Intraoperative anatomical navigation in asleep deep brain stimulation as a tool for the interpretation of microelectrode recordings: a prospective study

• Introduction: Microelectrode Recording (MER) is still regarded as a fundamental feature of Deep Brain Stimulation (DBS). In awake DBS, MERs are better characterized due to lack of sedation. During asleep DBS, general anesthesia interferes with MERs. Therefore, basing intraoperative lead localization in asleep DBS on extracellular recordings alone, requires huge expertise by the surgeon, who risks sub-optimal final electrode placement. This study aims to investigate whether anatomical navigation during asleep DBS surgery is a reliable and useful additional tool. The intraoperative association of anatomical (imaging studies and 3D reconstructions) and electrophysiological (microelectrode recordings) information would in fact permit a facilitated surgical procedure. • Methods/Materials: Patients enrolled in this study undergo asleep DBS in the Pediatric and Functional Neurosurgery Department of Padova. During surgery, intraoperative MERs are integrated with deterministic anatomical imaging of the structures crossed by the trajectory, obtained using a dedicated software. This allows to visualize exact anatomical relationships of each point along the trajectory of the lead with the 3D reconstructed areas of interest. For Subthalamic Nucleus (STN) DBS these areas include the thalamus, the zona incerta, the STN and the substantia nigra, whereas for Globus Pallidus Internus (GPi) DBS these include the striatum, GPe, GPi, and the optic tract. To investigate whether this feature of anatomical navigation is a reliable and helpful additional factor in the decision-making for the placement of the definitive electrode, we compare the intraoperatively planned electrode placement with the postoperatively reconstructed electrode position. • Results: Preliminary results show that the mean distance between the intraoperatively planned target and the postoperatively reconstructed target is <1 mm and the mean trajectory deviation <1°. There is a significant increase in target deviation between the first performed trajectory and the second one. This is coherent with the hypothesis that there’s an increase of brain shift as the procedure goes on due to intraoperative liquor loss. • Discussion: The study suggests that intraoperative anatomical navigation in DBS, using the dedicated software may be adequate for facilitated precise electrode placement, as there is no relevant difference between the intraoperatively planned electrode placement and the postoperatively reconstructed electrode position. • Conclusion: Preliminary results suggest that the anatomical navigation is a useful and reliable tool to significantly facilitate the interpretation of intraoperative MERs.• Introduction: Microelectrode Recording (MER) is still regarded as a fundamental feature of Deep Brain Stimulation (DBS). In awake DBS, MERs are better characterized due to lack of sedation. During asleep DBS, general anesthesia interferes with MERs. Therefore, basing intraoperative lead localization in asleep DBS on extracellular recordings alone, requires huge expertise by the surgeon, who risks sub-optimal final electrode placement. This study aims to investigate whether anatomical navigation during asleep DBS surgery is a reliable and useful additional tool. The intraoperative association of anatomical (imaging studies and 3D reconstructions) and electrophysiological (microelectrode recordings) information would in fact permit a facilitated surgical procedure. • Methods/Materials: Patients enrolled in this study undergo asleep DBS in the Pediatric and Functional Neurosurgery Department of Padova. During surgery, intraoperative MERs are integrated with deterministic anatomical imaging of the structures crossed by the trajectory, obtained using a dedicated software. This allows to visualize exact anatomical relationships of each point along the trajectory of the lead with the 3D reconstructed areas of interest. For Subthalamic Nucleus (STN) DBS these areas include the thalamus, the zona incerta, the STN and the substantia nigra, whereas for Globus Pallidus Internus (GPi) DBS these include the striatum, GPe, GPi, and the optic tract. To investigate whether this feature of anatomical navigation is a reliable and helpful additional factor in the decision-making for the placement of the definitive electrode, we compare the intraoperatively planned electrode placement with the postoperatively reconstructed electrode position. • Results: Preliminary results show that the mean distance between the intraoperatively planned target and the postoperatively reconstructed target is <1 mm and the mean trajectory deviation <1°. There is a significant increase in target deviation between the first performed trajectory and the second one. This is coherent with the hypothesis that there’s an increase of brain shift as the procedure goes on due to intraoperative liquor loss. • Discussion: The study suggests that intraoperative anatomical navigation in DBS, using the dedicated software may be adequate for facilitated precise electrode placement, as there is no relevant difference between the intraoperatively planned electrode placement and the postoperatively reconstructed electrode position. • Conclusion: Preliminary results suggest that the anatomical navigation is a useful and reliable tool to significantly facilitate the interpretation of intraoperative MERs

