Search

International audience; Deep brain stimulation (DBS) represents today a well-established treatment for movement disorders. Nevertheless the exact mechanism of action of DBS remains incompletely known. During surgery, numerous stimulation tests are frequently performed in order to evaluate therapeutic and adverse effects before choosing the optimal implantation site for the DBS lead. Anatomical structures responsible for the induced adverse effects have been investigated previously, but only based on stimulation data obtained with the implanted DBS lead. The present study introduces a methodology to identify these anatomical structures during intraoperative stimulation tests based on patient-specific electric field simulations and visualization on the patient specific anatomy. The application to 4 patients undergoing DBS surgery and presenting dysarthria, paresthesia or pyramidal effects shows the different anatomical structures, which might be responsible for the adverse effects. Several of the identified structures have been previously described in the literature. To draw any statistically significant conclusions, the methodology has to be applied to further patients. Together with the visualization of the therapeutic effects, this new approach could assist the neurosurgeons in the future in choosing the optimal implant position.

International audience; Deep brain stimulation (DBS) is used for symptomatic treatment of movement disorders. In many centers, the optimal DBS position is identified by intra-operative stimulation tests, which are performed at several positions along the planned trajectories toward the target structure with various stimulation amplitudes. The aim of the study was to propose a methodology summarizing all available intra-operative data of different patients to an atlas to provide targeting guidelines in the thalamus.

Deep brain stimulation is a well-established technique for symptomatic treatment of e.g. Parkinsons disease and essential tremor. Computer simulations using the finite element method (FEM) are widely used to estimate the affected area around the DBS electrodes. For the reliability of the simulations, it is important to match used simulation parameters with experimental data. One such parameter is the electric field magnitude threshold EFt required for axon stimulation. Another is the conductivity of the perielectrode space (PES) around the electrode. At the acute stage after surgery the PES will be characterized by an increased conductivity due to inflammation and edema while the later chronic stage will be characterized by a lower conductivity due to gliosis and minor scar formation. In this study, the EFt and the electric conductivity of the PES have been estimated by comparing FEM simulations with clinical studies of activation distance, pulse length and electrode impedance. The resulting estimates are an EFt of 0.2 V/mm at the common pulse width of 60 mu s and a chronaxie of 62 mu s. Estimated electric conductivities for the PES are 0.14 S/m in the acute stage and 0.05 S/m in the chronic stage, assuming a PES width of 250 mu m. These values are thus experimentally justified to use in FEM simulations of DBS. Funding Agencies|Swedish Research Council (Vetenskapsradet) [2016-03564]; Swedish Foundation for Strategic Research [BD15-0032]; Knut and Alice Wallenberg Foundation

Background: Laser Doppler flowmetry (LDF) can be used to measure cerebral microcirculation in relation to stereotactic deep brain stimulation (DBS) implantations. Objective: To investigate the microcirculation and total light intensity (TLI) corresponding to tissue grayness in DBS target regions with high-resolution LDF recordings, and to define a resolution which enables detection of small vessels. Methods: Stereotactic LDF measurements were made prior to DBS implantation with 0.5-mm steps in the vicinity to 4 deep brain targets (STN, GPi, Vim, Zi) along 20 trajectories. The Mann-Whitney U test was used to compare the microcirculation and TLI between targets, and the measurement resolution (0.5 vs. 1 mm). The numbers of high blood flow spots along the trajectories were calculated. Results: There was a significant difference (p < 0.05) in microcirculation between the targets. High blood flow spots were present at 15 out of 510 positions, 7 along Vim and GPi trajectories, respectively. There was no statistical difference between resolutions even though both local blood flow and TLI peaks could appear at 0.5-mm steps. Conclusions: LDF can be used for online tracking of critical regions presenting blood flow and TLI peaks, possibly relating to vessel structures and thin laminas along stereotactic trajectories.

Summary Background Using 5-aminolevulinic acid (ALA) as an intraoperative fluorescence contrast has been proven to improve the resection of glioblastoma and contribute to prolonged patient survival. ALA accumulates as protoporphyrin IX (PpIX) in the tumor cells and is administered in an advised dose of 20 mg/kg body weight (b.w.) for brain tumor resection using fluorescence surgical microscopes. PpIX fluorescence availability and intensities of a four folds lower ALA dose (5 mg/kg b.w.) has been investigated in glioblastomas and skin using a spectroscopy system adapted for surgical guidance. Methods A total of 30 adult patients diagnosed with high grade gliomas were included in the analysis. ALA was orally administered in doses of 5 mg/kg b.w. ( n = 15) dissolved in orange juice or 20 mg/kg b.w. ( n = 15) dissolved in water. A fluorescence spectroscopy system with a handheld fiber-optical probe was used for performing the quantitative fluorescence measurements. Results The binominal comparison of the diagnostic performance parameters showed no significant statistical difference ( p > 0.05). The median fluorescence values in tumor were 2–3 times higher for the high ALA dose group. No PpIX was detected in the skin of the patients in the low dose group (0/4) while PpIX was detected in the skin of the majority of the patients in the high ALA dose group (13/14). Conclusions Application of 5 mg/kg ALA was evaluated as equally reliable as the higher dose regarding the diagnostic performance when guidance was performed using a spectroscopic system. Moreover, no PpIX was detected in the skin of the patients.

