人腦海馬迴的結構複雜細緻，但過去往往受限於磁共振造影有限的空間解析度，難以從影像進一步分析海馬迴內部，本研究使用Iglesias J.E.於2015年所提出的演算法，使用最小達0.1mm的超高解析度ex vivo影像搭配in vivo影像所做出的海馬迴圖譜，將海馬迴分成12個分區並統計其體積。在這個研究中，先使用OASIS的公開磁共振影像磁料庫，對20位受試者在間隔90以內獲得的兩組T1權重影像進行再現性測試，比較前後兩次之間所估計海馬迴分區體積之百分誤差，結果發現海馬迴總體積大約相差1.5%，且大部分的分區體積差異不大，僅有少數平均體積較小的分區，其百分誤差會大於5%。

此外，本研究對15位極低出生體重之青少年(早產組)與17位同齡正常人(對照組)進行海馬迴體積比較，結果顯示在絕對體積上，早產組在諸多分區與總體積都有顯著性小於對照組的情形，而在經過顱內體積修正的相對體積上，就沒有顯著性的差異。此外，海馬迴分區的絕對體積或相對體積與出生體重、年齡、記憶測驗分數、及FSIQ分數之間均無明顯相關性。最後，本研究使用百分誤差低於5%的分區，與先前發現早產兒大腦皮質較厚的五個DKT皮質區域、以及與海馬迴相鄰的兩個皮質區域(entorhinal cortex, parahippocampal gyrus)進行相關性分析，結果顯示left lateral occipital cortex的皮質厚度與右側海馬迴subiculum、hippocampal tail及whole hippocampus有明顯負相關，也就是皮質厚度較薄者其海馬迴分區體積可能較大，似乎對應到大腦發展的過程。同時，對照組中並沒有發現任何顯著的相關性，這可能是該年齡層的大腦正常發展已趨成熟所致。此外，與海馬迴相鄰之大部分皮質區域厚度與海馬迴中鄰近皮質的分區體積，例如:presubiculum、subiculum和CA1，有顯著正相關性。

Despite the hippocampal formation is complex and worthy to further investigate, in vivo hippocampal subfield is very difficult due to the limited spatial resolution of magnetic resonance imaging. In this study, the automatic segmentation proposed by Iglesias J.E. in 2015, which used ex vivo MRI with ultra-high resolution reaching 0.1 mm, along with in vivo MRI to build a computational atlas, is performed to obtain 12 hippocampal subfields. In the first part of this thesis, the reproducibility of this algorithm is examined by using the test-retest imaging data of 20 healthy volunteers provided by the OASIS public database. It is found that the percentage error of the whole hippocampus is around 1.5% and those in most subfields are ranging from 2% to 4%. Only few regions, usually in smaller size, have percentage error larger than 5%.
In the second part, the hippocampal subfield is applied on 15 teenagers born preterm with very-low-birth-weight and 17 age-matched controls. It is shown that the volume of many subfields and the whole hippocampus of the preterm group is significantly smaller than the control. However, no significant result is observed in the comparison of relative volume, in which the intracranial volume is used for normalization. In addition, no correlation is found between the hippocampal volume and the birth weight, age, nor the full-scale intelligent quotient of in the preterm group. Furthermore, the Pearson’s correlation test is evaluated between the hippocampal volume and several cortical regions in DKT atlas, including five regions reported with thicker cortical thickness in preterm and two regions adjacent to hippocampus. It is found that the preterm teenagers with thinner cortical thickness of left lateral occipital gyrus tends to have larger size in right subiculum, right hippocampal tail, and the whole right hippocampus, which seems to correspond to the development of the brain. Meanwhile, no correlation is observed in controls between cortical thickness and hippocampal volume, possibly because the development of human brain structure already reached stable in normal subjects of this age. For the mostly cortical regions attached to hippocampus, the cortical thickness is positively related to the volume of several hippocampal subregions close to cortex, such as presubiculum, subiculum, and CA1.

論文審定書 i
致謝 ii
摘要 iii
Abstract iv
目錄 vi
圖目錄 viii
表目錄 ix
介紹 1
1.1背景 1
1.2海馬迴自動分區之研究回顧 3
1-3研究目的 6
資料與方法 7
2.1 技術原理 7
2.1.1 海馬迴分區原理 7
2.1.2 海馬迴分區定義 9
2.2 開放軟體：Freesurfer ver. 6.0 10
2.3 影像資料 11
2.4實驗方法 12
2.4.1 再現性分析實驗流程 12
2.4.2 早產兒海馬迴體積分析流程 12
實驗結果 15
3.1 再現性分析結果 15
3.2 早產兒海馬迴體積分析結果 19
3.2.1 早產兒與對照組之海馬迴分區體積 19
3.2.2 海馬迴體積與出生體重、受試者年齡及智力測驗商數之相關性分析 22
3.2.3 海馬迴體積與大腦皮質厚度之相關性分析 27
討論與結論 45
4.1 再現性分析討論 45
4.2 早產兒海馬迴體積分析討論 46
4.2.1早產兒與對照組之海馬迴分區體積 46
4.2.2海馬迴體積與出生體重、受試者年齡及智力測驗商數之相關性討論 47
4.2.3 海馬迴體積與大腦皮質厚度之相關性分析 47
4.3 結論 50
參考文獻 51

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