Skip to main content
Log in

Anatomical Road Mapping Using CT and MR Enterography for Ultrasound Molecular Imaging of Small Bowel Inflammation in Swine

  • Ultrasound
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

To evaluate the feasibility and time saving of fusing CT and MR enterography with ultrasound for ultrasound molecular imaging (USMI) of inflammation in an acute small bowel inflammation of swine.

Methods

Nine swine with ileitis were scanned with either CT (n = 3) or MR (n = 6) enterography. Imaging times to load CT/MR images onto a clinical ultrasound machine, fuse them to ultrasound with an anatomical landmark-based approach, and identify ileitis were compared to the imaging times without anatomical road mapping. Inflammation was then assessed by USMI using dual selectin-targeted (MBSelectin) and control (MBControl) contrast agents in diseased and healthy control bowel segments, followed by ex vivo histology.

Results

Cross-sectional image fusion with ultrasound was feasible with an alignment error of 13.9 ± 9.7 mm. Anatomical road mapping significantly reduced (P < 0.001) scanning times by 40%. Localising ileitis was achieved within 1.0 min. Subsequently performed USMI demonstrated significantly (P < 0.001) higher imaging signal using MBSelectin compared to MBControl and histology confirmed a significantly higher inflammation score (P = 0.006) and P- and E-selectin expression (P ≤ 0.02) in inflamed vs. healthy bowel.

Conclusions

Fusion of CT and MR enterography data sets with ultrasound in real time is feasible and allows rapid anatomical localisation of ileitis for subsequent quantification of inflammation using USMI.

Key Points

Real-time fusion of CT/MRI with ultrasound to localise ileitis is feasible.

Anatomical road mapping using CT/MRI significantly decreases the scanning time for USMI.

USMI allows quantification of inflammation in swine, verified with ex vivo histology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Loftus EV Jr (2004) Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology 126:1504–1517

    Article  PubMed  Google Scholar 

  2. Danese S (2012) New therapies for inflammatory bowel disease: from the bench to the bedside. Gut 61:918–932

    Article  CAS  PubMed  Google Scholar 

  3. Molodecky NA, Soon IS, Rabi DM et al (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142:46–54 e42; quiz e30

    Article  PubMed  Google Scholar 

  4. Malaty HM, Fan X, Opekun AR, Thibodeaux C, Ferry GD (2010) Rising incidence of inflammatory bowel disease among children: a 12-year study. J Pediatr Gastroenterol Nutr 50:27–31

    Article  PubMed  Google Scholar 

  5. Benchimol EI, Mack DR, Nguyen GC et al (2014) Incidence, outcomes, and health services burden of very early onset inflammatory bowel disease. Gastroenterology 147:803–813 e807; quiz e814-805

    Article  PubMed  Google Scholar 

  6. Ahluwalia JP (2012) Immunotherapy in inflammatory bowel disease. Med Clin North Am 96:525–544

    Article  CAS  PubMed  Google Scholar 

  7. Speight RA, Mansfield JC (2013) Drug advances in inflammatory bowel disease. Clin Med 13:378–382

    Article  Google Scholar 

  8. Vilela EG, Torres HO, Martins FP, Ferrari Mde L, Andrade MM, Cunha AS (2012) Evaluation of inflammatory activity in Crohn's disease and ulcerative colitis. World J Gastroenterol 18:872–881

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kiessling F, Fokong S, Bzyl J, Lederle W, Palmowski M, Lammers T (2014) Recent advances in molecular, multimodal and theranostic ultrasound imaging. Adv Drug Deliv Rev 72:15–27

    Article  CAS  PubMed  Google Scholar 

  10. Pysz MA, Willmann JK (2011) Targeted contrast-enhanced ultrasound: an emerging technology in abdominal and pelvic imaging. Gastroenterology 140:785–790 e786

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kircher MF, Willmann JK (2012) Molecular body imaging: MR imaging, CT, and US. Part II. Applications. Radiology 264:349–368