Lead-OR: A multimodal platform for deep brain stimulation surgery

Background: Deep brain stimulation (DBS) electrode implant trajectories are stereotactically defined using preoperative neuroimaging. To validate the correct trajectory, microelectrode recordings (MERs) or local field potential recordings can be used to extend neuroanatomical information (defined by MRI) with neurophysiological activity patterns recorded from micro- and macroelectrodes probing the surgical target site. Currently, these two sources of information (imaging vs. electrophysiology) are analyzed separately, while means to fuse both data streams have not been introduced. Methods: Here, we present a tool that integrates resources from stereotactic planning, neuroimaging, MER, and high-resolution atlas data to create a real-time visualization of the implant trajectory. We validate the tool based on a retrospective cohort of DBS patients (N = 52) offline and present single-use cases of the real-time platform. Results: We establish an open-source software tool for multimodal data visualization and analysis during DBS surgery. We show a general correspondence between features derived from neuroimaging and electrophysiological recordings and present examples that demonstrate the functionality of the tool. Conclusions: This novel software platform for multimodal data visualization and analysis bears translational potential to improve accuracy of DBS surgery. The toolbox is made openly available and is extendable to integrate with additional software packages

Indirect Targeting of Subthalamic Deep Brain Stimulation Guided by Stereotactic Computed Tomography and Microelectrode Recordings in Patients With Parkinson’s Disease

Objective: Magnetic resonance imaging fusion techniques guided by frame-based stereotactic computed tomography and microelectrode recordings are widely used to target the subthalamic nucleus. However, MRI is not always available. The aim of this study was to determine whether the indirect targeting of the subthalamic nucleus for deep brain stimulation using frame-based stereotactic computed tomography and microelectrode recording guidance in patients with advanced idiopathic Parkinson’s disease was an effective and safe treatment and to determine the factors that contributed to outcome.Methods: Thirty-four consecutive patients with Parkinson’s disease who were treated from 2010 to 2012 were enrolled in this retrospective cohort study. The patients were assessed with the Unified Parkinson’s Disease Rating Scale-part III (UPDRS-III) and other clinical profiles peri- and post-operatively. The horizontal and vertical distances between the midpoint of the head frame and the brain midline at the septum pellucidum level and the upper edge of the bilateral lens, respectively, on a thin-section brain computed tomography scan were defined as the horizontal and vertical deviations, respectively.Results: After the deep brain stimulation surgery, the patients’ UPDRS-III scores improved 48 ± 2.8% (range, 20–81%) compared to the patients’ baseline off-levodopa scores. No surgery-associated complications were found. The mean recorded length difference of the subthalamic nucleus between the initial and final single microelectrode recording trajectories was 5.37 ± 0.16 mm (range, 3.99–7.50). Multiple linear regression analyses revealed that the increased lengths of the vertical (regression coefficient [B]: -0.0626; 95% confidence interval [CI]: -0.113 to -0.013) and horizontal deviations (B: -0.0497; 95% CI: -0.083 to -0.017) were associated with less improvement in the patients’ UPDRS scores.Conclusion: These results showed that the indirect targeting of the subthalamic nucleus for deep brain stimulation using frame-based stereotactic computed tomography and microelectrode recording guidance in patients with advanced idiopathic Parkinson’s disease was effective and safe. Greater symmetry of the head frame fixation resulted in better outcomes of the deep brain stimulation of the subthalamic nucleus in patients with Parkinson’s disease, especially when the horizontal deviation was 2 mm or less and the vertical deviation was 1 mm or less

