Non-Interpolated Tract-Based Statistic Analysis for Estimating The Corticospinal Tract: A Comparison with Parkinson's Disease, Essential Tremor and The Normal Control

Diffusion tensor imaging (DTI) has been proved as a powerful tool for parameterizing microstructure changes with various neurodegenerative diseases such as Parkinson's disease (PD) or essential tremor (ET). Although these two diseases have been reported as involving motor cortical dysfunction, the central mechanisms to induce their tremor symptoms are still remain unclear. Previously, researchers started using DTI to quantify white matter changes. However, they barely draw congruent conclusions. Among these studies, we found group quantifications with ROI-based methods seem to provide better sensitivity in detecting subtle changes than those with methods containing spatial normalization. In light of these findings, we hypothesize DTI quantification method that applied with minimal spatial transformation or interpolation could be more sensitive in detecting such alterations. In this thesis, we provided a full investigation to all mainstream DTI quantification approaches, including their concepts and features. We also compared their advantages and drawbacks. Then, we extended the application of the traditional ROI-based method to a 3D tract-specific one. In chapter 4, we provided a tract-based quantitative framework combined with minimal spatial preprocessing and performed a head-to-head comparison between PD, ET and the normal subjects. We also provided a small pilot study to determine the suitable protocol setting of the DTI sequence. The results showed that the FA distributions along the corticospinal tract have significant differences across groups. The ET group showed significant higher mean FAs in the internal capsule level of the CST bilaterally as compared to the normal group. The PD group also showed higher mean FAs, but in region near the level of thalamus. Comparing between the PD and ET groups, the ET group showed lower mean FA values around the midbrain region. Our presented approach successfully demonstrates the white matter changes to the PD, ET and normal subjects by estimating their corticospinal tracts. In such tractography-based statistical approach, we not only proved its advantages in giving detail along certain fiber tract compare to traditional ROI-based approach but also provided better sensitivity to detect subtle microstructure changes than other approaches involving spatial transformation.磁振張量影像(DTI)是一種強而有力的非侵入性影像技術，可用於觀察各種神經退化性疾病所造成的白質損傷。而帕金森氏症 (Parkinson's disease, 簡稱PD) 以及原發性顫動症 (essential tremor, 簡稱ET) 則是兩種常見的動作障礙疾病。目前雖已證實這兩種疾病與大腦皮質的運動機能不良有相關性，然其導致顫動症狀的神經機轉目前仍尚未確定。近年來，科學家開始將磁振張量影像技術應用於這兩種疾病的探討，然而，這些研究的結果並未表現出高度的一致性。藉由歸納這些研究的結果，我們發現採用傳統ROI (region of interest) 方式進行量化統計的DTI實驗似乎比採用包含影像前處理的方式 (如VBM或是TBSS) 更能觀察到細微的白質變異。因此，我們認為盡可能減少任何破壞性的影像前處理可以有效地提升偵測白質差異的敏感度。 在本論文中，我們探討了所有主流的磁振張量影像量化方式，包含其基本觀念及其特質。也對其優缺點進行觀察和比較。最終，我們提出一個基於神經纖維束影像 (tractography-based) 所發展出的DTI量化分析方式。Tractography-based方式可視為傳統 ROI-based方式的延伸應用, 其利用追蹤出來的神經纖維束影像對沿著特定走向的神經束做非等向性的分析。在論文第四章中，我們將所發展的量化分析方法對皮質脊髓神經束 (corticospinal tract, CST) 進行量化分析，並比較帕金森氏症，原發性顫動症患者與健康受試者之間的差異。實驗中，我們額外進行了一個小型試驗用以定義出最適合臨床使用的DTI掃描參數。 根據結果，三個群組在皮質脊髓神經束可觀察到顯著差異。原發性顫動症患者的質脊髓神經束在靠近內囊的區域 (internal capsule) 較一般受試者在兩側皆有顯著的非等向性值 (fractional anisotropy, FA) 上升。而帕金森氏症患者患者相較於一般受試者則在右側丘腦 (thalamus) 高度的位置有顯著的FA值上升。而比較原發性顫動症及帕金森氏症患者，原發性顫動症族群的FA值在中腦區域較帕金森氏症患者來的低。 透過我們的量化分析方式，成功的觀察到帕金森氏症，原發性顫動症患者與正常受試者在皮質脊髓神經束上的差異。同時，藉由此試驗證實此分析方式應用於磁振張量影像的量化分析上足以提供好的敏感度。Acknowledgements........................................................................................i Chinese Abstract..........................................................................................iii English Abstract.............................................................................................v Contents......................................................................................................vii List of Figures................................................................................................x List of Tables................................................................................................xii Chapter 1 Introduction..................................................................................1 1.1 Motivations and Contributions.................................................................1 1.2 Outline.....................................................................................................2 Chapter 2 Diffusion Tensor Imaging...............................................................6 2.1 Magnetic Resonance Imaging (MRI)...........................................................6 2.2 The Diffusion Theory................................................................................7 2.3 Diffusion Weight Imaging.........................................................................7 2.4 Diffusion Tensor Imaging (DTI)...............................................................10 2.4.1 Basic Principles....................................................................................10 2.4.2 Quantification Indexes.........................................................................13 2.4.2.1 Apparent Diffusion Coefficient (ADC Map).......................................13 2.4.2.2 Fractional Anisotropy (FA Map) and Color-Coded FA (cFA Map).......14 2.4.2.3 Geometrical Maps (CL, CP and CS Map)............................................17 2.4.2.4 Other Indexes (RA, VR)....................................................................19 2.4.3 Tractography......................................................................................20 2.4.3.1 Streamline Propagation...................................................................20 2.4.3.2 Other Approaches...........................................................................21 2.4.4 Limitations..........................................................................................22 Chapter 3 DTI Quantification Statistics.........................................................24 3.1 Conventional Approaches.......................................................................25 3.1.1 ROI-Based Approach (Region of Interest).............................................25 3.1.2 Voxel-Based Approach........................................................................25 3.1.2.1 Basic Concepts................................................................................25 3.1.2.2 Advantages and Drawbacks of VBM.................................................26 3.1.2.3 Potential Bias of DTI Analysis by Using VBM-Based Approach..........27 3.1.3 Discussion About These Two Approaches............................................29 3.2 Advanced Approaches............................................................................30 3.2.1 Atlas-Based Approach.........................................................................30 3.2.2 The TBSS Approach (Tract-Based Spatial Statistics)..............................32 3.2.2.1 Processing Steps.............................................................................32 3.2.2.2 Features of TBSS.............................................................................33 3.3 Tractography-Based Approach...............................................................35 3.3.1 Concepts and General Frameworks.....................................................35 3.3.2 Coordinated Methods for Tractography-Based Approaches.................36 3.3.3 Advantages and Drawbacks.................................................................36 Chapter 4 Non-Interpolated Tract-Based Statistic Analysis For Estimating The Corticospinal Tract: A Comparison with Parkinson's Disease, Essential Tremor and The Normal Control.............................................................38 4.1 Background............................................................................................38 4.2 Introduction of Diseases.........................................................................40 4.2.1 Parkinson's Disease (PD)......................................................................40 4.2.1.1 Pathophysiology..............................................................................40 4.2.1.2 Diagnosis and Treatment.................................................................42 4.2.1.3 DTI Studies of Parkinson's Disease...................................................43 4.2.2. Essential Tremor (ET)..........................................................................45 4.2.2.1 Pathophysiology, Diagnosis and Treatments....................................46 4.2.2.2 DTI Studies of Essential Tremor.......................................................46 4.3 Methods................................................................................................49 4.3.1 Subjects..............................................................................................49 4.3.2 Image Acquisitions..............................................................................50 4.3.3 Image Processing................................................................................50 4.4 Results...................................................................................................56 4.4.1 DTI Protocol Optimization For Clinical Application...............................56 4.4.2 Group Comparison: PD, ET and The Normal.........................................58 4.4.3 Group Comparison of the Calibration Value.........................................60 4.5 Discussions............................................................................................60 4.5.1 The Dissimilarities of Corticospinal Tract Between Different Groups....60 4.5.2 Individual FA Calibration.....................................................................61 4.5.3 DTI Quantification Approaches............................................................62 4.5.4 Clinical Applicable DTI Protocol...........................................................62 4.6 Conclusion.............................................................................................63 Chapter 5 Summary......................................................................................64 5.1 Conclusion.............................................................................................64 5.2 Limitations.............................................................................................66 5.3 Future Works..........................................................................................66 5.4 Summary................................................................................................67 Reference.....................................................................................................6