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the lesion and adjacent structures and CT en-hancement characteristics such as phase and pattern. Most parenchymal organs and the le-sions affecting them have similar attenuation values, which lie within a relatively narrow range, typically 30–80 HU. IV contrast materi-al is used to increase the attenuation difference between normal and abnormal tissue. The re-sult is increased lesion conspicuity, which is of particular importance in lesions in which FDG does not accumulate (Figs. 1–3). Furthermore, IV contrast enhancement can help differenti-ate benign from malignant lesions that have nonspecific FDG PET uptake. Similarly, IV contrast material may outline lesions within vascular structures (Figs. 1 and 4) and local-ize lesions that have increased FDG uptake but that would not be clearly seen on unenhanced CT images because of absence of a contour ab-normality due to their size or would have sim-ilar attenuation to the surrounding structures (Fig. 5). The pyeloureteral system may not be well visualized at PET/CT because urinary excretion of FDG masks lesions. In addition, some renal lesions do not exhibit substantial FDG uptake (Fig. 6). Asymmetric FDG up-take should raise suspicion of transitional cell cancer, renal cancer, lymphoma, and ureteric obstruction or diverticulum. Asymmetric lack of uptake raises suspicion of renal cell cancer and renal cysts (Fig. 7).

Clinical ApplicationPrevious studies [3, 4] have shown that use

of IV contrast material for PET/CT yields considerable additional information. The greatest benefit of diagnostic CT is in the categories of improved localization of FDG uptake and improved local tumor staging, re-sulting in a change in clinical management in 21% of cases, often because of better plan-ning of interventions and radiotherapy.

The use of IV contrast material facilitates discrimination of benign from malignant liver

Oral and IV Contrast Agents for the CT Portion of PET/CT

Carmel G. Cronin1

Priyanka Prakash Michael A. Blake

Cronin CG, Prakash P, Blake MA

1All authors: Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St., Boston, MA 02114. Address correspondence to M. A. Blake (mblake2@partners.org).

Res idents ’ Sect ion • Structured Review Ar t ic le

CMEThis article is available for CME credit.See www.arrs.org for more information.

WEBThis is a Web exclusive article.

AJR 2010; 195:W5–W13

0361–803X/10/1951–W5

© American Roentgen Ray Society

Educational Objectives and Key Points1. IV contrast-enhanced FDG PET/CT has

been found to be superior to contrast-en-hanced CT alone and to unenhanced FDG PET/CT.

2. Use of IV contrast material increases le-sion conspicuity, which is of particular importance in the evaluation of lesions that do not always accumulate FDG.

3. The CT component of PET/CT can be tai-lored to include diagnostic-quality unen-hanced, arterial phase, and delayed imaging as needed to characterize a particular lesion.

4. Use of low-density oral contrast agents can aid in the evaluation of gastrointes-tinal FDG uptake because distending the bowel can reduce FDG uptake and simul-taneously facilitate confident exclusion or diagnosis of luminal and mural disease.

5. High attenuation values associated with the presence of high-density IV contrast material in vascular structures or of con-centrated barium can cause attenuation-correction artifacts during attenuation correction for PET/CT.The benefits of the use of oral and IV con-

trast media for diagnostic CT are well estab-lished. The combination of FDG PET and contrast-enhanced CT has been found to be superior to contrast-enhanced CT alone and to unenhanced FDG PET/CT for precise def-inition of disease in patients with abdominal and pelvic malignant diseases [1, 2]. Pitfalls exist, however, when certain contrast agents cause attenuation-correction anomalies that simulate or mask pathologic changes. We de-scribe and illustrate the use of oral and IV contrast agents for PET/CT and show how to take advantage of their benefits and recog-nize and avoid their pitfalls.

IV Contrast AgentsLesion detection with CT is based on fea-

tures such as attenuation differences between

Keywords: contrast material, IV contrast agents, oral contrast agents, PET/CT, small bowel

DOI:10.2214/AJR.09.3844

Received October 18, 2009; accepted after revision November 27, 2009.

