European Radiology

, Volume 22, Issue 8, pp 1789–1796 | Cite as

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

  • Christoph Grouls
  • Max Hatting
  • Isabelle Tardy
  • Jessica Bzyl
  • Georg Mühlenbruch
  • Florian F. Behrendt
  • Tobias Penzkofer
  • Christian Trautwein
  • Christiane Kuhl
  • Fabian Kiessling
  • Moritz Palmowski
Molecular Imaging

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.

Keywords

Gating Ultrasound Contrast enhanced Functional imaging Molecular imaging 

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

Notes

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.

References

  1. 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 36:68–77PubMedCrossRefGoogle Scholar
  2. 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 206:1727–1737PubMedCrossRefGoogle Scholar
  3. 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 17:481–496PubMedCrossRefGoogle Scholar
  4. 4.
    Blessberger H, Binder T (2010) Non-invasive imaging. Two dimensional speckle tracking echocardiography: basic principles. Heart 96:716–722PubMedCrossRefGoogle Scholar
  5. 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 21:1988–1995PubMedCrossRefGoogle Scholar
  6. 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 959PubMedCrossRefGoogle Scholar
  7. 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–e98PubMedCrossRefGoogle Scholar
  8. 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 16:4779–4788PubMedCrossRefGoogle Scholar
  9. 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 10:201–215PubMedCrossRefGoogle Scholar
  10. 10.
    Kiessling F, Gaetjens J, Palmowski M (2011) Application of molecular ultrasound for imaging integrin expression. Theranostics 1:127–134PubMedCrossRefGoogle Scholar
  11. 11.
    Kiessling F, Huppert J, Palmowski M (2009) Functional and molecular ultrasound imaging: concepts and contrast agents. Curr Med Chem 16:627–642PubMedCrossRefGoogle Scholar
  12. 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 56:5153–5165PubMedCrossRefGoogle Scholar
  13. 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 37:1–6PubMedCrossRefGoogle Scholar
  14. 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 7:101–109PubMedCrossRefGoogle Scholar
  15. 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–e153PubMedCrossRefGoogle Scholar
  16. 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 11:856–863PubMedGoogle Scholar
  17. 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 46:149–158PubMedGoogle Scholar
  18. 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 21:556–562CrossRefGoogle Scholar
  19. 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 45:89–95PubMedCrossRefGoogle Scholar
  20. 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 50:4465–4480PubMedCrossRefGoogle Scholar
  21. 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 246:508–518PubMedCrossRefGoogle Scholar
  22. 22.
    Willmann JK, van Bruggen N, Dinkelborg LM, Gambhir SS (2008) Molecular imaging in drug development. Nat Rev Drug Discov 7:591–607PubMedCrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2012

Authors and Affiliations

  • Christoph Grouls
    • 1
    • 2
  • Max Hatting
    • 3
  • Isabelle Tardy
    • 4
  • Jessica Bzyl
    • 1
  • Georg Mühlenbruch
    • 5
  • Florian F. Behrendt
    • 6
  • Tobias Penzkofer
    • 2
  • Christian Trautwein
    • 3
  • Christiane Kuhl
    • 2
  • Fabian Kiessling
    • 1
  • Moritz Palmowski
    • 1
    • 2
    • 6
  1. 1.Department of Experimental Molecular ImagingRWTH-Aachen UniversityAachenGermany
  2. 2.Department of Diagnostic and Interventional RadiologyRWTH-Aachen UniversityAachenGermany
  3. 3.Medical Clinic II, University HospitalRWTH-Aachen UniversityAachenGermany
  4. 4.Bracco Suisse SAGenevaSwitzerland
  5. 5.Department of Diagnostic and Interventional NeuroradiologyRWTH-Aachen UniversityAachenGermany
  6. 6.Department of Nuclear MedicineRWTH-Aachen UniversityAachenGermany

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