Title: In vivo colonoscopic optical coherence tomography for transmural inflammation in inflammatory bowel disease
Abstract: Background & Aims: Transmural inflammation, a distinguishing feature of Crohn's disease (CD), cannot be assessed by conventional colonoscopy with mucosal biopsy. Our previous ex vivo study of histology-correlated optical coherence tomography (OCT) imaging on colectomy specimens of CD and ulcerative colitis (UC) showed that disruption of the layered structure of colon wall on OCT is an accurate marker for transmural inflammation of CD. We performed an in vivo colonoscopic OCT in patients with a clinical diagnosis of CD or UC using the previously established, histology-correlated OCT imaging criterion. Methods: OCT was performed in 40 patients with CD (309 images) and 30 patients with UC (292 images). Corresponding endoscopic features of mucosal inflammation were documented. Two gastroenterologists blinded to endoscopic and clinical data scored the OCT images independently to assess the feature of disrupted layered structure. Results: Thirty-six CD patients (90.0%) had disrupted layered structure, whereas 5 UC patients (16.7%) had disrupted layered structure (P < .001). Using the clinical diagnosis of CD or UC as the gold standard, the disrupted layered structure on OCT indicative of transmural inflammation had a diagnostic sensitivity and specificity of 90.0% (95% CI: 78.0%, 96.5%) and 83.3% (95% CI: 67.3%, 93.3%) for CD, respectively. The κ coefficient in the interpretation of OCT images was 0.80 (95% CI: 0.75, 0.86, P < .001). Conclusions: In vivo colonoscopic OCT is feasible and accurate to detect disrupted layered structure of the colon wall indicative of transmural inflammation, providing a valuable tool to distinguish CD from UC. Background & Aims: Transmural inflammation, a distinguishing feature of Crohn's disease (CD), cannot be assessed by conventional colonoscopy with mucosal biopsy. Our previous ex vivo study of histology-correlated optical coherence tomography (OCT) imaging on colectomy specimens of CD and ulcerative colitis (UC) showed that disruption of the layered structure of colon wall on OCT is an accurate marker for transmural inflammation of CD. We performed an in vivo colonoscopic OCT in patients with a clinical diagnosis of CD or UC using the previously established, histology-correlated OCT imaging criterion. Methods: OCT was performed in 40 patients with CD (309 images) and 30 patients with UC (292 images). Corresponding endoscopic features of mucosal inflammation were documented. Two gastroenterologists blinded to endoscopic and clinical data scored the OCT images independently to assess the feature of disrupted layered structure. Results: Thirty-six CD patients (90.0%) had disrupted layered structure, whereas 5 UC patients (16.7%) had disrupted layered structure (P < .001). Using the clinical diagnosis of CD or UC as the gold standard, the disrupted layered structure on OCT indicative of transmural inflammation had a diagnostic sensitivity and specificity of 90.0% (95% CI: 78.0%, 96.5%) and 83.3% (95% CI: 67.3%, 93.3%) for CD, respectively. The κ coefficient in the interpretation of OCT images was 0.80 (95% CI: 0.75, 0.86, P < .001). Conclusions: In vivo colonoscopic OCT is feasible and accurate to detect disrupted layered structure of the colon wall indicative of transmural inflammation, providing a valuable tool to distinguish CD from UC. Preoperative distinction between Crohn's disease (CD) and ulcerative colitis (UC) is important, but can be difficult. In approximately 25% of patients with CD, the disease is limited to the colon (Crohn's colitis).1Farmer R.G. Hawk W.A. Turnbull Jr, R.B. Clinical patterns in Crohn's disease a statistical study of 615 cases.Gastroenterology. 1975; 68: 627-635Abstract Full Text PDF PubMed Scopus (555) Google Scholar Two thirds of patients with Crohn's colitis have pancolitis,2Stenson W.F. Inflammatory bowel disease.in: Yamada T. Alpers D.H. Laine L. Owyang C. Powell D.W. Textbook of gastroenterology. 