Preoperative nTMS analysis: a sensitive tool to detect imminent motor deficits in brain tumor patients.

BACKGROUND: One of the challenges in surgery of tumors in motor eloquent areas is the individual risk assessment for postoperative motor disorder. Previously a regression model was developed that permits estimation of the risk prior to surgery based on topographical and neurophysiological data derived from investigation with nTMS (navigated Transcranial Magnetic Stimulation). This study aims to analyze the impact of including additional neurophysiological TMS parameters into the established risk stratification model for motor outcome after brain tumor surgery. METHODS: Biometric and clinical data of 170 patients with glioma in motor eloquent areas were collected prospectively. In addition, the following nTMS parameters were collected bihemispherically prior to surgery: resting motor threshold (RMT), recruitment curve (RC), cortical silent period (CSP) and a nTMS based fibertracking to measure the tumor tract distance (TTD). Motor function was quantified by Medical Research Council Scale (MRCS) preoperatively, seven days and three months postoperatively. Association between nTMS parameters and postoperative motor outcome was investigated in bivariate and multivariable analyses. RESULTS: The bivariate analysis confirmed the association of RMT ratio with the postoperative motor outcome after seven days with higher rates of worsening in patients with RMT ratio > 1.1 compared to patients with RMT ratio ≤ 1.1 (31.6% vs. 15.1%, p = 0.009). Similarly, an association between a pathological CSP ratio and a higher risk of new postoperative motor deficits after seven days was observed (35.3% vs. 16.7% worsening, p = 0.025). A pathological RC Ratio was associated postoperative deterioration of motor function after three months (42.9% vs. 16.2% worsening, p = 0.004). In multiple regression analysis, none of these associations were statistically robust. CONCLUSIONS: The current results suggest that the RC ratio, CSP ratio and RMT ratio individually are sensitive markers associated with the motor outcome 7 days and 3 months after tumor resection in a presumed motor eloquent location. They can therefore supply valuable information during preoperative risk-benefit-balancing. However, underlying neurophysiological mechanisms might be too similar to make the parameters meaningful in a combined model.

Improved prediction of glioma-related aphasia by diffusion MRI metrics, machine learning, and automated fiber bundle segmentation.

White matter impairments caused by gliomas can lead to functional disorders. In this study, we predicted aphasia in patients with gliomas infiltrating the language network using machine learning methods. We included 78 patients with left-hemispheric perisylvian gliomas. Aphasia was graded preoperatively using the Aachen aphasia test (AAT). Subsequently, we created bundle segmentations based on automatically generated tract orientation mappings using TractSeg. To prepare the input for the support vector machine (SVM), we first preselected aphasia-related fiber bundles based on the associations between relative tract volumes and AAT subtests. In addition, diffusion magnetic resonance imaging (dMRI)-based metrics [axial diffusivity (AD), apparent diffusion coefficient (ADC), fractional anisotropy (FA), and radial diffusivity (RD)] were extracted within the fiber bundles' masks with their mean, standard deviation, kurtosis, and skewness values. Our model consisted of random forest-based feature selection followed by an SVM. The best model performance achieved 81% accuracy (specificity = 85%, sensitivity = 73%, and AUC = 85%) using dMRI-based features, demographics, tumor WHO grade, tumor location, and relative tract volumes. The most effective features resulted from the arcuate fasciculus (AF), middle longitudinal fasciculus (MLF), and inferior fronto-occipital fasciculus (IFOF). The most effective dMRI-based metrics were FA, ADC, and AD. We achieved a prediction of aphasia using dMRI-based features and demonstrated that AF, IFOF, and MLF were the most important fiber bundles for predicting aphasia in this cohort.

Personalizing Deep Brain Stimulation Using Advanced Imaging Sequences.