Continuous optical monitoring of local cerebral microcirculation could benefit neurointensive care patients treated for subarachnoid hemorrhage (SAH). The aim of the study was to evaluate laser Doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) for long-term monitoring of brain microcirculation and oxygen saturation (SO2) in the neurointensive care unit (NICU). A fiber optic probe was designed for intraparenchymal use and connected to LDF and DRS for assessment of the local blood flow (perfusion and tissue reflectance (TLI)) and SO2in the brain. The optically monitored parameters were compared with conventional NICU monitors and Xe-CT. The LDF signals were low with median and 25 to 75% interquartiles of perfusion = 70 (59 to 83) a.u. and TLI = 2.0 (1.0 to 2.4) a.u. and showed correlation with the NICU monitors in terms of heart rate. Median and interquartiles of SO2 were 17.4 (15.7 to 19.8) %. The lack of correlation between local perfusion and cerebral perfusion pressure indicated intact cerebral autoregulation. The systems were capable of monitoring both local perfusion and SO2 with stable signals in the NICU over 4 days. Further clinical studies are required to evaluate the optical systems’ potential for assessing the onset of secondary brain injury. Funding agencies: Swedish Research Council [621-2010-4216, 621-2013-6078]; ALF Grants Region Ostergotland [LIO-599651]

PURPOSE: Protoporphyrin (PpIX) fluorescence allows discrimination of tumor and normal brain tissue during neurosurgery. A handheld fluorescence (HHF) probe can be used for spectroscopic measurement of 5-ALA-induced PpIX to enable objective detection compared to visual evaluation of fluorescence. However, current technology requires that the surgeon either views the measured values on a screen or employs an assistant to verbally relay the values. An auditory feedback system was developed and evaluated for communicating measured fluorescence intensity values directly to the surgeon. METHODS: The auditory display was programmed to map the values measured by the HHF probe to the playback of tones that represented three fluorescence intensity ranges and one error signal. Ten persons with no previous knowledge of the application took part in a laboratory evaluation. After a brief training period, participants performed measurements on a tray of 96 wells of liquid fluorescence phantom and verbally stated the perceived measurement values for each well. The latency and accuracy of the participants' verbal responses were recorded. The long-term memorization of sound function was evaluated in a second set of 10 participants 2-3 and 7-12 days after training. RESULTS: The participants identified the played tone accurately for 98% of measurements after training. The median response time to verbally identify the played tones was 2 pulses. No correlation was found between the latency and accuracy of the responses, and no significant correlation with the musical proficiency of the participants was observed on the function responses. Responses for the memory test were 100% accurate. CONCLUSION: The employed auditory display was shown to be intuitive, easy to learn and remember, fast to recognize, and accurate in providing users with measurements of fluorescence intensity or error signal. The results of this work establish a basis for implementing and further evaluating auditory displays in clinical scenarios involving fluorescence guidance and other areas for which categorized auditory display could be useful. Funding agencies: Swedish Childhood Cancer foundation [MT 2013-0043]; Cancer network at Linkoping University (LiU-cancer); National Institutes of Health [P41 EB015902, P41 EB015898, R01EB014955, U24CA180918] OTP

To provide guidance during stereotactic biopsy in brain tumors, fluorescence spectroscopy was used in ten patients. It was shown that the fiber optical probe could provide real-time guidance with clear fluorescence in all patients.

Poster; International audience; I. INTRODUCTIONDeep brain stimulation (DBS) is a treatment for movement disorders such as Essential Tremor (ET). The implant position of the electrode is crucial. After preoperative surgical planning and intraoperative tests, the collected data is only “mentally” visualized and analyzed by the physician to decide on the optimal implant position of the DBS lead. We propose a method to combine and visually present this multitude of data for surgical decision making using patient-specific simulations of the electric field (EF) distribution, intraoperative accelerometry based tremor evaluations and direct-targeting technique of DBS.II. METHODFive ET patients participating in a clinical study (Ref: 2011-A00774-37/AU905, CPP Sud-Est 6, Clermont-Ferrand, France; written informed consent) were included in the presented protocol in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and 2008. Patients underwent routine stereotactic bilateral implantation of the DBS electrodes in the ventro-intermediate nucleus of the thalamus (VIM) [1].During planning, the target structure and the anatomical neighbours were outlined on patient images and an anatomical target was selected. Two microelectrodes were intraoperatively inserted per hemisphere on parallel trajectories. Stimulation tests were performed on 5 to 10 positions pertrajectory with several stimulation amplitudes per position to evaluate side effects and changes in tremor using an accelerometer fixed to the patient's wrist [2]. To estimate the extension of the stimulation, the EF was simulated using a finite-element model for several amplitudes per position related to different tremor improvements [3]. To identify the optimal implant position for chronic stimulation, we summarized all data in "Improvement Maps” by assigning to each voxel in the stimulation test region the highest improvement in tremor. Improvements were visualized on the patient-specific anatomical outlines using a green color scale and simulations of side-effects in red (Paraview, Kitware Inc). Postoperatively the optimal implant positions with the highest improvement were identified for the five patients.III. RESULTSThe clinical teams were able to identify the optimal implant positions with more ease and in less time compared to the routine discussion using pen and paper. Additionally, for 7 out of the 9 improvement maps, the highest improvement region was found to be in the posterior subthalamic area inferior and posterior to the surgical target, the VIM.IV. CONCLUSIONSVisual analysis of the results of intraoperative stimulation tests in form of improvement maps assists the clinicians in determining the optimal implant location of the chronic DBS lead and in comparing results between patients.

In the routine of stereotactic biopsy on suspected tumors located deep in the brain or patients with multiple lesions, tissue samples are harvested to determine the type of malignancy. Biopsies are taken from pre-calculated positions based on the preoperative radiologic images susceptible to brain shift. In such cases the biopsy procedure may need to be repeated leading to a longer operation time. To provide guidance for targeting diagnostic tumor tissue and to avoid vessel rupture on the insertion path of the tumor, an application specific fiber optic probe was developed. The setup incorporated spectroscopy for 5-aminolevulinic acid induced protopophyrin IX (PpIX) fluorescence in the tumor and laser Doppler for measuring microvascular blood flow which recorded backscattered light (TLI) at 780 nm and blood perfusion. The recorded signals were compared to the histopathologic diagnosis of the tissue samples (n=16) and to the preoperative radiologic images. All together 146 fluorescence and 276 laser Doppler signals were recorded along 5 trajectories in 4 patients. On all occasions strong PpIX fluorescence peaks were visible during real-time guidance. Comparing the gliotic tumor marginal zone with the tumor, the PpIX (51 vs. 528 a.u., [0-1790], p 0.05) and blood perfusion (8.3 vs. 17 a.u., [0-254], p > 0.05) were not significantly different. In conclusion, the optical guidance probe made real-time tumor detection and vessel tracking possible during the stereotactic biopsy procedures. Moreover, the fluorescence and blood perfusion in the tumor could be studied at controlled positions in the brain and the tumor.