Residents

inRadiology

Cronin et al.Contrast Agents for CT in PET/CT

Residents’ SectionStructured Review Article

W6 AJR:195, July 2010

Cronin et al.

lesions, depending on the enhancement char-acteristics. For example, the enhancement pat-terns of hepatic abscess versus metastasis and hepatocellular carcinoma, all of which can ac-cumulate FDG, can be identified. In the case of liver metastasis, the addition of IV contrast ma-terial leads to significantly better performance in terms of lesion detection, segmental local-ization, and characterization at PET/CT [5]. Furthermore, in disease restaging when steato-sis secondary to chemotherapy or other causes exists, use of contrast enhancement for CT im-proves sensitivity and specificity in the detec-tion of liver metastasis. In the case of regional nodal assessment, contrast-enhanced PET/CT has been found superior to unenhanced PET/CT for precise definition of regional nodal sta-tus in patients with rectal cancer [6]. The same finding may apply to other types of cancer.

Early-detected disease and small-volume disease may not cause a significant attenua-tion difference between the small lesion and the surrounding normal tissue. Furthermore, owing to size, location, and tissue type, small-volume disease may not cause a focal struc-tural or contour abnormality and thus may not produce a CT-appreciable correlate for a fo-cus of FDG uptake at PET/CT. Use of IV con-trast material helps identify pathologic chang-es in structures that may be normal appearing at unenhanced CT. Identification of the pres-ence of this disease may lead to reassessment to a more severe stage of cancer or to a change in prognosis or patient care in the form of al-tering chemoradiotherapy or the surgical reg-imen. Contrast-enhanced PET/CT can deliv-er the comprehensive and precise information needed for surgical planning regarding lesion location and relations to adjacent vessels that unenhanced PET/CT cannot.

Certain tumors and their metastatic le-sions, including mucinous tumors, neuroen-docrine tumors, cystic pancreatic neoplasms, and bronchoalveolar cell cancer, do not reli-ably accumulate FDG. Other tumors, includ-ing hepatocellular and renal cell cancer and even some subtypes of lymphoma, exhibit variable FDG uptake. The causes of lack of uptake include relatively low glucose metab-olism, as in well-differentiated tumors; high mucin content; low proliferation rates; and necrosis (Figs. 3, 4, and 7). Use of IV con-trast material is of particular importance in identification and characterization of these tumors. Knowledge of the tumor types that do not take up FDG and the cell type of the primary tumor is important at the time of PET/CT reporting [7].

The roles and applications of PET/CT are ever increasing. Incidental and noninciden-tal nonmalignant pathologic findings that can be found at PET/CT include diverticu-litis, appendicitis, cholecystitis, Crohn’s dis-ease, and radiation enterocolitis (Fig. 8). The availability of diagnostic-quality contrast-enhanced CT images improves identification and characterization of the process and iden-tification of the extent of disease. The PET portion offers information on the metabolic activity or inflammatory process. Contrast-enhanced CT also aids in the diagnosis of anatomic features and physiologic uptake of FDG (Fig. 9).

LimitationsThe higher attenuation values associat-

ed with use of IV contrast agents, as when a concentrated contrast bolus passes within vascular structures, can cause artifacts when these examinations are used for attenuation correction at PET/CT. The abnormality can be resolved through assessment of the non-attenuation-corrected CT images. It has been suggested [8], however, that such changes in attenuation correction are not statistically or clinically significant. Use of IV contrast ma-terial adds cost and the risk of possible aller-gic reactions and nephrotoxicity to PET/CT, but these disadvantages are considered clini-cally acceptable as part of standard CT pro-tocols for oncologic indications.

Oral Contrast AgentsOral contrast agents distend the bowel, in-

creasing the conspicuity of luminal, mural, and extraluminal bowel disease. Nonspecific intestinal FDG uptake of moderate degree is commonly encountered at PET and PET/CT [9–12] and is thought to be due to peristalsis, bowel mucosal structures, lymphocytic cell concentration, and intestinal bacteria [9, 10]. Use of oral contrast material can aid in the evaluation of this false-positive gastrointes-tinal FDG uptake because distending these segments at CT can negate the effect and si-multaneously allow confident exclusion or diagnosis of luminal and mural disease.