OBJECTIVE: With a growing appreciation for interindividual anatomical variability and patient-specific brain connectivity, advanced imaging sequences offer the opportunity to directly visualize anatomical targets for deep brain stimulation (DBS). The lack of quantitative evidence demonstrating their clinical utility, however, has hindered their broad implementation in clinical practice. METHODS: Using fast gray matter acquisition T1 inversion recovery (FGATIR) sequences, the present study identified a thalamic hypointensity that holds promise as a visual marker in DBS. To validate the clinical utility of the identified hypointensity, we retrospectively analyzed 65 patients (26 female, mean age = 69.1 ± 12.7 years) who underwent DBS in the treatment of essential tremor. We characterized its neuroanatomical substrates and evaluated the hypointensity's ability to predict clinical outcome using stimulation volume modeling and voxelwise mapping. Finally, we determined whether the hypointensity marker could predict symptom improvement on a patient-specific level. RESULTS: Anatomical characterization suggested that the identified hypointensity constituted the terminal part of the dentatorubrothalamic tract. Overlap between DBS stimulation volumes and the hypointensity in standard space significantly correlated with tremor improvement (R2  = 0.16, p = 0.017) and distance to hotspots previously reported in the literature (R2  = 0.49, p = 7.9e-4). In contrast, the amount of variance explained by other anatomical atlas structures was reduced. When accounting for interindividual neuroanatomical variability, the predictive power of the hypointensity increased further (R2  = 0.37, p = 0.002). INTERPRETATION: Our findings introduce and validate a novel imaging-based marker attainable from FGATIR sequences that has the potential to personalize and inform targeting and programming in DBS for essential tremor. ANN NEUROL 2022;91:613-628.

Personalized surgical informed consent with stereoscopic visualization in neurosurgery-real benefit for the patient or unnecessary gimmick?

BACKGROUND: Informed consent of the patient prior to surgical procedures is obligatory. A good and informative communication improves patients' understanding and confidence, thus may strengthen the patient-doctor relationship. The aim of our study was to investigate the usefulness of additional stereoscopic visualization of patient-specific imaging during informed consent conversation. METHODS: Patients scheduled for a brain tumor surgery were screened for this study prospectively. The primary exclusion criteria were cognitive or visual impairments. The participants were randomized into two groups. The first group underwent a conventional surgical informed consent performed by a neurosurgeon including a demonstration of the individual MRI on a 2D computer screen. The second group received an additional stereoscopic visualization of the same imaging to explain the pathology more in-depth. The patients were then asked to fill in a questionnaire after each part. This questionnaire was designed to assess the potential information gained from the patients with details on the anatomical location of the tumor as well as the surgical procedure and possible complications. Patients' subjective impression about the informed consent was assessed using a 5-point Likert scale. RESULTS: A total of 27 patients were included in this study. After additional stereoscopic visualization, no significant increase in patient understanding was found for either objective criteria or subjective assessment. Participants' anxiety was not increased by stereoscopic visualization. Overall, patients perceived stereoscopic imaging as helpful from a subjective perspective. Confidence in the department was high in both groups. CONCLUSION: Stereoscopic visualization of MRI images within informed consent conversation did not improve the objective understanding of the patients in our series. Although no objective anatomical knowledge gain was noted in this series, patients felt that the addition of stereoscopic visualization improved their overall understanding. It therefore potentially increases patient confidence in treatment decisions.

Does stereoscopic imaging improve the memorization of medical imaging by neurosurgeons? Experience of a single institution.

Stereoscopic imaging has increasingly been used in anatomical teaching and neurosurgery. The aim of our study was to analyze the potential utility of stereoscopic imaging as a tool for memorizing neurosurgical patient cases compared to conventional monoscopic visualization. A total of 16 residents and 6 consultants from the Department of Neurosurgery at Charité - Universitätsmedizin Berlin were recruited for the study. They were divided into two equally experienced groups. A comparative analysis of both imaging modalities was conducted in which four different cases were assessed by the participants. Following the image assessment, two questionnaires, one analyzing the subjective judgment using the 5-point Likert Scale and the other assessing the memorization and anatomical accuracy, were completed by all participants. Both groups had the same median year of experience (5) and stereoacuity (≤ 75 s of arc). The analysis of the first questionnaire demonstrated significant subjective superiority of the monoscopic imaging in evaluation of the pathology (median: monoscopic: 4; stereoscopic: 3; p = 0.020) and in handling of the system (median: monoscopic: 5; stereoscopic: 2; p < 0.001). The second questionnaire showed that the anatomical characterization of the pathologies was comparable between both visualization methods. Most participants rated the stereoscopic visualization as worse compared to the monoscopic visualization, probably due to a lack of familiarity with the newer technique. Stereoscopic imaging, however, was not objectively inferior to traditional monoscopic imaging for anatomical comprehension. Further methodological developments and incorporation in routine clinical workflows will most likely enhance the usability and acceptance of stereoscopic visualization.

Clinical implementation of a 3D4K-exoscope (Orbeye) in microneurosurgery.

