Towards Tracking of Deep Brain Stimulation Electrodes Using an Integrated Magnetometer.

This paper presents a tracking system using magnetometers, possibly integrable in a deep brain stimulation (DBS) electrode. DBS is a treatment for movement disorders where the position of the implant is of prime importance. Positioning challenges during the surgery could be addressed thanks to a magnetic tracking. The system proposed in this paper, complementary to existing procedures, has been designed to bridge preoperative clinical imaging with DBS surgery, allowing the surgeon to increase his/her control on the implantation trajectory. Here the magnetic source required for tracking consists of three coils, and is experimentally mapped. This mapping has been performed with an in-house three-dimensional magnetic camera. The system demonstrates how magnetometers integrated directly at the tip of a DBS electrode, might improve treatment by monitoring the position during and after the surgery. The three-dimensional operation without line of sight has been demonstrated using a reference obtained with magnetic resonance imaging (MRI) of a simplified brain model. We observed experimentally a mean absolute error of 1.35 mm and an Euclidean error of 3.07 mm. Several areas of improvement to target errors below 1 mm are also discussed.

Cortical stimulation in aphasia following ischemic stroke: toward model-guided electrical neuromodulation.

The aim of this paper is to integrate different bodies of research including brain traveling waves, brain neuromodulation, neural field modeling and post-stroke language disorders in order to explore the opportunity of implementing model-guided, cortical neuromodulation for the treatment of post-stroke aphasia. Worldwide according to WHO, strokes are the second leading cause of death and the third leading cause of disability. In ischemic stroke, there is not enough blood supply to provide enough oxygen and nutrients to parts of the brain, while in hemorrhagic stroke, there is bleeding within the enclosed cranial cavity. The present paper focuses on ischemic stroke. We first review accumulating observations of traveling waves occurring spontaneously or triggered by external stimuli in healthy subjects as well as in patients with brain disorders. We examine the putative functions of these waves and focus on post-stroke aphasia observed when brain language networks become fragmented and/or partly silent, thus perturbing the progression of traveling waves across perilesional areas. Secondly, we focus on a simplified model based on the current literature in the field and describe cortical traveling wave dynamics and their modulation. This model uses a biophysically realistic integro-differential equation describing spatially distributed and synaptically coupled neural networks producing traveling wave solutions. The model is used to calculate wave parameters (speed, amplitude and/or frequency) and to guide the reconstruction of the perturbed wave. A stimulation term is included in the model to restore wave propagation to a reasonably good level. Thirdly, we examine various issues related to the implementation model-guided neuromodulation in the treatment of post-stroke aphasia given that closed-loop invasive brain stimulation studies have recently produced encouraging results. Finally, we suggest that modulating traveling waves by acting selectively and dynamically across space and time to facilitate wave propagation is a promising therapeutic strategy especially at a time when a new generation of closed-loop cortical stimulation systems is about to arrive on the market.

Probabilistic stimulation mapping from intra-operative thalamic deep brain stimulation data in essential tremor.

Deep brain stimulation (DBS) is a therapy for Parkinson's disease (PD) and essential tremor (ET). The mechanism of action of DBS is still incompletely understood. Retrospective group analysis of intra-operative data recorded from ET patients implanted in the ventral intermediate nucleus of the thalamus (Vim) is rare. Intra-operative stimulation tests generate rich data and their use in group analysis has not yet been explored.Objective.To implement, evaluate, and apply a group analysis workflow to generate probabilistic stimulation maps (PSMs) using intra-operative stimulation data from ET patients implanted in Vim.Approach.A group-specific anatomical template was constructed based on the magnetic resonance imaging scans of 6 ET patients and 13 PD patients. Intra-operative test data (total:n= 1821) from the 6 ET patients was analyzed: patient-specific electric field simulations together with tremor assessments obtained by a wrist-based acceleration sensor were transferred to this template. Occurrence and weighted mean maps were generated. Voxels associated with symptomatic response were identified through a linear mixed model approach to form a PSM. Improvements predicted by the PSM were compared to those clinically assessed. Finally, the PSM clusters were compared to those obtained in a multicenter study using data from chronic stimulation effects in ET.Main results.Regions responsible for improvement identified on the PSM were in the posterior sub-thalamic area (PSA) and at the border between the Vim and ventro-oral nucleus of the thalamus (VO). The comparison with literature revealed a center-to-center distance of less than 5 mm and an overlap score (Dice) of 0.4 between the significant clusters. Our workflow and intra-operative test data from 6 ET-Vim patients identified effective stimulation areas in PSA and around Vim and VO, affirming existing medical literature.Significance.This study supports the potential of probabilistic analysis of intra-operative stimulation test data to reveal DBS's action mechanisms and to assist surgical planning.

