- Email: [email protected]
Computerized Tomography Enterography and Its Role in Small-Bowel Imaging
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2008;6:283–289
CLINICAL IMAGING Computerized Tomography Enterography and Its Role in Small-Bowel Imaging JOEL G. FLETCHER,* JAMES HUPRICH,* EDWARD V. LOFTUS, JR,‡ DAVID H. BRUINING,‡ and JEFF L. FIDLER* *Department of Radiology, and ‡Division of Gastroenterology & Hepatology, Mayo Clinic Rochester, Rochester, Minnesota
Computerized tomography enterography is being adopted rapidly by many institutions as the primary technique used to image the small bowel. The purpose of this article is to summarize how the examination is performed, and to specify appropriate indications and alternatives, performance characteristics, and anticipated future developments.
C
omputerized tomography (CT) enterography is a CT of the abdomen and pelvis designed to image the lumen and wall of the small bowel. Such optimization requires luminal distention (with a larger than normal volume of ingested oral contrast material), high-resolution imaging, and the appropriate phase of intravenous contrast enhancement. Although positive (high attenuation) oral contrast can be used, the oral contrast used for CT enterography is generally a neutral enteric contrast, meaning that its CT attenuation is similar to water. When used with iodinated intravenous contrast agents at CT enterography, neutral oral contrast agents maximize the conspicuity of hypervascular pathologies such as inflamed bowel loops or masses. For a CT enterography examination, 1500 to 2000 mL of oral contrast is ingested over approximately 60 minutes before the examination to distend the small bowel. Polyethylene glycol solution and low-concentration barium suspension (which contains sorbitol) are the most commonly used oral contrast agents because they result in superior small-bowel distention relative to water, but may cause self-limited diarrhea or gas shortly after the examination.1 Although the examination is highly robust in an outpatient setting, gastroenterologists should be aware that hospitalized patients or patients who are unable to drink large volumes of contrast usually cannot undergo CT enterography successfully. Contraindications also include severe contrast dye allergies and significant renal insufficiency. To adequately visualize the small-bowel lumen and wall at CT enterography, slice thicknesses of 3 mm or less are used in an overlapping fashion. Because of the increased number of images generated during a CT enterography examination, gastroenterologists will find it most helpful to review images in an electronic fashion, with routine coronal images generated, to facilitate visualization of tortuous small-bowel loops and fistulae. Maximal mural enhancement of the normal small bowel occurs 50 seconds after intravenous contrast material injection or 14 seconds after peak aortic enhancement2; CT imaging normally is initiated at this time. However, CT scanning up to 70 seconds after contrast injection permits routine hepatic
phase imaging, but does not compromise the ability to identify Crohn’s disease.3,4 Imaging of the small bowel may be performed in multiple vascular phases in the setting of occult gastrointestinal (GI) bleeding (see later).
Normal Findings at Computerized Tomography Enterography Gastroenterologists should be familiar with the normal appearance of the small bowel at CT enterography. Although the jejunum possesses the valvulae conniventes, which are seen as thin, closely spaced folds resulting in a feathery appearance, the ileum possesses few, if any, folds. The small-bowel wall should be less than 3 mm in thickness when the lumen is distended by fluid. When imaging is performed in the enteric phase of maximal small-bowel enhancement, the jejunum normally will have greater attenuation than the ileum, with a gradual decrease in attenuation of the enhancing small-bowel wall as one moves toward the terminal ileum. Intramural fat can be a normal finding in the terminal ileum, but is a sign of chronic inflammation elsewhere in the small bowel. In Crohn’s disease, it often is accompanied by mucosal hyperenhancement, pointing to both active and chronic inflammation. The jejunum occasionally is collapsed at enterography, which can be a normal finding in the minority of cases, but the ileum almost always is distended adequately.5 Notwithstanding this weakness, CT enterography is acceptable for most small-bowel indications, particularly given the fact that many small-bowel diseases, such as Crohn’s, or masses will mildly obstruct the lumen as a result of transmural inflammation, edema, or involvement. Moreover, mural and mesenteric pathologies often are occult at luminal imaging such as fluoroscopy or capsule endoscopy.
Imaging Findings at Computerized Tomography Enterography Although multiple indications exist for CT enterography (Table 1), the overwhelming indication is known or suspected Crohn’s disease. In this setting, the goal of CT enterography is to identify active Crohn’s disease, CT findings Abbreviations used in this paper: CT, computerized tomography; GI, gastrointestinal; MR, magnetic resonance. © 2008 by the AGA Institute 1542-3565/08/$34.00 doi:10.1016/j.cgh.2007.12.049
284
FLETCHER ET AL
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 3
Table 1. Indications for CT Enterography Type of examination
Indication
Single-phase CT enterography
Rule out Crohn’s disease Stage Crohn’s disease activity Rule out small-bowel mass Assess for complications of celiac sprue Unexplained diarrhea Occult GI bleeding
Multiphase CT enterography
indicating bowel wall and adjacent mesenteric inflammation, fistulizing disease (including abscess), small-bowel obstruction (if present), and any extraintestinal manifestations. Findings of active inflammatory Crohn’s disease include mural hyperenhancement, thickening, and stratification, in addition to peri-enteric fat stranding and the comb sign. Mural hyperenhancement is segmental attenuation greater than adjacent small-bowel loops and is the most sensitive CT finding for active inflammatory Crohn’s disease.6 Mural thickening is considered present when the small-bowel wall is greater than 3 mm in thickness and the lumen is filled with oral contrast. Although segmental mural hyperenhancement alone is a nonspecific finding for Crohn’s disease, asymmetric mural enhancement and thickening are pathognomonic for Crohn’s disease (Figure 1). Mural stratification refers to a laminated appearance to the bowel wall and is seen with more advanced small-bowel inflammation (Figure 2).7 With mural stratification, the mucosa is hyperenhancing, with the submucosa being of lower attenuation representing edema (water attenuation) or inflammatory infiltrate (soft-tissue attenuation). Because the transmural inflammation of Crohn’s disease extends into the mesentery, there is stranding in the peri-enteric fat, which is associated with increased serum concentrations of C-reactive protein.8 Fibro-fatty proliferation is distinct from increased fat density and refers to the surgical and imaging findings of fatty proliferation along the mesenteric side of the bowel, which may participate in the Crohn’s inflammatory response, and typically reflects chronic Crohn’s inflammation.9 The comb sign heralds significant inflammation in the small bowel or colon and refers to engorged vasa recta (or the vessels supplying the bowel).10 When these vessels become enlarged during acute inflammation, they resemble the teeth of a comb (Figure 2). The comb sign is associated with increased serum C-reactive protein levels and length of hospital stay during Crohn’s flares.11 Penetrating disease is seen frequently at CT enterography in the Crohn’s disease population (up to 20% of the time12). Penetrating complications, particularly entero-enteric and enterocolic fistulas, frequently are unsuspected clinically yet identified incidentally during CT enterography (Figure 2). Fistulas generally appear as hyperenhancing extra-enteric tracks with or without air or fluid.13 Although routine CT can detect fistulae and abscess,14 CT enterography can describe the type of fistula (ie, its connections), its size, whether or not it is associated with proximal obstruction, whether it arises from active inflammatory disease, or whether it is associated with abscess.13 In our experience, smaller fistulas associated with active disease will resolve with medical treatment. Perianal fistulas or fistulas arising in the postoperative setting unassociated with Crohn’s disease may not be hyperenhancing, potentially because of their lack of acute inflammatory response.
