Eloquent Cortical Areas Research Articles

Preparation of simulate craniocerebral models via three dimensional printing technique

Three dimensional (3D) printing technique was used to prepare the simulate craniocerebral models, which were applied to preoperative planning and surgical simulation. The image data was collected from PACS system. Image data of skull bone, brain tissue and tumors, cerebral arteries and aneurysms, and functional regions and relative neural tracts of the brain were extracted from thin slice scan (slice thickness 0.5 mm) of computed tomography (CT), magnetic resonance imaging (MRI, slice thickness 1mm), computed tomography angiography (CTA), and functional magnetic resonance imaging (fMRI) data, respectively. MIMICS software was applied to reconstruct colored virtual models by identifying and differentiating tissues according to their gray scales. Then the colored virtual models were submitted to 3D printer which produced life-sized craniocerebral models for surgical planning and surgical simulation. 3D printing craniocerebral models allowed neurosurgeons to perform complex procedures in specific clinical cases though detailed surgical planning. It offered great convenience for evaluating the size of spatial fissure of sellar region before surgery, which helped to optimize surgical approach planning. These 3D models also provided detailed information about the location of aneurysms and their parent arteries, which helped surgeons to choose appropriate aneurismal clips, as well as perform surgical simulation. The models further gave clear indications of depth and extent of tumors and their relationship to eloquent cortical areas and adjacent neural tracts, which were able to avoid surgical damaging of important neural structures. As a novel and promising technique, the application of 3D printing craniocerebral models could improve the surgical planning by converting virtual visualization into real life-sized models.It also contributes to functional anatomy study.

38. Mapping eloquent cortical areas with direct electrical stimulation

Neurosurgical treatment of lesions in close spatial proximity to eloquent areas of the brain remains a challenge. The knowledge of topographical anatomy is not always enough to determine resection extension of the lesion. To identify the anatomical relation of a lesion to a cortical area, and to define the maximum limits of such resection, several techniques are used to guide the procedure. Using such techniques, resection of lesions previously classified as unresectable became possible, with relative low morbidity. In order to maximize the extent of the resection, the available neurophysiological and non-neurophysiological tools include imaging studies, both structural and functional like intraoperative MRI. Critical functional areas of the brain like cognitive, motor and language function can be mapped preoperatively with functional MRI, diffusion tensor imaging fiber tracking, magnetoencephalography, and navigated transcranial magnetic stimulation, or intraoperatively by direct electrical stimulation of the cortex or subcortical white matter tracts. Cortical Stimulation Mapping using electrical stimulation is considered the gold standard for mapping functional regions of the brain to create a presurgical plan that maximizes the patient’s functional outcome.

Synchrotron X-ray microtransections: a non invasive approach for epileptic seizures arising from eloquent cortical areas.

Synchrotron-generated X-ray (SRX) microbeams deposit high radiation doses to submillimetric targets whilst minimizing irradiation of neighboring healthy tissue. We developed a new radiosurgical method which demonstrably transects cortical brain tissue without affecting adjacent regions. We made such image-guided SRX microtransections in the left somatosensory cortex in a rat model of generalized epilepsy using high radiation doses (820 Gy) in thin (200 μm) parallel slices of tissue. This procedure, targeting the brain volume from which seizures arose, altered the abnormal neuronal activities for at least 9 weeks, as evidenced by a decrease of seizure power and coherence between tissue slices in comparison to the contralateral cortex. The brain tissue located between transections stayed histologically normal, while the irradiated micro-slices remained devoid of myelin and neurons two months after irradiation. This pre-clinical proof of concept highlights the translational potential of non-invasive SRX transections for treating epilepsies that are not eligible for resective surgery.

