透過分析心臟結構、心肌功能與血流狀況，本研究旨在評估法洛氏四重症患者心臟的適應性重塑機制。藉由定量心肌與血流之間動能的交互作用，也幫助釐清心臟過荷對心臟順應性的影響。實驗群體為47位法洛氏四重症患者及38位年齡匹配的正常受試者。利用心肌組織運動速率影像技術，分析左心室與右心室的局部運動及扭轉功能。利用四維流場分析技術，對肺動脈與心室內部血流的流動模式及血液動力學進行視覺化與相關定量分析。
法洛氏四重症患者普遍擁有較為扁平的心室中隔及對應的較大半徑比例(P<0.001)。在整個右心室及部分左心室，患者心肌縱向最大運動速度於收縮期與舒張期皆小於正常人。至於患者的右心室壁的徑向運動速度，收縮期時運動速度小於正常人，但舒張期時運動速度顯著地大於正常人。患者的肺動脈與心室內部血流狀況也跟正常人有所差異，包括在舒張末期時，並無發現任何渦流及殘存有較大的心室內部血流流速。而較大的舒張末期心臟內部血流動能與肺動脈動能、逆流動能皆有正向的相關性，也證實了右心與肺動脈之間的交互作用。另一方面，利用動能梯度定量出的心臟內部血流的延遲狀況，也與右心、肺動脈之間的壓力梯度有密切的相關性。
在左心室功能損壞之前，本研究中建立的指標用於釐清法洛氏四重症患者心臟的適應性重塑機制，並有助於臨床管理患者進行肺動脈瓣膜置換手術的時間安排。

The purpose of this study was to evaluate the adaptive remodeling mechanism by assessing cardiac morphology, myocardial function, and flow in patients with repaired tetralogy of Fallot (rTOF) and preserved left ventricle (LV) global function. Interaction of myocardium and flow was also assessed in kinetic energy (KE) aspects so as to realize the impact of overloading pathology on the cardiac compliance. We recruited 47 rTOF patients and 38 age-matched normal volunteers. Tissue phase mapping (TPM) was performed for evaluating the LV and RV regional myocardial motion and twist function. Flow pattern and hemodynamic parameter in the pulmonary and intraventricular flow were visualized and quantified based on 4D flow MRI.
Most rTOF patient revealed flatter interventricular septum and thus larger radius ratio (P < 0.001). They also showed significantly decreased systolic and diastolic longitudinal velocity (Vz) on most of the RV segments and several LV segments. As for radial velocity (Vr), patients showed significantly decreased Vr in systole but substantially increased Vr in diastole on RV free wall. Flow pattern of intraventricular flow revealed differences between rTOF patients and normal subjects in late diastolic period for absent vortex with a high velocity. The observation of increased late diastolic RV intraventricular flow KE was also correlated with KE of regurgitation as well as pulmonary flow, suggesting the impaired RV-PA coupling. Retarded intraventricular flow at the downstream was detected in using KE gradient and the retarded flow propagation were closely correlated with elevated RVPA pressure gradient.
The establishments of those indices in this study can help to comprehend the adaptive remodeling mechanism of rTOF patients before LV global dysfunction and might be helpful for patient managements regarding the timing of undergoing pulmonary valve replacement (PVR) surgery.

