rg%2E245035725

EDUCATION EXHIBIT 1411

PET-CT FusionImaging in Differenti-ating Physiologic fromPathologic FDG Uptake1

LEARNINGOBJECTIVESFOR TEST 5After reading thisarticle and takingthe test, the reader

will be able to:

Describe the physi-ologic uptake pat-terns that can mimicdisease at FDG PET.

Discuss the advan-tages and limitationsof PET-CT fusionimaging in differenti-ating normal frompathologic findings.

Lale Kostakoglu, MD Ruth Hardoff, MD Rosna Mirtcheva, MDStanley J. Goldsmith, MD

Interpretation of positron emission tomographic (PET) scans in theabsence of correlative anatomic information can be challenging. PETcomputed tomography (CT) fusion imaging is a novel multimodalitytechnology that allows the correlation of findings from two concurrentimaging modalities in a comprehensive examination. CT demonstratesexquisite anatomic detail but does not provide functional information,whereas 2-[fluorine 18]fluoro-2-deoxy-d-glucose (FDG) PET revealsaspects of tumor function and allows metabolic measurements. Subtlefindings at FDG PET that might otherwise be disregarded or inter-preted as physiologic variants may lead to detection of a malignant pro-cess after being correlated with simultaneously acquired CT findings.Alternatively, equivocal CT findings, which could represent malignanttumor, reactive changes, or fibrosis, can be clarified with the help of theadditional metabolic information provided by concurrent FDG PET.Accurate interpretation of FDG PET scans requires a thorough knowl-edge of the normal physiologic distribution of FDG and of normal vari-ants that may reduce the accuracy of PET studies, thereby significantlyaffecting patient treatment. Although in rare instances PET-CT can-not help resolve the diagnostic dilemma, it is enjoying widespread ac-ceptance in the medical imaging community, usually allowing differen-tiation of physiologic variants from juxtaposed or mimetic neoplasticlesions and more accurate tumor localization.RSNA, 2004

Abbreviation: FDG 2-[fluorine 18]fluoro-2-deoxy-d-glucose

Index terms: Computed tomography (CT), **.12112 Computed tomography (CT), utilization Fluorine, radioactive Positron emission tomogra-phy (PET), **.12163 Radionuclide imaging, in diagnosis of neoplasms, **.12163

RadioGraphics 2004; 24:14111431 Published online 10.1148/rg.245035725 Content Codes:

1From 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, SacklerSchool of Medicine, Tel-Aviv University, Tel-Aviv, Israel (R.H.). Received October 6, 2003; revision requested November 25 and received January24, 2004; accepted January 30. All authors have no financial relationships to disclose. Address correspondence to L.K. (e-mail: [email protected]).

2** multiple body systems

RSNA, 2004

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CME FEATURESee accompanying

test at http://www.rsna.org

/education/rg_cme.html

IntroductionAccurate evaluation of disease extent prior totherapy and of response to therapy have a signifi-cant impact on the clinical management of onco-logic disorders. Positron emission tomography(PET) with 2-[fluorine 18]fluoro-2-deoxy-d-glu-cose (FDG) provides valuable metabolic informa-tion and has recently become an essential diag-nostic modality in the staging and restaging ofvarious cancers. Increased FDG accumulation inneoplastic tissues is a function of increased ex-pression and activity of glucose transporter pro-teins and of the glucose phosphorylating enzymehexokinase, which result from increased anaero-bic metabolism in cancer cells as well as meta-bolic trapping of FDG within the tumor cells dueto the lack of further metabolic pathways forFDG (1). Nevertheless, FDG is not specific forneoplastic processes; it accumulates physiologi-cally in various normal organs, including thebrain, muscles, salivary glands, myocardium, gas-trointestinal tract, urinary tract, brown adiposetissue, thyroid gland, and gonadal tissues (24).

FDG PET is a strictly functional modality andlacks anatomic landmarks for precise morpho-logic orientation. Unless anatomic correlation isavailable to delineate normal structures, patho-logic sites of FDG accumulation can easily beconfused with normal physiologic uptake, leadingto false-positive or false-negative findings. This isan important shortcoming in the determination ofactive disease sites, particularly for small lesionsand lesions located near sites of physiologic up-take. Coregistration of PET scans (functional andmorphologic information) with computed tomo-graphic (CT) scans (anatomic information) usinga combined PET-CT scanner improves the over-all sensitivity and specificity of information pro-vided by PET or CT alone (4,5). The unique ad-vantage of PET-CT fusion imaging is the ability

to correlate findings at two complementary imag-ing modalities in a comprehensive examination.Hence, PET-CT provides more precise anatomicdefinition for both the physiologic and pathologicuptake seen at FDG PET. In particular, in theposttherapy period, subtle metabolic findings atFDG PET that might otherwise be overlookedmay allow detection of residual disease after cor-relation with the simultaneously acquired CTdata. Conversely, equivocal CT findings can bebetter evaluated with the help of the additionalfunctional information provided by FDG PET.

In this article, we discuss and illustrate normalphysiologic patterns of FDG uptake and patho-logic patterns of uptake at PET in various ana-tomic locations (head and neck, chest, abdomenand pelvis). We also discuss the utility of PET-CTin differentiating malignant processes from physi-ologic uptake, since in some cases such differen-tiation cannot be made with certainty with FDGPET alone.

