Brain tumor surgery in so-called "eloquent" brain areas aims to remove as much tumor as possible while preserving neurological functions. Standard surgical planning typically focuses on discrete, anatomically defined cortical regions. However, modern neuroscience demonstrates that most brain functions arise from distributed networks of interconnected areas rather than isolated spots - a concept that standard navigation tools do not fully capture.
The CORTEX study evaluates a surgical workflow - termed "connectome-guided network-based navigation" - in which advanced diffusion MRI processing is used to reconstruct patient-specific maps of white matter pathways and large-scale brain networks. These maps are imported into a clinical neuronavigation system to guide preoperative planning and intraoperative decision-making for patients with gliomas or brain metastases in eloquent regions.
The primary aims are to determine how often network-based information leads to meaningful changes in surgical strategy compared with conventional anatomy-based planning, and to assess early neurological outcomes. Secondary objectives include characterizing the extent of tumor removal, the proximity of the resection to critical white matter tracts, and the feasibility of implementing this pipeline in a high-volume clinical setting.
Indication for supratentorial brain tumor surgery (glioma or metastasis)
Lesion located within or adjacent to eloquent cortical or subcortical regions (motor, language, visual, or higher-order associative networks, as defined by clinical and neuroimaging criteria)
Availability of standardized preoperative and early postoperative brain MRI (including high-direction diffusion tensor imaging, ≥64 directions)
Consistent postoperative clinical follow-up planned at the treating centre
Inability to undergo pre- or postoperative MRI
Significant comorbidities precluding surgery
Incomplete imaging or clinical data
Purely infratentorial lesions or non-tumoral pathologies
Consecutive adult patients referred to the Unit of Neurosurgery of A.R.N.A.S. Civico Di Cristina Benfratelli (Palermo, Italy) for surgical treatment of supratentorial gliomas or brain metastases involving or adjacent to eloquent cortical or subcortical regions, enrolled prospectively from January 2022.
Cohort
Prospective
Connectome-guided network-based neuronavigation
Procedure/SurgeryIntegration of patient-specific white matter tractography and large-scale brain network overlays, derived from advanced diffusion MRI processing, into a clinical neuronavigation platform for preoperative planning and intraoperative guidance of brain tumor resection in eloquent regions
Advanced diffusion MRI tractography and connectome pipeline
Diagnostic testOpen-source multi-tissue constrained spherical deconvolution tractography, cortical parcellation and segmentation, diffusion preprocessing and brain connectivity mapping with automated Bash/Python scripting for streamlined and reproducible clinical implementation.
Rate of Major Change in Surgical Plan
Proportion of surgical procedures in which integration of network-based tractography information results in a major modification of the initial anatomy-centered surgical plan, defined as a change in the surgical corridor, the planned extent of resection, or the operative indication. Assessed by the operating neurosurgeon at the time of surgical planning.
Incidence of major neurological deficit at 3-month follow-up
3 months after surgery
Extent of Resection
Proportion of procedures achieving supratotal resection, gross-total resection, or partial resection, as determined on early postoperative contrast-enhanced MRI reviewed by the treating neurosurgeon
Minimum Distance Between Resection Cavity and Key White Matter Tracts
Minimum distance (mm) between the resection cavity and functionally relevant white matter tracts (corticospinal tract, arcuate fasciculus, inferior fronto-occipital fasciculus, optic radiations), estimated intraoperatively from subcortical stimulation thresholds and cross-validated by postoperative tractographic reconstructions.
Rate of Intraoperative Mapping and Awake Surgery
Proportion of procedures performed with awake craniotomy and/or continuous intraoperative neurophysiological monitoring; rate of concordance between intraoperative stimulation-induced responses and preoperative tractographic predictions.
Pipeline Implementation Feasibility
Proportion of enrolled patients in whom the full connectome-guided pipeline (diffusion MRI processing, tractogram generation, neuronavigation import) was successfully completed within the clinical workflow and used for preoperative planning.
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