Evidence for potentials and limitations of brain plasticity using an atlas of functional resectability of WHO grade II gliomas: Towards a “minimal common brain”
Research highlights
►Resectability of brain areas is unpredictable before tumor surgery due to reshaping. ►Electrical mapping allows the study of potentials and limitations of plasticity. ►We build an atlas of functional resectability based on postoperative residue. ►Each voxel represents the probability to observe non-compensable area. ►Our atlas highlights the existence of a “minimal common brain” among patients.
Introduction
Current developments in functional mapping and neuroimaging techniques have radically changed the classical static view on the functional organization of cortical areas, for a new dynamic perspective of the brain (Duffau, 2005). Indeed, many recent investigations have highlighted the dynamic capability of the brain to reorganize itself, both during everyday life (i.e. learning) and after a pathological event (e.g. stroke or glioma). This reorganization would be based on the existence of multiple and overlapping redundancies hierarchically organized (Bavelier and Neville, 2002, Duffau, 2001, Duffau et al., 2000, Rossini et al., 2003, Sanes et al., 1995, Schieber and Hibbard, 1993). These findings have testified that neuronal aggregates, beside or outlying a lesion, can increasingly adopt the function of the damaged area and switch their own activation pattern to substitute the lesioned area while facilitating functional recovery following brain damage (Duffau, 2006a). Advances in neuroimaging have enabled a better comprehension of the dynamic interaction between a tumor and functional cortical sites, usually preoperatively assessed by non-invasive functional examinations such as positron emission tomography (PET), functional magnetic resonance imaging (fMRI), MRI-based diffusion tensor imaging (DTI) and magnetoencephalography (MEG). Nevertheless, despite efforts to improve these techniques, their sensitivity and specificity are still limited due to perturbations induced by tumor on local neurovascular and metabolic coupling (sensitivity for the identification of sensorimotor sites ranges from 82% to 100%, whereas it ranges from 66% to 100% for language sites) (Aubert et al., 2002, Bartos et al., 2009, Roux et al., 2003) and neuroimaging is not able to differentiate essential cortical areas (which should be surgically preserved) from the “modulatory” areas that can be functionally compensated and resected without inducing permanent deficits (Duffau et al., 2003).
Axonal pathways also play a crucial role in glioma surgery, considering their infiltrative growth patterns along white matter fiber tracks (Chen et al., 2010, Mandonnet et al., 2006, Pallud et al., 2005). Recent developments in DTI have allowed to track non-invasively in vivo subcortical fibers (Catani et al., 2002, Catani and Thiebaut de Schotten, 2008) providing information on displacements, infiltrations or disruptions of fibers induced by the tumor (Witwer et al., 2002). Nevertheless, tracking algorithms may strongly influence the anatomical data of DTI (Kinoshita et al., 2005), even if some reports have provided some validation on postmortem studies (Thiebaut de Schotten et al., 2011; Lawes et al., 2008). Finally, DTI is not yet able to highlight the functional role of the tracts.
Considering (1) the large variability in structural and functional networks among healthy volunteers (Brett et al., 2002, Tzourio-Mazoyer et al., 2004), (2) functional limitations in neuroimaging, and (3) functional modifications induced by tumoral growing patterns both at cortical and axonal levels (Duffau, 2006a), the study of the brain functional cortical organization and connectivity is needed for individual patients to both select the best indications for surgery and to perform a resection with the optimal benefit/risk ratio. As a consequence, the use of intraoperative direct electrical stimulation (DES) is considered as the “gold standard” to detect both the eloquent cortical areas and subcortical pathways at the individual level (Duffau et al., 2008b, Mandonnet et al., 2010b). Indeed, DES provides accurate and real-time data on the distribution not only of the cortical eloquent areas (Ojemann et al., 1989, Sanai et al., 2008), but also of the functional white matter bundles (Bello et al., 2007, Duffau et al., 2008b, Sanai and Berger, 2010). Thus, DES allows to tailor the tumoral resection according to individual functional boundaries, maximizing the extent of resection while minimizing the risk of permanent neurological deficits.
Combining intraoperative anatomofunctional data with pre and post-operative fMRI and DTI imaging is currently the best approach to assess the functional role of the cortical areas and the white matter fiber tracts (Kamada et al., 2007). For this reason, we propose in this paper the elaboration of a probabilistic postsurgical residue atlas computed on a series of patients who underwent incomplete tumor resection on the basis of intraoperative DES brain mapping. The anatomo-functional correlations we obtained by combining the DES data with postoperative anatomical MRI findings will provide a greater understanding of the functional limits of surgical removal, and will provide new insights into the potentials and limitations of brain plasticity. Especially, this probabilistic atlas highlights the crucial role of the axonal pathways in the reshaping and reorganization of the brain after a lesion. Finally, beyond its fundamental interest, we hope this atlas will be an essential tool for surgery planning, by allowing an objective pre-operative estimation of the expected extent of the resection.
Section snippets
Patients
In this retrospective study, we analyzed a homogenous group, for radiological and neuropathological features, of 58 patients who underwent surgery for WHO grade II glioma (low-grade glioma, LGG) between 2005 and 2009. All the procedures were performed by the same neurosurgeon (H.D.). All patients had a lesion in eloquent regions, which required intraoperative functional mapping achieved with both cortical and subcortical stimulations. Considering that the aim of this study is to evaluate the
Patients
Among the 58 lesions, the right hemisphere was involved in 25 cases and the left in 33 cases. The median preoperative tumoral volume was 65 cm3 (range: 15–202 cm3). Patients with right-sided lesions displayed a right dominant hemisphere in 10 cases. The hemispheric dominance was established using the Edinburg test and the index of dominance was calculated on the basis of fMRI findings (Gaillard et al., 2002). In particular preoperative MRI revealed 24 precentral lesions (8 on the right side and
A new tool to study the potentialities and limitations of interindividual variability and plasticity in patients with LGG
Low-grade gliomas are slow-growing tumors, but hamper functional prognosis, as they infiltrate functional areas, and are ultimately prone to undergo anaplastic transformation (Wessels et al., 2003). Numerous pre-operative neurofunctional imaging studies have shown that tumor invasion triggers a neural reorganization, explaining the fact that a majority of LGG patients exhibit normal clinical exams (Walker and Kaye, 2003), even if slight cognitive disorders can be detected using extensive
Conclusions and perspectives
The proposed atlas of functional resectability of WHO grade II glioma provides a new generic tool to study the potentials and limitations of brain plasticity and the role of interindividual variability for resection of WHO grade II gliomas. In addition, our atlas highlights the existence of a “minimal common brain” among patients.
Several ways can be foreseen to improve the quality of the present work:
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to enhance the accuracy of the registration procedure in order to optimize the spatial
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