CT and MR techniques depict pathology beyond the range of endoscopy.

Enterography is the story of progress made possible from better chemistry applied to contrast media development and the recent leaps in engineering that have revolutionized CT.

This unique imaging technology is directed at the small bowel, an overlapping, undulating, 22-ft-long section of the gastrointestinal (GI) tract remotely located between the stomach and large intestine.

Compared with other organs, the small bowel is subject to a relatively low incidence of disease, according to Dr. Dean Maglinte, a distinguished professor of radiology and imaging sciences at Indiana University School of Medicine. But the symptoms of disorders that do affect it are often nonspecific. For these reasons, the primary role of small-bowel imaging is to rule out the presence of fairly uncommon pathology. These are inflammatory bowel disease, gastrointestinal tract bleeding, and small bowel tumors.

About 80% of the demand for small-bowel imaging stems from Crohn’s disease, which affects up to 600,000 Americans. Disease prevalence has increased 31% since 1991, with pediatric patients accounting for 25% to 30% of the affected population (Inflammatory Bowel Diseases, March 2007, Vol. 13:3, pp. 254-261).

Roles for diagnostic imaging

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Patient with active ileocolonic Crohn’s disease.

Small-bowel imaging guides therapeutic management of Crohn’s disease by informing the clinician about the location, extent, and activity of pathology, according to Dr. Sam Stuart, a radiologist with Royal Free Hospital in London. Imaging aids diagnosis, monitors progression, assists treatment, and identifies small-bowel strictures that may need surgical resection.

CT enterography (CTE) has largely replaced small-bowel follow-through as the imaging modality of choice for Crohn’s disease. Its popularity stems from its ability to noninvasively investigate extraintestinal effects of inflammatory small-bowel disease located outside the reach of x-ray barium imaging.

The Mayo Clinic in Rochester, MN, adopted CT enterography for routine clinical use after the publication of a pivotal study by its own Dr. Craig Solem and colleagues in 2008 (Gastrointestinal Endoscopy, August 2008, Vol. 68:2, pp. 255-266).

Solem’s team prospective efficacy study compared the relative abilities of CT enterography, capsule endoscopy, ileocolonoscopy, and small-bowel follow-through to diagnose Crohn’s disease and determine whether it was active or inactive.

Based on experience with 42 patients, the researchers found that ileocolonoscopy is only slightly more accurate than CT enterography (86% versus 85%) for diagnosis. It was far more sensitive than small-bowel follow-through (82% versus 65%) and significantly more specific than either capsule endoscopy or small-bowel follow-through (89% versus 53%).

“Solem’s study showed us that small-bowel follow-through was inferior,” said Dr. David Bruining, an assistant professor of gastroenterology at the Mayo Clinic. “One of the reasons we have been pushing forward with CTE is because it is a better test.”

Members of Mayo Clinic’s small-bowel imaging group also were drawn to CT — and later MR — enterography because of endoscopy’s limitations. Endoscopes are sometimes unable to extend to areas of disease involvement, and endoscopy findings do not necessarily correlate with disease activity.

“It is not enough to see the patient’s symptoms and to tell patients that they are failing therapy. We need objective evidence,” Bruining said. “That is where CT or MR enterography has made a big impact in practice.”

CT enterography utilization increased steadily at the Mayo Clinic after 2006. It reached a plateau in 2009, with the initial adoption of MR enterography (MRE). Most of the growth in the past two years has shifted to MRE, Bruining said.

Keys to CTE’s diagnostic power

Enterography could not have been developed without high-speed multislice CT. Its development moved in lockstep with the progress of CT from four-slice acquisition in the late 1990s to current 320-detector-row scanners that can complete a whole-body scan in three seconds. Such ultrahigh temporal and spatial resolution can be focused on the small bowel to freeze motion for even a pain-ridden child, while rendering diagnostically superb images of the intestinal lumen, mucosa, and extraintestinal region.

The full extent of the benefits from multislice CT were not revealed, however, until radiologists shifted away from positive contrast material that was so bright that it washed out indications of inflammation in the bowel wall, according to Dr. Peter Higgins, PhD, an assistant professor of gastroenterology at the University of Michigan.

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Increased mesenteric vascularity.

The problem was solved when researchers inadvertently tried a negative oral contrast medium.

“It became apparent that just filling the small bowel with negative contrast, food, or fluid was actually better than very bright contrast,” Higgins said.

Decades of experience with barium imaging taught radiologists the value of complete bowel dissention for ensuring thorough examination. The use of neutral enteric contrast agents has proved to be especially well-suited for this role. Such agents allow water in the gut to remain there without bowel wall absorption, Higgins said.

Complete small-bowel distention requires lots of oral contrast. The protocol for routine CT enterography at the Mayo Clinic calls for patients to drink 1.35 L of it in the two hours before imaging. The radiologist also administers intravenous iodinated contrast to enhance extraluminal structures.

