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European Radiology

, Volume 28, Issue 5, pp 2068–2076 | Cite as

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

  • Huaijun Wang
  • Stephen A. Felt
  • Ismayil Guracar
  • Valentina Taviani
  • Jianhua Zhou
  • Rosa Maria Silveira Sigrist
  • Huiping Zhang
  • Joy Liau
  • José G. Vilches-Moure
  • Lu Tian
  • Yamil Saenz
  • Thierry Bettinger
  • Brian A. Hargreaves
  • Amelie M. Lutz
  • Jürgen K. Willmann
Ultrasound

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.

Keywords

Image fusion Molecular imaging Ultrasound CT enterography MR enterography 

Notes

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).

Compliance with ethical standards

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

Supplementary material

330_2017_5148_MOESM1_ESM.docx (31 kb)
ESM 1 (DOCX 31 kb)

References

  1. 1.
    Loftus EV Jr (2004) Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology 126:1504–1517CrossRefPubMedGoogle Scholar
  2. 2.
    Danese S (2012) New therapies for inflammatory bowel disease: from the bench to the bedside. Gut 61:918–932CrossRefPubMedGoogle Scholar
  3. 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 e30CrossRefPubMedGoogle Scholar
  4. 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 50:27–31CrossRefPubMedGoogle Scholar
  5. 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 e814-805CrossRefPubMedGoogle Scholar
  6. 6.
    Ahluwalia JP (2012) Immunotherapy in inflammatory bowel disease. Med Clin North Am 96:525–544CrossRefPubMedGoogle Scholar
  7. 7.
    Speight RA, Mansfield JC (2013) Drug advances in inflammatory bowel disease. Clin Med 13:378–382CrossRefGoogle Scholar
  8. 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 18:872–881CrossRefPubMedPubMedCentralGoogle Scholar
  9. 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 72:15–27CrossRefPubMedGoogle Scholar
  10. 10.
    Pysz MA, Willmann JK (2011) Targeted contrast-enhanced ultrasound: an emerging technology in abdominal and pelvic imaging. Gastroenterology 140:785–790 e786CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Kircher MF, Willmann JK (2012) Molecular body imaging: MR imaging, CT, and US. Part II. Applications. Radiology 264:349–368CrossRefPubMedGoogle Scholar
  12. 12.
    Kircher MF, Willmann JK (2012) Molecular body imaging: MR imaging, CT, and US. part I. principles. Radiology 263:633–643CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kamaya A, Machtaler S, Safari Sanjani S et al (2013) New technologies in clinical ultrasound. Semin Roentgenol 48:214–223CrossRefPubMedGoogle Scholar
  14. 14.
    Abou-Elkacem L, Bachawal SV, Willmann JK (2015) Ultrasound molecular imaging: Moving toward clinical translation. Eur J Radiol 84:1685–1693CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Kiessling F, Huppert J, Palmowski M (2009) Functional and molecular ultrasound imaging: concepts and contrast agents. Curr Med Chem 16:627–642CrossRefPubMedGoogle Scholar
  16. 16.
    Lindner JR (2009) Contrast ultrasound molecular imaging of inflammation in cardiovascular disease. Cardiovasc Res 84:182–189CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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 262:172–180CrossRefPubMedPubMedCentralGoogle Scholar
  18. 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 276:809–817CrossRefPubMedPubMedCentralGoogle Scholar
  19. 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 267:818–829CrossRefPubMedPubMedCentralGoogle Scholar
  20. 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 5:1175–1186CrossRefPubMedPubMedCentralGoogle Scholar
  21. 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 8:124–131CrossRefPubMedPubMedCentralGoogle Scholar
  22. 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–W255CrossRefPubMedGoogle Scholar
  23. 23.
    Lee MW (2014) Fusion imaging of real-time ultrasonography with CT or MRI for hepatic intervention. Ultrasonography 33:227–239CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Diana M, Halvax P, Mertz D et al (2015) Improving echo-guided procedures using an ultrasound-CT image fusion system. Surg Innov 22:217–222CrossRefPubMedGoogle Scholar
  25. 25.
    Burke CJ, Bencardino J, Adler R (2017) The potential use of ultrasound-magnetic resonance imaging fusion applications in musculoskeletal intervention. J Ultrasound Med 36:217–224CrossRefPubMedGoogle Scholar
  26. 26.
    Kilcoyne A, Kaplan JL, Gee MS (2016) Inflammatory bowel disease imaging: current practice and future directions. World J Gastroenterol 22:917–932CrossRefPubMedPubMedCentralGoogle Scholar
