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

Computer-Assisted Planning and Robotics in Epilepsy Surgery

Epilepsy is a severe and devastating condition that affects ~1% of the population. Around 30% of these patients are drug-refractory. Epilepsy surgery may provide a cure in selected individuals with drug-resistant focal epilepsy if the epileptogenic zone can be identified and safely resected or ablated. Stereoelectroencephalography (SEEG) is a diagnostic procedure that is performed to aid in the delineation of the seizure onset zone when non-invasive investigations are not sufficiently informative or discordant. Utilizing a multi-modal imaging platform, a novel computer-assisted planning (CAP) algorithm was adapted, applied and clinically validated for optimizing safe SEEG trajectory planning. In an initial retrospective validation study, 13 patients with 116 electrodes were enrolled and safety parameters between automated CAP trajectories and expert manual plans were compared. The automated CAP trajectories returned statistically significant improvements in all of the compared clinical metrics including overall risk score (CAP 0.57 +/- 0.39 (mean +/- SD) and manual 1.00 +/- 0.60, p < 0.001). Assessment of the inter-rater variability revealed there was no difference in external expert surgeon ratings. Both manual and CAP electrodes were rated as feasible in 42.8% (42/98) of cases. CAP was able to provide feasible electrodes in 19.4% (19/98), whereas manual planning was able to generate a feasible electrode in 26.5% (26/98) when the alternative generation method was not feasible. Based on the encouraging results from the retrospective analysis a prospective validation study including an additional 125 electrodes in 13 patients was then undertaken to compare CAP to expert manual plans from two neurosurgeons. The manual plans were performed separately and blindly from the CAP. Computer-generated trajectories were found to carry lower risks scores (absolute difference of 0.04 mm (95% CI = -0.42-0.01), p = 0.04) and were subsequently implanted in all cases without complication. The pipeline has been fully integrated into the clinical service and has now replaced manual SEEG planning at our institution. Further efforts were then focused on the distillation of optimal entry and target points for common SEEG trajectories and applying machine learning methods to develop an active learning algorithm to adapt to individual surgeon preferences. Thirty-two patients were prospectively enrolled in the study. The first 12 patients underwent prospective CAP planning and implantation following the pipeline outlined in the previous study. These patients were used as a training set and all of the 108 electrodes after successful implantation were normalized to atlas space to generate ‘spatial priors’, using a K-Nearest Neighbour (K-NN) classifier. A subsequent test set of 20 patients (210 electrodes) were then used to prospectively validate the spatial priors. From the test set, 78% (123/157) of the implanted trajectories passed through both the entry and target spatial priors defined from the training set. To improve the generalizability of the spatial priors to other neurosurgical centres undertaking SEEG and to take into account the potential for changing institutional practices, an active learning algorithm was implemented. The K-NN classifier was shown to dynamically learn and refine the spatial priors. The progressive refinement of CAP SEEG planning outlined in this and previous studies has culminated in an algorithm that not only optimizes the surgical heuristics and risk scores related to SEEG planning but can also learn from previous experience. Overall, safe and feasible trajectory schema were returning in 30% of the time required for manual SEEG planning. Computer-assisted planning was then applied to optimize laser interstitial thermal therapy (LITT) trajectory planning, which is a minimally invasive alternative to open mesial temporal resections, focal lesion ablation and anterior 2/3 corpus callosotomy. We describe and validate the first CAP algorithm for mesial temporal LITT ablations for epilepsy treatment. Twenty-five patients that had previously undergone LITT ablations at a single institution and with a median follow up of 2 years were included. Trajectory parameters for the CAP algorithm were derived from expert consensus to maximize distance from vasculature and ablation of the amygdalohippocampal complex, minimize collateral damage to adjacent brain structures whilst avoiding transgression of the ventricles and sulci. Trajectory parameters were also optimized to reduce the drilling angle to the skull and overall catheter length. Simulated cavities attributable to the CAP trajectories were calculated using a 5-15 mm ablation diameter. In comparison to manually planned and implemented LITT trajectories,CAP resulted in a significant increase in the percentage ablation of the amygdalohippocampal complex (manual 57.82 +/- 15.05% (mean +/- S.D.) and unablated medial hippocampal head depth (manual 4.45 +/- 1.58 mm (mean +/- S.D.), CAP 1.19 +/- 1.37 (mean +/- S.D.), p = 0.0001). As LITT ablation of the mesial temporal structures is a novel procedure there are no established standards for trajectory planning. A data-driven machine learning approach was, therefore, applied to identify hitherto unknown CAP trajectory parameter combinations. All possible combinations of planning parameters were calculated culminating in 720 unique combinations per patient. Linear regression and random forest machine learning algorithms were trained on half of the data set (3800 trajectories) and tested on the remaining unseen trajectories (3800 trajectories). The linear regression and random forest methods returned good predictive accuracies with both returning Pearson correlations of ρ = 0.7 and root mean squared errors of 0.13 and 0.12 respectively. The machine learning algorithm revealed that the optimal entry points were centred over the junction of the inferior occipital, middle temporal and middle occipital gyri. The optimal target points were anterior and medial translations of the centre of the amygdala. A large multicenter external validation study of 95 patients was then undertaken comparing the manually planned and implemented trajectories, CAP trajectories targeting the centre of the amygdala, the CAP parameters derived from expert consensus and the CAP trajectories utilizing the machine learning derived parameters. Three