Application of Awake Craniotomy and Intraoperative Brain Mapping for Surgical Resection of Insular Gliomas of the Dominant Hemisphere

Radical resection of dominant insular gliomas is difficult because of their close vicinity with internal capsule, basal ganglia, and speech centers. Brain mapping techniques can be used to maximize the extent of tumor removal and to minimize postoperative morbidities by precise localization of eloquent cortical and subcortical areas. Patients with newly diagnosed gliomas of dominant insula were enrolled. The exclusion criteria were severe cognitive disturbances, communication difficulty, age greater than 75 years, severe obesity, difficult airways for intubation and severe cardiopulmonary diseases. All were evaluated preoperatively with contrast-enhanced brain magnetic resonance imaging (MRI), functional brain MRI, and diffusion tensor tractography of language and motor systems. All underwent awake craniotomy with the same anesthesiology protocol. Intraoperative monitoring included continuous motor-evoked potential, electromyography, electrocorticography, direct electrical stimulation of cortex, and subcortical tracts. The patients were followed with serial neurologic examination and imaging. Ten patients were enrolled (4 men, 6 women) with a mean age of 43.6 years. Seven patients suffered from low-grade glioma, and 3 patients had high-grade glioma. The most common clinical presentation was seizure followed by speech disturbance, hemiparesis, and memory loss. Extent of tumor resection ranged from 73% to 100%. No mortality or new major postoperative neurologic deficit was encountered. Seizure control improved in three fourths of patients with medical refractory epilepsy. In one patient with speech disorder at presentation, the speech problem became worse after surgery. Brain mapping during awake craniotomy helps to maximize extent of tumor resection while preserving neurologic function in patients with dominant insular lobe glioma.

High density EEG: Could it be useful for language localization?

In patients with pharmacoresistant epilepsy, pre-surgical planning requires precise localization of both the epileptic zone and the eloquent cortical areas. In some patients, electrode implantation is necessary to achieve this goal. Electrocortical stimulation (ECS) of the individual contacts has been established as the gold-standard for individual cortical localization of critical brain regions. However, ECS is not suitable for all patients. Therefore, to overcome the limitations of ECS, non-invasive and invasive functional mapping approaches based mainly on functional magnetic resonance imaging (fMRI) and subdural electrocorticographic recordings (ECoG) have been developed. Although fMRI is frequently used as a complementary tool for surgical planning, less is known about the use of high density electroencephalography (EEG). Very few high density EEG studies have shown consistent results for language lateralization. Here, we will discuss our experience with 256-channel EEG in language localization in the individual brain.

A structural and functional magnetic resonance imaging dataset of brain tumour patients

We collected high resolution structural (T1, T2, DWI) and several functional (BOLD T2*) MRI data in 22 patients with different types of brain tumours. Functional imaging protocols included a motor task, a verb generation task, a word repetition task and resting state. Imaging data are complemented by demographics (age, sex, handedness, and pathology), behavioural results to motor and cognitive tests and direct cortical electrical stimulation data (pictures of stimulation sites with outcomes) performed during surgery. Altogether, these data are suited to test functional imaging methods for single subject analyses, in particular methods that focus on locating eloquent cortical areas, critical functional and/or structural network hubs, and predict patient status based on imaging data (presurgical mapping).

Intraoperative optical mapping of epileptogenic cortices during non-ictal periods in pediatric patients.

Complete removal of epileptogenic cortex while preserving eloquent areas is crucial in patients undergoing epilepsy surgery. In this manuscript, the feasibility was explored of developing a new methodology based on dynamic intrinsic optical signal imaging (DIOSI) to intraoperatively detect and differentiate epileptogenic from eloquent cortices in pediatric patients with focal epilepsy. From 11 pediatric patients undergoing epilepsy surgery, negatively-correlated hemodynamic low-frequency oscillations (LFOs, ~ 0.02–0.1 Hz) were observed from the exposed epileptogenic and eloquent cortical areas, as defined by electrocorticography (ECoG), using a DIOSI system. These LFOs were classified into multiple groups in accordance with their unique temporal profiles. Causal relationships within these groups were investigated using the Granger causality method, and 83% of the ECoG-defined epileptogenic cortical areas were found to have a directed influence on one or more cortical areas showing LFOs within the field of view of the imaging system. To understand the physiological origins of LFOs, blood vessel density was compared between epileptogenic and normal cortical areas and a statistically-significant difference (p < 0.05) was detected. The differences in blood-volume and blood-oxygenation dynamics between eloquent and epileptogenic cortices were also uncovered using a stochastic modeling approach. This, in turn, yielded a means by which to separate epileptogenic from eloquent cortex using hemodynamic LFOs. The proposed methodology detects epileptogenic cortices by exploiting the effective connectivity that exists within cortical regions displaying LFOs and the biophysical features contributed by the altered vessel networks within the epileptogenic cortex. It could be used in conjunction with existing technologies for epileptogenic/eloquent cortex localization and thereby facilitate clinical decision-making.

