Intraoperative computed tomography, navigated ultrasound, 5-amino-levulinic acid fluorescence and neuromonitoring in brain tumor surgery: overtreatment or useful tool combination?

Background: Brain tumor surgery is routinely supported by several intraoperative techniques, such as fluorescence, brain mapping and neuronavigation, which are often used independently. Efficacy of navigation is limited by the brain-shift phenomenon, particularly in cases of large or deep-sited lesions. Intraoperative imaging was introduced also to update neuronavigation data, to try and solve the brain-shift phenomenon-related pitfalls and increase overall safety. Nevertheless, each intraoperative imaging modality has some intrinsic limitations and technical shortcomings, making its clinical use challenging. We used a multimodal intraoperative imaging protocol to update neuronavigation, based on the combination of intraoperative Ultrasound (i-US) and intraoperative Computed Tomography (i-CT) integrated with 5-ALA fluorescence and neuromonitoring-guided resection.

Methods: This is a pilot study on 52 patients (29 men), including four children, with a mean age of 57.67 years, suffering from brain low- (N.=10) or high-grade (N.=34) glioma or metastasis (N.=8), prospectively and consecutively enrolled. They underwent 5-ALA fluorescence-guided microsurgical tumor resection and neuromonitoring was used in cases of lesions located in eloquent areas, according to preoperative clinical and neuroradiological features. Navigated B-mode ultrasound acquisition was carried out after dural opening to identify the lesion. After tumor resection, i-US was used to identify residual tumor. Following further tumor resection or in cases of unclear US images, post-contrast i-CT was performed to detect and localize small tumor remnants and to allow further correction for brain shift. A final i-US check was performed to verify the completeness of resection. Clinical evaluation was based on comparison of pre- and postoperative Karnofsky Performance Score (KPS) and assessment of overall survival (OS) and progression-free survival (PFS). Extent of tumor resection (EOTR) was evaluated by volumetric postoperative Magnetic Resonance performed within 48 h after surgery.

Results: Forty-one of the 52 (78.8%) patients were alive and still under follow-up in December 2017. 5-ALA was strongly or vaguely positive in 45 cases (86.5%). Seven lesions (four low-grade glioma, one high-grade glioma, and two metastases) were not fluorescent. i-US visualized residual tumor after resection of all fluorescent or pathological tissue in 22 cases (42.3%). After i-US guided resection, i-CT documented the presence of further residual tumor in 11 cases (21.1%). Mean EOTR was 98.79% in the low-grade gliomas group, 99.84% in the high-grade gliomas group and 100% in the metastases group. KPS changed from 77.88, preoperatively, to 72.5, postoperatively. At the last follow-up, mean KPS was 84.23.

Conclusions: The combination of different intraoperative imaging modalities may increase brain tumor safety and extent of resection. In particular, i-US seems to be highly sensitive to detect residual tumors, but it may generate false positives due to artifacts. Conversely, i-CT is more specific to localize remnants, allowing a more reliable updating of navigation data.