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Introduction: Stereotactic brain biopsies are essential for obtaining tissue samples from brain lesions, crucial for comprehensive histological analysis and subsequent adjuvant therapies. While most biopsies target supratentorial lesions, those involving the posterior fossa are less frequent but pose significant technical and surgical challenges, necessitating careful patient management., Methods: We present our experience with stereotactic biopsies of the posterior fossa using the Leksell Vantage frame (Elekta, Stockholm, Sweden) and the ZD Inomed frame (Inomed Medizintechnik GmbH, Emmendingen, Germany). For the ZD frame, we either mounted it upside down or employed a frontal approach, while for the Leksell Vantage frame, we utilized a reverse x-axis orientation. Planning was based on 3-T MRI scans and preoperative MRI merged with stereotactic CT for coordinate generation., Results: From 2006 to 2023, we performed 25 stereotactic biopsies of the posterior fossa in our department-9 with the ZD Inomed frame and 16 with the Leksell Vantage frame. The cohort included 14 male and 11 female patients, with an average age of 60.6 years (range 36-80 years). The average surgery duration was shorter with the Leksell Vantage frame (32.6 min vs. 44.8 min, p = 0.05). The average length of the planned trajectory was 41.7 mm for the Leksell Vantage frame and 52.2 mm for the ZD Inomed frame. Postoperativ bleeding occurred in two cases-one managed conservatively, the other required surgical intervention. Additionally, two other cases presented new postoperative focal neurological deficit. The overall mortality rate was 34.8% and a 40-day postoperative mortality rate of 13.0%., Conclusion: Our experience demonstrates that stereotactic biopsies of lesions in the posterior fossa can be effectively managed with different frame systems, though they present a higher degree of complexity. Notably, the Leksell Vantage frame was associated with a significantly shorter surgery duration. This technical note provides valuable insights and detailed technical guidance for neurosurgeons facing similar challenges., Competing Interests: Declarations. Ethical approval: This study protocol was reviewed and approved by ethic committee of the technical university of Dresden, approval number EK224072012. Consent to participate: For using human participant data for this study, in every case the written informed consent was obtained from participants. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Raman spectroscopy (RS) is a promising method for brain tumor detection. Near-infrared autofluorescence (AF) acquired during RS provides additional useful information for tumor identification and was investigated in comparison with RS for delineating brain tumors in situ., Methods: Raman spectra were acquired together with AF in situ within the solid tumor and at the tumor border during routine brain tumor surgeries (218 spectra; glioma WHO II-III, n = 6; GBM, n = 10; metastases, n = 10; meningioma, n = 3). Tissue classification for tumor identification in situ was trained on ex vivo data (375 spectra; glioma/GBM patients, n = 20; metastases, n = 11; meningioma, n = 13; and epileptic hippocampi, n = 4)., Results: Both in situ and ex vivo data showed that AF intensity in brain tumors was lower than that in border regions and normal brain tissue. Moreover, a positive correlation was observed between the AF intensity and the intensity of the Raman band corresponding to lipids at 1437 cm - 1 , while a negative correlation was found with the intensity of the protein band at 1260 cm - 1 . The classification of in situ AF and RS datasets matched the surgeon's evaluation of tissue type, with correct rates of 0.83 and 0.84, respectively. Similar correct rates were achieved in comparison to histopathology of tissue biopsies resected in selected measurement positions (AF: 0.80, RS: 0.83)., Conclusions: Spectroscopy was successfully integrated into existing neurosurgical workflows, and in situ spectroscopic data could be classified based on ex vivo data. RS confirmed its ability to detect brain tumors, while AF emerged as a competitive method for intraoperative tumor delineation., (© 2024. The Author(s).)

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD). The long-term benefit in PD patients with STN-DBS in comparison to medical treatment (MT) alone has not yet been demonstrated conclusively., Objectives: To judge the long-term outcome of patients with STN-DBS., Methods: To assess the evolution of PD symptoms and health-related quality of life (HRQoL) after deep brain stimulation (DBS) surgery, we conducted a cross-sectional analysis of 115 patients with STN-DBS with rater-based scales and self-reported questionnaires. In addition, we screened records of all our STN-DBS patients (2001-2019, n = 162 patients) for the onset of the morbidity milestones (falls, hallucinations, dementia, and nursing home placement) to assess disability-free life expectancy., Results: In the first year of STN-DBS, levodopa equivalent dose was reduced and motor function improved. Nonmotor symptoms and cognition remained stable. These effects were similar to previous studies. Morbidity milestones occurred 13 ± 7 years after diagnosis. Motor function, cognition, and HRQoL significantly worsened after the occurrence of any milestone, confirming the clinical relevance of these milestones. After onset of the first milestone, mean survival time was limited to 5 ± 0.8 years, which is comparable with patients with PD but without STN-DBS., Conclusions: On average, PD patients with STN-DBS live with their disease for a longer time, and morbidity milestones occur later in the disease course than in PD patients with MT. As judged by morbidity milestones, morbidity remains compressed into the final 5 years of life in PD patients with STN-DBS., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Purpose: Infrared (IR) spectroscopy has the potential for tumor delineation in neurosurgery. Previous research showed that IR spectra of brain tumors are generally characterized by reduced lipid-related and increased protein-related bands. Therefore, we propose the exploitation of these common spectral changes for brain tumor recognition., Methods: Attenuated total reflection IR spectroscopy was performed on fresh specimens of 790 patients within minutes after resection. Using principal component analysis and linear discriminant analysis, a classification model was developed on a subset of glioblastoma (n = 135) and non-neoplastic brain (n = 27) specimens, and then applied to classify the IR spectra of several types of brain tumors., Results: The model correctly classified 82% (517/628) of specimens as "tumor" or "non-tumor", respectively. While the sensitivity was limited for infiltrative glioma, this approach recognized GBM (86%), other types of primary brain tumors (92%) and brain metastases (92%) with high accuracy and all non-tumor samples were correctly identified., Conclusion: The concept of differentiation of brain tumors from non-tumor brain based on a common spectroscopic tumor signature will accelerate clinical translation of infrared spectroscopy and related technologies. The surgeon could use a single instrument to detect a variety of brain tumor types intraoperatively in future clinical settings. Our data suggests that this would be associated with some risk of missing infiltrative regions or tumors, but not with the risk of removing non-tumor brain., (© 2022. The Author(s).)

The determination of exact tumor boundaries within eloquent brain regions is essential to maximize the extent of resection. Recent studies showed that intraoperative optical imaging (IOI) combined with median nerve stimulation is a helpful tool for visualization of the primary sensory cortex (PSC). In this technical note, we describe a novel approach of using IOI with painless tactile irritation to demonstrate the feasibility of topographic mapping of different body regions within the PSC. In addition, we compared the IOI results with preoperative functional MRI (fMRI) findings. In five patients with tumors located near the PSC who received tumor removal, IOI with tactile irritation of different body parts and fMRI was applied. We showed that tactile irritation of the hand in local and general anesthesia leads to reliable changes of cerebral blood volume during IOI. Hereby, we observed comparable IOI activation maps regarding the median nerve stimulation, fMRI and tactile irritation of the hand. The tactile irritation of different body areas revealed a plausible topographic distribution along the PSC. With this approach, IOI is also suitable for awake surgeries, since the tactile irritation is painless compared with median nerve stimulation and is congruent to fMRI findings. Further studies are ongoing to standardize this method to enable a broad application within the neurosurgical community., (© 2022. The Author(s).)