How Sample Size Impacts Probabilistic Stimulation Maps in Deep Brain Stimulation.

Probabilistic stimulation maps of deep brain stimulation (DBS) effect based on voxel-wise statistics (p-maps) have increased in literature over the last decade. These p-maps require correction for Type-1 errors due to multiple testing based on the same data. Some analyses do not reach overall significance, and this study aims to evaluate the impact of sample size on p-map computation. A dataset of 61 essential tremor patients treated with DBS was used for the investigation. Each patient contributed with four stimulation settings, one for each contact. From the dataset, 5 to 61 patients were randomly sampled with replacement for computation of p-maps and extraction of high- and low-improvement volumes. For each sample size, the process was iterated 20 times with new samples generating in total 1140 maps. The overall p-value corrected for multiple comparisons, significance volumes, and dice coefficients (DC) of the volumes within each sample size were evaluated. With less than 30 patients (120 simulations) in the sample, the variation in overall significance was larger and the median significance volumes increased with sample size. Above 120 simulations, the trends stabilize but present some variations in cluster location, with a highest median DC of 0.73 for n = 57. The variation in location was mainly related to the region between the high- and low-improvement clusters. In conclusion, p-maps created with small sample sizes should be evaluated with caution, and above 120 simulations in single-center studies are probably required for stable results.

Test-re-test reliability and dynamics of the Fukuda-Unterberger stepping test.

Background: The Fukuda-stepping-test (FST), i.e., repetitive walking on the spot while blindfolded, has been proposed as a means to assess the integrity of the vestibular pathways. While its sensitivity to detect abnormalities in patients is limited, it may be useful in studying the physiology of the subjective-straight-ahead (SSA). Considering reported systematic shifts in SSA in humans, we hypothesize that such asymmetries arise from individual differences in the orientation/configuration of the macular organs and in central processing of vestibular input. We hypothesize that such asymmetries are stable over time in individual subjects. Alternatively, such asymmetries may arise from random noise in the sensory/motor systems involved, demonstrating low reproducibility over time. Materials and methods: Twenty-four subjects walked on the spot over 60 s while blindfolded (n = 6 trials per subject). Using an inertial measurement unit (IMU) placed at the chest, angular deviations were recorded and compared to manually-measured final positions. Both static (direction, magnitude) and dynamic (time-to-onset of deviation, pattern of deviations) parameters were retrieved from the yaw slopes. Results: Significant deviations were found in 15/24 participants for the manual measurements (leftwards = 8; rightwards = 7), whereas when using the IMU-sensor 13/24 participants showed significant shifts (leftwards = 9; rightwards = 4). There was a high correlation (0.98) between manually measured rotation angles (average absolute deviations = 58.0 deg ± 48.6 deg; intra-individual variability = 39 deg ± 24 deg) and sensor-based yaw slopes (1.00 deg/s ± 0.88 deg/s; 0.67 deg/s ± 0.41 deg/s). Relevant yaw deviation was detected 22.1 s ± 12.3 s (range = 5.6 s-59.2 s) after the onset of marching (no relevant yaw-deviation in 15/139 measurements), showing a mostly linear behavior over time. Conclusion: We observed significant inter-individual variability in task performance in the FST, reproducing findings from previous studies. With test-re-test reliability being moderate only, but at the same time observing a preference in the side of shifts in most trials and subjects, we conclude that likely both individually varying estimates of straight-ahead and random noise contribute to the pattern of angular deviations observed. Using an IMU-sensory based approach, additional dynamic parameters could be retrieved, emphasizing the value of such a quantitative approach over manual measurements. Such an approach may provide useful additional information to distinguish patients from healthy controls.

Heading Direction Is Significantly Biased by Preceding Whole-Body Roll-Orientation While Lying.