Exoscopic surgery promises alleviation of physical strain, improved intraoperative visualization and facilitation of the clinical workflow. In this prospective observational study, we investigate the clinical usability of a novel 3D4K-exoscope in routine neurosurgical interventions. Questionnaires on the use of the exoscope were carried out. Exemplary cases were additionally video-documented. All participating neurosurgeons (n = 10) received initial device training. Changing to a conventional microscope was possible at all times. A linear mixed model was used to analyse the impact of time on the switchover rate. For further analysis, we dichotomized the surgeons in a frequent (n = 1) and an infrequent (n = 9) user group. A one-sample Wilcoxon signed rank test was used to evaluate, if the number of surgeries differed between the two groups. Thirty-nine operations were included. No intraoperative complications occurred. In 69.2% of the procedures, the surgeon switched to the conventional microscope. While during the first half of the study the conversion rate was 90%, it decreased to 52.6% in the second half (p = 0.003). The number of interventions between the frequent and the infrequent user group differed significantly (p = 0.007). Main reasons for switching to ocular-based surgery were impaired hand-eye coordination and poor depth perception. The exoscope investigated in this study can be easily integrated in established neurosurgical workflows. Surgical ergonomics improved compared to standard microsurgical setups. Excellent image quality and precise control of the camera added to overall user satisfaction. For experienced surgeons, the incentive to switch from ocular-based to exoscopic surgery greatly varies.

360° 3D virtual reality operative video for the training of residents in neurosurgery.

OBJECTIVE: Training of residents is an essential but time-consuming and costly task in the surgical disciplines. During the coronavirus disease 2019 pandemic, surgical education became even more challenging because of the reduced caseload due to the increased shift to corona care. In this context, augmented 360° 3D virtual reality (VR) videos of surgical procedures enable effective off-site training through virtual participation in the surgery. The goal of this study was to establish and evaluate 360° 3D VR operative videos for neurosurgical training. METHODS: Using a 360° camera, the authors recorded three standard neurosurgical procedures: a lumbar discectomy, brain metastasis resection, and clipping of an aneurysm. Combined with the stereoscopic view of the surgical microscope, 7- to 10-minute 360° 3D VR videos augmented with annotations, overlays, and commentary were created. These videos were then presented to the neurosurgical residents at the authors' institution using a head-mounted display. Before viewing the videos, the residents were asked to fill out a questionnaire indicating their VR experience and self-assessment of surgical skills regarding the specific procedure. After watching the videos, the residents completed another questionnaire to evaluate their quality and usefulness. The parameters were scaled with a 5-point Likert scale. RESULTS: Twenty-two residents participated in this study. The mean years of experience of the participants in neurosurgery was 3.2 years, ranging from the 1st through the 7th year of training. Most participants (86.4%) had no or less than 15 minutes of VR experience. The overall quality of the videos was rated good to very good. Immersion, the feeling of being in the operating room, was high, and almost all participants (91%) stated that 360° VR videos provide a useful addition to the neurosurgical training. VR sickness was negligible in the cohort. CONCLUSIONS: In this study, the authors demonstrated the feasibility and high acceptance of augmented 360° 3D VR videos in neurosurgical training. Augmentation of 360° videos with complementary and interactive content has the potential to effectively support trainees in acquiring conceptual knowledge. Further studies are necessary to investigate the effectiveness of their use in improving surgical skills.

Augmented reality visualization in brain lesions: a prospective randomized controlled evaluation of its potential and current limitations in navigated microneurosurgery.