external blinded expert surgeons were then selected to undertake feasibility ratings and preference rankings of the trajectories. CAP generated trajectories result in a significant improvement in many of the planning metrics, notably the risk score (manual 1.3 +/- 0.1 (mean +/- S.D.), CAP 1.1 +/- 0.2 (mean +/- S.D.), p<0.000) and overall ablation of the amygdala (manual 45.3 +/- 22.2 % (mean +/- S.D.), CAP 64.2 +/- 20 % (mean +/- S.D.), p<0.000). Blinded external feasibility ratings revealed that manual trajectories were less preferable than CAP planned trajectories with an estimated probability of being ranked 4th (lowest) of 0.62. Traditional open corpus callosotomy requires a midline craniotomy, interhemispheric dissection and disconnection of the rostrum, genu and body of the corpus callosum. In cases where drop attacks persist a completion corpus callosotomy to disrupt the remaining fibres in the splenium is then performed. The emergence of LITT technology has raised the possibility of being able to undertake this procedure in a minimally invasive fashion and without the need for a craniotomy using two or three individual trajectories. Early case series have shown LITT anterior two-thirds corpus callosotomy to be safe and efficacious. Whole-brain probabilistic tractography connectomes were generated utilizing 3-Tesla multi-shell imaging data and constrained spherical deconvolution (CSD). Two independent blinded expert neurosurgeons with experience of performing the procedure using LITT then planned the trajectories in each patient following their current clinical practice. Automated trajectories returned a significant reduction in the risk score (manual 1.3 +/- 0.1 (mean +/- S.D.), CAP 1.1 +/- 0.1 (mean +/- S.D.), p<0.000). Finally, we investigate the different methods of surgical implantation for SEEG electrodes. As an initial study, a systematic review and meta-analysis of the literature to date were performed. This revealed a wide variety of implantation methods including traditional frame-based, frameless, robotic and custom-3D printed jigs were being used in clinical practice. Of concern, all comparative reports from institutions that had changed from one implantation method to another, such as following the introduction of robotic systems, did not undertake parallel-group comparisons. This suggests that patients may have been exposed to risks associated with learning curves and potential harms related to the new device until the efficacy was known. A pragmatic randomized control trial of a novel non-CE marked robotic trajectory guidance system (iSYS1) was then devised. Before clinical implantations began a series of pre-clinical investigations utilizing 3D printed phantom heads from previously implanted patients was performed to provide pilot data and also assess the surgical learning curve. The surgeons had comparatively little clinical experience with the new robotic device which replicates the introduction of such novel technologies to clinical practice. The study confirmed that the learning curve with the iSYS1 devices was minimal and the accuracies and workflow were similar to the conventional manual method. The randomized control trial represents the first of its kind for stereotactic neurosurgical procedures. Thirty-two patients were enrolled with 16 patients randomized to the iSYS1 intervention arm and 16 patients to the manual implantation arm. The intervention allocation was concealed from the patients. The surgical and research team could be not blinded. Trial management, independent data monitoring and trial steering committees were convened at four points doing the trial (after every 8 patients implanted). Based on the high level of accuracy required for both methods, the main distinguishing factor would be the time to achieve the alignment to the prespecified trajectory. The primary outcome for comparison, therefore, was the time for individual SEEG electrode implantation. Secondary outcomes included the implantation accuracy derived from the post-operative CT scan, infection, intracranial haemorrhage and neurological deficit rates. Overall, 32 patients (328 electrodes) completed the trial (16 in each intervention arm) and the baseline demographics were broadly similar between the two groups. The time for individual electrode implantation was significantly less with the iSYS1 device (median of 3.36 (95% CI 5.72 to 7.07) than for the PAD group (median of 9.06 minutes (95% CI 8.16 to 10.06), p=0.0001). Target point accuracy was significantly greater with the PAD (median of 1.58 mm (95% CI 1.38 to 1.82) compared to the iSYS1 (median of 1.16 mm (95% CI 1.01 to 1.33), p=0.004). The difference between the target point accuracies are not clinically significant for SEEG but may have implications for procedures such as deep brain stimulation that require higher placement accuracy. All of the electrodes achieved their respective intended anatomical targets. In 12 of 16 patients following robotic implantations, and 10 of 16 following manual PAD implantations a seizure onset zone was identified and resection recommended. The aforementioned systematic review and meta-analysis were updated to include additional studies published during the trial duration. In this context, the iSYS1 device entry and target point accuracies were similar to those reported in other published studies of robotic devices including the ROSA, Neuromate and iSYS1. The PAD accuracies, however, outperformed the previously published results for other frameless stereotaxy methods. In conclusion, the presented studies report the integration and validation of a complex clinical decision support software into the clinical neurosurgical workflow for SEEG planning. The stereotactic planning platform was further refined by integrating machine learning techniques and also extended towards optimisation of LITT trajectories for ablation of mesial temporal structures and corpus callosotomy. The platform was then used to seamlessly integrate with a novel trajectory planning software to effectively and safely guide the implantation of the SEEG electrodes. Through a single-blinded randomised control trial, the ISYS1 device was shown to reduce the time taken for individual electrode insertion. Taken together, this work presents and validates the first fully integrated stereotactic trajectory planning platform that can be used for both SEEG and LITT trajectory planning followed by surgical implantation through the use of a novel trajectory guidance system