In a large retrospective review of patients, Bruining et al12 found that extraintestinal manifestations of Crohn’s disease were seen in about 12% to 15% of patients, including sacroiliitis, nephrolithiasis, and portal or mesenteric vein thrombosis. Moreover, non–inflammatory bowel disease–related abnormalities including pulmonary nodules, adrenal nodules, lymphoma, and other malignancies were detected. Certainly, patients with Crohn’s disease also have an increased susceptibility to enteric and hepatic malignancies and lymphoma.15 CT enterography also can be used for a variety of nonCrohn’s indications. Besides active Crohn’s disease, the most common finding at CT enterography is a mass. Masses can include carcinoid tumors, adenocarcinomas, lymphomas, GI stromal tumors, and Meckel’s diverticula (and their complications). Carcinoid tumors are the most frequently seen tumors in our practice, and are seen as hyperenhancing polypoid or carpet lesions that can invade the mesentery, with characteristic softtissue attenuation mesenteric metastases (Figure 3). The appearance of other small-bowel tumors and celiac disease at CT enterography has been described elsewhere.6
Performance of Computerized Tomography Enterography for Active Crohn’s Disease Before 2000, sensitivity estimates of CT enterography for active inflammatory Crohn’s disease were based largely on surgical or fluoroscopic series without a reliable endoscopic
Figure 1. Asymmetric mural hyperenhancement in Crohn’s disease. Note additional presence of intramural fat, indicating there also has been chronic inflammation.
March 2008
CT ENTEROGRAPHY
285
Figure 2. (A) Enterocolic fistula (arrows) arising from the top of an inflamed jejunal loop (large arrowhead) and connecting to the hepatic flexure. (B) The proximal jejunum shows mural stratification (large arrow), with the distal jejunum being decompressed (arrowhead). (B) Engorged vasa recta (or the comb sign; small arrows) supply the (C) mildly inflamed proximal jejunal loop (arrows), which contains an enterolith (arrowhead).
reference standard. Since that time, most assessments have shown a sensitivity for active inflammatory Crohn’s disease on the order of 80% to 90%,3,4,16,17 with some showing sensitivity around 60%.18,19 When quantitative and visual measures of segmental hyperenhancement are compared with endoscopy and small-bowel biopsy, the odds ratio for active disease is greater than 10, and the sensitivity for histologic inflammation is about 80%, similar to endoscopic assessment alone.3 We recently conducted a head-to-head trial comparing CT enterography, capsule endoscopy, ileocolonoscopy, and small-bowel
follow-through in 42 patients with suspected or known Crohn’s disease. The sensitivity of capsule endoscopy and CT enterography was almost identical (83% and 82%, respectively), with the specificity of CT being significantly higher (89% vs 53%; P ⫽ .02).16 In addition, although we excluded patients with symptoms of obstructive disease, 17% of the patients had asymptomatic strictures, which precluded capsule assessment. In a secondary analysis of 27 patients who received both capsule endoscopy and CT enterography, capsule endoscopy identified 2 additional patients with active Crohn’s disease who had no
286
FLETCHER ET AL
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 3
endoscopy, the capsule failed to reach the colon in 25% of the patients. In the Voderholzer et al18 experience, only 1 of 41 patients had a retained capsule. In summary, CT enterography is moderately sensitive and highly accurate for active Crohn’s disease and can exclude significant strictures that may result in retained capsules. Nevertheless, capsule endoscopy may identify some patients with mild active inflammatory disease occult at CT imaging.
Clinical Contribution of Computerized Tomography Enterography CT enterography provides objective evidence of active Crohn’s disease or small-bowel mass proximal to the reach of the endoscope, as well as providing visualization of the mesentery and liver. Studies examining the clinical benefit of CT enterography are beginning to emerge.12,20 Higgins et al20 recently had gastroenterologists review clinical information before the revelation of CT enterography findings, to make a clinical assessment on whether or not patients would benefit from corticosteroid treatment. Subsequent to these predictions, CT enterography information was provided. Their study showed that CT enterography did not replicate original clinical impressions, and changed the impression of corticosteroid benefit in 61% of these patients. Similarly, in our experience, approximately half of the patients with penetrating Crohn’s disease had no symptoms or signs of a fistula at their initial clinical assessment.21 Detection of unsuspected fistulizing Crohn’s disease resulted in either escalation of medical therapy or surgical/procedural intervention in the majority of these patients. Prospective trials detailing the effect of CT enterography results on clinical decision making are needed.
