Acta Neurochirurgica

, Volume 158, Issue 4, pp 685–694 | Cite as

Intraoperative 3D contrast-enhanced ultrasound (CEUS): a prospective study of 50 patients with brain tumours

  • Felix Arlt
  • Claire Chalopin
  • Andrea Müns
  • Jürgen Meixensberger
  • Dirk Lindner
Clinical Article - Brain Tumors



Reliable intraoperative resection control during surgery of malignant brain tumours is associated with the longer overall survival of patients. B-mode ultrasound (BUS) is a familiar intraoperative imaging application in neurosurgical procedures and supplies excellent image quality. However, due to resection-induced artefacts, its ability to distinguish between tumour borders, oedema, surrounding tissue and tumour remnants is sometimes limited. In experienced hands, this “bright rim effect” could be reduced. However, it should be determined, if contrast-enhanced ultrasound can improve this situation by providing high-quality imaging during the resection. The aim of this clinical study was to examine contrast-enhanced and three-dimensional reconstructed ultrasound (3D CEUS) in brain tumour surgery regarding the uptake of contrast agent pre- and post-tumour resection, imaging quality and in comparison with postoperative magnetic resonance imaging in different tumour entities.


Fifty patients, suffering from various brain tumours intra-axial and extra-axial, who had all undergone surgery with the support of neuronavigation in our neurosurgical department, were included in the study. Their median age was 56 years (range, 28–79). Ultrasound imaging was performed before the Dura was opened and for resection control at the end of tumour resection as defined by the neurosurgeon. A high-end ultrasound (US) device (Toshiba Aplio XG®) with linear and sector probes for B-mode and CEUS was used. Navigation and 3D reconstruction were performed with a LOCALITE SonoNavigator® and the images were transferred digitally (DVI) to the navigation system. The contrast agent consists of echoic micro-bubbles showing tumour vascularisation. The ultrasound images were compared with the corresponding postoperative MR data in order to determine the accuracy and imaging quality of the tumours and tumour remnants after resection.


Different types of tumours were investigated. High, dynamic contrast agent uptake was observed in 19 of 21 patients (90 %) suffering from glioblastoma, while in 2 patients uptake was low and insufficient. In 52.4 % of glioblastoma and grade III astrocytoma patients CEUS led to an improved delineation in comparison to BUS and showed a high-resolution imaging quality of the tumour margins and tumour boarders. Grade II and grade III astrocytoma (n = 6) as well as metastasis (n = 18) also showed high contrast agent uptake, which led in 50 % to an improved imaging quality. In 5 of these 17 patients, intraoperative CEUS for resection control showed tumour remnants, leading to further tumour resection. Patients treated with CEUS showed no increased neurological deficits after tumour resection. No pharmacological side-effects occurred.


Three-dimensional CEUS is a reliable intraoperative imaging modality and could improve imaging quality. Ninety percent of the high-grade gliomas (HGG, glioblastoma and astrocytoma grade III) showed high contrast uptake with an improved imaging quality in more than 50 %. Gross total resection and incomplete resection of glioblastoma were adequately highlighted by 3D CEUS intraoperatively. The application of US contrast agent could be a helpful imaging tool, especially for resection control in glioblastoma surgery.


Intraoperative ultrasound Contrast-enhanced ultrasound Resection control Brain tumour surgery Navigated ultrasound 


Compliance with ethical standards


DFG (Deutsche Forschungsgemeinschaft) provided financial support in the form of hardware and personal costs funding. The sponsor had no role in the design or execution of this research.

Human and Animal Rights and Informed Consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent was obtained from all individual participants included in the study.

