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Development and validation of an intrinsic landmark-based gating protocol applicable for functional and molecular ultrasound imaging

  • Molecular Imaging
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

To implement a retrospective intrinsic landmark-based (ILB) gating protocol for contrast-enhanced ultrasound (CEUS) and to compare its efficiency to non-gated, manually gated and extrinsically gated CEUS.

Methods

CEUS of the liver was performed in healthy mice (n = 5) and in NEMO knockout mice with dysplastic livers (n = 5). In healthy animals, first-pass kinetics of non-specific microbubbles was recorded. Knockout mice were analysed regarding retention of VEGFR2-specific microbubbles. For retrospective gating, a landmark which showed respiratory movement was encircled as a region of interest (ROI). During inspiration, the signal intensity within the ROI altered, which served as gating signal. To evaluate the accuracy, non-gated, extrinsically gated and ILB-gated time-intensity curves were created. For each curve, descriptive parameters were calculated and compared to the gold standard (manual frame-by-frame gating).

Results

No significant differences in the variation of ILB- and extrinsically gated time-intensity curves from the gold standard were observed. Non-gated data showed significantly higher variations. Also the variation of molecular ultrasound data was significantly lower for ILB-gated compared to non-gated data.

Conclusion

ILB gating is a robust and easy method to improve data accuracy in functional and molecular ultrasound liver imaging. This technique can presumably be translated to contrast-enhanced ultrasound examinations in humans.

Key Points

Quantitative analysis of the uptake of contrast agents during ultrasound is complex.

Intrinsic landmark-based gating (ILB) offers a simple implementable method for motion correction.

Results using ILB-gating are comparable to extrinsic gating using external biomonitoring devices.

Functional and molecular imaging of mobile organs will benefit from ILB gating.

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Abbreviations

ROI:

Region of interest

CEUS:

Contrast-enhanced ultrasound

ILB-gating:

Intrinsic landmark-based gating

AUC:

Area under the curve

VEGFR2:

Vascular endothelial growth factor receptor type 2

References

  1. Averkiou M, Lampaskis M, Kyriakopoulou K et al (2010) Quantification of tumor microvascularity with respiratory gated contrast enhanced ultrasound for monitoring therapy. Ultrasound Med Biol 36:68–77

    Article  PubMed  Google Scholar 

  2. Beraza N, Malato Y, Sander LE et al (2009) Hepatocyte-specific NEMO deletion promotes NK/NKT cell- and TRAIL-dependent liver damage. J Exp Med 206:1727–1737

    Article  PubMed  CAS  Google Scholar 

  3. Bettermann K, Vucur M, Haybaeck J et al (2010) TAK1 suppresses a NEMO-dependent but NF-kappaB-independent pathway to liver cancer. Cancer Cell 17:481–496

    Article  PubMed  CAS  Google Scholar 

  4. Blessberger H, Binder T (2010) Non-invasive imaging. Two dimensional speckle tracking echocardiography: basic principles. Heart 96:716–722

    Article  PubMed  Google Scholar 

  5. Bzyl J, Lederle W, Rix A et al (2011) Molecular and functional ultrasound imaging in differently aggressive breast cancer xenografts using two novel ultrasound contrast agents (BR55 and BR38). Eur Radiol 21:1988–1995

    Article  PubMed  Google Scholar 

  6. Garbow JR, Ackerman JJ (2011) Imaging primary lung cancers in mice to study radiation biology: in regard to Kirsch et al. (Int J Radiat Oncol Biol Phys 2010;76:973–977). Int J Radiat Oncol Biol Phys 79:959, author reply 959

    Article  PubMed  Google Scholar 

  7. Hotz HG, Reber HA, Hotz B et al (2003) An orthotopic nude mouse model for evaluating pathophysiology and therapy of pancreatic cancer. Pancreas 26:e89–e98

    Article  PubMed  Google Scholar 

  8. Kang BH, Siegelin MD, Plescia J et al (2010) Preclinical characterization of mitochondria-targeted small molecule hsp90 inhibitors, gamitrinibs, in advanced prostate cancer. Clin Cancer Res 16:4779–4788