Multiphase Computerized Tomography Enterography for Occult Gastrointestinal Bleeding
Figure 3. Ileal carcinoid with typical mesenteric metastasis. (A) Axial image shows an ileal loop with focal mural thickening and enhancement (arrowhead) associated with a soft-tissue mesenteric mass with excentric calcifications and stranding to adjacent small-bowel loops (arrow). (B) Coronal image shows similar findings (bowel loops, arrowheads; mesenteric metastasis, arrow). The surgical specimen showed a cluster of mural carcinoids with metastases to local nodes.
evidence of Crohn’s disease at CT imaging, but again showed significantly lower specificity (53% vs 100%). Although a recent trial by Voderholzer et al18 showed superior performance of capsule endoscopy versus CT enteroclysis (ie, with a nasojejunal tube) for patients undergoing both tests, 27% of their study population was excluded from undergoing capsule endoscopy because of small-bowel strictures at CT enteroclysis. Moreover, in the 41 patients who underwent CT enterography and capsule
Although earlier radiologic literature was disappointing for the ability of CT to detect the causes of occult GI bleeding,22 recent work with multiphase CT enterography has shown that CT has an important role to play in this clinical setting. Because of the requirement for rapid multiphase imaging, this technique is best performed on a 64-channel (or higher) CT scanner.23 Neutral oral contrast and iodinated intravenous contrast are the same as for a single-phase examination. Scanning is performed from the diaphragm to the symphysis pubis during each of 3 phases, with scanning initiated when a region-ofinterest attenuation threshold in the aorta is reached. The first phase is a bolus-triggered arterial phase, followed by an enteric phase (20 seconds after trigger), and a delayed phase (70 seconds after trigger). Once the region-of-interest trigger threshold is reached by iodinated contrast arriving in the aorta, the arterial phase is initiated after a short 6-second delay. During the arterial phase, vascular ectasias such as AVMs and their early draining veins are seen. The enteric phase often highlights enhancing tumors, with delayed images showing that iodinated contrast is accumulating in the small-bowel lumen, indicating active bleeding (Figure 4). Huprich et al23 showed the benefit of CT enterography in identifying multiple small-bowel tumors and vascular lesions detected and undetected at capsule endoscopy, with a larger prospective study underway. In the
March 2008
CT ENTEROGRAPHY
287
Figure 4. Active bleeding at multiphase CT enterography. (A) Arterial, (B) enteric, and (C) delayed phase images show progressive focal contrast accumulation (arrows in A, B, and C) in an ileal angiodysplasia confirmed at intraoperative endoscopy. (C) Additional focus (arrows) of contrast on delayed image is also presumed to be active bleeding.
setting of occult GI bleeding, CT enterography and capsule endoscopy are not competitive imaging modalities but complementary ones, because findings from each imaging study may be nonspecific.
Appropriate Use of Cross-Sectional Alternatives to Computerized Tomography Enterography Table 2 lists alternative tests preferred over CT enterography in certain clinical settings. Because CT and magnetic resonance (MR) enteroclysis (after nasojejunal tube placement) permit the rapid infusion of large volumes of enteric contrast at faster rates, these examinations better show small-bowel caliber changes reflecting low-grade obstruction. Similarly, because CT
enterography can result in collapsed jejunal loops, we perform CT or MR enteroclysis to investigate further nonspecific capsule endoscopy findings in the jejunum. CT enteroclysis is not performed for patients with known or suspected Crohn’s disease or occult GI bleeding because of the acceptable performance characteristics of CT enterography, patient objections to, and time required for nasojejunal tube placement. Because of the marked increase in signal differences between pathology and anatomic structures near the anus, we perform MR imaging to stage perianal disease or investigate potential J-pouch complications after ileal pouch–anal anastomosis. MR enterography is preferred to CT enterography when imaging to determine if inflammed bowel loops or fistulas have responded to therapy (owing to lack of radiation), and in patients with contraindica-
288
FLETCHER ET AL
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 3
Table 2. Cross-Sectional Alternatives to CT Enterography and Suggested Indications
Table 3. Relative Strengths and Weaknesses of MR vs CT Enterography
Type of examination
Indication
MR
Strengths
CT
MR or CT enteroclysis
Suspected low-grade partial small-bowel obstruction Questionable or nonspecific capsule endoscopy findings, particularly if jejunal Staging of perianal fistulas Suspected complications after ileal pouch–anal anastomosis Monitoring response to therapy Fluoroscopic, dynamic characterization of stenotic or adhesive lesions Contraindications to CT
⫹⫹⫹ ⫹⫹⫹ ⫹⫹ ⫹⫹ ⫹ ⫹⫹⫹ ⫹⫹⫹ ⫹ ⫹
Visualize bowel wall Bowel wall signal Mesenteric signal to noise ratio Spatial resolution Temporal resolution Ionizing radiation Dynamic characterization of stenotic lesions Amount of data Length of examination
⫹⫹⫹ ⫹⫹ ⫹⫹⫹ ⫹⫹⫹ ⫹⫹⫹ ⫺ ⫺ ⫹⫹ ⫹⫹
Pelvic MR
MR enterography
tions to CT. In addition, there are several advantages to MR imaging not seen at CT enterography, which include the ability to perform MR fluoroscopy to observe bowel peristalsis in real time and dynamically characterize stenotic lesions.24 Table 3 lists the relative strengths of CT versus MR enterography. In our experience, CT enterography is used frequently as a firstline test given its speed (scanning takes seconds rather than 45– 60 min), robustness (it rarely fails to generate high-quality images), spatial and temporal resolution (which are important
NOTE. Relative strength: ⫹⫹⫹ ⬎ ⫹⫹ ⬎ ⫹; weekness: “–.”
for visualizing small masses and fistulizing disease), and CT scanner access.
The Future We believe that CT enterography will continue to be incorporated into wider clinical measures of Crohn’s disease, particularly given the promise that objective CT findings such as mural hyperenhancement can be quantitated.3,25 Moreover, we anticipate that continuing technical developments in CT image reconstruction will substantially reduce the radiation
Figure 5. Potential for dramatic radiation dose reduction at CT enterography shown using dual-energy CT enterography. (A) Normal dose CT enterography is achieved by combining the output from 2 radiograph tubes (each with half the normal dose), and shows mild wall thickening and mural hyperenhancement in the ascending colon (arrow) compared with the normal enhancement in the descending colon (arrowhead). (B) The 140-kV tube and (C) the 80-kV tube also are diagnostic, but were performed at half the radiation dose. Note the increased conspicuity of the iodine signal showing mural enhancement at the lower tube energy.