The Effect of Vascular Segmentation Methods on Stereotactic Trajectory Planning for Drug-Resistant Focal Epilepsy: A Retrospective Cohort Study

Background: Stereotactic neurosurgical procedures carry a risk of intracranial hemorrhage, which may result in significant morbidity and mortality. Vascular imaging is crucial for planning stereotactic procedures to prevent conflicts with intracranial vasculature. There is a wide range of vascular imaging methods used for stereoelectroencephalography (SEEG) trajectory planning. Computer-assisted planning (CAP) improves planning time and trajectory metrics. We aimed to quantify the effect of different vascular imaging protocols on CAP trajectories for SEEG. Methods: Ten patients who had undergone SEEG (95 electrodes) following preoperative acquisition of gadolinium-enhanced magnetic resonance imaging (MR + Gad), magnetic resonance angiography and magnetic resonance angiography (MRV + MRA), and digital subtraction catheter angiography (DSA) were identified from a prospectively maintained database. SEEG implantations were planned using CAP using DSA segmentations as the gold standard. Strategies were then recreated using MRV + MRA and MR + Gad to define the “apparent” and “true” risk scores associated with each modality. Vessels of varying diameter were then iteratively removed from the DSA segmentation to identify the size at which all 3 vascular modalities returned the same safety metrics. Results: CAP performed using DSA vessel segmentations resulted in significantly lower “true” risk scores and greater minimum distances from vasculature compared with the “true” risk associated with MR + Gad and MRV + MRA. MRV + MRA and MR + Gad returned similar risk scores to DSA when vessels <2 mm and <4 mm were not considered, respectively. Conclusions: Significant variability in vascular imaging and trajectory planning practices exist for SEEG. CAP performed with MR + Gad or MRV + MRA alone returns “falsely” lower risk scores compared with DSA. It is unclear whether DSA is oversensitive and thus restricting potential trajectories