Safe Resection of Gliomas of the Dominant Angular Gyrus Availing of Preoperative FMRI and Intraoperative DTI: Preliminary Series and Surgical Technique

Language dysfunction, visual deficit, numeracy impairment, and Gerstmann syndrome often occur in the cortical area; furthermore, the subcortical white matter is the inviolable limit of "functional neurosurgery." Preoperative functional magnetic resonance imaging (fMRI) and tractography are capable of providing the data required for safe "surgical planning" at both the cortical and subcortical levels. We report our experience regarding high-grade gliomas affecting the dominant angular gyrus (AG), supramarginal gyrus (SMG), intraparietal sulcus (IPS), and their respective subcortical areas using intraoperative MRI and diffusion tensor imaging (DTI). Retrospectively, we reviewed a consecutive series of 27 patients operated in a BrainSuite for high-grade intraparenchymal tumors of the left posterior temporoparietal junction. We included tumors involving the dominant AG, SMG, and/or IPS and the subcortical course of arcuate fasciculus (AF) and all the patients who underwent preoperative fMRI and DTI to localize the AF and the eloquent cortical areas. Just after craniotomy, new volumetric MRI and DTI verified and corrected possible brain shift. After the gross total resection was carried out, and before approaching the residual mass close to the white matter tract, an intraoperative MRI was again performed. We operated on 27 patients, 15 males and 12 females, whose diagnosis was always high-grade glioma. During the preoperative neurologic examination, 6 patients were asymptomatic; 3 presented a Gerstmann syndrome; 16 showed dysphasic disturbances, 6 of which were associated with visual field deficits; and 2 showed weakness of the right limb. Our results suggest that this approach is completely safe and effective as an alternative to awake surgery.

Trends in pediatric epilepsy surgery.

Epilepsy surgery has become an accepted treatment for drug resistant epilepsy in infants and children. It has gained ground in India over the last decade. Certain epilepsy surgically remediable syndromes have been delineated and should be offered surgery earlier rather than later, especially if cognitive/behavioral development is being compromised. Advances in imaging, particularly in MRI has helped identify surgical candidates. Pre-surgical evaluation includes clinical assessment, structural and functional imaging, inter-ictal EEG, simultaneous video -EEG, with analysis of seizure semiology and ictal EEG and other optional investigations like neuropsychology and other newer imaging techniques. If data are concordant resective surgery is offered, keeping in mind preservation of eloquent cortical areas subserving motor, language and visual functions. In case of discordant data or non-lesional MRI, invasive EEG maybe useful using a two-stage approach. With multi-focal / generalized disease, palliative surgery like corpus callosotomy and vagal nerve stimulation maybe useful. A good outcome is seen in about 2/3rd of patients undergoing resective surgery with a low morbidity and mortality. This review outlines important learning aspects of pediatric epilepsy surgery for the general pediatrician.

Integration of multimodal neuroimaging methods: a rationale for clinical applications of simultaneous EEG-fMRI

Functional magnetic resonance imaging (fMRI), which has high spatial resolution, is increasingly used to evaluate cerebral functions in neurological and psychiatric diseases. The main limitation of fMRI is that it detects neural activity indirectly, through the associated slow hemodynamic variations. Because neurovascular coupling can be regionally altered by pathological conditions or drugs, fMRI responses may not truly reflect neural activity. Electroencephalography (EEG) recordings, which directly detect neural activity with optimal temporal resolution, can now be obtained during fMRI data acquisition. Therefore, there is a growing interest in combining the techniques to obtain simultaneous EEG-fMRI recordings. The EEG-fMRI approach has several promising clinical applications. The first is the detection of cortical areas involved in interictal and ictal epileptic activity. Second, combining evoked potentials with fMRI could be an accurate way to study eloquent cortical areas for the planning of neurosurgery or rehabilitation, circumventing the above-mentioned limitation of fMRI. Finally, the use of this approach to evaluate the functional connectivity of resting-state networks would extend the applications of EEG-fMRI to uncooperative or unconscious patients. Integration of multimodal neuroimaging methods: a rationale for clinical applications of simultaneous EEG-fMRI.

