Wireless Multichannel Electrocorticogram Recording for Epilepsy Monitoring

描述(由申请人提供)：外科手术切除致痫灶是一种常见且通常有益的治疗方法，用于治疗因其他顽固性癫痫引起的衰弱发作的患者。这一手术的成功取决于医疗团队能否准确定位患者大脑中的致痫区域，以及识别在切除过程中必须避免的重要皮质区域。公认的最好的定位致痫区域的方法是记录癫痫发作的活动，长期植入几天的颅内硬膜下电极阵列。在监测期间，电极阵列通过电缆连接到外部记录设备。这种侵入性手术有缺点：1)住院时间长，费用高；2)家人或保姆必须时刻陪伴患者，3)患者被电缆拴在墙上，使一些患者难以应对；4)长时间植入增加了严重感染的可能性；5)如果电缆被意外拔出，网格移动，有脑出血的风险；6)10%至20%的患者在住院期间癫痫发作太少，无法确定地识别癫痫区。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外科放置的开颅手术，并将避免使用将记录电极连接到数据处理和存储硬件的经颅多线电缆。完全关闭硬脑膜和头骨的能力，避免了连接到大脑的有线管道，将通过允许患者在大部分监测阶段离开医院来降低感染引起的发病风险并降低成本。无线门诊监测的一个潜在显著好处是能够提供更长的监测期，这允许在患者接受完整的抗癫痫药物治疗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。无线电极阵列将通过避免使用头戴式脐带进行硬连线记录以及通过改善患者的移动性来减少患者的痛苦和不适。该阵列在体液中的稳定性是通过使用无定形碳化硅(a-碳化硅)和有机硅封装实现的，这是通过EIC实验室在薄膜处理方面的进步以及用于聚合物基质上的神经记录和刺激电极的封装策略而实现的。第一阶段的目标是完成带有集成电路控制器的通道硬膜下网格阵列的设计、制造和体外测试。该测试将在体外证明该阵列的功能稳定性，预计将在第二阶段进行动物安全性研究。第一阶段的目标如下：目的1.设计一种用于通道记录和皮层脑电波形无线传输的专用集成电路，并提供用于皮层标测的无线双极刺激手段；目的2.制作集成了专用集成电路和射频线圈、a-SiC/硅胶封装和低阻抗溅射氧化Ir(SIROF)记录和刺激部位的通道无线记录阵列；目的3.对具有电激活ASIC和线圈的通道阵列进行正常和加速条件下的体外功能测试。该项目是马萨诸塞州诺伍德的EIC实验室公司和伊利诺伊州芝加哥的Sigics公司的合作项目。在第一阶段，EIC将进行阵列制造和测试，而Sigics将设计集成电路和遥测系统。公共卫生相关性：正在提议开发无线硬膜下电极阵列，用于在癫痫手术前定位致痫灶中记录癫痫发作活动。无线阵列将降低手术成本，降低患者的风险，改善癫痫手术的结果。无线阵列将使难治性癫痫患者受益，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.