Retrospective evaluation and SEEG trajectory analysis for interactive multi-trajectory planner assistant

Purpose: Focal epilepsy is a neurological disease that can be surgically treated by removing area of the brain generating the seizures. The stereotactic electroencephalography (SEEG) procedure allows patient brain activity to be recorded in order to localize the onset of seizures through the placement of intracranial electrodes. The planning phase can be cumbersome and very time consuming, and no quantitative information is provided to neurosurgeons regarding the safety and efficacy of their trajectories. In this work, we present a novel architecture specifically designed to ease the SEEG trajectory planning using the 3D Slicer platform as a basis. Methods: Trajectories are automatically optimized following criteria like vessel distance and insertion angle. Multi-trajectory optimization and conflict resolution are optimized through a selective brute force approach based on a conflict graph construction. Additionally, electrode-specific optimization constraints can be defined, and an advanced verification module allows neurosurgeons to evaluate the feasibility of the trajectory. Results: A retrospective evaluation was performed using manually planned trajectories on 20 patients: the planning algorithm optimized and improved trajectories in 98% of cases. We were able to resolve and optimize the remaining 2% by applying electrode-specific constraints based on manual planning values. In addition, we found that the global parameters used discards 68% of the manual planned trajectories, even when they represent a safe clinical choice. Conclusions: Our approach improved manual planned trajectories in 98% of cases in terms of quantitative indexes, even when applying more conservative criteria with respect to actual clinical practice. The improved multi-trajectory strategy overcomes the previous work limitations and allows electrode optimization within a tolerable time span

Multi-trajectories automatic planner for StereoElectroEncephaloGraphy (SEEG)

open13E. De Momi; C. Caborni; F. Cardinale; G. Casaceli; L. Castana; M. Cossu; R. Mai; F. Gozzo; S. Francione; L. Tassi; G. Lo Russo; L. Antiga; G. FerrignoDE MOMI, Elena; Caborni, Chiara; F., Cardinale; G., Casaceli; L., Castana; M., Cossu; R., Mai; F., Gozzo; S., Francione; L., Tassi; G., Lo Russo; L., Antiga; Ferrigno, Giancarl

Population-level neural coding for higher cognition

Higher cognition encompasses advanced mental processes that enable complex thinking, decision-making, problem-solving, and abstract reasoning. These functions involve integrating information from multiple sensory modalities and organizing action plans based on the abstraction of past information. The neural activity underlying these functions is often complex, and the contribution of single neurons in supporting population-level representations of cognitive variables is not yet clear. In this thesis, I investigated the neural mechanisms underlying higher cognition in higher-order brain regions with single-neuron resolution in human and non-human primates performing working memory tasks. I aimed to understand how representations are arranged and how neurons contribute to the population code. In the first manuscript, I investigated the population-level neural coding for the maintenance of numbers in working memory within the parietal association cortex. By analyzing intra-operative intracranial micro-electrode array recording data, I uncovered distinct representations for numbers in both symbolic and nonsymbolic formats. In the second manuscript, I delved deeper into the neuronal organizing principles of population coding to address the ongoing debate surrounding memory maintenance mechanisms. I unveiled sparse structures in the neuronal implementation of representations and identified biologically meaningful components that can be directly communicated to downstream neurons. These components were linked to subpopulations of neurons with distinct physiological properties and temporal dynamics, enabling the active maintenance of working memory while resisting distraction. Lastly, using an artificial neural network model, I demonstrated that the sparse implementation of temporally modulated working memory representations is preferred in recurrently connected neural populations such as the prefrontal cortex. In summary, this thesis provides a comprehensive investigation of higher cognition in higher-order brain regions, focusing on working memory tasks involving numerical stimuli. By examining neural population coding and unveiling sparse structures in the neuronal implementation of representations, our findings contribute to a deeper understanding of the mechanisms underlying working memory and higher cognitive functions