MR enterography

Because of radiation concerns about CT enterography, European researchers began developing MR enterography in the early 2000s as an alternative for pediatric patients. The first feasibility study was published in 2005.

A single CTE exam exposes the patient to about 4 mSv of radiation, though the effective dose can be much higher. A longitudinal European study found that 15% of Crohn’s disease patients accumulated more than 75 mSv from radiological procedures in 15 years. The risk of high radiation exposure doubled for patients diagnosed with Crohn’s disease before the age of 17 years (Gut, November 2008, Vol. 57:11, pp. 1524-1529).

The CTE protocol served as a natural template for MRE’s development, with variations added to reflect individual preferences to capitalize on MRI’s inherently higher contrast resolution.

The preferred agent for bowel distention during MR enterography varies from institution to institution, according to Dr. Michael Gee, PhD, an assistant professor of radiology at Massachusetts General Hospital (MGH) in Boston. Most radiologists use a neutral enteric agent, but some Europeans prefer polyethylene glycol (PEG).

Gee’s group at MGH mix a neutral enteric agent mixed with an oral suspension of ultrasmall iron oxide particles. When mixed with water in the bowel, the mixture looks dark on T2-weighted MRI. Before MRE, an intravenous gadolinium-based contrast medium is injected to enhance extraluminal tissue.

Pivotal MRE trial

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MR enterography detection of active inflammation and fibrosis.

The Mayo Clinic was the site for a key efficacy trial of MR enterography. The prospective study of 23 adult patients by Dr. Hassan Siddiki and colleagues in 2009 concluded that MRE and CTE are about equally sensitive for detecting active small-bowel inflammation, though the CT’s image quality was judged slightly superior (American Journal of Roentgenology, July 2009, Vol. 193:1, pp. 113-121).

Overall, CTE and MRE were both more than 90% sensitive to the presence of positive findings for Crohn’s disease. CTE was somewhat more specific than MRE (88.9% versus 66.7%), but the difference was not statistically significant.

A small prospective trial by Gee and colleagues at MGH published this year found that MRE is at least as good as CTE for determining the initial presence, extent, and severity of Crohn’s disease for pediatric patients (AJR, July 2011, Vol. 197:1, pp. 224-229).

The findings were based on 18 consecutive patients, all of whom were less than 18 years old. They underwent both CTE and MRE to establish an initial primary diagnosis of Crohn’s disease. CTE was used as the reference standard. The sensitivity, specificity, and accuracy of MRE were 90%, 82.6%, and 86.7%, respectively.

Though MRE spares children from radiation exposure, CTE remains the first choice for many radiologists for imaging young patients. They prefer CTE because it is incredibly fast. CTE imaging can be completed in five minutes, compared with 45 minutes for an MRE evaluation. The higher speed greatly reduces the risk of motion artifacts and vomiting from children whose stomachs have been filled with oral contrast.

Diagnostic gold standard

Despite imaging advancements, histology remains the gold standard for Crohn’s disease diagnosis. CTE or MRE help confirm such findings, while establishing the disease’s extent and severity. After a negative biopsy in the face of persistent symptoms, enterography is used to identify inflammatory areas of the bowel for tissue sampling.

Because of superb spatial resolution, CTE is a good choice for establishing the presence and extent of active inflammatory disease. Mural stratification characterized at CTE is the most sensitive finding for active inflammatory disease, according to Dr. Khaled Elsayes, an associate professor of radiology at MD Anderson Cancer Center in Houston. Mural stratification can be appreciated by its trilaminar appearance, with enhanced outer serosal and inner mucosal layers and an interposed submucosal layer of lower attenuation.

A prominent vasa recta, often referred to as a “comb sign,” and increased mesenteric fat attenuation are the most specific features of active Crohn’s disease described by CTE.

Though MRE also can establish these findings, its capabilities extend to water-sensitive, T2-weighted imaging that differentiates between active inflammation and fibrosis. Active inflammation on MRI is characterized by bright areas of the bowel wall on T2-weighted imaging, whereas fibrosis is characterized by a hypointense presentation and also a T2-weighted sequence.

Dynamic gadolinium-contrast enhancement also aids the assessment of bowel wall pathology, with active inflammation revealing itself from early mucosal enhancement followed by delayed enhancement of the rest of the bowel wall. Fibrosis is characterized by an absence of enhancement of the mucosa, according to Gee.

“Between the T2-weighted images and the postcontrast images, we basically get two shots to try to detect fibrosis on MRI that we wouldn’t have the opportunity to look at with CT,” Gee said.

The ability to differentiate between active inflammation and fibrosis is crucial for effective patient management. Active inflammation indicates the presence of reversible strictures that can be treated with anti-inflammatory drugs. Fibrotic strictures require surgical intervention to avoid future bowel obstructions, Elsayes said.