Background: After a prolonged static whole-body roll-tilt, a significant bias of the internal estimates of the direction of gravity has been observed when assessing the subjective visual vertical. Objective: We hypothesized that this post-tilt bias represents a more general phenomenon, broadly affecting spatial orientation and navigation. Specifically, we predicted that after the prolonged roll-tilt to either side perceived straight-ahead would also be biased. Methods: Twenty-five healthy participants were asked to rest in three different lying positions (supine, right-ear-down, and left-ear-down) for 5 min ("adaptation period") prior to walking straight-ahead blindfolded for 2 min. Walking was recorded with the inertial measurement unit sensors attached to different body locations and with sensor shoe insoles. The raw data was segmented with a gait-event detection method. The Heading direction was determined and linear mixed-effects models were used for statistical analyses. Results: A significant bias in heading into the direction of the previous roll-tilt position was observed in the post-adaptation trials. This bias was identified in both measurement systems and decreased again over the 2-min walking period. Conclusions: The bias observed further confirms the influence of prior knowledge on spatial orientation and navigation. Specifically, it underlines the broad impact of a shifting internal estimate of direction of gravity over a range of distinct paradigms, illustrating similar decay time constants. In the broader context, the observed bias in perceived straight-ahead emphasizes that getting up in the morning after a good night's sleep is a vulnerable period, with an increased risk of falls and fall-related injuries due to non-availability of optimally tuned internal estimates of the direction of gravity and the direction of straight-ahead.

Deep Brain Stimulation: Emerging Tools for Simulation, Data Analysis, and Visualization.

Deep brain stimulation (DBS) is a well-established neurosurgical procedure for movement disorders that is also being explored for treatment-resistant psychiatric conditions. This review highlights important consideration for DBS simulation and data analysis. The literature on DBS has expanded considerably in recent years, and this article aims to identify important trends in the field. During DBS planning, surgery, and follow up sessions, several large data sets are created for each patient, and it becomes clear that any group analysis of such data is a big data analysis problem and has to be handled with care. The aim of this review is to provide an update and overview from a neuroengineering perspective of the current DBS techniques, technical aids, and emerging tools with the focus on patient-specific electric field (EF) simulations, group analysis, and visualization in the DBS domain. Examples are given from the state-of-the-art literature including our own research. This work reviews different analysis methods for EF simulations, tractography, deep brain anatomical templates, and group analysis. Our analysis highlights that group analysis in DBS is a complex multi-level problem and selected parameters will highly influence the result. DBS analysis can only provide clinically relevant information if the EF simulations, tractography results, and derived brain atlases are based on as much patient-specific data as possible. A trend in DBS research is creation of more advanced and intuitive visualization of the complex analysis results suitable for the clinical environment.

Probabilistic maps for deep brain stimulation - Impact of methodological differences.

BACKGROUND: Group analysis of patients with deep brain stimulation (DBS) has the potential to help understand and optimize the treatment of patients with movement disorders. Probabilistic stimulation maps (PSM) are commonly used to analyze the correlation between tissue stimulation and symptomatic effect but are applied with different methodological variations. OBJECTIVE: To compute a group-specific MRI template and PSMs for investigating the impact of PSM model parameters. METHODS: Improvement and occurrence of dizziness in 68 essential tremor patients implanted in caudal zona incerta were analyzed. The input data includes the best parameters for each electrode contact (screening), and the clinically used settings. Patient-specific electric field simulations (n = 488) were computed for all DBS settings. The electric fields were transformed to a group-specific MRI template for analysis and visualization. The different comparisons were based on PSMs representing occurrence (N-map), mean improvement (M-map), weighted mean improvement (wM-map), and voxel-wise t-statistics (p-map). These maps were used to investigate the impact from input data (clinical/screening settings), clustering methods, sampling resolution, and weighting function. RESULTS: Screening or clinical settings showed the largest impacts on the PSMs. The average differences of wM-maps were 12.4 and 18.2% points for the left and right sides respectively. Extracting clusters based on wM-map or p-map showed notable variation in volumes, while positioning was similar. The impact on the PSMs was small from weighting functions, except for a clear shift in the positioning of the wM-map clusters. CONCLUSION: The distribution of the input data and the clustering method are most important to consider when creating PSMs for studying the relationship between anatomy and DBS outcome.

Lamb Waves and Adaptive Beamforming for Aberration Correction in Medical Ultrasound Imaging.