3rd ed. Lippincott Williams and Wilkins, Philadelphia1999: 1775-1839Google Scholar which contributes to the difficulty in distinguishing this disease entity from UC.2Stenson W.F. Inflammatory bowel disease.in: Yamada T. Alpers D.H. Laine L. Owyang C. Powell D.W. Textbook of gastroenterology. 3rd ed. Lippincott Williams and Wilkins, Philadelphia1999: 1775-1839Google Scholar, 3Kirsner J.B. Problems in the differentiation of ulcerative colitis and Crohn's disease of the colon the need for repeated diagnostic evaluation.Gastroenterology. 1975; 68: 187-191PubMed Scopus (57) Google Scholar, 4Clamp S.E. Myren J. Bouchier I.A. Watkinson G. de Dombal F.T. Diagnosis of inflammatory bowel disease an international multicentre scoring system.BMJ. 1982; 284: 91-95Crossref PubMed Scopus (45) Google Scholar It is not possible to distinguish CD from UC in approximately 15% of cases, even by histopathology. This difficulty may persist even after colectomy, and patients are diagnosed with indeterminate colitis (IC).5Margulis A.B. Goldberg H.I. Lawson T.L. Montgomery C.K. The overlapping spectrum of ulcerative and granulomatous colitis. A roentgenographic-pathologic study.Am J Roentgenol Radium Thera Nuc Med. 1971; 113: 325-334Crossref PubMed Scopus (48) Google Scholar, 6Hodgson H.J.F. Ulcerative colitis versus Crohn's disease—one disease or two?.in: Allan R.N. Rhodes J.M. Hanauer S.B. Keighley M.R.B. Alexander-Williams J. Fazio V.W. Inflammatory bowel disease. 3rd ed. Churchill Livingstone, New York1997: 343-347Google Scholar, 7Mac Dermott M.P. Indeterminate colitis.in: Bayless T.M. Hanauer S.B. Advanced therapy of inflammatory bowel disease. 2nd ed. B.C. Decker, Hamilton, Ontario2001: 157-160Google Scholar, 8Hyman N.H. Fazio V.W. Tuckson W.B. Lavery I.C. Consequence of ileal pouch-anal anastomosis for Crohn's colitis.Dis Colon Rectum. 1991; 34: 653-657Crossref PubMed Scopus (173) Google Scholar, 9Delaney C.P. Remzi F.H. Gramlich T. Dadvand B. Fazio V.W. Equivalent function, quality of life and pouch survival rates after ileal pouch-anal anastomosis for indeterminate and ulcerative colitis.Ann Surg. 2002; 236: 43-48Crossref PubMed Scopus (139) Google Scholar, 10Asplund S. Gramlich T. Fazio V. Petras R. Histologic changes in defunctioned rectums in patients with inflammatory bowel disease a clinicopathologic study of 82 patients with long-term follow-up.Dis Colon Rectum. 2002; 45: 1206-1213Crossref PubMed Scopus (29) Google Scholar Transmural inflammation, a hallmark of CD, distinguishes CD from UC,11Shimizu S. Tada M. Kawai K. Endoscopic ultrasonography in the assessment of inflammatory bowel disease.Gastrointest Endosc Clin North Am. 1995; 5: 851-859PubMed Google Scholar, 12Whitehead R. Ulcerative colitis, Crohn's colitis, ischemic colitis, pseudomembranous colitis, and antibiotic-associated colitis.in: Whitehead R. Mucosal biopsy of the gastrointestinal tract. 5th ed. Saunders, Philadelphia1997: 305-354Google Scholar which is not accessible to conventional colonoscopy with mucosal biopsy. Optical coherence tomography (OCT), an optical imaging technique, produces high-resolution cross-sectional images of tissue ex vivo and in vivo on a micrometer scale.13Bouma B.E. Tearney G.J. Compton C.C. Nishioka N.S. High-resolution imaging of the human esophagus and stomach in vivo using optical coherence tomography.Gastrointest Endosc. 2000; 51: 467-474Abstract Full Text Full Text PDF PubMed Scopus (314) Google Scholar, 14Das A. Sivak M.V. Chak A. Wong R.C. Westpal V. Rollins A.M. Willis J. Isenberg G. Izatt J.A. 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Measurement of corneal thickness by low-coherence interferometry.Appl Opt. 1992; 31: 6637-6642Crossref PubMed Scopus (125) Google Scholar We recently conducted an ex vivo OCT study on colectomy specimens from 24 patients with CD and 24 patients with UC.18Shen B. Zuccaro Jr, G. Gramlich T.L. Gladkova N. Delaney C.P. Connor J.T. Kareta M. Lashner B.A. Bevins C.L. Feldchtein F. Strong S.A. Bambrick M.L. Trolli P. Fazio V.W. Ex vivo histology-correlated optical coherence tomography in the detection of transmural inflammation in inflammatory bowel disease.Clin Gastroenterol Hepatol. 