BACKGROUND: Augmented reality (AR) has the potential to support complex neurosurgical interventions by including visual information seamlessly. This study examines intraoperative visualization parameters and clinical impact of AR in brain tumor surgery. METHODS: Fifty-five intracranial lesions, operated either with AR-navigated microscope (n = 39) or conventional neuronavigation (n = 16) after randomization, have been included prospectively. Surgical resection time, duration/type/mode of AR, displayed objects (n, type), pointer-based navigation checks (n), usability of control, quality indicators, and overall surgical usefulness of AR have been assessed. RESULTS: AR display has been used in 44.4% of resection time. Predominant AR type was navigation view (75.7%), followed by target volumes (20.1%). Predominant AR mode was picture-in-picture (PiP) (72.5%), followed by 23.3% overlay display. In 43.6% of cases, vision of important anatomical structures has been partially or entirely blocked by AR information. A total of 7.7% of cases used MRI navigation only, 30.8% used one, 23.1% used two, and 38.5% used three or more object segmentations in AR navigation. A total of 66.7% of surgeons found AR visualization helpful in the individual surgical case. AR depth information and accuracy have been rated acceptable (median 3.0 vs. median 5.0 in conventional neuronavigation). The mean utilization of the navigation pointer was 2.6 × /resection hour (AR) vs. 9.7 × /resection hour (neuronavigation); navigation effort was significantly reduced in AR (P < 0.001). CONCLUSIONS: The main benefit of HUD-based AR visualization in brain tumor surgery is the integrated continuous display allowing for pointer-less navigation. Navigation view (PiP) provides the highest usability while blocking the operative field less frequently. Visualization quality will benefit from improvements in registration accuracy and depth impression. GERMAN CLINICAL TRIALS REGISTRATION NUMBER: DRKS00016955.

Motor excitability in bilateral moyamoya vasculopathy and the impact of revascularization.

OBJECTIVE: Motor cortical dysfunction has been shown to be reversible in patients with unilateral atherosclerotic disease after cerebral revascularization. Moyamoya vasculopathy (MMV) is a rare bilateral stenoocclusive cerebrovascular disease. The aim of this study was to analyze the corticospinal excitability and the role of bypass surgery in restoring cortical motor function in patients by using navigated transcranial magnetic stimulation (nTMS). METHODS: Patients with bilateral MMV who met the criteria for cerebral revascularization were prospectively included. Corticospinal excitability, cortical representation area, and intracortical inhibition and facilitation were assessed by nTMS for a small hand muscle (first dorsal interosseous) before and after revascularization. The clinically and/or hemodynamically more severely affected hemisphere was operated first as the leading hemisphere. Intra- and interhemispheric differences were analyzed before and after direct or combined revascularization. RESULTS: A total of 30 patients with bilateral MMV were examined by nTMS prior to and after revascularization surgery. The corticospinal excitability was higher in the leading hemisphere compared with the non-leading hemisphere prior to revascularization. This hyperexcitability was normalized after revascularization as demonstrated in the resting motor threshold ratio of the hemispheres (preoperative median 0.97 [IQR 0.89-1.08], postoperative median 1.02 [IQR 0.94-1.22]; relative effect = 0.61, p = 0.03). In paired-pulse paradigms, a tendency for a weaker inhibition of the leading hemisphere was observed compared with the non-leading hemisphere. Importantly, the paired paradigm also demonstrated approximation of excitability patterns between the two hemispheres after surgery. CONCLUSIONS: The study results suggested that, in the case of a bilateral chronic ischemia, a compensation mechanism between both hemispheres seemed to exist that normalized after revascularization surgery. A potential role of nTMS in predicting the efficacy of revascularization must be further assessed.

T2 mapping of molecular subtypes of WHO grade II/III gliomas.

BACKGROUND: According to the new WHO classification from 2016, molecular profiles have shown to provide reliable information about prognosis and treatment response. The purpose of our study is to evaluate the diagnostic potential of non-invasive quantitative T2 mapping in the detection of IDH1/2 mutation status in grade II-III gliomas. METHODS: Retrospective evaluation of MR examinations in 30 patients with histopathological proven WHO-grade II (n = 9) and III (n = 21) astrocytomas (18 IDH-mutated, 12 IDH-wildtype). Consensus annotation by two observers by use of ROI's in quantitative T2-mapping sequences were performed in all patients. T2 relaxation times were measured pixelwise. RESULTS: A significant difference (p = 0,0037) between the central region of IDH-mutated tumors (356,83 ± 114,97 ms) and the IDH-wildtype (199,92 ± 53,13 ms) was found. Furthermore, relaxation times between the central region (322,62 ± 127,41 ms) and the peripheral region (211,1 ± 74,16 ms) of WHO grade II and III astrocytomas differed significantly (p = 0,0021). The central regions relaxation time of WHO-grade II (227,44 ± 80,09 ms) and III gliomas (322,62 ± 127,41 ms) did not differ significantly (p = 0,2276). The difference between the smallest and the largest T2 value (so called "range") is significantly larger (p = 0,0017) in IDH-mutated tumors (230,89 ± 121,11 ms) than in the IDH-wildtype (96,33 ± 101,46 ms). Interobserver variability showed no significant differences. CONCLUSIONS: Quantitative evaluation of T2-mapping relaxation times shows significant differences regarding the IDH-status in WHO grade II and III gliomas adding important information regarding the new 2016 World Health Organization (WHO) Classification of tumors of the central nervous system. This to our knowledge is the first study regarding T2 mapping and the IDH1/2 status shows that the mutational status seems to be more important for the appearance on T2 images than the WHO grade.

