馬凡氏綜合症是一種遺傳性結締組織疾病，為常染色體顯性遺傳，患病特徵為四肢、手指、腳趾細長不勻稱，身高明顯超出常人，伴有心血管系統異常，特別是合併的心臟瓣膜異常和主動脈瘤。該病同時可能影響其他器官，包括肺、眼、硬脊膜、硬顎等。馬凡氏綜合症患者可以根據臨床表現骨骼、眼、心血管三個主要特徵的改變三個主要特徵和家族史即可診斷。但馬凡氏綜合症在臨床早期的症狀相對不明顯，有報告指出馬凡氏綜合症被檢出年齡段正逐年遞增，而被檢出時往往已經發生了主動脈剝離的情況，即馬凡氏綜合症最嚴重的併發症。且目前關於馬凡氏綜合症的研究大多數局限在對患者主動脈功能的研究，雖然近幾年來，越來越多的研究將焦點放在患者的心肌功能，但我們仍然無法得知兩者之間是否存在交互作用。因此為了避免馬凡氏綜合症患者錯過早期調養時段而直接產生晚期病變至關重要。我們的目的是早期評估患者主動脈血流參數與心肌功能的病變風險並觀察對馬凡氏綜合症的影響。
我們招募了36名健康受試者和17名馬凡氏綜合症患者進行檢查。掃描動態短軸影像，用於評估心臟體積、質量和功能。組織相位圖以評估左心室整體的心肌運動。獲得的四維血流磁振造影用於分析主動脈血流。我們將健康受試者及馬凡氏綜合症患者以年齡分組進行討論，並對心肌運動和主動脈血流進行相關性分析。
馬凡氏綜合症患者在升主動脈有較低的血流平均速度，搏動指數和較高的逆流，硬化指數，壓力差。在左心室基底有著較低的收縮縱向峰值速度，舒張縱向峰值速度，舒張徑向峰值速度和較長的舒張縱向到達峰值速度的時間。病人的主動脈血流平均速度與左心室收縮縱向峰值速度，舒張縱向峰值速度，舒張徑向峰值速度有正向相關性，逆流與左心室舒張縱向到達峰值速度的時間有正向相關性。搏動指數與左心室舒張縱向峰值速度，舒張徑向峰值速度有正向相關性。此外，硬化係數，壓力差都與左心室舒張縱向峰值速度，舒張徑向峰值速度有負向相關性。
本研究中的參數與相關性分析有助於在馬凡氏綜合症患者早期評估主動脈及心肌功能時給予病人適當的風險警告及預防病情的演進。

Marfan syndrome is an autosomal dominant hereditary connective tissue disease. The disease is characterized by unevenness of the limbs, fingers, and toes, and the height is significantly higher than that of ordinary people, accompanied by abnormal cardiovascular system, especially combined heart valve abnormalities and aortic aneurysms. The disease may also affect other organs, including the lungs, eyes, dura mater, hard palate and so on. Patients with Marfan syndrome can be diagnosed according to the three main signs of clinical manifestations of bone, eye, and cardiovascular changes or family history. However, the symptoms of Marfan syndrome in the early stage of the disease are relatively insignificant. It has been reported that the age at which Marfan syndrome is detected is increasing year by year, and the aortic dissection which is the most serious complication often occurs when it is detected. And most of the current research on Marfan syndrome is limited to the study of aortic function in patients. Although in recent years, more and more research has focused on the myocardial function of patients, but we still don't know if there is any interaction between them. Therefore, in order to avoid patients with Marfan syndrome miss the early nursery time instead of direct production of advanced lesions is essential. Our aim was to early evaluate the risk of lesions in patients with aortic blood flow parameters and myocardial function and to observe the effect on Marfan syndrome.
We recruited 36 normal volunteers and 17 patients with Marfan syndrome for examination. Scan dynamic short-axis images for heart volume, quality, and myocardial function. Tissue phase mapping were used to assess myocardial motion throughout the left ventricle. The obtained four-dimensional flow magnetic resonance imaging was used to analyze aortic blood flow. We discuss normal volunteers and Marfan syndrome in groups by age and correlate myocardial motion and aortic blood flow.
Patients with Marfan syndrome have lower mean velocity, distensibility and higher regurgitation fraction, β index, and pressure difference (PD) in the ascending aorta. In left ventricular base area, patients has a lower systolic longitudinal peak velocity, diastolic longitudinal peak velocity, diastolic radial peak velocity, and longer diastolic longitudinal time to peak velocity. The patient's aortic mean velocity was positively correlated with the left ventricular systolic longitudinal peak velocity, diastolic longitudinal peak velocity, diastolic radial peak velocity, and the regurgitation fraction was positively correlated with the left ventricular diastolic longitudinal time to peak velocity.
The pulsation index is positively correlated with the left ventricular diastolic longitudinal peak velocity and the diastolic radial peak velocity. In addition, the β index and PD are negatively correlated with the left ventricular diastolic longitudinal peak velocity and the diastolic radial peak velocity.
The parameters and correlation analysis in this study are helpful to give patients a risk warning and prevent the progression of the disease in the early evaluation of aortic and myocardial function in patients with Marfan syndrome.