Sites of Physiologic FDG UptakeThere are several sites of normal physiologic ac-cumulation of FDG (Fig 1). FDG accumulationis most intense in the cerebral cortex, basal gan-glia, thalamus, and cerebellum, since the brain isexclusively dependent on glucose metabolism.The myocardium expresses insulin-sensitive glu-cose transporters, which facilitate the transport ofglucose into muscle. Although the myocardiumuses free fatty acids as its primary substrate, in thenonfasting state the antilipolytic effect of insulinreduces the delivery of free fatty acids, and theheart relies more on glycolytic metabolism. A re-cent meal often causes intense myocardial FDGuptake because of the associated elevated seruminsulin levels. Fasting for 46 hours before FDGadministration decreases the availability of bothglucose and insulin in the circulation, which usu-ally leads to decreased accumulation of FDGwithin the myocardium.

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Because FDG appears in the glomerular fil-trate and, unlike glucose, is not reabsorbed in thetubules, intense FDG activity is seen in the intra-renal collecting systems, ureters, and bladder.Less intense radiotracer activity is present in theliver, spleen, bone marrow, and renal cortex. At 1hour after radiotracer injection, blood pool activ-ity results in moderate background activity in themediastinum, whereas lung activity is low.

Significant muscle uptake is observed in theskeletal muscles with exercise, in the breathingmuscles with hyperventilation, in the cervicalmuscles with tension, and in the laryngeal mus-cles with vocalization. Uptake in lymphatic

tissues and salivary glands may also be seen as anormal variant. Uptake in the gastrointestinaltract is variable. Normal stomach, small intestine,and colon may demonstrate increased FDG up-take due to a combination of factors, includingsmooth muscle contraction and metabolicallyactive mucosa (2). FDG uptake in bone marrowis normally modest. Patients undergoing treat-ment with granulocyte-stimulating factors havediffuse intense FDG uptake in the bone marrow(6).

Figure 1. Normal distribution of FDG. Coronal CT (a), PET (b), and PET-CT fusion (c) images demonstratethe 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 andbilaterally in the lower cervical and psoas muscles.

RG f Volume 24 Number 5 Kostakoglu et al 1413

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Physiologic versusPathologic FDG Uptake

Head and NeckAlthough muscle uptake anywhere in the bodymay make the interpretation of FDG PET scansdifficult, the abundance of small muscle groups inthe neck constitutes a diagnostic dilemma, par-ticularly in patients with head and neck neo-plasms. Differentiation of physiologic muscle up-take from pathologic uptake is even more criticalin the posttherapy follow-up period. Moderate tohigh FDG uptake is noticeable in the muscles,including the ocular muscles, and may be a po-tential source of false-positive findings in patientswith malignant head and neck tumors and central

nervous system tumors. Even without the help ofCT, the origin of such FDG uptake is usually ob-vious due to the symmetric uptake pattern andthe typical anatomic location. Contraction-in-duced FDG uptake in cervical muscles in tensepatients can be confused with lymph node metas-tasis or, alternatively, may lead to false-negativefindings of disease in the underlying lymph nodes(Fig 2), which constitutes a serious problem inpatients with asymmetric muscle uptake due toprior neck dissection (Fig 3).

Physiologic FDG uptake in the normal thyroidgland is usually absent or minimal, whereas inadenomas, uptake can be as high as that which isobserved in malignant processes (7). In the ab-sence of correlative imaging with an anatomicmodality, focal uptake in the thyroid gland can befalsely interpreted as metastatic disease in thelower cervical lymph node stations (Figs 4, 5).

Figure 2. Contraction-induced FDG uptake in a 50-year-old woman with advanced nonsmall cell lung can-cer who was referred for presurgical evaluation. (a) Axial FDG PET scans demonstrate multiple hypermeta-bolic foci in the anterior cervical region. Intense symmetric and superficial uptake in the anterior neck (arrow-heads) suggests tense sternocleidomastoid muscle uptake. An additional asymmetric focus of uptake posteriorto the right sternocleidomastoid muscle (arrows) suggests cervical lymph node metastasis, which represents amore advanced disease stage and renders the patient ineligible for surgery until after neoadjuvant chemo-therapy. (b, c) Axial CT (b) and PET-CT fusion (c) images demonstrate that the unilateral uptake in the rightcervical region corresponds to the anterior scalene muscle (long arrow) and that the superficially located sym-metric FDG uptake corresponds to the sternocleidomastoid muscles (short arrows). Evaluation with PET-CTexcluded the possibility of a false-positive finding (ie, metastatic disease in the neck), which would subject thepatient to unnecessary chemotherapy.


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Figure 3. Asymmetric muscle uptake in a 62-year-old woman with squamous cell carcinoma of thetongue who had undergone neck dissection. (a) Axial FDG PET scans demonstrate multiple hypermeta-bolic foci in the right anterolateral cervical region. Asymmetric and superficial uptake in the right anteriorportion of the neck (arrowheads) suggests tense sternocleidomastoid muscle uptake. An additional asym-metric focus of uptake is noted posterior to the right sternocleidomastoid muscle (long arrow) and sug-gests cervical lymph node metastasis, although unilateral cervical muscle uptake cannot be excluded (cfFig 4). Symmetric foci seen within the larynx (short arrows) probably represent the intrinsic laryngealmuscles. (b, c) Axial CT (b) and PET-CT fusion (c) images help confirm that the superficial asymmet-ric FDG uptake in the anterior cervical region corresponds to the right sternocleidomastoid muscle (ar-rowhead). The absence of contralateral muscle uptake is due to prior neck dissection. The unilateral fo-cus of uptake posterior to the right sternocleidomastoid muscle (long arrow) corresponds to a cervicallymph node, and symmetric foci within the larynx (short arrows) correspond to the intrinsic laryngealmuscles and cricoarytenoid muscles posteriorly. The results of simultaneous evaluation with PET andCT confirmed the diagnosis of (advanced) metastatic disease in the neck and had a significant impact onclinical management. The patient was started on therapy on the basis of the PET-CT findings.

