Raman and autofluorescence spectroscopy for in situ identification of neoplastic tissue during surgical treatment of brain tumors.

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.

A new approach for clinical translation of infrared spectroscopy: exploitation of the signature of glioblastoma for general brain tumor recognition.

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.

Topographic Mapping of the Primary Sensory Cortex Using Intraoperative Optical Imaging and Tactile Irritation.

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.

Characterization of cortical hemodynamic changes following sensory, visual, and speech activation by intraoperative optical imaging utilizing phase-based evaluation methods.

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.

Comparison of Automatic Segmentation Algorithms for the Subthalamic Nucleus.

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.

Parcellation of the Subthalamic Nucleus in Parkinson's Disease: A Retrospective Analysis of Atlas- and Diffusion-Based Methods.

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.

Mapping of language and motor function during awake neurosurgery with intraoperative optical imaging.

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.

Clinical Validation of Quality Improvements Using the Six Sigma Concept: A Case Study for Deep Brain Stimulation in Parkinson's Disease.

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.

Somatosensory functional MRI tractography for individualized targeting of deep brain stimulation in patients with chronic pain after brachial plexus injury.

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.

Application of the Six Sigma concept for quality assessment of different strategies in DBS surgery.

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.

Enhancing tumor apparent diffusion coefficient histogram skewness stratifies the postoperative survival in recurrent glioblastoma multiforme patients undergoing salvage surgery.

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.

Accuracy of subthalamic nucleus targeting by T2, FLAIR and SWI-3-Tesla MRI confirmed by microelectrode recordings.

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.

Autologous bone flap cranioplasty following decompressive craniectomy is combined with a high complication rate in pediatric traumatic brain injury patients.

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.

Anticoagulation management of myocardial infarction after deep brain stimulation: a comparison of two cases.

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.

Morbidity Milestones Demonstrate Long Disability-Free Survival in Parkinson's Disease Patients with Deep Brain Stimulation of the Subthalamic Nucleus.

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.

Serum neurofilament indicates that DBS surgery can cause neuronal damage whereas stimulation itself does not.

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.

Raman spectroscopic grading of astrocytoma tissues: using soft reference information.

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.

Intra-operative optical diagnostics with vibrational spectroscopy.

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.

Vestibular Schwannoma Surgery: Outcome and Complications in Lateral Decubitus Position versus Semi-sitting Position-A Personal Learning Curve in a Series of 544 Cases over 3 Decades.

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.