Recent progress in surgery of malignant gliomas in and near eloquent cortical areas

Recent progress in surgery of malignant gliomas in and near eloquent cortical areas

Professor Hans Otto Lüders

Professor Lüders has made significant contributions to Clinical Neurology and particularly to Epilepsy and Clinical Neurophysiology. Some of his most important contributions include the following: 1.He pioneered the use of chronically implanted, large plates of subdural electrodes in the presurgical evaluation of patient who were candidates for epilepsy surgery. These electrodes were used to record epileptic seizures and by electrical stimulation to establish the location of eloquent cortex. Lately he has also advocated the use in the USA of stereotactically implanted depth electrodes for presurgical evaluation of epilepsy patients who had deep seated epileptic foci which were impossible to assess with subdural electrodes. These techniques were imported from Europe. 2.Mapping studies with subdural electrodes led to the discovery of a number of cortical eloquent areas that had not been described before: a. The basal temporal language area located in the dominant fusiform gyrus. b. The "negative motor areas" located in the caudal region of the inferior frontal gyrus (bilaterally) and immediately in mesial frontal pre-SMA region (also bilaterally). He concluded that these "negative motor areas" most likely correspond to praxis regions. c. The dominant posterior fusiform gyrus which plays a crucial role in processing reading material. Stimulation of that area produces "alexia without agraphia". 3.He developed a new classification of epileptic seizures based exclusively on semiological ictal characteristics. With the development of the semiological seizure classification he also defined several new seizure types: a. Dialeptic seizures, b. Hypnopompic seizures, c. Hypomotor seizures. 4.Working with general epilepsy principles, he established the existence of 6 zones that characterize the epilepsies: the epileptogenic zone, the irritative zone, the seizure onset zone, the epileptogenic lesion, the symptomatogenic zone and functional deficit zone. 5.He described the ictal DC (direct current) shift seen at the beginning of focal seizures and its value for localization of the seizure onset zone.

Indications and selection criteria for invasive monitoring in children with cortical dysplasia

In order to presurgically define the anatomical location of the epileptogenic zone (EZ) and its proximity to possible cortical and subcortical eloquent areas in pediatric patients with medically intractable focal epilepsy, an array of noninvasive tools are available: recorded seizure semiology, scalp electroencephalographic (EEG) recordings (ictal and interictal epileptic patterns), magnetic resonance imaging (MRI), positron emission tomography (PET), ictal single-photon emission computed tomography (SPECT), neuropsychological testing, and/or magnetoencephalography. When the noninvasive tools fail or are insufficient in precisely localizing the EZ and its functional and anatomical interphase with potential eloquent cortical areas, invasive extra-operative monitoring procedures might be needed. In this chapter, we will discuss the main goals of extra-operative invasive evaluation for children with medically intractable epilepsy in whom cortical dysplasia is a possible etiology. We will specifically discuss the possible indications, surgical strategies, results, and morbidity associated with the placement of subdural and stereoelectroencephalography (SEEG) electrodes. The rationale behind the choice of each one of the above techniques will also be discussed.

Tumor surgery within cerebral eloquent areas: A two-institutions experience

Introduction: Tumor surgery within eloquent areas represents a formidable challenge and the use of electrical cortico-subcortical stimulation mapping (ESM), allows to localize sensorimotor and language areas and pathways. Our aim is to point out methodological issues of ESM and its impact on outcome at the light of a prospective analysis of a two-institution series of 159 patients with lesions involving eloquent areas with a lengthy follow up. Material and Methods: All patients operated on for lesions involving eloquent areas between May 2000 and May 2010 at the Neurosurgical Department of the Neurological and Neurosurgical Hospital 'P. Wertheimer' in Lyon (France) and at the Neurosurgical Department of the University Hospital in Catanzaro (Italy), were enrolled prospectively in our study. Results: Of 159 consecutive patients, 141 of them underwent surgical removal of the lesion with the aid of electrical cortico-subcortical stimulation mapping integrated in a setting of intraoperative localization of anatomic landmarks for eloquent areas. For the remaining 18 patients ESM was not deemed useful or feasible: 15 patients received a biopsy and 3 patients received tumor debulking under general anesthesia. For patients operated with ESM, it was possible to achieve a gross total removal of the lesion in 67,4% of cases (95 patients). One patient died in the immediate postoperative period for a pulmonary embolism. At a total mean follow-up of 62.8 months 78 patients were alive, 62 of which were recurrence free and had a KPS of 70% or more, while the other 80 patients had a mean survival time of 23.9 months, with a mean high quality survival period (KPS ≥ 70) of21.6 months. Discussion and Conclusion: Intraoperative electrical language and motor mapping, when feasible and indicated, consistently localizes eloquent cortical areas and subcortical pathways and allows to set the tumor resection boundaries according to functional limits, with a favorable impact on survival and quality of life. Integration of neurofunctional data with anatomic landmarks is nonetheless useful to expedite the surgical procedure and improve specificity and sensibility of functional mapping.

