設計一個具有核磁共振相容性的微電極陣探討大鼠腦功能

Abstract

此研究之主要目的是設計與製造一個具有核磁共振相容性的微電極陣列，經實驗結果證實該微電極陣列具有良好的生物相容性，長時間紀錄神經訊號仍維持良好的訊號品質，應用於電損傷實驗時具高重複使用率，且在功能性核磁共振系統下有良好的核磁共振相容性。本研究的軟性微電極陣列以無毒性的高分子材料聚醯亞胺(Polyimide)為基材，其陣陣列長度為14.9 mm且具有16個直徑16 μm、厚度5 μm的電極。使用聚醯亞胺為基材是因其具有較小的楊氏係數，與腦組織間的協調性較好，可降低長期的免疫反應，進而增加電極可使用的時間與穩定度，但只以聚醯亞胺材料當作基材的微電極陣列太軟，造成植入時的困難且產生植入目標區的誤差，因此本研究在兩層聚醯亞胺間加入金屬強化層，用以強化軟性的高分子材料。此外，本研究在電極的形成以電鍍(electroplating)法取代薄膜沉積(thin-film deposited)法，進而形成具有三維結構且表面粗糙的電極，不均勻的電極表面可增加總表面積而降低其阻抗值，在食鹽水中量測頻率1kHz時的電極阻抗值為2.4 ± 0.52 MΩ。經連續七週的動物實驗測試，證實其在長期神經訊號紀錄時能維持穩定的訊號品質，且重複使用於電損傷(electrolytic lesion)高達60次仍未損壞，證實電極對電損傷實驗有很好的耐受性。此外，應用於功能性核磁共振造影的實驗中，預先透過有限元素法與神經模型的模擬，評估電刺激參數能影響的組織活化體積(volume of tissue activated, VTA)，再經由功能性核磁共振造影系統的影像得到血氧濃度相關(Blood oxygenation level dependent, BOLD)效應的變化，探討大鼠丘腦電刺激時腦部區域與功能的反應。以上實驗結果證實本研究提出核磁共振相容的微電極陣列，提供了一個有效的新工具，可同步從解剖與電生理了解腦部功能的傳遞關係，對於了解中樞神經系統的運作與路徑傳遞有很大的幫助。

The design and testing of a magnetic resonance compatible microelectrode array, the National Chiao Tung University (NCTU) probe, was presented. Evaluation results showed it has good biocompatibility, high signal-to-noise ratio (SNR: the average peak-to-peak amplitude of spikes to the root mean square of background noise) during chronic neural recordings, high reusability for electrolytic lesions, and good MR-compatibility for fMRI studies. The probe was a flexible, polyimide-based microelectrode array with a long shaft (14.9 mm in length) and 16 electrodes (5 μm thick and 16 μm in radius); its performance in chronic in vivo recordings was examined in rodents. To improve the precision of implantation, a metallic, impact-resistant layer was sandwiched between the polyimide layers to strengthen the probe. The three-dimensional (3D) structure of electrodes fabricated by electroplating produced rough textures that increased the effective surface area. The in vitro impedance of electrodes on the NCTU probe was 2.4 ± 0.52 MΩ at 1 kHz. In addition, post-surgical neural recordings of implanted NCTU probes were conducted for up to 40 days in awake, normally-behaving rats. The electrodes on the NCTU probe functioned well and had a high SNR (range: 4-5) with reliable in vivo impedance (< 0.7 MΩ). The electrodes were also robust enough to functionally record events, even after the anodal current (30 μA, 10 sec) was repeatedly applied for 60 times. The volume of tissue activated estimated by excitation threshold was more accurate than those estimated by activating function. Two inherent factors, tissue conductivity and fiber direction, were the major influence on the volume of tissue activated. The effect of electrode configuration on the volume of tissue activated was unobvious. NCTU probe used in the fMRI study obtained the less image artifact and MR signal loss. The positive blood oxygen level-dependent (BOLD) signals were observed in the ipsilateral primary forelimb somatosensory (S1FL) during the direct thalamic stimulation in rats’ brain. With good biocompatibility, high and stable SNR for chronic recording, high tolerance for electrolytic lesion, and advantage of MR-compatibility, the NCTU probe would serve as a useful device in future neuroscience research.