Alterations within cerebral hemodynamics are the intrinsic signal source for a wide variety of neuroimaging techniques. Stimulation of specific functions leads due to neurovascular coupling, to changes in regional cerebral blood flow, oxygenation and volume. In this study, we investigated the temporal characteristics of cortical hemodynamic responses following electrical, tactile, visual, and speech activation for different stimulation paradigms using Intraoperative Optical Imaging (IOI). Image datasets from a total of 22 patients that underwent surgical resection of brain tumors were evaluated. The measured reflectance changes at different light wavelength bands, representing alterations in regional cortical blood volume (CBV), and deoxyhemoglobin (HbR) concentration, were assessed by using Fourier-based evaluation methods. We found a decrease of CBV connected to an increase of HbR within the contralateral primary sensory cortex (SI) in patients that were prolonged (30 s/15 s) electrically stimulated. Additionally, we found differences in amplitude as well as localization of activated areas for different stimulation patterns. Contrary to electrical stimulation, prolonged tactile as well as prolonged visual stimulation are provoking increases in CBV within the corresponding activated areas (SI, visual cortex). The processing of the acquired data from awake patients performing speech tasks reveals areas with increased, as well as areas with decreased CBV. The results lead us to the conclusion, that the CBV decreases in connection with HbR increases in SI are associated to processing of nociceptive stimuli and that stimulation type, as well as paradigm have a nonnegligible impact on the temporal characteristics of the following hemodynamic response., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Deep brain stimulation (DBS) is a potent symptomatic therapy for Parkinson's disease, but it is debated whether it causes or prevents neurodegeneration. We used serum neurofilament light chain (NFL) as a reporter for neuronal damage and found no difference between 92 patients with chronic STN-DBS and 57 patients on best medical treatment. Serum NFL transiently increased after DBS surgery whereas the initiation of STN stimulation did not affect NFL levels, suggesting that DBS surgery can be associated with neuronal damage whereas stimulation itself is not., (© 2022. The Author(s).)

Objective: To retrospectively evaluate influence of intraoperative positioning (semisitting vs. lateral decubitus) and surgeon's learning curve with regard to functional outcome of patients with vestibular schwannoma., Methods: This study included 544 patients (median age 57 years) and spanned 3 decades: 1991-1999 (n = 103), 2000-2009 (n = 210), and 2010-2019 (n = 231). Surgery was performed in the lateral decubitus position in 318 patients and the semisitting position in 163 patients. Large T3 and T4 tumors were present in 77% of patients., Results: Complete tumor removal was achieved in 94.3% of patients. A significant reduction in surgery duration and blood loss was observed over 3 decades for T3 (from 325 to 261 minutes, P < 0.001) and T4 (from 440 to 330 minutes, P < 0.001), but not for T1 and T2, tumors. The semisitting position diminished surgical time in T3 and T4 tumors by 1 more hour (P < 0.001). Over 3 decades, facial nerve outcome improved significantly from 59.8% House-Brackmann grade 1-2 in the first decade to 81.7% in the last decade (P < 0.001). Furthermore, hearing was preserved in 45.3%: 23.3% of patients in the first decade and 50.5% in the last decade (P = 0.03). However, neither facial nerve outcome nor hearing preservation significantly differed in patients operated on in the lateral decubitus versus the semisitting position. The most common complication was cerebrospinal fluid leak (6.1%) followed by hemorrhage (3.5%) and pulmonary embolism (2.2%)., Conclusions: Follow-up over 3 decades illustrates a learning curve with significantly improved results. While the semisitting position accelerates the procedure and is associated with reduced blood loss, it does not significantly influence functional outcome., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To prevent further brain tumour growth, malignant tissue should be removed as completely as possible in neurosurgical operations. Therefore, differentiation between tumour and brain tissue as well as detecting functional areas is very important. Hyperspectral imaging (HSI) can be used to get spatial information about brain tissue types and characteristics in a quasi-continuous reflection spectrum. In this paper, workflow and some aspects of an adapted hardware system for intraoperative hyperspectral data acquisition in neurosurgery are discussed. By comparing an intraoperative with a laboratory setup, the influences of the surgical microscope are made visible through the differences in illumination and a pixel- and wavelength-specific signal-to-noise ratio (SNR) calculation. Due to the significant differences in shape and wavelength-dependent intensity of light sources, it can be shown which kind of illumination is most suitable for the setups. Spectra between 550 and 1,000 nm are characterized of at least 40 dB SNR in laboratory and 25 dB in intraoperative setup in an area of the image relevant for evaluation. A first validation of the intraoperative hyperspectral imaging hardware setup shows that all system parts and intraoperatively recorded data can be evaluated. Exemplarily, a classification map was generated that allows visualization of measured properties of raw data. The results reveal that it is possible and beneficial to use HSI for wavelength-related intraoperative data acquisition in neurosurgery. There are still technical facts to optimize for raw data detection prior to adapting image processing algorithms to specify tissue quality and function.

Intraoperative optical imaging (IOI) is a marker-free, contactless, and noninvasive imaging technique that is able to visualize metabolic changes of the brain surface following neuronal activation. Although it has been used in the past mainly for the identification of functional brain areas under general anesthesia, the authors investigated the potential of the method during awake surgery. Measurements were performed in 10 patients who underwent resection of lesions within or adjacent to cortical language or motor sites. IOI was applied in 3 different scenarios: identification of motor areas by using finger-tapping tasks, identification of language areas by using speech tasks (overt and silent speech), and a novel approach-the application of IOI as a feedback tool during direct electrical stimulation (DES) mapping of language. The functional maps, which were calculated from the IOI data (activity maps), were qualitatively compared with the functional MRI (fMRI) and the electrophysiological testing results during the surgical procedure to assess their potential benefit for surgical decision-making.The results reveal that the intraoperative identification of motor sites with IOI in good agreement with the preoperatively acquired fMRI and the intraoperative electrophysiological measurements is possible. Because IOI provides spatially highly resolved maps with minimal additional hardware effort, the application of the technique for motor site identification seems to be beneficial in awake procedures. The identification of language processing sites with IOI was also possible, but in the majority of cases significant differences between fMRI, IOI, and DES were visible, and therefore according to the authors' findings the IOI results are too unspecific to be useful for intraoperative decision-making with respect to exact language localization. For this purpose, DES mapping will remain the method of choice.Nevertheless, the IOI technique can provide additional value during the language mapping procedure with DES. Using a simple difference imaging approach, the authors were able to visualize and calculate the spatial extent of activation for each stimulation. This might enable surgeons in the future to optimize the mapping process. Additionally, differences between tumor and nontumor stimulation sites were observed with respect to the spatial extent of the changes in cortical optical properties. These findings provide further evidence that the method allows the assessment of the functional state of neurovascular coupling and is therefore suited for the delineation of pathologically altered tissue.