Role of intraoperative neurophysiological monitoring during fluorescence-guided resection surgery

Fluorescence-guided resection (FGR) using 5-aminolevulinic acid (5-ALA) exhibits a potential risk of permanent neurological deficits that can be minimized using intraoperative neurophysiological monitoring (IONM). We assessed the role of IONM in FGR surgery in patients harboring tumors in or near eloquent areas. IONM and FGR surgeries were performed on 34 patients (49.8 ± 2.4 years) harbored malignant primary gliomas near eloquent cortical areas or semioval center. Different combinations of neurophysiological techniques were used depending on each patient. Gross total resection (GTR) was achieved in 66.7 % of the patients, mean 90.4 ± 3.7 % without neurological deficits. Resection in four patients was stopped by the occurrence of severe warning criteria despite the presence of fluorescence. Hemispheric transcranial electrical stimulation was safe and confident even in cortical surgery. Notably, a significant percentage of patients exhibited clinical improvement after the surgery. One week after surgery, only one patient worsened, and seven patients improved. At 3 months, 27.8 % of the patients improved, and the other patients maintained a similar status to their pre-surgery condition. Warning common criteria (amplitude reduction and/or latency increase) appeared in 68.2 and 50.0 % of patients during cortical or semioval surgery, respectively, with neither a false-negative nor a false-positive clinical outcome. Although 5-ALA exhibits phototoxicity, VEP did not induce any secondary effects in the visual system, including eyelids. IONM can be helpful during surgery to maximize the tumor resection, meanwhile help to avoid neurological deficits and, therefore, to improve the quality of life of these patients.

Electrode localization for planning surgical resection of the epileptogenic zone in pediatric epilepsy

In planning for a potentially curative resection of the epileptogenic zone in patients with pediatric epilepsy, invasive monitoring with intracranial EEG is often used to localize the seizure onset zone and eloquent cortex. A precise understanding of the location of subdural strip and grid electrodes on the brain surface, and of depth electrodes in the brain in relationship to eloquent areas is expected to facilitate pre-surgical planning. We developed a novel algorithm for the alignment of intracranial electrodes, extracted from post-operative CT, with pre-operative MRI. Our goal was to develop a method of achieving highly accurate localization of subdural and depth electrodes, in order to facilitate surgical planning. Specifically, we created a patient-specific 3D geometric model of the cortical surface from automatic segmentation of a pre-operative MRI, automatically segmented electrodes from post-operative CT, and projected each set of electrodes onto the brain surface after alignment of the CT to the MRI. Also, we produced critical visualization of anatomical landmarks, e.g., vasculature, gyri, sulci, lesions, or eloquent cortical areas, which enables the epilepsy surgery team to accurately estimate the distance between the electrodes and the anatomical landmarks, which might help for better assessment of risks and benefits of surgical resection. Electrode localization accuracy was measured using knowledge of the position of placement from 2D intra-operative photographs in ten consecutive subjects who underwent intracranial EEG for pediatric epilepsy. Average spatial accuracy of localization was 1.31 ± 0.69 mm for all 385 visible electrodes in the photos. In comparison with previously reported approaches, our algorithm is able to achieve more accurate alignment of strip and grid electrodes with minimal user input. Unlike manual alignment procedures, our algorithm achieves excellent alignment without time-consuming and difficult judgements from an operator.