2004; 2: 754-760Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar Transmural inflammation involving the tissue planes in CD was characterized by the presence of disrupted layered structures on OCT imaging. By applying the OCT feature as the diagnostic criterion for transmural inflammation in CD, we have demonstrated a sensitivity and specificity 86% and 91%, respectively. The aim of this in vivo study was to assess the feasibility and diagnostic accuracy of OCT imaging in patients with CD or UC during routine colonoscopy by applying the previously established ex vivo histology-correlated OCT criterion. The study was approved by the Institutional Review Board of the Cleveland Clinic Foundation. Written informed consent was obtained from all patients. From May 2002 to October 2003, 40 consecutive patients with CD and 30 consecutive patients with UC who underwent clinically indicated outpatient colonoscopy were enrolled in the study. The colonoscopy was performed for diagnosis, assessment of disease activity or extent, or surveillance of dysplasia or cancer. Inclusion criteria were age ≥18 years and a history of CD or UC. Patients with a pre-procedural diagnosis of IC or fulminant colitis were excluded. In this in vivo study, CD was diagnosed clinically based on small intestine disease, granulomas on histology, or perianal/fistulous diseases; UC was diagnosed clinically based on continuous disease from the rectum proximally and no small intestine, perianal or fistulous diseases, or granulomas. A final diagnosis of CD or UC was based on the combined assessment of clinical, endoscopic, radiographic, and histologic evaluation. The areas of mucosal inflammation imaged by OCT were also assessed with colonoscopy. The endoscopic features were photo documented in an endoscopic database and were later assessed with corresponding OCT features. The OCT scanning system includes a compact tabletop console (scanner) and a catheter-based optical probe.19Zuccaro G. Gladkova N. Vargo J. Feldchtein F. Zagaynova E. Conwell D. Falk G. Goldblum J. Dumot J. Ponsky J. Gelikonov G. Davros B. Donchenko E. Richter J. Optical coherence tomography of the esophagus and proximal stomach in health and disease.Am J Gastroenterol. 2001; 96: 2633-2639Crossref PubMed Google Scholar The scanner console includes an optoelectronic module (interferometer) and user interface. The probe relays the light to and from the tissue specimen; the light is collected and analyzed by the scanner console unit. In addition, the probe contains an electrical mechanism to move the optical beam across a surface. The OCT probe has an outer diameter of 2.7 mm and is sealed by a quartz window at the distal end that can be easily passed down the operating channel of diagnostic or therapeutic colonoscopes. Our OCT device uses low coherent radiation with a wavelength of 1270 nm and 1.5 mW power at the tissue surface and has a spatial resolution of 10–20 μm. The depth of penetration is approximately 1.5 mm. However, image depth corresponded to up to 2.5–3.5 mm uncompressed tissue, when the probe was pressed firmly against the tissue. Real-time in vivo OCT imaging was performed during colonoscopy. The OCT probe was passed through the single operating channel of a diagnostic colonoscope (CF-160; Olympus America, Melville, NY) by the endoscopist (B.S.). Various anatomic locations of the colon and rectum were imaged with the probe placed at diseased areas with the most obvious inflammation. Because CD or UC often affects various segments of the colon, multiple OCT images were generated for each patient representing various anatomic locations throughout the colon and rectum. For CD patients with partial colectomy, a minimum of 4 