Introduction: Various automatic segmentation algorithms for the subthalamic nucleus (STN) have been published recently. However, most of the available software tools are not approved for clinical use., Objective: The aim of this study is to evaluate a clinically available automatic segmentation tool of the navigation planning software Brainlab Elements (BL-E) by comparing the output to manual segmentation and a nonclinically approved research method using the DISTAL atlas (DA) and the Horn electrophysiological atlas (HEA)., Methods: Preoperative MRI data of 30 patients with idiopathic Parkinson's disease were used, resulting in 60 STN segmentations. The segmentations were created manually by two clinical experts. Automatic segmentations of the STN were obtained from BL-E and Advanced Normalization Tools using DA and HEA. Differences between manual and automatic segmentations were quantified by Dice and Jaccard coefficient, target overlap, and false negative/positive value (FNV/FPV) measurements. Statistical differences between similarity measures were assessed using the Wilcoxon signed-rank test with continuity correction, and comparison with interrater results was performed using the Mann-Whitney U test., Results: For manual segmentation, the mean size of the segmented STN was 133 ± 24 mm3. The mean size of the STN was 121 ± 18 mm3 for BL-E, 162 ± 21 mm3 for DA, and 130 ± 17 mm3 for HEA. The Dice coefficient for the interrater comparison was 0.63 and 0.54 ± 0.12, 0.59 ± 0.13, and 0.52 ± 0.14 for BL-E, DA, and HEA, respectively. Significant differences between similarity measures were found for Dice and Jaccard coefficient, target overlap and FNV between BL-E and DA; and FPV between BL-E and HEA. However, none of the differences were significant compared to interrater variability. The analysis of the center of gravity of the segmentations revealed that the BL-E STN ROI was located more medially, superior and posterior compared to other segmentations. Regarding the target overlap for beta power within the STN ROI included with the HEA, the BL-E segmentation showed a significantly higher value compared to manual segmentation., Conclusion: Automatic image segmentation by means of the clinically approved software BL-E provides STN segmentations with similar accuracy like research tools, and differences are in the range of observed interrater variability. Further studies are required to investigate the clinical validity, for example, by comparing segmentation results of BL-E with electrophysiological data., (© 2020 S. Karger AG, Basel.)

Background: Deep brain stimulation (DBS) is an established method of treatment for Parkinson's disease (PD). A stimulation sweet spot at the interface between the motor and associative clusters of the subthalamic nucleus (STN) has recently been postulated. The aim of this study was to analyze the available clustering methods for the STN and their correlation to outcome., Methods: This is a retrospective analysis of a group of 20 patients implanted with a DBS device for PD. Atlas-based and diffusion tractography-based parcellation of the STN was performed. The distances of the electrode to the obtained clusters were compared to each other and to outcome parameters, which included levodopa equivalent dose (LED) reduction, Unified Parkinson's Disease Rating Scale (UPDRS)-III scores, and reduction in scores for items 32 and 36 of the UPDRS-IV., Results: The implanted electrodes were located nearest to the motor clusters of the STN. The following significant associations with postoperative LED reduction were found: (1) distance of the electrode to the motor cluster in the Accolla and DISTAL atlases (p < 0.01) and (2) distance of the electrode to the supplementary motor area cluster (p = 0.02). There was no association with either the UPDRS-III or the UPDRS-IV score., Conclusions: The results of this study suggest the possibility that atlas-based clustering, as well as diffusion tractography-based parcellation, can be useful in estimating the stimulation target ("sweet spot") for STN-DBS in PD patients. Atlas-based as well as diffusion-based clustering might become a useful tool in DBS trajectory planning., (© 2020 S. Karger AG, Basel.)

Background: The optimal targets for deep brain stimulation (DBS) in patients with refractory chronic pain are not clearly defined. We applied sensory functional MRI (fMRI)- and diffusion tensor imaging (DTI)-based DBS in chronic pain patients into 3 different targets to ascertain the most beneficial individual stimulation site., Methods: Three patients with incapacitating chronic pain underwent DBS into 3 targets (periventricular gray (PVG), ventroposterolateral thalamus (VPL), and posterior limb of the internal capsule according to fMRI and DTI (PLIC). The electrodes were externalized and double-blinded tested for several days. Finally, the two electrodes with the best pain reduction were kept for permanent stimulation. The patients were then followed up for 12 months. Outcome measures comprised the numerical rating scale (NRS), short-form McGill's score (SF-MPQ), and health-related quality of life (SF-36)., Results: Continuous pain (mean NRS 6.6) was reduced to NRS 3.6 after 12 months. Only with stimulation of the PLIC pain attacks, that occurred at least 3 times a week (mean NRS 9.6) resolved in 2 patients and improved in one patient concerning both intensity (NRS 5) and frequency (twice a month). The mean SF-MPQ decreased from 92.7 to 50. The health-related quality of life improved considerably., Conclusion: fMRI- and DTI-based DBS to the PLIC was the only target with a significant effect on pain attacks and seems to be the most promising target in chronic pain patients after brachial plexus injury. The combination with PVG or VPL can further improve patients' outcome especially in terms of reducing the continuous pain.

Background: The aim of this study was to elucidate whether measures of quality management and digitization have the potential to reduce treatment risks in patients of a surgical clinic., Methods: All health professional involved in the treatment of patients were asked to participate in a systematic, process-orientated and anonymous survey to assess the probability of occurrence of 69 treatment risks in stationary patients. The surveys were conducted in 2006 before establishing quality management (QM) and digitization, and recently after various certification activities have been performed and the digitization has been completed., Results: According to the survey respondents, QM measures and digitization have led to a significant reduction of the probability of occurrence of 20 treatment risks, although the number of surgeries performed rose 1.8-fold while the number of employees increased by just 1.2-fold to 1.4-fold. The risk reduction was most pronounced regarding mistaken patient identity errors, while complex process risks like insufficient postoperative aftercare or patient dissatisfaction with ineffective communication remained unchanged., Discussion: An increase in process risks that may be due to an increased workload can be mitigated by QM and digitization measures. This requires a quality and risk management system that is organized by the administration, supported by responsible and risk-aware employees and not imposed., Conclusion: Health professionals estimate that digitization and QM measures have the potential to reduce patients' treatment risks and help offset the increased workload. In particular, accreditations can help implement and maintain quality management measures., (Copyright © 2019. Published by Elsevier GmbH.)

Background: The Six Sigma concept allows for the evaluation of quality changes after the implementation of new technical equipment or adjustment of perioperative procedures. Exemplarily, we applied this method for quality assessment in deep brain stimulation surgery (DBS) for Parkinson's disease., Methods: The medical procedure and possible errors were registered. Then, 6 critical-to-quality characteristics regarding clinical outcome, surgical precision, and the surgical process were measured. The surgical procedure was then optimized in 2 steps, and its measurement, along with the analysis, was repeated twice., Results: By optimizing perioperative settings, the operation time could be reduced, and the precision of the lead placement could be increased. Clinical outcome, as measured by improvement in UPDRS-III, IV, and reduction of medication could also be improved with smaller required stimulation voltage. With directional leads considerable reduction of medication was achieved in 97% of patients (σ-value 3.39) compared to 83.7% (σ-value 2.53) with nondirectional leads., Conclusion: This study shows that the Six Sigma concept is a suitable quality tool to analyze and improve treatment quality of complex medical procedures such as lead positioning in DBS surgery in clinical routine. Our results suggest that directional leads in subthalamic nucleus DBS may have a favorable impact on patients' outcome., (© 2019 S. Karger AG, Basel.)

Background: For quality analysis, we applied the Six Sigma concept to define quality indicators and their boundaries as well as to compare treatment-dependent outcome data of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD)., Methods: The Unified Parkinson Disease Rating Scale (UPDRS) III with on medication and on stimulation, the reduction of daily levodopa equivalence doses (LED), and the stimulation amplitude 1 year after surgery were registered. Regarding the results of the EARLYSTIM study, sigma values for applicable studies were calculated and compared. Further, the impact of perioperative conditions on patients' outcomes was analyzed., Results: Forty-one studies with 2184 patients were included. The bleeding risk was 1.36%. In median, UPDRS III on/on improved by 19.9% while the LED was reduced by 45.2%. The median stimulation amplitude was 2.84 V. With the Six Sigma principle, a comparison between different centers was possible. Microelectrode recordings (MER) did not correlate with occurrence of bleedings and did not impact patient outcome., Conclusions: The Six Sigma principle can be simply used to analyze, improve and compare complex medical processes, particularly, the DBS surgery. Based on these data, higher sigma values were reached for clinical improvement in UPDRS III on/on for patients who underwent surgery in local anesthesia with intraoperative test stimulation compared to surgery in general anesthesia. However, the difference was not statistically significant. Application of MER was found to be optional with no increased bleeding risk and no improvement on patient's outcome.

