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.
調査の概要
状態
詳細な説明
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.
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：Giovanni Tringali, M.D.
- 電話番号：+390916661111
- メール：giovanni.tringali@arnascivico.it
研究場所
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PA
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Palermo、PA、イタリア、90127
- 募集
- Unit of Neurosurgery - A.R.N.A.S. Civico Di Cristina Benfratelli - 90127, Palermo - Italy
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コンタクト：
- Giovanni Tringali, M.D.
- 電話番号：+390916661111
- メール：giovanni.tringali@arnascivico.it
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主任研究者：
- Giovanni Tringali, M.D.
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副調査官：
- Umberto Emanuele Benigno, M.D.
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副調査官：
- Lapo Bonosi, M.D.
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副調査官：
- Giuseppe Roberto Giammalva, M.D. PhD
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副調査官：
- Gabriele Costantino, M.D.
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
サンプリング方法
調査対象母集団
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
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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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Rate of Major Change in Surgical Plan
時間枠：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
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Extent of Resection
時間枠：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
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
捜査官
- 主任研究者：Giovanni Tringali, M.D.、Unit of Neurosurgery - A.R.N.A.S. Civico Di Cristina Benfratelli - 90127, Palermo - Italy
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- ARNAS_NCH_2022_1
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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