Resection probability maps for quality assessment of glioma surgery without brain location bias

Intraoperative brain stimulation mapping reduces permanent postoperative deficits and extends tumor removal in resective surgery for glioma patients. Successful functional mapping is assumed to depend on the surgical team's expertise. In this study, glioma resection results are quantified and compared using a novel approach, so-called resection probability maps (RPM), exemplified by a surgical team comparison, here with long and short experience in mapping. Adult patients with glioma were included by two centers with two and fifteen years of mapping experience. Resective surgery was targeted at non-enhanced MRI extension and was limited by functional boundaries. Neurological outcome was compared. To compare resection results, we applied RPMs to quantify and compare the resection probability throughout the brain at 1 mm resolution. Considerations for spatial dependence and multiple comparisons were taken into account. The senior surgical team contributed 56, and the junior team 52 patients. The patient cohorts were comparable in age, preoperative tumor volume, lateralization, and lobe localization. Neurological outcome was similar between teams. The resection probability on the RPMs was very similar, with none (0%) of 703,967 voxels in left-sided tumors being differentially resected, and 124 (0.02%) of 644,153 voxels in right-sided tumors. RPMs provide a quantitative volumetric method to compare resection results, which we present as standard for quality assessment of resective glioma surgery because brain location bias is avoided. Stimulation mapping is a robust surgical technique, because the neurological outcome and functional-based resection results using stimulation mapping are independent of surgical experience, supporting wider implementatio

Association between tumor location and neurocognitive functioning using tumor localization maps

Introduction: Patients with diffuse glioma often experience neurocognitive impairment already prior to surgery. Pertinent information on whether damage to a specific brain region due to tumor activity results in neurocognitive impairment or not, is relevant in clinical decision-making, and at the same time renders unique information on brain lesion location and functioning relationships. To examine the impact of tumor location on preoperative neurocognitive functioning (NCF), we performed MRI based lesion-symptom mapping. Methods: Seventy-two patients (mean age 40 years) with a radiologically suspected glioma were recruited preoperatively. For each of the six cognitive domains tested, we used tumor localization maps and voxel-based lesion-symptom mapping analyses to identify cortical and subcortical regions associated with NCF impairment. Results: Compared to healthy controls, preoperative NCF was significantly impaired in all cognitive domains. Most frequently affected were attention (30% of patients) and working memory (20% of patients). Deficits in attention were significantly associated with regions in the left frontal and parietal cortex, including the precentral and parietal-opercular cortex, and in left-sided subcortical fiber tracts, including the arcuate fasciculus and corticospinal tract. Surprisingly, no regions could be related to working memory capacity. For the other neurocognitive domains, impairments were mainly associated with regions in the left hemisphere. Conclusions: Prior to treatment, patients with diffuse glioma in the left hemisphere run the highest risk to have NCF deficits. Identification of a left frontoparietal network involved in NCF not only may optimize surgical procedures but may also be integrated in counseling and cognitive rehabilitation for these patients

Linking late cognitive outcome with glioma surgery location using resection cavity maps

Patients with a diffuse glioma may experience cognitive decline or improvement upon resective surgery. To examine the impact of glioma location, cognitive alteration after glioma surgery was quantified and related to voxel-based resection probability maps. A total of 59 consecutive patients (range 18-67 years of age) who had resective surgery between 2006 and 2011 for a supratentorial nonenhancing diffuse glioma (grade I-III, WHO 2007) were included in this observational cohort study. Standardized neuropsychological examination and MRI were obtained before and after surgery. Intraoperative stimulation mapping guided resections towards neurological functions (language, sensorimotor function, and visual fields). Maps of resected regions were constructed in standard space. These resection cavity maps were compared between patients with and without new cognitive deficits (z-score difference >1.5 SD between baseline and one year after resection), using a voxel-wise randomization test and calculation of false discovery rates. Brain regions significantly associated with cognitive decline were classified in standard cortical and subcortical anatomy. Cognitive improvement in any domain occurred in 10 (17%) patients, cognitive decline in any domain in 25 (42%), and decline in more than one domain in 10 (17%). The most frequently affected subdomains were attention in 10 (17%) patients and information processing speed in 9 (15%). Resection regions associated with decline in more than one domain were predominantly located in the right hemisphere. For attention decline, no specific region could be identified. For decline in information speed, several regions were found, including the frontal pole and the corpus callosum. Cognitive decline after resective surgery of diffuse glioma is prevalent, in particular, in patients with a tumor located in the right hemisphere without cognitive function mappin

Patient characteristics.