images were obtained. To achieve the maximal tissue penetration by OCT imaging, the OCT probe was pressed firmly against the tissue specimens without interrupting the mucosal layer. A research nurse assisted with the procedure by storing and labeling OCT images and documenting the corresponding endoscopic features of the area imaged by OCT. Routine segmental mucosal biopsy specimens from various anatomic locations of the colon and rectum were obtained as clinically indicated, although mucosal biopsy was not required by our study protocol. OCT was used to assess the cross-sectional plane of the colonic wall. It is not possible to correlate in vivo OCT images obtained during colonoscopy with the biopsy-based mucosal histology because the depth of mucosal biopsy could not reach the level deeper than the superficial submucosa. Therefore, we used the histology-correlated OCT imaging criterion generated from our previous ex vivo study,18Shen B. Zuccaro Jr, G. Gramlich T.L. Gladkova N. Delaney C.P. Connor J.T. Kareta M. Lashner B.A. Bevins C.L. Feldchtein F. Strong S.A. Bambrick M.L. Trolli P. Fazio V.W. Ex vivo histology-correlated optical coherence tomography in the detection of transmural inflammation in inflammatory bowel disease.Clin Gastroenterol Hepatol. 2004; 2: 754-760Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar and applied the criteria in vivo in patients with CD or UC. The OCT criterion of transmural inflammation was the disruption of layered structure, reflecting the disruption of tissue planes by infiltration of inflammatory cells, granulomas, or fibrosis. Inflammation limited to the level of the mucosa or superficial submucosa, as seen in UC, was characterized by the presence of an intact layered structure. The stored OCT images were later retrieved, interpreted, and scored by 2 investigators with extensive experience with OCT (B.S. and G.Z.). All stored OCT images were de-identified before reading. The 2 investigators, blinded to patients' identity and the demographic, clinical, radiographic, endoscopic, and histologic data, independently assessed whether the layered structure of the colon wall was disrupted, which is a central feature of the transmural inflammation process (Figure 1, Figure 2, Figure 3). If the OCT imaging showed the characteristic disruption of layered structure, we assumed that the tissue planes were disrupted by transmural inflammation, which would have been shown on resection histopathology. Each endoscopist scored the OCT images using either "0" for an intact layered structure or "1" for a disrupted layered structure. Disruption of layers was considered present if the 2 endoscopists agreed.Figure 2Endoscopy and optical coherence tomography (OCT) imaging of ulcerative colitis. (A) Nodular mucosa on endoscopy. (B) The layered structure shown on OCT imaging.View Large Image Figure ViewerDownload (PPT)Figure 3Endoscopy and optical coherence tomography (OCT) imaging of Crohn's disease. (A) Nodular mucosa on endoscopy, similar to that in ulcerative colitis. (B) Disrupted layered structure on OCT imaging.View Large Image Figure ViewerDownload (PPT) The identification of disrupted layered structure (based on a consensus reading of 2 endoscopists) outside deep or linear ulcers, ulcerated stricture, or polypoid lesions was considered as evidence of transmural inflammation for CD. The disrupted layered structure at the areas with deep or linear ulcers on endoscopy was not counted as a diagnostic feature in both CD and UC groups because transmural inflammation can be seen in UC with deep ulcers. Ulcerated stricture is a hallmark for CD. Adenomas itself with or without CD or UC can lead to loss of orientation of tissue planes, causing disrupted layered structure on OCT.20Shen B. Zuccaro G. Optical coherence tomography in the gastrointestinal tract.Gastrointest Endosc North Am. 2004; 14: 555-571Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar Diagnostic accuracy (sensitivity and