The Future of Intestinal Fibrosis Imaging

  • Ryan W. StidhamEmail author
  • Mahmoud Al-Hawary


Though the capabilities of available imaging technologies to assess intestinal damage have substantially improved, emerging alternative non-invasive imaging methods may offer advancements in detecting and quantifying intestinal fibrosis in the inflammatory bowel diseases. Both the immediate clinical need to measure fibrosis for therapeutic decision-making and the near-future need for tools to assess pipeline anti-fibrotic medications highlight the demand for better non-invasive biomarkers of fibrosis in Crohn’s disease. Developing imaging platforms assessing tissue mechanical properties, perfusion characteristics, and structural protein content provide new perspectives and possibilities for approaching intestinal fibrosis quantitation. In this chapter, we will discuss existing, emerging, and experimental imaging methods using ultrasound elastography, novel MRI sequences, and photoacoustic imaging to measure fibrosis in Crohn’s disease.


Intestinal fibrosis Fibrosis Crohn’s disease Ultrasound elastography Stiffness imaging Shear wave Photoacoustic imaging Magnetization transfer MRI Fibrostenotic disease Stricturing disease 



NIH K23DK101687 (Stidham).


  1. 1.
    Horsthuis K, Bipat S, Bennink RJ, Stoker J. Inflammatory bowel disease diagnosed with US, MR, scintigraphy, and CT: meta-analysis of prospective studies. Radiology. 2008;247(1):64–79.CrossRefPubMedGoogle Scholar
  2. 2.
    Panés J, Bouzas R, Chaparro M, García-Sánchez V, Gisbert JP, Martínez de Guereñu B, et al. Systematic review: the use of ultrasonography, computed tomography and magnetic resonance imaging for the diagnosis, assessment of activity and abdominal complications of Crohn’s disease. Aliment Pharmacol Ther. 2011;34(2):125–45.CrossRefPubMedGoogle Scholar
  3. 3.
    Ordás I, Rimola J, Rodriguez S, Paredes JM, Martínez-Pérez MJ, Blanc E, et al. Accuracy of magnetic resonance enterography in assessing response to therapy and mucosal healing in patients with Crohn’s disease. Gastroenterology. 2014;146(2):374–82.e1.CrossRefPubMedGoogle Scholar
  4. 4.
    Adler J, Punglia DR, Dillman JR, Polydorides AD, Dave M, Al-Hawary MM, et al. Computed tomography enterography findings correlate with tissue inflammation, not fibrosis in resected small bowel Crohn’s disease. Inflamm Bowel Dis. 2012;18(5):849–56.CrossRefPubMedGoogle Scholar
  5. 5.
    Chiorean MV, Sandrasegaran K, Saxena R, Maglinte DD, Nakeeb A, Johnson CS. Correlation of CT enteroclysis with surgical pathology in Crohn’s disease. Am J Gastroenterol. 2007;102(11):2541–50.CrossRefPubMedGoogle Scholar
  6. 6.
    Pariente B, Mary J-Y, Danese S, Chowers Y, De Cruz P, D’Haens G, et al. Development of the Lémann index to assess digestive tract damage in patients with Crohn’s disease. Gastroenterology. 2015;148(1):52–3.CrossRefPubMedGoogle Scholar
  7. 7.
    Zappa M, Stefanescu C, Cazals-Hatem D, Bretagnol F, Deschamps L, Attar A, et al. Which magnetic resonance imaging findings accurately evaluate inflammation in small bowel Crohn’s disease? A retrospective comparison with surgical pathologic analysis. Inflamm Bowel Dis. 2011;17(4):984–93.CrossRefPubMedGoogle Scholar
  8. 8.
    Johnson LA, Luke A, Sauder K, Moons DS, Horowitz JC, Higgins PDR. Intestinal fibrosis is reduced by early elimination of inflammation in a mouse model of IBD: impact of a “Top-Down” approach to intestinal fibrosis in mice. Inflamm Bowel Dis. 2012;18(3):460–71.CrossRefPubMedGoogle Scholar
  9. 9.
    Ophir J, Céspedes I, Ponnekanti H, Yazdi Y, Li X. Elastography: a quantitative method for imaging the elasticity of biological tissues. Ultrason Imaging. 1991;13(2):111–34.CrossRefPubMedGoogle Scholar
  10. 10.