    Article  PubMed  CAS  Google Scholar 

  9. Kerbel RS, Cornil I, Theodorescu D (1991) Importance of orthotopic transplantation procedures in assessing the effects of transfected genes on human tumor growth and metastasis. Cancer Metastasis Rev 10:201–215

    Article  PubMed  CAS  Google Scholar 

  10. Kiessling F, Gaetjens J, Palmowski M (2011) Application of molecular ultrasound for imaging integrin expression. Theranostics 1:127–134

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  12. Mule S, Kachenoura N, Lucidarme O et al (2011) An automatic respiratory gating method for the improvement of microcirculation evaluation: application to contrast-enhanced ultrasound studies of focal liver lesions. Phys Med Biol 56:5153–5165

    Article  PubMed  CAS  Google Scholar 

  13. Orlacchio A, Bolacchi F, Petrella MC et al (2011) Liver contrast enhanced ultrasound perfusion imaging in the evaluation of chronic hepatitis C fibrosis: preliminary results. Ultrasound Med Biol 37:1–6

    Article  PubMed  Google Scholar 

  14. Palmowski M, Huppert J, Ladewig G et al (2008) Molecular profiling of angiogenesis with targeted ultrasound imaging: early assessment of antiangiogenic therapy effects. Mol Cancer Ther 7:101–109

    Article  PubMed  CAS  Google Scholar 

  15. Palmowski M, Lederle W, Gaetjens J et al (2010) Comparison of conventional time-intensity curves vs. maximum intensity over time for post-processing of dynamic contrast-enhanced ultrasound. Eur J Radiol 75:e149–e153

    Article  PubMed  Google Scholar 

  16. Palmowski M, Peschke P, Huppert J et al (2009) Molecular ultrasound imaging of early vascular response in prostate tumors irradiated with carbon ions. Neoplasia 11:856–863

    PubMed  CAS  Google Scholar 

  17. Paprottka PM, Cyran CC, Zengel P et al (2010) Non-invasive contrast enhanced ultrasound for quantitative assessment of tumor microcirculation. Contrast mixed mode examination vs. only contrast enhanced ultrasound examination. Clin Hemorheol Microcirc 46:149–158

    PubMed  CAS  Google Scholar 

  18. Pillai R, Marinelli ER, Fan H et al (2010) A phospholipid-PEG2000 conjugate of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeting heterodimer peptide for contrast-enhanced ultrasound imaging of angiogenesis. Bioconjug Chem 21:556–562

    Article  CAS  Google Scholar 

  19. Pochon S, Tardy I, Bussat P et al (2010) BR55: a lipopeptide-based VEGFR2-targeted ultrasound contrast agent for molecular imaging of angiogenesis. Invest Radiol 45:89–95

    Article  PubMed  CAS  Google Scholar 

  20. Renault G, Tranquart F, Perlbarg V, Bleuzen A, Herment A, Frouin F (2005) A posteriori respiratory gating in contrast ultrasound for assessment of hepatic perfusion. Phys Med Biol 50:4465–4480

    Article  PubMed  CAS  Google Scholar 

  21. Willmann JK, Paulmurugan R, Chen K et al (2008) US imaging of tumor angiogenesis with microbubbles targeted to vascular endothelial growth factor receptor type 2 in mice. Radiology 246:508–518

    Article  PubMed  Google Scholar 

  22. Willmann JK, van Bruggen N, Dinkelborg LM, Gambhir SS (2008) Molecular imaging in drug development. Nat Rev Drug Discov 7:591–607

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by the German Ministry for Education and Research (BMBF), project “Virtual Liver Consortium”, number 0315743 and by the German Research Foundation (DFG) SFB TRR57.

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Correspondence to Moritz Palmowski.

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Grouls, C., Hatting, M., Tardy, I. et al. Development and validation of an intrinsic landmark-based gating protocol applicable for functional and molecular ultrasound imaging. Eur Radiol 22, 1789–1796 (2012). https://doi.org/10.1007/s00330-012-2429-y

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  • DOI: https://doi.org/10.1007/s00330-012-2429-y

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