Brain tumor resection is even today one of the most challenging disciplines in neurosurgery. The current state of the art for the identification of tumor tissue during the surgical procedure comprises a wide variety of different tools, each with its own limitations and drawbacks. In this paper, we present a novel approach, the use of optical imaging in connection with direct electrical cortical stimulation (DCS), for identification of impaired tumor tissue and functional intact normal brain tissue under intraoperative conditions. Measurements with an optical imaging setup were performed as a proof of concept on three patients who underwent tumor resection of superficial gliomas. Direct electrical stimulations were applied on tumor tissue and surrounding brain tissue in each patient and characteristic features from the observed changes in the optical properties were compared between the different groups. The results reveal that in all patients a differentiation between non-functional tumor tissue and functional intact brain tissue was possible, and the technique might be a useful clinical tool in the future.

Objective: Multiple recent studies have reported on diffusion tensor-based fiber tracking of cranial nerves in vestibular schwannoma, with conflicting results as to the accuracy of the method and the occurrence of cochlear nerve depiction. Probabilistic nontensor-based tractography might offer advantages in terms of better extraction of directional information from the underlying data in cranial nerves, which are of subvoxel size., Methods: Twenty-one patients with large vestibular schwannomas were recruited. The probabilistic tracking was run preoperatively and the position of the potential depictions of the facial and cochlear nerves was estimated postoperatively by 3 independent observers in a blinded fashion. The true position of the nerve was determined intraoperatively by the surgeon. Thereafter, the imaging-based estimated position was compared with the intraoperatively determined position. Tumor size, cystic appearance, and postoperative House-Brackmann score were analyzed with regard to the accuracy of the depiction of the nerves., Results: The probabilistic tracking showed a connection that correlated to the position of the facial nerve in 81% of the cases and to the position of the cochlear nerve in 33% of the cases. Altogether, the resulting depiction did not correspond to the intraoperative position of any of the nerves in 3 cases., Conclusions: In a majority of cases, the position of the facial nerve, but not of the cochlear nerve, could be estimated by evaluation of the probabilistic tracking results. However, false depictions not corresponding to any nerve do occur and cannot be discerned as such from the image only., (Copyright © 2017 Elsevier Inc. All rights reserved.)

OBJECTIVE The depiction of cranial nerves (CNs) using diffusion tensor imaging (DTI) is of great interest in skull base tumor surgery and DTI used with deterministic tracking methods has been reported previously. However, there are still no good methods usable for the elimination of noise from the resulting depictions. The authors have hypothesized that probabilistic tracking could lead to more accurate results, because it more efficiently extracts information from the underlying data. Moreover, the authors have adapted a previously described technique for noise elimination using gradual threshold increases to probabilistic tracking. To evaluate the utility of this new approach, a comparison is provided with this work between the gradual threshold increase method in probabilistic and deterministic tracking of CNs. METHODS Both tracking methods were used to depict CNs II, III, V, and the VII+VIII bundle. Depiction of 240 CNs was attempted with each of the above methods in 30 healthy subjects, which were obtained from 2 public databases: the Kirby repository (KR) and Human Connectome Project (HCP). Elimination of erroneous fibers was attempted by gradually increasing the respective thresholds (fractional anisotropy [FA] and probabilistic index of connectivity [PICo]). The results were compared with predefined ground truth images based on corresponding anatomical scans. Two label overlap measures (false-positive error and Dice similarity coefficient) were used to evaluate the success of both methods in depicting the CN. Moreover, the differences between these parameters obtained from the KR and HCP (with higher angular resolution) databases were evaluated. Additionally, visualization of 10 CNs in 5 clinical cases was attempted with both methods and evaluated by comparing the depictions with intraoperative findings. RESULTS Maximum Dice similarity coefficients were significantly higher with probabilistic tracking (p < 0.001; Wilcoxon signed-rank test). The false-positive error of the last obtained depiction was also significantly lower in probabilistic than in deterministic tracking (p < 0.001). The HCP data yielded significantly better results in terms of the Dice coefficient in probabilistic tracking (p < 0.001, Mann-Whitney U-test) and in deterministic tracking (p = 0.02). The false-positive errors were smaller in HCP data in deterministic tracking (p < 0.001) and showed a strong trend toward significance in probabilistic tracking (p = 0.06). In the clinical cases, the probabilistic method visualized 7 of 10 attempted CNs accurately, compared with 3 correct depictions with deterministic tracking. CONCLUSIONS High angular resolution DTI scans are preferable for the DTI-based depiction of the cranial nerves. Probabilistic tracking with a gradual PICo threshold increase is more effective for this task than the previously described deterministic tracking with a gradual FA threshold increase and might represent a method that is useful for depicting cranial nerves with DTI since it eliminates the erroneous fibers without manual intervention.

OBJECTIVE Direct stimulation of the peroneal nerve by the ActiGait implantable drop foot stimulator is a potent therapy that was described previously for stroke-related drop foot. The authors report here successful long-term application of the ActiGait implantable drop foot stimulator in patients with multiple sclerosis (MS). METHODS Six patients with MS and 2 years of persisting central leg paresis received an implantable ActiGait drop foot stimulator after successful surface test stimulation. Ten weeks and 1 year after surgery, their gait speed, endurance, and safety were evaluated. Patient satisfaction was assessed with a questionnaire. RESULTS In the 20-m gait test, stimulation with the ActiGait stimulator significantly reduced the time needed, on average, by approximately 23.6% 10 weeks after surgery, and the time improved further by 36.3% after 1 year. The median distance covered by patients with the stimulator after 6 minutes of walking increased significantly from 217 m to 321 m and remained stable for 1 year; the distance covered by patients after surface stimulation was 264 m. Patients with an implanted ActiGait stimulator noticed pronounced improvement in their mobility, social participation, and quality of life. CONCLUSIONS The ActiGait implantable drop foot stimulator improved gait speed, endurance, and quality of life in all patients over a period of 1 year. It may serve as a new therapeutic option for patients with MS-related drop foot.

Objective To determine the value of apparent diffusion coefficient (ADC) histogram parameters for the prediction of individual survival in patients undergoing surgery for recurrent glioblastoma (GBM) in a retrospective cohort study. Methods Thirty-one patients who underwent surgery for first recurrence of a known GBM between 2008 and 2012 were included. The following parameters were collected: age, sex, enhancing tumor size, mean ADC, median ADC, ADC skewness, ADC kurtosis and fifth percentile of the ADC histogram, initial progression free survival (PFS), extent of second resection and further adjuvant treatment. The association of these parameters with survival and PFS after second surgery was analyzed using log-rank test and Cox regression. Results Using log-rank test, ADC histogram skewness of the enhancing tumor was significantly associated with both survival (p = 0.001) and PFS after second surgery (p = 0.005). Further parameters associated with prolonged survival after second surgery were: gross total resection at second surgery (p = 0.026), tumor size (0.040) and third surgery (p = 0.003). In the multivariate Cox analysis, ADC histogram skewness was shown to be an independent prognostic factor for survival after second surgery. Conclusion ADC histogram skewness of the enhancing lesion, enhancing lesion size, third surgery, as well as gross total resection have been shown to be associated with survival following the second surgery. ADC histogram skewness was an independent prognostic factor for survival in the multivariate analysis.