Personalized computational models of deep brain stimulation

University of Minnesota Ph.D. dissertation. December 2016. Major: Biomedical Engineering. Advisor: Matthew Johnson. 1 computer file (PDF); xii, 138 pages.Deep brain stimulation (DBS) therapy is used for managing symptoms associated with a growing number of neurological disorders. One of the primary challenges with delivering this therapy, however, continues to be accurate neurosurgical targeting of the DBS lead electrodes and post-operative programming of the stimulation settings. Two approaches for addressing targeting have been advanced in recent years. These include novel DBS lead designs with more electrodes and computational models that can predict cellular modulation during DBS. Here, we developed a personalized computational modeling framework to (1) thoroughly investigate the electrode design parameter space for current and future DBS array designs, (2) generate and evaluate machine learning feature sets for semi-automated programming of DBS arrays, (3) study the influence of model parameters in predicting behavioral and electrophysiological outcomes of DBS in a preclinical animal model of Parkinson’s disease, and (4) evaluate feasibility of a novel endovascular targeting approach to delivering DBS therapy in humans. These studies show how independent current controlled stimulation with advanced machine learning algorithms can negate the need for highly dense electrode arrays to shift, steer, and sculpt regions of modulation within the brain. Additionally, these studies show that while advanced and personalized computational models of DBS can predict many of the behavioral and electrophysiological outcomes of DBS, there are remaining inconsistencies that suggest there are additional physiological mechanisms of DBS that are not yet well understood. Finally, the results show how computational models can be beneficial for prospective development of novel approaches to neuromodulation prior to large-scale preclinical and clinical studies

Functional lesional neurosurgery for tremor: back to the future?

For nearly a century, functional neurosurgery has been applied in the treatment of tremor. While deep brain stimulation has been in the focus of academic interest in recent years, the establishment of incisionless technology, such as MRI-guided high-intensity focused ultrasound, has again stirred interest in lesional approaches.In this article, we will discuss the historical development of surgical technique and targets, as well as the technological state-of-the-art of conventional and incisionless interventions for tremor due to Parkinson's disease, essential and dystonic tremor and tremor related to multiple sclerosis (MS) and midbrain lesions. We will also summarise technique-inherent advantages of each technology and compare their lesion characteristics. From this, we identify gaps in the current literature and derive future directions for functional lesional neurosurgery, in particularly potential trial designs, alternative targets and the unsolved problem of bilateral lesional treatment. The results of a systematic review and meta-analysis of the consistency, efficacy and side effect rate of lesional treatments for tremor are presented separately alongside this article

Previous, current, and future stereotactic EEG techniques for localising epileptic foci

INTRODUCTION: Drug-resistant focal epilepsy presents a significant morbidity burden globally, and epilepsy surgery has been shown to be an effective treatment modality. Therefore, accurate identification of the epileptogenic zone for surgery is crucial, and in those with unclear noninvasive data, stereoencephalography is required. AREAS COVERED: This review covers the history and current practices in the field of intracranial EEG, particularly analyzing how stereotactic image-guidance, robot-assisted navigation, and improved imaging techniques have increased the accuracy, scope, and use of SEEG globally. EXPERT OPINION: We provide a perspective on the future directions in the field, reviewing improvements in predicting electrode bending, image acquisition, machine learning and artificial intelligence, advances in surgical planning and visualization software and hardware. We also see the development of EEG analysis tools based on machine learning algorithms that are likely to work synergistically with neurophysiology experts and improve the efficiency of EEG and SEEG analysis and 3D visualization. Improving computer-assisted planning to minimize manual input from the surgeon, and seamless integration into an ergonomic and adaptive operating theater, incorporating hybrid microscopes, virtual and augmented reality is likely to be a significant area of improvement in the near future

Methodological considerations for neuroimaging in deep brain stimulation of the subthalamic nucleus in Parkinson’s disease patients

