis allow definitive diagnosis.
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Figure 9c. Lymph node metastasis in a 48-year-old man with newly diagnosed squamous cell cancer of the tonsil. Axial PET scan (b) demonstrates intense FDG uptake in the region of the left tonsil (arrow) and in a left cervical lymph node (arrowhead), findings that are consistent with primary and metastatic disease, respectively. (a, c) Axial CT (a) and PET-CT fusion (c) images help confirm that the uptake corresponds to the left palatine tonsil (arrow) and left jugular lymph node (arrowhead). The asymmetric nature of the tonsillar uptake and the presence of lymph node metastasis allow definitive diagnosis.
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Figure 10a. Tonsillar lymphoma in a 20-year-old man with Burkitt lymphoma of the abdomen who was referred for posttherapy evaluation. Axial PET scan (b) demonstrates intense FDG uptake in the region of the tonsils with minimal asymmetry (arrows), a finding that is suspicious for extranodal lymphoma in the regional lymphatic tissues. (a, c) Axial CT (a) and PET-CT fusion (c) images help confirm that the uptake (arrows) corresponds to the palatine tonsils. Furthermore, asymmetric uptake in the left tonsil is seen as a mass that bulges into the lumen on the CT scan. The minimal asymmetry of the tonsillar uptake suggests disease; however, definitive diagnosis cannot be made on the basis of PET-CT findings alone. Subsequent biopsy revealed Burkitt lymphoma of the tonsils.
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Figure 10b. Tonsillar lymphoma in a 20-year-old man with Burkitt lymphoma of the abdomen who was referred for posttherapy evaluation. Axial PET scan (b) demonstrates intense FDG uptake in the region of the tonsils with minimal asymmetry (arrows), a finding that is suspicious for extranodal lymphoma in the regional lymphatic tissues. (a, c) Axial CT (a) and PET-CT fusion (c) images help confirm that the uptake (arrows) corresponds to the palatine tonsils. Furthermore, asymmetric uptake in the left tonsil is seen as a mass that bulges into the lumen on the CT scan. The minimal asymmetry of the tonsillar uptake suggests disease; however, definitive diagnosis cannot be made on the basis of PET-CT findings alone. Subsequent biopsy revealed Burkitt lymphoma of the tonsils.
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Figure 10c. Tonsillar lymphoma in a 20-year-old man with Burkitt lymphoma of the abdomen who was referred for posttherapy evaluation. Axial PET scan (b) demonstrates intense FDG uptake in the region of the tonsils with minimal asymmetry (arrows), a finding that is suspicious for extranodal lymphoma in the regional lymphatic tissues. (a, c) Axial CT (a) and PET-CT fusion (c) images help confirm that the uptake (arrows) corresponds to the palatine tonsils. Furthermore, asymmetric uptake in the left tonsil is seen as a mass that bulges into the lumen on the CT scan. The minimal asymmetry of the tonsillar uptake suggests disease; however, definitive diagnosis cannot be made on the basis of PET-CT findings alone. Subsequent biopsy revealed Burkitt lymphoma of the tonsils.
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Low to moderate FDG uptake is noted in the salivary glands, most prominently in the floor of the mouth. In the saliva, FDG concentration has been observed to be higher than physiologic glucose content (10). The difference between physiologic expected values and observed values may reflect a difference between the reabsorption process for glucose and that for FDG, similar to the processing of FDG by the renal tubules. Symmetric diffuse uptake in the parotid glands is usually physiologic, whereas focal and heterogeneous uptake is suggestive of a malignant process.
Chest
The thymus lies in the upper part of the mediastinum anterior to the great vessels and extends upward into the neck. Involution of the gland begins in adolescence. The proposed mechanism for therapy-related thymic rebound includes initial thymic regression secondary to chemotherapy or corticosteroids that trigger apoptosis of T cells and thymocyte death, with subsequent rebound on reversal of the predisposing condition (11,12). Moderate to high FDG uptake is noted in patients with thymic rebound (Fig 11) and should not be confused with asymmetric uptake due to lymphoma in this location (Fig 12). In pediatric patients, anatomic correlation is necessary following chemotherapy to differentiate the enlarged thymus from residual or recurrent disease at this location, especially with focal thymic uptake (Fig 13).