Robotically Steered Needles: A Survey of Neurosurgical Applications and Technical Innovations

This paper surveys both the clinical applications and main technical innovations related to steered needles, with an emphasis on neurosurgery. Technical innovations generally center on curvilinear robots that can adopt a complex path that circumvents critical structures and eloquent brain tissue. These advances include several needle-steering approaches, which consist of tip-based, lengthwise, base motion-driven, and tissue-centered steering strategies. This paper also describes foundational mathematical models for steering, where potential fields, nonholonomic bicycle-like models, spring models, and stochastic approaches are cited. In addition, practical path planning systems are also addressed, where we cite uncertainty modeling in path planning, intraoperative soft tissue shift estimation through imaging scans acquired during the procedure, and simulation-based prediction. Neurosurgical scenarios tend to emphasize straight needles so far, and span deep-brain stimulation (DBS), stereoelectroencephalography (SEEG), intracerebral drug delivery (IDD), stereotactic brain biopsy (SBB), stereotactic needle aspiration for hematoma, cysts and abscesses, and brachytherapy as well as thermal ablation of brain tumors and seizure-generating regions. We emphasize therapeutic considerations and complications that have been documented in conjunction with these applications

Doctor of Philosophy

dissertationThis dissertation describes the use of cortical surface potentials, recorded with dense grids of microelectrodes, for brain-computer interfaces (BCIs). The work presented herein is an in-depth treatment of a broad and interdisciplinary topic, covering issues from electronics to electrodes, signals, and applications. Within the scope of this dissertation are several significant contributions. First, this work was the first to demonstrate that speech and arm movements could be decoded from surface local field potentials (LFPs) recorded in human subjects. Using surface LFPs recorded over face-motor cortex and Wernickes area, 150 trials comprising vocalized articulations of ten different words were classified on a trial-by-trial basis with 86% accuracy. Surface LFPs recorded over the hand and arm area of motor cortex were used to decode continuous hand movements, with correlation of 0.54 between the actual and predicted position over 70 seconds of movement. Second, this work is the first to make a detailed comparison of cortical field potentials recorded intracortically with microelectrodes and at the cortical surface with both micro- and macroelectrodes. Whereas coherence in macroelectrocorticography (ECoG) decayed to half its maximum at 5.1 mm separation in high frequencies, spatial constants of micro-ECoG signals were 530-700 ?m-much closer to the 110-160 ?m calculated for intracortical field potentials than to the macro-ECoG. These findings confirm that cortical surface potentials contain millimeter-scale dynamics. Moreover, these fine spatiotemporal features were important for the performance of speech and arm movement decoding. In addition to contributions in the areas of signals and applications, this dissertation includes a full characterization of the microelectrodes as well as collaborative work in which a custom, low-power microcontroller, with features optimized for biomedical implants, was taped out, fabricated in 65 nm CMOS technology, and tested. A new instruction was implemented in this microcontroller which reduced energy consumption when moving large amounts of data into memory by as much as 44%. This dissertation represents a comprehensive investigation of surface LFPs as an interfacing medium between man and machine. The nature of this work, in both the breadth of topics and depth of interdisciplinary effort, demonstrates an important and developing branch of engineering

Technology of deep brain stimulation: current status and future directions

Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation. DBS is a standard of care in Parkinson disease, essential tremor and dystonia, and is also under active investigation for other conditions linked to pathological circuitry, including major depressive disorder and Alzheimer disease. Modern DBS systems, borrowed from the cardiac field, consist of an intracranial electrode, an extension wire and a pulse generator, and have evolved slowly over the past two decades. Advances in engineering and imaging along with an improved understanding of brain disorders are poised to reshape how DBS is viewed and delivered to patients. Breakthroughs in electrode and battery designs, stimulation paradigms, closed-loop and on-demand stimulation, and sensing technologies are expected to enhance the efficacy and tolerability of DBS. In this Review, we provide a comprehensive overview of the technical development of DBS, from its origins to its future. Understanding the evolution of DBS technology helps put the currently available systems in perspective and allows us to predict the next major technological advances and hurdles in the field.ope