Conflicts of interest



  1. 1.
    Coburger J, König RW, Scheuerle A, Engelke J, Hlavac M, Thal DR, Wirtz CR (2014) Navigated high frequency ultrasound: description of technique and clinical comparison with conventional intracranial ultrasound. World Surg 82:366–75Google Scholar
  2. 2.
    Lindner D, Trantakis C, Arnold S, Schmitgen A, Schneider J, Meixensberger J (2005) Neuronavigation based on intraoperative 3D-ultrasound during tumor resection. Proceedings of computer assisted radiology and surgery. CARS. 815–820Google Scholar
  3. 3.
    Selbekk T, Jakola AS, Solheim O (2013) Ultrasound imaging in neurosurgery: approaches to minimize surgically induced image artefacts for improved resection control. Acta Neurochir (Wein) 155:973–980CrossRefGoogle Scholar
  4. 4.
    Unsgaard G, Gronningsaeter A, Ommedal S, Nagelhus Hernes TA (2002) Brain operations guided by real-time two-dimensional ultrasound: new possibilities as a result of improved image quality. Neurosurgery 51:402–412PubMedGoogle Scholar
  5. 5.
    Willems PW, Taphoorn MJB, Burger H, van der Sprenkel JWB, Tulleken CAF (2006) Effectiveness of neuronavigation in resecting solitary intracerebral contrast-enhancing tumors: a randomized controlled trial. J Neurosurg 104:360–368CrossRefPubMedGoogle Scholar
  6. 6.
    Unsgaard G, Ommedal S, Muller T, Gronningsaeter A, Nagelhus Hernes TA (2002) Neuronavigation by intraoperative three-dimensional ultrasound: initial experience during brain tumor resection. Neurosurgery 50:804–812CrossRefPubMedGoogle Scholar
  7. 7.
    Busse H, Schmitgen A, Trantakis C, Schober R, Kahn T, Moche M (2006) Advanced approach for intraoperative MRI guidance and potential benefit for neurosurgical applications. J Magn Reson Imaging 24:140–151CrossRefPubMedGoogle Scholar
  8. 8.
    Chalopin C, Krissian K, Meixensberger J, Müns A, Arlt F, Lindner D (2013) Evaluation of a semi-automatic segmentation algorithm in 3D intraoperative ultrasound brain angiography. Biomed Tech 58:293–30CrossRefGoogle Scholar
  9. 9.
    Kaps M, Legemate DA, Ries F, Ackerstaff RG, Markus H, Pezzoll C, Llull JB, Spinazzi A (2001) SonoVue in transcranial Doppler investigations of the cerebral arteries. J Neuroimaging 11:261–7CrossRefPubMedGoogle Scholar
  10. 10.
    Mert A, Buehler K, Sutherland GR, Tomanek B, Widhalm G, Kasprian G, Knosp E, Wolfsberger S (2012) Brain tumor surgery with 3-dimensional surface navigation. Neurosurgery 71:286–94Google Scholar
  11. 11.
    Müns A, Mühl C, Haase R, Möckel H, Chalopin C, Meixensberger J, Lindner D (2014) A neurosurgical phantom-based training system with ultrasound simulation. Acta Neurochir (Wein) 156:1237–43CrossRefGoogle Scholar
  12. 12.
    Renovanz M, Hickmann AK, Henkel C, Nadji-Ohl M, Hopf NJ (2014) Navigated versus non-navigated intraoperative ultrasound: is there any impact on the extent of resection of high-grade gliomas? A retrospective clinical analysis. Neurol Surq A Centr Eur Neurosurq 75:224–30CrossRefGoogle Scholar
  13. 13.
    Trantakis C, Meixensberger J, Lindner D, Strauss G, Grunst G, Schmidtgen A, Arnold S (2002) Iterative neuronavigation using 3D ultrasound. A feasibility study. Neurol Res 24:666–670CrossRefPubMedGoogle Scholar
  14. 14.
    Lindseth F, Kaspersen JH, Ommedal S (2003) Multimodal image fusion in ultrasound-based neuronavigation: improving overview and interpretation by integrating preoperative MRI with intraoperative 3D ultrasound. Comput Aided Surg 8:49–69CrossRefPubMedGoogle Scholar