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Figure 11a. Thymic rebound in a 25-year-old woman with a history of Hodgkin disease who was referred for posttherapy evaluation. Axial PET scan (b) demonstrates findings that are consistent with posttherapy thymic rebound (arrows). (a, c) Axial CT (a) and PET-CT fusion (c) images reveal a symmetric hypermetabolic focus (arrows) that corresponds to the thymus and appears as a bilobed structure with convex lateral borders in the anterosuperior mediastinum at CT.
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Figure 11b. Thymic rebound in a 25-year-old woman with a history of Hodgkin disease who was referred for posttherapy evaluation. Axial PET scan (b) demonstrates findings that are consistent with posttherapy thymic rebound (arrows). (a, c) Axial CT (a) and PET-CT fusion (c) images reveal a symmetric hypermetabolic focus (arrows) that corresponds to the thymus and appears as a bilobed structure with convex lateral borders in the anterosuperior mediastinum at CT.
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Figure 11c. Thymic rebound in a 25-year-old woman with a history of Hodgkin disease who was referred for posttherapy evaluation. Axial PET scan (b) demonstrates findings that are consistent with posttherapy thymic rebound (arrows). (a, c) Axial CT (a) and PET-CT fusion (c) images reveal a symmetric hypermetabolic focus (arrows) that corresponds to the thymus and appears as a bilobed structure with convex lateral borders in the anterosuperior mediastinum at CT.
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Figure 12a. Lymphoma in a 36-year-old man with a history of Hodgkin disease who was referred for posttherapy evaluation for possible residual disease. Axial CT (a), PET (b), and PET-CT fusion (c) images demonstrate a convex right mediastinal hypermetabolic focus (arrow) that is suspicious for residual disease. Although the unilateral manifestation and midmediastinal location of this focus and the presence of associated other abnormal foci of mediastinal uptake do not support thymic rebound, the pattern of uptake resembles thymic uptake. This pattern may be confusing in certain clinical settings, particularly when the pathologic uptake is located more anteriorly in the mediastinum.
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Figure 12b. Lymphoma in a 36-year-old man with a history of Hodgkin disease who was referred for posttherapy evaluation for possible residual disease. Axial CT (a), PET (b), and PET-CT fusion (c) images demonstrate a convex right mediastinal hypermetabolic focus (arrow) that is suspicious for residual disease. Although the unilateral manifestation and midmediastinal location of this focus and the presence of associated other abnormal foci of mediastinal uptake do not support thymic rebound, the pattern of uptake resembles thymic uptake. This pattern may be confusing in certain clinical settings, particularly when the pathologic uptake is located more anteriorly in the mediastinum.
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Figure 12c. Lymphoma in a 36-year-old man with a history of Hodgkin disease who was referred for posttherapy evaluation for possible residual disease. Axial CT (a), PET (b), and PET-CT fusion (c) images demonstrate a convex right mediastinal hypermetabolic focus (arrow) that is suspicious for residual disease. Although the unilateral manifestation and midmediastinal location of this focus and the presence of associated other abnormal foci of mediastinal uptake do not support thymic rebound, the pattern of uptake resembles thymic uptake. This pattern may be confusing in certain clinical settings, particularly when the pathologic uptake is located more anteriorly in the mediastinum.
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Figure 13a. Physiologic thymic uptake in a 23-year-old woman with a history of Hodgkin disease of the chest who was referred for posttherapy evaluation. Axial PET scan (b) demonstrates a unilateral focus of FDG uptake in the superoanterior mediastinum (arrow), a finding that is suspicious for residual disease. Although the uptake is located in the thymic region, its midmediastinal location may suggest viable lymphoma (cf Fig 12). (a, c) Axial CT (a) and PET-CT fusion (c) images help confirm that the anterosuperior mediastinal uptake (arrow) corresponds to thymic tissue, thereby excluding the possibility of residual disease. Although PET-CT is convenient for immediate correlation of images obtained in the same anatomic planes, a recent, separately acquired CT scan would also be helpful in confirming thymic uptake.
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Figure 13b. Physiologic thymic uptake in a 23-year-old woman with a history of Hodgkin disease of the chest who was referred for posttherapy evaluation. Axial PET scan (b) demonstrates a unilateral focus of FDG uptake in the superoanterior mediastinum (arrow), a finding that is suspicious for residual disease. Although the uptake is located in the thymic region, its midmediastinal location may suggest viable lymphoma (cf Fig 12). (a, c) Axial CT (a) and PET-CT fusion (c) images help confirm that the anterosuperior mediastinal uptake (arrow) corresponds to thymic tissue, thereby excluding the possibility of residual disease. Although PET-CT is convenient for immediate correlation of images obtained in the same anatomic planes, a recent, separately acquired CT scan would also be helpful in confirming thymic uptake.