Chapter 1 Introduction 1
1.1 Tetralogy of Fallot 1
1.1.1 Pathophysiology 1
1.1.2 Effect of Pulmonary Regurgitation on Ventricular Mechanics 1
1.2 Diagnosis of TOF 3
1.2.1 Echocardiography 3
1.2.2 Cardiac Computed Tomography 6
1.2.3 Cardiac Catheterization with X-Ray Angiography 8
1.2.4 Cardiac Magnetic Resonance 9
1.3 Pulmonary Valve Replacement Surgery 12
1.4 Limitations of the Current Study in rTOF 15
1.4.1 PVR Criteria 15
1.4.2 Diagnostic Modality 16
1.5 Motivation 18
1.6 Dissertation Orientation 19
Chapter 2 Theory 20
2.1 Phase-Contrast MRI 20
2.2 4D Flow MRI 22
2.3 Tissue Phase Mapping 25
Chapter 3 Materials and Methods 27
3.1 Study Cohort 27
3.2 Cardiopulmonary Exercise and Laboratory Testing 28
3.3 MRI Acquisition 29
3.3.1 Steady State Free Precession Imaging 29
3.3.2 Tissue Phase Mapping 31
3.3.3 2D Flow MRI 32
3.3.4 4D Flow MRI 32
3.4 Data Analysis: Cardiac Morphology 34
3.4.1 Septal Flattening 34
3.4.2 PA Distensibility 35
3.5 Data Analysis: Myocardial Function 36
3.5.1 Three-Directional Myocardial Motion Velocity 37
3.5.2 Bullseye Plot 39
3.5.3 Color Plot 40
3.5.4 Myocardial Twist and Dyssynchrony 41
3.5.5 RV Myocardial KE 42
3.6 Data Analysis: Flow 43
3.6.1 Pulmonary Regurgitation Fraction 44
3.6.2 Intraventricular Flow: Visualization 45
3.6.3 Pulmonary Flow and Intraventricular Flow KE 45
3.6.4 Late Diastolic High KE 46
3.7 Data Analysis: Interaction of Myocardium and Flow 47
3.7.1 KE Gradient Delay 47
3.7.2 KE Balance Time 48
3.7.3 Clustering Analysis 49
3.8 Statistical Analysis 50
Chapter 4 Results and Discussion: Cardiac Morphology 51
4.1 Demographic Characteristics 51
4.2 Septal Flattening 55
4.3 PA Distensibility 56
4.4 Discussion 57
Chapter 5 Results and Discussion: Myocardial Function 58
5.1 Segmental Motion Velocity and TTP in Bullseye Plot 58
5.2 Dynamic Segmental Myocardial Velocity in Color Plot 62
5.3 Myocardial Twist and Dyssynchrony 66
5.3.1 LV VØ-derived Indices 66
5.3.2 LV Rotation 67
5.4 Discrimination Between Normal and rTOF Groups 68
5.5 RV Myocardial KE 70
5.5.1 RV Myocardial KE 70
5.5.2 Three-Directional KE 71
5.6 Discussion 73
5.6.1 Longitudinal and Radial Motion 73
5.6.2 Twist Function 75
5.6.3 Discrimination Between Normal and rTOF Groups 76
Chapter 6 Results and Discussion: Flow 77
6.1 Pulmonary Flow Rate and Regurgitation Fraction 77
6.2 Pulmonary Flow KE 78
6.3 Intraventricular Flow: Visualization 79
6.4 Intraventricular Flow KE 81
6.4.1 Diastolic KE 81
6.4.2 Late Diastolic High KE 81
6.5 Correlation Analysis 85
6.5.1 Impact of PR on function, geometry, and pressure 85
6.5.2 Interaction among function, geometry, and pressure 86
6.6 Discussion 87
6.6.1 Pulmonary Flow 87
6.6.2 Intraventricular Flow 87
6.6.3 Impact of PR on function, geometry, and pressure 87
Chapter 7 Results and Discussion: Interaction of Myocardium and Flow 89
7.1 Correlation Analysis 89
7.2 KE Gradient Delay 90
7.3 KE Balance Time 92
7.4 Clustering of rTOF Patients 95
7.5 Subgroup Analysis 98
7.6 Discussion 101
7.6.1 Interaction of Myocardium and Flow 101
7.6.2 KE Gradient Delay 102
7.6.3 KE Balance Time 103
7.6.4 Clustering Analysis 104
7.6.5 Subgroup Analysis 105
Chapter 8 Conclusions 107
8.1 Limitations and Future Work 107
8.2 Conclusions 109
Chapter 9 References 111
Chapter 10 Appendix 122
10.1 Abbreviation List 122
10.2 Definition List of Quantitative Indices 123

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