<p>Patient characteristics.</p

Resection probability maps for left-sided gliomas.

<p>Results comparing the junior surgical team, n = 23, and the senior surgical team, n = 27. Coding and legends as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073353#pone-0073353-g003" target="_blank">Fig. 3</a>. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073353#pone.0073353.s003" target="_blank">Movie S3</a> for all transversal sections.</p

The minimal common brain for the left and right hemisphere.

<p>Results of resection probability from the junior (n = 52) and senior team (n = 56) were combined. Legend as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073353#pone-0073353-g003" target="_blank">Fig. 3A and 3B</a>. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073353#pone.0073353.s004" target="_blank">Movie S4</a> for all transversal sections.</p

Resection probability maps for right-sided gliomas.

<p>Results comparing (A) the junior surgical team, n = 29, and (B) the senior surgical team, n = 29, are shown superimposed on standard brain space (MNI152). A probability of 0 (red) represents locations where tumor was never resected, and a probability of 1 (green) represents locations where tumor was resected in all patients. An intermediate probability (yellow) represents locations where glioma was removed in a subset of patients. (C) Relative differences in probability of resection as log odds ratio. (D) The adjusted p-value map adjusted by the empirical null-distribution to address spatial dependency of voxels. Values less than 0.15 are plotted in shades of red. (E) The q-value map to address multiple testing. Values below 0.2 are plotted in shades of red, values between 0.2 and 0.8 in shades of blue. (F) Differences in probability of resection as log odds ratio for voxels with a q-value less than 0.2 demonstrate similar resection results between the two patient cohorts. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073353#s3" target="_blank">Results</a> are superimposed on a transversal section at z = 0 of MNI152. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073353#pone.0073353.s002" target="_blank">Movie S2</a> for all transversal sections.</p

Identifying the epileptogenic zone in interictal resting-state MEG source-space networks

Objective: In one third of patients, seizures remain after epilepsy surgery, meaning that improved preoperative evaluation methods are needed to identify the epileptogenic zone. A potential framework for such a method is network theory, as it can be applied to noninvasive recordings, even in the absence of epileptiform activity. Our aim was to identify the epileptogenic zone on the basis of hub status of local brain areas in interictal magnetoencephalography (MEG) networks. Methods: Preoperative eyes-closed resting-state MEG recordings were retrospectively analyzed in 22 patients with refractory epilepsy, of whom 14 were seizure-free 1 year after surgery. Beamformer-based time series were reconstructed for 90 cortical and subcortical automated anatomic labeling (AAL) regions of interest (ROIs). Broadband functional connectivity was estimated using the phase lag index in artifact-free epochs without interictal epileptiform abnormalities. A minimum spanning tree was generated to represent the network, and the hub status of each ROI was calculated using betweenness centrality, which indicates the centrality of a node in a network. The correspondence of resection cavity to hub values was evaluated on four levels: resection cavity, lobar, hemisphere, and temporal versus extratemporal areas. Results: Hubs were localized within the resection cavity in 8 of 14 seizure-free patients and in zero of 8 patients who were not seizure-free (57% sensitivity, 100% specificity, 73% accuracy). Hubs were localized in the lobe of resection in 9 of 14 seizure-free patients and in zero of 8 patients who were not seizure-free (64% sensitivity, 100% specificity, 77% accuracy). For the other two levels, the true negatives are unknown; hence, only sensitivity could be determined: hubs coincided with both the resection hemisphere and the resection location (temporal versus extratemporal) in 11 of 14 seizure-free patients (79% sensitivity). Significance: Identifying hubs noninvasively before surgery is a valuable approach with the potential of indicating the epileptogenic zone in patients without interictal abnormalities

Glioma locations within the brain are dissimilar between cohorts.

<p>Four transversal sections from (A) the junior team's cohort, n = 52, and (B) the senior team's cohort, n = 56, are shown superimposed on standard brain space (MNI152). More gliomas are located in the left insula and left temporal lobe in the senior team's cohort. More gliomas are located in the left supplementary motor cortex and right temporal lobe in the junior team's cohort. The legend refers to the number of patients with glioma tissue at a voxel. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073353#pone.0073353.s001" target="_blank">Movie S1</a> for all transversal sections.</p