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Figure 13c. Physiologic thymic uptake in a 23-year-old woman with a history of Hodgkin disease of the chest who was referred for posttherapy evaluation. Axial PET scan (b) demonstrates a unilateral focus of FDG uptake in the superoanterior mediastinum (arrow), a finding that is suspicious for residual disease. Although the uptake is located in the thymic region, its midmediastinal location may suggest viable lymphoma (cf Fig 12). (a, c) Axial CT (a) and PET-CT fusion (c) images help confirm that the anterosuperior mediastinal uptake (arrow) corresponds to thymic tissue, thereby excluding the possibility of residual disease. Although PET-CT is convenient for immediate correlation of images obtained in the same anatomic planes, a recent, separately acquired CT scan would also be helpful in confirming thymic uptake.
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High FDG uptake is seen in the brown adipose tissue in the supraclavicular regions, midaxillary line, and paraspinal regions in the posterior mediastinum (13,14). In contrast to other tissue, brown adipose tissue expresses the mitochondrial uncoupling protein, which allows the cell mitochondria to uncouple oxidative phosphorylation and generate heat rather than adenosine triphosphate (15). Metabolism within the brown adipose tissue is increased by means of anaerobic metabolism to prevent this highly metabolic tissue from becoming adenosine triphosphate deficient. In patients with increased activity in the brown adipose tissue, usually pediatric patients and females, symmetric FDG uptake can mimic pathologic uptake (13,14). Simultaneously acquired PET and CT scans allow delineation of normal anatomic structures and precise localization of FDG uptake. Discordant findings in which intense FDG uptake is seen on high-quality PET scans but no corresponding abnormality is seen at CT suggest brown adipose tissue (Fig 14). Because brown adipose tissue has rich sympathetic innervation, administration of diazepam can prevent observed uptake in the brown adipose tissue by means of a sympathetic nervous system blockade (16). However, ß-blockers of the sympathetic nervous system may be more useful in inhibiting FDG uptake in the brown adipose tissue.
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Figure 14a. Residual disease in a 36-year-old man with a history of Hodgkin disease who was referred for postchemotherapy evaluation. (a-c) Coronal PET scan (b) shows symmetric hypermetabolic foci in the cervical and supraclavicular regions (small arrows). In addition, there is asymmetric uptake in the right axillary region (large arrow). Coronal CT (a) and PET-CT fusion (c) images help confirm persistent lymphoma in the right axillary lymph nodes (large arrow). No abnormality is seen in the cervical supraclavicular regions that corresponds to the FDG uptake in these regions (small arrows), a finding that is consistent with brown adipose tissue. (d-f) Axial PET scan (e) demonstrates multiple foci of increased FDG uptake in the cervical region. There is also a unilateral focus of uptake in the right jugular region (arrow) that is suspicious for malignancy. CT (d) and PET-CT fusion (f) images help confirm that the focal FDG uptake on the right side (arrowhead) corresponds to a jugular lymph node, a finding that is consistent with residual Hodgkin disease. The uptake in the brown adipose tissue renders interpretation difficult by obscuring the underlying lymph nodes that harbor viable residual disease. It is essential that this pattern of uptake be evaluated simultaneously with CT.
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Figure 14b. Residual disease in a 36-year-old man with a history of Hodgkin disease who was referred for postchemotherapy evaluation. (a-c) Coronal PET scan (b) shows symmetric hypermetabolic foci in the cervical and supraclavicular regions (small arrows). In addition, there is asymmetric uptake in the right axillary region (large arrow). Coronal CT (a) and PET-CT fusion (c) images help confirm persistent lymphoma in the right axillary lymph nodes (large arrow). No abnormality is seen in the cervical supraclavicular regions that corresponds to the FDG uptake in these regions (small arrows), a finding that is consistent with brown adipose tissue. (d-f) Axial PET scan (e) demonstrates multiple foci of increased FDG uptake in the cervical region. There is also a unilateral focus of uptake in the right jugular region (arrow) that is suspicious for malignancy. CT (d) and PET-CT fusion (f) images help confirm that the focal FDG uptake on the right side (arrowhead) corresponds to a jugular lymph node, a finding that is consistent with residual Hodgkin disease. The uptake in the brown adipose tissue renders interpretation difficult by obscuring the underlying lymph nodes that harbor viable residual disease. It is essential that this pattern of uptake be evaluated simultaneously with CT.
