Cancers

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19 pages, 4695 KiB

Open AccessArticle

BOLD Coupling between Lesioned and Healthy Brain Is Associated with Glioma Patients’ Recovery

by Rafael Romero-Garcia, Michael G. Hart, Richard A. I. Bethlehem, Ayan Mandal, Moataz Assem, Benedicto Crespo-Facorro, Juan Manuel Gorriz, G. A. Amos Burke, Stephen J. Price, Thomas Santarius, Yaara Erez and John Suckling

Cancers 2021, 13(19), 5008; https://doi.org/10.3390/cancers13195008 - 06 Oct 2021

Cited by 7 | Viewed by 2918

Abstract

Predicting functional outcomes after surgery and early adjuvant treatment is difficult due to the complex, extended, interlocking brain networks that underpin cognition. The aim of this study was to test glioma functional interactions with the rest of the brain, thereby identifying the risk [...] Read more.

Predicting functional outcomes after surgery and early adjuvant treatment is difficult due to the complex, extended, interlocking brain networks that underpin cognition. The aim of this study was to test glioma functional interactions with the rest of the brain, thereby identifying the risk factors of cognitive recovery or deterioration. Seventeen patients with diffuse non-enhancing glioma (aged 22–56 years) were longitudinally MRI scanned and cognitively assessed before and after surgery and during a 12-month recovery period (55 MRI scans in total after exclusions). We initially found, and then replicated in an independent dataset, that the spatial correlation pattern between regional and global BOLD signals (also known as global signal topography) was associated with tumour occurrence. We then estimated the coupling between the BOLD signal from within the tumour and the signal extracted from different brain tissues. We observed that the normative global signal topography is reorganised in glioma patients during the recovery period. Moreover, we found that the BOLD signal within the tumour and lesioned brain was coupled with the global signal and that this coupling was associated with cognitive recovery. Nevertheless, patients did not show any apparent disruption of functional connectivity within canonical functional networks. Understanding how tumour infiltration and coupling are related to patients’ recovery represents a major step forward in prognostic development. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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14 pages, 1231 KiB

Open AccessArticle

Predicting Overall Survival Time in Glioblastoma Patients Using Gradient Boosting Machines Algorithm and Recursive Feature Elimination Technique

by Golestan Karami, Marco Giuseppe Orlando, Andrea Delli Pizzi, Massimo Caulo and Cosimo Del Gratta

Cancers 2021, 13(19), 4976; https://doi.org/10.3390/cancers13194976 - 04 Oct 2021

Cited by 11 | Viewed by 2176

Abstract

Despite advances in tumor treatment, the inconsistent response is a major challenge among glioblastoma multiform (GBM) that lead to different survival time. Our aim was to integrate multimodal MRI with non-supervised and supervised machine learning methods to predict GBM patients’ survival time. To [...] Read more.

Despite advances in tumor treatment, the inconsistent response is a major challenge among glioblastoma multiform (GBM) that lead to different survival time. Our aim was to integrate multimodal MRI with non-supervised and supervised machine learning methods to predict GBM patients’ survival time. To this end, we identified different compartments of the tumor and extracted their features. Next, we applied Random Forest-Recursive Feature Elimination (RF-RFE) to identify the most relevant features to feed into a GBoost machine. This study included 29 GBM patients with known survival time. RF-RFE GBoost model was evaluated to assess the survival prediction performance using optimal features. Furthermore, overall survival (OS) was analyzed using univariate and multivariate Cox regression analyses, to evaluate the effect of ROIs and their features on survival. The results showed that a RF-RFE Gboost machine was able to predict survival time with 75% accuracy. The results also revealed that the rCBV in the low perfusion area was significantly different between groups and had the greatest effect size in terms of the rate of change of the response variable (survival time). In conclusion, not only integration of multi-modality MRI but also feature selection method can enhance the classifier performance. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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23 pages, 10045 KiB

Open AccessFeature PaperArticle

Glioblastoma Surgery Imaging–Reporting and Data System: Validation and Performance of the Automated Segmentation Task

by David Bouget, Roelant S. Eijgelaar, André Pedersen, Ivar Kommers, Hilko Ardon, Frederik Barkhof, Lorenzo Bello, Mitchel S. Berger, Marco Conti Nibali, Julia Furtner, Even Hovig Fyllingen, Shawn Hervey-Jumper, Albert J. S. Idema, Barbara Kiesel, Alfred Kloet, Emmanuel Mandonnet, Domenique M. J. Müller, Pierre A. Robe, Marco Rossi, Lisa M. Sagberg, Tommaso Sciortino, Wimar A. Van den Brink, Michiel Wagemakers, Georg Widhalm, Marnix G. Witte, Aeilko H. Zwinderman, Ingerid Reinertsen, Philip C. De Witt Hamer and Ole Solheim Show full author list Hide full author list

Cancers 2021, 13(18), 4674; https://doi.org/10.3390/cancers13184674 - 17 Sep 2021

Cited by 9 | Viewed by 4030

Abstract

For patients with presumed glioblastoma, essential tumor characteristics are determined from preoperative MR images to optimize the treatment strategy. This procedure is time-consuming and subjective, if performed by crude eyeballing or manually. The standardized GSI-RADS aims to provide neurosurgeons with automatic tumor segmentations [...] Read more.

For patients with presumed glioblastoma, essential tumor characteristics are determined from preoperative MR images to optimize the treatment strategy. This procedure is time-consuming and subjective, if performed by crude eyeballing or manually. The standardized GSI-RADS aims to provide neurosurgeons with automatic tumor segmentations to extract tumor features rapidly and objectively. In this study, we improved automatic tumor segmentation and compared the agreement with manual raters, describe the technical details of the different components of GSI-RADS, and determined their speed. Two recent neural network architectures were considered for the segmentation task: nnU-Net and AGU-Net. Two preprocessing schemes were introduced to investigate the tradeoff between performance and processing speed. A summarized description of the tumor feature extraction and standardized reporting process is included. The trained architectures for automatic segmentation and the code for computing the standardized report are distributed as open-source and as open-access software. Validation studies were performed on a dataset of 1594 gadolinium-enhanced T1-weighted MRI volumes from 13 hospitals and 293 T1-weighted MRI volumes from the BraTS challenge. The glioblastoma tumor core segmentation reached a Dice score slightly below 90%, a patientwise F1-score close to 99%, and a 95th percentile Hausdorff distance slightly below