    Castéra L, Foucher J, Bernard P-H, Carvalho F, Allaix D, Merrouche W, et al. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology. 2010;51:828.PubMedGoogle Scholar
  11. 11.
    Correas J-M, Tissier A-M, Khairoune A, Vassiliu V, Méjean A, Hélénon O, et al. Prostate cancer: diagnostic performance of real-time shear-wave elastography. Radiology. 2015;275(1):280–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Stidham RW, Xu J, Johnson LA, Kim K, Moons DS, McKenna BJ, et al. Ultrasound elasticity imaging for detecting intestinal fibrosis and inflammation in rats and humans with Crohn’s disease. Gastroenterology. 2011;141(3):819–826.e1.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Johnson LA, Rodansky ES, Sauder KL, Horowitz JC, Mih JD, Tschumperlin DJ, et al. Matrix stiffness corresponding to strictured bowel induces a fibrogenic response in human colonic fibroblasts. Inflamm Bowel Dis. 2013;19(5):891–903.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Castéra L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol. 2008;48(5):835–47.CrossRefPubMedGoogle Scholar
  15. 15.
    Ganne-Carrié N, Ziol M, de Ledinghen V, Douvin C, Marcellin P, Castéra L, et al. Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases. Hepatology. 2006;44(6):1511–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Colombo S, Belloli L, Zaccanelli M, Badia E, Jamoletti C, Buonocore M, et al. Normal liver stiffness and its determinants in healthy blood donors. Dig Liver Dis. 2011;43(3):231–6.CrossRefPubMedGoogle Scholar
  17. 17.
    Castéra L. Noninvasive methods to assess liver disease in patients with hepatitis B or C. Gastroenterology. 2012;142(6):1293–4.CrossRefPubMedGoogle Scholar
  18. 18.
    Friedrich-Rust M, Ong M-F, Martens S, Sarrazin C, Bojunga J, Zeuzem S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology. 2008;134(4):960–74.CrossRefPubMedGoogle Scholar
  19. 19.
    Liu X, Squire LC. The shock-wave/turbulent boundary-layer interaction on curved surface at transonic speed. In: Turbulent shear-layer/shock-wave interactions. Berlin: Springer; 1986. p. 93–104.CrossRefGoogle Scholar
  20. 20.
    Lerner RM, Huang SR, Parker KJ. “Sonoelasticity” images derived from ultrasound signals in mechanically vibrated tissues. Ultrasound Med Biol. 1990;16(3):231–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Lubinski MA, Emelianov SY, O'Donnell M. Speckle tracking methods for ultrasonic elasticity imaging using short-time correlation. IEEE Trans Ultrason Ferroelectr Freq Control. 1999;46(1):82–96.CrossRefPubMedGoogle Scholar
  22. 22.
    Li P-C, Lee W-N. An efficient speckle tracking algorithm for ultrasonic imaging. Ultrason Imaging. 2002;24(4):215–28.CrossRefPubMedGoogle Scholar
  23. 23.
    Baumgart DC, Müller HP, Grittner U, Metzke D, Fischer A, Guckelberger O, et al. US-based real-time elastography for the detection of fibrotic gut tissue in patients with stricturing Crohn disease. Radiology. 2015;275(3):889–99.CrossRefPubMedGoogle Scholar
  24. 24.
    Sconfienza LM, Cavallaro F, Colombi V, Pastorelli L, Tontini G, Pescatori L, et al. In-vivo axial-strain sonoelastography helps distinguish acutely-inflamed from fibrotic terminal ileum strictures in patients with Crohn’s disease: preliminary results. Ultrasound Med Biol. 2016;42(4):855–63.CrossRefPubMedGoogle Scholar
  25. 25.
    Fufezan O, Asavoaie C, Tamas A, Farcau D, Serban D. Bowel elastography - a pilot study for developing an elastographic scoring system to evaluate disease activity in pediatric Crohn’s disease. Med Ultrason. 2015;17(4):422–30.PubMedGoogle Scholar
  26. 26.
    Fraquelli M, Branchi F, Cribiù FM, Orlando S, Casazza G, Magarotto A, et al. The role of ultrasound elasticity imaging in predicting ileal fibrosis in Crohn’s disease patients. Inflamm Bowel Dis. 2015;21(11):2605–12.CrossRefPubMedGoogle Scholar
  27. 27.