The surgical treatment of secondary epilepsy caused by glioma in the eloquent cortical areas

Objective To investigate surgical methods,secure and curative effects under intraoperative awake anesthesia combined with a multimodal approach of cerebral functional localization for the resection of glioma and epileptogenic foci in eloquent Cortical area.Methods 31 Consecutive patients suffering from secondary epilepsy caused by glioma in the eloquent area were treated with the asleep-awake -asleep-technique.According to MRIs,DTT and functional MRIs design operative plans before the operations.Craniotomy was performed under general anesthesia with the laryngeal mask.Then,awake anesthesia,and functional mapping,such as sense,motion,and language zones,was judged via intraoperative neurophysiologic monitoring (IOM).Epileptogenic foci were localized by electrocorticography (ECoG) monitoring and assisted with an intra-operative real-time ultrasound to locate the anatomical boundary of the tumors.Surgical resected tumors and epileptogenic foci were performed under awake surgery.Finally,the skull was closed under general anesthesia.Results 28 patients underwent asleep-awake-asleep successfully in 31 cases; other than a short period of delirium post operation in older patients,no painful or dreaded experiences occurred before and after operations.18 patients remained on laryngeal masks,while 10 patients pulled out the laryngeal mask before language mapping and reinserted the mask after mapping was finished.23 patients' cerebral functional areas were located by IOM; in five cases,eloquent areas were not found.Epileptogenic foci were discovered in 21 cases through ECoG monitoring.Total resection was achieved in 21 patients and subtotal resection in 7.Preoperative dysfunctions aggravated in 17 cases 2 days after operation,but all patients recovered in one month; no permanent or new complications were noted.Pathology:astrocytoma Ⅰ ～ Ⅱ grade was noted in 14 patients,Ⅲ ～ Ⅳgrade in 3,oligodendroglioma in 4,oligodendroglioma and glioblastoma in 2,and other types in 3 respectively.All patients were followed-up from 8 months to 4.3 years.In 18 cases,epileptic seizures disappeared completely and severity decreased in10 patients.Consequently,the effective rate was 100％.Unfortunately,tumor recurrences were noted in 16 cases; operation was performed in 9 Cases,radiotherapy in 4,relinquishment of treatment in 2 and fatality in 2.Conclusion The combination of awake anesthesia and the modern,multimodal Cerebral functional localization monitoring technique for secondary epilepsy caused by glioma in eloquent areas is a safe,effective and microinvasive treatment method. Key words: Eloquent area; Glioma; Secondary epilepsy; Awake anaesthesia; Intraoperative neurophysiologic monitoring; Electrocorticography

Advanced neuroimaging techniques for diagnosis and treatment evaluation in neuro-oncology

Novel therapies of central nervous system (CNS) malignancies have evoked the demand to increasingly integrate dedicated imaging techniques into the diagnostic work-up and treatment evaluation in neuro-oncology. In primary and secondary malignancies of the CNS, advanced neuroimaging techniques enable non-invasive assessment of tissue microstructure, cellular and vascular proliferation and capillary permeability. Furthermore, eloquent cortical areas in the vicinity of tumours and the course of white matter pathways are rendered visible to facilitate surgical therapy.

Comparison of navigated transcranial magnetic stimulation and functional magnetic resonance imaging for preoperative mapping in rolandic tumor surgery

Navigated transcranial magnetic stimulation (nTMS) is a novel tool for preoperative functional mapping. It detects eloquent cortical areas directly, comparable to intraoperative direct cortical stimulation (DCS). The aim of this study was to evaluate the advantage of nTMS in comparison with functional magnetic resonance imaging (fMRI) in the clinical setting. Special focus was placed on accuracy of motor cortex localization in patients with rolandic lesions. Thirty consecutive patients were enrolled in the study. All patients received an fMRI and nTMS examination preoperatively. Feasibility of the technique and spatial resolution of upper and lower extremity cortical mapping were compared with fMRI. Consistency of preoperative mapping with intraoperative DCS was assessed via the neuronavigation system. nTMS was feasible in all 30 patients. fMRI was impossible in 7 out of 30 patients with special clinical conditions, pediatric patients, central vascular lesions, or compliance issues. The mean accuracy to localize motor cortex of nTMS was higher than in fMRI. In the subgroup of intrinsic tumors, nTMS produced statistically significant higher accuracy scores of the lower extremity localization than fMRI. fMRI failed to localize hand or leg areas in 6 out of 23 cases. Using nTMS, a preoperative localization of the central sulcus was possible in all patients. Verification of nTMS motor cortex localization with DCS was achieved in all cases. The fMRI localization of the hand area proved to be postcentral in one case. nTMS has fewer restrictions for preoperative functional mapping than fMRI and requires only a limited level of compliance. nTMS scores higher on the accuracy scale than fMRI. nTMS represents a highly valuable supplement for the preoperative functional planning in the clinical routine.