4.0

mm on average with either architecture and the heavy preprocessing scheme. A patient MRI volume can be segmented in less than one minute, and a standardized report can be generated in up to five minutes. The proposed GSI-RADS software showed robust performance on a large collection of MRI volumes from various hospitals and generated results within a reasonable runtime. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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13 pages, 2055 KiB

Open AccessArticle

Raman Spectroscopy and Machine Learning for IDH Genotyping of Unprocessed Glioma Biopsies

by Tommaso Sciortino, Riccardo Secoli, Ester d’Amico, Sara Moccia, Marco Conti Nibali, Lorenzo Gay, Marco Rossi, Nicolò Pecco, Antonella Castellano, Elena De Momi, Bethania Fernandes, Marco Riva and Lorenzo Bello

Cancers 2021, 13(16), 4196; https://doi.org/10.3390/cancers13164196 - 20 Aug 2021

Cited by 21 | Viewed by 2762

Abstract

Isocitrate dehydrogenase (IDH) mutational status is pivotal in the management of gliomas. Patients with IDH-mutated (IDH-MUT) tumors have a better prognosis and benefit more from extended surgical resection than IDH wild-type (IDH-WT). Raman spectroscopy (RS) is a minimally invasive optical technique with great [...] Read more.

Isocitrate dehydrogenase (IDH) mutational status is pivotal in the management of gliomas. Patients with IDH-mutated (IDH-MUT) tumors have a better prognosis and benefit more from extended surgical resection than IDH wild-type (IDH-WT). Raman spectroscopy (RS) is a minimally invasive optical technique with great potential for intraoperative diagnosis. We evaluated the RS’s ability to characterize the IDH mutational status onto unprocessed glioma biopsies. We extracted 2073 Raman spectra from thirty-eight unprocessed samples. The classification performance was assessed using the eXtreme Gradient Boosted trees (XGB) and Support Vector Machine with Radial Basis Function kernel (RBF-SVM). Measured Raman spectra displayed differences between IDH-MUT and IDH-WT tumor tissue. From the 103 Raman shifts screened as input features, the cross-validation loop identified 52 shifts with the highest performance in the distinction of the two groups. Raman analysis showed differences in spectral features of lipids, collagen, DNA and cholesterol/phospholipids. We were able to distinguish between IDH-MUT and IDH-WT tumors with an accuracy and precision of 87%. RS is a valuable and accurate tool for characterizing the mutational status of IDH mutation in unprocessed glioma samples. This study improves RS knowledge for future personalized surgical strategy or in situ target therapies for glioma tumors. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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20 pages, 5171 KiB

Open AccessArticle

Targeting Primary Motor Cortex (M1) Functional Components in M1 Gliomas Enhances Safe Resection and Reveals M1 Plasticity Potentials

by Marco Rossi, Luca Viganò, Gugliemo Puglisi, Marco Conti Nibali, Antonella Leonetti, Lorenzo Gay, Tommaso Sciortino, Luca Fornia, Vincenzo Callipo, Marta Lamperti, Marco Riva, Gabriella Cerri and Lorenzo Bello

Cancers 2021, 13(15), 3808; https://doi.org/10.3390/cancers13153808 - 28 Jul 2021

Cited by 11 | Viewed by 2285

Abstract

Primary-Motor-Cortex (M1) hosts two functional components, at its posterior and anterior borders, being the first faster and more excitable. We developed a mapping-technique for M1 components identification and determined their functional cortical-subcortical architecture in M1 gliomas and the impact of their identification on [...] Read more.

Primary-Motor-Cortex (M1) hosts two functional components, at its posterior and anterior borders, being the first faster and more excitable. We developed a mapping-technique for M1 components identification and determined their functional cortical-subcortical architecture in M1 gliomas and the impact of their identification on tumor resection and motor performance. A novel advanced mapping technique was used in 102 tumors within M1 or CorticoSpinal-Tract to identify M1-two components. High-Frequency-stimulation (2–5 pulses) with an on-line qualitative and quantitative analysis of motor responses was used; the two components’ cortical/subcortical spatial distribution correlated to clinical, tumor-related factor and patients’ motor outcome; a cohort treated with standard-mapping was used for comparison. The two functional components were always identified on-line; in tumors not affecting M1, its functional segregation was preserved. In M1 tumors, two architectures, both preserving the two components, were disclosed: in 50%, a normal cortical/subcortical architecture emerged, while 50% revealed a distorted architecture with loss of anatomical reference and somatotopy, not associated with tumor histo-molecular features or volume, but with a previous treatment. Motor performance was maintained, suggesting functional compensation. By preserving the highest and resecting the lowest excitability component, the complete-resection increased with low morbidity. The real-time identification of two M1 functional components and the preservation of the highest excitability one increases safe resection, revealing M1 plasticity potentials. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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12 pages, 2385 KiB

Open AccessArticle

Impaired Set-Shifting from Dorsal Stream Disconnection: Insights from a European Series of Right Parietal Lower-Grade Glioma Resection

by Suzanne L. Hartung, Emmanuel Mandonnet, Philip de Witt Hamer, Martin Klein, Michel Wager, Fabien Rech, Johan Pallud, Catarina Pessanha Viegas, Sebastian Ille, Sandro M. Krieg, Pierre A. Robe and Martine J. E. van Zandvoort

Cancers 2021, 13(13), 3337; https://doi.org/10.3390/cancers13133337 - 03 Jul 2021

Cited by 7 | Viewed by 2106

Abstract

Awake surgery with cognitive monitoring has increasingly been implemented to preserve brain networks and functionality. More recently, not only surgery in the left but also in the right hemisphere, i.c., the parietal lobe, was associated with potential risk for deficits in cognitive functions, [...] Read more.