BACKGROUND: Deep brain stimulation (DBS) in patients with severe, refractory Tourette syndrome (TS) has demonstrated promising but variable results thus far. The thalamus and anteromedial globus pallidus internus (amGPi) have been the most commonly stimulated sites within the cortico-striato thalamic circuit, but an optimal target is yet to be elucidated. OBJECTIVES: This study of 15 patients with long-term amGPi DBS for severe TS investigated whether a specific anatomical site within the amGPi correlated with optimal clinical outcome for the measures of tics, obsessive compulsive behaviour (OCB), and mood. METHODS: Validated clinical assessments were used to measure tics, OCB, quality of life, anxiety, and depression before DBS and at the latest follow-up (17-82 months). Electric field simulations were created for each patient using information on electrode location and individual stimulation parameters. A subsequent regression analysis correlated these patient-specific simulations to percentage changes in outcome measures in order to identify any significant voxels related to clinical improvement. RESULTS: A region within the ventral limbic GPi, specifically on the medial medullary lamina in the pallidum at the level of the AC-PC, was significantly associated with improved tics but not mood or OCB outcome. CONCLUSIONS: This study adds further support to the application of DBS in a tic-related network, though factors such as patient sample size and clinical heterogeneity remain as limitations and replication is required. Funding agencies: National Institute of Health Research (NIHR) Biomedical Research Centre at the UCL Institute of Neurology and UCLH-National Hospital for Neurology and Neurosurgery, London, UK; Swedish Research Council (Vetenskapsradet) [2016-03564]; Swedish Foundation fo

Background The mechanism by which deep brain stimulation of the nucleus subthalamicus improves Parkinson’s disease symptoms remains unclear. In a previous perioperative study, we showed that there ...

Background: Intracerebral hemorrhage (ICH) is the most feared complication in deep brain stimulation (DBS) surgery. The aim of the study was to evaluate patient safety and outcome using laser Doppler flowmetry (LDF) as guidance tool during DBS implantations. Methods: An LDF probe adapted for the stereotactic system was used as guide for creation of the trajectory. The microcirculation along 83 preplanned trajectories was measured with the guide during DBS surgery for movement disorders. The microvascular blood flow levels were investigated for all measurement positions. Medical record and postoperative radiology were retrospectively reviewed. Results: Of 2,963 measurement positions, 234 (7.9%) showed at least a doubled blood flow compared to the surrounding tissue. Of these 2.2% had a more than 5 times higher blood flow in front of the probe tip. Along 1 trajectory, a small ICH was detected during surgery. Increased blood flow was more common close to sulci and verticals. Conclusion: Real-time LDF measurement of the microcirculation using a forward-looking probe during DBS surgery can detect blood flow peaks and further minimize the risk of developing ICH. No separate guide tube is necessary as the probe also creates the trajectory for the DBS lead.

Background Visualization of the tumor is crucial for differentiating malignant tissue from healthy brain during surgery, especially in the tumor marginal zone. The aim of the study was to introduce a fluorescence spectroscopy-based hand-held probe (HHF-probe) for tumor identification in combination with the fluorescence guided resection surgical microscope (FGR-microscope), and evaluate them in terms of diagnostic performance and practical aspects of fluorescence detection. Material and Methods Eighteen operations were performed on 16 patients with suspected high-grade glioma. The HHF-probe and the FGR-microscope were used for detection of protoporphyrin (PpIX) fluorescence induced by 5-aminolevulinic acid (5-ALA) and evaluated against histopathological analysis and visual grading done through the FGR-microscope by the surgeon. A ratio of PpIX fluorescence intensity to the autofluorescence intensity (fluorescence ratio) was used to quantify the spectra detected by the probe. Results Fluorescence ratio medians (range 0 – 40) measured by the probe were related to the intensity of the fluorescence in the FGR-microscope, categorized as “none” (0.3, n = 131), “weak” (1.6, n = 34) and “strong” (5.4, n = 28). Of 131 “none” points in the FGR-microscope, 88 (67%) exhibited fluorescence with the HHF-probe. For the tumor marginal zone, the area under the receiver operator characteristics (ROC) curve was 0.49 for the FGR-microscope and 0.65 for the HHF-probe. Conclusions The probe was integrated in the established routine of tumor resection using the FGR-microscope. The HHF-probe was superior to the FGR-microscope in sensitivity; it detected tumor remnants after debulking under the FGR-microscope. The combination of the HHF-probe and the FGR-microscope was beneficial especially in the tumor marginal zone. Funding agencies: Swedish Governmental Agency for Innovation Systems (Vinnova); Swedish Foundation for Strategic Research (SSF); Swedish Research Council (VR) [311-2006-7661, 523-2013-2735]; NovaMedTech; Swedish Childhood Cancer Foundation [MT 2013-0043]; ALF Grants Region

Poster; International audience; Despite an increasing use of deep brain stimulation (DBS), the fundamental mechanisms underlying therapeutic and adverse effects as well as the optimal stimulation site remain largely unknown. The aim of the present study was to develop a method to correlate electric field simulations for intraoperative stimulation tests with quantitatively evaluated symptom improvement and patient specific anatomy to estimate the optimal stimulation site. One essential tremor patient, bilaterally implanted in the ventro-intermediate nucleus (Vim) has been included. Preoperatively Vim and its anatomic neighbors were manually outlined according to spontaneous MRI contrasts using the commercial planning software from where the structures could be exported via a specifically designed interface. During the intervention, intraoperative stimulation tests were performed on two trajectories per hemisphere (8 positions per trajectory). The change in tremor at each stimulation position compared to baseline was evaluated using a 3-axis accelerometer. Based on accelerometer data, two stimulation amplitudes (low and high improvement) were identified per position and corresponding electric-field isosurfaces (0.2V/mm) were simulated. As each voxel in the region of interest may be part of several isosurfaces -each surface depicting one amplitude responsible for one improvement in tremor- the voxel was assigned to the isosurface representing the minimum improvement using Matlab. Data were imported into Paraview (VTK based 3D visualization software). Color-coded minimum 3D-improvement maps were visualized on the patient's MR images together with the manually outlined anatomical structures. The resulting visualization was evaluated by clinicians.The software allowed 3D visualization as well as orthographic slices parallel to the trajectory. Clinicians confirmed that it enables the identification of the most effective stimulation areas with respect to the anatomy. This new concept based on quantitative symptom evaluation, electric field simulations, and patient specific anatomical data will allow the analysis of a high amount of intraoperative data which might help to elucidate the mechanism of action of DBS.

