title: Intraoperative 3D contrast-enhanced ultrasound (CEUS): a prospective study of 50 patients with brain tumours.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Klinik und Poliklinik für Neurochirurgie, Universitätsklinik Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany. felix.arlt@medizin.uni-leipzig.de.
authors.forename: Felix
authors.initials: F
authors.lastname: Arlt
authors.affiliation: ICCAS (Innovation Centre Computer Assisted Surgery), Semmelweisstr 14, 04103, Leipzig, Germany.
authors.forename: Claire
authors.initials: C
authors.lastname: Chalopin
authors.affiliation: Klinik und Poliklinik für Neurochirurgie, Universitätsklinik Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Müns
authors.affiliation: Klinik und Poliklinik für Neurochirurgie, Universitätsklinik Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany.|ICCAS (Innovation Centre Computer Assisted Surgery), Semmelweisstr 14, 04103, Leipzig, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Meixensberger
authors.affiliation: Klinik und Poliklinik für Neurochirurgie, Universitätsklinik Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Lindner
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000601:surgery*; D004453:Echoencephalography / Q000295:instrumentation / Q000379:methods*; D005260:Female; D005909:Glioblastoma / Q000601:surgery*; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000295:instrumentation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D038361:Neuronavigation / Q000295:instrumentation / Q000379:methods*; D011446:Prospective Studies
keywords: Brain tumour surgery; Contrast-enhanced ultrasound; Intraoperative ultrasound; Navigated ultrasound; Resection control