**Multimodal Approach to the Surgical Removal of Gliomas in Eloquent Brain Regions**

Giannantonio Spena1, Antonio Pepoli2, Marcella Bruno2, Federico D'Agata3, Franco Cauda3, Katiuscia Sacco3, Sergio Duca3 and Pietro Versari1

*1Division of Neurosurgery, Civil Hospital, Alessandria* 

*2Division of Neurology and Neuropsychology, Civil Hospital, Alessandria, 3CCS fMRI, Koelliker Hospital and Department of Psychology, University of Turin, Turin Italy* 

#### **1. Introduction**

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> Supratentorial glial neoplasms are the most common primary brain tumor in adults and one of the leading causes of cancer-related death in the general population. Glioblastomas carry the worst prognosis, while low-grade gliomas have the best chance for survival. It has been demonstrated, however, that low-grade gliomas represent a precancerous state, as they have the potential to evolve into higher-grade malignancies. Although management algorithms vary among different types of tumors, surgery remains the mainstay of treatment for several reasons. Surgical resection allows the opportunity to obtain a sufficient amount of tumor for histological identification. This point is of utmost importance, as the best predictors of survival are the World Health Organization (WHO) grade and other immunohistological characteristics of the tumor. Additionally, it has been demonstrated that radical or subtotal resection correlates positively with prolongation of survival and longer time to progression. Given this information, neurosurgeons aim to achieve maximal surgical resection of these tumors whenever feasible. Unfortunately, gliomas are often located in regions of the brain defined as "eloquent" or "critical," meaning that physical damage to these areas can create permanent neurological deficits. A careful evaluation of surgical strategy is mandatory in light of this fact, with the goal being to maximize tumor resection while respecting the highly functional cortical and subcortical regions of the brain.

> Different techniques are available that allow the neurosurgeon to study the brain function topography both preoperatively and intraoperatively. These methods of preoperative and intraoperative brain mapping are used to gain essential information about functional and topographic organization in a specific patient. Functional magnetic resonance imaging (fMR) is the most commonly used tool for preoperative visualization of the motor, sensory, language, and visual functional organization of a patient's brain. Since gliomas typically invade white matter, the extent of resection is additionally limited by the degree of infiltration, particularly when critical bundles are involved (e.g., the pyramidal tract). As with the eloquent cortical areas, the relationship of the tumor to the subcortical pathways should be defined in order to avoid permanent deficits. Diffusion tensor imaging (DTI), the

Multimodal Approach to the Surgical Removal of Gliomas in Eloquent Brain Regions 341

neurological diseases (Annet 1992; Thompson et al. 1998; Toga et al. 2001; Ballmaier et al. 2004; Luders et al. 2005; Narr et al. 2007). In the complex relationship between neuroanatomy and function, the significance of neuroanatomical variability is evidenced by its association with and probable contribution to distinct patterns of functional organization. For example, interhemispheric anatomical asymmetries (especially with respect to the planum temporale) have repeatedly been shown to be related to language lateralization (Josse et al. 2003; Steinmets et al. 1991). A trustworthy functional representation of a defined anatomical landmark is typically feasible for the hand motor area, showing as a correlate a characteristic dorsally oriented convexity in the precentral gyrus (the so-called "handknob") (Yousry et al. 1997; Boling et al. 2008). However, motor activity can also be detected outside of the typical landmarks, and the pattern of motor cortex activation is modulated by different physiological factors (Yousry et al. 2001; Mattay & Weinberger 1999). The discrepancy between anatomical references and functions becomes even more complex when dealing with higher cognitive functions, such as language, which have multiple and extensively distributed epicenters. It is nowadays accepted that the classical language model (Lichtheim 1885; Geschwind 1971) is not sufficient to reflect the complexity of cortical language representations (Gabrieli et al. 1998; Grabowski 2000; Bookheimer 2002). The view that there are no well-defined language areas is strongly supported by many fMR studies, as well as cortical and subcortical electrical stimulation (CSES) studies, that have identified widespread and overlapping networks for phonological, semantic, orthographic, and syntactic processing (Ojeman et al. 1989; Herolz et al. 1996; Tzourio-Mazoyer et al. 2004). In an extensive analysis performed on more than 200 patients operated on for intrinsic brain tumor through an awake craniotomy and CSES, Berger et al. (Sanai et al. 2008) showed that sites associated with speech function are variably located along the cortex and can go well

In the neurosurgical population, additional inter-patient anatomical variability arises from the presence of intracranial pathology. Brain tumors can alter the understanding of neuroanatomy and function localization through two mechanisms. The first is related to the deformity created by the space-occupying lesion on adjacent sulci such that normal anatomical and imaging landmarks are more difficult or impossible to identify. The second is related to the reorganization and redistribution that occur in the cortical functional maps as a consequence of the presence of the brain tumor. Post-lesional recovery and the pattern of brain reorganization involved in functional compensations have been well documented in stroke patients (Rijntes & Weiller 2002; Rossini et al. 2003; Ward 2004). These studies have elucidated the concept of cerebral plasticity: the natural capacity of the brain to remodel itself as a consequence of learning and developmental strategy. Cerebral plasticity defines a continuous process that allows reshaping of the neuronosynaptic maps to optimize the functioning of brain networks. It is also the way to recover from lesions of different origin. Gliomas, especially low-grade gliomas, have in the very recent years increasingly attracted researchers because of their tendency to reach large volumes in eloquent areas, frequently without causing neurological symptoms. Functional MR studies have shown how these slow growing tumors can induce functional reshaping by displacing critical epicenters either around the tumor or even to the contralateral hemisphere (Mueller et al., 1996; Carpentier et al. 2001; Baciu et al. 2003). Moreover, several authors have reported series of patients who have undergone awake craniotomy and CSES in whom tumors in critical areas were safely and efficiently removed without permanent morbidity. In these series authors have documented different types and mechanisms of tumor-induced functional

beyond the classic anatomical boundaries.

latest MR imaging advancement, allows reconstruction of the anatomy of the main white matter tracts. Using this imaging modality, further information can be gathered on the status of these tracts (e.g., infiltration, displacement, interruption).

It is crucial that contemporary neurosurgeons understand how to properly use these technological advancements to improve postoperative neurological results. It is also vital that critical analysis and discussion of the limits and appropriate use of these devices is part of the neurosurgical routine.

In this chapter, we will focus on some fundamental aspects of brain mapping, particularly regarding the surgical resection of gliomas. First, we will review the concept of eloquent brain regions and the evolution of the concept of critical areas. Then, we will deal with stateof-the-art functional imaging and diffusion tensor imaging, underlining their conceptual and technical limitations and explaining how to use them in surgical planning. Direct brain mapping by CSES will also be examined from a practical point of view, focusing on basic technique, anesthesia, equipment, patient selection, limitations, and future directions. Finally, we will discuss how to integrate these different mapping modalities while highlighting clinical evidence from our experience and that of other authors.

We hope that this chapter will help those who are approaching brain mapping in a clinical and neurosurgical setting not only by showing mechanisms and usefulness but also in posing questions and criticisms.