Clinical ApplicationBowel luminal distention is key to preven-

tion of false-positive and false-negative find-ings. Use of oral contrast agents can be of benefit in the interpretation of PET/CT im-ages because it leads to better distention and thus visualization of the large and small bow-el [9] (Figs. 8, 10, and 11). Bowel distention

can increase the conspicuity of bowel disease and adjacent mesenteric and retroperitoneal metastatic deposits and facilitate identifica-tion of synchronous small-bowel and colon-ic lesions. Low-density and neutral contrast agents can be useful in the evaluation of mu-cosal and mural disease and complement IV contrast enhancement; use of positive con-trast enhancement also helps identify struc-tures near the FDG uptake (Fig. 12).

LimitationsThe main limitation of use of oral contrast

material is the effect on attenuation correc-tion. High-density contrast material can cause reconstruction artifacts whereby artificially high FDG uptake is caused by inconsistencies in attenuation correction. This phenomenon is thought to be secondary to contrast desicca-tion in the right colon that results in concen-tration of barium. It also occurs when metallic devices are present [10, 13, 14] (Fig. 12).

Solutions to the attenuation-correction problem include review of the non-attenu-ation-corrected images, which should not show the artificially high FDG uptake, and, preferably, avoiding the issue entirely by us-ing low-density barium. Dilute concentra-tions of positive oral contrast agents may not significantly affect attenuation correc-tion [13]. Water-attenuation oral contrast agents not readily absorbed or desiccated improve image interpretation in 20% cases and do not appear to induce clinically signif-icant artifacts [15]. These contrast agents do not contain glucose and include diatrizoate meglumine and diatrizoate sodium solution 8 mL/500 mL water [9], 0.2% locust bean gum and 2.5% mannitol [14], and low-den-sity barium [9, 13]. Automated segmentation algorithms are being developed to address the problem of attenuation correction.

It was initially thought that use of oral contrast material might lead to increased bowel activity, adversely affecting PET ac-quisition and resulting in misregistration. Several studies, however, have shown no sig-nificant effect of dilute oral contrast material on small-bowel activity. Dizendorf et al. [15] reported FDG uptake in the ascending colon but no correlation with oral contrast loca-tion, and Blake et al. [9] found that distended bowel loops had less FDG PET uptake with lower standardized uptake values.

RecommendationA low-density oral contrast agent should

be used that distends the bowel uniformly

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Contrast Agents for CT in PET/CT

and improves image interpretation without inducing artifacts.

ConclusionWe have outlined and illustrated the ad-

vantages and disadvantages of oral and IV contrast agents at PET/CT. Understanding of contrast behavior aids in recognition of and limits the occurrence of PET/CT artifacts. Although both IV and oral contrast adminis-tration involve extra cost, contrast agents are routinely used in clinical CT. We believe the advantages of both types of agent in PET/CT outweigh the disadvantages and facilitate a fully comprehensive diagnostic examination.

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A

Fig. 1—40-year-old man with cardiac sarcoma that has been partially debulked. Case illustrates utility of IV contrast material in visualization of possibly life-threatening tumors, tumor thrombi, and thrombosis within vascular structures, which may not be evident on PET images and would not be seen without contrast administration.A, Axial unenhanced CT image does not show left atrial sarcoma.B, Contrast-enhanced CT image shows left atrial sarcoma (arrow).C, FDG PET image does not show tumor.

CB

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A

C

Fig. 2—60-year-old man with hepatic metastatic lesion of neuroendocrine tumor (arrows).A and B, Arterial phase PET/CT image shows lesion (arrows), but corresponding PET image does not.C and D, Delayed PET/CT and PET images do not show lesions.

B

D

A

C

Fig. 3—56-year-old woman with mucinous metastasis to liver.A and B, Unenhanced CT (A) and fused PET/CT (B) images do not show mucinous metastatic lesion (arrow) or increased FDG uptake.C and D, Contrast-enhanced CT (C) and PET/CT (D) images show conspicuous lesion (arrow).

B

D

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A

Fig. 4—53-year-old man with osteosarcoma with tumor thrombus.A, Contrast-enhanced CT image clearly shows tumor thrombosis (arrow) because it is outlined with contrast material.B, Fused PET/CT image shows increased FDG uptake by thrombus (arrow).