Coping with pediatric radiation exposure

Some clinicians believe that fears about CTE-related radiation will diminish as improved dose reduction techniques are introduced. Two recent studies in particular exemplify how CTE radiation can be reduced without losing image quality.

Dr. Avinash Kambadakone at MGH used iterative reconstruction to cut dose from CTE by about one-third compared with a traditional filtered back-projection reconstruction technique (AJR, June 2011, Vol. 196:6, pp. W743-W752). And at the Cleveland Clinic in Ohio, Dr. Brian C. Allen and colleagues drew from the findings of a prospective trial to recommend optimal settings for an automatic exposure control during CTE performed with 16- and 64-slice scanners (AJR, July 2010; Vol. 195:1, pp. 89-100).

Generally, radiologists have decreased exposure in CTE exams by restricting imaging acquisition to either the vascular or arterial phase, depending on the application.

Dealing with MRE’s high costs

The relatively high cost of MRE can be a problem for clinicians who order it for their young patients. The University of Michigan Medical Center charges $7,000 for an MRE exam compared with $1,500 for CTE, according to Higgins. The higher charge has a few insurers insisting on bizarre ways to reduce their costs, he noted. One payor approved payment for the pelvic portion of an MRE exam, but denied it for the abdominal portion.

At MGH, Gee has seen no evidence of payor resistance to MRE, though his department seeks reimbursement for MRE to only cover specific indications for pediatric patients or evaluations of small-bowel fistulas or abscesses.

In response to an email inquiry, an Aetna spokesperson wrote that it has no clinical policy preventing the use of MRE in younger patients with Crohn’s disease. But he admitted that prior authorization policies applied by individual Aetna plans could be an impediment.

In response to email inquiries, Cigna replied that it covers MRE for children and adults when deemed medically necessary, recognizing the need for MRE for young patients to avoid radiation exposure.

Cigna’s payment experience indicates that MRE is twice as expense as CTE, however. Its average cost for CTE is about $950, compared with about $1,800 for MRE.

In Europe, higher MRE costs have not discouraged clinicians from ordering it, according to Dr. Julian Panes, chief of gastroenterology at the Hospital Clinic of Barcelona in Spain. The costs at Panes’ hospital and the Academic Medical Center in Amsterdam, the Netherlands, are comparable. Both charge from $400 to $467 for MRE and $266 to $300 for CTE.

Other applications

In addition to Crohn’s disease, CTE and MRE are being used to detect small-bowel tumors. Such malignancies are rare, and their symptoms are nonspecific. Clinicians typically test for more likely causes before considering the possibility of small-bowel cancer. At a result, diagnosis is often delayed, thereby increasing the need for a highly sensitive test when it is finally performed, Elsayes said. CTE meets that need with a 90% detection rate for carcinoid and other tumors.

CTE is also showing early promise for tracking down the sources of obscure GI bleeding that evades detection with conventional and capsule endoscopy. These techniques have been typically less than 50% sensitive for localizing the cause of bleeding.

In a recently published trial, Dr. James Huprich, an associate professor of radiology at the Mayo Clinic, and colleagues determined that multiphasic CTE was more than twice as sensitive as capsule endoscopy for finding the source of obscure GI bleeding. The sensitivity of CTE for 16 patients was 88%, compared with 38% for capsule endoscopy (Radiology, September 2011, Vol. 260:3, pp. 744-751).

Future development

MGH radiologists have begun performing 3-tesla MRE, though it has been a challenge, Gee said. Imaging with 3-tesla systems offers an improved signal-to-noise ratio that can be used to either cut exam times or boost image resolution, but the risk of susceptibility artifact is much greater than during 1.5-tesla imaging. Air must be carefully eliminated from the bowel to avoid susceptibility artifacts from affecting the evaluation of the mucosa, he said.

Dr. Seung Soo Lee and colleagues from the University of Ulsan College of Medicine in Seoul, South Korea, reported encouraging results with a triphasic CTE protocol involving 1,800 mL of a neutral enteric agent for bowel distention. The scheme achieved 71% sensitivity this year with CTE in seven patients with positive at capsule endoscopy (Radiology, June 2011, Vol. 259:3, pp. 739-748).

Researchers are also investigating a possible role for diffusion-weighted MR. It may emerge as another way to identify active inflammatory Crohn’s disease by mapping the pattern of edema that restricts water diffusion in the bowel wall, Gee said.

Bruining envisions a promising future for CT enterography. The modality has all the ingredients for broad community-based adoption, he said. Multislice CT is widely available and inexpensive compared with MRI. Low-dose techniques will likely calm fears about radiation exposure, while improved CTE applications, especially the ability to distinguish inflammatory processes from fibrotic disease, will win over gastrointestinal radiologists and gastroenterologist to the merits of the technology.

“These are the kinds of things that are being looked at to see if we can predict the inflammatory component for people with strictures and how well they are likely to respond to therapy,” Bruining said.

source:GE imaging newsletter