Figure 4. Thyroid carcinoma in a 45-year-old woman with a history of breast cancer who was referred for post-therapy evaluation. Axial PET scan (b) reveals a hypermetabolic focus in a cervical lymph node in the left side of theneck (arrowhead) that is highly suspicious for metastatic disease. (a, c) Axial CT (a) and PET-CT fusion (c) imagesdemonstrate 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. Fur-ther investigation with needle biopsy revealed follicular carcinoma of the thyroid gland. PET-CT findings confirmedthat the patient had thyroid disease (adenoma or carcinoma) rather than lymph node metastasis; however, the nodulecould not be characterized on the basis of PET-CT findings alone.


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Figure 5. Thyroid nodule in a 51-year-old man with a history of squamous cell carcinoma of the tonsil who wasreferred 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 demon-strate that the focus (arrow) corresponds to the right thyroid lobe and is consistent with a thyroid nodule, a findingthat was confirmed with subsequent ultrasonography. PET-CT findings confirmed that the patient did not havelymph node metastasis; however, a thyroid nodule requires further investigation with biopsy to rule out a malignantcause within the thyroid gland.

Figure 6. Primary tumor of the larynx in a 45-year-old man with epiglottic carcinoma who was referred for presur-gical evaluation. Axial CT (a), PET (b), and PET-CT fusion (c) images show a focus of uptake (arrow) that corre-sponds to a mass that originates from the larynx and nearly obliterates the lumen on the CT scan. Correlation withCT and PET-CT helped greatly in establishing the diagnosis of primary laryngeal malignancy rather than activatedlaryngeal muscles. In cases of occult head and neck tumor, differentiation may be difficult without CT correlation. Itis essential that the patient remain silent during the period of FDG uptake.

Figure 7. Physiologic laryngeal uptake in a 52-year-old woman with squamouscell carcinoma of the floor of the mouth who had undergone surgery and radiationtherapy. Axial CT (a), PET (b), and PET-CT fusion (c) images clearly demon-strate a midline focus of uptake (arrow) that corresponds to the cricoarytenoidmuscles located posterior to the thyrocricoid cartilage. Although this site and pat-tern of uptake are typical for activated vocal cords, CT helps confirm the physi-ologic nature of the FDG accumulation. Without CT correlation, this focus of up-take may lead to a false-positive finding in patients with malignant processes in thislocation, particularly in the posttherapy setting.


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The intrinsic laryngeal muscles serve both as asphincter and as an organ of phonation. FDGaccumulates in the striated laryngeal muscles inproportion to contractile activity during speech.This phenomenon is a major concern and maylead to false readings in patients with head andneck cancers (Figs 6, 7) (8,9). A rigorous ap-proach to preventing physiologic FDG uptakein the laryngeal muscles should be adopted toavoid false-positive findings. In practice, patientsshould be encouraged to remain silent beginning15 minutes prior to injection and continuing untilthe study is completed.

Low to moderate FDG uptake occurs in thelymphatic tissues in the pharynx, consisting of the

nasopharyngeal, palatine, and lingual tonsils(Waldeyer ring) (Figs 810 ) (4). The Waldeyerring is a common site of head and neck manifesta-tions of extranodal non-Hodgkin lymphoma (Fig8). Furthermore, primary squamous cell carci-noma of the head and neck may occur within thecrypts of the Waldeyer ring (Fig 9). In cases oftonsillar lymphoma, the asymmetric nature ofFDG uptake suggests a pathologic process (Fig10). However, in the absence of CT guidance,malignant processes arising from the lymphatictissues may be difficult to identify at FDG PET.

Figures 8, 9. (8) Extranodal disease in a 33-year-old man with a history of ag-gressive non-Hodgkin lymphoma who had undergone chemotherapy 1 year earlier.Axial PET scan (b) demonstrates intense FDG uptake in the posterosuperior oralcavity (arrows). (a, c) Axial CT (a) and PET-CT fusion (c) images demonstratethat the uptake (arrows) corresponds to the palatine tonsils, with minimal asymme-try seen at CT. In the tonsillar lymphatic tissues, physiologic uptake cannot be dif-ferentiated from extranodal lymphoma, especially in cases of subtle CT findings.(9) Lymph node metastasis in a 48-year-old man with newly diagnosed squamouscell cancer of the tonsil. Axial PET scan (b) demonstrates intense FDG uptake inthe 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 uptakecorresponds to the left palatine tonsil (arrow) and left jugular lymph node (arrow-head). The asymmetric nature of the tonsillar uptake and the presence of lymphnode metastasis allow definitive diagnosis.


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Low to moderate FDG uptake is noted in thesalivary glands, most prominently in the floor ofthe mouth. In the saliva, FDG concentration hasbeen observed to be higher than physiologic glu-cose content (10). The difference between physi-ologic expected values and observed values mayreflect a difference between the reabsorption pro-cess for glucose and that for FDG, similar to theprocessing of FDG by the renal tubules. Symmet-ric diffuse uptake in the parotid glands is usuallyphysiologic, whereas focal and heterogeneous up-take is suggestive of a malignant process.

ChestThe thymus lies in the upper part of the mediasti-num anterior to the great vessels and extends up-ward into the neck. Involution of the gland beginsin adolescence. The proposed mechanism fortherapy-related thymic rebound includes initialthymic regression secondary to chemotherapy orcorticosteroids that trigger apoptosis of T cellsand thymocyte death, with subsequent reboundon reversal of the predisposing condition (11,12).Moderate to high FDG uptake is noted in pa-

tients with thymic rebound (Fig 11) and shouldnot be confused with asymmetric uptake due tolymphoma in this location (Fig 12). In pediatricpatients, anatomic correlation is necessary follow-ing chemotherapy to differentiate the enlargedthymus from residual or recurrent disease at thislocation, especially with focal thymic uptake (Fig13).