Deep brain stimulation (DBS) of the subthalamic nucleus is a neurosurgical intervention for Parkinson’s disease patients who no longer appropriately respond to drug treatments. A small fraction of patients will fail to respond to DBS, develop psychiatric and cognitive side-effects, or incur surgery-related complications such as infections and hemorrhagic events. In these cases, DBS may require recalibration, reimplantation, or removal. These negative responses to treatment can partly be attributed to suboptimal pre-operative planning procedures via direct targeting through low-field and low-resolution magnetic resonance imaging (MRI). One solution for increasing the success and efficacy of DBS is to optimize preoperative planning procedures via sophisticated neuroimaging techniques such as high-resolution MRI and higher field strengths to improve visualization of DBS targets and vasculature. We discuss targeting approaches, MRI acquisition, parameters, and post-acquisition analyses. Additionally, we highlight a number of approaches including the use of ultra-high field (UHF) MRI to overcome limitations of standard settings. There is a trade-off between spatial resolution, motion artifacts, and acquisition time, which could potentially be dissolved through the use of UHF-MRI. Image registration, correction, and post-processing techniques may require combined expertise of traditional radiologists, clinicians, and fundamental researchers. The optimization of pre-operative planning with MRI can therefore be best achieved through direct collaboration between researchers and clinicians

Customizable Intraoperative Neural Stimulator and Recording System for Deep Brain Stimulation Research and Surgery.

Intraoperative targeting systems provide neurosurgeons with raw electrophysiological data through microelectrodes used for determining location in the brain. There are significant deficits to the available targeting systems, limiting the use in both clinical and research applications. The work presented in this dissertation is of the development and validation of an intraoperative neural stimulator and recording system for use in deep brain stimulation (DBS) surgeries. This intraoperative data acquisition system (IODA) was validated in three applications to ensure efficacy and improvements in research and clinical studies. The first application investigated was a clinical study illustrating the improvement IODA had on the targeting accuracy of DBS leads in the subthalamic nucleus (STN) over current targeting methods. It was demonstrated that the novel navigation algorithm developed for use with IODA targeted microelectrode probe locations significantly closer to final DBS lead positions compared to preoperatively planned trajectory positions. The second study investigated a clinical science application. There are considerable differences in recently published studies for the optimal chronic stimulation site in the STN region. It was shown, using beta oscillations of local field potentials (LFP) recorded by IODA, that optimal stimulation sites were significantly correlated with locations of peak beta activity when DBS leads were medial to the STN midpoint. While DBS lead trajectories lateral of the STN midpoint were significantly correlated with the dorsal border of the STN. The third study explored a basic science application involving the role of the STN in movement inhibition. Through wideband recordings made with IODA, it was shown that the STN is significantly activated during movement and movement inhibition cues as seen in the theta, alpha, and beta bands and single unit activity. Overall the results indicate the utility and adaptability of this system for use within DBS surgeries. There are many applications of IODA for use in research for other neurodegenerative disease including Essential Tremor and Depression. The use of this system has enables neurosurgeons to reduce surgical time, risk, and error for DBS procedures and made entry for those less experienced in this procedure easier.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/99771/1/dodani_1.pd

Deep Brain Stimulation: A Paradigm Shifting Approach to Treat Parkinson's Disease

Parkinson disease (PD) is a chronic and progressive movement disorder classically characterized by slowed voluntary movements, resting tremor, muscle rigidity, and impaired gait and balance. Medical treatment is highly successful early on, though the majority of people experience significant complications in later stages. In advanced PD, when medications no longer adequately control motor symptoms, deep brain stimulation (DBS) offers a powerful therapeutic alternative. DBS involves the surgical implantation of one or more electrodes into specific areas of the brain, which modulate or disrupt abnormal patterns of neural signaling within the targeted region. Outcomes are often dramatic following DBS, with improvements in motor function and reductions motor complications having been repeatedly demonstrated. Given such robust responses, emerging indications for DBS are being investigated. In parallel with expansions of therapeutic scope, advancements within the areas of neurosurgical technique and the precision of stimulation delivery have recently broadened as well. This review focuses on the revolutionary addition of DBS to the therapeutic armamentarium for PD, and summarizes the technological advancements in the areas of neuroimaging and biomedical engineering intended to improve targeting, programming and overall management