Awake surgery with cognitive monitoring has increasingly been implemented to preserve brain networks and functionality. More recently, not only surgery in the left but also in the right hemisphere, i.c., the parietal lobe, was associated with potential risk for deficits in cognitive functions, such as cognitive flexibility. In this explorative pilot study, we compare cognitive performance more than three months after surgery with baseline measurements and explore the association between cognitive decline and subcortical tracts that may have been severed during surgery in the right hemisphere. Twenty-two patients who underwent surgery for a right parietal low-grade glioma were assessed pre- and postoperatively using the Trail Making Test and the Stroop task to administer set-shifting abilities and inhibition. Volume measurements and lesion–symptom mapping analyses were performed on postoperative MRI scans. Careful interpretation of the results shows a change in TMT performance and not on the Stroop Task when the lateral part of the arcuate fasciculus is damaged, indicating that disconnection of the lateral part of the dorsal stream might be correlated specifically with impaired set-shifting and not with inhibition. More importantly, this study underlines the need for international concertation to allow larger studies to increase power and perform more detailed analyses. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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16 pages, 1191 KiB

Open AccessArticle

An Evaluation of the Tolerability and Feasibility of Combining 5-Amino-Levulinic Acid (5-ALA) with BCNU Wafers in the Surgical Management of Primary Glioblastoma

by Colin Watts, Keyoumars Ashkan, Michael D. Jenkinson, Stephen J. Price, Thomas Santarius, Tomasz Matys, Ting Ting Zhang, Alina Finch, Peter Collins, Kieren Allinson, Sarah J. Jefferies, Daniel J. Scoffings, Athanasios Zisakis, Mark Phillips, Katharina Wanek, Paul Smith, Laura Clifton-Hadley and Nicholas Counsell

Cancers 2021, 13(13), 3241; https://doi.org/10.3390/cancers13133241 - 29 Jun 2021

Cited by 3 | Viewed by 2004

Abstract

Background Glioblastoma (GBM) is the commonest primary malignant brain tumour in adults and effective treatment options are limited. Combining local chemotherapy with enhanced surgical resection using 5-aminolevulinic acid (5-ALA) could improve outcomes. Here we assess the safety and feasibility of combining BCNU wafers [...] Read more.

Background Glioblastoma (GBM) is the commonest primary malignant brain tumour in adults and effective treatment options are limited. Combining local chemotherapy with enhanced surgical resection using 5-aminolevulinic acid (5-ALA) could improve outcomes. Here we assess the safety and feasibility of combining BCNU wafers with 5-ALA-guided surgery. Methods We conducted a multicentre feasibility study of 5-ALA with BCNU wafers followed by standard-of-care chemoradiotherapy (chemoRT) in patients with suspected GBM. Patients judged suitable for radical resection were administered 5-ALA pre-operatively and BCNU wafers at the end resection. Post-operative treatment continued as per routine clinical practice. The primary objective was to establish if combining 5-ALA and BCNU wafers is safe without compromising patients from receiving standard chemoRT. Results Seventy-two patients were recruited, sixty-four (88.9%) received BCNU wafer implants, and fifty-nine (81.9%) patients remained eligible following formal histological diagnosis. Seven (11.9%) eligible patients suffered surgical complications but only two (3.4%) were not able to begin chemoRT, four (6.8%) additional patients did not begin chemoRT within 6 weeks of surgery due to surgical complications. Eleven (18.6%) patients did not begin chemoRT for other reasons (other toxicity (n = 3), death (n = 3), lost to follow-up/withdrew (n = 3), clinical decision (n = 1), poor performance status (n = 1)). Median progression-free survival was 8.7 months (95% CI: 6.4–9.8) and median overall survival was 14.7 months (95% CI: 11.7–16.8). Conclusions Combining BCNU wafers with 5-ALA-guided surgery in newly diagnosed GBM patients is both feasible and tolerable in terms of surgical morbidity and overall toxicity. Any potential therapeutic benefit for the sequential use of 5-ALA and BCNU with chemoRT requires further investigation with improved local delivery technologies. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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10 pages, 3084 KiB

Open AccessArticle

The Impact of an Ultra-Early Postoperative MRI on Treatment of Lower Grade Glioma

by Andrej Pala, Gregor Durner, Michael Braun, Bernd Schmitz, Christian Rainer Wirtz and Jan Coburger

Cancers 2021, 13(12), 2914; https://doi.org/10.3390/cancers13122914 - 10 Jun 2021

Cited by 4 | Viewed by 2033

Abstract

The timing of MRI imaging after surgical resection may have an important role in assessing the extent of resection (EoR) and in determining further treatment. The aim of our study was to evaluate the time dependency of T2 and FLAIR changes after surgery [...] Read more.

The timing of MRI imaging after surgical resection may have an important role in assessing the extent of resection (EoR) and in determining further treatment. The aim of our study was to evaluate the time dependency of T2 and FLAIR changes after surgery for LGG. The Log-Glio database of patients treated at our hospital from 2016 to 2021 was searched for patients >18a and non-enhancing intra-axial lesion with complete MR-imaging protocol. A total of 16 patients matched the inclusion criteria and were thus selected for volumetric analysis. All patients received an intraoperative scan (iMRI) after complete tumor removal, an ultra-early postoperative scan after skin closure, an early MRI within 48 h and a late follow up MRI after 3–4 mo. Detailed volumetric analysis of FLAIR and T2 abnormalities was conducted. Demographic data and basic characteristics were also analyzed. An ultra-early postoperative MRI was performed within a median time of 30 min after skin closure and showed significantly lower FLAIR (p = 0.003) and T2 (p = 0.003) abnormalities when compared to early postoperative MRI (median 23.5 h), though no significant difference was found between ultra-early and late postoperative FLAIR (p = 0.422) and T2 (p = 0.575) images. A significant difference was calculated between early and late postoperative FLAIR (p = 0.005) and T2 (p = 0.019) MRI scans. Additionally, we found no significant difference between intraoperative and ultra-early FLAIR/T2 (p = 0.919 and 0.499), but we found a significant difference between iMRI and early MRI FLAIR/T2 (p = 0.027 and p = 0.035). Therefore, a postoperative MRI performed 24 h or 48 h might lead to false positive findings. An MRI scan in the first hour after surgery (ultra-early) correlated best with residual tumor at 3 months follow up. An iMRI with open skull, at the end of resection, was similar to an ultra-early MRI with regard to residual tumor. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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22 pages, 58385 KiB

Open AccessArticle

Feasibility, Safety and Impact on Overall Survival of Awake Resection for Newly Diagnosed Supratentorial IDH-Wildtype Glioblastomas in Adults

by Alessandro Moiraghi, Alexandre Roux, Sophie Peeters, Jean-Baptiste Pelletier, Marwan Baroud, Bénédicte Trancart, Catherine Oppenheim, Emmanuèle Lechapt, Chiara Benevello, Eduardo Parraga, Pascale Varlet, Fabrice Chrétien, Edouard Dezamis, Marc Zanello and Johan Pallud

Cancers 2021, 13(12), 2911; https://doi.org/10.3390/cancers13122911 - 10 Jun 2021

Cited by 13 | Viewed by 2330

Abstract

Background: Although awake resection using intraoperative cortico-subcortical functional brain mapping is the benchmark technique for diffuse gliomas within eloquent brain areas, it is still rarely proposed for IDH-wildtype glioblastomas. We have assessed the feasibility, safety, and efficacy of awake resection for IDH-wildtype glioblastomas. [...] Read more.