ABSTRACT i
CONTENTS v
TABLES vii
FIGURES ix
Chapter 1 Introduction 1
1.1 Marfan syndrome (MFS) 1
1.1.1 Pathophysiology 1
1.1.2 Aortic Complications 2
1.2 Diagnosis of Marfan syndrome 4
1.2.1 Diagnostic criteria 4
1.2.2 Ultrasound 6
1.2.3 Cardiovascular Magnetic Resonance 9
1.3 Treatment in MFS 13
1.4 Motivation 15
1.5 Orientation of Dissertation 15
Chapter 2 Theory 17
2.1 Phase-Contrast MRI 17
2.2 Tissue Phase Mapping 18
2.3 4D Flow MRI 18
Chapter 3 Materials and Methods 22
3.1 Study Cohort 22
3.2 MRI Acquisition 22
3.2.1 Steady State Free Precession Imaging 22
3.2.2 Tissue Phase Mapping 23
3.2.3 4D flow MRI 23
3.3 Data Analysis: Myocardial Motion 25
3.3.1 Myocardial Peak Velocity and Time to Peak 27
3.3.2 Myocardial Twist 29
3.4 Data Analysis: Aortic Flow 30
3.4.1 Aortic root diameter 30
3.4.2 Flow Parameter 31
3.4.3 β Index 32
3.4.4 Pressure Difference 32
3.5 Statistical Analysis 33
Chapter 4 Results 34
4.1 Demographics of study cohorts 34
4.2 Cardiac volumetric index 36
4.3 Myocaridal Motion 38
4.3.1 Segmental TPM parameters 38
4.3.2 Regional TPM parameters 45
4.3.3 Myocaridal Twist 50
4.4 Aortic Flow 52
4.4.1 4D flow parameters 52
4.4.2 Pressure Difference 56
4.5 Correlation analysis 59
4.5.1 Correlation analysis: Aortic root diameter and all the other parameters 59
4.5.2 Correlation analysis: Age and all the other parameters 62
4.5.3 Correlation analysis: LVEF and all the other parameters 65
4.5.4 Correlation analysis: Mean velocity and Myocaridal systolic Motion 68
4.5.5 Correlation analysis: Aortic flow and Myocardial diastolic Motion 68
4.5.6 Correlation analysis: Distensibility and Myocardial diastolic Motion 70
4.5.7 Correlation analysis: β index and Myocardial diastolic Motion 71
4.5.8 Correlation analysis: Pressure Difference and Myocardial Motion 72
Chapter 5 Discussion 83
5.1 Demographics of study cohorts 83
5.2 Myocardial Motion 83
5.2.1 TPM parameters 83
5.2.2 Myocardial Twist 84
5.3 Aortic flow 85
5.3.1 4D Flow parameters 85
5.3.2 Pressure Difference 86
5.4 Correlation analysis 86
5.4.1 Correlation analysis: Aortic root diameter and all the other parameters 86
5.4.2 Correlation analysis: Age and all the other parameters 86
5.4.3 Correlation analysis: LVEF and all the other parameters 87
5.4.4 Correlation analysis: Mean velocity and Myocardial Motion 87
5.4.5 Correlation analysis: Retrograde and Myocardial Motion 88
5.4.6 Correlation analysis: Distensibility, β index and Myocardial Motion 89
5.4.7 Correlation analysis: Pressure Difference and Myocardial Motion 89
5.5 Multivariable regression analysis 89
5.6 ROC curve 90
5.7 Limitations 91
5.8 Future work 91
Chapter 6 Conclusion 92
Chapter 7 References 93
Chapter 8 Appendix 98
8.1. Abbreviation list 98
8.2. Plane 2 hemodynamic parameters 100
8.3. Q & A 101

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