    Article  PubMed  Google Scholar 

  12. Kircher MF, Willmann JK (2012) Molecular body imaging: MR imaging, CT, and US. part I. principles. Radiology 263:633–643

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kamaya A, Machtaler S, Safari Sanjani S et al (2013) New technologies in clinical ultrasound. Semin Roentgenol 48:214–223

    Article  PubMed  Google Scholar 

  14. Abou-Elkacem L, Bachawal SV, Willmann JK (2015) Ultrasound molecular imaging: Moving toward clinical translation. Eur J Radiol 84:1685–1693

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kiessling F, Huppert J, Palmowski M (2009) Functional and molecular ultrasound imaging: concepts and contrast agents. Curr Med Chem 16:627–642

    Article  CAS  PubMed  Google Scholar 

  16. Lindner JR (2009) Contrast ultrasound molecular imaging of inflammation in cardiovascular disease. Cardiovasc Res 84:182–189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Deshpande N, Lutz AM, Ren Y et al (2012) Quantification and monitoring of inflammation in murine inflammatory bowel disease with targeted contrast-enhanced US. Radiology 262:172–180

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wang H, Felt SA, Machtaler S et al (2015) Quantitative assessment of inflammation in a porcine acute terminal ileitis model: US with a molecularly targeted contrast agent. Radiology 276:809–817

    Article  PubMed  PubMed Central  Google Scholar 

  19. Wang H, Machtaler S, Bettinger T et al (2013) Molecular imaging of inflammation in inflammatory bowel disease with a clinically translatable dual-selectin-targeted US contrast agent: comparison with FDG PET/CT in a mouse model. Radiology 267:818–829

    Article  PubMed  PubMed Central  Google Scholar 

  20. Machtaler S, Knieling F, Luong R, Tian L, Willmann JK (2015) Assessment of inflammation in an acute on chronic model of inflammatory bowel disease with ultrasound molecular imaging. Theranostics 5:1175–1186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Haas K, Rubesova E, Bass D (2016) Role of imaging in the evaluation of inflammatory bowel disease: How much is too much? World J Radiol 8:124–131

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ewertsen C, Saftoiu A, Gruionu LG, Karstrup S, Nielsen MB (2013) Real-time image fusion involving diagnostic ultrasound. AJR American Journal of Roentgenology 200:W249–W255

    Article  PubMed  Google Scholar 

  23. Lee MW (2014) Fusion imaging of real-time ultrasonography with CT or MRI for hepatic intervention. Ultrasonography 33:227–239

    Article  PubMed  PubMed Central  Google Scholar 

  24. Diana M, Halvax P, Mertz D et al (2015) Improving echo-guided procedures using an ultrasound-CT image fusion system. Surg Innov 22:217–222

    Article  PubMed  Google Scholar 

  25. Burke CJ, Bencardino J, Adler R (2017) The potential use of ultrasound-magnetic resonance imaging fusion applications in musculoskeletal intervention. J Ultrasound Med 36:217–224

    Article  PubMed  Google Scholar 

  26. Kilcoyne A, Kaplan JL, Gee MS (2016) Inflammatory bowel disease imaging: current practice and future directions. World J Gastroenterol 22:917–932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Puylaert CA, Tielbeek JA, Bipat S, Stoker J (2015) Grading of Crohn's disease activity using CT, MRI, US and scintigraphy: a meta-analysis. Eur Radiol 25:3295–3313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Deepak P, Kolbe AB, Fidler JL, Fletcher JG, Knudsen JM, Bruining DH (2016) Update on magnetic resonance imaging and ultrasound evaluation of Crohn's disease. Gastroenterol Hepatol (N Y) 12:226–236

    Google Scholar 

  29. Al-Bawardy B, Hansel SL, Fidler JL, Barlow JM, Bruining DH (2017) Endoscopic and radiographic assessment of Crohn's disease. Gastroenterol Clin North Am 46:493–513

    Article  PubMed  Google Scholar 

  30. Moran CP, Neary B, Doherty GA (2016) Endoscopic evaluation in diagnosis and management of inflammatory bowel disease. World J Gastrointest Endosc 8:723–732