Background: Although awake resection using intraoperative cortico-subcortical functional brain mapping is the benchmark technique for diffuse gliomas within eloquent brain areas, it is still rarely proposed for IDH-wildtype glioblastomas. We have assessed the feasibility, safety, and efficacy of awake resection for IDH-wildtype glioblastomas. Methods: Observational single-institution cohort (2012–2018) of 453 adult patients harboring supratentorial IDH-wildtype glioblastomas who benefited from awake resection, from asleep resection, or from a biopsy. Case matching (1:1) criteria between the awake group and asleep group: gender, age, RTOG-RPA class, tumor side, location and volume and neurosurgeon experience. Results: In patients in the awake resection subgroup (n = 42), supratotal resections were more frequent (21.4% vs. 3.1%, p < 0.0001) while partial resections were less frequent (21.4% vs. 40.1%, p < 0.0001) compared to the asleep (n = 222) resection subgroup. In multivariable analyses, postoperative standard radiochemistry (aHR = 0.04, p < 0.0001), supratotal resection (aHR = 0.27, p = 0.0021), total resection (aHR = 0.43, p < 0.0001), KPS score > 70 (HR = 0.66, p = 0.0013), MGMT promoter methylation (HR = 0.55, p = 0.0031), and awake surgery (HR = 0.54, p = 0.0156) were independent predictors of overall survival. After case matching, a longer overall survival was found for awake resection (HR = 0.47, p = 0.0103). Conclusions: Awake resection is safe, allows larger resections than asleep surgery, and positively impacts overall survival of IDH-wildtype glioblastoma in selected adult patients. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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23 pages, 7581 KiB

Open AccessArticle

Glioblastoma Surgery Imaging—Reporting and Data System: Standardized Reporting of Tumor Volume, Location, and Resectability Based on Automated Segmentations

by Ivar Kommers, David Bouget, André Pedersen, Roelant S. Eijgelaar, Hilko Ardon, Frederik Barkhof, Lorenzo Bello, Mitchel S. Berger, Marco Conti Nibali, Julia Furtner, Even H. Fyllingen, Shawn Hervey-Jumper, Albert J. S. Idema, Barbara Kiesel, Alfred Kloet, Emmanuel Mandonnet, Domenique M. J. Müller, Pierre A. Robe, Marco Rossi, Lisa M. Sagberg, Tommaso Sciortino, Wimar A. van den Brink, Michiel Wagemakers, Georg Widhalm, Marnix G. Witte, Aeilko H. Zwinderman, Ingerid Reinertsen, Ole Solheim and Philip C. De Witt Hamer Show full author list Hide full author list

Cancers 2021, 13(12), 2854; https://doi.org/10.3390/cancers13122854 - 08 Jun 2021

Cited by 6 | Viewed by 3841

Abstract

Treatment decisions for patients with presumed glioblastoma are based on tumor characteristics available from a preoperative MR scan. Tumor characteristics, including volume, location, and resectability, are often estimated or manually delineated. This process is time consuming and subjective. Hence, comparison across cohorts, trials, [...] Read more.

Treatment decisions for patients with presumed glioblastoma are based on tumor characteristics available from a preoperative MR scan. Tumor characteristics, including volume, location, and resectability, are often estimated or manually delineated. This process is time consuming and subjective. Hence, comparison across cohorts, trials, or registries are subject to assessment bias. In this study, we propose a standardized Glioblastoma Surgery Imaging Reporting and Data System (GSI-RADS) based on an automated method of tumor segmentation that provides standard reports on tumor features that are potentially relevant for glioblastoma surgery. As clinical validation, we determine the agreement in extracted tumor features between the automated method and the current standard of manual segmentations from routine clinical MR scans before treatment. In an observational consecutive cohort of 1596 adult patients with a first time surgery of a glioblastoma from 13 institutions, we segmented gadolinium-enhanced tumor parts both by a human rater and by an automated algorithm. Tumor features were extracted from segmentations of both methods and compared to assess differences, concordance, and equivalence. The laterality, contralateral infiltration, and the laterality indices were in excellent agreement. The native and normalized tumor volumes had excellent agreement, consistency, and equivalence. Multifocality, but not the number of foci, had good agreement and equivalence. The location profiles of cortical and subcortical structures were in excellent agreement. The expected residual tumor volumes and resectability indices had excellent agreement, consistency, and equivalence. Tumor probability maps were in good agreement. In conclusion, automated segmentations are in excellent agreement with manual segmentations and practically equivalent regarding tumor features that are potentially relevant for neurosurgical purposes. Standard GSI-RADS reports can be generated by open access software. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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21 pages, 6957 KiB

Open AccessArticle

What Can Glioma Patients Teach Us about Language (Re)Organization in the Bilingual Brain: Evidence from fMRI and MEG

by Ileana Quiñones, Lucia Amoruso, Iñigo Cristobal Pomposo Gastelu, Santiago Gil-Robles and Manuel Carreiras

Cancers 2021, 13(11), 2593; https://doi.org/10.3390/cancers13112593 - 25 May 2021

Cited by 9 | Viewed by 3193

Abstract

Recent evidence suggests that the presence of brain tumors (e.g., low-grade gliomas) triggers language reorganization. Neuroplasticity mechanisms called into play can transfer linguistic functions from damaged to healthy areas unaffected by the tumor. This phenomenon has been reported in monolingual patients, but much [...] Read more.