specificity) of OCT for the detection of transmural inflammation was calculated with reference to the clinical diagnosis of UC or UC as a gold standard. The proposed sample size of 30 CD and 30 UC patients with a total number of 60 patients provided standard errors of .07, .07, and .08 for the estimated sensitivities and specificities of 90%, 80%, and 70% for OCT, respectively. Likewise, a sample of 60 patients offered standard errors for the κ coefficient measuring inter-rater agreement of less than .10 units wide for κ scores >.6. In addition, a minimum of 4 OCT images were obtained from each patient, and thus repeat reading of histology and OCT images occurred in each patient. The sensitivity and specificity of OCT imaging were evaluation with the provision of 95% confidence intervals (CI). Inter-rater agreement in interpreting OCT images was estimated using the κ coefficient. Fisher exact tests were used to compare OCT findings versus endoscopic features. P values <.05 were considered statistically significant. Seventy patients with a clinical diagnosis of either CD (N = 40) or UC (N = 30) were enrolled (Table 1). One patient had newly diagnosed UC, and the remaining 69 patients had a confirmed diagnosis of CD or UC and had colonoscopy for the assessment of disease activity or extent or for surveillance of dysplasia. Granulomas were rarely detected on mucosal biopsy.Table 1Demographic and Clinical DataCrohn's disease N = 40Ulcerative colitis N = 30P valueAge, y ± SD41.3 ± 13.755.8 ± 16.8<.001Male, n (%)17 (42.5)16 (53.0).37Duration of disease, y ± SD11.4 ± 9.011.7 ± 11.5.89Disease locations, n (%)<.001 Small bowel and colon30 (75.0)0 Pancolitis5 (12.5)20 (66.7) Segmental colitis3 (7.5)0 Left sided colitis/proctitis010 (33.3) Perianal disease/fistulae18 (45.0)0Disease activity, n (%).009 Active disease36 (90.0)19 (63.3) Quiescent disease4 (10.0)11 (36.7)Colonoscopy for assessing disease activity and extent, n (%)38 (95.0)17 (56.7)<.001Colonoscopy for surveillance, n (%)15 (37.5)14 (46.7).44IBD in first-degree relatives, n (%)4 (10.0)2 (6.7).62Smoking, n (%)12 (30.0)5 (16.7).20Previous IBD-related surgery, n (%)24 (60.0)0<.001NSAID use, n (%)9 (22.5)7 (23.3).93Extraintestinal manifestations, n (%).52 Arthralgias13 (32.5)8 (26.7) Primary sclerosing cholangitis1 (4.0)2 (6.7) Eyes01 (3.3) Skin1 (4.0)0Granulomas on mucosal biopsy, n (%)3 (7.5)0.13 Open table in a new tab A total of 601 OCT images were obtained from colonoscopy in 40 patients with CD (309 images) and 30 patients with UC (292 images). In each patient, multiple (ranging from 4 to 16) OCT images were obtained. Endoscopic features of CD and UC were normal appearance, quiescent changes with mucosal scarring, aphthous or small ulcers, deep or linear ulcers, stricture with ulcerated overlying mucosa, edema, nodularity, loss of vascular pattern, erythema, and hemorrhagic spots. Normal colon wall clearly showed the layered structure on OCT (Figure 1). The layers reflecting tissue planes were distinguished by relative differences in the intensity of their backscattered reflection. In UC, the majority of OCT images showed intact layered structures with the characteristic "fried bacon strip" pattern (Figure 2). In CD, a number of OCT images showed loss or disruption of the layered structure or tissue plane of the colon wall, and the images of the superficial areas appeared bright and heterogeneous because of alterations in light scattering, propagation, and back reflection by inflammation, fibrosis, and disruption of tissue planes. Visualization of deeper structures was difficult due to loss of signals or shadowing from strong scattering within the superficial structures (Figure 3). Indications for colonoscopy included assessment of disease activity and extent, or dysplasia surveillance. Therefore, multiple biopsy specimens were taken throughout the colon and rectum. Although the study protocol did not require assessment of correlation between OCT imaging and biopsy histology, all