    Article  PubMed  PubMed Central  Google Scholar 

  31. Stanley E, Moriarty HK, Cronin CG (2016) Advanced multimodality imaging of inflammatory bowel disease in 2015: an update. World J Radiol 8:571–580

    Article  PubMed  PubMed Central  Google Scholar 

  32. Kljucevsek D, Vidmar D, Urlep D, Dezman R (2016) Dynamic contrast-enhanced ultrasound of the bowel wall with quantitative assessment of Crohn's disease activity in childhood. Radiol Oncol 50:347–354

    Article  PubMed  PubMed Central  Google Scholar 

  33. Ripolles T, Rausell N, Paredes JM, Grau E, Martinez MJ, Vizuete J (2013) Effectiveness of contrast-enhanced ultrasound for characterisation of intestinal inflammation in Crohn's disease: a comparison with surgical histopathology analysis. J Crohns Colitis 7:120–128

    Article  PubMed  Google Scholar 

  34. Wong DD, Forbes GM, Zelesco M, Mason R, Pawlik J, Mendelson RM (2012) Crohn's disease activity: quantitative contrast-enhanced ultrasound assessment. Abdom Imaging 37:369–376

    Article  PubMed  Google Scholar 

  35. Bachmann C, Klibanov AL, Olson TS et al (2006) Targeting mucosal addressin cellular adhesion molecule (MAdCAM)-1 to noninvasively image experimental Crohn's disease. Gastroenterology 130:8–16

    Article  CAS  PubMed  Google Scholar 

  36. Eppihimer MJ, Wolitzky B, Anderson DC, Labow MA, Granger DN (1996) Heterogeneity of expression of E- and P-selectins in vivo. Circ Res 79:560–569

    Article  CAS  PubMed  Google Scholar 

  37. Homeister JW, Zhang M, Frenette PS et al (1998) Overlapping functions of E- and P-selectin in neutrophil recruitment during acute inflammation. Blood 92:2345–2352

    CAS  PubMed  Google Scholar 

  38. Henseleit U, Steinbrink K, Goebeler M et al (1996) E-selectin expression in experimental models of inflammation in mice. J Pathol 180:317–325

    Article  CAS  PubMed  Google Scholar 

  39. Labow MA, Norton CR, Rumberger JM et al (1994) Characterization of E-selectin-deficient mice: demonstration of overlapping function of the endothelial selectins. Immunity 1:709–720

    Article  CAS  PubMed  Google Scholar 

  40. Bhatti M, Chapman P, Peters M, Haskard D, Hodgson HJ (1998) Visualising E-selectin in the detection and evaluation of inflammatory bowel disease. Gut 43:40–47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Schurmann GM, Bishop AE, Facer P et al (1995) Increased expression of cell adhesion molecule P-selectin in active inflammatory bowel disease. Gut 36:411–418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Jubeli E, Moine L, Vergnaud-Gauduchon J, Barratt G (2012) E-selectin as a target for drug delivery and molecular imaging. J Control Release 158:194–206

    Article  CAS  PubMed  Google Scholar 

  43. Magro F, Araujo F, Pereira P, Meireles E, Diniz-Ribeiro M, Velosom FT (2004) Soluble selectins, sICAM, sVCAM, and angiogenic proteins in different activity groups of patients with inflammatory bowel disease. Dig Dis Sci 49:1265–1274

    Article  CAS  PubMed  Google Scholar 

  44. Willmann JK, Bonomo L, Carla Testa A et al (2017) Ultrasound molecular imaging with BR55 in patients with breast and ovarian lesions: first-in-human results. J Clin Oncol 35:2133–2140

  45. Kim AY, Lee MW, Cha DI et al (2016) Automatic registration between real-time ultrasonography and pre-procedural magnetic resonance images: a prospective comparison between two registration methods by liver surface and vessel and by liver surface only. Ultrasound Med Biol 42:1627–1636