Background/aims: Many subjects have stated that they can sense the laser light during cutaneous laser Doppler recordings. The aim of the study was therefore to investigate if low power laser light used in laser Doppler systems affects the sensory nerves. Methods: Single point recording as well as imaging was performed with the laser Doppler perfusion imager at the finger pulp, dorsal and ventral side of the hand and the forearm skin in 12 healthy volunteers. The hypothesis “the subject can not sense the laser beam” was tested by double blind random control of the on-off pattern of the laser light reaching the skin. In total, 96 trials (each including 12 recordings) were performed. Furthermore, it was investigated if the blood flow level was influenced by the subjects “sense” of being measured. Results: The hypothesis was rejected in 92 out of 96 trials. Three of the trials that could not be rejected were recorded from the same subject. In further trials no reproducibility was found. The blood flow level was not influenced by the subjects “sense” of being measured. Conclusions: In general, the laser light used in laser Doppler imaging systems does not influence the sensory nerves. However, it can not be excluded that the laser light used in laser Soppier perfusion imaging (LDPI) affects sensory nerves under unknown circumstances and at specific spots in cutaneous tissue.

Cutaneous microdialysis enables in vivo sampling of substances in the extracellular space in human skin. It is usual to allow an equilibration time to elapse after tissue trauma caused by probe insertion. One of the prerequisites for correct interpretation of data is detailed knowledge of the effect of insertion and presence of the probe in the skin, especially in the tissue closest to the membrane.Laser Doppler perfusion imaging was used to investigate the time required for blood perfusion to return to near normal levels after probe insertion. The standard system was used in parallel with a high resolution system. The latter gave 3600 measurement sites in an area of 2 cm × 2 cm and thus enabled a detailed study of circulatory changes immediately around the membrane. Perfusion levels prior to probe insertion as well as the perfusion response to probe insertion were recorded by both systems.In agreement with previous findings, the perfusion levels were found to return to near normal levels within 60 min. Individual variations were, however, seen. High resolution laser Doppler perfusion imaging provided detailed visualisation of these variations both spatially and over time.High resolution laser Doppler perfusion imaging is superior to standard laser Doppler perfusion imaging in detailed visualisation of the variations in skin blood perfusion after microdialysis probe insertion. The individual variations seen can be of importance in the interpretation of microdialysis data.

Background/aims: Laser Doppler perfusion imaging (LDPI) permits measurement of skin blood flow changes in patch test reactions. It is, as yet, unclear how collected data can best be handled and presented in order to maximize the possible discriminatory advantage of the imaging technique and to make the selection of data for statistical analysis as objective as possible. The aim of the present study was to compare a new software program (LDISOFT) for the analysis of LDPI images with the built-in standard statistical functions in the LDPI system (PIM 1.0). In addition, a modification of the software was used to gather additional data by performing sequential perfusion images. Methods: A dithranol cream was applied under Finn chambers for 30, 60 and 90 min on the ventral forearm skin of three volunteers. Photographic documentation and LDPI recordings were performed immediately after the removal of the Finn chambers and at 24, 48, 72 and 96 h. By the use of the above mentioned software, rectangular and threshold selected regions of interest were used to find an optimal way of calculating the mean perfusion and extent of the reactions. Results: An LDISOFT threshold of 2 V was adequate and showed agreement (r

Background and Objective: Glioblastoma multiforme is a highly malignant primary brain tumor. It has no border but at best a marginal zone, however, invisible to the surgeon. An optical touch pointe ...

In this paper, we investigate the possibility of using accurate prediction models for the prediction of protoporphyrin bleaching dynamics to achieve photobleaching-insensitive methods to improve the evaluation of data in an existing clinical fluorescence-guided resection technique. To simulate the scenario, measurements were carried out in vivo on skin of healthy volunteers using a compact fiber-based fluorescence spectroscopy system. We have developed an effective method for the parameterization of sequences of bleaching spectra. We analyze convergence and decay rates with respect to initial conditions and excitation irradiance. We also discuss the consequences and the potential for bleaching-insensitive measurements and their applicability in a few examples from in vivo open brain surgery.

Background and Objective: Total tumor resection in patients with glioblastoma multiforme (GBM) is difficult to achieve due to the tumor’s infiltrative way of growing and morphological similarity to the surrounding functioning brain tissue. The diagnosis is usually subjectively performed using a surgical microscope. The objective of this study was to develop and evaluate a hand-held optical touch pointer using a fluorescence spectroscopy system to quantitatively distinguish healthy from malignant brain tissue intraoperatively. Study Design/Materials and Methods: A fluorescence spectroscopy system with pulsed modulation was designed considering optimum energy delivery to the tissue, minimal photobleaching of PpIX and omission of the ambient light background in the operating room (OR). 5-Aminolevulinic acid (5-ALA) of 5 mg/kg body weight was given to the patients with a presumed GBM prior to surgery. During the surgery a laser pulse at 405 nm was delivered to the tissue. PpIX in glioblastoma tumor cells assigned with peaks at 635 and 704 nm was detected using a fiber optical probe. Results/Conclusion: By using the pulsed fluorescence spectroscopy, PpIX fluorescence is quantitatively detected in the GBM. An effective suppression of low power lamp background from the recorded spectra in addition to a significant reduction of high power surgical lights is achieved. Lasers Surg. Med. 42:9–14, 2010. 2010 Wiley-Liss, Inc.

