Understanding the clinical significance of disease detected by imaging but not by ileoscopy or biopsy

April 18, 2020

Crohn's disease (CD) most commonly affects the terminal ileum, with 30% of patients having disease confined to the small bowel. Because the inflammation associated with CD is both segmental and transmural in nature, no single endoscopic or radiological test can be used to definitively confirm or exclude its diagnosis in every patient.

Computerized tomography enterography (CTE) and magnetic resonance enterography (MRE) of the small bowel have become routine and show a high degree of accuracy in evaluating patients with established or suspected CD in the small bowel. While CTE and MRE provide complementary findings to ileocolonoscopy, small bowel inflammation may exist, even when concurrent endoscopic examination of the terminal ileum is negative (normal appearance).

When enterography and ileocolonoscopy offer what appears to be conflicting information, how should clinicians interpret these findings and use them to guide management of these patients? Noting the lack of data addressing this question, a team of Mayo Clinic researchers conducted a study published in the Journal of Crohn's and Colitis (JCC) in 2020.

Study methods

In a retrospective review, researchers identified 1,471 individuals diagnosed with CD who underwent ileoscopy and biopsy within 30 days of CT or MRE showing ileal inflammation. All imaging studies exceeded the minimum technical criteria for these exams as specified by the Society of Abdominal Radiology.

Researchers used enterography results to document the severity and length of inflammation within the distal 20 cm of the terminal ileum for each of the 1,471 individuals. They also reviewed the study population's subsequent medical records for evidence of surgery, ulceration at ileoscopy, histological inflammation, or new or worsening ileal inflammation or stricture on enterography. With this information, they then placed participants into one of the following categories:

  1. Confirmed progression: evidence of subsequent surgery, radiological worsening, new ulcers at ileoscopy or positive histology
  2. Radiologic response: evidence of decreased inflammation after medical therapy (biologic or immunomodulator)
  3. Unlikely or unconfirmed inflammation: no evidence of inflammation on subsequent CTE/MRE, subsequent negative ileocolonoscopy and biopsies, or no subsequent Crohn's-related medical therapy or surgery


Of the 1,471 study participants who underwent enterography and ileoscopy at the time of initial consultation, 8% (112/1,471) had imaging findings of inflammation on CTE/MRE within the distal 20 cm of the terminal ileum, but negative ileoscopy results (normal appearance of the intubated terminal ileum). And 6% (88/1,471) had imaging findings of inflammation on CTE/MRE, but results of both ileoscopy and ileal biopsy were negative. Within this group of 88 patients, researchers noted these additional significant findings:

  • 50% (44/88) of patients with negative ileoscopy and ileal biopsy results had moderate or severe inflammation on enterography. Within this group of 44, 45% had proximal small bowel inflammation, 32% had stricture and 11% had fistulas.
  • 67% (59/88) of patients with negative ileoscopy and ileal biopsy results had evidence of confirmed progression. Within this group of 59, 68% had subsequent surgical resection with active inflammatory CD in the pathological specimen, 70% had radiographic worsening of disease and 61% had ulcers observed at subsequent ileoscopy. Mean length and severity of ileal inflammation within this group were 10 cm and 1.6, respectively.
  • 15% (13/88) of patients with negative ileoscopy and ileal biopsy results showed evidence of radiologic response, and 18% (16/88) were classified as unlikely or unconfirmed inflammation.


According to Mayo Clinic researchers, these study results suggest that patients with unequivocal evidence of ileal inflammation on enterography are likely to have active inflammatory disease, even when results of ileoscopy and biopsy appear normal. Additionally, disease detected by imaging but not ileoscopy may worsen over time or respond to medical therapy.

"This study demonstrates the importance of recognizing small bowel disease with either CT or MR enterography when the ileoscopy is normal," explains David H. Bruining, M.D., a gastroenterologist at Mayo Clinic's campus in Rochester, Minnesota, and a co-author on the JCC article. "Our results suggest that on follow-up, two-thirds of these patients will demonstrate disease progression with radiologic worsening, surgery or ulcerations on endoscopy. To accurately assess disease extent and severity in individuals with Crohn's disease, cross-sectional imaging has become an essential tool that complements ileocolonoscopy," says Dr. Bruining.

Stephanie L. Hansel, M.D., M.S., a co-author of the JCC article and a gastroenterologist at Mayo Clinic's campus in Rochester, Minnesota, also notes that future research is warranted to further validate the results obtained to date.

"A prospective study with combined endoscopic and transmural assessment by enterography would strengthen the findings derived from our recent retrospective study," explains Dr. Hansel. "Our multidisciplinary group of abdominal radiologists and gastroenterologists continues to engage in a number of research projects focusing on Crohn's disease that should further our understanding of these issues."

For more information

Nehra AK, et al. Imaging findings of ileal inflammation at computed tomography and magnetic resonance enterography: What do they mean when ileoscopy and biopsy are negative? Journal of Crohn's and Colitis. In press.