    Dillman JR, Stidham RW, Higgins PDR, Moons DS, Johnson LA, Rubin JM. US elastography-derived shear wave velocity helps distinguish acutely inflamed from fibrotic bowel in a Crohn disease animal model. Radiology. 2013;267(3):757–66.CrossRefPubMedGoogle Scholar
  28. 28.
    Dillman JR, Stidham RW, Higgins PDR, Moons DS, Johnson LA, Keshavarzi NR, et al. Ultrasound shear wave elastography helps discriminate low-grade from high-grade bowel wall fibrosis in ex vivo human intestinal specimens. J Ultrasound Med. 2014;33(12):2115–23.CrossRefPubMedGoogle Scholar
  29. 29.
    Lu C, Gui X, Chen W, Fung T, Novak K, Wilson SR. Ultrasound shear wave elastography and contrast enhancement: effective biomarkers in Crohn’s disease strictures. Inflamm Bowel Dis. 2017;23(3):421–30.CrossRefPubMedGoogle Scholar
  30. 30.
    Danese S, Sans M, la Motte de C, Graziani C, West G, Phillips MH, et al. Angiogenesis as a novel component of inflammatory bowel disease pathogenesis. Gastroenterology. 2006;130(7):2060–73.CrossRefPubMedGoogle Scholar
  31. 31.
    Tielbeek JAW, Ziech MLW, Li Z, Lavini C, Bipat S, Bemelman WA, et al. Evaluation of conventional, dynamic contrast enhanced and diffusion weighted MRI for quantitative Crohn’s disease assessment with histopathology of surgical specimens. Eur Radiol. 2014;24(3):619–29.CrossRefPubMedGoogle Scholar
  32. 32.
    Rimola J, Planell N, Rodriguez S, Delgado S, Ordás I, Ramírez-Morros A, et al. Characterization of inflammation and fibrosis in Crohn’s disease lesions by magnetic resonance imaging. Am J Gastroenterol. 2015;110(3):432–40.CrossRefPubMedGoogle Scholar
  33. 33.
    Rimola J, Planell N, Rodriguez S, Delgado S, Ordás I, Ramírez-Morros A, et al. Corrigendum: Characterization of inflammation and fibrosis in Crohn’s disease lesions by magnetic resonance imaging. Am J Gastroenterol. 2015;110(3):480.CrossRefPubMedGoogle Scholar
  34. 34.
    Ripollés T, Rausell N, Paredes JM, Grau E, Martínez MJ, Vizuete J. Effectiveness of contrast-enhanced ultrasound for characterisation of intestinal inflammation in Crohn’s disease: a comparison with surgical histopathology analysis. J Crohns Colitis. 2013;7(2):120–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Dillman JR, Rubin JM, Johnson LA, Moons DS, Higgins PDR. Can contrast-enhanced sonography detect bowel wall fibrosis in mixed inflammatory and fibrotic Crohn disease lesions in an animal model? J Ultrasound Med. 2017;36(3):523–30.CrossRefPubMedGoogle Scholar
  36. 36.
    Saevik F, Nylund K, Hausken T, Ødegaard S, Gilja OH. Bowel perfusion measured with dynamic contrast-enhanced ultrasound predicts treatment outcome in patients with Crohn’s disease. Inflamm Bowel Dis. 2014;20(11):2029–37.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Nylund K, Jirik R, Mezl M, Leh S, Hausken T, Pfeffer F, et al. Quantitative contrast-enhanced ultrasound comparison between inflammatory and fibrotic lesions in patients with Crohn’s disease. Ultrasound Med Biol. 2013;39(7):1197–206.CrossRefPubMedGoogle Scholar
  38. 38.
    Quaia E, Gennari AG, van Beek EJR. Differentiation of inflammatory from fibrotic ileal strictures among patients with Crohn’s disease through analysis of time-intensity curves obtained after microbubble contrast agent injection. Ultrasound Med Biol. 2017;43(6):1171–8.CrossRefPubMedGoogle Scholar
  39. 39.