High FDG uptake is seen in the brown adiposetissue in the supraclavicular regions, midaxillaryline, and paraspinal regions in the posterior medi-astinum (13,14). In contrast to other tissue,brown adipose tissue expresses the mitochondrialuncoupling protein, which allows the cell mito-chondria to uncouple oxidative phosphorylationand generate heat rather than adenosine triphos-phate (15). Metabolism within the brown adiposetissue is increased by means of anaerobic metabo-lism to prevent this highly metabolic tissue frombecoming adenosine triphosphate deficient. Inpatients with increased activity in the brown adi-pose tissue, usually pediatric patients and fe-males, symmetric FDG uptake can mimic patho-logic uptake (13,14). Simultaneously acquiredPET and CT scans allow delineation of normalanatomic structures and precise localization ofFDG uptake. Discordant findings in which in-

Figure 10. Tonsillar lymphoma in a 20-year-old man with Burkitt lymphoma ofthe abdomen who was referred for posttherapy evaluation. Axial PET scan (b)demonstrates intense FDG uptake in the region of the tonsils with minimal asym-metry (arrows), a finding that is suspicious for extranodal lymphoma in the regionallymphatic tissues. (a, c) Axial CT (a) and PET-CT fusion (c) images help confirmthat the uptake (arrows) corresponds to the palatine tonsils. Furthermore, asym-metric uptake in the left tonsil is seen as a mass that bulges into the lumen on theCT scan. The minimal asymmetry of the tonsillar uptake suggests disease; how-ever, 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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tense FDG uptake is seen on high-quality PETscans but no corresponding abnormality is seen atCT suggest brown adipose tissue (Fig 14). Be-cause brown adipose tissue has rich sympatheticinnervation, administration of diazepam can pre-vent observed uptake in the brown adipose tissue

by means of a sympathetic nervous system block-ade (16). However, -blockers of the sympatheticnervous system may be more useful in inhibitingFDG uptake in the brown adipose tissue.

Figures 1113. (11) Thymic rebound in a 25-year-old woman with a history of Hodgkin disease who was referredfor posttherapy evaluation. Axial PET scan (b) demonstrates findings that are consistent with posttherapy thymicrebound (arrows). (a, c) Axial CT (a) and PET-CT fusion (c) images reveal a symmetric hypermetabolic focus (ar-rows) that corresponds to the thymus and appears as a bilobed structure with convex lateral borders in the anterosu-perior mediastinum at CT. (12) Lymphoma in a 36-year-old man with a history of Hodgkin disease who was referredfor posttherapy evaluation for possible residual disease. Axial CT (a), PET (b), and PET-CT fusion (c) images dem-onstrate a convex right mediastinal hypermetabolic focus (arrow) that is suspicious for residual disease. Although theunilateral manifestation and midmediastinal location of this focus and the presence of associated other abnormal fociof mediastinal uptake do not support thymic rebound, the pattern of uptake resembles thymic uptake. This patternmay be confusing in certain clinical settings, particularly when the pathologic uptake is located more anteriorly in themediastinum. (13) Physiologic thymic uptake in a 23-year-old woman with a history of Hodgkin disease of the chestwho was referred for posttherapy evaluation. Axial PET scan (b) demonstrates a unilateral focus of FDG uptake inthe superoanterior mediastinum (arrow), a finding that is suspicious for residual disease. Although the uptake is lo-cated 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 thy-mic tissue, thereby excluding the possibility of residual disease. Although PET-CT is convenient for immediate cor-relation of images obtained in the same anatomic planes, a recent, separately acquired CT scan would also be helpfulin confirming thymic uptake.


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Low to moderate FDG uptake is noted in thedistal esophagus, particularly in patients with gas-troesophageal reflux secondary to inflammatorychanges (Fig 15). In some patients, activity in thedistal esophagus without supporting evidence ofdisease is observed due to muscle contraction atthe gastroesophageal junction or inflammatorychanges caused by gastroesophageal reflux. How-ever, high-grade uptake in the same location maybe caused by malignant processes (ie, carcinomaof the distal esophagus, usually associated withmorphologic esophageal changes) (Fig 16). Insome malignant lesions that demonstrate subtleFDG uptake and equivocal morphologic changessuch as lack of significant mucosal and wall thick-ening, correlative imaging may not be useful incharacterizing the function and morphologic fea-tures of the lesions.

Abdomen and PelvisCoregistration of simultaneously acquired PETand CT scans is particularly helpful in the abdo-men and pelvis. PET-CT provides significantlyimproved localization of abnormal or unexpectedFDG findings compared with PET or CT alone.Moderate to high FDG uptake is visible in themuscles that contribute to breathing in patientswith chronic obstructive pulmonary disease dueto difficulty in breathing and use of accessorymuscles to facilitate breathing. In addition, due toan imbalance between oxygen supply and in-creased demand, the decrease in oxygen deliverycauses a switch to anaerobic metabolism (17).Hence, the increased uptake seen in the diaphrag-matic cruces may be the result of accentuatedabdominal breathing effort and the anaerobic me-tabolism that leads to increased FDG uptakesimilar to the physiologic alterations in cancer

Figure 14. Residual disease in a 36-year-old man with a history of Hodgkin disease who was referredfor postchemotherapy evaluation. (ac) Coronal PET scan (b) shows symmetric hypermetabolic foci inthe cervical and supraclavicular regions (small arrows). In addition, there is asymmetric uptake in theright axillary region (large arrow). Coronal CT (a) and PET-CT fusion (c) images help confirm persis-tent lymphoma in the right axillary lymph nodes (large arrow). No abnormality is seen in the cervical su-praclavicular regions that corresponds to the FDG uptake in these regions (small arrows), a finding thatis consistent with brown adipose tissue. (df) Axial PET scan (e) demonstrates multiple foci of increasedFDG 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 thefocal FDG uptake on the right side (arrowhead) corresponds to a jugular lymph node, a finding that isconsistent with residual Hodgkin disease. The uptake in the brown adipose tissue renders interpretationdifficult by obscuring the underlying lymph nodes that harbor viable residual disease. It is essential thatthis pattern of uptake be evaluated simultaneously with CT.