March 2008
dose at CT enterography, which is already the same or less than routine abdominal CT. The use of dual-source CT systems will permit wider use of low-energy CT scanning, which will increase the conspicuity of hypervascular inflammation and permit further radiation dose reduction (Figure 5). Developments in MR technology will facilitate rapid growth of MR enterography. Finally, we believe that there will be routine correlation of CT enterography and capsule endoscopy findings, and that these examinations will be used in combination in more patients, combining the exquisite mucosal visualization of capsule endoscopy with the mural and mesenteric images of CT enterography. References 1. Young B, Fletcher J, Booya F, et al. Head-to-head comparison of oral contrast agents for cross-sectional enterography: small bowel distention, timing and side effects. J Comput Assist Tomogr 2008;32:32–38. 2. Schindera ST, Nelson RC, DeLong DM, et al. Multi-detector row CT of the small bowel: peak enhancement temporal window— initial experience. Radiology 2007;243:438 – 444. 3. Bodily KD, Fletcher JG, Solem CA, et al. Crohn disease: mural attenuation and thickness at contrast-enhanced CT enterography— correlation with endoscopic and histologic findings of inflammation. Radiology 2006;238:505–516. 4. Booya F, Fletcher JG, Huprich JE, et al. Active Crohn disease: CT findings and interobserver agreement for enteric phase CT enterography. Radiology 2006;241:787–795. 5. Wold P, Fletcher J, Johnson C, et al. Assessment of small bowel Crohn disease: noninvasive perioral enterography compared with other imaging methods and endoscopy-feasibility study. Radiology 2003;229:275–281. 6. Paulsen SR, Huprich JE, Fletcher JG, et al. CT enterography as a diagnostic tool in evaluating small bowel disorders: review of clinical experience with over 700 cases. Radiographics 2006;26: 641– 662. 7. Macari M, Megibow AJ, Balthazar EJ. A pattern approach to the abnormal small bowel: observations at MDCT and CT enterography. AJR Am J Roentgenol 2007;188:1344 –1355. 8. Colombel JF, Solem CA, Sandborn WJ, et al. Quantitative measurement and visual assessment of ileal Crohn’s disease activity by computed tomography enterography: correlation with endoscopic severity and C reactive protein. Gut 2006;55:1561–1567. 9. Desreumaux P, Ernst O, Geboes K, et al. Inflammatory alterations in mesenteric adipose tissue in Crohn’s disease. Gastroenterology 1999;117:73– 81. 10. Meyers MA, McGuire PV. Spiral CT demonstration of hypervascularity in Crohn’s disease: “vascular jejunization of the ileum” or the “comb sign”. Abdom Imaging 1995;20:327–332. 11. Lee S, Ha H, Yang S, et al. CT of prominent pericolic or perienteric vasculature in patients with Crohn’s disease: correlation with
CT ENTEROGRAPHY
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24. 25.
289
clinical disease activity and findings on barium studies. AJR Am J Roentgenol 2002;179:1029 –1036. Bruining DH, Fletcher JG, Tremaine WJ, et al. Prevalence of penetrating disease and extraintestinal manifestations of Crohn’s disease with CT enterography. Gastroenterology 2007; 132:650. Vogel J, da Luz Moreira A, Baker M, et al. CT Enterography for Crohn’s disease: accurate preoperative diagnostic imaging. Dis Colon Rectum 2007;50:1761–1769. Maconi G, Sampietro GM, Parente F, et al. Contrast radiology, computed tomography and ultrasonography in detecting internal fistulas and intra-abdominal abscesses in Crohn’s disease: a prospective comparative study. Am J Gastroenterol 2003;98: 1545–1555. Bernstein CN, Blanchard JF, Kliewer E, et al. Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer 2001;91:854 – 862. Solem CA, Loftus LV, Fletcher JG, et al. Small bowel (SB) imaging in Crohn’s disease (CD): a prospective, blinded, 4-way comparison trial. Gastroenterology 2005;128(Suppl 2):A-74. Hassan C, Cerro P, Zullo A, et al. Computed tomography enteroclysis in comparison with ileoscopy in patients with Crohn’s disease. Int J Colorectal Dis 2003;18:121–125. Voderholzer WA, Beinhoelzl J, Rogalla P, et al. Small bowel involvement in Crohn’s disease: a prospective comparison of wireless capsule endoscopy and computed tomography enteroclysis. Gut 2005;54:369 –373. Hara A, Leighton J, Sharma V, et al. Small bowel: preliminary comparison of capsule endoscopy with barium study and CT. Radiology 2004;230:260 –265. Higgins PD, Caoili E, Zimmermann M, et al. Computed tomographic enterography adds information to clinical management in small bowel Crohn’s disease. Inflamm Bowel Dis 2007;13:262–268. Booya F. CT enterography findings in fistulizing Crohn’s disease (abstract 1982 GI-e). In: Radiological Society of North America Scientific Assembly and Annual Meeting, Chicago, IL, 2004:768. Hara AK, Leighton JA, Sharma VK, et al. Small bowel: preliminary comparison of capsule endoscopy with barium study and CT. Radiology 2004;230:260 –265. Huprich JE, Fletcher JG, Alexander J, et al. Obscure GI bleeding: 64-channel multiphase, multiplanar CT enterography has a role. Radiology 2008;246:562–571. Fidler J. MR imaging of the small bowel. Radiol Clin North Am 2007;45:317–331. Loftus E. Objective measures of disease activity: alternatives to symptom indices. Rev Gastroenterol Dis 2007;7:S8 –S16.
Address requests for reprints to: J. G. Fletcher, MD, Department of Radiology, 200 First St. SW, Mayo Building, West 2-B, Rochester, Minnesota 55905. e-mail: fl[email protected]; fax: (507) 2664609.
