Wireless Multichannel Electrocorticogram Recording for Epilepsy Monitoring

描述（由申请人提供）：手术切除致癫痫灶是一种常用的治疗方法，通常对因其他难治性癫痫引起的衰弱性癫痫发作患者有益。手术的成功取决于医疗团队精确定位患者大脑中癫痫发生区域的能力，以及确定切除过程中必须避免的重要皮质区域的能力。定位癫痫区公认的最佳方法是用长期植入数天的颅内硬膜下电极阵列记录癫痫发作活动。在监测期间，电极阵列通过电缆连接到外部记录设备。这种侵入性手术有以下缺点：1)住院时间长，费用高；2)必须有一名家庭成员或保姆一直与患者在一起；3)患者被电缆拴在墙上，使一些患者难以应付；4)长时间植入增加严重感染的可能性；5)电缆不小心被拉扯，网格移动有脑出血的危险；10%到20%的病人在住院期间癫痫发作太少，无法确定癫痫区。我们建议开发无线颅内硬膜下电极阵列，以避免这些缺点。无线硬膜下阵列将允许完全关闭用于手术放置的开颅手术，并避免使用连接记录电极与数据处理和存储硬件的经颅多线电缆。完全关闭硬脑膜和颅骨的能力，避免了通往大脑的有线导管，将减少因感染引起的发病率风险，并通过允许患者在大部分监测阶段离开医院来降低成本。无线门诊监测的一个潜在的显著好处是能够提供更长的监测周期，这允许在患者服用抗癫痫药物的整个方案时记录习惯性癫痫发作活动。基于习惯性癫痫发作活动的定位有望改善切除手术的结果。无线电极阵列将避免使用头戴式脐带进行硬连线记录，并改善患者的活动能力，从而减少患者的痛苦和不适。通过使用非晶碳化硅（a-SiC）和硅酮封装，阵列在体液中的稳定性得以实现，这是通过EIC实验室在薄膜加工和封装策略方面的进步实现的，这些策略用于聚合物基板上的神经记录和刺激电极。第一阶段的目标是完成带有集成电路控制器（ASIC）的64通道硬膜下网格阵列的设计、制造和体外测试。该测试将证明该阵列在体外的功能稳定性，并为第二阶段的动物安全性研究做准备。第一阶段的目标如下：目标1。设计用于64通道ECoG波形记录和无线传输的ASIC，并提供用于皮质映射的双极刺激无线手段；目标2。制造64通道无线记录阵列，集成ASIC和RF线圈，a-SiC/硅胶封装，低阻抗溅射氧化铱（SIROF）记录和刺激位点；目标3。通过正常和加速条件下的体外功能测试，对64通道电源asic和线圈阵列进行评价。该项目是EIC实验室公司（马萨诸塞州诺伍德）和Sigenics公司（伊利诺伊州芝加哥）的合作项目。在第一阶段，EIC将进行阵列制造和测试，而Sigenics将设计集成电路和遥测系统。公共卫生相关性：正在提出开发无线硬膜下电极阵列，用于在癫痫手术前记录癫痫灶定位的发作活动。无线阵列将降低手术成本，降低患者的风险，并改善癫痫手术的结果。无线阵列将使顽固性癫痫患者受益，这些患者的癫痫发作无法通过药物很好地控制。

DESCRIPTION (provided by applicant): Surgical resection of epileptogenic foci is a commonly practiced and often beneficial treatment for patients suffering debilitating seizures arising from otherwise intractable epilepsy. The success of this procedure depends on the ability of the medical team to precisely locate the epileptogenic zones in the patient's brain and to identify important cortical regions that must be avoided during resection. The accepted best method for locating the epileptogenic zones is to record seizure activity with intracranial, subdural electrode arrays implanted chronically for several days. The electrode arrays are connected by cables to external recording equipment for the duration of the monitoring period. This invasive procedure has disadvantages: 1) a lengthy and costly hospital stay is required; 2) a family member or sitter must be with the patient at all times, 3) the patient is tethered to the wall by cables making it difficult for some patients to cope; 4) the long duration implantation increases the likelihood of serious infection; 5) there is a risk of intracerebral hemorrhage if the cables are accidentally pulled and the grids move; and 6) ten to twenty percent of patients have too few seizures during the hospitalization to identify the epileptic zone with certainty. We propose to develop wireless intracranial, subdural electrode arrays that will avoid these disadvantages. The wireless subdural arrays will allow complete closure of the craniotomy used for surgical placement and will avoid the use of the transcranial multiwire cables that connect the recording electrodes to data processing and storage hardware. The ability to completely close the dura and skull, avoiding wired conduits to the brain, will reduce the risk of morbidity due to infection and reduce cost by allowing the patient to leave the hospital for the majority of the monitoring phase. A potentially significant benefit of wireless outpatient monitoring is the ability to provide longer monitoring periods, which allows the recording of habitual seizure activity while the patient is on his full regimen of anti-seizure medication. Localization based on habitual seizure activity is expected to improve outcomes of the resective surgery. The wireless electrode arrays will reduce patient distress and discomfort by avoiding the use of a head mounted umbilical for hardwired recording and by improving patient mobility. The stability of the arrays in body fluids is obtained through the use of amorphous SiC (a-SiC) and silicone encapsulation, made possible through advances at EIC Laboratories in thin film processing and encapsulation strategies for neural recording and stimulation electrodes on polymer substrates. The Phase I objective is to complete the design, fabrication and in vitro testing of a 64-channel subdural grid array with an integrated circuit controller (an ASIC). The testing would demonstrate the functional stability of the array, in vitro, in anticipation of animal safety studies to be performed in a Phase II effort. The Phase I Aims are as follows: Aim 1. To design an ASIC for 64-channel recording and wireless transmission of ECoG waveforms with the additional capability of providing a wireless means of bipolar stimulation for cortical mapping; Aim 2. To fabricate 64-channel wireless recording arrays with integrated ASIC and RF coils, a-SiC/silicone encapsulation, and low-impedance sputtered iridium oxide (SIROF) recording and stimulation sites; Aim 3. To evaluate the 64-channel arrays with electrically active ASICs and coils by in vitro functional testing under normal and accelerated conditions. The program is a collaboration between EIC Laboratories Inc. (Norwood, MA) and Sigenics Inc. (Chicago, Ill). In Phase I, EIC will conduct the array fabrication and testing while Sigenics will design the integrated circuit and telemetry system. PUBLIC HEALTH RELEVANCE: The development of wireless subdural electrode arrays for recording seizure activity in the localization of epileptogenic foci prior to epilepsy surgery is being proposed. The wireless arrays will reduce the cost of the procedure, decrease the risk to the patient, and improve the outcome of the epilepsy surgery. The wireless arrays will benefit patients with intractable epilepsy whose seizures are not well-controlled by medication.