Recent evidence suggests that the presence of brain tumors (e.g., low-grade gliomas) triggers language reorganization. Neuroplasticity mechanisms called into play can transfer linguistic functions from damaged to healthy areas unaffected by the tumor. This phenomenon has been reported in monolingual patients, but much less is known about the neuroplasticity of language in the bilingual brain. A central question is whether processing a first or second language involves the same or different cortical territories and whether damage results in diverse recovery patterns depending on the language involved. This question becomes critical for preserving language areas in bilingual brain-tumor patients to prevent involuntary pathological symptoms following resection. While most studies have focused on intraoperative mapping, here, we go further, reporting clinical cases for five bilingual patients tested before and after tumor resection, using a novel multimethod approach merging neuroimaging information from fMRI and MEG to map the longitudinal reshaping of the language system. Here, we present four main findings. First, all patients preserved linguistic function in both languages after surgery, suggesting that the surgical intervention with intraoperative language mapping was successful in preserving cortical and subcortical structures necessary for brain plasticity at the functional level. Second, we found reorganization of the language network after tumor resection in both languages, mainly reflected by a shift of activity to right hemisphere nodes and the recruitment of ipsilesional left nodes. Third, we found that this reorganization varied according to the language involved, indicating that L1 and L2 follow different reshaping patterns after surgery. Fourth, oscillatory longitudinal effects were correlated with BOLD laterality changes in superior parietal and middle frontal areas. These findings may reflect that neuroplasticity impacts on the compensatory involvement of executive control regions, supporting the allocation of cognitive resources as a consequence of increased attentional demands. Furthermore, these results hint at the complementary role of this neuroimaging approach in language mapping, with fMRI offering excellent spatial localization and MEG providing optimal spectrotemporal resolution. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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20 pages, 5109 KiB

Open AccessArticle

fMRI Retinotopic Mapping in Patients with Brain Tumors and Space-Occupying Brain Lesions in the Area of the Occipital Lobe

by Katharina Hense, Tina Plank, Christina Wendl, Frank Dodoo-Schittko, Elisabeth Bumes, Mark W. Greenlee, Nils Ole Schmidt, Martin Proescholdt and Katharina Rosengarth

Cancers 2021, 13(10), 2439; https://doi.org/10.3390/cancers13102439 - 18 May 2021

Cited by 1 | Viewed by 2221

Abstract

Functional magnetic resonance imaging (fMRI) is a valuable tool in the clinical routine of neurosurgery when planning surgical interventions and assessing the risk of postoperative functional deficits. Here, we examined how the presence of a brain tumor or lesion in the area of [...] Read more.

Functional magnetic resonance imaging (fMRI) is a valuable tool in the clinical routine of neurosurgery when planning surgical interventions and assessing the risk of postoperative functional deficits. Here, we examined how the presence of a brain tumor or lesion in the area of the occipital lobe affects the results of fMRI retinotopic mapping. fMRI data were evaluated on a retrospectively selected sample of 12 patients with occipital brain tumors, 7 patients with brain lesions and 19 control subjects. Analyses of the cortical activation, percent signal change, cluster size of the activated voxels and functional connectivity were carried out using Statistical Parametric Mapping (SPM12) and the CONN and Marsbar toolboxes. We found similar but reduced patterns of cortical activation and functional connectivity between the two patient groups compared to a healthy control group. Here, we found that retinotopic organization was well-preserved in the patients and was comparable to that of the age-matched controls. The results also showed that, compared to the tumor patients, the lesion patients showed higher percent signal changes but lower values in the cluster sizes of the activated voxels in the calcarine fissure region. Our results suggest that the lesion patients exhibited results that were more similar to those of the control subjects in terms of the BOLD signal, whereas the extent of the activation was comparable to that of the tumor patients. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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30 pages, 1618 KiB

Open AccessArticle

Voxelwise Principal Component Analysis of Dynamic [S-Methyl-¹¹C]Methionine PET Data in Glioma Patients

by Corentin Martens, Olivier Debeir, Christine Decaestecker, Thierry Metens, Laetitia Lebrun, Gil Leurquin-Sterk, Nicola Trotta, Serge Goldman and Gaetan Van Simaeys

Cancers 2021, 13(10), 2342; https://doi.org/10.3390/cancers13102342 - 12 May 2021

Cited by 10 | Viewed by 1983

Abstract

Recent works have demonstrated the added value of dynamic amino acid positron emission tomography (PET) for glioma grading and genotyping, biopsy targeting, and recurrence diagnosis. However, most of these studies are based on hand-crafted qualitative or semi-quantitative features extracted from the mean time [...] Read more.

Recent works have demonstrated the added value of dynamic amino acid positron emission tomography (PET) for glioma grading and genotyping, biopsy targeting, and recurrence diagnosis. However, most of these studies are based on hand-crafted qualitative or semi-quantitative features extracted from the mean time activity curve within predefined volumes. Voxelwise dynamic PET data analysis could instead provide a better insight into intra-tumor heterogeneity of gliomas. In this work, we investigate the ability of principal component analysis (PCA) to extract relevant quantitative features from a large number of motion-corrected [S-methyl-¹¹C]methionine ([¹¹C]MET) PET frames. We first demonstrate the robustness of our methodology to noise by means of numerical simulations. We then build a PCA model from dynamic [¹¹C]MET acquisitions of 20 glioma patients. In a distinct cohort of 13 glioma patients, we compare the parametric maps derived from our PCA model to these provided by the classical one-compartment pharmacokinetic model (1TCM). We show that our PCA model outperforms the 1TCM to distinguish characteristic dynamic uptake behaviors within the tumor while being less computationally expensive and not requiring arterial sampling. Such methodology could be valuable to assess the tumor aggressiveness locally with applications for treatment planning and response evaluation. This work further supports the added value of dynamic over static [¹¹C]MET PET in gliomas. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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12 pages, 6353 KiB

Open AccessArticle

Tractography for Subcortical Resection of Gliomas Is Highly Accurate for Motor and Language Function: ioMRI-Based Elastic Fusion Disproves the Severity of Brain Shift

by Sebastian Ille, Maximilian Schwendner, Wei Zhang, Axel Schroeder, Bernhard Meyer and Sandro M. Krieg

Cancers 2021, 13(8), 1787; https://doi.org/10.3390/cancers13081787 - 09 Apr 2021

Cited by 8 | Viewed by 2642

Abstract

When using preoperative tractography intraoperatively, inaccuracies due to brain shift might occur. Intraoperative tractography is rarely performed. Elastic fusion (EF) is a tool developed to compensate for brain shift, gravity, and tissue resection based on intraoperative images. Our hypothesis was that preoperative tractography [...] Read more.