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Figure 14c. Residual disease in a 36-year-old man with a history of Hodgkin disease who was referred for postchemotherapy evaluation. (a-c) Coronal PET scan (b) shows symmetric hypermetabolic foci in the cervical and supraclavicular regions (small arrows). In addition, there is asymmetric uptake in the right axillary region (large arrow). Coronal CT (a) and PET-CT fusion (c) images help confirm persistent lymphoma in the right axillary lymph nodes (large arrow). No abnormality is seen in the cervical supraclavicular regions that corresponds to the FDG uptake in these regions (small arrows), a finding that is consistent with brown adipose tissue. (d-f) Axial PET scan (e) demonstrates multiple foci of increased FDG uptake in the cervical region. There is also a unilateral focus of uptake in the right jugular region (arrow) that is suspicious for malignancy. CT (d) and PET-CT fusion (f) images help confirm that the focal FDG uptake on the right side (arrowhead) corresponds to a jugular lymph node, a finding that is consistent with residual Hodgkin disease. The uptake in the brown adipose tissue renders interpretation difficult by obscuring the underlying lymph nodes that harbor viable residual disease. It is essential that this pattern of uptake be evaluated simultaneously with CT.
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Figure 14d. Residual disease in a 36-year-old man with a history of Hodgkin disease who was referred for postchemotherapy evaluation. (a-c) Coronal PET scan (b) shows symmetric hypermetabolic foci in the cervical and supraclavicular regions (small arrows). In addition, there is asymmetric uptake in the right axillary region (large arrow). Coronal CT (a) and PET-CT fusion (c) images help confirm persistent lymphoma in the right axillary lymph nodes (large arrow). No abnormality is seen in the cervical supraclavicular regions that corresponds to the FDG uptake in these regions (small arrows), a finding that is consistent with brown adipose tissue. (d-f) Axial PET scan (e) demonstrates multiple foci of increased FDG uptake in the cervical region. There is also a unilateral focus of uptake in the right jugular region (arrow) that is suspicious for malignancy. CT (d) and PET-CT fusion (f) images help confirm that the focal FDG uptake on the right side (arrowhead) corresponds to a jugular lymph node, a finding that is consistent with residual Hodgkin disease. The uptake in the brown adipose tissue renders interpretation difficult by obscuring the underlying lymph nodes that harbor viable residual disease. It is essential that this pattern of uptake be evaluated simultaneously with CT.
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Figure 14e. Residual disease in a 36-year-old man with a history of Hodgkin disease who was referred for postchemotherapy evaluation. (a-c) Coronal PET scan (b) shows symmetric hypermetabolic foci in the cervical and supraclavicular regions (small arrows). In addition, there is asymmetric uptake in the right axillary region (large arrow). Coronal CT (a) and PET-CT fusion (c) images help confirm persistent lymphoma in the right axillary lymph nodes (large arrow). No abnormality is seen in the cervical supraclavicular regions that corresponds to the FDG uptake in these regions (small arrows), a finding that is consistent with brown adipose tissue. (d-f) Axial PET scan (e) demonstrates multiple foci of increased FDG uptake in the cervical region. There is also a unilateral focus of uptake in the right jugular region (arrow) that is suspicious for malignancy. CT (d) and PET-CT fusion (f) images help confirm that the focal FDG uptake on the right side (arrowhead) corresponds to a jugular lymph node, a finding that is consistent with residual Hodgkin disease. The uptake in the brown adipose tissue renders interpretation difficult by obscuring the underlying lymph nodes that harbor viable residual disease. It is essential that this pattern of uptake be evaluated simultaneously with CT.
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Figure 14f. Residual disease in a 36-year-old man with a history of Hodgkin disease who was referred for postchemotherapy evaluation. (a-c) Coronal PET scan (b) shows symmetric hypermetabolic foci in the cervical and supraclavicular regions | |
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Abstract
LEARNING OBJECTIVES FOR TEST...
