Real-Time Imaging of Epileptic Seizures with stereo Electrical Impedance Tomography (sEIT)

在英国，大约有40万人患有癫痫，其中30%的人对任何抗癫痫药物都没有反应。对于其中很大一部分人来说，手术切除导致癫痫发作的脑组织是摆脱癫痫的最佳治疗选择。然而，利用现有的方法(3T MRI和立体脑电(SEEG))，绘制大脑中的癫痫路径图并精确地定位癫痫起始区(“焦点”)仍然是一项挑战。在精确定位癫痫灶方面的困难限制了符合手术条件的患者的数量，并降低了手术的有效性，其中一半以上的人癫痫复发就是明证。SEIT是最近开发的一种方法，它具有更准确地定位病灶的巨大潜力，而不会扰乱医院目前的手术前实践。这个想法是，癫痫发作期间发生的生理变化--如脑细胞肿胀和同步神经元活动--改变了脑组织的电阻。通过向大脑注入安全水平的电流(使用已经植入大脑进行术前评估的“深度”电极)，我们可以成像这些阻力的变化，并绘制癫痫发作的开始和传播图。这种方法已经在动物模型中得到了验证，在这些动物模型中，癫痫灶和随后的传播被识别出来，准确度为5 mm。我们建议将SEIT技术移植到人类患者身上，目的是首先(A)增加手术摄取量，改善手术后结果，并最终(B)用SEIT控制的闭环式脑深部刺激取代手术。如果成功，这种方法将直接有益于手术前的中短期规划，并在长期内革新癫痫的治疗。该项目的具体目标是：1)提高癫痫灶的定位准确性，并通过SEIT利用已被常规放置用于术前评估的深度电极来研究随后的癫痫发作进展。2)研究癫痫发作进展的机制和不应切除的有能力的皮质区域，以最大限度地减少术后功能缺陷。3)设计和测试最佳的闭环式刺激范例，以抑制癫痫发作，而不需要外科手术。新奇：SEIT方法已在动物模型中得到验证，然而，这项技术还没有在人类患者身上实施。成功的翻译将允许使用SEIT来改善手术结果，并可能创建一个闭环式DBS范例，它将取代人脑切除手术。与EPSRC结盟：这项研究将专注于在人类患者中实施新的SEIT技术。该项目有可能改变癫痫发作灶的定位程序和切除手术后的情况。一旦技术得到优化和符合相应标准的测试，国家神经病学和神经外科医院遥测病房的患者将被招募。与一家世界知名的英国医院的合作将在英国的研发部门吸引更多的投资机会，并为其他研究人员和工程师提供机会，加入到技术实施的后期阶段，形成适销对路的产品。任何参与的公司或合作者：CyQiq Ltd.

Around 400,000 people suffer from epilepsy in the UK, and 30% of this population do not respond to any anti-epileptic drug. For a significant proportion of these, surgical removal of the brain tissue generating the seizures is the best treatment option for becoming seizure-free. However, with the existing methods (3T MRI and stereo-electroencephalography (sEEG)), it can remain a challenge to map the seizure pathways in the brain and localise the seizure onset zone (the "focus") with precision. Difficulties in the precise localisation of seizure foci have limited the number of patients eligible for surgery and lowered its effectiveness, evidenced by seizure recurrence in over half of these individuals. sEIT is a recently developed method that has great potential to localise the focus more accurately, without disrupting current pre-surgical practice at the hospital. The idea is that physiological changes that occur during seizures - such as swelling of the brain cells and synchronous neuronal activity - change the electrical resistance of the brain tissue. By injecting safe levels of current into the brain (using the 'depth' electrodes already implanted into the brain for presurgical evaluation), we can image these changes in resistance and map the initiation and propagation of seizures. This method has already been validated in animal models in which the seizure focus and subsequent propagation were identified with the accuracy of 5 mm. We propose to translate sEIT technology to human patients with the aims to first (a) increase surgery uptake and improve post-surgical outcomes, and eventually (b) replace the surgery with the sEIT controlled closed-loop deep brain stimulation. If successful, this method will directly benefit pre-surgical planning in the short-to-medium term and revolutionize epilepsy treatment in the long term.The specific aims of the project are:1) Improve localisation accuracy of seizure foci and study subsequent seizure progression by sEIT using the depth electrodes already routinely placed for presurgical evaluation.2) Study the mechanisms of seizure progression and areas of the eloquent cortex, which should not be resected to minimise postsurgical functional deficits.3) Design and test the optimal closed-loop stimulation paradigm to suppress the seizures without the need of surgical recession.Novelty:The sEIT method has been validated in animal models, however the technique is not yet implemented in human patients. Successful translation will allow to use sEIT to improve surgical outcomes and potentially create a close-loop DBS paradigm, which would replace a human brain resection surgery.Alignment with EPSRC:The research will be focused on the implementation of novel sEIT technique in human patients. The project has a potential to transform epileptic seizure focus localization procedure and following resection surgery. National Hospital for Neurology and Neurosurgery Telemetry ward patients will be recruited once the technology is optimised and tested for compliance with corresponding standards. The collaboration with a world-renown UK hospital will attract additional investment opportunities in the UK R&D sector and provide opportunities for other researchers and engineers to join in later stages of the technology implementation into a marketable product.Any companies or collaborators involved:Cyqiq LTD