Recent advances in preoperative and postoperative imaging have an increasing influence on surgical decision-making and make more complex surgical interventions possible. This improves the possibilities for frequently occurring challenges and promoting improved functional and oncological outcome. This manuscript reviews the role of preoperative and intraoperative imaging in surgery. Various techniques are explained based on examples from hepatobiliary surgery and neurosurgery, in particular real-time procedures, such as the online use of augmented reality and in vivo fluorescence, as well as new and promising optical techniques including imaging of intrinsic signals and vibrational spectroscopy.

OBJECT The ActiGait drop foot stimulator is a promising technique for restoration of lost ankle function by an implantable hybrid stimulation system. It allows ankle dorsiflexion by active peroneal nerve stimulation during the swing phase of gait. In this paper the authors report the outcome of the first prospective study on a large number of patients with stroke-related drop foot. METHODS Twenty-seven patients who experienced a stroke and with persisting spastic leg paresis received an implantable ActiGait drop foot stimulator for restoration of ankle movement after successful surface test stimulation. After 3 to 5 weeks, the stimulator was activated, and gait speed, gait endurance, and activation time of the system were evaluated and compared with preoperative gait tests. In addition, patient satisfaction was assessed using a questionnaire. RESULTS Postoperative gait speed significantly improved from 33.9 seconds per 20 meters to 17.9 seconds per 20 meters (p < 0.0001), gait endurance from 196 meters in 6 minutes to 401 meters in 6 minutes (p < 0.0001), and activation time from 20.5 seconds to 10.6 seconds on average (p < 0.0001). In 2 patients with nerve injury, surgical repositioning of the electrode cuff became necessary. One patient showed a delayed wound healing, and in another patient the system had to be removed because of a wound infection. Marked improvement in mobility, social participation, and quality of life was confirmed by 89% to 96% of patients. CONCLUSIONS The ActiGait implantable drop foot stimulator improves gait speed, endurance, and quality of life in patients with stroke-related drop foot. Regarding gait speed, the ActiGait system appears to be advantageous compared with foot orthosis or surface stimulation devices. Randomized trials with more patients and longer observation periods are needed to prove the long-term benefit of this device.

A drop foot occurs in up to 20% of stroke patients and leads to an increased risk of falls. Until recently, only a foot orthosis or surface stimulation was able to improve the gait of these patients. Recent studies have shown that direct peroneal nerve stimulation with an implantable 4-channel peroneal nerve stimulator (ActiGait) allows independent electrode adjustment and leads to better functional results and an improved quality of life. The application of this therapeutic option is restricted to patients with a drop foot attributable to a lesion of the first motor neuron caused by stroke, multiple sclerosis, or tumors. In this paper, we present the first technical note with possible pitfalls of the surgical procedure and the perioperative care after implantation of ActiGait drop foot stimulators in 50 patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Acute hydrocephalus ensues from various intracranial processes and is usually treated using external ventricular drainage (EVD). After the acute phase, a clamp trial is usually performed to identify patients requiring permanent CSF shunting. The aim of our study was to identify simple and clinically accessible factors that can help predict the result of the EVD clamp trial., Methods: 86 patients were selected for this retrospective analysis. Average CSF drained volume over 3 days given a constant EVD pressure level of 15 cm H2O and other clinical and laboratory parameters were statistically compared with the result of an EVD clamp trial., Results: The univariate analysis identified significant differences between the groups of patients who failed or passed the EVD clamp trial for the mean daily drained volume over 3 days (Mann-Whitney U-test, p<0.01). In the multivariate logistic regression, the average daily CSF output over 3 days was also significant (p=0.02), no other significant factors could be identified. Using hierarchical clustering, the best threshold daily value for EVD clamp trial failure was found at 130 ml (mean daily drained CSF volume) with the sensitivity of 64.5% and specificity of 83.6% (chi-square 20.6, p<0.01)., Conclusion: We have identified a simple, clinically available factor for identifying patients who are likely to fail the EVD clamp trial., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Successful deep brain stimulation is mostly dependent on accurate positioning of the leads at the optimal target points. We investigated whether the identification of the subthalamic nucleus in T2-weighted 3-T MRI, fluid-attenuated inversion recovery 3-T MRI and susceptibility-weighted 3-T MRI is confirmed by intraoperative neurological microelectrode recording., Methods: We evaluated 182 microelectrode recording leads in 21 patients with bilateral deep brain stimulation, retrospectively. Consequently, 728 electrode contact positions in T2-weighted 3-T MRI, 552 electrode contact positions in fluid-attenuated inversion recovery 3-T MRI and 490 electrode contact positions in susceptibility-weighted 3-T MRI were evaluated for a positive nucleus subthalamicus signal., Results: The highest sensitivity was measured for fluid-attenuated inversion recovery 3-T MRI with 82.5 %, while the highest specificity was observed for susceptibility-weighted 3-T MRI with 90.6 %. The negative predictive value was nearly equal for susceptibility-weighted MRI and fluid-attenuated inversion recovery MRI with 87.5 % vs. 87.1 %, but the positive predictive value was higher in susceptibility-weighted 3-T MRI (86.0 %) than in the other MRI sequences., Conclusions: The susceptibility-weighted 3-T MRI-based subthalamic nucleus localization shows the best accuracy compared with T2-weighted and fluid-attenuated inversion recovery 3-T MRI. Therefore, the susceptibility-weighted 3-T MRI should be preferred for surgical planning when the operation procedure is performed under general anesthesia without microelectrode recordings.

Background: Traumatic brain injury (TBI) is a leading cause of death and permanent disability and a common and important global problem. The contribution of secondary posttraumatic brain damage to overall disability in TBI is significant, underlining the importance of prompt and comprehensive treatment for affected patients., Methods: This article focuses on current concepts of prehospital and emergency room management of patients with severe TBI to prevent secondary brain injuries., Results and Discussion: Preclinical prevention and treatment of hypoxia, hypotension and hypercarbia are essential, as they affect the long-term outcome in TBI patients. Prehospital intubation should be critically weighed and in the context of an individual decision. In general, prehospital intubation is more difficult than in the clinical setting. The combination of ketamine and benzodiazepines are commonly used to induce anesthesia before intubation in hemodynamic instable patients. The choice of a muscle relaxant for anesthesia induction is either a non-depolarizing neuromuscular blocking agent or succinylcholine. Administration of mannitol or hypertonic saline is effective to rapidly decrease intracranial pressure. Whenever possible the final destination for transport of TBI patients should be a level I center with round the clock neurosurgical expertise. Trauma-induced coagulopathy should be recognized and immediately treated using a point-of-care testing., Conclusion: Hypoxia, hypotension and hypercarbia should strictly be avoided to improve survival and neurological outcome in patients with severe TBI. The prehospital decision to intubate must be made on a case by case basis at the accident site. A level I trauma center should be the destination for this patient group.

