Brain (Nervous System) CancersCORTExNCT07717827
Connectome-guided Onco-functional Resection With Tractography-Extended Neuronavigation in Brain Tumor Surgery
An observational study of Brain (Nervous System) Cancers and Glioma, run by ARNAS Civico Di Cristina Benfratelli Hospital at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain (Nervous System) Cancers, Glioma, Brain Metastasases
- What is being tested?
- Connectome-guided network-based neuronavigation and Advanced diffusion MRI tractography and connectome pipeline
- Type of treatment
- Surgery or procedure
- How many people
- 400 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jan 2022to Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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.
Who may be able to join
- 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
- Provision of informed consent for use of anonymized clinical and imaging data
Who cannot join
- Inability to undergo pre- or postoperative MRI
- Significant comorbidities precluding surgery
- Incomplete imaging or clinical data
- Purely infratentorial lesions or non-tumoral pathologies
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Unit of Neurosurgery - A.R.N.A.S. Civico Di Cristina Benfratelli - 90127, Palermo - Italy
Palermo, PA, 90127
Giovanni Tringali, M.D., +390916661111, giovanni.tringali@arnascivico.it
Giovanni Tringali, M.D.
About this study
Official title: Connectome-guided Onco-functional Resection With Tractography-Extended Neuronavigation in Brain Tumor Surgery Involving Eloquent Regions: a Prospective Single-centre Cohort Study Integrating Advanced Diffusion MRI Into Clinical Neuronavigation for Gliomas and Metastases
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.
Read the detailed description
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.
- Being tested
- Connectome-guided network-based neuronavigation, Advanced diffusion MRI tractography and connectome pipeline
- Keywords
- diffusion MRI, tractography, neuronavigation, connectome, eloquent cortex, brain tumor surgery, white matter, glioma, brain metastasis, extent of resection, onco-functional balance, network neuroscience, neural networks, CORTEx
- Medical subject headings
- Neurologic Manifestations, Neoplasms, Glioma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Connectome-guided network-based neuronavigationProcedure or surgery
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
Advanced diffusion MRI tractography and connectome pipelineDiagnostic test
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.
| Study group | Role | What they receive |
|---|---|---|
| CORTEx cohort | 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. Receives: Procedure: Connectome-guided network-based neuronavigation; Diagnostic Test: Advanced diffusion MRI tractography and connectome pipeline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Intraoperative (day of surgery)
Incidence of major neurological deficit at 3-month follow-up
3 months after surgery
Measured: 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
Secondary outcomes (4)
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Preoperative (day of surgical planning)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2026
- Study start1 Jan 2022
- Primary completionDec 2026 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain (Nervous System) CancersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ARNAS Civico Di Cristina Benfratelli Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giovanni Tringali, ARNAS Civico Di Cristina Benfratelli Hospital
- Investigators
- Giovanni Tringali, M.D., Principal investigator, Unit of Neurosurgery - A.R.N.A.S. Civico Di Cristina Benfratelli - 90127, Palermo - Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07717827
- Sponsor's protocol ID
- ARNAS_NCH_2022_1
- Acronym
- CORTEx
- Status last verified
- Jul 2026
- First submitted
- 16 Jul 2026
- Last updated
- 21 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be made available due to patient privacy considerations. Deidentified aggregate results will be reported in future publications.
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Connectome-guided Onco-functional Resection With Tractography-Extended Neuronavigation in Brain Tumor Surgery Involving Eloquent Regions: a Prospective Single-centre Cohort Study Integrating Advanced Diffusion MRI Into Clinical Neuronavigation for Gliomas and Metastases
- ClinicalTrials.gov ID
- NCT07717827
- Acronym / sponsor ID
- CORTEx / ARNAS_NCH_2022_1
- Keywords
- diffusion MRI, tractography, neuronavigation, connectome, eloquent cortex, brain tumor surgery, white matter, glioma
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- ARNAS Civico Di Cristina Benfratelli HospitalUniversity, hospital or other
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 21 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CORTEx cohort | – | Procedure: Connectome-guided network-based neuronavigation, Diagnostic Test: Advanced diffusion MRI tractography and connectome pipelineConsecutive 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 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.
Key inclusion criteria (5 listed)
- 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
- Provision of informed consent for use of anonymized clinical and imaging data
Key exclusion criteria (4 listed)
- Inability to undergo pre- or postoperative MRI
- Significant comorbidities precluding surgery
- Incomplete imaging or clinical data
- Purely infratentorial lesions or non-tumoral pathologies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Connectome-guided network-based neuronavigationIntegration 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 | Procedure or surgery | CORTEx cohort |
| Advanced diffusion MRI tractography and connectome pipelineOpen-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. | Diagnostic test | CORTEx cohort |
Primary outcome
Rate of Major Change in Surgical Plan
Time frame: Intraoperative (day of surgery)
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
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
3 months after surgery
4 secondary outcomes
Extent of Resection
Time frame: Within 72 hours after surgery
Minimum Distance Between Resection Cavity and Key White Matter Tracts
Time frame: Intraoperative and within 72 hours after surgery
Rate of Intraoperative Mapping and Awake Surgery
Time frame: Intraoperative (day of surgery)
Pipeline Implementation Feasibility
Time frame: Preoperative (day of surgical planning)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
- Individual participant dataSharing planned: No. Individual participant data will not be made available due to patient privacy considerations. Deidentified aggregate results will be reported in future publications.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Giovanni Tringali, M.D. principal investigator
Unit of Neurosurgery - A.R.N.A.S. Civico Di Cristina Benfratelli - 90127, Palermo - Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Brain (Nervous System) Cancers and Glioma, run by ARNAS Civico Di Cristina Benfratelli Hospital at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Giovanni Tringali, M.D. (+390916661111, giovanni.tringali@arnascivico.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Major Change in Surgical Plan (time frame: Intraoperative (day of surgery)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026; AzTrials last refreshed its copy on 3 Nov 2026.