OCT images were obtained from the areas where biopsies were performed later. During the OCT imaging, none of patients experienced discomfort and no complications related to colonoscopy, mucosal biopsy, or OCT imaging occurred. In per-patient-based analysis, 36 patients (90.0%) with CD had disrupted layered structure of the colonic wall on at least one OCT image, suggesting transmural inflammation, whereas 5 patients (16.7%) with UC had disrupted layered structure of colon wall on at least one OCT image. In per-image-based analysis, 89 of 309 OCT images (30.5%) from the 40 CD patients showed disrupted layered structure, whereas 28 of 292 images (9.1%) from the 30 UC patients showed disrupted layered structure (Table 2).Table 2Diagnostic Accuracy of OCT for the Transmural Inflammation in Crohn's DiseaseCrohn's diseaseUlcerative colitisCases with disrupted layers on OCT36/405/30Estimate (95% confidence interval)90.0% (78.0%, 96.5%)16.7% (6.7%, 32.7%)Images with disrupted layers on OCT89/30928/292Estimate (95% confidence interval)30.5% (24.0%, 34.0%)9.1% (6.6%, 13.4%) Open table in a new tab Using a clinical diagnosis of CD or UC as the gold standard, the disrupted layered structure on OCT indicative of transmural inflammation in CD had a diagnostic sensitivity and specificity of 90.0% (95% CI: 78.0%, 96.5%) and 83.3% (95% CI: 67.3%, 93.3%) for CD, respectively. Endoscopic features ranged from quiescent to severe inflammation. Endoscopic features of areas imaged by OCT were photo-documented and were compared with OCT features. Of note, disrupted layered structure of the colon wall on OCT was seen in both CD and UC patients and was associated with a variety of endoscopic features (Table 3). Particularly in the areas of deep or linear ulcers in both UC and CD groups, there was an association with disrupted layered structure on OCT.Table 3Association Between Features on Endoscopy and OCTEndoscopic featuresCrohn's diseaseUlcerative colitisP valueNumber of imagesNumber of images with disrupted layered structure (%)Number of imagesNumber of images of disrupted layered structure (%)Normal-appearing mucosa13101120NAQuiescent/mucosal scarring101 (10)502 (4.0).43Aphthous or shallow ulcers3012 (40)255 (20.0).15Deep or linear ulcers2827 (96.4)107 (70.0).019Ulcerated strictures2420 (83.3)00NAHemorrhagic spots/erythema123 (35)81 (12.5).49Nodularity, edema, loss of vascular pattern4416 (36.4)9410 (10.6)<.001Polypoid lesions1310 (76.9)103 (30.0).02Total29289 (30.5)30928 (9.1)<.001 Open table in a new tab All 13 polypoid lesions in the CD group were the hyperplastic type on biopsy histology, and 10 of them showed disrupted layered structure on OCT. Of the 10 polypoid lesions in the UC group, 8 were hyperplastic polyps and 2 were adenomatous polyps on biopsy histology. Two adenomatous polyps and 1 hyperplastic polyp in the UC group had disrupted layered structure on OCT. The κ coefficient was calculated to assess the inter-rater agreement between the 2 endoscopists who interpreted the OCT images. The overall κ coefficient in the interpretation of 601 OCT images was .80 (95% CI: .75, .86; P < .001), indicating an excellent agreement (Table 4).Table 4κ Coefficient Values for the Assessment of Inter-rater Agreement in Interpreting Optical Coherence Tomography ImagesNo. of imagesκ coefficient (95% CI)P valueAgreement observedAgreement expectedAll images6010.80 (0.75, 0.86)<.0010.930.66Images in the CD group3090.90 (0.84 (0.95)<.0010.960.56Images in the UC group2920.62 (0.50, 0.74)<.0010.910.77 Open table in a new tab Optical coherence tomography provides real-time, cross-sectional, high-resolution images of the colonic wall. As a natural extension of our previous ex vivo resection histology-correlated study, this in vivo study shows that OCT imaging is safe and feasible during colonoscopy, providing essential information for differential diagnosis of CD and UC. Disruption of the layered structure of the colon wall, indicative of transmural