Mapping and monitoring are believed to provide an early warning sign to determine when to stop tumor removal to avoid mechanical damage to the corticospinal tract (CST). The objective of this study ...was to systematically compare subcortical monopolar stimulation thresholds (1-20 mA) with direct cortical stimulation (DCS)-motor evoked potential (MEP) monitoring signal abnormalities and to correlate both with new postoperative motor deficits. The authors sought to define a mapping threshold and DCS-MEP monitoring signal changes indicating a minimal safe distance from the CST.
A consecutive cohort of 100 patients underwent tumor surgery adjacent to the CST while simultaneous subcortical motor mapping and DCS-MEP monitoring was used. Evaluation was done regarding the lowest subcortical mapping threshold (monopolar stimulation, train of 5 stimuli, interstimulus interval 4.0 msec, pulse duration 500 μsec) and signal changes in DCS-MEPs (same parameters, 4 contact strip electrode). Motor function was assessed 1 day after surgery, at discharge, and at 3 months postoperatively.
The lowest individual motor thresholds (MTs) were as follows (MT in mA, number of patients): > 20 mA, n = 12; 11-20 mA, n = 13; 6-10 mA, n = 20; 4-5 mA, n = 30; and 1-3 mA, n = 25. Direct cortical stimulation showed stable signals in 70 patients, unspecific changes in 18, irreversible alterations in 8, and irreversible loss in 4 patients. At 3 months, 5 patients had a postoperative new or worsened motor deficit (lowest mapping MT 20 mA, 13 mA, 6 mA, 3 mA, and 1 mA). In all 5 patients DCS-MEP monitoring alterations were documented (2 sudden irreversible threshold increases and 3 sudden irreversible MEP losses). Of these 5 patients, 2 had vascular ischemic lesions (MT 20 mA, 13 mA) and 3 had mechanical CST damage (MT 1 mA, 3 mA, and 6 mA; in the latter 2 cases the resection continued after mapping and severe DCS-MEP alterations occurred thereafter). In 80% of patients with a mapping MT of 1-3 mA and in 75% of patients with a mapping MT of 1 mA, DCS-MEPs were stable or showed unspecific reversible changes, and none had a permanent motor worsening at 3 months. In contrast, 25% of patients with irreversible DCS-MEP changes and 75% of patients with irreversible DCS-MEP loss had permanent motor deficits.
Mapping should primarily guide tumor resection adjacent to the CST. DCS-MEP is a useful predictor of deficits, but its value as a warning sign is limited because signal alterations were reversible in only approximately 60% of the present cases and irreversibility is a post hoc definition. The true safe mapping MT is lower than previously thought. The authors postulate a mapping MT of 1 mA or less where irreversible DCS-MEP changes and motor deficits regularly occur. Therefore, they recommend stopping tumor resection at an MT of 2 mA at the latest. The limited spatial and temporal coverage of contemporary mapping may increase error and may contribute to false, higher MTs.
A main concern with regard to surgery for low-grade glioma (LGG, WHO Grade II) is maintenance of the patient's functional integrity. This concern is particularly relevant for gliomas in the central ...region, where damage can have grave repercussions. The authors evaluated postsurgical outcomes with regard to neurological deficits, seizures, and quality of life.
Outcomes were compared for 33 patients with central LGG (central cohort) and a control cohort of 31 patients with frontal LGG (frontal cohort), all of whom had had medically intractable seizures before undergoing surgery with mapping while awake. All surgeries were performed in the period from February 2007 through April 2010 at the same institution.
For the central cohort, the median extent of resection was 92% (range 80%-97%), and for the frontal cohort, the median extent of resection was 93% (range 83%-98%; p = 1.0). Although the rate of mild neurological deficits was similar for both groups, seizure freedom (Engel Class I) was achieved for only 4 (12.1%) of 33 patients in the central cohort compared with 26 (83.9%) of 31 patients in the frontal cohort (p < 0.0001). The rate of return to work was lower for patients in the central cohort (4 12.1% of 33) than for the patients in the frontal cohort (28 90.3% of 31; p < 0.0001).