  27. 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 25:3295–3313CrossRefPubMedPubMedCentralGoogle Scholar
  28. 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) 12:226–236Google Scholar
  29. 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 46:493–513CrossRefPubMedGoogle Scholar
  30. 30.
    Moran CP, Neary B, Doherty GA (2016) Endoscopic evaluation in diagnosis and management of inflammatory bowel disease. World J Gastrointest Endosc 8:723–732CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Stanley E, Moriarty HK, Cronin CG (2016) Advanced multimodality imaging of inflammatory bowel disease in 2015: an update. World J Radiol 8:571–580CrossRefPubMedPubMedCentralGoogle Scholar
  32. 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 50:347–354CrossRefPubMedPubMedCentralGoogle Scholar
  33. 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 7:120–128CrossRefPubMedGoogle Scholar
  34. 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 37:369–376CrossRefPubMedGoogle Scholar
  35. 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 130:8–16CrossRefPubMedGoogle Scholar
  36. 36.
    Eppihimer MJ, Wolitzky B, Anderson DC, Labow MA, Granger DN (1996) Heterogeneity of expression of E- and P-selectins in vivo. Circ Res 79:560–569CrossRefPubMedGoogle Scholar
  37. 37.
    Homeister JW, Zhang M, Frenette PS et al (1998) Overlapping functions of E- and P-selectin in neutrophil recruitment during acute inflammation. Blood 92:2345–2352PubMedGoogle Scholar
  38. 38.
    Henseleit U, Steinbrink K, Goebeler M et al (1996) E-selectin expression in experimental models of inflammation in mice. J Pathol 180:317–325CrossRefPubMedGoogle Scholar
  39. 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 1:709–720CrossRefPubMedGoogle Scholar
  40. 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 43:40–47CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Schurmann GM, Bishop AE, Facer P et al (1995) Increased expression of cell adhesion molecule P-selectin in active inflammatory bowel disease. Gut 36:411–418CrossRefPubMedPubMedCentralGoogle Scholar
  42. 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 158:194–206CrossRefPubMedGoogle Scholar
  43. 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 49:1265–1274CrossRefPubMedGoogle Scholar
  44. 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 35:2133–2140Google Scholar
  45. 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 42:1627–1636CrossRefPubMedGoogle Scholar
  46. 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 34:338–344CrossRefPubMedGoogle Scholar
  47. 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 31:302–309CrossRefPubMedGoogle Scholar
  48. 48.
    Prada F, Del Bene M, Mattei L et al (2014) Fusion imaging for intra-operative ultrasound-based navigation in neurosurgery. J Ultrasound 17:243–251CrossRefPubMedPubMedCentralGoogle Scholar
  49. 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 86:108–114CrossRefPubMedGoogle Scholar
  50. 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 40:021704CrossRefPubMedGoogle Scholar
  51. 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 23:301–309CrossRefPubMedGoogle Scholar
  52. 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. 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 52:179–186PubMedGoogle Scholar
  54. 54.
    Amalou H, Wood BJ (2012) Multimodality fusion with MRI, CT, and ultrasound contrast for ablation of renal cell carcinoma. Case Rep Urol 2012:390912Google Scholar
  55. 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 50:1409–1413CrossRefPubMedGoogle Scholar
  56. 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 36:803–809CrossRefPubMedGoogle Scholar

Copyright information

© European Society of Radiology 2017

Authors and Affiliations

  • Huaijun Wang
    • 1
  • Stephen A. Felt
    • 2
  • Ismayil Guracar
    • 3
  • Valentina Taviani
    • 1
  • Jianhua Zhou
    • 1
  • Rosa Maria Silveira Sigrist
    • 1
  • Huiping Zhang
    • 1
  • Joy Liau
    • 1
  • José G. Vilches-Moure
    • 2
  • Lu Tian
    • 4
  • Yamil Saenz
    • 2
  • Thierry Bettinger
    • 5
  • Brian A. Hargreaves
    • 1
  • Amelie M. Lutz
    • 1
  • Jürgen K. Willmann
    • 1
  1. 1.Department of RadiologyStanford University, School of MedicineStanfordUSA
  2. 2.Department of Comparative MedicineStanford UniversityStanfordUSA
  3. 3.Siemens HealthcareUltrasound Business UnitMountain ViewUSA
  4. 4.Department of Health, Research & PolicyStanford UniversityStanfordUSA
  5. 5.Bracco Suisse SAGenevaSwitzerland

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