An observational study in Brain (Nervous System) Cancers, Glioma and Brain Metastasases, sponsored by ARNAS Civico Di Cristina Benfratelli Hospital. Recruiting at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-21.
Sponsored by ARNAS Civico Di Cristina Benfratelli Hospital · Observational
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.
The CORTEX study is a prospective, single-centre cohort study conducted at the Unit of Neurosurgery of A.R.N.A.S. Civico Di Cristina Benfratelli, Palermo, Italy. Consecutive eligible patients are enrolled from January 2022 onwards.
Background and Rationale:
Contemporary understanding of brain organization emphasizes the distributed, network-based nature of neurological and cognitive functions. Surgical planning centered exclusively on anatomical landmarks - a "localist" approach - may fail to account for the role of long-range white matter pathways, association fasciculi, and large-scale cortico-subcortical networks in sustaining higher-order functions. The concept of "extended eloquence" extends surgical risk stratification beyond classical primary cortices to include associative and integrative networks, whose disruption may produce clinically relevant higher-order deficits even in the absence of damage to traditional eloquent areas.
Diffusion MRI Processing Pipeline:
Preoperative high-direction diffusion MRI is processed using an open-source pipeline integrating MRtrix3 (denoising, Gibbs correction, multi-tissue constrained spherical deconvolution, anatomically constrained tractography with the iFOD2 algorithm, SIFT2 tractogram filtering), FSL (eddy current and motion correction, susceptibility distortion correction), and FreeSurfer (cortical and subcortical segmentation, atlas-based parcellation). In a subset of patients with optimal data quality, an HCP-style surface-based analysis is performed using the Ciftify framework. Workflow automation is achieved through custom Bash and Python scripts, reducing operator-dependent variability.
Neuronavigation Integration:
Tractograms and volumetric overlays of clinically relevant white matter tracts - including the corticospinal tract, arcuate and superior longitudinal fasciculi, inferior fronto-occipital fasciculus, optic radiations, and frontal aslant tract - are co-registered to anatomical space and imported into neuronavigation platform. These overlays are used during preoperative planning to define craniotomy location, surgical corridor, and intended extent of resection relative to critical network architecture.
Intraoperative Integration:
Where applicable, connectome-guided navigation is integrated with intraoperative neurophysiological monitoring and, in selected cases, awake craniotomy with direct electrical stimulation. Concordance between tractographic predictions and intraoperative stimulation findings is recorded prospectively.
Outcome Assessment:
Postoperative MRI is obtained within 48-72 hours of surgery. Neurological assessment is performed at discharge and at 3-month follow-up by the treating neurosurgical team.
198 studies on the registry are indexed under Neurologic Manifestations; 67 are open to participants now.
This study's planned enrollment of 400 is above the median of 184 across 82 observational studies indexed under Neurologic Manifestations.
Browse Neurologic Manifestations studies →ARNAS Civico Di Cristina Benfratelli Hospital is the lead sponsor of 4 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
Exclusion Criteria:
Consecutive patients undergoing resection of supratentorial gliomas or brain metastases in eloquent or adjacent regions, enrolled in the CORTEX study and treated with integration of advanced diffusion MRI tractography and connectome-based network overlays into the clinical neuronavigation workflow.
Procedure: Connectome-guided network-based neuronavigation · Diagnostic Test: Advanced diffusion MRI tractography and connectome pipeline
Integration 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
Open-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.
Time frame: Intraoperative (day of surgery)
Incidence of major neurological deficit at 3-month follow-up
3 months after surgery
Time frame: Proportion of patients with persistent major neurological deficits with functional impact (motor, language, or visual deficits) 3-month post-op, as evaluated by the treating neurosurgical team using standardized neurological examination
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
Time frame: Within 72 hours after surgery
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.
Time frame: Intraoperative and within 72 hours after surgery
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.
Time frame: Intraoperative (day of surgery)
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.
Time frame: Preoperative (day of surgical planning)
Plan to share: No — Individual participant data will not be made available due to patient privacy considerations. Deidentified aggregate results will be reported in future publications.
No publications or documents are linked to this record.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
ARNAS Civico Di Cristina Benfratelli Hospital