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.

Molecular background of the undesired odor of polypropylene materials and insights into the sources of key odorants.

Screening the volatiles isolated from a standard polypropylene material consisting of a polypropylene homopolymer, the filler talcum, and a mixture of antioxidants, for odor-active compounds by application of an aroma extract dilution analysis revealed 30 odorants with flavor dilution factors ranging from 1 to 64. Eighteen odor-active compounds were subsequently quantitated by gas chromatography-mass spectrometry using stable isotopically substituted odorants as internal standards, and their odor activity values (OAVs) were calculated as ratios of the concentrations to the odor threshold values. Five odorants showed OAVs ≥1, among which were hex-1-en-3-one (OAV 12), butanoic acid (OAV 3), as well as 4-methylphenol, butan-1-ol, and 2-tert-butylphenol (all OAV 1). A comparative analysis of polypropylene materials with different additives suggested plastic-like, pungent smelling hex-1-en-3-one as an ubiquitous key odorant. Odor-active amounts of alkylphenols, in particular plastic-like, phenolic smelling 2-tert-butylphenol, were additionally formed in the presence of talcum and phenolic antioxidants. Whereas the precursors of the phenols were thus obvious, the origin of hex-1-en-3-one was unknown. Injection molding showed only little influence on odorant concentrations.

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.

A head phantom prototype to verify subdural electrode localization tools in epilepsy surgery.

When planning epilepsy surgery, the position of subdural electrodes in relation to the cortex is crucial. Electrodes may dislocate after implantation. Neurosurgeons are highly interested in the accuracy of methods that visualize these electrodes. In order to determine the accuracy of an electrode visualization method, we have developed a physical head phantom and evaluated our new method of subdural electrode localization. This method projects automatically segmented electrodes of a preimplantation computed tomography (CT) data set onto the segmented brain surface of a postimplantation magnetic resonance imaging (MRI) data set within 2 to 5 min. The phantom consists of a skull, an adipose layer for skin replication, and a deformable brain. It further contains gyri and sulci structures, composed of gelatin and different additives used as phantom material for white matter, gray matter, and cerebrospinal fluid. The phantom allows a well-defined displacement of an "implanted" electrode grid perpendicular to the brain surface. By using the phantom data, we demonstrated that our electrode visualization tool did in fact function accurately. The image contrasts between different phantom materials in MRI and CT phantom data sets were similar to patient data sets. The phantom appears suitable for obtaining a more complex patient data replication, as well as for simulating different deformation scenarios.

Workflow and hardware for intraoperative hyperspectral data acquisition in neurosurgery.

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 of metabolic changes after direct cortical stimulation - a clinical tool for guidance during tumor resection?

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.

Continuous cerebral autoregulation monitoring by improved cross-correlation analysis: comparison with the cuff deflation test.

OBJECTIVES: To improve the cross-correlation method for noninvasive, continuous monitoring of cerebral autoregulation, to evaluate this method in humans with intact and impaired autoregulatory capacity, and to compare it to the cuff deflation test. DESIGN AND SETTING: Prospective study in the intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: Fourteen patients with severe head injury, six patients with subarachnoid hemorrhage, and nine healthy volunteers. INTERVENTIONS AND MEASUREMENTS: Middle cerebral artery flow velocities and arterial blood pressure were monitored continuously. Aaslid's thigh cuff tests were performed and results were scored using Tiecks' model for autoregulation index. Data were then collected without any patient manipulation. The mean time delay between slow spontaneous oscillations of blood pressure and middle cerebral artery flow velocity was calculated by cross-correlation analysis. Data are expressed as median (lower/upper quartile). RESULTS: Healthy subjects had a higher autoregulation index than patients, 5.0 (5.0/5.5) vs. 3.3 (2.0/4.5). Slow oscillations of blood pressure and middle cerebral artery flow velocity showed a time delay of -2.0 s (-2.7/-1.7) in healthy subjects but were almost synchronal in patients, -0.07 s (-0.5/0.45). Inter-method agreement in diagnosing an intact or impaired cerebral autoregulation was obtained in 108 of 147 examinations of autoregulation (73.5%) and was considered moderate. CONCLUSIONS: Cross-correlation analysis may serve as a simple, noninvasive, and continuous measure of cerebral autoregulation. The time delay of -2.0[Symbol: see text]s in healthy subjects is in good agreement with other studies. Short-term autoregulation tests and monitoring techniques based on slow spontaneous oscillations should not be used interchangeably.

Assessment of dynamic changes in cerebral autoregulation.

Cerebral autoregulation (CA) is a control mechanism that adjusts cerebral vasomotor tone in response to changes in arterial blood pressure (ABP) to ensure a nearly constant cerebral blood flow. Patient treatment could be optimized if CA monitoring were possible. Whereas the concept of static CA assessment is simply based on comparison of mean values obtained from two stationary states (e.g., before and after a pressure change), the evaluation of dynamic CA is more complex. Among other methods, moving cross-correlation analysis of slow waves in ABP and cerebral blood flow velocity (CBFV) seems to be appropriate to monitor CA quasi-continuously. The calculation of an "instantaneous transfer function" between ABP and CBFV oscillations in the low-frequency band using the Wigner-Ville distribution may represent an acceptable compromise in time-frequency resolution for continuous CA monitoring.