CLINICAL IMAGING Computerized Tomography Enterography and Its Role in Small-Bowel Imaging JOEL G. FLETCHER,* JAMES HUPRICH,* EDWARD V. LOFTUS, JR,‡ DAVID H. BRUINING,‡ and JEFF L. FIDLER* *Department of Radiology, and ‡Division of Gastroenterology & Hepatology, Mayo Clinic Rochester, Rochester, Minnesota
Computerized tomography enterography is being adopted rapidly by many institutions as the primary technique used to image the small bowel. The purpose of this article is to summarize how the examination is performed, and to specify appropriate indications and alternatives, performance characteristics, and anticipated future developments.
C
omputerized tomography (CT) enterography is a CT of the abdomen and pelvis designed to image the lumen and wall of the small bowel. Such optimization requires luminal distention (with a larger than normal volume of ingested oral contrast material), high-resolution imaging, and the appropriate phase of intravenous contrast enhancement. Although positive (high attenuation) oral contrast can be used, the oral contrast used for CT enterography is generally a neutral enteric contrast, meaning that its CT attenuation is similar to water. When used with iodinated intravenous contrast agents at CT enterography, neutral oral contrast agents maximize the conspicuity of hypervascular pathologies such as inflamed bowel loops or masses. For a CT enterography examination, 1500 to 2000 mL of oral contrast is ingested over approximately 60 minutes before the examination to distend the small bowel. Polyethylene glycol solution and low-concentration barium suspension (which contains sorbitol) are the most commonly used oral contrast agents because they result in superior small-bowel distention relative to water, but may cause self-limited diarrhea or gas shortly after the examination.1 Although the examination is highly robust in an outpatient setting, gastroenterologists should be aware that hospitalized patients or patients who are unable to drink large volumes of contrast usually cannot undergo CT enterography successfully. Contraindications also include severe contrast dye allergies and significant renal insufficiency. To adequately visualize the small-bowel lumen and wall at CT enterography, slice thicknesses of 3 mm or less are used in an overlapping fashion. Because of the increased number of images generated during a CT enterography examination, gastroenterologists will find it most helpful to review images in an electronic fashion, with routine coronal images generated, to facilitate visualization of tortuous small-bowel loops and fistulae. Maximal mural enhancement of the normal small bowel occurs 50 seconds after intravenous contrast material injection or 14 seconds after peak aortic enhancement2; CT imaging normally is initiated at this time. However, CT scanning up to 70 seconds after contrast injection permits routine hepatic
phase imaging, but does not compromise the ability to identify Crohn’s disease.3,4 Imaging of the small bowel may be performed in multiple vascular phases in the setting of occult gastrointestinal (GI) bleeding (see later).
Normal Findings at Computerized Tomography Enterography Gastroenterologists should be familiar with the normal appearance of the small bowel at CT enterography. Although the jejunum possesses the valvulae conniventes, which are seen as thin, closely spaced folds resulting in a feathery appearance, the ileum possesses few, if any, folds. The small-bowel wall should be less than 3 mm in thickness when the lumen is distended by fluid. When imaging is performed in the enteric phase of maximal small-bowel enhancement, the jejunum normally will have greater attenuation than the ileum, with a gradual decrease in attenuation of the enhancing small-bowel wall as one moves toward the terminal ileum. Intramural fat can be a normal finding in the terminal ileum, but is a sign of chronic inflammation elsewhere in the small bowel. In Crohn’s disease, it often is accompanied by mucosal hyperenhancement, pointing to both active and chronic inflammation. The jejunum occasionally is collapsed at enterography, which can be a normal finding in the minority of cases, but the ileum almost always is distended adequately.5 Notwithstanding this weakness, CT enterography is acceptable for most small-bowel indications, particularly given the fact that many small-bowel diseases, such as Crohn’s, or masses will mildly obstruct the lumen as a result of transmural inflammation, edema, or involvement. Moreover, mural and mesenteric pathologies often are occult at luminal imaging such as fluoroscopy or capsule endoscopy.
Imaging Findings at Computerized Tomography Enterography Although multiple indications exist for CT enterography (Table 1), the overwhelming indication is known or suspected Crohn’s disease. In this setting, the goal of CT enterography is to identify active Crohn’s disease, CT findings Abbreviations used in this paper: CT, computerized tomography; GI, gastrointestinal; MR, magnetic resonance. © 2008 by the AGA Institute 1542-3565/08/$34.00 doi:10.1016/j.cgh.2007.12.049
284
FLETCHER ET AL
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 3
Table 1. Indications for CT Enterography Type of examination
Indication
Single-phase CT enterography
Rule out Crohn’s disease Stage Crohn’s disease activity Rule out small-bowel mass Assess for complications of celiac sprue Unexplained diarrhea Occult GI bleeding
Multiphase CT enterography
indicating bowel wall and adjacent mesenteric inflammation, fistulizing disease (including abscess), small-bowel obstruction (if present), and any extraintestinal manifestations. Findings of active inflammatory Crohn’s disease include mural hyperenhancement, thickening, and stratification, in addition to peri-enteric fat stranding and the comb sign. Mural hyperenhancement is segmental attenuation greater than adjacent small-bowel loops and is the most sensitive CT finding for active inflammatory Crohn’s disease.6 Mural thickening is considered present when the small-bowel wall is greater than 3 mm in thickness and the lumen is filled with oral contrast. Although segmental mural hyperenhancement alone is a nonspecific finding for Crohn’s disease, asymmetric mural enhancement and thickening are pathognomonic for Crohn’s disease (Figure 1). Mural stratification refers to a laminated appearance to the bowel wall and is seen with more advanced small-bowel inflammation (Figure 2).7 With mural stratification, the mucosa is hyperenhancing, with the submucosa being of lower attenuation representing edema (water attenuation) or inflammatory infiltrate (soft-tissue attenuation). Because the transmural inflammation of Crohn’s disease extends into the mesentery, there is stranding in the peri-enteric fat, which is associated with increased serum concentrations of C-reactive protein.8 Fibro-fatty proliferation is distinct from increased fat density and refers to the surgical and imaging findings of fatty proliferation along the mesenteric side of the bowel, which may participate in the Crohn’s inflammatory response, and typically reflects chronic Crohn’s inflammation.9 The comb sign heralds significant inflammation in the small bowel or colon and refers to engorged vasa recta (or the vessels supplying the bowel).10 When these vessels become enlarged during acute inflammation, they resemble the teeth of a comb (Figure 2). The comb sign is associated with increased serum C-reactive protein levels and length of hospital stay during Crohn’s flares.11 Penetrating disease is seen frequently at CT enterography in the Crohn’s disease population (up to 20% of the time12). Penetrating complications, particularly entero-enteric and enterocolic fistulas, frequently are unsuspected clinically yet identified incidentally during CT enterography (Figure 2). Fistulas generally appear as hyperenhancing extra-enteric tracks with or without air or fluid.13 Although routine CT can detect fistulae and abscess,14 CT enterography can describe the type of fistula (ie, its connections), its size, whether or not it is associated with proximal obstruction, whether it arises from active inflammatory disease, or whether it is associated with abscess.13 In our experience, smaller fistulas associated with active disease will resolve with medical treatment. Perianal fistulas or fistulas arising in the postoperative setting unassociated with Crohn’s disease may not be hyperenhancing, potentially because of their lack of acute inflammatory response.
