動物實驗用癲癇治療電子系統之實現

Abstract

由於近年生醫科技迅速發展，現已有數種針對「癲癇症」之治療方法與植入元件問世，用以取代或補足藥物及外科手術之不足；其中，「深部腦刺激」與「迷走神經刺激」此二種療法由於該相關元件之開發已臻成熟，目前已實際應用於臨床治療中。但此類元件皆採用開迴路刺激，意即不問病患是否發作癲癇症狀，均定時給予電刺激以控制其病情。這種較為簡單的元件雖然對無法以藥物控制的「難治型癲癇」確實有其成效，但有效治療率僅約達四成。為提升治療的成功率，本計畫提出一個「閉鎖路」癲癇治療元件，可以在時間、空間域中測得癲癇發作並給予相對應的電刺激以抑制癲癇症狀。 本計畫所提之癲癇治療元件包含：(1)三維穿刺型與平面型電極陣列，可提供精細的局部刺激；(2)類比前端、生物信號處理器與電刺激器組合成之單封裝系統(SIP)。微電極陣列可用於記錄腦波信號與電刺激，微小化的SIP系統則提供腦波放大、記錄與判斷的功能，並在癲癇發作的狀況下，開啟電刺激器以局部抑制癲癇，避免擴散至全腦使病患產生危險。 我們也將採用高精準度的癲癇偵測演算法，前期研究顯示新的偵測演算法的準確度高達92%以上，本計畫將更進一步將此演算法實現於晶片系統中，並實際應用於動物實驗中。我們將整合上述電極陣列、系統晶片與演算法來開發動物實驗用的微小化低功率雛型系統，整合後的系統將穿戴於實驗大鼠身上，即時偵測與抑制癲癇的發作，以完整測試元件的功能，並觀察長期元件運作下的安全性。除了元件的開發，我們也將進行大鼠癲癇的基礎研究實驗，以進行棘徐波在同側大腦皮層之間及兩側大腦之間同步關係之分析，並評估大腦電刺激參數在癲癇行為調控之調控作用，以作為後續設計元件之參考。

In recent years, alternative treatments and devices are proposed to investigate and treat epilepsy in addition to pharmacological and surgical treatments. Several prosthesis devices with deep brain stimulation (DBS) or vagus nerve stimulation are becoming popular treatment for epilepsy clients. These devices use the open-loop continuous neural stimulations to control medical refractory epilepsies complementarily with the limited effective rate around 45%. Besides, by using continuous stimulations and an implantable battery, lifetime of such a device is often limited and periodically operations for clients are required to replace the battery/devices. To overcome above limitations, this research proposed close-loop epilepsy prosthesis devices with temporospatial seizure detection and responsively therapeutic stimulation. The proposed prostheses devices contain: 1) three-dimensional micromachining electrodes and highly compact flexible planner electrods with localize cortical stimulation drivers; 2) a system-in-a-chip(SIP) with ECoG recoder, bio-signal processing unit, and current stimulator. The low-power ECoG recorder and bio-signal processing circuitries are used to detect the seizure’s signal before it propagates to the whole cortex and activating localized cortical stimulation on the electrodes. The prototype SIP system and ECoG flexible electrodes will be developed and verified in this project. A portable seizure controller assembled by commercial discrete devices with our real-time seizure detection algorithms has been developed for two epileptic animal models for evaluation of the algorithm. Preliminarily experimental result on Long-Evans rats reveals at least 92% of seizure detection rate and stopping of seizure activity by responsively stimulation. Furthering animal tests with integrated prototype using our designed chips and electrodes will be carried on in this project. And the prototype will also be used in epileptic animal models for further studies in their ictogenesis. The successful of this research yields the first close-loop temporal seizure detection and spatial cortex stimulation prosthesis devices with more than 92% detection and suppression rate, which is a promising treatment for absence epilepsy.