    Jacene HA, Ginsburg P, Kwon J, Nguyen GC, Montgomery EA, Bayless TM, et al. Prediction of the need for surgical intervention in obstructive Crohn’s disease by 18F-FDG PET/CT. J Nucl Med. 2009;50(11):1751–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Lenze F, Wessling J, Bremer J, Ullerich H, Spieker T, Weckesser M, et al. Detection and differentiation of inflammatory versus fibromatous Crohn’s disease strictures: prospective comparison of 18F-FDG-PET/CT, MR-enteroclysis, and transabdominal ultrasound versus endoscopic/histologic evaluation. Inflamm Bowel Dis. 2012;18(12):2252–60.CrossRefPubMedGoogle Scholar
  41. 41.
    Catalano OA, Gee MS, Nicolai E, Selvaggi F, Pellino G, Cuocolo A, et al. Evaluation of quantitative PET/MR enterography biomarkers for discrimination of inflammatory strictures from fibrotic strictures in Crohn disease. Radiology. 2015;278:792.CrossRefPubMedGoogle Scholar
  42. 42.
    Wolff SD, Eng J, Balaban RS. Magnetization transfer contrast: method for improving contrast in gradient-recalled-echo images. Radiology. 1991;179(1):133–7.CrossRefPubMedGoogle Scholar
  43. 43.
    Adler J, Swanson SD, Schmiedlin-Ren P, Higgins PDR, Golembeski CP, Polydorides AD, et al. Magnetization transfer helps detect intestinal fibrosis in an animal model of Crohn disease. Radiology. 2011;259(1):127–35.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Dillman JR, Swanson SD, Johnson LA, Moons DS, Adler J, Stidham RW, et al. Comparison of noncontrast MRI magnetization transfer and T2 -Weighted signal intensity ratios for detection of bowel wall fibrosis in a Crohn's disease animal model. J Magn Reson Imaging. 2015;42(3):801–10.CrossRefPubMedGoogle Scholar
  45. 45.
    Pazahr S, Blume I, Frei P, Chuck N, Nanz D, Rogler G, et al. Magnetization transfer for the assessment of bowel fibrosis in patients with Crohn’s disease: initial experience. MAGMA. 2013;26(3):291–301.CrossRefPubMedGoogle Scholar
  46. 46.
    Wang LV, Hu S. Photoacoustic tomography: in vivo imaging from organelles to organs. Science. 2012;335(6075):1458–62.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Jacques SL. Optical properties of biological tissues: a review. Phys Med Biol. 2013;58(11):R37–61.CrossRefPubMedGoogle Scholar
  48. 48.
    Lei H, Johnson LA, Liu S, Moons DS, Ma T, Zhou Q, et al. Characterizing intestinal inflammation and fibrosis in Crohn’s disease by photoacoustic imaging: feasibility study. Biomed Opt Express. 2016;7(7):2837–48.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Knieling F, Neufert C, Hartmann A, Claussen J, Urich A, Egger C, et al. Multispectral optoacoustic tomography for assessment of Crohn’s disease activity. N Engl J Med. 2017;376(13):1292–4.CrossRefPubMedGoogle Scholar
  50. 50.
    Rath T, Bojarski C, Neurath MF, Atreya R. Molecular imaging of mucosal α4β7 integrin expression with the fluorescent anti-adhesion antibody vedolizumab in Crohn’s disease. Gastrointest Endosc. 2017;86:406.CrossRefPubMedGoogle Scholar
  51. 51.
    Van den Brande JMH, Koehler TC, Zelinkova Z, Bennink RJ, te Velde AA, ten FJW C, et al. Prediction of antitumour necrosis factor clinical efficacy by real-time visualisation of apoptosis in patients with Crohn’s disease. Gut. 2007;56(4):509–17.CrossRefPubMedGoogle Scholar
  52. 52.
    Joshi BP, Wang TD. Imaging: dynamic imaging of gut function—allowing the blind to see. Nat Rev Gastroenterol Hepatol. 2014;11(10):584–6.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Zhang Y, Jeon M, Rich LJ, Hong H, Geng J, Zhang Y, et al. Non-invasive multimodal functional imaging of the intestine with frozen micellar naphthalocyanines. Nat Nanotechnol. 2014;9(8):631–8.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Gastroenterology and Hepatology, Department of Internal MedicineUniversity of MichiganAnn ArborUSA
  2. 2.Department of RadiologyUniversity of MichiganAnn ArborUSA

Personalised recommendations