## 2 Materials and Methods  
The prospective study included initially 37 patients, who were operated between February 2019 and July 2020. In the course of the study, two cases had to be excluded due incomplete image acquisition. In all participants, preoperative MRI detected at least one lesion suggestive of brain metastasis and an interdisciplinary tumor board recommended resection. We obtained informed consent from all patients included in this study and received ethics approval for prospectively archiving clinical and technical data applying intraoperative imaging and navigation (study no. 99/18). All patients received an MRI within a few days before resection, typically encompassing a 3D data set of T1-weighted contrast-enhanced images. These were transferred to the navigational system (Brainlab, Munich, Germany), which consists of a ceiling mounted double monitor (Curve, Brainlab, Munich, Germany) and two displays (Buzz, Brainlab, Munich, Germany) and navigational software. All patients were operated under general anesthesia. After narcosis induction the patients were positioned on the operating room (OR) table and the head was fixed to a radiolucent carbon Doro head clamp with metallic pins. A reference array with four reflective markers was attached to the head clamp. Three fiducial markers were placed on the head within the scanning area, which were not needed for registration. The OR table was rotated 90\({}^{\circ}\) to the 32-slice mobile CT scanner (AIRO, Brainlab, Munich) and a low-dose registration scan of 62 mm scan length was performed. Reflective markers, which are permanently attached to the AIRO scanner, and the reference array must be in the field of view of the navigational camera during the scanning process. The CT scan was automatically transferred to the navigational system and fused with the preoperative imaging datasets, establishing automatic patient registration. The patient was rotated back, and registration accuracy was checked by placing the navigational pointer into the divot of each skin fiducial. This allows the calculation of a target registration error as the Euclidian offset of the pointer tip. The reference array was removed and replaced by a sterile one after draping. Details of the aforementioned set-up, scanning process, and patient registration were published before [35]. All patients received 40 mg of dexamethasone. After team time-out, skin disinfection, and sterile draping, the skin was incised. One-hundred-and-twenty-five milliliters of mannitol 15% was administered before craniotomy. After bone flap removal, and before dural opening, a navigated i3D US dataset was acquired using the bk5000 system (bk medical, Herlev, Denmark), which was connected to the navigational system. For acquisition, a reference array with three reflective markers is attached to the precalibrated bk medical transducer N13C5, which is fully immersible, can be sterilized and therefore be used without a sterile cover. The transducer offers a convex contact surface of \(29\times 10\) mm and has a scanning frequency of 5-13 MHz. Whenever possible, the patient's head was positioned in a way exposing the dura horizontally after bone removal, allowing a saline depot to be administered as a coupling fluid. During image acquisition the probe was smoothly swept over the dura, whilst the reference arrays attached to the head clamp and the transducer were in the line of sight of the navigational camera (Figure 11). The bk5000 actually generated 2D slices of 0.3 mm, which were transformed into 3D image volumes and automatically registered by the navigational software (Figure 1a). Those 3D data sets, which were now available during the further surgical procedure, were displayed in an overlay or side-by-side fashion, or as a standalone and could be reformatted to an oblique plane matching the surgeon's view through the operating microscope (Figure 1b,c). A second image acquisition was performed after tumor removal as a resection control or if demanded at any timepoint during the surgery.