Fusion of Intraoperative 3D B-mode and Contrast-Enhanced Ultrasound Data for Automatic Identification of Residual Brain Tumors  
[PERSON], [PERSON], [PERSON], [PERSON], [PERSON], [PERSON]  
imaging is therefore crucial to provide the surgeon with an update representation of the current tumor state during the operation. Modern intraoperative imaging modalities for neurosurgery are MR, fluorescence and ultrasound modalities. Intraoperative MR imaging delivers image data of quality similar to pre- and post-operative datasets. However, investment and follow-up costs limit its use to a few hospitals only. Fluorescence imaging requires the oral taking by patients of a contrast agent, 5-aminolevulinic acid (5-ALA). This substance accumulates in malignant tumor cells and is emitted as a red fluorescence under blue light excitation (400 nm). Margins of surface tumor are visualized in the operating microscope view during the operation. The main limitations of this technique are: (1) the high cost of the drug and (2) the visualization of brain and tumor surface only. Therefore, intraoperative ultrasound (iUS) imaging is the most used imaging modality during brain tumor operations. Ultrasound devices have the advantage of being easy to use in the operating room and provide the benefit of real-time visualization of the brain anatomical structures. Hence, extra image acquisitions may modify the surgical workflow a little. Additionally, they are relatively low cost in comparison to other medical imaging systems. This intraoperative modality is routinely used to guide brain tumor operations. Particularly, iUS aims at identifying the presence of possible tumor residuals at the end of the operation, in order to remove as much tumor tissue as possible [1; 2]. This is a crucial aspect since several studies showed that a gross-total resection has a positive impact on the progression-free survival of patients. Figure 1 illustrates the surgeon using a US probe placed at the patient open head surface during the intraoperative US image acquisition. Intraoperative B-mode ultrasound (iB-mode) remains the most popular modality used to support brain tumor surgery, but is not always suitable. Hence, specific brain tumors (e.g., glial tumors) are often represented by a weak contrast, and the exact position of tumor boundaries is hard to define. Furthermore, the tumor residuals, which are located beyond the borders of the resection cavity, are hardly differentiable from blood and artifacts. The use of an ultrasound contrast agent to enhance brain tumor tissue and residual tumor is currently being developed. The technique is not new; contrast enhanced ultrasound (CEUS) imaging is routinely performed, and it was already tested in other medical areas like breast tumor diagnosis [3; 4], liver lesions [5; 6], renal masses [7; 8; 9] or blood vessel identification [10; 11; 12]. Additionally, improvements of brain tumor tissues and tumor residuals enhancement by using CEUS were effectively demonstrated by several recent studies [13; 14; 15; 16; 17]. However, the identification of tumor residuals in the iUS data remains in general complex for the expert-eye. Depending on the position of the tumor within the patient's head, the resection cavity, as well as other cerebral structures like blood vessels, potentially ventricles and bone structures, are usually well depicted in the iB-mode image data. However, the possible tumor residuals are hardly differentiable from other hyperechogenic structures, like the border of the resection cavity,  
Figure 1: Intraoperative 2D image acquisition with an ultrasound (US) probe placed at the patient open head surface during brain tumor surgery. blood or artifacts (Figure 2, left). Furthermore, it is only attempted to enhance the blood vessels and vascularized structures, like tumors, in the iCEUS image data. Furthermore, the borders of the resection cavity, which are important structures that are needed to analyze the images correctly, are hardly or not at all visible (Figure 2, right).