In a large retrospective review of patients, Bruining et al12 found that extraintestinal manifestations of Crohn’s disease were seen in about 12% to 15% of patients, including sacroiliitis, nephrolithiasis, and portal or mesenteric vein thrombosis. Moreover, non–inflammatory bowel disease–related abnormalities including pulmonary nodules, adrenal nodules, lymphoma, and other malignancies were detected. Certainly, patients with Crohn’s disease also have an increased susceptibility to enteric and hepatic malignancies and lymphoma.15 CT enterography also can be used for a variety of nonCrohn’s indications. Besides active Crohn’s disease, the most common finding at CT enterography is a mass. Masses can include carcinoid tumors, adenocarcinomas, lymphomas, GI stromal tumors, and Meckel’s diverticula (and their complications). Carcinoid tumors are the most frequently seen tumors in our practice, and are seen as hyperenhancing polypoid or carpet lesions that can invade the mesentery, with characteristic softtissue attenuation mesenteric metastases (Figure 3). The appearance of other small-bowel tumors and celiac disease at CT enterography has been described elsewhere.6
Performance of Computerized Tomography Enterography for Active Crohn’s Disease Before 2000, sensitivity estimates of CT enterography for active inflammatory Crohn’s disease were based largely on surgical or fluoroscopic series without a reliable endoscopic
Figure 1. Asymmetric mural hyperenhancement in Crohn’s disease. Note additional presence of intramural fat, indicating there also has been chronic inflammation.
March 2008
CT ENTEROGRAPHY
285
Figure 2. (A) Enterocolic fistula (arrows) arising from the top of an inflamed jejunal loop (large arrowhead) and connecting to the hepatic flexure. (B) The proximal jejunum shows mural stratification (large arrow), with the distal jejunum being decompressed (arrowhead). (B) Engorged vasa recta (or the comb sign; small arrows) supply the (C) mildly inflamed proximal jejunal loop (arrows), which contains an enterolith (arrowhead).
reference standard. Since that time, most assessments have shown a sensitivity for active inflammatory Crohn’s disease on the order of 80% to 90%,3,4,16,17 with some showing sensitivity around 60%.18,19 When quantitative and visual measures of segmental hyperenhancement are compared with endoscopy and small-bowel biopsy, the odds ratio for active disease is greater than 10, and the sensitivity for histologic inflammation is about 80%, similar to endoscopic assessment alone.3 We recently conducted a head-to-head trial comparing CT enterography, capsule endoscopy, ileocolonoscopy, and small-bowel
follow-through in 42 patients with suspected or known Crohn’s disease. The sensitivity of capsule endoscopy and CT enterography was almost identical (83% and 82%, respectively), with the specificity of CT being significantly higher (89% vs 53%; P ⫽ .02).16 In addition, although we excluded patients with symptoms of obstructive disease, 17% of the patients had asymptomatic strictures, which precluded capsule assessment. In a secondary analysis of 27 patients who received both capsule endoscopy and CT enterography, capsule endoscopy identified 2 additional patients with active Crohn’s disease who had no
286
FLETCHER ET AL
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 3
endoscopy, the capsule failed to reach the colon in 25% of the patients. In the Voderholzer et al18 experience, only 1 of 41 patients had a retained capsule. In summary, CT enterography is moderately sensitive and highly accurate for active Crohn’s disease and can exclude significant strictures that may result in retained capsules. Nevertheless, capsule endoscopy may identify some patients with mild active inflammatory disease occult at CT imaging.
Clinical Contribution of Computerized Tomography Enterography CT enterography provides objective evidence of active Crohn’s disease or small-bowel mass proximal to the reach of the endoscope, as well as providing visualization of the mesentery and liver. Studies examining the clinical benefit of CT enterography are beginning to emerge.12,20 Higgins et al20 recently had gastroenterologists review clinical information before the revelation of CT enterography findings, to make a clinical assessment on whether or not patients would benefit from corticosteroid treatment. Subsequent to these predictions, CT enterography information was provided. Their study showed that CT enterography did not replicate original clinical impressions, and changed the impression of corticosteroid benefit in 61% of these patients. Similarly, in our experience, approximately half of the patients with penetrating Crohn’s disease had no symptoms or signs of a fistula at their initial clinical assessment.21 Detection of unsuspected fistulizing Crohn’s disease resulted in either escalation of medical therapy or surgical/procedural intervention in the majority of these patients. Prospective trials detailing the effect of CT enterography results on clinical decision making are needed.