When using preoperative tractography intraoperatively, inaccuracies due to brain shift might occur. Intraoperative tractography is rarely performed. Elastic fusion (EF) is a tool developed to compensate for brain shift, gravity, and tissue resection based on intraoperative images. Our hypothesis was that preoperative tractography is accurate and adjustments of tractography by intraoperative magnetic resonance imaging (ioMRI)-based EF (IBEF) compensate for brain shift. Between February 2018 and June 2019, 78 patients underwent eloquent (46 motor, 32 language) glioma resection in our department using intraoperative MRI. Mean distances between the resection cavity and tractography were analyzed and correlated with clinical outcomes. The mean ± standard deviation (range) distance after the application of IBEF was 5.0 ± 2.9 mm (0–10 mm) in patients without surgery-related motor deficits compared with 1.1 ± 1.6 mm (0–5 mm) in patients who showed new permanent surgery-related motor deficits postoperatively (p < 0.001). For language, the distance was 0.7 ± 1.2 mm (0–2 mm) in patients with new permanent deficits compared with 3.1 ± 4.5 mm (0–14 mm) in patients without new permanent surgery-related language deficits (p = 0.541). Preoperative tractography corrected by IBEF for subcortical resection of gliomas is highly accurate. However, at least for such subcortical anatomy, the severity of brain shift was considerably overestimated in the past. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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14 pages, 2986 KiB

Open AccessArticle

Glioma biopsies Classification Using Raman Spectroscopy and Machine Learning Models on Fresh Tissue Samples

by Marco Riva, Tommaso Sciortino, Riccardo Secoli, Ester D’Amico, Sara Moccia, Bethania Fernandes, Marco Conti Nibali, Lorenzo Gay, Marco Rossi, Elena De Momi and Lorenzo Bello

Cancers 2021, 13(5), 1073; https://doi.org/10.3390/cancers13051073 - 03 Mar 2021

Cited by 40 | Viewed by 4398

Abstract

Identifying tumor cells infiltrating normal-appearing brain tissue is critical to achieve a total glioma resection. Raman spectroscopy (RS) is an optical technique with potential for real-time glioma detection. Most RS reports are based on formalin-fixed or frozen samples, with only a few studies [...] Read more.

Identifying tumor cells infiltrating normal-appearing brain tissue is critical to achieve a total glioma resection. Raman spectroscopy (RS) is an optical technique with potential for real-time glioma detection. Most RS reports are based on formalin-fixed or frozen samples, with only a few studies deployed on fresh untreated tissue. We aimed to probe RS on untreated brain biopsies exploring novel Raman bands useful in distinguishing glioma and normal brain tissue. Sixty-three fresh tissue biopsies were analyzed within few minutes after resection. A total of 3450 spectra were collected, with 1377 labelled as Healthy and 2073 as Tumor. Machine learning methods were used to classify spectra compared to the histo-pathological standard. The algorithms extracted information from 60 different Raman peaks identified as the most representative among 135 peaks screened. We were able to distinguish between tumor and healthy brain tissue with accuracy and precision of 83% and 82%, respectively. We identified 19 new Raman shifts with known biological significance. Raman spectroscopy was effective and accurate in discriminating glioma tissue from healthy brain ex-vivo in fresh samples. This study added new spectroscopic data that can contribute to further develop Raman Spectroscopy as an intraoperative tool for in-vivo glioma detection. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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14 pages, 4487 KiB

Open AccessArticle

Non-Invasive Mapping for Effective Preoperative Guidance to Approach Highly Language-Eloquent Gliomas—A Large Scale Comparative Cohort Study Using a New Classification for Language Eloquence

by Sebastian Ille, Axel Schroeder, Lucia Albers, Anna Kelm, Doris Droese, Bernhard Meyer and Sandro M. Krieg

Cancers 2021, 13(2), 207; https://doi.org/10.3390/cancers13020207 - 08 Jan 2021

Cited by 12 | Viewed by 3103

Abstract

Objective: A considerable number of gliomas require resection via direct electrical stimulation (DES) during awake craniotomy. Likewise, the feasibility of resecting language-eloquent gliomas purely based on navigated repetitive transcranial magnetic stimulation (nrTMS) has been shown. This study analyzes the outcomes after preoperative nrTMS-based [...] Read more.

Objective: A considerable number of gliomas require resection via direct electrical stimulation (DES) during awake craniotomy. Likewise, the feasibility of resecting language-eloquent gliomas purely based on navigated repetitive transcranial magnetic stimulation (nrTMS) has been shown. This study analyzes the outcomes after preoperative nrTMS-based and intraoperative DES-based glioma resection in a large cohort. Due to the necessity of making location comparable, a classification for language eloquence for gliomas is introduced. Methods: Between March 2015 and May 2019, we prospectively enrolled 100 consecutive cases that were resected based on preoperative nrTMS language mapping (nrTMS group), and 47 cases via intraoperative DES mapping during awake craniotomy (awake group) following a standardized clinical workflow. Outcome measures were determined preoperatively, 5 days after surgery, and 3 months after surgery. To make functional eloquence comparable, we developed a classification based on prior publications and clinical experience. Groups and classification scores were correlated with clinical outcomes. Results: The functional outcome did not differ between groups. Gross total resection was achieved in more cases in the nrTMS group (87%, vs. 72% in the awake group, p = 0.04). Nonetheless, the awake group showed significantly higher scores for eloquence than the nrTMS group (median 7 points; interquartile range 6–8 vs. 5 points; 3–6.75; p < 0.0001). Conclusion: Resecting language-eloquent gliomas purely based on nrTMS data is feasible in a high percentage of cases if the described clinical workflow is followed. Moreover, the proposed classification for language eloquence makes language-eloquent tumors comparable, as shown by its correlation with functional and radiological outcomes. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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15 pages, 1381 KiB

