Abstract
Purpose
To compare terminal ileum (TI) mucosal iodine density obtained at dual-energy CT enterography (DECTE) with conventional CT interpretation and endoscopy in patients with Crohn’s disease (CD).
Materials and Methods
Twenty-three CD patients (14 men; mean[SD] age:48.1[16.7] years) with endoscopy within 30 days of DECTE were retrospectively identified. An inflammatory bowel disease gastroenterologist reviewed endoscopic images. Two radiologists qualitatively assessed the presence of active TI inflammation. Mean iodine density normalized to the aorta (I%), mean absolute iodine density (I), and iodine density standard deviation (ISD) from the distal 2 cm ileum (TI) mucosa obtained using semiautomatic prototype software were compared with endoscopic assessment using Mann Whitney tests. The optimal threshold I% and I were determined from receiver operating curves (ROC). Sensitivity and specificity of conventional interpretation and determined iodine thresholds were compared using McNemar’s test. Inter-reader agreement was assessed using kappa. A p < 0.05 indicated statistical significance.
Results
Twelve (52.1%) patients had endoscopic active inflammation. I% was 37.9[13.3]% for patients with and 21.7[7.5]% for patients without endoscopic active inflammation (p = 0.001). The optimal ROC threshold 24.6% had 100% sensitivity and 81.8% specificity (AUC = 0.909, 95% CI 0.777–1). I was 2.44[0.73]mg/mL for patients with and 1.77[1.00]mg/mL for patients without active endoscopic inflammation (p = 0.0455). The optimal ROC threshold 1.78 mg/mL I had 91.7% sensitivity and 63.6% specificity (AUC = 0.75, 95% CI 0.532–0.968). ISD was similar for patients with and without endoscopic active inflammation (0.82[0.33]mg/mL and 0.77[0.28]mg/mL, respectively, p = 0.37). Conventional interpretation sensitivity and specificity (R1/R2) were 83.3%/91.7% and 72.7%/54.5%, respectively (all p > 0.05) with moderate inter-reader agreement (Κ = 0.542[95% CI 0.0202–0.088]).
Conclusion
Mean normalized iodine density is highly sensitive and specific for endoscopic active inflammation. DECTE could be considered as a surrogate to endoscopy in CD patients. Despite trends towards improved sensitivity and specificity compared with conventional interpretation, future larger studies are needed.
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References
Loftus EV, Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology 2004;126(6):1504-1517. https://doi.org/10.1053/j.gastro.2004.01.063
Turner D, Ricciuto A, Lewis A, D'Amico F, Dhaliwal J, Griffiths AM, Bettenworth D, Sandborn WJ, Sands BE, Reinisch W, Scholmerich J, Bemelman W, Danese S, Mary JY, Rubin D, Colombel JF, Peyrin-Biroulet L, Dotan I, Abreu MT, Dignass A, International Organization for the Study of IBD. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology 2021;160(5):1570-1583. https://doi.org/10.1053/j.gastro.2020.12.031
Klenske E, Bojarski C, Waldner M, Rath T, Neurath MF, Atreya R. Targeting mucosal healing in Crohn's disease: what the clinician needs to know. Therap Adv Gastroenterol 2019;12:1756284819856865. https://doi.org/10.1177/1756284819856865
Samuel S, Bruining DH, Loftus EV, Jr., Becker B, Fletcher JG, Mandrekar JN, Zinsmeister AR, Sandborn WJ. Endoscopic skipping of the distal terminal ileum in Crohn's disease can lead to negative results from ileocolonoscopy. Clin Gastroenterol Hepatol 2012;10(11):1253-1259. https://doi.org/10.1016/j.cgh.2012.03.026
Regueiro M, Kip KE, Schraut W, Baidoo L, Sepulveda AR, Pesci M, El-Hachem S, Harrison J, Binion D. Crohn's disease activity index does not correlate with endoscopic recurrence one year after ileocolonic resection. Inflamm Bowel Dis 2011;17(1):118-126. https://doi.org/10.1002/ibd.21355