  15. 15.
    Reinertsen I, Lindseth F, Askeland C, Iversen DH, Unsgård G (2014) Intra-operative correction of brain-shift. Acta Neurochir (Wein) 156:1301–10CrossRefGoogle Scholar
  16. 16.
    Senft C, Bink A, Franz K, Vatter H, Gasser T, Seifert V (2011) Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncol 12:997–1003CrossRefPubMedGoogle Scholar
  17. 17.
    Prada F, Perin A, Martegani A (2014) Intraoperative contrast enhanced ultra-sound (iCEUS) for brain surgery. Neurosurgery 74:542–552CrossRefPubMedGoogle Scholar
  18. 18.
    Kate GL, van Dijk AC, van den Oord SC, Hussain B, Verhagen HJ, Sijbrands EJ, van der Steen AF, van der Lugt A, Schinkel AF (2013) Usefulness of contrast-enhanced ultrasound for detection of carotid plaque ulceration in patients with symptomatic carotid atherosclerosis. Am J Cardiol 112:292–8CrossRefPubMedGoogle Scholar
  19. 19.
    Nanda NC, Wistran DC, Karlsberg RP, Hack TC, Smith WB, Foley DA, Picard MH, Cotter B (2002) Multicenter evaluation of SonoVue for improved endocardial border delineation. Echocardiography 19:27–36CrossRefPubMedGoogle Scholar
  20. 20.
    Park KH, Kwon SH, Lee YS, Jeong SW, Jang JY, Lee SH, Kim SG, Cha SW, Kim YS, Cho YD, Kim HS, Kim BS, Kim YJ (2015) Predictive factors of contrast-enhanced ultrasonography for the response to transarterial chemoembolization in hepatocellular carcinoma. Clin Mol Hepatol 21:158–64CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Bogdahn U, Fröhlich T, Becker G (1994) Vascularization of primary central nervous system tumors: detection with contrast-enhanced transcranial color-coded real-time sonography. Radiology 192:141–148CrossRefPubMedGoogle Scholar
  22. 22.
    Claudon M, Cosgrove D, Albrecht T (2008) Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS)—update 2008. Ultraschall Med 29:28–44CrossRefPubMedGoogle Scholar
  23. 23.
    Engelhardt M, Hansen C, Eyding J (2007) Feasibility of contrast-enhanced sonography during resection of cerebral tumours: initial results of a prospective study. Ultrasound Med Biol 33:571–575CrossRefPubMedGoogle Scholar
  24. 24.
    He W, Jiang X-Q, Wang S (2008) Intraoperative contrast-enhanced ultrasound for brain tumors. Clin Imaging 32:419–424CrossRefPubMedGoogle Scholar
  25. 25.
    Prada F, Mattei L, DelBene M, Aiani L, Saini M (2014) Intraoperative cerebral glioma characterization with contrast enhanced ultrasound. Biomed Res Int. 484261Google Scholar
  26. 26.
    Quaia E (2011) Assessment of tissue perfusion by contrast-enhanced ultrasound. Eur Radiol 21:604–615CrossRefPubMedGoogle Scholar
  27. 27.
    Woydt M, Krone A, Becker G, Schmidt K, Roggendorf W, Roosen K (1996) Correlation of intra-operative ultrasound with histopathologic findings after tumour resection in supratentorial gliomas. A method to improve gross total tumour resection. Acta Neurochir (Wein) 138:1391–1398CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Felix Arlt
    • 1
  • Claire Chalopin
    • 2
  • Andrea Müns
    • 1
  • Jürgen Meixensberger
    • 1
    • 2
  • Dirk Lindner
    • 1
  1. 1.Klinik und Poliklinik für NeurochirurgieUniversitätsklinik LeipzigLeipzigGermany
  2. 2.ICCAS (Innovation Centre Computer Assisted Surgery)LeipzigGermany

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