由於核磁共振造影技術的進步，現代醫學可利用此非侵入式的磁振影像來評估母體內人類胎兒大腦的發展，提供了關於大腦皺摺發展的珍貴訊息。然而，過去磁振影像相關研究多以定性的方式來觀察胎腦皺褶的發展，定量分析則尚未廣泛應用。因此，本論文著重於以多樣化的定量方法來分析成長中的胎腦磁振影像，並借由這些定量結果，深入探討關於大腦皮質在皺褶發育過程中的重要訊息。
本論文主要分成三個部分。
第一部分為探討正常胎兒大腦皺摺和體積發展過程中，是否有成長速度上的局部差異。在這個部分中，作者提出兩種可能的方法來合理地分區連續的二維胎兒大腦影像。我們發現不同區域的皮質皺褶有相同的成長速率，這顯示了不同區域的皮質層隨著時間有相同的變化量。相反的，大腦體積的發展呈現局部性的差異，前額葉區和頂顳葉區成長速率比其它區域快，這個結果是由基底核的體積成長所造成的。這個分區量化的訊息顯示對於量測大腦皺摺量，腦體積不是一個很有意義的參數，而皮質層的大小可能和腦皺褶有較直接的關係。
在第二部份中，作者將胎腦皺摺的定量分析擴展至三維立體腦的計算。我們利用超解析重組法(super-resolution reconstruction)來重組出胎兒的三維立體腦，並提出一個新的分割大腦腦區的方法。研究結果顯示型態指標(shap index)可以正確地顯示不同的皺褶型態，並在枕葉區有較其它區域更快速的發展。這表示皮質表面的形狀(shape)是一個新的方向可用來評估大腦皺摺的發展。
在第三部分中，本研究闡明大腦皮質之複雜度與形狀之差異，並發現相對複雜度而言，大腦皮質腦迴頂端之形狀與神經軸索密度有較高度的相關性。這結果強調在分析大腦皮質發展時，區分其複雜度與形狀之重要性。
本論文提供不同的量化方式應用於母體內胎兒大腦磁振影像，建立正常大腦皺摺發展過程的模型，未來可推廣應用至患有神經系統成長相關疾病的胎兒，提供更準確合理的方式來評估大腦發育的狀況。

Magnetic resonance (MR) imaging is a noninvasive and safe tool for assessing the development of fetal brains in utero. Fetal MR brain images provide important information about the maturation of cortical folding. In the past, most of neuroimaging studies investigated the fetal folding development via qualitative analyses. However, the quantitative analysis of fetal brains is quite limited. This thesis aims at using various methods to quantify the folding development of fetal brains, and gives insights into the development of fetal brains.
This thesis is divided into three major sections.
In the first section, this thesis investigates the regional difference of growth rate between the fetal gyrification and cerebral volume. In this section, the authors propose two parcellations that reasonably dissect a series of two-dimensional fetal brain images. Our finding shows the similar growth rates of fetal gyrification across brain areas, suggesting a similar uniformity of changes in size of the cortical sheet in these areas over time. On the contrary, our results show that the regional difference in the development of cerebral volume is stemmed from the enlargement of deep brain nuclei. These results suggest that the cerebral volume is not a relevant parameter to measure in relation to gyrification, and that the size of the cortical sheet is more likely to be directly related to cortical folding.
In the second section, the author extends the quantification of fetal cortical folding from two-dimensionally to three-dimensionally. This study uses the super-resolution technique to reconstruct the three-dimensional fetal brain surfaces, and provides a novel parcellation on theses brain surfaces. The results of our study show that the shape index can accurately capture the distinct shapes of cortical folding and presents a faster growth in occipital lobe than other lobes. This suggests that cortical shape is a new a perspective in the assessment of brain development.
In the third section, this thesis clarifies the difference between the complexity and the shape of cerebral cortex. Out finding shows that the shape of gyral crown is correlated to the fiber density more than the cortical complexity does. This supports the importance of dividing the complexity and the shape in the assessment of brain development.
This thesis provides the important quantitative results that combine distinct morphological indices with fetal MR brain images, and establishes the growth model of normally developing brains. These results may be helpful in the developmental assessment of fetuses with neuro-developmental disorders in the future.

CONTENTS I
LIST OF FIGURES V
LIST OF TABLES VIII
致謝 IX
ENGLISH ABSTRACT X
中文摘要 XII
CHAPTER 1 INTRODUCTION 1
1.1 BACKGROUND 1
1.2 AIM OF DISSERTATION 3
1.3 OVERVIEW 3
1.4 FETAL BRAIN RECONSTRUCTION: SUPER-RESOLUTION 4
CHAPTER 2 MORPHOLOGICAL REGIONALIZATION USING FETAL MAGNETIC RESONANCE (MR) IMAGES OF NORMAL DEVELOPING BRAINS 8
2.1 ABSTRACT 8
2.2 INTRODUCTION 9
2.3 MATERIALS AND METHODS 11
2.3.1 Subjects 11
2.3.2 Image acquisition 12
2.3.3 Semiautomatic cerebrum extraction 13
2.3.4 Parcellation of fetal brain 14
2.3.5 Morphological indices for the assessment of brain development 16
2.3.6 Statistical analyses 18
2.4 RESULTS 19
2.5 DISCUSSION 22
2.5.1 Comparable growth rate in cortical folding addressed by the tension-based theory of morphogenesis 24
2.5.2 The age effect on cerebral volume and gyrification in utero 25
2.6 CONCLUSION 26
CHAPTER 3 REGIONAL QUANTIFICATION OF DEVELOPING HUMAN CORTICAL SHAPE USING A THREE-DIMENSIONAL SURFACE-BASED MAGNETIC RESONANCE IMAGING ANALYSIS IN UTERO 28
3.1 ABSTRACT 28
3.2 INTRODUCTION 29
3.3 MATERIALS AND METHOD 31
3.3.1 Subjects 31
3.3.2 Neuroimaging 32
3.3.3 Reconstruction of fetal brain image with 3D coherence 33
3.3.4 Fetal brain image extraction 34
3.3.5 Fetal brain parcellation 36
3.3.6 Quantification of cortical surface shape by shape index (SI) 38
3.3.7 Statistical analysis 41
3.4 RESULTS 43
3.4.1 Surface shape encoding by shape index 44
3.4.2 Global shape patterns between sulci and gyri 44
3.4.3 Regional shape patterns across four brain lobes 45
3.4.4 Absolute SI frequencies at particular GAs 47
3.4.5 Correlation between SI and GA for 9 shape scales 48
3.5 DISCUSSION 49
3.5.1 Limitations and technical remarks 51
3.6 CONCLUSION 53
3.7 APPENDIX: NINE SCALES OF SHAPE INDEX 53
CHAPTER 4 BRAIN COMPLEXITY AND SHAPE: PRELIMINARY RESULTS 55
4.1 INTRODUCTION 55
4.2 METHODS 58
4.3 RESULTS 65
4.3.1 Complexity-shape analysis v.s. cerebral volume (Vol) 65
4.3.2 Complexity-shape analysis v.s. fiber density (FD) 67
4.4 SUMMARY 69
CHAPTER 5 CONCLUSION 71
5.1 CONTRIBUTION OF DISSERTATION 71
5.2 FUTURE WORK 71
REFERENCES 75
PUBLICATIONS 80

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