Comparison of BOLD Cerebrovascular Reactivity Mapping and DSC MR Perfusion Imaging for Prediction of Neurovascular Uncoupling Potential in Brain Tumors

The coupling mechanism between neuronal firing and cerebrovascular dilatation can be significantly compromised in cerebral diseases, making it difficult to identify eloquent cortical areas near or within resectable lesions by using Blood Oxygen Level Dependent (BOLD) fMRI. Several metabolic and vascular factors have been considered to account for this lesion-induced neurovascular uncoupling (NVU), but no imaging gold standard exists currently for the detection of NVU. However, it is critical in clinical fMRI studies to evaluate the risk of NVU because the presence of NVU may result in false negative activation that may result in inadvertent resection of eloquent cortex, resulting in permanent postoperative neurologic deficits. Although NVU results from a disruption of one or more components of a complex cellular and chemical neurovascular coupling cascade (NCC) MR imaging is only able to evaluate the final step in this NCC involving the ultimate cerebrovascular response. Since anything that impairs cerebrovascular reactivity (CVR) will necessarily result in NVU, regardless of its effect more proximally along the NCC, we can consider mapping of CVR as a surrogate marker of NVU potential. We hypothesized that BOLD breath-hold (BH) CVR mapping can serve as a better marker of NVU potential than T2* Dynamic Susceptibility Contrast gadolinium perfusion MR imaging, because the latter is known to only reflect NVU risk associated with high grade gliomas by determining elevated relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) related to tumor angiogenesis. However, since low and intermediate grade gliomas are not associated with such tumoral hyperperfusion, BOLD BH CVR mapping may be able to detect such NVU potential even in lower grade gliomas without angiogenesis, which is the hallmark of glioblastomas. However, it is also known that glioblastomas are associated with variable NVU, since angiogenesis may not always result in NVU. Perfusion metrics obtained by T2* gadolinium perfusion MR imaging were compared to BOLD percentage signal change on BH CVR maps in a group of 19 patients with intracranial brain tumors of different nature and grade. Single pixel maximum rCBV and rCBF within holotumoral regions of interest (i.e., "ipsilesional" ROIs) were normalized to contralateral hemispheric homologous (i.e., "contralesional") normal tissue. Furthermore, percentage signal change on BH CVR maps within ipsilesional ROIs were normalized to the percentage signal change within contralesional homologous ROIs. Inverse linear correlation was found between normalized rCBF (r(flow)) or rCBV (r(vol)) and normalized CVR percentage signal change (r(CVR)) in grade IV lesions. In the grade III lesions a less steep inverse linear trend was seen that did not reach statistical significance, whereas no correlation at all was seen in the grade II group. Statistically significant difference was present for r(flow) and r(vol) between the grade II and IV groups and between the grade III and IV groups but not for r(CVR). The r(CVR) was significantly lower than 1 in every group. Our results demonstrate that while T2*MR perfusion maps and CVR maps are both adequate to map tumoral regions at risk of NVU in high grade gliomas, CVR maps can detect areas of decreased CVR also in low and intermediate grade gliomas where NVU may be caused by factors other than tumor neovascularity alone. Comparison of areas of abnormally decreased regional CVR with areas of absent BOLD task-based activation in expected eloquent cortical regions infiltrated by or adjacent to the tumors revealed overall 95% concordance, thus confirming the capability of BH CVR mapping to effectively demonstrate areas of NVU. ed by factors other than tumor neovascularity alone. Comparison of areas of abnormally decreased regional CVR with areas of absent BOLD task-based activation in expected eloquent cortical regions infiltrated by or adjacent to the tumors revealed overall 95% concordance, thus confirming the capability of BH CVR mapping to effectively demonstrate areas of NVU.