B

A

Fig. 5—60-year-old man with increasing carcinoembryonic antigen level who has undergone abdominoperineal resection, chemotherapy, and radiation therapy for adenocarcinoma.A, Axial contrast-enhanced CT image shows focus of enhancement in anterior abdominal wall.B, PET image shows focus (arrow) of increased FDG uptake.

B

A

Fig. 6—60-year-old man with squamous cell lung cancer undergoing staging PET/CT. Biopsy finding was metastasis of squamous cell carcinoma.A, Unenhanced CT image does not clearly show fullness (arrow) in lower part of right kidney.B, Contrast-enhanced CT image clearly shows mass (arrow) in right renal pelvis.

(Fig. 6 continues on next page)B

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C

E

Fig. 6 (continued)—60-year-old man with squamous cell lung cancer undergoing staging PET/CT. Biopsy finding was metastasis of squamous cell carcinoma.C–F, Axial and coronal PET/CT and FDG PET images do not clearly show lesions in kidney (arrow) because radiotracer is excreted into urinary system, causing normal uptake in ureter. Asymmetric renal FDG uptake should heighten level of suspicion of urothelial malignancy, metastasis, and lymphoma.

D

F

A

Fig. 7—Examples of conflicting FDG uptake of similar lesions.A–D, 60-year-old man with right renal cyst and left exophytic mass (arrow, A and C) suspicious for renal cell carcinoma and undergoing staging PET/CT for lymphoma. Axial and coronal fused PET/CT and PET images do not show FDG PET uptake. Case shows that renal cell cancer may not show FDG PET uptake, so careful examination of contrast-enhanced CT images is important for its detection and evaluation.

(Fig. 7 continues on next page)

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A

Fig. 8—40-year-old woman undergoing radiation therapy for cervical cancer.A and B, Staging PET/CT (A) and PET (B) images show small-bowel wall thickening and enhancing mucosa and increased FDG PET uptake (arrow, A) consistent with radiation enteritis.C, Contrast-enhanced CT image shows neutral intraluminal enhancement (arrow), facilitating assessment of enhancing small-bowel mucosa in active enteritis.

CB

E

I

Fig. 7 (continued)—Examples of conflicting FDG uptake of similar lesions.E–I, 65-year-old man with renal lesion (arrow, E, F, and H) similar to that in A–D, history of lymphoma, and finding of B-cell lymphoma at CT-guided biopsy. Axial CT image (E) shows location of lesion, and axial and coronal fused PET/CT and PET images (F–I) show intense FDG PET uptake.

HGF

A

Fig. 9—43-year-old woman undergoing restaging of lymphoma.A and B, Axial contrast-enhanced CT (A) and fused PET/CT (B) images show focus of FDG uptake (arrow, A) in right side of pelvis. Finding is consistent with corpus luteum cyst diagnosed on basis of appearance at contrast-enhanced CT.

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Fig. 11—72-year-old man with history of gastrointestinal stromal tumor.A, Axial fused PET/CT image does not clearly show tumor recurrence (arrow) because adjacent small-bowel loops are collapsed without intraluminal contrast. Tumor is not FDG avid.B, Axial oral and IV contrast-enhanced CT image shows recurrent tumor (arrow) better than does A because bowel is distended with intraluminal contrast material.

B

A

E

Fig. 10—60-year-old man with history of lymphoma.A–D, Axial and coronal fused PET/CT and PET images show focus of FDG uptake (arrow) in descending colon without CT correlate, but colon is partially collapsed and stool filled.E–H, Follow-up PET/CT and PET images show colon is distended and less stool filled. Polyp (arrow) corresponding to FDG uptake also is evident. Polyp was removed at colonoscopy; pathologic finding was dysplastic polyp.

D

H

C

G

B

F

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C

Fig. 12—58-year-old woman undergoing PET/CT for restaging of colorectal cancer.A and B, Axial fused PET/CT (A) and PET (B) images show attenuation-correction artifact (arrow) in region of high-density barium.C and D, Axial fused PET/CT (C) and PET (D) images without attenuation correction do not show FDG PET uptake in region of barium (arrow, D), indicating spurious artifactual uptake in A and B.

B

D

F O R Y O U R I N F O R M A T I O N

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