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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80344完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蔡力凱(Li-Kai Tsai) | |
| dc.contributor.author | Hsin-Hsi Tsai | en |
| dc.contributor.author | 蔡欣熹 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:04:50Z | - |
| dc.date.available | 2021-07-07 | |
| dc.date.available | 2022-11-24T03:04:50Z | - |
| dc.date.copyright | 2021-07-07 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-06-22 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80344 | - |
| dc.description.abstract | 大腦類澱粉血管病變是一種β澱粉樣蛋白沈積在大腦皮質層和腦膜的小血管中引起的疾病，是自發性大葉型腦出血的主要病因。由於目前臨床治診斷方式侷限，對其致病機制也尚未了解，因此本研究包括三個具體目標，包括：（1）使用多重神經影像技術的方法研究大腦類澱粉血管病變的影像學特徵；（2）在同時患有大葉和深部出血（混合型腦出血）的患者中診斷大腦類澱粉血管病變；（3）建立血管間隙擴大與類澱粉血管病變之關聯性，並使用動物模型確定血管澱粉樣蛋白經由淋巴引流系統清除。 我們前瞻性地招募了症狀性腦出血的患者進行血液敏感性磁振造影和澱粉樣蛋白正子攝影檢查，以研究大腦類澱粉血管病變的影像學表現。我們發現，大腦澱粉樣血管病變不僅會導致大腦出血，也會導致小腦淺層微出血。我們同時建立了大腦類澱粉血管病變與腦葉裂隙性梗塞之間的關聯性，因此將此疾病的腦實質損傷從出血性表現擴展到了缺血性表現，這些影像標誌都可提高未來大腦類澱粉血管病變臨床診斷的敏感性。由於目前混合型腦出血的患者的致病原因還有所爭議，我們進一步利用澱粉樣蛋白正子攝影檢查，確認了他們主要的致病機轉是高血壓性小血管病變，而非大腦類澱粉血管病變。然而，一小部分混合型腦出血的病人同時患有兩種血管病變，而我們的兩年縱向追蹤資料證實了大腦類澱粉血管病變是其未來發生不良血管事件的危險因子，再次證明了在腦出血族群的患者中，診斷類澱粉血管病變的重要性。 為了進一步了解其致病機轉，我們在大腦類澱粉血管病變的病人中，研究磁振造影下可見的擴大血管周隙，發現其與澱粉樣蛋白沈積量增加有關。由於擴大的血管周隙暗示了大分子物質從大腦排除的淋巴引流功能受損，我們接著使用表現血管沈積澱粉樣蛋白的基因轉殖小鼠模型，破壞其腦膜淋巴引流途徑，發現會導致後續大腦的血管周隙擴大與血管澱粉樣蛋白沉積加劇，證實了腦膜淋巴引流是大腦類澱粉血管病變致病機轉的關鍵路徑，這也是未來發展大腦類澱粉血管病變治療策略的潛在標的。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:04:50Z (GMT). No. of bitstreams: 1 U0001-2006202116394300.pdf: 25298352 bytes, checksum: ffb18db22a821eb09820862752a2dcbe (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 口試委員會審定書……………………………………………………………… i 誌謝……………………………………………………………………………… ii 中文摘要………………………………………………………………………… iii 英文摘要………………………………………………………………………… iv 目錄……………………………………………………………………………… v 圖目錄…………………………………………………………………………… vii 表目錄…………………………………………………………………………… ix 第一章 緒論 (Introduction) ……………………………………………………………… 1 1.1 Cerebral amyloid angiopathy and the clinical diagnostic criteria ……………………. 1 1.2 Conventional neuroimaging characteristics in cerebral amyloid angiopathy ………… 4 1.3 Functional and molecular imaging in cerebral amyloid angiopathy …………………. 9 1.4 Cerebral amyloid angiopathy and microbleed distribution pattern …………………. 12 1.5 Pathogenic mechanisms in cerebral amyloid angiopathy ……………….…………… 17 1.6 Research hypothesis and specific aims ………….…………………………………. 21 第二章 研究方法與材料 (Method and Material) …………………………………………. 23 2.1 Clinical study ………………………………………………………………………... 23 2.2 Animal model ………………………………………………………………...……... 27 第三章 結果 (Results) ………………………………………………………………………… 30 3.1 Superficial cerebellar microbleeds and cerebral amyloid angiopathy ………………. 30 3.2 Lobar lacunes and cerebral amyloid angiopathy ……………………………………. 