Aim: The aim of this study is to investigate reflected light intensity combined with impedance for navigation aid during stereotactic neurosurgery. Methods: During creation of 21 trajectories for stereotactic implantation of deep brain stimulation electrodes in the globus pallidus internus or subthalamus (zona incerta or subthalamic nucleus), impedance at 512 kHz and reflected light intensity at 780 nm were measured continuously and simultaneously with a radio frequency electrode containing optical fibres. The signals were compared with anatomy determined from pre- and postoperative MRI and CT. The measurements were performed within minutes and signal analysis was done post-operatively. Results: Reflected light intensity was low from cortex, lateral ventricle, caudate nucleus and putamen. It was intermediate from globus pallidus and thalamus while it was high from subcortical white matter, internal capsule and the subthalamus. The electric impedance was less consistent but generally low in the cortex, intermediate in subcortical white matter, the putamen, the globus pallidus and the thalamus and high in the internal capsule and the subthalamus. Conclusion: Reflected light intensity and electric impedance give complementary information about passed tissue and the combination seems promising for navigation aid during stereotactic neurosurgery. Original Publication: Johannes D. Johansson, Patric Blomstedt, Neda Haj-Hosseini, Tommy Bergenheim, Ola Eriksson and Karin Wårdell, Combined diffuse light reflectance and electric impedance measurements for navigation aid in deep brain surgery, 2009, Stereotactic and Functional Neurosurgery, (87), 2, 105-113. http://dx.doi.org/10.1159/000202977 Copyright: S. Karger AG http://www.karger.com/

Diffuse reflectance spectroscopy as a method for improving intracerebral guidance during functional neurosurgery has been investigated. An optical probe was developed for measurements during stereotactic and functional neurosurgery in man. The aim of the study was to investigate the spectral differences between white and grey matter and between white matter and functional targets. Diffuse reflectance spectroscopy measurements in ten patients were recorded at incremental steps towards and in three different functional targets (STN, GPi and Zi). The recorded spectra along the trajectory were sorted into white or grey matter, based on preoperative MRI images or the recorded spectral shape and intensity. The difference between tissue types was calculated as a quotient. Significant intensity differences between white and grey matter were found to be at least 14% (p < 0.05) and 20% (p < 0.0001) for MRI and spectral-sorted data respectively. The reflectance difference between white matter and the functional targets of GPi was higher than for STN and Zi. The results indicate that diffuse reflectance spectroscopy has a potential to be developed to a suitable complement to other intracerebral guidance methods.

A better understanding of bioelectrodes can be acquired with extended testing, which will lead to better methodology and data quality. Today electrodes are evaluated for intraelectrode differences ...

The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon's action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1-40 in incremental steps of 1) and the node drive potential (0-2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxon's programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems.

Human in vivo microdialysis technique can be used to measure cytokines in contact reactions.

Although the therapeutic effect of deep brain stimulation (DBS) is well recognized, a fundamental understanding of the mechanisms responsible is still not known. In this study finite element method (FEM) modelling and simulation was used in order to study relative changes of the electrical field extension surrounding a monopolar DBS electrode positioned in grey matter. Due to the frequently appearing cystic cavities in the DBS-target globus pallidus internus, a nucleus of grey matter with and without a cerebrospinal fluid filled cystic cavity was modelled. The position, size and shape of the cyst were altered in relation to the electrode. The simulations demonstrated an electrical field around the active element with decreasing values in the radial direction. A stepwise change was present at the edge between grey and white matters. The cyst increased the radial extension and changed the shape of the electrical field substantially. The position, size and shape of the cyst were the main influencing factors. We suggest that cystic cavities in the DBS-target may result in closely related unexpected structures or neural fibre bundles being stimulated and could be one of the reasons for suboptimal clinical effects or stimulation-induced side effects.

The aim of this study was to evaluate in vivo a laser Doppler measurement system in porcine brain tissue during thermal lesioning. A 2-mm monopolar radiofrequency lesioning electrode was equipped with optical fibers in order to monitor the lesioning procedure. Laser Doppler and backscattered light intensity signals were measured along the electrode trajectory and during bilateral lesioning in the central gray (70, 80 and 90°C, n = 14). The time course of the coagulation process could be followed by optical recordings. Two separate groups of tissue were identified from the intensity signals. The changes in the perfusion levels in both groups displayed significant changes (p < 0.05, n = 48) at all temperature settings, while backscattered light intensity was significant for only one group at the different temperatures (p < 0.05, n = 39). These results indicate that optical measurements correlate with lesion development in vivo. The study also indicates that it is possible to follow the lesioning process intra-operatively.

Electrocardiogram (ECG)-triggered laser Doppler perfusion monitoring (LDPM) was used to assess myocardial perfusion, with minimum myocardial tissue motion influence, during coronary artery bypass grafting (CABG). Thirteen subjects were investigated at six phases: pre- and post-CABG; post aorta cross-clamping; pre and post left internal mammary artery (LIMA) graft declamping; and post aorta declamping. The perfusion signal was calculated in late systole and late diastole, with expected minimum tissue motion, and compared with arrested heart measurements. Patient conditions or artifacts caused by surgical activity made it impossible to perform and analyse data in all six phases for some patients. No significant (n = 5) difference between perfusion signals pre- and post-CABG was found. Diastolic perfusion signal levels were significantly (p0.02) lower compared with systolic levels. After aorta cross-clamping, the signal level was almost zero. A distinct perfusion signal increase after LIMA and aorta declamping, compared with pre-LIMA declamping, was found in ten cases out of 13. A significantly (p0.04) lower perfusion signal in the arrested heart compared with in the beating heart was registered. Influence from mechanical ventilation was observed in 14 measurements out of 17. In conclusion, ECG-triggered LDPM can be used to assess myocardial perfusion during CABG. Perfusion signals were lower in the arrested heart compared with in the beating heart and in late diastole compared with late systole. No significant difference between pre- and post-CABG was found.

