大腦皮質厚度可以提供臨床上重要的資訊，並且診斷特定神經退化疾病嚴重程度，現今自動化量測方法可分為Surface-based或Voxel-based方式，本研究比較三種量測方法的再現性程度，分別為Surface-based方式中的FreeSurfer和Voxel-based方式中的DiReCT、Laplace-VBCT兩種。再現性分析於單一受試者重複進行MR掃瞄時，比較全域及區域皮質的厚度變異係數大小，結果顯示三種方法於全域比較中再現性程度相差不大，在根據DKT atlas所進行的皮質分區比較中，FreeSurfer相較於兩種Voxel-based方法在絕大數的區域中具有最小的變異係數。

此外，本研究使用這三種量測方法，對於15位具有極低出生體重且排除腦部傷害的早產青少年（平均年齡12.8歲）與17位同年齡出生體重正常的對照組（平均年齡13.8歲）進行大腦皮質厚度分析。結果顯示不管使用何種量測方法，早產組相對於同齡對照組在部分區域發現較厚皮質，且只有在使用Laplace-VBCT方法時才發現有極小區域有較薄的皮質。若將受試者採用13歲分為高低次群組比較，早產兒皮質較厚的現象在低齡群組的比較中依舊存在，在高齡群組中反而出現較厚和較薄區域共陳的結果。發現支持人腦大腦皮質於青春期發展有皮質修剪現象，且極低出生體重早產兒有延遲的大腦成長，所以早產兒之皮質修剪現象相對同齡對照組較慢發生，但隨著歲數增長，兩群組之間差異縮小。

Cerebral cortical thickness can provide important clinical information, helping the diagnosis of specific neurodegenerative diseases. In general, the automatic cortical thickness measurement methods can be classified into two types, surface-based and voxel-based. In this study, three methods, including one surface-based FreeSurfer and two voxel-based methods, DiReCT and Laplace-VBCT, are compared. A single subject was scanned for 24 times in a period of three and half months. The global and regional mean of cortical thickness are obtained for each experiment to exam the reproducibility. Results show that the coefficients of variance (CV) of three methods are very close to each other while FreeSurfer is found to have the smallest CV in most of DKT cortical regions than two other voxel-based methods.

In addition, magnetic resonance imaging experiments were performed on 15 young teenagers very-low-birth-weight born preterm (mean age 12.8 yr), all without brain injury, and age-matched 17 normal peers (mean age 13.8 yr) to assess the cerebral cortical thickness. The two-sample t-test with a p value of 0.05 is used to detect the statistical difference. Thicker cortical thickness was found in parietal, temporal, and occipital lobes of the preterm group by using all three measurement methods. In a sub-group comparison, thicker cortices are found in similar areas of young preterm compared with young control. However, when the old preterm is compared to the old control group, more cortical regions with thinner thickness are found than those with thicker cortex. In addition, the young preterm group has thinner cortex than old preterm, revealing the cortical thinning during childhood and early adolescence, which can be also observed but in much less area. All of our results suggest that the developmental cortical thinning of preterm born children is delayed to their term born peers, but the group deviation of cortical thickness is narrowed with increasing age.

論文審定書 i
致謝 ii
摘要 iii
Abstract iv
目錄 vi
圖目錄 viii
表目錄 x
第一章 介紹 1
1.1 背景 1
1.2 文獻探討 4
1.2.1 皮質自動化量測方法 4
1.2.2 皮質厚度發展曲線 6
1.2.3 早產兒皮質厚度 9
1.3 研究動機 11
第二章 資料與方法 12
2.1 影像資料 12
2.2 皮質厚度量測方法 14
2.2.1 Surface-based : FreeSurfer 14
2.2.2 Voxel-based : Laplace-VBCT演算法 19
2.2.3 Voxel-based : DiReCT演算法 23
2.2.4 皮質厚度量測流程 25
2.3 大腦皮質分區 26
2.4 實驗設計 28
第三章 實驗結果 30
3.1 再現性分析結果 30
3.1.1 全域(Global)皮質厚度分析 30
3.1.2 區域(Region)皮質厚度分析 32
3.2 早產兒皮質厚度分析結果 37
3.2.1分析流程說明 37
3.2.2 Vertex-wise分析 38
3.2.3 Region-wise分析 44
第四章 討論與結論 57
4.1 再現性分析討論 57
4.2 早產兒皮質厚度分析討論 58
4.3 結論 61
參考文獻 62

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