32 3.3 Mixed location intracerebral hemorrhages/microbleeds ……………………………. 34 3.4 Cerebral amyloid angiopathy and enlarged perivascular spaces ……………………. 38 3.5 Impaired meningeal lymphatic drainage function facilitates vascular amyloid deposition ……………………………………………………………...………………… 39 第四章 討論 (Discussion) …….……………………………………………………………… 40 4.1 Strictly superficial cerebellar microbleeds are associated with CAA ….…………… 40 4.2 CAA induces not only lobar hemorrhages but also lacunar infarcts ……….……… 43 4.3 Microangiopathy underlying Mixed-ICH is predominantly HTN-SVD .……………. 46 4.4 Coexisting CAA and HTN-SVD in Mixed-ICH predicts long-term vascular event .... 49 4.5 Centrum semiovale perivascular space is a severity marker in CAA and suggests possible pathogenic mechanism .……………………………………...………………… 52 4.6 Vascular amyloid clearance potentially via meningeal lymphatic drainage route …... 55 第五章 展望 (Contribution and Future Work) …………………………………………… 57 5.1 Expanding the radiological spectrum in cerebral amyloid angiopathy ……………… 57 5.2 Deciphering the causes of nontraumatic intracerebral hemorrhage .……...…………. 59 5.3 Clearance pathway as potential therapeutic targets in CAA .……………………… 62 5.4 Future work .………………………………………………………...……………… 64 第六章 簡述 (Summary) …………………………………………………………………… 66 第七章 參考文獻 (Reference) ……………………………………………………………… 75 第八章 附錄 (Appendix) ……………………………………………………………… 92 | |
| dc.language.iso | en | |
| dc.subject | 腦膜淋巴管 | zh_TW |
| dc.subject | 類澱粉血管病變 | zh_TW |
| dc.subject | 大腦小血管病變 | zh_TW |
| dc.subject | 腦出血 | zh_TW |
| dc.subject | 大腦血管周隙 | zh_TW |
| dc.subject | Intracerebral Hemorrhage | en |
| dc.subject | Meningeal Lymphatic Vessel | en |
| dc.subject | Brain Perivascular Space | en |
| dc.subject | Cerebral Amyloid Angiopathy | en |
| dc.subject | Cerebral Small Vessel Disease | en |
| dc.title | 大腦類澱粉血管病變之診斷與病態生理機轉之探討 | zh_TW |
| dc.title | Multimodal Diagnosis and Pathophysiology of Cerebral Amyloid Angiopathy | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.author-orcid | 0000-0002-4721-1468 | |
| dc.contributor.coadvisor | 張哲逢(Che-Feng Chang) | |
| dc.contributor.oralexamcommittee | 林靜嫻(Hsin-Tsai Liu),曾明宗(Chih-Yang Tseng),吳文超,李怡慧,李俊泰 | |
| dc.subject.keyword | 類澱粉血管病變,大腦小血管病變,腦出血,大腦血管周隙,腦膜淋巴管, | zh_TW |
| dc.subject.keyword | Cerebral Amyloid Angiopathy,Cerebral Small Vessel Disease,Intracerebral Hemorrhage,Brain Perivascular Space,Meningeal Lymphatic Vessel, | en |
| dc.relation.page | 133 | |
| dc.identifier.doi | 10.6342/NTU202101066 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-06-22 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
| 顯示於系所單位： | 臨床醫學研究所 | |
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| U0001-2006202116394300.pdf 授權僅限NTU校內IP使用（校園外請利用VPN校外連線服務） | 24.71 MB | Adobe PDF |
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