    Article  PubMed  Google Scholar 

  46. Hakime A, Deschamps F, De Carvalho EG, Teriitehau C, Auperin A, De Baere T (2011) Clinical evaluation of spatial accuracy of a fusion imaging technique combining previously acquired computed tomography and real-time ultrasound for imaging of liver metastases. Cardiovasc Intervent Radiol 34:338–344

    Article  PubMed  Google Scholar 

  47. Walter U, Muller JU, Rosche J et al (2016) Magnetic resonance-transcranial ultrasound fusion imaging: A novel tool for brain electrode location. Mov Disord 31:302–309

    Article  PubMed  Google Scholar 

  48. Prada F, Del Bene M, Mattei L et al (2014) Fusion imaging for intra-operative ultrasound-based navigation in neurosurgery. J Ultrasound 17:243–251

    Article  PubMed  PubMed Central  Google Scholar 

  49. Maxeiner A, Stephan C, Durmus T, Slowinski T, Cash H, Fischer T (2015) Added value of multiparametric ultrasonography in magnetic resonance imaging and ultrasonography fusion-guided biopsy of the prostate in patients with suspicion for prostate cancer. Urology 86:108–114

    Article  PubMed  Google Scholar 

  50. Baek J, Huh J, Kim M et al (2013) Accuracy of volume measurement using 3D ultrasound and development of CT-3D US image fusion algorithm for prostate cancer radiotherapy. Med Phys 40:021704

    Article  PubMed  Google Scholar 

  51. Kousaka J, Nakano S, Ando T et al (2016) Targeted sonography using an image fusion technique for evaluation of incidentally detected breast lesions on chest CT: a pilot study. Breast Cancer 23:301–309

    Article  PubMed  Google Scholar 

  52. Pickles MD, Gibbs P, Hubbard A et al (2015) Registration of supine MR mammography with breast ultrasound for surgical planning of breast conserving surgery: a feasibility study. Ultraschall Med. https://doi.org/10.1055/s-0041-108008

  53. Helck A, Notohamiprodjo M, Danastasi M, Meinel F, Reiser M, Clevert DA (2012) Ultrasound image fusion - clinical implementation and potential benefits for monitoring of renal transplants. Clin Hemorheol Microcirc 52:179–186

    CAS  PubMed  Google Scholar 

  54. Amalou H, Wood BJ (2012) Multimodality fusion with MRI, CT, and ultrasound contrast for ablation of renal cell carcinoma. Case Rep Urol 2012:390912

  55. Iagnocco A, Perella C, D'Agostino MA, Sabatini E, Valesini G, Conaghan PG (2011) Magnetic resonance and ultrasonography real-time fusion imaging of the hand and wrist in osteoarthritis and rheumatoid arthritis. Rheumatology 50:1409–1413

    Article  PubMed  Google Scholar 

  56. Liu J, Zhan W, Zhou M, Zhang X, Hu Y, Zhu Y (2012) The feasibility study of US-MRI virtual navigation in the shoulder. Clin Imaging 36:803–809

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Rebecca Fahrig, PhD, and the Zeego Laboratory at Stanford University for the C-arm CT imaging technical support.

Funding

This study has received funding by NIH R01DK092509 grant (JKW).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jürgen K. Willmann.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Jürgen K. Willmann.

Conflict of interest:

The authors of this manuscript except T.B. declare no relationships with any companies, whose products or services may be related to the subject matter of the article. T.B. is an employee of Bracco Suisse SA. Bracco Suisse SA only provided the contrast agents used in this study, but was not involved in planning and performing of the study, nor in analyzing or interpretation of the data.

Statistics and biometry

One of the authors has significant statistical expertise.

Ethical approval

Approval from the institutional animal care committee was obtained.

Methodology

• prospective

• experimental

• performed at one institution

Electronic supplementary material

ESM 1

(DOCX 31 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, H., Felt, S.A., Guracar, I. et al. Anatomical Road Mapping Using CT and MR Enterography for Ultrasound Molecular Imaging of Small Bowel Inflammation in Swine. Eur Radiol 28, 2068–2076 (2018). https://doi.org/10.1007/s00330-017-5148-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-017-5148-6

Keywords

Navigation