Open AccessArticle

Non-Invasive Prediction of IDH Mutation in Patients with Glioma WHO II/III/IV Based on F-18-FET PET-Guided In Vivo ¹H-Magnetic Resonance Spectroscopy and Machine Learning

by Elisabeth Bumes, Fro-Philip Wirtz, Claudia Fellner, Jirka Grosse, Dirk Hellwig, Peter J. Oefner, Martina Häckl, Ralf Linker, Martin Proescholdt, Nils Ole Schmidt, Markus J. Riemenschneider, Claudia Samol, Katharina Rosengarth, Christina Wendl, Peter Hau, Wolfram Gronwald and Markus Hutterer

Cancers 2020, 12(11), 3406; https://doi.org/10.3390/cancers12113406 - 17 Nov 2020

Cited by 18 | Viewed by 2837

Abstract

Isocitrate dehydrogenase (IDH)-1 mutation is an important prognostic factor and a potential therapeutic target in glioma. Immunohistological and molecular diagnosis of IDH mutation status is invasive. To avoid tumor biopsy, dedicated spectroscopic techniques have been proposed to detect D-2-hydroxyglutarate (2-HG), the main [...] Read more.

Isocitrate dehydrogenase (IDH)-1 mutation is an important prognostic factor and a potential therapeutic target in glioma. Immunohistological and molecular diagnosis of IDH mutation status is invasive. To avoid tumor biopsy, dedicated spectroscopic techniques have been proposed to detect D-2-hydroxyglutarate (2-HG), the main metabolite of IDH, directly in vivo. However, these methods are technically challenging and not broadly available. Therefore, we explored the use of machine learning for the non-invasive, inexpensive and fast diagnosis of IDH status in standard ¹H-magnetic resonance spectroscopy (¹H-MRS). To this end, 30 of 34 consecutive patients with known or suspected glioma WHO grade II-IV were subjected to metabolic positron emission tomography (PET) imaging with O-(2-¹⁸F-fluoroethyl)-L-tyrosine (¹⁸F-FET) for optimized voxel placement in ¹H-MRS. Routine ¹H-magnetic resonance (¹H-MR) spectra of tumor and contralateral healthy brain regions were acquired on a 3 Tesla magnetic resonance (3T-MR) scanner, prior to surgical tumor resection and molecular analysis of IDH status. Since 2-HG spectral signals were too overlapped for reliable discrimination of IDH mutated (IDHmut) and IDH wild-type (IDHwt) glioma, we used a nested cross-validation approach, whereby we trained a linear support vector machine (SVM) on the complete spectral information of the ¹H-MRS data to predict IDH status. Using this approach, we predicted IDH status with an accuracy of 88.2%, a sensitivity of 95.5% (95% CI, 77.2–99.9%) and a specificity of 75.0% (95% CI, 42.9–94.5%), respectively. The area under the curve (AUC) amounted to 0.83. Subsequent ex vivo ¹H-nuclear magnetic resonance (¹H-NMR) measurements performed on metabolite extracts of resected tumor material (eight specimens) revealed myo-inositol (M-ins) and glycine (Gly) to be the major discriminators of IDH status. We conclude that our approach allows a reliable, non-invasive, fast and cost-effective prediction of IDH status in a standard clinical setting. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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Graphical abstract

18 pages, 3223 KiB

Open AccessArticle

Short-Interval Intracortical Facilitation Improves Efficacy in nTMS Motor Mapping of Lower Extremity Muscle Representations in Patients with Supra-Tentorial Brain Tumors

by Haosu Zhang, Petro Julkunen, Axel Schröder, Anna Kelm, Sebastian Ille, Claus Zimmer, Minna Pitkänen, Bernhard Meyer, Sandro M. Krieg and Nico Sollmann

Cancers 2020, 12(11), 3233; https://doi.org/10.3390/cancers12113233 - 02 Nov 2020

Cited by 6 | Viewed by 2323

Abstract

Navigated transcranial magnetic stimulation (nTMS) is increasingly used for mapping of motor function prior to surgery in patients harboring motor-eloquent brain lesions. To date, single-pulse nTMS (sp-nTMS) has been predominantly used for this purpose, but novel paired-pulse nTMS (pp-nTMS) with biphasic pulse application [...] Read more.

Navigated transcranial magnetic stimulation (nTMS) is increasingly used for mapping of motor function prior to surgery in patients harboring motor-eloquent brain lesions. To date, single-pulse nTMS (sp-nTMS) has been predominantly used for this purpose, but novel paired-pulse nTMS (pp-nTMS) with biphasic pulse application has been made available recently. The purpose of this study was to systematically evaluate pp-nTMS with biphasic pulses in comparison to conventionally used sp-nTMS for preoperative motor mapping of lower extremity (lE) muscle representations. Thirty-nine patients (mean age: 56.3 ± 13.5 years, 69.2% males) harboring motor-eloquent brain lesions of different entity underwent motor mapping of lE muscle representations in lesion-affected hemispheres and nTMS-based tractography of the corticospinal tract (CST) using data from sp-nTMS and pp-nTMS with biphasic pulses, respectively. Compared to sp-nTMS, pp-nTMS enabled motor mapping with lower stimulation intensities (61.8 ± 13.8% versus 50.7 ± 11.6% of maximum stimulator output, p < 0.0001), and it provided reliable motor maps even in the most demanding cases where sp-nTMS failed (pp-nTMS was able to provide a motor map in five patients in whom sp-nTMS did not provide any motor-positive points, and pp-nTMS was the only modality to provide a motor map in one patient who also did not show motor-positive points during intraoperative stimulation). Fiber volumes of the tracked CST were slightly higher when motor maps of pp-nTMS were used, and CST tracking using pp-nTMS data was also possible in the five patients in whom sp-nTMS failed. In conclusion, application of pp-nTMS with biphasic pulses enables preoperative motor mapping of lE muscle representations even in the most challenging patients in whom the motor system is at high risk due to lesion location or resection. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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16 pages, 3925 KiB

Open AccessArticle

Improved Diagnostic Imaging of Brain Tumors by Multimodal Microscopy and Deep Learning

by Johanna Gesperger, Antonia Lichtenegger, Thomas Roetzer, Matthias Salas, Pablo Eugui, Danielle J. Harper, Conrad W. Merkle, Marco Augustin, Barbara Kiesel, Petra A. Mercea, Georg Widhalm, Bernhard Baumann and Adelheid Woehrer

Cancers 2020, 12(7), 1806; https://doi.org/10.3390/cancers12071806 - 06 Jul 2020

Cited by 19 | Viewed by 3254

Abstract

Fluorescence-guided surgery is a state-of-the-art approach for intraoperative imaging during neurosurgical removal of tumor tissue. While the visualization of high-grade gliomas is reliable, lower grade glioma often lack visible fluorescence signals. Here, we present a hybrid prototype combining visible light optical coherence microscopy [...] Read more.