Phase aberration in transcranial ultrasound imaging (TUI) caused by the human skull leads to an inaccurate image reconstruction. In this article, we present a novel method for estimating the speed of sound and an adaptive beamforming technique for phase aberration correction in a flat polyvinylchloride (PVC) slab as a model for the human skull. First, the speed of sound of the PVC slab is found by extracting the overlapping quasi-longitudinal wave velocities of symmetrical Lamb waves in the frequency-wavenumber domain. Then, the thickness of the plate is determined by the echoes from its front and back side. Next, an adaptive beamforming method is developed, utilizing the measured sound speed map of the imaging medium. Finally, to minimize reverberation artifacts caused by strong scatterers (i.e., needles), a dual probe setup is proposed. In this setup, we image the medium from two opposite directions, and the final image can be the minimum intensity projection of the inherently co-registered images of the opposed probes. Our results confirm that the Lamb wave method estimates the longitudinal speed of the slab with an error of 3.5% and is independent of its shear wave speed. Benefiting from the acquired sound speed map, our adaptive beamformer reduces (in real time) a mislocation error of 3.1, caused by an 8 mm slab, to 0.1 mm. Finally, the dual probe configuration shows 7 dB improvement in removing reverberation artifacts of the needle, at the cost of only 2.4-dB contrast loss. The proposed image formation method can be used, e.g., to monitor deep brain stimulation procedures and localization of the electrode(s) deep inside the brain from two temporal bones on the sides of the human skull.

Evaluation of the Potential of Automatic Naming Latency Detection for Different Initial Phonemes during Picture Naming Task.

Naming latency (NL) represents the speech onset time after the presentation of an image. We recently developed an extended threshold-based algorithm for automatic NL (aNL) detection considering the envelope of the speech wave. The present study aims at exploring the influence of different manners (e.g., "m" and "p") and positions (e.g., "t" and "p") of articulation on the differences between manual NL (mNL) and aNL detection.Speech samples were collected from 123 healthy participants. They named 118 pictures in German, including different initial phonemes. NLs were manually (Praat, waveform and spectrogram) and automatically (developed algorithm) determined. To investigate the accuracy of automatic detections, correlations between mNLs and aNLs were analyzed for different initial phonemes.ANLs and mNLs showed a strong positive correlation and similar tendencies in initial phoneme groups. ANL mean values were shorter than the ones of mNLs. Nasal sounds (e.g., /m/) showed the largest and those for fricatives (e.g., /s/) the smallest difference. However, in fricatives, 39% of NLs were detected later by automatic detections than by manual detections, which led to a reduced mean difference with mNLs. The signal energy of the initial phonemes, i.e., if they are voiced or voiceless, influences the form of the speech envelope: initial high signal energy is often responsible for an early detection by the algorithm.Our study provides evidence of a similar tendency in mNL and aNL according to different positions of articulation in each initial phoneme group. ANLs are highly sensitive to detection of speech onsets across different initial phonemes. The dependency of the NL differences on the initial phonemes will lose importance during progress evaluations in aphasia patients if the relative changes for each picture are considered separately. Nevertheless, the algorithm will be further optimized by adapting its parameters for each initial phoneme group individually.Clinical Relevance- This underlines the feasibility to use automatic naming latency detection for the evaluation of patients with aphasia in a clinical setting as well as for practices at home during picture naming.

Anatomical brain structures normalization for deep brain stimulation in movement disorders.

Deep brain stimulation (DBS) therapy requires extensive patient-specific planning prior to implantation to achieve optimal clinical outcomes. Collective analysis of patient's brain images is promising in order to provide more systematic planning assistance. In this paper the design of a normalization pipeline using a group specific multi-modality iterative template creation process is presented. The focus was to compare the performance of a selection of freely available registration tools and select the best combination. The workflow was applied on 19 DBS patients with T1 and WAIR modality images available. Non-linear registrations were computed with ANTS, FNIRT and DRAMMS, using several settings from the literature. Registration accuracy was measured using single-expert labels of thalamic and subthalamic structures and their agreement across the group. The best performance was provided by ANTS using the High Variance settings published elsewhere. Neither FNIRT nor DRAMMS reached the level of performance of ANTS. The resulting normalized definition of anatomical structures were used to propose an atlas of the diencephalon region defining 58 structures using data from 19 patients.