Multiphase Computerized Tomography Enterography for Occult Gastrointestinal Bleeding
Figure 3. Ileal carcinoid with typical mesenteric metastasis. (A) Axial image shows an ileal loop with focal mural thickening and enhancement (arrowhead) associated with a soft-tissue mesenteric mass with excentric calcifications and stranding to adjacent small-bowel loops (arrow). (B) Coronal image shows similar findings (bowel loops, arrowheads; mesenteric metastasis, arrow). The surgical specimen showed a cluster of mural carcinoids with metastases to local nodes.
evidence of Crohn’s disease at CT imaging, but again showed significantly lower specificity (53% vs 100%). Although a recent trial by Voderholzer et al18 showed superior performance of capsule endoscopy versus CT enteroclysis (ie, with a nasojejunal tube) for patients undergoing both tests, 27% of their study population was excluded from undergoing capsule endoscopy because of small-bowel strictures at CT enteroclysis. Moreover, in the 41 patients who underwent CT enterography and capsule
Although earlier radiologic literature was disappointing for the ability of CT to detect the causes of occult GI bleeding,22 recent work with multiphase CT enterography has shown that CT has an important role to play in this clinical setting. Because of the requirement for rapid multiphase imaging, this technique is best performed on a 64-channel (or higher) CT scanner.23 Neutral oral contrast and iodinated intravenous contrast are the same as for a single-phase examination. Scanning is performed from the diaphragm to the symphysis pubis during each of 3 phases, with scanning initiated when a region-ofinterest attenuation threshold in the aorta is reached. The first phase is a bolus-triggered arterial phase, followed by an enteric phase (20 seconds after trigger), and a delayed phase (70 seconds after trigger). Once the region-of-interest trigger threshold is reached by iodinated contrast arriving in the aorta, the arterial phase is initiated after a short 6-second delay. During the arterial phase, vascular ectasias such as AVMs and their early draining veins are seen. The enteric phase often highlights enhancing tumors, with delayed images showing that iodinated contrast is accumulating in the small-bowel lumen, indicating active bleeding (Figure 4). Huprich et al23 showed the benefit of CT enterography in identifying multiple small-bowel tumors and vascular lesions detected and undetected at capsule endoscopy, with a larger prospective study underway. In the
March 2008
CT ENTEROGRAPHY
287
Figure 4. Active bleeding at multiphase CT enterography. (A) Arterial, (B) enteric, and (C) delayed phase images show progressive focal contrast accumulation (arrows in A, B, and C) in an ileal angiodysplasia confirmed at intraoperative endoscopy. (C) Additional focus (arrows) of contrast on delayed image is also presumed to be active bleeding.
setting of occult GI bleeding, CT enterography and capsule endoscopy are not competitive imaging modalities but complementary ones, because findings from each imaging study may be nonspecific.
Appropriate Use of Cross-Sectional Alternatives to Computerized Tomography Enterography Table 2 lists alternative tests preferred over CT enterography in certain clinical settings. Because CT and magnetic resonance (MR) enteroclysis (after nasojejunal tube placement) permit the rapid infusion of large volumes of enteric contrast at faster rates, these examinations better show small-bowel caliber changes reflecting low-grade obstruction. Similarly, because CT
enterography can result in collapsed jejunal loops, we perform CT or MR enteroclysis to investigate further nonspecific capsule endoscopy findings in the jejunum. CT enteroclysis is not performed for patients with known or suspected Crohn’s disease or occult GI bleeding because of the acceptable performance characteristics of CT enterography, patient objections to, and time required for nasojejunal tube placement. Because of the marked increase in signal differences between pathology and anatomic structures near the anus, we perform MR imaging to stage perianal disease or investigate potential J-pouch complications after ileal pouch–anal anastomosis. MR enterography is preferred to CT enterography when imaging to determine if inflammed bowel loops or fistulas have responded to therapy (owing to lack of radiation), and in patients with contraindica-
288
FLETCHER ET AL
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 3
Table 2. Cross-Sectional Alternatives to CT Enterography and Suggested Indications
Table 3. Relative Strengths and Weaknesses of MR vs CT Enterography
Type of examination
Indication
MR
Strengths
CT
MR or CT enteroclysis
Suspected low-grade partial small-bowel obstruction Questionable or nonspecific capsule endoscopy findings, particularly if jejunal Staging of perianal fistulas Suspected complications after ileal pouch–anal anastomosis Monitoring response to therapy Fluoroscopic, dynamic characterization of stenotic or adhesive lesions Contraindications to CT
⫹⫹⫹ ⫹⫹⫹ ⫹⫹ ⫹⫹ ⫹ ⫹⫹⫹ ⫹⫹⫹ ⫹ ⫹
Visualize bowel wall Bowel wall signal Mesenteric signal to noise ratio Spatial resolution Temporal resolution Ionizing radiation Dynamic characterization of stenotic lesions Amount of data Length of examination
⫹⫹⫹ ⫹⫹ ⫹⫹⫹ ⫹⫹⫹ ⫹⫹⫹ ⫺ ⫺ ⫹⫹ ⫹⫹
Pelvic MR
MR enterography
tions to CT. In addition, there are several advantages to MR imaging not seen at CT enterography, which include the ability to perform MR fluoroscopy to observe bowel peristalsis in real time and dynamically characterize stenotic lesions.24 Table 3 lists the relative strengths of CT versus MR enterography. In our experience, CT enterography is used frequently as a firstline test given its speed (scanning takes seconds rather than 45– 60 min), robustness (it rarely fails to generate high-quality images), spatial and temporal resolution (which are important
NOTE. Relative strength: ⫹⫹⫹ ⬎ ⫹⫹ ⬎ ⫹; weekness: “–.”
for visualizing small masses and fistulizing disease), and CT scanner access.
The Future We believe that CT enterography will continue to be incorporated into wider clinical measures of Crohn’s disease, particularly given the promise that objective CT findings such as mural hyperenhancement can be quantitated.3,25 Moreover, we anticipate that continuing technical developments in CT image reconstruction will substantially reduce the radiation
Figure 5. Potential for dramatic radiation dose reduction at CT enterography shown using dual-energy CT enterography. (A) Normal dose CT enterography is achieved by combining the output from 2 radiograph tubes (each with half the normal dose), and shows mild wall thickening and mural hyperenhancement in the ascending colon (arrow) compared with the normal enhancement in the descending colon (arrowhead). (B) The 140-kV tube and (C) the 80-kV tube also are diagnostic, but were performed at half the radiation dose. Note the increased conspicuity of the iodine signal showing mural enhancement at the lower tube energy.