NTMS mapping of non-primary motor areas in brain tumour patients and healthy volunteers.

OBJECTIVE: Navigated transcranial magnetic stimulation (nTMS) has been increasingly used for presurgical cortical mapping of the primary motor cortex (M1) but remains controversial for the evaluation of non-primary motor areas (NPMA). This study investigates clinical and neurophysiological parameters in brain tumour patients and healthy volunteers to decide whether single-pulse biphasic nTMS allows to reliably elicite MEP outside from M1 or not. MATERIALS AND METHODS: Twelve brain tumour patients and six healthy volunteers underwent M1 nTMS mapping. NPMA nTMS mapping followed using 120% and 150% M1 resting motor threshold (RMT) stimulation intensity. Spearman's correlation analysis tested the association of clinical and neurophysiological parameters between M1 and NPMA mapping. RESULTS: A total of 88.81% of nTMS stimulations in NPMA in patients/83.87% in healthy volunteers in patients/83.87% in healthy volunteers did not result in MEPs ≥ 50 µV. Positive nTMS mapping in NPMA correlated with higher stimulation intensity and larger M1 areas in patients (120% M1 RMT SI p = 0.005/150% M1 RMT SI p = 0.198). CONCLUSION: Our findings indicate that in case of positive nTMS mapping in NPMA, MEPs originate mostly from M1. For future studies, MEP parameters and TMS coil rotation should be studied closely to assess the risk for postoperative motor deterioration.

Development and initial evaluation of a novel simulation model for comprehensive brain tumor surgery training.

BACKGROUND: Increasing technico-manual complexity of procedures and time constraints necessitates effective neurosurgical training. For this purpose, both screen- and model-based simulations are under investigation. Approaches including 3D printed brains, gelatin composite models, and virtual environments have already been published. However, quality of brain surgery simulation is limited due to discrepancies in visual and haptic experience. Similarly, virtual training scenarios are still lacking sufficient real-world resemblance. In this study, we introduce a novel simulator for realistic neurosurgical training that combines real brain tissue with 3D printing and augmented reality. METHODS: Based on a human CT scan, a skull base and skullcap were 3D printed and equipped with an artificial dura mater. The cerebral hemispheres of a calf's brain were placed in the convexity of the skullcap and tumor masses composed of aspic, water, and fluorescein were injected in the brain. The skullcap and skull base were placed on each other, glued together, and filled up with an aspic water solution for brain fixation. Then, four surgical scenarios were performed in the operating room as follows: (1) simple tumor resection, (2) complex tumor resection, (3) navigated biopsy via burr hole trepanation, and (4) retrosigmoidal craniotomy. Neuronavigation, augmented reality, fluorescence, and ocular-as well as screen-based (exoscopic)-surgery were available for the simulator training. A total of 29 participants performed at least one training scenario of the simulator and completed a 5-item Likert-like questionnaire as well as qualitative interviews. The questionnaire assessed the realism of the tumor model, skull, and brain tissue as well as the capability for training purposes. RESULTS: Visual and sensory realism of the skull and brain tissue were rated,"very good," while the sensory and visual realism of the tumor model were rated "good." Both overall satisfaction with the model and eligibility of the microscope and neurosurgical instruments for training purposes were rated with "very good." However, small size of the calf's brain, its limited shelf life, and the inability to simulate bleedings due to the lack of perfusion were significant drawbacks. CONCLUSION: The combination of 3D printing and real brain tissue provided surgical scenarios with very good real-life resemblance. This novel neurosurgical model features a versatile setup for surgical skill training and allows for efficient training of technological support like image and fluorescence guidance, exoscopic surgery, and robotic technology.

Monitor-based exoscopic 3D4k neurosurgical interventions: a two-phase prospective-randomized clinical evaluation of a novel hybrid device.