The focus of this paper is to identify and quantify risk factors for early hemorrhagic progression of brain contusions (HPC) in patients with traumatic brain injury (TBI) and to evaluate their impact on patients' outcome. Further, based on abnormal values in routine blood tests, the role of trauma-induced coagulopathy is analyzed in detail. Therefore, a prospective study of 153 TBI patients was completed at one institution between January 2008 and June 2012. The collected data included demographics, initial Glasgow Coma Scale pupillary response, initial and 6 h follow-up computed tomography scan findings, coagulation parameters (international normalized ratio, partial thromboplastin time, platelet count, fibrinogen, D-dimer and factor XIII), as well as outcome data using the modified Rankin score at discharge and after one year. The overall rate of early HPC within the first 6 h was 43.5%. The frequency of coagulopathy was 47.1%. When analyzing for risk factors that independently influenced outcome in the form of mRS ≥4 at both points, the following variables appeared: elevated D-dimer level (≥10,000 μg/L), HPC, and initial brain contusions ≥3 cm. Patients sustaining early HPC had a hazard ratio of 5.4 for unfavorable outcome at discharge (p=0.002) and of 3.9 after one year (p=0.006). Overall, patients who developed early HPC were significantly more likely to be gravely disabled or to die. Unfavorable neurological outcome after an isolated TBI is determined largely by early HPC and coagulopathy, which seem to occur very frequently in TBI patients, irrespective of the severity of the trauma.

Objective: To present midterm to long-term results obtained in carpal tunnel release, in situ decompression, and anterior transposition of the ulnar nerve using the retractor integrated endoscope., Methods: During the period 2000-2010, 145 patients underwent endoscopic carpal tunnel releases (n = 47), endoscopic in situ decompression of the ulnar nerve (n = 55), and endoscopic anterior transposition of the ulnar nerve (n = 52). Bilateral surgery was performed in 9 patients. Independent examinations at 24 months after surgery were used for objective results (Bishop score). Subjective results were procured using a questionnaire., Results: After endoscopic carpal tunnel release, 59.6% of patients showed excellent results, 21.2% showed good results, 12.8% showed fair results, and 6.4% showed poor results according to objective scoring. In 85% of patients, subjective improvement was noted after surgery; symptoms were the same as before surgery in 12.8% of patients and were worse in 2.1% of patients after surgery. After endoscopic in situ decompression, 56.4% of patients showed excellent results on objective scoring, 32.7% showed good results, 9.1% showed fair results, and 1.8% showed poor results. On subjective questioning, 72.7% of patients reported improvement, 20% reported no change in symptoms, and 7.3% reported worse symptoms. After endoscopic anterior transposition of the ulnar nerve, 48.1% of patients showed excellent results on objective scoring, 26.9% showed good results, 23.1% showed fair results, and 1.9% showed poor results. Subjectively, 65.4% of patients reported improvement, 26.9% reported no change in symptoms, and 7.7% reported worse symptoms. Patients with symptom duration of <9 months before surgery showed better results than patients with symptom duration of >9 months., Conclusions: The retractor-endoscopic technique provides good long-term results after carpal tunnel release, in situ decompression, and anterior subcutaneous transposition of the ulnar nerve. Outcomes showed some correlation to the duration of preoperative symptoms., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Decompressive craniectomy (DC) is a last treatment option of refractory intracranial hypertension in traumatic brain injury (TBI) patients. Replacement of the autologous bone flap is the preferred method to cover the cranial defect after brain swelling has subsided. Long term outcomes and complications after replacement of the autologous bone flap in pediatric patients were studied in comparison to young, healthy adults., Methods: Medical records of 27 pediatric patients who underwent DC and subsequent replacement of the bone flap between 1998 and 2011 were reviewed retrospectively. Patients were divided into two age groups (group 1: 18 children < 15 years; group 2:9 adolescents 15-18 years). For comparative reasons, a young adult control group of 39 patients between 18 and 30 years was additionally evaluated., Results: With 81.8 % resorption of the bone flap, this was the major complication in young children. In up to 54.4 % of patients, a surgical revision of the osteolytic bone flap became necessary. However, in some pediatric patients, the osteolysis resolved spontaneously and further operations were not required. Probable enabling factors for bone flap resorption were young age (0-7 years), size of craniectomy, permanent shunt placement, and extent of dural opening/duraplasty. Other complications were bone flap infections, loosening of the re-inserted bone flap, and postoperative hematomas., Conclusion: There is an unacceptably high complication rate after reimplantation of the autologous bone following DC in pediatric TBI patients, especially in young children up to seven years of age. Artificial or synthetic cranioplasties may be considered as alternatives to initial bone flap reimplantation in the growing child. Despite the fact that DC is an effective treatment in TBI with persistent intracranial hypertension, it is important to realize that DC is not only combined with replacement of the autologous bone flap but also with a high rate of additional complications especially in pediatric patients.

Object: Intraoperative optical imaging (IOI) is an experimental technique used for visualizing functional brain areas after surgical exposure of the cerebral cortex. This technique identifies areas of local changes in blood volume and oxygenation caused by stimulation of specific brain functions. The authors describe a new IOI method, including innovative data analysis, that can facilitate intraoperative functional imaging on a routine basis. To evaluate the reliability and validity of this approach, they used the new IOI method to demonstrate visualization of the median nerve area of the somatosensory cortex., Methods: In 41 patients with tumor lesions adjacent to the postcentral gyrus, lesions were surgically removed by using IOI during stimulation of the contralateral median nerve. Optical properties of the cortical tissue were measured with a sensitive camera system connected to a surgical microscope. Imaging was performed by using 9 cycles of alternating prolonged stimulation and rest periods of 30 seconds. Intraoperative optical imaging was based on blood volume changes detected by using a filter at an isosbestic wavelength (λ = 568 nm). A spectral analysis algorithm was used to improve computation of the activity maps. Movement artifacts were compensated for by an elastic registration algorithm. For validation, intraoperative conduction of the phase reversal over the central sulcus and postoperative evaluation of the craniotomy site were used., Results: The new method and analysis enabled significant differentiation (p < 0.005) between functional and nonfunctional tissue. The identification and visualization of functionally intact somatosensory cortex was highly reliable; sensitivity was 94.4% and specificity was almost 100%. The surgeon was provided with a 2D high-resolution activity map within 12 minutes. No method-related side effects occurred in any of the 41 patients., Conclusions: The authors' new approach makes IOI a contact-free and label-free optical technique that can be used safely in a routine clinical setup. Intraoperative optical imaging can be used as an alternative to other methods for the identification of sensory cortex areas and offers the added benefit of a high-resolution map of functional activity. It has great potential for visualizing and monitoring additional specific functional brain areas such as the visual, motor, and speech cortex. A prospective national multicenter clinical trial is currently being planned.

Deep brain stimulation (DBS) is an established treatment of various diseases, particularly used for idiopathic Parkinson's disease. Frequently, DBS patients are multimorbid and managing them may be challenging, since postoperative complications can become more likely with age. In this article, we present two cases of myocardial infarction after DBS with different therapeutic strategies. Case 1 was anticoagulated with a heparin infusion with a target partial thromboplastine time (PTT) between 50 and 60 s after the myocardial infarction and showed 3 days later, after an initial postoperative inconspicuous cranial computer tomography, an intracerebral haematoma, which was evacuated without explanting the DBS lead. Case 2 was only treated with enoxaparine 40 mg s.c. twice a day after the myocardial infarction without any further complications. Both cases benefited from the DBS with respect to the motor fluctuations, but case 1 continued to suffer from psychomotor slowdown, mild hemiparesis of the left side, visual neglect and a gaze paresis. Unfortunately, there are no established guidelines or therapy recommendations for the management of such patients. An individual therapy regime is necessary for this patient population regarding the bleeding risk, the cardial risk and the symptoms of the patient. Retrospectively, the rejection of the intravenous application of heparin in case 2 seems to be the right decision. But regarding the small number of cases, it remains still an individual therapy. Further experience will help us to develop optimal therapy strategies for this patient population.