Assessing the eligibility of a non-invasive continuous blood pressure measurement technique for application during total intravenous anaesthesia.

OBJECTIVE: To assess the eligibility for replacement of invasive blood pressure as measured "within" the arterial vessel (IBP) with non-invasive continuous arterial blood pressure (cNIP) monitoring during total intravenous anaesthesia (TIVA), the ability of cNiP to track fast blood pressure changes needs to be quantified. A new method of statistical data analysis is developed for this purpose. METHODS: In a pilot study on patients undergoing neurosurgical anaesthesia, mean arterial pressure MAPIBP measured with IBP was compared to MAPCNP measured by the CNAP Monitor 500 in ten patients (age: 63±13 a). Correlation analysis of changes of device differences ΔeMAP=ΔMAPCNP-ΔMAPIBP with changes of MAPIBP (ΔMAPIBP) during intervals of vasoactivity was conducted. An innovative technique, of linear trend analysis (LTA) applied to two signals, is described to perform this analysis without a priori knowledge of intervals of vasoactivity. RESULTS: Analysis of ΔeMAP during vasoactivity revealed that ΔMAPCNP systematically underestimated ΔMAPIBP by 37%. This was confirmed in the complete data set using LTA technique showing a systematic, yet patient specific, underestimation in tracking ΔMAPIBP (16…120%). CONCLUSION: The proposed LTA technique is able to detect systematic errors in tracking short-term blood pressure changes otherwise masked by established analysis. LTA may thus be a useful tool to assess the eligibility of cNIP to replace IBP during TIVA.

Improved visualization of intracranial vessels with intraoperative coregistration of rotational digital subtraction angiography and intraoperative 3D ultrasound.

INTRODUCTION: Ultrasound can visualize and update the vessel status in real time during cerebral vascular surgery. We studied the depiction of parent vessels and aneurysms with a high-resolution 3D intraoperative ultrasound imaging system during aneurysm clipping using rotational digital subtraction angiography as a reference. METHODS: We analyzed 3D intraoperative ultrasound in 39 patients with cerebral aneurysms to visualize the aneurysm intraoperatively and the nearby vascular tree before and after clipping. Simultaneous coregistration of preoperative subtraction angiography data with 3D intraoperative ultrasound was performed to verify the anatomical assignment. RESULTS: Intraoperative ultrasound detected 35 of 43 aneurysms (81%) in 39 patients. Thirty-nine intraoperative ultrasound measurements were matched with rotational digital subtraction angiography and were successfully reconstructed during the procedure. In 7 patients, the aneurysm was partially visualized by 3D-ioUS or was not in field of view. Post-clipping intraoperative ultrasound was obtained in 26 and successfully reconstructed in 18 patients (69%) despite clip related artefacts. The overlap between 3D-ioUS aneurysm volume and preoperative rDSA aneurysm volume resulted in a mean accuracy of 0.71 (Dice coefficient). CONCLUSIONS: Intraoperative coregistration of 3D intraoperative ultrasound data with preoperative rotational digital subtraction angiography is possible with high accuracy. It allows the immediate visualization of vessels beyond the microscopic field, as well as parallel assessment of blood velocity, aneurysm and vascular tree configuration. Although spatial resolution is lower than for standard angiography, the method provides an excellent vascular overview, advantageous interpretation of 3D-ioUS and immediate intraoperative feedback of the vascular status. A prerequisite for understanding vascular intraoperative ultrasound is image quality and a successful match with preoperative rotational digital subtraction angiography.

Assessment of visual function during brain surgery near the visual cortex by intraoperative optical imaging.

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.

Intraoperative optical imaging of intrinsic signals: a reliable method for visualizing stimulated functional brain areas during surgery.

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.

Intraoperative optical imaging of functional brain areas for improved image-guided surgery.

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.

Evaluation of intraoperative optical imaging analysis methods by phantom and patient measurements.

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.

Evaluation of the clinical practicability of intraoperative optical imaging comparing three different camera setups.

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.

Quantitative fluorescence angiography for neurosurgical interventions.

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.

Autostereoscopic 3D visualization and image processing system for neurosurgery.

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.

An integrated tool for automated visualization of subdural electrodes in epilepsy surgery evaluation.

PURPOSE: An automated tool embedded in image processing and visualization software should be developed to visualize subdural electrodes on the human cortical surface of the brain. METHODS: For accurate positioning of electrodes on the cortical surface, preoperative magnetic resonance imaging (MRI) and postoperative computed tomography (CT) datasets of pharmacoresistant epilepsy patients were co-registered and segmented. For the brain segmentation of preoperative MRI a new algorithm was implemented. To account for the radial electrode displacement due to cortical deformation, a radial replacement function was developed. The automated tool was evaluated using intraoperative photographs and using a bimodal phantom. RESULTS: The tool visualizes electrodes fully automated in 1-5 min. The mismatch between calculated and reference electrode position derived from intraoperative photographs was