Knowledge of the optical properties of tissues can be applied in numerous medical and scientific fields, including cancer diagnostics and therapy. There are many different ways of determining the optical properties of turbid media. The paper describes measurements of the optical properties of porcine brain tissue using novel instrumentation for simultaneous absorption and scattering characterisation of small turbid samples. Integrating sphere measurements are widely used as a reference method for determination of the optical properties of relatively thin turbid samples. However, this technique is associated with bulky equipment, complicated measuring techniques, interference compensation techniques and inconvenient sample handling. It is believed that the sphere for some applications can be replaced by a new, compact device, called the combined angular and spatially resolved head sensor, to measure the optical properties of thin turbid samples. The results compare very well with data obtained with an integrating sphere for well-defined samples. The instrument was shown to be accurate to within 12% for microa and 1% for micro's in measurements of intralipid-ink samples. The corresponding variations of data were 17% and 2%, respectively. The reduced scattering coefficient for porcine white matter was measured to be 100 cm(-1) at 633 nm, and the value for coagulated brain tissue was 65 cm(-1). The corresponding absorption coefficients were 2 and 3 cm(-1), respectively.

Development of a non-invasive method for measuring the blood glucose level is an urgent necessity, and putting such a method into practical use will enable some of the physical and mental stress that patients with diabetes have to endure to be removed. To realise a non-invasive blood glucose monitor, the gingival crevicular fluid (GCF) was measured. A GCF-collecting device was developed that was designed to be disposable, biocompatible and small enough to be inserted in the gingival crevice for collection of a sub-microlitre sample of GCF. Also, a high-sensitivity glucose testing tape incorporated in the device was developed. Red laser light in a portable optical device measured the colour density of the testing tape. Standard glucose solutions were used to investigate the measurement accuracy of the GCF glucose monitor and showed a correlation coefficient of R = 0.99 (n = 20) between the optical density and the glucose levels. The GCF glucose monitor was evaluated on healthy Swedish and Japanese adults (n = 10) and both GCF glucose levels (GCFLs) and blood glucose levels (BGLs) were measured in conjunction with meal loads. The GCFLs were about 1/10-1/560 lower than the BGLs. No difference in the range of GCFLs between the Swedish and the Japanese subjects was observed. Therefore it was concluded that physique, body mass index and life-style, such as dietary habit, did not significantly influence the GCFLs. Further, the correlation coefficients of all the subjects were 0.70 and 0.88 with each group. It was suggested that GCF could be used as a method of non-invasive blood glucose measurement.

Background: Phototesting based on a single exposure to a divergent ultraviolet B (UVB) beam with radially decreasing UVB doses can be used to determine an individual's minimal erythema dose (MED). ...

Laser Doppler perfusion monitoring (LDPM) can be used for monitoring myocardial perfusion in the non-beating heart. However, the movement of the beating heart generates large artifacts. Therefore the aim of the study was to develop an LDPM system capable of correlating the laser Doppler signals to the cardiac cycle and to process the signals to reduce the movement artifacts. Measurements were performed on three calves, both on the normal beating heart and during occlusion of the left anterior descending coronary artery (LAD). The recorded LDPM signals were digitally processed and correlated to the sampled ECG. Large variations in the output (perfusion) and DC signals during the cardiac cycle were found, with average coefficients of variation of 0.36 and 0.14 (n = 14), respectively. However, sections with a relatively low, stable output signal were found in late diastole, where the movement of the heart is at a minimum. Occlusion of the LAD showed the importance of recording the laser Doppler signals at an appropriate point in the cardiac cycle, in this case late systole, to minimise movement artifacts. It is possible to further reduce movement artifacts by increasing the lower cutoff frequency when calculating the output signal.

Background: Deep brain stimulation (DBS) systems in current mode and new lead designs are recently available. To switch between DBS-systems remains complicated as clinicians may lose their reference for programming. Simulations can help increase the understanding. Objective: To quantitatively investigate the electric field (EF) around two lead designs simulated to operate in voltage and current mode under two time points following implantation. Methods: The finite element method was used to model Lead 3389 (Medtronic) and 6148 (St Jude) with homogenous surrounding grey matter and a peri-electrode space (PES) of 250 μm. The PES-impedance mimicked the acute (extracellular fluid) and chronic (fibrous tissue) time-point. Simulations at different amplitudes of voltage and current (n=236) were performed using two different contacts. Equivalent current amplitudes were extracted by matching the shape and maximum EF of the 0.2 V/mm isolevel. Results: The maximum EF extension at 0.2 V/mm varied between 2-5 mm with a small difference between the leads. In voltage mode EF increased about 1 mm at acute compared to the chronic PES. Current mode presented the opposite relationship. Equivalent EFs for lead 3389 at 3 V were found for 7 mA (acute) and 2.2 mA (chronic). Conclusions: Simulations showed a major impact on the electric field extension between postoperative time points. This may explain the clinical decisions to reprogram the amplitude weeks after implantation. Neither the EF extension nor intensity is considerably influenced by the lead design. However, the EF distribution is affected by the larger contact of Lead 6148 generating an electric field below the tip.

Models and simulations are commonly used to study deep brain stimulation (DBS). Simulated stimulation fields are often defined and visualized by electric field isolevels or volumes of tissue activated (VTA). The aim of the present study was to evaluate the relationship between stimulation field strength as defined by the electric potential V, the electric field E, and the divergence of the electric field ∇(2) V, and neural activation. Axon cable models were developed and coupled to finite-element DBS models in three-dimensional (3-D). Field thresholds ( VT , ET, and ∇(2) VT ) were derived at the location of activation for various stimulation amplitudes (1 to 5 V), pulse widths (30 to 120 μs), and axon diameters (2.0 to 7.5 μm). Results showed that thresholds for VT and ∇(2) VT were highly dependent on the stimulation amplitude while ET were approximately independent of the amplitude for large axons. The activation field strength thresholds presented in this study may be used in future studies to approximate the VTA during model-based investigations of DBS without the need of computational axon models. This work was supported by the European Union's Seventh Framework Programme IMPACT (Grant 305814) and by the Swedish Research Council (Grant 621-2013-6078). Asterisk indicates corresponding author.