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cells. Any disease process involving the celiac orperigastric lymph nodes (eg, lymphoma, nodalmetastatic disease) can be difficult to interpret inpatients with diaphragmatic uptake, especially inthe posttherapy setting. Nevertheless, PET-CT is

particularly helpful in this group of patients indistinguishing physiologic uptake in the diaphrag-matic cruces from neoplastic processes (Figs 17,18).

Figures 15, 16. (15) Nonneoplastic esophageal uptake in a 21-year-old woman with a history of non-Hodgkin lymphoma who was referred for restaging following therapy. Axial PET scan (b) shows a focus ofmetabolic activity in the midline in the lower chest, inferior to the heart and adjacent to the abdominal aorta(arrowhead). A malignant process in a lymph node in this region cannot be excluded on the basis of PET find-ings alone. (a, c) Axial CT (a) and PET-CT fusion (c) images reveal that the focal FDG uptake in the infero-posterior mediastinum (arrowhead) corresponds to the distal esophagus. This focus of uptake is probably dueto physiologic muscle uptake at the gastroesophageal junction or inflammatory changes secondary to gastro-esophageal reflux. No tumor, wall thickening, or lymphadenopathy is appreciated in this region. (16) Esopha-geal adenocarcinoma in a 52-year-old man who was referred for presurgical evaluation. Axial PET scan (b)demonstrates an intense focus of metabolic activity (arrowhead) (cf Fig 15). If no clinical information wereavailable, it would be unclear whether this focus represented physiologic FDG uptake in the distal esophagusor a lymphatic or esophageal malignancy. (a, c) Axial CT (a) and PET-CT fusion (c) images show significantthickening of the distal esophagus that almost obliterates the lumen (arrowhead). This finding corresponds tothe intense uptake seen at PET and is consistent with esophageal adenocarcinoma.

Figure 17. Physiologic diaphragmatic uptake in a 49-year-old woman with a history of abdominal lymphomaand severe chronic obstructive pulmonary disease who was referred for posttherapy follow-up. Axial PETscan (b) demonstrates bilateral hypermetabolic foci in the upper midabdomen that are slightly more prominenton the right side than on the left (arrowheads). These foci of uptake may be attributed to recurrent lymphomain the regional abdominal lymph nodes. (a, c) Axial CT (a) and PET-CT fusion (c) images demonstrate thatthese foci (arrowheads) correspond to the diaphragmatic cruces. The combined use of PET and CT in thiscase allowed definitive exclusion of relapse of lymphoma.


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Low to moderate uptake is usually observed inthe stomach. The diffuse uptake pattern, typicallylocated in the fundus, is rarely confused with

pathologic FDG uptake. However, focal FDGaccumulation can give rise to misinterpretationsin the absence of correlative imaging, which pro-vides exquisite delineation of the local anatomy,

Figure 18. Recurrent disease in a 56-year-old man with esophageal carcinoma. The patient had undergoneesophagectomy and was referred for follow-up evaluation. Axial PET scan (b) demonstrates a hypermeta-bolic focus left of the midline in the upper abdomen (arrow) (cf Fig 17). This focus is consistent with meta-static esophageal carcinoma in the regional lymph nodes or unilateral uptake in the left diaphragmatic crux.(a, c) Axial CT (a) and PET-CT fusion (c) images demonstrate that the hypermetabolic focus seen at PETcorresponds to an enlarged lymph node (arrow), a finding that is consistent with recurrent disease. The patientsubsequently underwent chemotherapy on the basis of the PET-CT findings.

Figures 19, 20. (19) Physiologic gastric uptake in a 52-year-old man with colorectal cancer who had undergonesurgical tumor resection. (a) Coronal PET scans demonstrate a diffuse hypermetabolic focus in the left upper quad-rant (arrow) that corresponds to the stomach or the transverse colon. (bd) Coronal CT (b), PET (c), and PET-CT fusion (d) images help confirm that the focus of activity (arrow) corresponds to physiologic uptake in the stom-ach. (20) Gastritis in a 47-year-old woman with a history of breast cancer. (a) Coronal PET scans demonstrate ahypermetabolic area in the left upper quadrant of the abdomen in the stomach region (arrow). (bd) Coronal PETscan (c) shows linear activity (black arrow). Coronal CT (b) and PET-CT fusion (d) images demonstrate that thisarea of uptake (white arrow) corresponds to the contour of the stomach. It was later confirmed that the patient suf-fered from gastritis at the time of the PET-CT study. Note the asymmetric uptake in the left breast, a finding that isconsistent with breast cancer.


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including the lymph nodes, liver, and pancreas(Figs 19, 20). Focal and irregular uptake in thestomach is usually due to a malignant process;nevertheless, local gastritis cannot be excludedwith certainty without the help of CT (Fig 21)(18).

The importance of FDG PET in the evalua-tion of colorectal cancer is well established. Both

small and large bowel may demonstrate varyingdegrees of FDG uptake, usually with a diffuse andlinear pattern. However, focal physiologic uptakeis not an uncommon finding in short segments ofthe bowel (Figs 22, 23). Unless CT correlation is

Figure 21. Newly diagnosed gastric cancer in a 59-year-old woman who was referred for presurgical evalua-tion. (a) Coronal PET scans demonstrate a hypermetabolic focus in the left upper quadrant (arrow) in the re-gion of the stomach, transverse colon, or lymph nodes. (bd) Coronal PET scan (c) demonstrates irregularFDG uptake (black arrow). Coronal CT (b) and PET-CT fusion (d) images show that this uptake (white ar-row) corresponds to a mass that originates from the antral portion of the stomach and nearly obliterates thelumen, a finding that is consistent with gastric cancer. PET-CT correlation helped establish the diagnosis ofgastric cancer with no metastasis in the locoregional lymph nodes.