Resection of central LGG is feasible and safe when appropriate intraoperative mapping is used. However, seizure control for these patients remains poor, a finding that contrasts markedly with seizure control for patients in the frontal cohort and with that reported in the literature. For patients with central LGG, poor seizure control ultimately determines quality of life because most will not be able to return to work.
GABA+ and Glx (glutamate and glutamine) are widely studied metabolites, yet the commonly used magnetic resonance spectroscopy (MRS) techniques have significant limitations, including sensitivity to B
...and B
-inhomogeneities, limited bandwidth of MEGA-pulses, high SAR which is accentuated at 7T. To address these limitations, we propose SLOW-EPSI method, employing a large 3D MRSI coverage and achieving a high resolution down to 0.26 ml. Simulation results demonstrate the robustness of SLOW-editing for both GABA+ and Glx against B
and B
-inhomogeneities within the range of -0.3, +0.3 ppm and 40 %, 250 %, respectively. Two protocols, both utilizing a 70 mm thick FOV slab, were employed to target distinct brain regions in vivo, differentiated by their orientation: transverse and tilted. Protocol 1 (n = 11) encompassed 5 locations (cortical gray matter, white matter, frontal lobe, parietal lobe, and cingulate gyrus). Protocol 2 (n = 5) involved 9 locations (cortical gray matter, white matter, frontal lobe, occipital lobe, cingulate gyrus, caudate nucleus, hippocampus, putamen, and inferior thalamus). Quantitative analysis of GABA+ and Glx was conducted in a stepwise manner. First, B
/B
-inhomogeneities were corrected using water reference data. Next, GABA+ and Glx values were calculated employing spectral fitting. Finally, the GABA+ level for each selected region was compared to the global Glx within the same subject, generating the GABA+/Glx_global ratio. Our findings from two protocols indicate that the GABA+/Glx_global level in cortical gray matter was approximately 16 % higher than in white matter. Elevated GABA+/Glx_global levels acquired with protocol 2 were observed in specific regions such as the caudate nucleus (0.118±0.067), putamen (0.108±0.023), thalamus (0.092±0.036), and occipital cortex (0.091±0.010), when compared to the cortical gray matter (0.079±0.012). Overall, our results highlight the effectiveness of SLOW-EPSI as a robust and efficient technique for accurate measurements of GABA+ and Glx at 7T. In contrast to previous SVS and 2D-MRSI based editing sequences with which only one or a limited number of brain regions can be measured simultaneously, the method presented here measures GABA+ and Glx from any brain area and any arbitrarily shaped volume that can be flexibly selected after the examination. Quantification of GABA+ and Glx across multiple brain regions through spectral fitting is achievable with a 9-minute acquisition. Additionally, acquisition times of 18-27 min (GABA+) and 9-18 min (Glx) are required to generate 3D maps, which are constructed using Gaussian fitting and peak integration.
Reproducible segmentation of brain tumors on magnetic resonance images is an important clinical need. This study was designed to evaluate the reliability of a novel fully automated segmentation tool ...for brain tumor image analysis in comparison to manually defined tumor segmentations.
We prospectively evaluated preoperative MR Images from 25 glioblastoma patients. Two independent expert raters performed manual segmentations. Automatic segmentations were performed using the Brain Tumor Image Analysis software (BraTumIA). In order to study the different tumor compartments, the complete tumor volume TV (enhancing part plus non-enhancing part plus necrotic core of the tumor), the TV+ (TV plus edema) and the contrast enhancing tumor volume CETV were identified. We quantified the overlap between manual and automated segmentation by calculation of diameter measurements as well as the Dice coefficients, the positive predictive values, sensitivity, relative volume error and absolute volume error.
