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，手术切除引起癫痫发作的脑组织是消除癫痫发作的最佳治疗选择。然而，利用现有的方法（3T MRI和立体脑电图（sEEG）），绘制大脑中的癫痫通路和精确定位癫痫发作区（“焦点”）仍然是一个挑战。癫痫发作病灶精确定位的困难限制了符合手术条件的患者数量，降低了手术的有效性，超过一半的患者癫痫发作复发证明了这一点。sEIT是最近开发的一种方法，具有更准确定位焦点的巨大潜力，而不会干扰医院目前的术前实践。这个想法是，癫痫发作期间发生的生理变化——比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手术前评估的“深度”电极），我们可以对这些电阻变化进行成像，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，在动物模型中，癫痫发作焦点和随后的传播被识别出来，精度为5毫米。我们建议将sEIT技术应用于人类患者，目的是首先(a)增加手术吸收并改善术后结果，最终(b)用sEIT控制的闭环深部脑刺激取代手术。如果成功，这种方法将在短期到中期直接有利于术前计划，并在长期内彻底改变癫痫治疗。该项目的具体目标是：1)提高癫痫病灶定位的准确性，并通过sEIT研究随后的癫痫进展，使用深度电极已经常规放置用于术前评估。2)研究癫痫发作进展的机制和不应切除的雄辩皮层区域，以尽量减少术后功能缺陷。3)设计和测试最优闭环刺激模式，以抑制癫痫发作，而无需手术退行。新颖性：sEIT方法已在动物模型中得到验证，但该技术尚未在人类患者中实施。成功的翻译将允许使用sEIT来改善手术结果，并有可能创建闭环DBS范例，这将取代人类大脑切除手术。与EPSRC保持一致：研究将侧重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焦点定位程序和随后的切除手术。国家神经内科和神经外科医院遥测病房的患者将在技术优化并测试符合相应标准后招募。与英国一家世界知名医院的合作将为英国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，参与技术实施到市场产品的后期阶段。任何涉及的公司或合作者：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