Cipriano LE, Levesque BG, Zaric GS, Loftus EV, Jr., Sandborn WJ. Cost-effectiveness of imaging strategies to reduce radiation-induced cancer risk in Crohn's disease. Inflamm Bowel Dis 2012;18(7):1240-1248. https://doi.org/10.1002/ibd.21862
Bruining DH, Siddiki HA, Fletcher JG, Sandborn WJ, Fidler JL, Huprich JE, Mandrekar JN, Harmsen WS, Evans PE, Faubion WA, Hanson KA, Ingle SB, Pardi DS, Schroeder KW, Tremaine WJ, Loftus EV, Jr. Benefit of computed tomography enterography in Crohn's disease: effects on patient management and physician level of confidence. Inflamm Bowel Dis 2012;18(2):219-225. https://doi.org/10.1002/ibd.21683
Peyrin-Biroulet L, Reinisch W, Colombel JF, Mantzaris GJ, Kornbluth A, Diamond R, Rutgeerts P, Tang LK, Cornillie FJ, Sandborn WJ. Clinical disease activity, C-reactive protein normalisation and mucosal healing in Crohn's disease in the SONIC trial. Gut 2014;63(1):88-95. https://doi.org/10.1136/gutjnl-2013-304984
Hindryckx P, Baert F, Hart A, Armuzzi A, Panes J, Peyrin-Biroulet L, Clinical Trial Committee Clincom of the European Cs, Colitis O. Clinical trials in luminal Crohn's disease: a historical perspective. J Crohns Colitis 2014;8(11):1339-1350. https://doi.org/10.1016/j.crohns.2014.04.007
Walsh AJ, Bryant RV, Travis SP. Current best practice for disease activity assessment in IBD. Nat Rev Gastroenterol Hepatol 2016;13(10):567-579. https://doi.org/10.1038/nrgastro.2016.128
Bruining DH, Zimmermann EM, Loftus EV, Jr., Sandborn WJ, Sauer CG, Strong SA, Society of Abdominal Radiology Crohn's Disease-Focused P. Consensus Recommendations for Evaluation, Interpretation, and Utilization of Computed Tomography and Magnetic Resonance Enterography in Patients With Small Bowel Crohn's Disease. Radiology 2018;286(3):776-799. https://doi.org/10.1148/radiol.2018171737
Li Y, Li Y, Jackson A, Li X, Huang N, Guo C, Zhang H. Comparison of virtual unenhanced CT images of the abdomen under different iodine flow rates. Abdom Radiol (NY) 2017;42(1):312-321. https://doi.org/10.1007/s00261-016-0842-4
McCollough CH, Leng S, Yu L, Fletcher JG. Dual- and Multi-Energy CT: Principles, Technical Approaches, and Clinical Applications. Radiology 2015;276(3):637-653. https://doi.org/10.1148/radiol.2015142631
Kim H, Goo JM, Kang CK, Chae KJ, Park CM. Comparison of Iodine Density Measurement Among Dual-Energy Computed Tomography Scanners From 3 Vendors. Invest Radiol 2018;53(6):321-327. https://doi.org/10.1097/RLI.0000000000000446
Sellerer T, Noel PB, Patino M, Parakh A, Ehn S, Zeiter S, Holz JA, Hammel J, Fingerle AA, Pfeiffer F, Maintz D, Rummeny EJ, Muenzel D, Sahani DV. Dual-energy CT: a phantom comparison of different platforms for abdominal imaging. Eur Radiol 2018;28(7):2745-2755. https://doi.org/10.1007/s00330-017-5238-5
De Kock I, Delrue L, Lecluyse C, Hindryckx P, De Vos M, Villeirs G. Feasibility study using iodine quantification on dual-energy CT enterography to distinguish normal small bowel from active inflammatory Crohn's disease. Acta Radiol 2019;60(6):679-686. https://doi.org/10.1177/0284185118799508
Villanueva Campos AM, Tardaguila de la Fuente G, Utrera Perez E, Jurado Basildo C, Mera Fernandez D, Martinez Rodriguez C. Value of dual-energy CT enterography in the analysis of pathological bowel segments in patients with Crohn's disease. Radiologia 2018;60(3):223-229. https://doi.org/10.1016/j.rx.2018.01.004
Kim YS, Kim SH, Ryu HS, Han JK. Iodine Quantification on Spectral Detector-Based Dual-Energy CT Enterography: Correlation with Crohn's Disease Activity Index and External Validation. Korean J Radiol 2018;19(6):1077-1088. https://doi.org/10.3348/kjr.2018.19.6.1077
Dane B DS, Han J, O'Donnell T, Ream J, Chang S, Megibow A. Crohn's disease activity quantified by iodine density obtained from dual-energy CT enterography. JCAT 2020.
