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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳志宏 | zh_TW |
| dc.contributor.advisor | Jyh-Horng Chen | en |
| dc.contributor.author | 阮唯紘 | zh_TW |
| dc.contributor.author | Wei-Hong Ruan | en |
| dc.date.accessioned | 2025-11-26T16:27:11Z | - |
| dc.date.available | 2025-11-27 | - |
| dc.date.copyright | 2025-11-26 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-09-22 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/101009 | - |
| dc.description.abstract | 癲癇是一種神經系統疾病，特徵為大腦神經元的異常同步放電。部分病患無法以傳統抗癲癇藥物進行治療，需使用替代療法，如反應式神經刺激、迷走神經刺激、深部腦刺激、經顱磁刺激、經顱直流電刺激等，而這些療法多屬侵入式。近年，聚焦式超音波(Focus Ultrasound, FUS) 作為一種非侵入式，且被認為具有神經調控潛力。故本研究基於腦電訊號(Electroencephalography, EEG) 回饋，開發一套閉迴路(Closed-Loop) 超音波系統，並使用EEG, 功能性磁振造影(functional MRI)，及組織切片等多模態評估方式，以驗證癲癇的抑制效果及系統的可行性。
本研究建構一癲癇大鼠模型，並採用閉迴路與開放迴路兩種模式，結合不同機械指數（0.25 MI 與0.75 MI），對視丘進行超音波治療。EEG 結果顯示，0.25 MI下閉迴路模式在後期具有較佳的抑制效果；0.75 MI 雖在中期表現良好，惟後期癲癇尖波略有上升。fMRI 分析顯示，開放迴路組BOLD 訊號於第40 分鐘下降，但隨後回升，顯示其抑制效果有限。區域分析發現，視丘與海馬迴呈現明顯調控反應，後扣帶皮質與初級聽覺皮質則變化不明顯。功能性連結分析顯示，癲癇發作後腦區連結性上升，經開放迴路治療後下降，其中0.25 MI 效果優於0.75 MI。雖視丘與其他腦區的連結未達統計顯著，0.25 MI 仍展現出明確的抑制趨勢。組織切片分析顯示，癲癇發作後c-Fos 表現上升，反映神經過度活化，經閉迴路治療可恢復至接近對照組，具神經抑制效果。GAD65/67 表現則於癲癇後下降，顯示抑制性神經元功能受損，閉迴路刺激後回升，維持抑制網路穩定性。結果驗證閉迴路聚焦式超音波具神經調控潛力。 綜合三個評估方式結果，基於EEG 的閉迴路fcFUS 系統在抑制癲癇發作、穩定神經網絡與維持神經功能方面展現潛力，尤以低機械指數（0.25 MI）表現最穩定。惟0.25 與0.75 MI 間差異仍需更大樣本與長期研究佐證。整體結果支持閉迴路聚焦式超音波為具發展潛力的癲癇干預工具，未來可望實現即時監控與個體化刺激的精準神經調控應用。 | zh_TW |
| dc.description.abstract | Epilepsy is a neurological disorder characterized by abnormal synchronous neuronal discharges. While various neuromodulatory therapies such as RNS, VNS, DBS, TMS, and tDCS have shown efficacy, most are invasive. Focused ultrasound (FUS) offers a non-invasive alternative with neuromodulatory potential. This study developed a closed-loop FUS system driven by electroencephalography (EEG) feedback and evaluated its efficacy using EEG, functional MRI (fMRI), and histological analysis in a rat epilepsy model.
Closed-loop and open-loop stimulation modes were applied to the thalamus using two acoustic pressures (0.25 MI and 0.75 MI). EEG results showed that 0.25 MI under closed-loop conditions provided better seizure suppression in the later phase. fMRI analysis indicated limited effects in the open-loop group, with transient BOLD signal reduction. Regional and connectivity analyses revealed modulation in the thalamus and hippocampus, with 0.25 MI showing more consistent inhibitory trends. Histology showed that closed-loop stimulation reduced seizure-induced c-Fos expression and restored GAD65/67 levels, suggesting reduced neuronal hyperactivity and preserved inhibitory function. Overall, the EEG-based closed-loop FUS system demonstrated potential in seizure suppression and network stabilization, especially under low acoustic pressure. These findings support its development as a precise and non-invasive neuromodulation strategy for epilepsy. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-11-26T16:27:11Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-11-26T16:27:11Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員審定書i
致謝ii 摘要iv Abstract vi 目次vii 圖次xi 表次xiv 第一章緒論1 1.1 癲癇疾病介紹. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 聚焦式超音波之神經調控應用於癲癇抑制. . . . . . . . . . . . . . 2 1.3 基於EEG 訊號回饋以進行超音波治療及應用於閉迴路控制之可行性7 1.4 研究目的及貢獻. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 第二章方法與理論11 2.1 實驗架構. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 2.2 聚焦式超音波. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 2.2.1 硬體配置. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 2.2.2 聲場特性及強度換算. . . . . . . . . . . . . . . . . . . . . . . . 13 2.2.3 刺激參數. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 2.3 動物模型準備及實驗分組. . . . . . . . . . . . . . . . . . . . . . . . 17 2.3.1 動物準備. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 2.3.2 癲癇模型建立及麻醉藥物選用. . . . . . . . . . . . . . . . . . . 17 2.3.3 實驗分組. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 2.3.4 目標腦區選擇及實驗操作定位. . . . . . . . . . . . . . . . . . . 21 2.4 閉迴路控制系統架構與設計. . . . . . . . . . . . . . . . . . . . . . 21 2.4.1 LSL 資料傳輸. . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 2.4.2 EEG 特徵擷取及小波轉換闕值設定. . . . . . . . . . . . . . . . 