BACKGROUND: Promoting a disruptive innovation in microsurgery, exoscopes promise alleviation of physical strain and improved image quality through digital visualization during microneurosurgical interventions. This study investigates the impact of a novel 3D4k hybrid exoscope (i.e., combining digital and optical visualization) on surgical performance and team workflow in preclinical and clinical neurosurgical settings. METHODS: A pre-clinical workshop setting has been developed to assess usability and implementability through skill-based scenarios (neurosurgical participants n = 12). An intraoperative exploration in head and spine surgery (n = 9) and a randomized clinical study comparing ocular and monitor mode in supratentorial brain tumor cases (n = 20) followed within 12 months. Setup, procedure, case characteristics, surgical performance, and user experience have been analyzed for both ocular group (OG) and monitor group (MG). RESULTS: Brain tumor cases using frontal, frontoparietal, or temporal approaches have been identified as favorable use cases for introducing exoscopic neurosurgery. Mean monitor distance and angle were 180 cm and 10°. Surgical ergonomics when sitting improved significantly in MG compared with OG (P = .03). Hand-eye coordination required familiarization in MG. Preclinical data showed a positive correlation between lateral camera inclination and impact on hand-eye coordination (rs = 0.756, P = .01). There was no significant added surgical time in MG. Image quality in current generation 3D4k monitors has been rated inferior to optic visualization yet awaits updates. CONCLUSIONS: The hybrid exoscopic device can be integrated into established neurosurgical workflows. Currently, exoscopic interventions seem most suited for cranial tumor surgery in lesions that are not deep-seated. Ergonomics improve in monitor mode compared to conventional microsurgery.

Left perisylvian tumor surgery aided by TMS language mapping in a 6-year-old boy: case report.

BACKGROUND: Awake surgery to preserve language function in young children is challenging, therefore reliable non-invasive work-up of language functional anatomy is needed to preserve language function at any cost. Furthermore, there are obvious limitations of an awake craniotomy with direct stimulation on a child. CASE REPORT: A 6-year-old boy with a low-grade glioma of the left temporal lobe suffering from epileptic seizures underwent surgery, guided by preoperative transcranial magnetic stimulation (TMS) language mapping and consecutive DTI fiber tracking. DISCUSSION AND CONCLUSION: We report successful surgery of a language eloquent brain tumor in a young child based on TMS mapping and DTI fiber tracking alone. Surgical treatment of left-sided perisylvian tumors in children is discussed.

TMS motor mapping in brain tumor patients: more robust maps with an increased resting motor threshold.

OBJECTIVE: Navigated transcranial magnetic stimulation (nTMS) has found widespread usage across many clinical centers as part of their surgical planning routines. NTMS offers a non-invasive approach to delineation of the motor cortex, in which the region is outlined through electromagnetic stimulation and electromyographic recordings of target muscles. Several neurophysiological parameters such as the motor evoked potential (MEP) and its derivatives, the resting motor threshold (RMT) and motor latency, are collected. The present study investigates the clinical feasibility and reproducibility of increasing the MEP threshold in brain tumor patients, with the goal to improve the robustness of the procedure. MATERIALS AND METHODS: Twenty-three subjects with peri-motor cortex tumors underwent motor mapping with nTMS. RMT was calculated with both conventional 50-µV and experimental 500-µV MEP amplitude thresholds. Motor mapping was performed with 105% of both RMTs stimulator intensity using the FDI as the target muscle. RESULTS: Motor mapping was possible in 20 patients with both the conventional and experimental thresholds. No significant differences in area size were found between motor area maps generated with a conventional 50-µV threshold in comparison to those generated with the higher 500-µV threshold (50 µV 272.56 mm2 [170.47-434.31] vs. 500 µV 240.54 mm2 [169.77-362.84], P = 0.34). Latency time was significantly reduced in 500-µV recordings relative to 50-µV recordings (50 µV 23.38 ms [22.55-24.51] vs. 500 µV 22.57 ms [21.41-23.70], P < 0.001). Both electric field intensity (50 µV 63.81 V/m [54.26-76.11] vs. 500 µV 77.83 V/m [65.21-93.94], P < 0.001) and RMT (50 µV 33 MSO% [28-36] vs. 500 µV 39.5 MSO% [32-44], P < 0.001) were significantly greater with the higher 500-µV threshold. CONCLUSIONS: Our study demonstrates the feasibility of increasing the MEP detection threshold to 500 µV in brain tumor patients for RMT determination and motor area mapping with nTMS.

Estimation of the resting motor threshold (RMT) in transcranial magnetic stimulation using relative-frequency and threshold-hunting methods in brain tumor patients.