Stimulation maps: visualization of results of quantitative intraoperative testing for deep brain stimulation surgery.

Deep brain stimulation (DBS) is an established therapy for movement disorders such as essential tremor (ET). Positioning of the DBS lead in the patient's brain is crucial for effective treatment. Extensive evaluations of improvement and adverse effects of stimulation at different positions for various current amplitudes are performed intraoperatively. However, to choose the optimal position of the lead, the information has to be "mentally" visualized and analyzed. This paper introduces a new technique called "stimulation maps," which summarizes and visualizes the high amount of relevant data with the aim to assist in identifying the optimal DBS lead position. It combines three methods: outlines of the relevant anatomical structures, quantitative symptom evaluation, and patient-specific electric field simulations. Through this combination, each voxel in the stimulation region is assigned one value of symptom improvement, resulting in the division of stimulation region into areas with different improvement levels. This technique was applied retrospectively to five ET patients in the University Hospital in Clermont-Ferrand, France. Apart from identifying the optimal implant position, the resultant nine maps show that the highest improvement region is frequently in the posterior subthalamic area. The results demonstrate the utility of the stimulation maps in identifying the optimal implant position. Graphical abstract.

Erratum: Lamb Waves and Adaptive Beamforming for Aberration Correction in Medical Ultrasound Imaging.

In our paper titled "Lamb Waves and Adaptive Beamforming for Aberration Correction in Medical Ultrasound Imaging" [1], we mentioned that the superposition of the different symmetric (S) modes in the frequency-wavenumber (f-k) domain results in a high intensity region where its slope corresponds to the longitudinal wave speed in the slab. However, we have recently understood that this high intensity region belongs to the propagation of a wave called lateral wave or head wave [2-5]. It is generated if the longitudinal sound speed of the aberrator (i.e. the PVC slab) is larger than that of water and if the incident wavefront is curved. When the incidence angle at the interface between water and PVC is near the critical angle, the refracted wave in PVC re-radiates a small part of its energy into the fluid (i.e. the head wave). As discussed in [4], if the thickness of the waveguide is larger than the wavelength, the first arriving signal is the head wave. This is also the case in our study [1] where the ultrasound wavelength of a compressional wave in PVC was close to 1 mm, and a PVC slab with a thickness of 8 mm was used.

Contact position analysis of deep brain stimulation electrodes on post-operative CT images.

PURPOSE: Groups performing deep brain stimulation advocate post-operative imaging [magnetic resonance imaging (MRI) or computer tomography (CT)] to analyse the position of each electrode contact. The artefact of the Activa 3389 electrode had been described for MRI but not for CT. We undertook an electrode artefact analysis for CT imaging to obtain information on the artefact dimensions and related electrode contact positions. METHODS: The electrode was fixed on a phantom in a set position and six acquisitions were run (in-vitro study). The artefacts were compared with the real electrode position. Ten post-operative acquisitions were analysed (in-vivo analysis). We measured: H (height of the lateral black artefact), D (distance between the beginning of the white and the lateral black artefacts) and W (maximal artefact width), representing respectively the lengths of the four contacts and the electrode tip and width of the contact zone. A Student t-test compared the results: in vivo vs in vitro and coronal vs sagittal reconstructions along the electrode. RESULTS: The limits of the lateral black artefact around the electrode contacts corresponded to the final electrode position. There was no significant difference for D (in vivo, 1.1 +/- 0.1 mm; in vitro, 1.2 +/- 0.2 mm; p = 0.213), while W and H differed slightly (in vivo, W = 3.3 +/- 0.2 mm, H = 7.7 +/- 0.2 mm; in vitro, W = 3.1 +/- 0.1 mm, H = 7.5 +/- 0.2 mm). Results obtained with sagittal and coronal reconstructions were similar (p > 0.6). CONCLUSIONS: Precise three-dimensional (3D) localisation of the four-contact zone of the electrode can be obtained by CT identification of the limits of the lateral black artefact. The relative position of the four contacts is deduced from the size of the contacts and the inter-contact distance. Sagittal and coronal reconstructions along the electrode direction should be considered for the identification of the four electrode contacts. CT offers a useful alternative to post-operative MRI.

A System for Combined Laser Doppler Flowmetry and Microelectrode Recording during Deep Brain Stimulation Implantation.