23 2.4.3 癲癇Burst 定義. . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 2.4.4 訊號產生器程式控制. . . . . . . . . . . . . . . . . . . . . . . . 25 2.5 EEG 量測實驗. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 2.5.1 實驗環境及架設. . . . . . . . . . . . . . . . . . . . . . . . . . . 25 2.5.2 EEG 實驗流程. . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 2.6 fMRI 掃描實驗. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 2.6.1 實驗設備及架設. . . . . . . . . . . . . . . . . . . . . . . . . . . 28 2.6.2 MRI 掃描序列. . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 2.6.3 MRI 實驗流程. . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 2.7 組織學分析. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 2.7.1 腦組織切片製備. . . . . . . . . . . . . . . . . . . . . . . . . . . 32 2.7.2 免疫組織化學染色. . . . . . . . . . . . . . . . . . . . . . . . . . 33 2.8 資料分析. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 2.8.1 EEG 資料處理. . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 2.8.2 fMRI 影像處理. . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 2.8.2.1 SPM 影像前處理. . . . . . . . . . . . . . . . . . . . 34 2.8.2.2 RESTplus 影像後處理. . . . . . . . . . . . . . . . . 37 2.8.2.3 腦區功能性連結矩陣之建立. . . . . . . . . . . . . . 38 2.8.3 免疫組織化學影像分析. . . . . . . . . . . . . . . . . . . . . . . 40 2.9 統計分析. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 第三章實驗結果43 3.1 EEG 實驗結果. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 3.1.1 藥物誘發癲癇之EEG 效果. . . . . . . . . . . . . . . . . . . . . 43 3.1.2 超音波治療之EEG 效果評估. . . . . . . . . . . . . . . . . . . . 43 3.1.2.1 開放迴路及閉迴路尖波分布結果. . . . . . . . . . . 43 3.1.2.2 開放迴路及閉迴路尖波統計結果. . . . . . . . . . . 47 3.2 fMRI 實驗結果. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 3.2.1 BOLD map 結果. . . . . . . . . . . . . . . . . . . . . . . . . . . 50 3.2.2 功能性連結矩陣結果. . . . . . . . . . . . . . . . . . . . . . . . 56 3.3 組織切片分析結果. . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 3.3.1 H&E 染色結果分析. . . . . . . . . . . . . . . . . . . . . . . . . 63 3.3.2 c-Fos 染色結果分析. . . . . . . . . . . . . . . . . . . . . . . . . 63 3.3.3 GAD65/67 染色結果分析. . . . . . . . . . . . . . . . . . . . . . 68 第四章討論71 4.1 閉迴路聚焦式超音波系統於癲癇抑制之優勢探討. . . . . . . . . . 71 4.2 低頻超音波探頭及參數選用與抑制效果分析. . . . . . . . . . . . . 72 4.3 CM 腦區施打之效果評估. . . . . . . . . . . . . . . . . . . . . . . . 75 4.4 超音波神經調控之機制探討. . . . . . . . . . . . . . . . . . . . . . 76 4.5 臨床前癲癇治療技術之神經調控效果討論. . . . . . . . . . . . . . 78 第五章結論與未來展望81 5.1 結論. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 5.2 未來展望. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 5.2.1 EEG-fMRI 同步閉迴路系統架構實現. . . . . . . . . . . . . . . . 83 5.2.2 基於機器學習之自適應閉迴路系統：慢性癲癇長期治療策略. . 84 參考文獻86 附錄A — 實作演示影片100 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 閉迴路 | - |
| dc.subject | 聚焦式超音波 | - |
| dc.subject | 癲癇 | - |
| dc.subject | 腦電訊號 | - |
| dc.subject | 功能性磁振造影 | - |
| dc.subject | Closed Loop | - |
| dc.subject | Focus Ultrasound | - |
| dc.subject | Epilpesy | - |
| dc.subject | Electroencephalography | - |
| dc.subject | Functional Magnetic Resonance Imaging | - |
| dc.title | 非侵入式閉迴路超音波系統於大鼠癲癇發作之抑制效果評估 | zh_TW |
| dc.title | Evaluation of the Suppressive Effects of a Non-Invasive Closed-Loop Ultrasound System on Rodent Epileptic Seizure Activity | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 114-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.coadvisor | 劉浩澧 | zh_TW |
| dc.contributor.coadvisor | Hao-Li Liu | en |
| dc.contributor.oralexamcommittee | 謝寶育;葉秩光;謝宗勳;尤香玉 | zh_TW |
| dc.contributor.oralexamcommittee | Bao-Yu Hsieh;Chih-Kuang Yeh;Tsung-Hsun Hsieh;Hsiang-Yu Yu | en |
| dc.subject.keyword | 閉迴路,聚焦式超音波癲癇腦電訊號功能性磁振造影 | zh_TW |
| dc.subject.keyword | Closed Loop,Focus UltrasoundEpilpesyElectroencephalographyFunctional Magnetic Resonance Imaging | en |
| dc.relation.page | 100 | - |
| dc.identifier.doi | 10.6342/NTU202504492 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2025-09-23 | - |
| dc.contributor.author-college | 電機資訊學院 | - |
| dc.contributor.author-dept | 生醫電子與資訊學研究所 | - |
| dc.date.embargo-lift | 2025-11-27 | - |
| 顯示於系所單位： | 生醫電子與資訊學研究所 | |
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