Fluorescence-guided surgery is a state-of-the-art approach for intraoperative imaging during neurosurgical removal of tumor tissue. While the visualization of high-grade gliomas is reliable, lower grade glioma often lack visible fluorescence signals. Here, we present a hybrid prototype combining visible light optical coherence microscopy (OCM) and high-resolution fluorescence imaging for assessment of brain tumor samples acquired by 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery. OCM provides high-resolution information of the inherent tissue scattering and absorption properties of tissue. We here explore quantitative attenuation coefficients derived from volumetric OCM intensity data and quantitative high-resolution 5-ALA fluorescence as potential biomarkers for tissue malignancy including otherwise difficult-to-assess low-grade glioma. We validate our findings against the gold standard histology and use attenuation and fluorescence intensity measures to differentiate between tumor core, infiltrative zone and adjacent brain tissue. Using large field-of-view scans acquired by a near-infrared swept-source optical coherence tomography setup, we provide initial assessments of tumor heterogeneity. Finally, we use cross-sectional OCM images to train a convolutional neural network that discriminates tumor from non-tumor tissue with an accuracy of 97%. Collectively, the present hybrid approach offers potential to translate into an in vivo imaging setup for substantially improved intraoperative guidance of brain tumor surgeries. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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Review

Jump to: Research, Other

21 pages, 3298 KiB

Open AccessReview

Functional Mapping before and after Low-Grade Glioma Surgery: A New Way to Decipher Various Spatiotemporal Patterns of Individual Neuroplastic Potential in Brain Tumor Patients

by Hugues Duffau

Cancers 2020, 12(9), 2611; https://doi.org/10.3390/cancers12092611 - 13 Sep 2020

Cited by 41 | Viewed by 5531

Abstract

Intraoperative direct electrostimulation mapping (DEM) is currently the gold-standard for glioma surgery, since functional-based resection allows an optimization of the onco-functional balance (increased resection with preserved quality of life). Besides intrasurgical awake mapping of conation, cognition, and behavior, preoperative mapping by means of [...] Read more.

Intraoperative direct electrostimulation mapping (DEM) is currently the gold-standard for glioma surgery, since functional-based resection allows an optimization of the onco-functional balance (increased resection with preserved quality of life). Besides intrasurgical awake mapping of conation, cognition, and behavior, preoperative mapping by means of functional neuroimaging (FNI) and transcranial magnetic stimulation (TMS) has increasingly been utilized for surgical selection and planning. However, because these techniques suffer from several limitations, particularly for direct functional mapping of subcortical white matter pathways, DEM remains crucial to map neural connectivity. On the other hand, non-invasive FNI and TMS can be repeated before and after surgical resection(s), enabling longitudinal investigation of brain reorganization, especially in slow-growing tumors like low-grade gliomas. Indeed, these neoplasms generate neuroplastic phenomena in patients with usually no or only slight neurological deficits at diagnosis, despite gliomas involving the so-called “eloquent” structures. Here, data gained from perioperative FNI/TMS mapping methods are reviewed, in order to decipher mechanisms underpinning functional cerebral reshaping induced by the tumor and its possible relapse, (re)operation(s), and postoperative rehabilitation. Heterogeneous spatiotemporal patterns of rearrangement across patients and in a single patient over time have been evidenced, with structural changes as well as modifications of intra-hemispheric (in the ipsi-lesional and/or contra-lesional hemisphere) and inter-hemispheric functional connectivity. Such various fingerprints of neural reconfiguration were correlated to different levels of cognitive compensation. Serial multimodal studies exploring neuroplasticity might lead to new management strategies based upon multistage therapeutic approaches adapted to the individual profile of functional reallocation. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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Other

Jump to: Research, Review

48 pages, 2345 KiB

Open AccessSystematic Review

Motor Evoked Potential Warning Criteria in Supratentorial Surgery: A Scoping Review

by Evridiki Asimakidou, Pablo Alvarez Abut, Andreas Raabe and Kathleen Seidel

Cancers 2021, 13(11), 2803; https://doi.org/10.3390/cancers13112803 - 04 Jun 2021

Cited by 24 | Viewed by 3159

Abstract

During intraoperative monitoring of motor evoked potentials (MEP), heterogeneity across studies in terms of study populations, intraoperative settings, applied warning criteria, and outcome reporting exists. A scoping review of MEP warning criteria in supratentorial surgery was conducted in accordance with the Preferred Reporting [...] Read more.

During intraoperative monitoring of motor evoked potentials (MEP), heterogeneity across studies in terms of study populations, intraoperative settings, applied warning criteria, and outcome reporting exists. A scoping review of MEP warning criteria in supratentorial surgery was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Sixty-eight studies fulfilled the eligibility criteria. The most commonly used alarm criteria were MEP signal loss, which was always a major warning sign, followed by amplitude reduction and threshold elevation. Irreversible MEP alterations were associated with a higher number of transient and persisting motor deficits compared with the reversible changes. In almost all studies, specificity and Negative Predictive Value (NPV) were high, while in most of them, sensitivity and Positive Predictive Value (PPV) were rather low or modest. Thus, the absence of an irreversible alteration may reassure the neurosurgeon that the patient will not suffer a motor deficit in the short-term and long-term follow-up. Further, MEPs perform well as surrogate markers, and reversible MEP deteriorations after successful intervention indicate motor function preservation postoperatively. However, in future studies, a consensus regarding the definitions of MEP alteration, critical duration of alterations, and outcome reporting should be determined. Full article

(This article belongs to the Special Issue Perioperative Imaging and Mapping Methods in Glioma Patients)

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