This study describes the production, under strictly standardized and controlled conditions, of radiofrequency lesions with identical neurogenerator settings: in vitro in two different albumin solutions (nongelatinous and gelatinous) and in vivo in the thalamus of the pig.The radiofrequency lesions were investigated in vitro by the use of a specially designed video system and in vivo by magnetic resonance imaging. Moreover, the size of the in vivo lesions was estimated with the use of histological sectioning. The statistical analysis included the calculation of a correlation coefficient for the length, width, and volume for each lesion estimation.A high correlation (R = 0.96, P0.005; n = 14) was found between clot sizes in the two albumin solutions. Albumin clots generated in gelatinous albumin showed systematically larger volumes. In the pig, two concentric zones were seen in all magnetic resonance images and all histological preparations. The width correlation of the completely coagulated brain tissue (inner zones) was R = 0.94, P0.005, and n = 7. The corresponding correlation between magnetic resonance images and gelatinous albumin was R = 0.93, P0.005, and n = 7. As a rule, the in vitro clots were smaller than the outer zone but larger than the inner zone of the magnetic resonance imaging-recorded lesions for all of the electrode and temperature combinations tested. In vivo lesions generated with the same electrode and parameter settings showed high reproducibility.The value of presurgical electrode tests to validate the electrode function and lesion size in vitro has become evident in this study, which shows a high correlation between the in vitro albumin clots and the in vivo lesions observed on magnetic resonance images.

This report reviews how to set up a laser Doppler perfusion imaging system intended for visualization of skin blood perfusion, capture images and evaluate the results obtained. A brief summary of related papers published in the literature within the areas of skin irritant and allergy patch testing, microdialysis and skin tumour circulation is presented, as well as early applications within other fields such as diabetology, wound healing and microvascular research.

Despite an increasing use of deep brain stimulation (DBS) the fundamental mechanisms underlying therapeutic and adverse effects remain largely unknown. The simulations of electric entities are increasingly used to evaluate stimulation effects. To our knowledge, so far no group has considered such simulations combined with a side effect analysis of data obtained during intraoperative test stimulations. The aim of the present paper is to introduce a method allowing patient-specific electric field simulations for stimulation amplitudes inducing side effects during deep brain stimulation surgery. Two female patients presenting essential tremor, both bilaterally implanted in the ventral intermediate nucleus (VIM) region in the Clermont-Ferrand University Hospital were included in the study. Intraoperative test stimulations were performed on central and posterior trajectories in each hemisphere at 8-9 positions per trajectory. At each position in addition to the evaluation of the therapeutic effects, side effects such as pyramidal symptoms and paresthesia without localization indicator or paresthesia with localization indicated by the patient (in the hand or in the fingers) were noted. The anatomical structures such as VIM and its neighbors were preoperatively manually outlined using the iPlan software (Brainlab, Feldkirchen, Germany) according to spontaneous MRI contrasts [1]. The so identified structures were exported via a specifically designed interface (VVLink, Brainlab, Feldkirchen, Germany). Whenever side effects occurred the inducing stimulation amplitude was chosen for electric field simulations. A finite element method [2] was applied to calculate the electric field distribution. Conductivity values were deduced from the patient's T1 weighted MRI. An isofieldlevel of 0.2V/mm was chosen and the points of the isosurface were exported. They were visualized together with the extracted anatomical structures and the trajectories. The different structures present inside the volume defined by the isofield level and their appearance were determined. Combinations of structures always appearing together for a specific side effect were identified. For both patients, 8 electric field simulations were successfully performed. A first analysis showed that pyramidal effects appear when parts of the ventrooral nucleus (VO) and the VIM were present inside the isosurface. The ventrocaudal lateral nucleus (VCL), the ventrocaudal medial nucleus (VCM) and the VIM were among the identified structures in hand paresthesia (

International audience

The principles of cancer treatment has for years been radical resection of the primary tumor. In the oncologic surgeries where the affected cancer site is close to the lymphatic system, it is as important to detect the draining lymph nodes for metastasis (lymph node mapping). As a replacement for conventional radioactive labeling, indocyanine green (ICG) has shown successful results in lymph node mapping; however, most of the ICG fluorescence detection techniques developed are based on camera imaging. In this work, fluorescence spectroscopy using a fiber-optical probe was evaluated on a tissue-like ICG phantom with ICG concentrations of 6-64 μM and on breast tissue from five patients. Fiber-optical based spectroscopy was able to detect ICG fluorescence at low intensities; therefore, it is expected to increase the detection threshold of the conventional imaging systems when used intraoperatively. The probe allows spectral characterization of the fluorescence and navigation in the tissue as opposed to camera imaging which is limited to the view on the surface of the tissue

In a previous publication from our group, phototesting based on a single exposure to a divergent UVB beam with radially decreasing irradiance values was suggested. The aim of the present study was to evaluate technical, practical and biological aspects of the suggested method in normal subjects. Twenty healthy volunteers were provoked on the back with both a collimated beam (four fixed doses, in circular areas with a diameter of 1.5 cm) and the divergent beam (a continuous, radially attenuating dose spectrum covering an area with a diameter of 4.5 cm). Eleven of the subjects were subjected to double provocation with the divergent beam. Assessment was carried out at 6 and 24 h after exposure by measuring the diameter of the reactions both visually and by mapping the skin blood flow change with laser Doppler perfusion imaging (LDPI). Minimal erythemal dose (MED) was determined for both the collimated and the divergent provocation. The reaction diameters were used to decide MED by combination to a mm for mm mapped dose spectrum of the divergent beam profile. Dose-response curves were plotted using the quantitative response data of the LDPI-images against the corresponding dosimetry data. No systematic difference could be proven between LDPI and visual diameters and a 95% confidence interval for the mean difference was calculated to (-0.8, 2.0). Slightly greater diameters were found at the visual assessment performed at 6 h compared to 24 h (95% confidence interval (-0.1, 2.8)). Double provocation showed a good reproducibility both for the visual and the LDPI assessment (P

Background/aims: Cutaneous microdialysis can be used to follow the pharmacology and metabolism of an inflammatory reaction. It is assumed that an equilibration period compensates for the trauma of ...