Figure 22. Physiologic bowel uptake in a 36-year-old man with malignant thymoma who had undergone sur-gical tumor resection. Coronal PET scan (b) demonstrates two hypermetabolic foci in the right lower quadrant(arrows). These foci may represent physiologic bowel activity; however, mesenteric lymph node metastasis orsynchronous colon cancer cannot be definitively excluded. (a, c) Coronal CT (a) and PET-CT fusion (c) im-ages reveal that the hypermetabolic foci seen at PET correspond to small bowel loops (arrows). Simultaneousevaluation with CT helps exclude the possibility of lymph node metastasis or synchronous colonic malignancy.Although it is rare, small bowel malignancy is still a possibility, in which case correlation with CT would not behelpful.


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available, the configuration of uptake in thesecases may be indistinguishable from malignantprocesses (Figs 24, 25) (19). Nevertheless, if themalignant lesion is not well defined at CT, theguidance obtained from CT may not be suffi-cient.

Gallbladder uptake of FDG is not a commonfinding. In our limited experience, patients inwhom the gallbladder is visualized at FDG PEThave described postprandial discomfort, a symp-tom that suggests a chronic disorder such aschronic cholecystitis (Fig 26). When activity is

Figure 23. Physiologic bowel uptake in a 44-year-old man with squamous cancer of the oropharynx who wasreferred for posttherapy evaluation. Coronal PET scan (b) reveals hypermetabolic foci in the right lateral mid-abdomen near the hepatic flexure (short arrow) and in the region of the renal pelvis (long arrow). These focimay represent mesenteric lymph node metastasis, synchronous colon cancer, or physiologic bowel uptake.(a, c) Coronal CT (a) and PET-CT fusion (c) images demonstrate that the uptake corresponds to a bowelloop (white arrow in a, short arrow in c). In addition, the superior focus of uptake in the region of the renal pel-vis (black arrow in a, long arrow in c) is most consistent with the ureter. PET-CT correlation helped excludethe possibility of mesenteric lymph node metastasis; however, a second primary tumor in the colon could notbe excluded with this study.

Figure 24. Primary carcinoid tumor of the bowel in a 47-year-old woman with a history of breast cancer anda recent diagnosis of metastatic carcinoid tumor in the lung. Coronal PET scan (b) demonstrates an intensehypermetabolic focus in the right lower quadrant (arrow), a finding that may represent physiologic bowel up-take, carcinoid tumor in the bowel, or mesenteric lymph node. The faint focus in the right lower lung (arrow-head) is consistent with the known carcinoid metastasis. (a, c) Coronal CT (a) and PET-CT fusion (c) imagesreveal that the hypermetabolic focus in the right lower quadrant (arrow) corresponds to the bowel. This find-ing is highly suspicious for a primary carcinoid tumor, which was later confirmed at biopsy. Evaluation withPET-CT helped characterize the FDG uptake in this location, which would otherwise be less specific.


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Figure 25. Adenocarcinoma of the cecum in a 77-year-old man with a cecal polyp that had recently beendetected at colonoscopy. The histologic features of the lesion were consistent with tubular adenoma with high-grade dysplasia. The patient was referred for assessment of the metabolic status of the lesion. Coronal PETscan (b) demonstrates a hypermetabolic focus in the right lower quadrant (arrow) that corresponds to the cecalarea and is consistent with either physiologic bowel uptake or a malignant process. (a, c) Coronal CT (a) andPET-CT fusion (c) images help confirm that this hypermetabolic focus (arrow) corresponds to the cecum.This focus was confirmed to be adenocarcinoma at histologic analysis. Although PET-CT helped localize thefocus, physiologic uptake in the colon could not be excluded with certainty. In the absence of clinical informa-tion and biopsy, PET-CT may still fall short in differentiating physiologic bowel uptake from a malignantprocess.

Figure 26. Chronic cholecystitis in a patient with papil-lary thyroid cancer who underwent thyroidectomy andradioiodine ablation. Findings at iodine-131 whole-bodyscintigraphy were negative, but the patient was referred forevaluation of elevated thyroglobulin levels. (a) CoronalPET scans demonstrate a slightly hypermetabolic focus inthe lower medial aspect of the liver (arrow) that is sugges-tive of liver metastasis. (bd) Axial PET scan (c) dem-onstrates a focus of uptake (black arrow). CT (b) andPET-CT fusion (d) images reveal that the focus (whitearrow) localizes to the gallbladder, thereby excluding thepossibility of liver metastasis. Note the intense bilateraluptake in the renal collecting system. The patient subse-quently experienced postprandial discomfort, raising thepossibility of chronic cholecystitis, although further testsfor a definitive diagnosis were not performed.


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observed in this anatomic location, choleductalcancer, adenocarcinoma of the gallbladder, andprimary or metastatic disease of the liver shouldbe considered in the differential diagnosis (Fig27). CT correlation is most helpful in delineatinganatomic landmarks and distinguishing a benigngallbladder variant from juxtaposed malignantlesions.

Osteophytes are an outgrowth or excrescenceof bone and usually develop in areas of joints thatare subject to low stress. Osteophytes can demon-strate FDG uptake, which depends on the degreeof metabolic activity. Although osteophytes canoccur at any level of the vertebral column, thosethat are located anteriorly may be confused withthe paravertebral lymph nodes in the absence ofcorrelative imaging (Fig 28).

