Connectome-guided Onco-functional Resection With Tractography-Extended Neuronavigation in Brain Tumor Surgery (CORTEx)
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.
Studienübersicht
Status
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Geschätzt)
Kontakte und Standorte
Studienkontakt
- Name: Giovanni Tringali, M.D.
- Telefonnummer: +390916661111
- E-Mail: giovanni.tringali@arnascivico.it
Studienorte
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PA
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Palermo, PA, Italien, 90127
- Rekrutierung
- Unit of Neurosurgery - A.R.N.A.S. Civico Di Cristina Benfratelli - 90127, Palermo - Italy
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Kontakt:
- Giovanni Tringali, M.D.
- Telefonnummer: +390916661111
- E-Mail: giovanni.tringali@arnascivico.it
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Hauptermittler:
- Giovanni Tringali, M.D.
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Unterermittler:
- Umberto Emanuele Benigno, M.D.
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Unterermittler:
- Lapo Bonosi, M.D.
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Unterermittler:
- Giuseppe Roberto Giammalva, M.D. PhD
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Unterermittler:
- Gabriele Costantino, M.D.
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
- Erwachsene
- Älterer Erwachsener
Akzeptiert gesunde Freiwillige
Probenahmeverfahren
Studienpopulation
Beschreibung
Inclusion Criteria:
- 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
Exclusion Criteria:
- Inability to undergo pre- or postoperative MRI
- Significant comorbidities precluding surgery
- Incomplete imaging or clinical data
- Purely infratentorial lesions or non-tumoral pathologies
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
Kohorten und Interventionen
Gruppe / Kohorte |
Intervention / Behandlung |
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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.
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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.
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Rate of Major Change in Surgical Plan
Zeitfenster: Intraoperative (day of surgery)
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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.
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Intraoperative (day of surgery)
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Incidence of major neurological deficit at 3-month follow-up
Zeitfenster: 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
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3 months after surgery
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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
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Extent of Resection
Zeitfenster: Within 72 hours after surgery
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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
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Within 72 hours after surgery
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Minimum Distance Between Resection Cavity and Key White Matter Tracts
Zeitfenster: Intraoperative and within 72 hours after surgery
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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.
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Intraoperative and within 72 hours after surgery
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Rate of Intraoperative Mapping and Awake Surgery
Zeitfenster: Intraoperative (day of surgery)
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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.
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Intraoperative (day of surgery)
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Pipeline Implementation Feasibility
Zeitfenster: Preoperative (day of surgical planning)
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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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Preoperative (day of surgical planning)
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Mitarbeiter und Ermittler
Ermittler
- Hauptermittler: Giovanni Tringali, M.D., Unit of Neurosurgery - A.R.N.A.S. Civico Di Cristina Benfratelli - 90127, Palermo - Italy
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen des Gehirns
- Erkrankungen des zentralen Nervensystems
- Erkrankungen des Nervensystems
- Neubildungen nach Standort
- Neubildungen nach histologischem Typ
- Neubildungen, Drüsen und Epithelien
- Neubildungen, Neuroepithel
- Neuroektodermale Tumoren
- Neoplasmen, Keimzelle und Embryonal
- Neubildungen, Nervengewebe
- Neubildungen des Nervensystems
- Neubildungen des zentralen Nervensystems
- Pathologische Zustände, Anzeichen und Symptome
- Anzeichen und Symptome
- Neubildungen
- Neurologische Manifestationen
- Gliom
- Neubildungen des Gehirns
Andere Studien-ID-Nummern
- ARNAS_NCH_2022_1
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