Intraoperative technological advances and new frontiers in precision glioma surgery

Diffuse gliomas remain among the most surgically challenging tumors, characterized by their infiltrative nature, proximity to eloquent brain structures, and the formidable barrier posed by the BBB to systemic therapeutic delivery. Maximizing extent of resection (EOR) while preserving neurological function remains a central determinant of survival and quality of life, and the iterative integration of intraoperative technologies into surgical practice has become essential to achieving this balance.

We performed a comprehensive narrative review of established and emerging intraoperative technologies for glioma surgery, organized around two clinical imperatives: optimizing tumor delineation and safe resection, and enhancing local therapeutic delivery.

Awake craniotomy with direct electrical stimulation remains the gold standard for preserving eloquent cortex and subcortical tracts, consistently reducing postoperative neurological deficits while increasing gross total resection rates. Fluorescence-guided surgery with 5-ALA and fluorescein enhances real-time tumor margin visualization, and their combined use achieves greater EOR than either agent alone. Intraoperative MRI compensates for progressive brain shift and, when used alongside 5-ALA, provides the strongest currently available platform for maximizing safe resection. Augmented reality navigation further enhances spatial orientation by overlaying 3D virtual anatomy directly onto the operative field. Emerging tissue characterization tools, including stimulated Raman histology, confocal laser endomicroscopy, and AI-based platforms such as FastGlioma and DeepGlioma, enable rapid intraoperative molecular diagnosis without the delays of conventional frozen section pathology. For therapeutic delivery, low-frequency focused ultrasound and convection-enhanced delivery bypass the BBB to achieve high local drug concentrations, while endovascular intra-arterial infusion enables targeted delivery across the tumor vascular territory. Photodynamic and sonodynamic therapy generate localized cytotoxic effects within the resection cavity at the time of surgery. Intraoperative brachytherapy with Cesium-131 tile implants delivers conformal radiation at the time of resection and may potentiate antitumor immunity. Laser interstitial thermal therapy combines cytoreduction with sustained BBB disruption, creating a therapeutic window for otherwise CNS-impermeant agents including checkpoint inhibitors.

The deliberate integration of these complementary modalities into a phase-organized intraoperative workflow, spanning preoperative planning, real-time resection guidance, intraoperative margin and tissue assessment, and post-resection locoregional therapeutic delivery, defines the emerging paradigm of precision glioma surgery. Realizing the full potential of this framework will require prospective validation of combinatorial strategies, standardization of technology integration protocols, and rigorous evaluation of neurological and oncological outcomes.