Comparison of automated versus manual extraction of 2-dimensional diameter measurements showed no significant difference (p = 0.29). Comparison of automated versus manual segmentation of volumetric segmentations showed significant differences for TV+ and TV (p<0.05) but no significant differences for CETV (p>0.05) with regard to the Dice overlap coefficients. Spearman's rank correlation coefficients (ρ) of TV+, TV and CETV showed highly significant correlations between automatic and manual segmentations. Tumor localization did not influence the accuracy of segmentation.
In summary, we demonstrated that BraTumIA supports radiologists and clinicians by providing accurate measures of cross-sectional diameter-based tumor extensions. The automated volume measurements were comparable to manual tumor delineation for CETV tumor volumes, and outperformed inter-rater variability for overlap and sensitivity.
Background
The technique of 5-aminolevulinic acid (5-ALA) tumor fluorescence is increasingly used to improve visualization of tumor tissue and thereby to increase the rate of patients with gross ...total resections. In this study, we measured the resection volumes in patients who underwent 5-ALA-guided surgery for non-eloquent glioblastoma and compared them with the preoperative tumor volume.
Methods
We selected 13 patients who had received a complete resection according to intraoperative 5-ALA induced fluorescence and CRET according to post-operative T1 contrast-enhanced MRI. The volumes of pre-operative contrast enhancing tissue, post-operative resection cavity and resected tissue were determined through shift-corrected volumetric analysis.
Results
The mean resection cavity (29 cm
3
) was marginally smaller than the pre-operative contrast-enhancing tumor (39 cm
3
,
p
= 0.32). However, the mean overall resection volume (84 cm
3
) was significantly larger than the pre-operative contrast-enhancing tumor (39 cm
3
,
p
= 0.0087). This yields a mean volume of resected 5-ALA positive, but radiological non-enhancing tissue of 45 cm
3
. The mean calculated rim of resected tissue surpassed pre-operative tumor diameter by 6 mm (range 0–10 mm).
Conclusions
Results of the current study imply that (i) the resection cavity underestimates the volume of resected tissue and (ii) 5-ALA complete resections go significantly beyond the volume of pre-operative contrast-enhancing tumor bulk on MRI, indicating that 5-ALA also stains MRI non-enhancing tumor tissue. Use of 5-ALA may thus enable extension of coalescent tumor resection beyond radiologically evident tumor. The impact of this more extended resection method on time to progression and overall survival has not been determined, and potentially puts adjacent and functionally intact tissue at risk.
In a single-center, randomized trial involving 361 patients, the use of routine computed tomography after the removal of a chronic hematoma had no advantage over CT performed only in patients with ...clinical deterioration.
Background This study aims to identify robust radiomic features for Magnetic Resonance Imaging (MRI), assess feature selection and machine learning methods for overall survival classification of ...Glioblastoma multiforme patients, and to robustify models trained on single-center data when applied to multi-center data. Methods Tumor regions were automatically segmented on MRI data, and 8327 radiomic features extracted from these regions. Single-center data was perturbed to assess radiomic feature robustness, with over 16 million tests of typical perturbations. Robust features were selected based on the Intraclass Correlation Coefficient to measure agreement across perturbations. Feature selectors and machine learning methods were compared to classify overall survival. Models trained on single-center data (63 patients) were tested on multi-center data (76 patients). Priors using feature robustness and clinical knowledge were evaluated. Results We observed a very large performance drop when applying models trained on single-center on unseen multi-center data, e.g. a decrease of the area under the receiver operating curve (AUC) of 0.56 for the overall survival classification boundary at 1 year. By using robust features alongside priors for two overall survival classes, the AUC drop could be reduced by 21.2%. In contrast, sensitivity was 12.19% lower when applying a prior. Conclusions Our experiments show that it is possible to attain improved levels of robustness and accuracy when models need to be applied to unseen multi-center data. The performance on multi-center data of models trained on single-center data can be increased by using robust features and introducing prior knowledge. For successful model robustification, tailoring perturbations for robustness testing to the target dataset is key. Keywords: Glioblastoma multiforme, MRI radiomics, Overall survival classification, Multi-center, Robustness
Scientific research is typically performed by expert individuals or groups who investigate potential solutions in a sequential manner. Given the current worldwide exponential increase in technical ...innovations, potential solutions for any new problem might already exist, even though they were developed to solve a different problem. Therefore, in crowdsourcing ideation, a research question is explained to a much larger group of individuals beyond the specialist community to obtain a multitude of diverse, outside-the-box solutions. These are then assessed in parallel by a group of experts for their capacity to solve the new problem. The 2 key problems in brain tumor surgery are the difficulty of discerning the exact border between a tumor and the surrounding brain, and the difficulty of identifying the function of a specific area of the brain. Both problems could be solved by a method that visualizes the highly organized fiber tracts within the brain; the absence of fibers would reveal the tumor, whereas the spatial orientation of the tracts would reveal the area's function. To raise awareness about our challenge of developing a means of intraoperative, real-time, noninvasive identification of fiber tracts and tumor borders to improve neurosurgical oncology, we turned to the crowd with a crowdsourcing ideation challenge.