Background/aims: Confident diagnosis of photosensitivity in patients with light dermatoses requires skin exposure to well determined ultraviolet (UV) light doses, most often from a solar simulator ...

Background and Objectives When given intracutaneously, capsaicin can cause burning pain by central propagation in thin afferents, as well as neurogenic vasodilatation, reflecting antidromic conduction in the same fibers. We wanted to test the hypothesis that an intravenous regional block (IVRA) inhibits these two phenomena to a similar degree. Methods Sixteen healthy volunteers participated. A bilateral IVRA was performed by simultaneously injecting mepivacaine in one arm and normal saline in the other in a randomized, double-blind manner. Ten minutes after release of the tourniquet, neurogenic inflammation was inflicted in each forearm by intracutaneous capsaicin. Microvascular skin blood flow was measured with a laser Doppler perfusion imager. The area of the flare and the flow therein were measured, taking into account the change in baseline caused by mepivacaine treatment and the postischemic hyperemia. Pain was repeatedly evaluated by visual analog scale. Results The reactive hyperemia following arterial occlusion was less in the mepivacaine-treated arm 10 minutes after tourniquet release (P = .026). Intracutaneous capsaicin elicited a flare in both arms. The area of the flare was smaller 10 minutes after capsaicin (P = .009) in the mepivacaine-treated arm. There was no difference between the arms concerning the mean blood flow within the flare or in ischemic or capsaicin-induced pain. Conclusions Mepivacaine, given as an IVRA, had no effect on the post-IVRA sensory function of thin afferents but differentially decreased the spread of the capsaicin-induced flare.

Fluorescence guidance using 5-aminolevulinic acid (5-ALA) for brain tumor resection is a recent technique applied to the highly malignant brain tumors. Five-ALA accumulates as protoporphyrin IX fluorophore in the tumor cells in different concentrations depending on the tumor environment and cell properties. Our group has developed a fluorescence spectroscopy system used with a hand-held probe intra-operatively. The system has shown improvement of fluorescence detection and allows quantification that preliminarily correlates with tumor malignancy grade during surgery. However, quantification of fluorescence is affected by several factors including the initial fluorophore concentration, photobleaching due to operating lamps and attenuation from the blood. Accordingly, an optical phantom was developed to enable controlled fluorescence measurements and evaluation of the system outside of the surgical procedure. The phantom mimicked the optical properties of glioma at the specific fluorescence excitation wavelength when different concentrations of the fluorophore were included in the phantom. To allow evaluation of photobleaching, kinetics of fluorophore molecules in the phantom was restricted by solidifying the phantoms. Moreover, a model for tissue autofluorescence was added. The fluorescence intensity’s correlation with fluorophore concentration in addition to the photobleaching properties were investigated in the phantoms and were compared to the clinical data measured on the brain tumor.

Deep brain stimulation (DBS) is an effective treatment for movement disorders e.g. Parkinson’s disease. Thin electrodes are implanted into the deep brain structures by means of stereotactic technique and electrical stimulations are delivered to the brain tissue. Accuracy and safety during the implantation is important for optimal stimulation effect and minimization of bleedings. In addition to microelectrode recording and impedance measurements, intraoperative optical measurements using laser Doppler perfusion monitoring (LDPM) have previously been suggested as guidance tool during stereotactic DBS implantations.

Laser Doppler perfusion imaging offers a new modality for in vivo monitoring of the superficial blood perfusion in biological tissue. In this study, the superficial blood perfusion of malignant non-melanoma skin tumours and the surrounding normal skin was measured in conjunction with photodynamic therapy (PDT) using topical delta-aminolaevulinic acid (ALA)-induced protoporphyrin IX as a photosensitizer. The results clearly show that, in contradiction to PDT with the intravenously administered photosensitizer Photofrin, no direct vascular damage can be seen. With the topical sensitization the blood perfusion is increased immediately after the treatment irradiation. The increased blood flow is seen up to a week after treatment, in a similar way as for an inflammatory reaction. Despite this, all basal cell carcinoma and squamous cell carcinoma in situ lesions in this study healed without any sign of residual tumour after the treatment, suggesting an efficient direct tumour cell destruction induced by PDT.

A patient-specific modelling technique for simulation of the electric field surrounding deep brain stimulation (DBS) electrodes has been adapted to T1 and T2-weigthed, proton density (PrD) and spoiled gradient echo (SPGR) magnetic resonance imaging (MRI) sequences. Electrical conductivity (σ) assignment of gray and white matter was made dependent on the neuromodulator settings. Nine brain models with different σ were created. Four PrD/SPGR images tuned differently were fused. Five models based on the same T2 batch of MRI were set up with different σ. Finite element simulations (2, 3, 4, 5 V) of bilateral DBS electrodes positioned in the globus pallidus internus (GPi) were created. The electric field volumes were calculated for isosurfaces of 0.2V/mm and 0.1V/mm. A reference T2-model was used for comparison. At 0.1V/mm white matter had a larger influence when set to ten times the original value. Homogenous models responded similar. It was found that the method was sensitive to very small electrical conductivity variations and consequently to the corresponding anatomical variations in tissue type.

Microdialysis of the basal ganglia was recently used to study neurotransmitter levels in relation to deep brain stimulation. In order to estimate the anatomical origin of the obtained data, the maximum tissue volume of influence (TVImax) for a microdialysis catheter was simulated using the finite element method. This study investigates the impact of brain heterogeneity and anisotropy on the TVImax using diffusion tensor imaging (DTI) to create a second-order tensor model of the basal ganglia. Descriptive statistics showed that the maximum migration distance for neurotransmitters varied by up to 55% (n = 98,444) for DTI-based simulations compared with an isotropic reference model, and the anisotropy differed between different targets in accordance with theory. The size of the TVImax was relevant in relation to the size of the anatomical structures of interest, and local tissue properties should be accounted for when relating microdialysis data to their anatomical targets.