March 2008
dose at CT enterography, which is already the same or less than routine abdominal CT. The use of dual-source CT systems will permit wider use of low-energy CT scanning, which will increase the conspicuity of hypervascular inflammation and permit further radiation dose reduction (Figure 5). Developments in MR technology will facilitate rapid growth of MR enterography. Finally, we believe that there will be routine correlation of CT enterography and capsule endoscopy findings, and that these examinations will be used in combination in more patients, combining the exquisite mucosal visualization of capsule endoscopy with the mural and mesenteric images of CT enterography. References 1. Young B, Fletcher J, Booya F, et al. Head-to-head comparison of oral contrast agents for cross-sectional enterography: small bowel distention, timing and side effects. J Comput Assist Tomogr 2008;32:32–38. 2. Schindera ST, Nelson RC, DeLong DM, et al. Multi-detector row CT of the small bowel: peak enhancement temporal window— initial experience. Radiology 2007;243:438 – 444. 3. Bodily KD, Fletcher JG, Solem CA, et al. Crohn disease: mural attenuation and thickness at contrast-enhanced CT enterography— correlation with endoscopic and histologic findings of inflammation. Radiology 2006;238:505–516. 4. Booya F, Fletcher JG, Huprich JE, et al. Active Crohn disease: CT findings and interobserver agreement for enteric phase CT enterography. Radiology 2006;241:787–795. 5. Wold P, Fletcher J, Johnson C, et al. Assessment of small bowel Crohn disease: noninvasive perioral enterography compared with other imaging methods and endoscopy-feasibility study. Radiology 2003;229:275–281. 6. Paulsen SR, Huprich JE, Fletcher JG, et al. CT enterography as a diagnostic tool in evaluating small bowel disorders: review of clinical experience with over 700 cases. Radiographics 2006;26: 641– 662. 7. Macari M, Megibow AJ, Balthazar EJ. A pattern approach to the abnormal small bowel: observations at MDCT and CT enterography. AJR Am J Roentgenol 2007;188:1344 –1355. 8. Colombel JF, Solem CA, Sandborn WJ, et al. Quantitative measurement and visual assessment of ileal Crohn’s disease activity by computed tomography enterography: correlation with endoscopic severity and C reactive protein. Gut 2006;55:1561–1567. 9. Desreumaux P, Ernst O, Geboes K, et al. Inflammatory alterations in mesenteric adipose tissue in Crohn’s disease. Gastroenterology 1999;117:73– 81. 10. Meyers MA, McGuire PV. Spiral CT demonstration of hypervascularity in Crohn’s disease: “vascular jejunization of the ileum” or the “comb sign”. Abdom Imaging 1995;20:327–332. 11. Lee S, Ha H, Yang S, et al. CT of prominent pericolic or perienteric vasculature in patients with Crohn’s disease: correlation with
CT ENTEROGRAPHY
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24. 25.
289
clinical disease activity and findings on barium studies. AJR Am J Roentgenol 2002;179:1029 –1036. Bruining DH, Fletcher JG, Tremaine WJ, et al. Prevalence of penetrating disease and extraintestinal manifestations of Crohn’s disease with CT enterography. Gastroenterology 2007; 132:650. Vogel J, da Luz Moreira A, Baker M, et al. CT Enterography for Crohn’s disease: accurate preoperative diagnostic imaging. Dis Colon Rectum 2007;50:1761–1769. Maconi G, Sampietro GM, Parente F, et al. Contrast radiology, computed tomography and ultrasonography in detecting internal fistulas and intra-abdominal abscesses in Crohn’s disease: a prospective comparative study. Am J Gastroenterol 2003;98: 1545–1555. Bernstein CN, Blanchard JF, Kliewer E, et al. Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer 2001;91:854 – 862. Solem CA, Loftus LV, Fletcher JG, et al. Small bowel (SB) imaging in Crohn’s disease (CD): a prospective, blinded, 4-way comparison trial. Gastroenterology 2005;128(Suppl 2):A-74. Hassan C, Cerro P, Zullo A, et al. Computed tomography enteroclysis in comparison with ileoscopy in patients with Crohn’s disease. Int J Colorectal Dis 2003;18:121–125. Voderholzer WA, Beinhoelzl J, Rogalla P, et al. Small bowel involvement in Crohn’s disease: a prospective comparison of wireless capsule endoscopy and computed tomography enteroclysis. Gut 2005;54:369 –373. Hara A, Leighton J, Sharma V, et al. Small bowel: preliminary comparison of capsule endoscopy with barium study and CT. Radiology 2004;230:260 –265. Higgins PD, Caoili E, Zimmermann M, et al. Computed tomographic enterography adds information to clinical management in small bowel Crohn’s disease. Inflamm Bowel Dis 2007;13:262–268. Booya F. CT enterography findings in fistulizing Crohn’s disease (abstract 1982 GI-e). In: Radiological Society of North America Scientific Assembly and Annual Meeting, Chicago, IL, 2004:768. Hara AK, Leighton JA, Sharma VK, et al. Small bowel: preliminary comparison of capsule endoscopy with barium study and CT. Radiology 2004;230:260 –265. Huprich JE, Fletcher JG, Alexander J, et al. Obscure GI bleeding: 64-channel multiphase, multiplanar CT enterography has a role. Radiology 2008;246:562–571. Fidler J. MR imaging of the small bowel. Radiol Clin North Am 2007;45:317–331. Loftus E. Objective measures of disease activity: alternatives to symptom indices. Rev Gastroenterol Dis 2007;7:S8 –S16.
Address requests for reprints to: J. G. Fletcher, MD, Department of Radiology, 200 First St. SW, Mayo Building, West 2-B, Rochester, Minnesota 55905. e-mail: fl[email protected]; fax: (507) 2664609.