Dane B, Sarkar S, Nazarian M, Galitzer H, O'Donnell T, Remzi F, Chang S, Megibow A. Crohn Disease Active Inflammation Assessment with Iodine Density from Dual-Energy CT Enterography: Comparison with Histopathologic Analysis. Radiology 2021;301(1):144-151. https://doi.org/10.1148/radiol.2021204405
Dane B, O'Donnell T, Ream J, Chang S, Megibow A. Novel Dual-Energy Computed Tomography Enterography Iodine Density Maps Provide Unique Depiction of Crohn Disease Activity. J Comput Assist Tomogr 2020;44(5):772-779. https://doi.org/10.1097/RCT.0000000000001009
Booya F, Fletcher JG, Huprich JE, Barlow JM, Johnson CD, Fidler JL, Solem CA, Sandborn WJ, Loftus EV, Jr., Harmsen WS. Active Crohn disease: CT findings and interobserver agreement for enteric phase CT enterography. Radiology 2006;241(3):787-795. https://doi.org/10.1148/radiol.2413051444
Deepak P, Fletcher JG, Fidler JL, Barlow JM, Sheedy SP, Kolbe AB, Harmsen WS, Therneau T, Hansel SL, Becker BD, Loftus EV, Jr., Bruining DH. Predictors of Durability of Radiological Response in Patients With Small Bowel Crohn's Disease. Inflamm Bowel Dis 2018;24(8):1815-1825. https://doi.org/10.1093/ibd/izy074
Ordas I, Rimola J, Alfaro I, Rodriguez S, Castro-Poceiro J, Ramirez-Morros A, Gallego M, Giner A, Barastegui R, Fernandez-Clotet A, Masamunt M, Ricart E, Panes J. Development and Validation of a Simplified Magnetic Resonance Index of Activity for Crohn's Disease. Gastroenterology 2019;157(2):432-439 e431. https://doi.org/10.1053/j.gastro.2019.03.051
Rimola J, Ordas I, Rodriguez S, Garcia-Bosch O, Aceituno M, Llach J, Ayuso C, Ricart E, Panes J. Magnetic resonance imaging for evaluation of Crohn's disease: validation of parameters of severity and quantitative index of activity. Inflamm Bowel Dis 2011;17(8):1759-1768. https://doi.org/10.1002/ibd.21551
Baker ME, Walter J, Obuchowski NA, Achkar JP, Einstein D, Veniero JC, Vogel J, Stocchi L. Mural attenuation in normal small bowel and active inflammatory Crohn's disease on CT enterography: location, absolute attenuation, relative attenuation, and the effect of wall thickness. AJR Am J Roentgenol 2009;192(2):417-423. https://doi.org/10.2214/AJR.08.1267
Bachour SP, Shah RS, Lyu R, Nakamura T, Shen M, Li T, Dane B, Barnes EL, Rieder F, Cohen B, Qazi T, Lashner B, Achkar JP, Philpott J, Holubar SD, Lightner AL, Regueiro M, Axelrad J, Baker ME, Click B. Test Characteristics of Cross-sectional Imaging and Concordance With Endoscopy in Postoperative Crohn's Disease. Clin Gastroenterol Hepatol 2021. https://doi.org/10.1016/j.cgh.2021.12.033
Acknowledgements
We thank Kun Qian for assistance with statistical analysis.
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BD: None, AL: None, TO: Siemens Healthineers employee, RP: None, WR: None, SB: None, SC None, AM: Consultant for Bracco Diagnostic Inc.
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Alec Megibow consultant for Bracco Inc, Thomas O’Donnell Siemens Healthineers employee.
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Dane, B., Kernizan, A., O’Donnell, T. et al. Crohn’s disease active inflammation assessment with iodine density from dual-energy CT enterography: comparison with endoscopy and conventional interpretation. Abdom Radiol 47, 3406–3413 (2022). https://doi.org/10.1007/s00261-022-03605-2
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DOI: https://doi.org/10.1007/s00261-022-03605-2
Keywords
- Crohn disease
- Dual-energy CT enterography
- CT enterography
- Iodine density
- Inflammatory bowel disease