Intraoperative optical imaging of intrinsic signals can improve the localization of functional areas of the cortex. On the basis of a review of the current state of technology, a setup was developed and evaluated. The aim was to implement an easy-to-use and robust imaging setup that can be used in clinical routine with standard hardware equipment (surgical microscope, high-resolution camera, stimulator for peripheral nerve stimulation) and custom-made software for intraoperative and postoperative data analysis. Evaluation of different light sources (halogen, xenon) showed a sufficient temporal behavior of xenon light without using a stabilized power supply. Spatial binning (2×2) of the camera reduces temporal variations in the images by preserving a high spatial resolution. The setup was tested in eight patients. Images were acquired continuously for 9 min with alternating 30-s rest and 30-s stimulation conditions. Intraoperative measurement and visualization of high-resolution two-dimensional activity maps could be achieved in <15 min. The detected functional regions corresponded with anatomical and electrophysiological validation. The integration of optical imaging in clinical routine could successfully be achieved using standard hardware, which improves guidance for the surgeon during interventions near the eloquent areas of the brain.

A demonstrator system for planning neurosurgical procedures was developed based on commercial hardware and software. The system combines an easy-to-use environment for surgical planning with high-end visualization and the opportunity to analyze data sets for research purposes. The demonstrator system is based on the software AMIRA. Specific algorithms for segmentation, elastic registration, and visualization have been implemented and adapted to the clinical workflow. Modules from AMIRA and the image processing library Insight Segmentation and Registration Toolkit (ITK) can be combined to solve various image processing tasks. Customized modules tailored to specific clinical problems can easily be implemented using the AMIRA application programming interface and a self-developed framework for ITK filters. Visualization is done via autostereoscopic displays, which provide a 3D impression without viewing aids. A Spaceball device allows a comfortable, intuitive way of navigation in the data sets. Via an interface to a neurosurgical navigation system, the demonstrator system can be used intraoperatively. The precision, applicability, and benefit of the demonstrator system for planning of neurosurgical interventions and for neurosurgical research were successfully evaluated by neurosurgeons using phantom and patient data sets.

Intraoperative optical imaging (IOI) is a method to visualize functional activated brain areas during brain surgery using a camera system connected to a standard operating microscope. Three different high-resolution camera systems (Hamamatsu EB-CCD C7190-13W, Hamamatsu C4742-96-12G04, and Zeiss AxioCam MRm) have been evaluated for suitability to detect activated brain areas by detecting stimulation-dependent blood volume changes in the somatosensory cerebral cortex after median nerve stimulation. The image quality of the camera systems was evaluated in 14 patients with tumors around the somatosensory cortex. The intraoperative images of the brain surface were continuously recorded over 9 min. With all three camera systems, the activity maps of the median nerve area could be visualized. The image quality of a highly sensitive electron-bombarded camera was up to 10-fold lower compared with two less sensitive standard cameras. In each IOI-positive case, the activated area was in accordance with the anatomical and neurophysiological location of the corresponding cortex. The technique was found to be very sensitive, and several negative influencing factors were identified. However, all possible artifacts seem to be controllable in the majority of the cases, and the IOI method could be well adapted for routine clinical use. Nevertheless, further systematic studies are needed to demonstrate the reliability and validity of the method.

Intraoperative optical imaging (IOI) is a localization method for functional areas of the human brain cortex during neurosurgical procedures. The aim of the current work was to develop of a new analysis technique for the computation of two-dimensional IOI activity maps that is suited especially for use in clinical routine. The new analysis technique includes a stimulation scheme that comprises 30-s rest and 30-s stimulation conditions, in connection with pixelwise spectral power analysis for activity map calculation. A software phantom was used for verification of the implemented algorithms as well as for the comparison with the commonly used relative difference imaging method. Furthermore, the analysis technique was tested using intraoperative measurements on eight patients. The comparison with the relative difference algorithm revealed an averaged improvement of the signal-to-noise ratio between 95% and 130% for activity maps computed from intraoperatively acquired patient datasets. The results show that the new imaging technique improves the activity map quality of IOI especially under difficult intraoperative imaging conditions and is therefore especially suited for use in clinical routine.

Several functional brain imaging and mapping techniques have been used for the intraoperative identification and preservation of the sensory, motor, and speech areas of the brain. However, intraoperative monitoring and mapping of the visual function is less frequently performed in the clinical routine. To our knowledge, here we demonstrate for the first time that the individual visual cortex can be mapped to the brain surface using a contact-free optical camera system during brain surgery. Intraoperative optical imaging (IOI) was performed by visual stimulation of both eyes using stobe-light flashes. Images were acquired by a camera mounted to a standard surgical microscope. Activity maps could reproducibly be computed by detecting the blood volume-dependent signal changes of the exposed cortex. To the preliminary experience, the new technique seems to be suitable for mapping the visual function in any neurosurgical intervention that requires exposure of the visual cortex. However, the clinical relevance and reliability of the technique need to be confirmed in further studies.

Present methods for quantitative measurement of cerebral perfusion during neurosurgical operations require additional technology for measurement, data acquisition, and processing. This study used conventional fluorescence video angiography--as an established method to visualize blood flow in brain vessels--enhanced by a quantifying perfusion software tool. For these purposes, the fluorescence dye indocyanine green is given intravenously, and after activation by a near-infrared light source the fluorescence signal is recorded. Video data are analyzed by software algorithms to allow quantification of the blood flow. Additionally, perfusion is measured intraoperatively by a reference system. Furthermore, comparing reference measurements using a flow phantom were performed to verify the quantitative blood flow results of the software and to validate the software algorithm. Analysis of intraoperative video data provides characteristic biological parameters. These parameters were implemented in the special flow phantom for experimental validation of the developed software algorithms. Furthermore, various factors that influence the determination of perfusion parameters were analyzed by means of mathematical simulation. Comparing patient measurement, phantom experiment, and computer simulation under certain conditions (variable frame rate, vessel diameter, etc.), the results of the software algorithms are within the range of parameter accuracy of the reference methods. Therefore, the software algorithm for calculating cortical perfusion parameters from video data presents a helpful intraoperative tool without complex additional measurement technology.

Gliomas are the most frequent primary brain tumours. During neurosurgical treatment, locating the exact tumour border is often difficult. This study assesses grading of astrocytomas based on Raman spectroscopy for a future application in intra-surgical guidance. Our predictive classification models distinguish the surgically relevant classes "normal tissue" and "low" and "high grade astrocytoma" in Raman maps of moist bulk samples (80 patients) acquired with a fibre-optic probe. We introduce partial class memberships as a strategy to utilize borderline cases for classification. Borderline cases supply the most valuable training and test data for our application. They are (a) examples of the sought boundary and (b) the cases for which new diagnostics are needed. Besides, the number of suitable training samples increases considerably: soft logistic regression (LR) utilizes 85% more spectra and 50% more patients than linear discriminant analysis (LDA). The predictive soft LR models achieve ca. 85, 67 and 84% (normal, low and high grade) sensitivity and specificity. We discuss the different heuristics of LR and LDA in the light of borderline samples. While we focus on prediction, the spectroscopic interpretation of the predictive models agrees with previous descriptive studies. Unsaturated lipids are used to differentiate between normal and tumour tissues, while the total lipid content prominently contributes to the determination of the tumour grade. The high-wavenumber region above 2,800 cm(-1) alone did not allow successful grading. We give a proof of concept for Raman spectroscopic grading of moist astrocytoma tissues and propose to include borderline samples into classifier training and testing.