Our objective was to evaluate the feasibility of a crowdsourcing ideation campaign for finding novel solutions to challenges in neuroscience. The purpose of this paper is to introduce our chosen crowdsourcing method and discuss it in the context of the current literature.
We ran a prize-based crowdsourcing ideation competition called HORAO on the commercial platform HeroX. Prize money previously collected through a crowdfunding campaign was offered as an incentive. Using a multistage approach, an expert jury first selected promising technical solutions based on broad, predefined criteria, coached the respective solvers in the second stage, and finally selected the winners in a conference setting. We performed a postchallenge web-based survey among the solvers crowd to find out about their backgrounds and demographics.
Our web-based campaign reached more than 20,000 people (views). We received 45 proposals from 32 individuals and 7 teams, working in 26 countries on 4 continents. The postchallenge survey revealed that most of the submissions came from single solvers or teams working in engineering or the natural sciences, with additional submissions from other nonmedical fields. We engaged in further exchanges with 3 out of the 5 finalists and finally initiated a successful scientific collaboration with the winner of the challenge.
This open innovation competition is the first of its kind in medical technology research. A prize-based crowdsourcing ideation campaign is a promising strategy for raising awareness about a specific problem, finding innovative solutions, and establishing new scientific collaborations beyond strictly disciplinary domains.
Gliomas are intrinsic brain tumours, which are classified by the World Health Organization (WHO) into different grades of malignancy, with glioblastoma being the most frequent and most malignant ...subtype (WHO grade IV). Mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes are frequent in lower (WHO II/III) grade tumours but typically absent in classical glioblastoma. IDH mutations are associated with a better prognosis compared with IDH wild-type tumours of the same WHO grade. Following detection of a tumour mass by imaging, maximum safe surgery as feasible is commonly performed to reduce mass effect and to obtain tissue allowing histopathological diagnosis and molecular assessment. Radiotherapy has been the mainstay in the treatment of diffuse gliomas for several decades. It provides improved local control, but is not curative. Furthermore, several randomised trials have shown that the addition of alkylating chemotherapy, either temozolomide or nitrosourea-based regimens, to radiotherapy results in prolonged survival. Tumour-treating fields (TTFields) have emerged as an additional treatment option in combination with maintenance temozolomide treatment for patients with newly diagnosed glioblastoma. Treatment at recurrence is less standardised and depends on the patient’s performance status, symptom burden and prior treatments. Bevacizumab prolongs progression-free survival in newly diagnosed and recurrent glioblastoma, but does not impact overall survival. However, in Switzerland and some other countries, it is still considered a valuable treatment option to reduce clinical symptom burden. Given the generally poor outcome for these patients, various novel treatment approaches are currently being explored within clinical trials including immunotherapeutic strategies such as immune checkpoint inhibition and the brain-penetrant proteasome inhibitor marizomib.
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