Microelectrode recording (MER) and intraoperative test stimulations are commonly used during stereotactic implantation of deep brain stimulation (DBS) electrodes but they can increase the risk of hemorrhage. The aim of the study is to present and evaluate a system combining laser Doppler flowmetry (LDF) and MER. An optical probe was designed with an inner metal tube for the microelectrode. Calibration of the MER-LDF probe in a standard microsphere solution showed expected LDF pattern. No interferences of the MER probe with the LDF signals could be observed. LDF was also acquired in one Parkinson patient undergoing DBS implantation. LDF data were obtained along the precalculated trajectory i.e. from cortex towards the target in the subthalamic nucleus (STN). Results demonstrated the technical feasibility of the combined MER-LDF probe during in-vitro experiences and in one patient. The perfusion signal representing the microcirculation showed stable values with clear peaks from each heartbeat. This agreed with previous investigation using an optical probe without the MER function. Due to the forward-looking probe design, this new technology has a high potential to avoid vessels during MER recording. In addition, it could be possible to detect changes in microcirculatory blood flow during stimulation.

Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems-A Simulation Study.

The success of deep brain stimulation (DBS) relies primarily on the localization of the implanted electrode. Its final position can be chosen based on the results of intraoperative microelectrode recording (MER) and stimulation tests. The optimal position often differs from the final one selected for chronic stimulation with the DBS electrode. The aim of the study was to investigate, using finite element method (FEM) modeling and simulations, whether lead design, electrical setup, and operating modes induce differences in electric field (EF) distribution and in consequence, the clinical outcome. Finite element models of a MER system and a chronic DBS lead were developed. Simulations of the EF were performed for homogenous and patient-specific brain models to evaluate the influence of grounding (guide tube vs. stimulator case), parallel MER leads, and non-active DBS contacts. Results showed that the EF is deformed depending on the distance between the guide tube and stimulating contact. Several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution. The DBS EF volume can cover the intraoperatively produced EF, but can also extend to other anatomical areas. In conclusion, EF deformations between stimulation tests and DBS should be taken into consideration as they can alter the clinical outcome.

Analysis of adverse effects of stimulation during DBS surgery by patient-specific FEM simulations.

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.

A novel assistive method for rigidity evaluation during deep brain stimulation surgery using acceleration sensors.

OBJECTIVE Despite the widespread use of deep brain stimulation (DBS) for movement disorders such as Parkinson's disease (PD), the exact anatomical target responsible for the therapeutic effect is still a subject of research. Intraoperative stimulation tests by experts consist of performing passive movements of the patient's arm or wrist while the amplitude of the stimulation current is increased. At each position, the amplitude that best alleviates rigidity is identified. Intrarater and interrater variations due to the subjective and semiquantitative nature of such evaluations have been reported. The aim of the present study was to evaluate the use of an acceleration sensor attached to the evaluator's wrist to assess the change in rigidity, hypothesizing that such a change will alter the speed of the passive movements. Furthermore, the combined analysis of such quantitative results with anatomy would generate a more reproducible description of the most effective stimulation sites. METHODS To test the reliability of the method, it was applied during postoperative follow-up examinations of 3 patients. To study the feasibility of intraoperative use, it was used during 9 bilateral DBS operations in patients suffering from PD. Changes in rigidity were calculated by extracting relevant outcome measures from the accelerometer data. These values were used to identify rigidity-suppressing stimulation current amplitudes, which were statistically compared with the amplitudes identified by the neurologist. Positions for the chronic DBS lead implantation that would have been chosen based on the acceleration data were compared with clinical choices. The data were also analyzed with respect to the anatomical location of the stimulating electrode. RESULTS Outcome measures extracted from the accelerometer data were reproducible for the same evaluator, thus providing a reliable assessment of rigidity changes during intraoperative stimulation tests. Of the 188 stimulation sites analyzed, the number of sites where rigidity-suppressing amplitudes were found increased from 144 to 170 when the accelerometer evaluations were considered. In general, rigidity release could be observed at significantly lower amplitudes with accelerometer evaluation (mean 0.9 ± 0.6 mA) than with subjective evaluation (mean 1.4 ± 0.6 mA) (p < 0.001). Of 14 choices for the implant location of the DBS lead, only 2 were the same for acceleration-based and subjective evaluations. The comparison across anatomical locations showed that stimulation in the fields of Forel ameliorates rigidity at similar amplitudes as stimulation in the subthalamic nucleus, but with fewer side effects. CONCLUSIONS This article describes and validates a new assistive method for assessing rigidity with acceleration sensors during intraoperative stimulation tests in DBS procedures. The initial results indicate that the proposed method may be a clinically useful aid for optimal DBS lead placement as well as a new tool in the ongoing scientific search for the optimal DBS target for PD.