inflammation, was seen more often in patients with CD than in patients with UC. This important information is not available from conventional colonoscopy and mucosal biopsy. A disrupted layered structure of the colon wall on OCT imaging is sensitive and specific for CD, with an excellent inter-rater agreement in interpreting images. The OCT image pattern of disrupted layered structure corresponds to a variety of endoscopic features. Being able to distinguish CD from UC is important because their medical and surgical treatments and prognoses are different.21Fazio V.W. Ziv Y. Church J.M. Oakley J.R. Lavery I.C. Milsom J.W. Schroeder T.K. 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Decker, Hamilton, Ontario2001: 241-244Google Scholar However, preoperative differentiation of CD and UC may be impossible, even with extensive endoscopic, radiographic, and histologic evaluation. Up to 15% of patients with inflammatory bowel disease (IBD) involving the colon alone could not be categorized into either CD or UC, and they are classified as having IC.26Price A.B. Overlap in the spectrum of non-specific inflammatory bowel disease-"Colitis indeterminate".J Clin Pathol. 1978; 31: 567-577Crossref PubMed Scopus (303) Google Scholar IC is most commonly seen in patients with acute severe colitis, which is often associated with extensive nonspecific mucosal changes, precluding a diagnosis of CD or UC. Many patients with IC require colectomy because of either severe acute colitis refractory to medical therapy or steroid-dependent colitis. Often for patients with urgent colectomy, histologic examination of the colectomy specimen may not be diagnostic of either CD or UC. Pathologic interpretation can be confounded by the fact that transmural inflammation occasionally can be seen in severe UC, especially at the areas of deep ulceration.7Mac Dermott M.P. Indeterminate colitis.in: Bayless T.M. Hanauer S.B. Advanced therapy of inflammatory bowel disease. 2nd ed. B.C. Decker, Hamilton, Ontario2001: 157-160Google Scholar The clinical course and prognosis after restorative protocolectomy and ileal pouch-anal anastomosis for patients with IC is different from that of patients with typical UC. Patients with IC after ileal pouch-anal anastomosis tend to have more frequent perianal complications22McIntyre P.B. Pemberton J.H. Wolff B.G. Dozois R.R. Beart Jr, R.W. Indeterminate colitis. Long-term outcome in patients after ileal pouch-anal anastomosis.Dis Colon Rectum. 1995; 38: 51-54Crossref PubMed Scopus (116) Google Scholar, 23Koltun W.A. Schoetz Jr, D.J. Roberts P.L. Murray J.J. Coller J.A. Veidenheimer M.C. Indeterminate colitis predisposes to perineal complications after ileal pouch-anal anastomosis.Dis Colon Rectum. 1991; 34: 857-860Crossref PubMed Scopus (107) Google Scholar, 22McIntyre P.B. Pemberton J.H. Wolff B.G. Dozois R.R. Beart Jr, R.W. Indeterminate colitis. Long-term outcome in patients after ileal pouch-anal anastomosis.Dis Colon Rectum. 1995; 38: 51-54Crossref PubMed Scopus (116) Google Scholar and pouch failure.22McIntyre P.B. Pemberton J.H. Wolff B.G. Dozois R.R. Beart Jr, R.W. Indeterminate colitis. Long-term outcome in patients after ileal pouch-anal anastomosis.Dis Colon Rectum. 1995; 38: 51-54Crossref PubMed Scopus (116) Google Scholar, 24Atkinson K.G. Owen D.A. Wankling G. Restorative proctocolectomy and indeterminate colitis.Am J Surg. 1994; 167: 516-518Abstract Full Text PDF PubMed Scopus (71) Google Scholar, 27Fazio V.W. Tekkis P.P. Remzi F. Lavery I.C. Manilich E. Connor J. Preen M. Delaney C. Quantification of risk for pouch failure after ileal pouch anal anastomosis surgery.Ann Surg. 2003; 238: 605-617PubMed Google Scholar Thus, preoperative differentiation of CD and UC and further definition of IC is important to predict pouch outcome and to prevent pouch failure. Optical coherence tomography is safe and feasible for ex vivo and in vivo studies in IBD, providing a real-time cross-sectional image of the colon wall.