Unlike glucose, FDG is not reabsorbed by therenal tubules after filtration. Thus, significantFDG accumulation is seen in the intrarenal col-lecting system and renal pelvis. This accumula-tion may interfere with the identification of renalparenchymal or pelvic urothelial tumors. How-ever, contemporaneous anatomic informationprovided by CT allows proper assessment andcharacterization of renal masses (Fig 29).

Focal FDG accumulation in the ureters is acommon finding due to the pooling of radiotracerin the recumbent patient, although the intensityand location of uptake usually allow accurateidentification of the ureters in patients with ab-dominal malignancies. This finding can be misdi-agnosed as pelvic lymph node metastasis or nodallymphoma (Figs 30, 31). Unrecognized renaltransplants may also lead to false-positive findings(20). Although the absence of the native kidneysshould be alarming, simultaneously acquired CTscans delineate the anatomy and help avoid false-positive findings (Fig 32).

Figure 27. Liver metastasis in a 55-year-old man withrectal adenocarcinoma who was referred for posttherapyevaluation. (a) Coronal PET scans demonstrate a hyper-metabolic focus in the lower medial aspect of the liver (ar-row) (cf Fig 32). This lesion is suggestive of liver metas-tasis but can also be attributed to gallbladder activity.(bd) Axial PET scan (c) shows a focus of uptake in theregion of the gallbladder fossa (black arrow). Axial CT (b)and PET-CT fusion (d) images show that this focus(white arrow) is in fact within the hepatic parenchyma. Allthree images also demonstrate a hypermetabolic lesion(arrowhead) that is consistent with liver metastasis.


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Figure 28. Osteophyte in a 65-year-old man with a history of colorectal cancer who was referred for post-therapy evaluation. (a, b) Axial PET scans demonstrate a small focus of FDG uptake in the right paravertebralregion (arrow), a finding that is consistent with a mesenteric or paravertebral lymph node. Note also the uptakein the midabdomen (white arrowhead), a finding that is suggestive of a malignant process in the mesentericlymph nodes. The faint uptake in the anterior abdominal wall (black arrowhead) is consistent with postsurgicalchanges. (ce) Axial PET scan (d) demonstrates a focus of uptake in the right paravertebral region (black ar-row). Axial CT (c) and PET-CT fusion (e) images clearly show that this focus (white arrow) corresponds to anosteophyte in the lateral portion of the vertebral body. The midline abdominal uptake seen on all three images(arrowhead) is consistent with physiologic bowel uptake. PET-CT provided valuable anatomic informationand helped exclude the possibility of metastatic disease in the paravertebral and mesenteric lymph nodes in themidabdomen.

Figure 29. Renal cell carcinoma in a 60-year-old woman with a newly diagnosed renal mass who was re-ferred for presurgical evaluation. (a, b) Axial PET scans demonstrate intense FDG uptake in the midportion ofthe right kidney (arrow), a finding that is indistinguishable from physiologic renal uptake. (ce) Axial PETscan (d) shows uptake in the right kidney (black arrow). Axial CT (c) and PET-CT fusion (e) images helpconfirm that this focus (white arrow) corresponds to the known renal mass, which is most consistent with renalcarcinoma. In the absence of correlative CT, this pattern of uptake can be misinterpreted as physiologic uptakein the intrarenal collecting system. Although evaluation of renal masses with FDG PET is difficult, CT pro-vides valuable information for accurate interpretation of PET findings.


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There is usually no FDG accumulation in theuterus, although focal FDG uptake in the uterusduring menstruation has been described (21).FDG accumulation during menstruation can beattributed to heavy bleeding or to necrotic endo-metrial epithelium due to sudden reduction ofestrogen and progesterone levels at the end of thesecretory phase of the menstrual cycle. It may notbe possible to differentiate this uptake patternfrom uterine carcinoma, even with the help ofPET-CT (Figs 33, 34). However, FDG uptake isusually more irregular, diffuse, and extensive inuterine cancer (Fig 35).

ConclusionsThe primary advantage of PET-CT fusion tech-nology is the ability to correlate findings from twoconcurrent imaging modalities in a comprehen-sive examination that combines anatomic datawith functional and metabolic information. CT

demonstrates exquisite anatomic detail but doesnot provide functional information, whereas FDGPET lacks anatomic landmarks but reveals as-pects of tumor function and allows metabolicmeasurements. Physiologic FDG uptake in non-malignant conditions limits the specificity ofPET, particularly in the posttherapy setting. Hy-brid PET-CT scanners allow PET and CT imagefusion for differentiation of physiologic variantsfrom juxtaposed or mimetic neoplastic lesionsand more accurate tumor localization. Software-based fusion of separately acquired PET and CTscans is more likely to lead to misregistration dueto independent parameters and differences in pa-tient positioning (22,23). In addition, CT permitsrapid acquisition of attenuation correction datafor the PET scan.