Established methods for characterization of tissue and diagnostics, for example histochemistry, magnetic resonance imaging (MRI), X-ray tomography, or positron emission tomography (PET), are mostly not suitable for intra-operative use. However, there is a clear need for an intra-operative diagnostics especially to identify the borderline between normal and tumor tissue. Currently, vibrational spectroscopy techniques (both Raman and infrared) complement the standard methods for tissue diagnostics. Vibrational spectroscopy has the potential for intra-operative use, because it can provide a biochemically based profile of tissue in real time and without requiring additional contrast agents, which may perturb the tissue under investigation. In addition, no electric potential needs to be applied, and the measurements are not affected by electromagnetic fields. Currently, promising approaches include Raman fiber techniques and nonlinear Raman spectroscopy. Infrared spectroscopy is also being used to examine freshly resected tissue ex vivo in the operating theater. The immense volume of information contained in Raman and infrared spectra requires multivariate analysis to extract relevant information to distinguish different types of tissue. The promise and limitations of vibrational spectroscopy methods as intra-operative tools are surveyed in this review.

A new approach to cortical perfusion imaging is demonstrated using high-sensitivity thermography in conjunction with multivariate statistical data analysis. Local temperature changes caused by a cold bolus are imaged and transferred to a false color image. A cold bolus of 10 ml saline at ice temperature is injected systemically via a central venous access. During the injection, a sequence of 735 thermographic images are recorded within 2 min. The recorded data cube is subjected to a principal component analysis (PCA) to select slight changes of the cortical temperature caused by the cold bolus. PCA reveals that 11 s after injection the temperature of blood vessels is shortly decreased followed by an increase to the temperature before the cold bolus is injected. We demonstrate the potential of intraoperative thermography in combination with multivariate data analysis to image cortical cerebral perfusion without any markers. We provide the first in vivo application of multivariate thermographic imaging.

Six Sigma is an innovative management- approach to reach practicable zero- defect quality in medical service processes. The Six Sigma principle utilizes strategies, which are based on quantitative measurements and which seek to optimize processes, limit deviations or dispersion from the target process. Hence, Six Sigma aims to eliminate errors or quality problems of all kinds. A pilot project to optimize the preparation for neurosurgery could now show that the Six Sigma method enhanced patient safety in medical care, while at the same time disturbances in the hospital processes and failure costs could be avoided. All six defined safety relevant quality indicators were significantly improved by changes in the workflow by using a standardized process- and patient- oriented approach. Certain defined quality standards such as a 100% complete surgical preparation at start of surgery and the required initial contact of the surgeon with the patient/ surgical record on the eve of surgery could be fulfilled within the range of practical zero- defect quality. Likewise, the degree of completion of the surgical record by 4 p.m. on the eve of surgery and their quality could be improved by a factor of 170 and 16, respectively, at sigma values of 4.43 and 4.38. The other two safety quality indicators "non-communicated changes in the OR- schedule" and the "completeness of the OR- schedule by 12:30 a.m. on the day before surgery" also show an impressive improvement by a factor of 2.8 and 7.7, respectively, corresponding with sigma values of 3.34 and 3.51. The results of this pilot project demonstrate that the Six Sigma method is eminently suitable for improving quality of medical processes. In our experience this methodology is suitable, even for complex clinical processes with a variety of stakeholders. In particular, in processes in which patient safety plays a key role, the objective of achieving a zero- defect quality is reasonable and should definitely be aspirated., (Copyright © 2010. Published by Elsevier GmbH.)

Due to the knowledge gap that exists between patients and health care staff the quality of medical treatment usually cannot be assessed securely by patients. For an optimization of safety in treatment-related processes of medical care, the medical staff needs to be actively involved in preventive and proactive quality management. Using voluntary, confidential and non-punitive systematic employee surveys, vulnerable topics and areas in patient care revealing preventable risks can be identified at an early stage. Preventive measures to continuously optimize treatment quality can be defined by creating a risk portfolio and a priority list of vulnerable topics. Whereas critical incident reporting systems are suitable for continuous risk assessment by detecting safety-relevant single events, employee surveys permit to conduct a systematic risk analysis of all treatment-related processes of patient care at any given point in time.

Infrared spectroscopic imaging is a promising intraoperative tool which enables rapid, on-site diagnosis of brain tumors during neurosurgery. A classification model was recently developed using infrared spectroscopic images from thin tissue sections to grade malignant gliomas, the most frequent class of primary brain tumor. In this study the model was applied to 54 specimens from six patients with inhomogeneous gliomas composed of regions with different tumor density and morphology. The resection was controlled using neuronavigation which transfers the findings obtained by preoperative magnetic resonance imaging (MRI) into the operating field. For comparison, all specimens were independently evaluated by histopathology after hematoxylin and eosin staining. The infrared-derived grading agreed with histopathology and MRI findings for almost all specimens. With regard to histopathological assessment, sensitivities of 100% (22/22) and 93.1% (27/29) and specificities of 96.9% (31/32) and 88.0% (22/25) were achieved, depending on whether the classification was based on the predominant or maximal tumor grade, respectively, in the specimen. Altogether, in 98% (53/54) of all specimens the decision to continue or not continue tumor resection could have been made according to the infrared spectroscopic classification. This retrospective study clearly demonstrates that infrared spectroscopic imaging may help to define tumor margins intraoperatively and to detect high-grade tumor residues for achieving more radical tumor resection.

Infrared (IR) spectroscopy provides a sensitive molecular fingerprint for tissue without external markers. Supervised classification models can be trained to identify the tissue type based on the spectroscopic fingerprint. Infrared imaging spectrometers equipped with multi-channel detectors combine the spectral and spatial information. Tissue areas of 4 x 4 mm(2) can be analyzed within a few minutes in the macroscopic imaging mode. An approach is described to apply this methodology to human astrocytic gliomas, which are graded according to their malignancy from one to four. Multiple IR images of three tissue sections from one patient with a malignant glioma are acquired and assigned to the six classes normal brain tissue, astrocytoma grade II, astrocytoma grade III, glioblastoma multiforme grade IV, hemorrhage, and other tissue by a linear discriminant analysis model which was trained by data from a single-channel detector. Before the model is applied here, the spectra are shown to be virtually identical. The first specimen contained approximately 95% malignant glioma regions, that means astrocytoma grade III or glioblastoma. The smaller percentage of 12-34% malignant glioma in the second specimen is consistent with its location at the tumor periphery. The detection of less than 0.2% malignant glioma in the third specimen points to a location outside the tumor. The results were correlated with the cellularity of the tissue which was obtained from the histopathologic gold standard. Potential applications of IR spectroscopic imaging as a rapid tool to complement established diagnostic methods are discussed.

Brain metastases are secondary intracranial lesions which occur more frequently than primary brain tumors. The four most abundant types of brain metastasis originate from primary tumors of lung cancer, colorectal cancer, breast cancer and renal cell carcinoma. As metastatic cells contain the molecular information of the primary tissue cells and IR spectroscopy probes the molecular fingerprint of cells, IR spectroscopy based methods constitute a new approach to determine the origin of brain metastases. IR spectroscopic images of 4 by 4 mm2 tissue areas were recorded in transmission mode by a FTIR imaging spectrometer coupled to a focal plane array detector. Unsupervised cluster analysis revealed variances within each cryosection. Selected clusters of five IR images with known diagnoses trained a supervised classification model based on the algorithm soft independent modeling of class analogies (SIMCA). This model was applied to distinguish normal brain tissue from brain metastases and to identify the primary tumor of brain metastases in 15 independent IR images. All specimens were assigned to the correct tissue class. This proof-of-concept study demonstrates that IR spectroscopy can complement established methods such as histopathology or immunohistochemistry for diagnosis.