Patient-Specific Electric Field Simulations and Acceleration Measurements for Objective Analysis of Intraoperative Stimulation Tests in the Thalamus.

Despite an increasing use of deep brain stimulation (DBS) the fundamental mechanisms of action remain largely unknown. Simulation of electric entities has previously been proposed for chronic DBS combined with subjective symptom evaluations, but not for intraoperative stimulation tests. The present paper introduces a method for an objective exploitation of intraoperative stimulation test data to identify the optimal implant position of the chronic DBS lead by relating the electric field (EF) simulations to the patient-specific anatomy and the clinical effects quantified by accelerometry. To illustrate the feasibility of this approach, it was applied to five patients with essential tremor bilaterally implanted in the ventral intermediate nucleus (VIM). The VIM and its neighborhood structures were preoperatively outlined in 3D on white matter attenuated inversion recovery MR images. Quantitative intraoperative clinical assessments were performed using accelerometry. EF simulations (n = 272) for intraoperative stimulation test data performed along two trajectories per side were set-up using the finite element method for 143 stimulation test positions. The resulting EF isosurface of 0.2 V/mm was superimposed to the outlined anatomical structures. The percentage of volume of each structure's overlap was calculated and related to the corresponding clinical improvement. The proposed concept has been successfully applied to the five patients. For higher clinical improvements, not only the VIM but as well other neighboring structures were covered by the EF isosurfaces. The percentage of the volumes of the VIM, of the nucleus intermediate lateral of the thalamus and the prelemniscal radiations within the prerubral field of Forel increased for clinical improvements higher than 50% compared to improvements lower than 50%. The presented new concept allows a detailed and objective analysis of a high amount of intraoperative data to identify the optimal stimulation target. First results indicate agreement with published data hypothesizing that the stimulation of other structures than the VIM might be responsible for good clinical effects in essential tremor. (Clinical trial reference number: Ref: 2011-A00774-37/AU905).

Stereotactic coregistration of 201Tl SPECT and MRI applied to brain tumor biopsies.

UNLABELLED: The aim of the present study was to determine the clinical feasibility of integration of stereotactic SPECT (sSPECT) with 201Tl in the stereotactic MRI (sMRI)-based planning of brain tumor biopsy. Furthermore, the predictive value of the integrated techniques was analyzed by comparison with the corresponding histologically determined metabolic activity. METHODS: Ten patients underwent combined 201Tl SPECT- and MRI-guided stereotactic biopsy of intracranial lesions according to a previously described technique. An area of abnormal 201Tl uptake was used to guide the stereotactic biopsy trajectory. Several samples were taken along the trajectory above and beneath the target. An extensive histologic diagnosis (tumor grade, mitotic index [MI], and Ki67 index) and the 201Tl index were obtained for all samples and compared statistically. RESULTS: Combined 201Tl sSPECT- and sMRI-guided biopsy could be performed on all patients. Ki67 index, MI, and tumor grade correlated significantly. The correlations between MI or Ki67 index and 201Tl index were not significant (0.18 and 0.09, respectively). A trend to significance existed between tumor grade and 201Tl index (R = 0.31; P = 0.06). Mean 201Tl index for grade III tumors (3.27 +/- 1.89 [SD]) was significantly different from that for grade IV tumors (4.34 +/- 1.29). The sample position on the trajectory correlated with the MI (R = 0.39; P = 0.01). In 4 of the 10 patients, a variation in tumor grade could be observed along the trajectory. In all patients, the highest proliferative activity was within 5-10 mm of the target. CONCLUSION: These results support the view that 201Tl SPECT may contribute to the successful management of brain tumor patients requiring stereotactic biopsy, without causing a significant increase in discomfort or morbidity. The development of similar techniques integrating sSPECT data in the planning of stereotactic biopsy should be considered by centers performing stereotactic surgery and having access to SPECT technology. In the long term, this technique could become a support for focused gene therapy and cell transfer.