Introduction: Glioma surgery is aimed at obtaining maximal safe tumor resection while preserving or improving patient's neurological status. For this reason, there is growing interest for intra-operative imaging in neuro-oncological surgery. Intra-operative ultrasound (ioUS) provides the surgeon with real-time, anatomical and functional information. Despite this, in neurosurgery ioUS mainly relies only on gray-scale brightness mode (B-mode). Many other ultrasound imaging modalities, such as Fusion Imaging with pre-operative acquired magnetic resonance imaging (MRI), Doppler modes, Contrast Enhanced Ultrasound (CEUS), and elastosonography have been developed and have been extensively used in other organs. Although these modalities offer valuable real-time intra-operative information, so far their usage during neurosurgical procedures is still limited.Purpose: To present an US-based multimodal approach for image-guidance in glioma surgery, highlighting the different features of advanced US modalities: fusion imaging with pre-operative acquired MRI for Virtual Navigation, B-mode, Doppler (power-, color-, spectral-), CEUS, and elastosonography.Methods: We describe, in a step-by-step fashion, the applications of the most relevant advanced US modalities during different stages of surgery and their implications for surgical decision-making. Each US modality is illustrated from a technical standpoint and its application during glioma surgery is discussed.Results: B-mode offers dynamic morphological information, which can be further implemented with fusion imaging to improve image understanding and orientation. Doppler imaging permits to evaluate anatomy and function of the vascular tree. CEUS allows to perform a real-time angiosonography, providing valuable information in regards of parenchyma and tumor vascularization and perfusion. This facilitates tumor detection and surgical strategy, also allowing to characterize tumor grade and to identify residual tumor. Elastosonography is a promising tool able to better define tumor margins, parenchymal infiltration, tumor consistency and permitting differentiation of high grade and low grade lesions.Conclusions: Multimodal ioUS represents a valuable tool for glioma surgery being highly informative, rapid, repeatable, and real-time. It is able to differentiate low grade from high grade tumors and to provide the surgeon with relevant information for surgical decision-making. ioUS could be integrated with other intra-operative imaging and functional approaches in a synergistic manner to offer the best image guidance for each patient.