Charron et al (24) compared combinedPET-CT scans of different cancers with PETscans alone. In 31% of cases, variable amounts ofnormal physiologic FDG uptake were distin-guished from pathologic FDG uptake. In our ex-perience, the majority of cases in which PET-CT

Figures 30, 31. (30) Physiologic uptake in the renal pelvis in a 66-year-old man with a history of colorectalcancer who had undergone surgery and chemotherapy. Axial PET scan (b) demonstrates a focus of intenseFDG uptake in the left upper quadrant (arrow). This focus of uptake probably represents the renal pelvis; how-ever, mesenteric lymph node involvement cannot be definitively excluded. A focus of increased FDG uptake inthe lateral aspect of the liver (arrowhead) is consistent with liver metastasis. (a, c) Axial CT (a) and PET-CTfusion (c) images help confirm that the focal uptake in the left upper quadrant (arrow) corresponds to the renalpelvis, thereby excluding the possibility of metastatic disease. (31) Recurrent nodal disease in a 49-year-oldman with a history of abdominal lymphoma who had undergone chemotherapy. Axial PET scan (b) demon-strates a focus of intense FDG uptake in the left upper quadrant near the spleen (arrow) (cf Fig 30), a findingthat is consistent with the renal pelvis or recurrent lymphoma in the splenic hilum. (a, c) Axial CT (a) andPET-CT fusion (c) images reveal that the focus of uptake (arrow) corresponds to the splenic hilum, a findingthat is consistent with recurrent lymphoma in the regional lymph nodes.


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Figures 3234. (32) Bone and bone marrow involvement in a 42-year-old woman with a recent diagnosis oflymphoma. (ac) Coronal PET scan (b) demonstrates an area of intense FDG uptake in the left side of thepelvis (black arrow), a finding that is consistent with lymphomatous involvement in the soft tissues of the pelvisor a transplanted kidney. Coronal CT (a) and PET-CT fusion (c) images demonstrate uptake in the left lowerquadrant (white arrow), thereby helping confirm that the uptake is in the renal collecting system of a trans-planted kidney. (df) Axial PET scan (e) shows uptake in the anterior left side of the pelvis (black arrow).Axial CT (d) and PET-CT fusion (f) images help further confirm that this uptake (white arrow) correspondsto a transplanted kidney. In addition, the PET and PET-CT fusion images show multiple hypermetabolic fociin the osseous structures of the pelvis (arrowhead), a finding that is consistent with lymphomatous involve-ment. PET-CT helped differentiate the renal transplant from lymphoma and helped identify other sites of lym-phomatous involvement in the osseous structures. (33) Physiologic uterine uptake in a 40-year-old woman witha history of lymphoma who was referred for posttherapy evaluation. Axial PET scan (b) demonstrates a hyper-metabolic focus in the posterior midline pelvic region (arrow), a finding that is consistent with physiologicFDG uptake in the bowel or colorectal malignancy. (a, c) Axial CT (a) and PET-CT fusion (c) images dem-onstrate that this focus (arrow) corresponds to a retroverted uterus. Further inquiry revealed that the patientwas menstruating at the time of imaging. (34) Uterine carcinoma in a 45-year-old woman with a history ofcolorectal cancer. Axial PET scan (b) demonstrates a hypermetabolic focus in the anterior right pelvic region(arrow), a finding that is consistent with physiologic FDG uptake in the bowel, uterine malignancy, or physi-ologic uptake in the uterus during menstruation. (a, c) Axial CT (a) and PET-CT fusion (c) images demon-strate that this focus (arrow) corresponds to the anterior portion of the uterus. Results of laparoscopy con-firmed malignant invasion of the uterus by colorectal cancer. Although PET-CT helped localize the uptake tothe uterus, differentiation of pathologic from physiologic uptake cannot be achieved on the basis of PET-CTfindings alone without the patients medical history and inquiry regarding menstruation.


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findings either provided more diagnostic confi-dence or changed the interpretation of the studyinvolved the abdomen and pelvis (unpublisheddata). PET-CT is not helpful in differentiating(a) inflammatory changes from neoplastic pro-cesses in lymph node stations or lymphatic tissues(Waldeyer ring or appendix), (b) residual tumorfrom posttherapy changes immediately after sur-gery or radiation therapy, (c) benign thyroid ad-enoma from thyroid cancer, (d) focal physiologicbowel uptake from large or small bowel malignan-cies, or (e) focal physiologic uptake in the uterusduring menstruation from uterine cancer.

Awareness of the pitfalls associated withPET-CT allows accurate image interpretation.The use of CT attenuation correction may cause

diaphragmatic artifacts on reconstructed emissionimages if significant differences in respiratoryphases exist between the two methods. These ar-tifacts may give the spurious impression of sub-diaphragmatic lesions in the lungs and vice versa(25,26). Because metallic devices or implants cancause artifacts on CT scans, CT-based attenua-tion correction may induce artifacts on PET scans(4). The unenhanced portion of the PET-CT fu-sion image is appropriate for localization butcould potentially fail to depict lesions seen at rou-tine contrast materialenhanced CT (27).

In summary, combined PET-CT scans aremore effective than PET scans alone for preciselocalization of neoplastic lesions and differentia-tion of normal variants from juxtaposed neoplas-tic lesions. Hence, PET-CT may significantlyaffect patient treatment by improving diagnosticspecificity more than sensitivity.

Figure 35. Recently diagnosed endometrial can-cer in a 66-year-old woman. (ac) Axial PETscan (b) demonstrates a hypermetabolic focus ofuptake in the midpelvic region (black arrow), a find-ing that is consistent with physiologic FDG uptakein the bowel, uterine malignancy, or physiologic up-take in the uterus during menstruation. AxialCT (a) and PET-CT fusion (c) images demon-strate that this focus (white arrow) corresponds tothe uterine cavity. (df) Sagittal PET scan (e)shows a focus of FDG uptake (black arrow). SagittalCT (d) and PET-CT fusion (f) images help furtherconfirm that the focus of uptake (white arrow) cor-responds to the uterine cavity and involves the entireendometrium. PET-CT helped localize the uptaketo the uterine cavity, and irregular and extensiveFDG uptake strongly suggests endometrial cancer.Nevertheless, PET-CT cannot supplant biopsy forconfirmation.


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This article meets the criteria for 1.0 credit hour in category 1 of the AMA Physicians Recognition Award. To obtaincredit, see accompanying test at http://www.rsna.org/education/rg_cme.html.

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