BACKGROUND: Application of transcranial magnetic stimulation is often based on the resting motor threshold. The aim of this study was to validate recent findings on the advantage of resting motor threshold estimation using adaptive threshold-hunting algorithms over the Rossini-Rothwell method in a clinical sample and healthy subjects. METHODS: Resting motor thresholds in 115 patients with a brain tumor and 10 healthy subjects were assessed using the Rossini-Rothwell method and compared to an adaptive threshold-hunting algorithm. In healthy subjects, this measurement was repeated twice to capture test-retest reliability of both methods. Efficiency of both methods was assessed by comparing the number of pulses needed for resting motor threshold estimation. RESULTS: There was no significant difference between the Rossini-Rothwell method and the adaptive threshold-hunting algorithm in patients and healthy controls with limits of agreement between ± 12 V/m. There was a strong intraclass correlation and both methods showed a good test-retest reliability. However, the adaptive threshold-hunting algorithm was significantly faster. CONCLUSIONS: The adaptive threshold-hunting algorithm was more efficient in assessing the resting motor threshold, while reaching comparable results as the Rossini-Rothwell method. Thus, our results support the advantage of adaptive threshold-hunting algorithms to determine the resting motor threshold also in a clinical sample.

Manual for clinical language tractography.

BACKGROUND: We introduce a user-friendly, standardized protocol for tractography of the major language fiber bundles. METHOD: The introduced method uses dMRI images for tractography whereas the ROI definition is based on structural T1 MPRAGE MRI templates, without normalization to MNI space. ROIs for five language-relevant fiber bundles were visualized on an axial, coronal, or sagittal view of T1 MPRAGE images. The ROIs were defined based upon the tracts' obligatory pathways, derived from literature and own experiences in peritumoral tractography. RESULTS: The resulting guideline was evaluated for each fiber bundle in ten healthy subjects and ten patients by one expert and three raters. Overall, 300 ROIs were evaluated and compared. The targeted language fiber bundles could be tracked in 88% of the ROI pairs, based on the raters' result blinded ROI placements. The evaluation indicated that the precision of the ROIs did not relate to the varying experience of the raters. CONCLUSIONS: Our guideline introduces a standardized language tractography method for routine preoperative workup and for research contexts. The ROI placement guideline based on easy-to-identify anatomical landmarks proved to be user-friendly and accurate, also in inexperienced test persons.

Preservation of motor maps with increased motor evoked potential amplitude threshold in RMT determination.

OBJECTIVE: Non-invasive pre-surgical mapping of eloquent brain areas with navigated transcranial magnetic stimulation (nTMS) is a useful technique linked to the improvement of surgical planning and patient outcomes. The stimulator output intensity and subsequent resting motor threshold determination (rMT) are based on the motor-evoked potential (MEP) elicited in the target muscle with an amplitude above a predetermined threshold of 50 µV. However, a subset of patients is unable to achieve complete relaxation in the target muscles, resulting in false positives that jeopardize mapping validity with conventional MEP determination protocols. Our aim is to explore the feasibility and reproducibility of a novel mapping approach that investigates how an increase of the MEP amplitude threshold to 300 and 500 µV affects subsequent motor maps. MATERIALS AND METHODS: Seven healthy subjects underwent motor mapping with nTMS. RMT was calculated with the conventional methodology in conjunction with experimental 300- and 500-µV MEP amplitude thresholds. Motor mapping was performed with 105% of rMT stimulator intensity using the FDI as the target muscle. RESULTS: Motor mapping was possible in all patients with both the conventional and experimental setups. Motor area maps with a conventional 50-µV threshold showed poor correlation with 300-µV (α = 0.446, p < 0.001) maps, but showed excellent consistency with 500-µV motor area maps (α = 0.974, p < 0.001). MEP latencies were significantly less variable (23 ms for 50 µV vs. 23.7 ms for 300 µV vs. 23.7 ms for 500 µV, p < 0.001). A slight but significant increase of the electric field (EF) value was found (EF: 60.8 V/m vs. 64.8 V/m vs. 66 V/m p < 0.001). CONCLUSION: Our study demonstrates the feasibility of increasing the MEP detection threshold to 500 µV in rMT determination and motor area mapping with nTMS without losing precision.

Correction to: Preservation of motor maps with increased motor evoked potential amplitude threshold in RMT determination.

Funding information is added.