published_or_final_version / abstract / Medicine / Doctoral / Doctor of Philosophy

大动脉闭塞性疾病是脑卒中常见病因，包括颅内外狭窄性血管病变。本研究旨在分析卒中患者颅内外大动脉狭窄斑块的血管造影特征以及相关治疗方案。进一步了解颅内斑块的形态学变化，以及颅外大动脉狭窄的血管造影特征和侧枝循环状态，对于研究其发病机制及临床治疗有指导意义。 / 研究目的 / 研究1：通过前瞻性纵向研究，利用三维旋转血管造影（3D-RA），探讨颅内斑块形态学变化。 / 研究2：通过病例对照研究分析症状性放射性闭塞性血管病变(ORV)的血管造影特征及侧枝循环状态。 / 研究3：通过病例对照研究分析放射性血管病变（RIV）患者进行颈动脉支架治疗（CAS）后血管造影特征及临床预后。 / 研究方法 / 研究1：24例颅内重度狭窄(>70%)的急性缺血性卒中患者，严格控制其危险因素，应用3D-RA研究其发病时及12个月后颅内斑块的形态学变化。 / 研究2：分析96例ORV以及115例非放疗所致严重颈动脉狭窄（>70%）的缺血性卒中患者血管造影特点，比较其病变分布，形态学改变及侧枝循环状态。 / 研究3：比较63例ORV以及87例动脉粥样硬化性颈动脉狭窄的卒中患者的血管造影及预后。主要终点事件包括短暂性脑缺血发作，卒中和死亡。次要终点事件为24个月时支架内再狭窄。 / 结果 / 研究1：颅内动脉粥样硬化性斑块的厚长比不能预测其稳定性。12个月的血管造影提示：13例（50%)斑块逆转；10例（38.5%)斑块无明显变化；3例（11.5%)斑块进展。 / 研究2：ORV更多累及颈总动脉，多见双侧颈动脉受累（54% vs 22%)或出现闭塞（30% vs 9%），常见椎动脉受累(28% vs 14%)（均P<0.05）。ORV常见代偿性软脑膜动脉、前后交通动脉开放，及逆向眼动脉血流。 / 研究3：两组间围手术期并发症，长期生存率和卒中复发率无统计学差异。 / 结论 / 研究1：3D-RA可评价颅内斑块形态学变化；颅内光滑斑块亦可为易损斑块。严格控制危险因素可能逆转斑块。 / 研究2： ORV患者更多见颈动脉及椎基底动脉狭窄-闭塞性病变，并伴随侧枝循环开放。侧枝循环代偿功能减退可能诱导ORV患者发生卒中。 / 研究3：RIV患者与对照组相比，CAS的耐受性和临床预后无明显差异。 / Large artery occlusive disease, encompassing stenosis in intracranial and extracranial vasculature, is the most common stroke subtype worldwide. In this thesis, we aimed to investigate angiographic plaque morphology and treatments in stroke patients attributed to intracranial and/or extracranial stenosis. A better understanding of intracranial plaque morphology, angiographic characteristics and collateral circulations of extracranial occlusive vasculopathy may help clarify pathogenesis and formulate treatment. / Objectives / Study 1: In this prospective longitudinal study, we investigated the intracranial plaque morphology of acute stroke patients by three-dimensional rotational angiography (3D-RA). / Study 2: We aimed to delineate the angiographic attributes and collateral circulations in symptomatic occlusive radiation vasculopathy (ORV) patients by a case-controlled study. / Study 3: We investigated the angiographic and clinical outcome of carotid artery stenting (CAS) in stroke patients attributed to ORV. / Methods / Study 1: Twenty-four patients with acute strokes attributed to a >70% intracranial stenosis were recruited to undergo 3D-RA at baseline and in 12 months after an intensive control of atherosclerotic risks. We described the degree of stenosis and morphology that might be associated with plaque vulnerability. / Study 2: We performed digital subtraction angiograms (DSA) in 96 patients who had first-ever ischemic strokes attributed to ORV, and 115 referent patients who had no radiotherapy (RT) but symptomatic high-grade (>70%) atherosclerotic carotid stenoses. We compared the lesions’ distribution, morphology, and the resultant alteration of collateral flows in both patient groups. / Study 3: We compared the angiographic and clinical outcome of CAS in 63 symtomatic ORV patients and 87 patients with spontaneous atheromatous carotid stenoses. Primary end-points were transient ischemic attack, stroke and death of all causes. Secondary end-point was instent restenosis in 24 months. / Results / Study 1: Inracranial atherosclerotic plaque is a dynamic lesion.Thickness-to-length ratio may not indicate plaque vulnerability. In 12-month angiogram, 13 patients (50%) had plaque regression, 10 (38.5%) had static plaque, and 3 (11.5%) had plaque progression. / Study 2: Compared with spontaneous atheromatous carotid disease, ORV lesions diffusely involved common carotid artery, and were more frequently bilateral (54% vs 22%), associated with complete occlusion in one or both carotid arteries (30% vs 9%), vertebral artery steno-occlusions (27% vs 14%) (all p<0.05). ORV patients showed more established collateral circulations through leptomeningeal arteries, anterior communicating artery, posterior communicating artery and retrograde flow in ophthalmic artery. / Study 3: We found no significant differences in the frequency of periprocedural complications, the rates of patient survival and stroke recurrence between ORV and control groups. / Conclusions / Study 1: Evaluation of intracranial plaque morphology is feasible with 3D-RA. Smooth plaques might also be vulnerable in intracranial vasculature. Intensive risk factor control may halt progression of intracranial plaques. / Study 2: ORV patients had more steno-occlusions over carotid and vertebral arteries amid mature collateral circulations at initial stroke presentation. Decompensation of collateral flows may precipitate stroke in ORV. / Study 3: The durability and clinical outcome of CAS in ORV patients were comparable to those in patients with spontaneous atherosclerotic carotid stenosis. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Zou, Xinying. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 101-119). / Abstract also in Chinese. / ABSTRACT --- p.i / 摘要 --- p.vi / DECLARATION OF ORIGINALITY --- p.ix / ACKNOWLEDGEMENTS --- p.x / PUBLICATIONS AND PRESENTATIONS --- p.xii / LIST OF ABBREVIATIONS --- p.xiv / LIST OF TABLES --- p.xvii / LIST OF FIGURES --- p.xviii / TABLE OF CONTENTS --- p.xx / Chapter CHAPTER 1 --- INTRODUCTION AND LITERATURE REVIEW --- p.1 / Chapter 1.1 --- An overview of large artery occlusive disease in ischemic stroke --- p.1 / Chapter 1.2 --- Vulnerable plaque and plaque morphology in ischemic stroke --- p.3 / Chapter 1.2.1 --- Definition of vulnerable plaque and plaque morphology --- p.4 / Chapter 1.2.2 --- Imaging of vulnerable plaques --- p.5 / Chapter 1.2.3 --- Factors affecting plaque stability or arterial luminal narrowing --- p.7 / Chapter 1.2.3.1 --- Stenosis severity --- p.7 / Chapter 1.2.3.2 --- Thickness and length of plaque --- p.8 / Chapter 1.2.3.3 --- Mechanical stress, shear stress and hemodynamics on plaque stability --- p.9 / Chapter 1.2.3.4 --- Plaque eccentricity --- p.10 / Chapter 1.2.3.5 --- Plaque surface morphology --- p.11 / Chapter 1.2.4 --- Morphological characteristics of symptomatic plaque --- p.11 / Chapter 1.2.4.1 --- Carotid plaque morphology --- p.11 / Chapter 1.2.4.2 --- Intracranial plaque morphology --- p.12 / Chapter 1.2.5 --- Treatment of vulnerable intracranial stenosis --- p.12 / Chapter 1.3 --- Occlusive radiation vasculopathy (ORV) --- p.13 / Chapter 1.3.1 --- Epidemiology of ORV --- p.13 / Chapter 1.3.2 --- Pathogenesis and Pathophysiology of ORV --- p.14 / Chapter 1.3.3 --- Imaging and angiographic characteristics of ORV --- p.16 / Chapter 1.3.4 --- Collateralization in ORV --- p.18 / Chapter 1.3.5 --- Angioplasty and stenting for ORV --- p.19 / Chapter CHAPTER 2 --- OBJECTIVES --- p.22 / Chapter CHAPTER 3 --- RECRUITMENT OF STUDY PARTICIPANTS --- p.24 / Chapter CHAPTER 4 --- REGRESSION OF SYMPTOMATIC INTRACRANIAL PLAQUE BY INTENSIVE RISK FACTOR CONTROL: A LONGITUDIANL STUDY ON PLAQUE MORPHOLOGY BY 3D-ROTATIONAL ANGIOGRAPHY --- p.28 / Chapter 4.1. --- Background and objectives --- p.28 / Chapter 4.2 --- Methods --- p.32 / Chapter 4.2.1 --- Participants --- p.32 / Chapter 4.2.2 --- Risk factors and intensive control --- p.33 / Chapter 4.2.3 --- Evaluation of intracranial stenosis --- p.33 / Chapter 4.2.3.1 --- DSA and 3D-RA protocol --- p.33 / Chapter 4.2.3.2 --- Severity of stenosis --- p.34 / Chapter 4.2.3.3 --- Analysis of morphological characteristics on 3D-RA --- p.34 / Chapter 4.2.3.4 --- Plaque regression --- p.35 / Chapter 4.2.4 --- Statistical analysis --- p.36 / Chapter 4.3 --- Results --- p.36 / Chapter 4.4 --- Discussion --- p.54 / Chapter CHAPTER 5 --- ANGIOGRAPHY DISTINCTIONS AND COLLATERALIZATION IN SYMPTOMATIC CRANIO-CERVICAL OCCLUSIVE RADIATION VASCULOPATHY: A CASE-REFERENT STUDY --- p.58 / Chapter 5.1 --- Background and objectives --- p.58 / Chapter 5.2 --- Methods --- p.59 / Chapter 5.2.1 --- ORV and referent patients --- p.60 / Chapter 5.2.2 --- Evaluation of vascular lesions and collateral status --- p.61 / Chapter 5.2.3 --- Statistical analysis --- p.64 / Chapter 5.3 --- Results --- p.64 / Chapter 5.4 --- Discussion --- p.81 / Chapter CHAPTER 6 --- SAFETY AND CLINICAL OUTCOME OF CAROTID ARTERY STENTING IN STROKE PATIENTS WITH OCCLUSIVE RADIATION VASCULOPATHY --- p.86 / Chapter 6.1. --- Background and objectives --- p.86 / Chapter 6.2 --- Methods --- p.87 / Chapter 6.2.1 --- Participants --- p.87 / Chapter 6.2.2 --- Baseline clinical assessment --- p.87 / Chapter 6.2.3 --- Carotid artery stenting (CAS) --- p.88 / Chapter 6.2.4 --- Follow-up and end-points --- p.89 / Chapter 6.2.5 --- Statistical analysis --- p.89 / Chapter 6.3. --- Results --- p.90 / Chapter 6.4. --- Discussion --- p.96 / Chapter CHAPTER 7 --- CONCLUSIONS --- p.98 / REFERENCES --- p.101

Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Thesis (Ph.D.)--University of Delaware, 2009. / Principal faculty advisor: Jill S. Higginson, Dept. of Mechanical Engineering. Includes bibliographical references.

Thesis (M. Phil.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 57-61).

published_or_final_version / Public Health / Master / Master of Public Health

Background: Stroke has become the second most cause of death and leading cause of disability worldwide. Patients-reported health related quality of life measures are often used in evaluating stroke outcomes. However, many stroke patients can not participate in the outcome assessments due to severe disability or aphasia or cognitive impairment. In this case, proxy respondents can be used as secondary information sources. The principle thing needs to be paid attention to in using proxy’s assessments is the reliability or agreement between patient and proxy. Western studies have shown that the agreement between patient and proxy was moderate to substantial. However, such studies are limited in China. Simply applying overseas research outcomes on local population is not appropriate. Therefore, we conducted this study to find out the agreement between stroke patients and proxy assessments about quality of life in China. Methods: 100 patient-proxy pairs were enrolled in our study. Our study was a hospital-based study. The included patients were 3 months after stroke, and patients with more than moderate aphasia or cognitive impairment were excluded. Proxies were people who knew the patients > 1 year, contacted with the patients ≥ 3 days per week, were responsible for ≥ 2 caregiving tasks, and ≥ 18 years. The Chinese version of Stroke-specific quality of life scale (SS-QoL) was used to assess the stroke patients’ QoL, and proxy version of SS-QoL was used in proxies’ evaluation. The evaluation process of patient and proxy was separately and concurrently. Method of self-reported combined with interview-administered was adopted. Paired t tests or Wilcoxon signed ranks tests were performed to test the systematic differences between patient and proxy. The agreement level between patient and proxy assessments on stroke QoL was estimated by Intraclass correlation coefficient (ICC). Multiple linear regression was performed to find out factors affecting the patient-proxy agreement. Results: Patients were older (61 versus 48 years) and more often male (63% versus 44%). Mean systematic differences ranged from 0.03 to 0.44. Only 3 domains of differences were statistical significant (Language, Personality, and Work/productivity). The strength of agreement between patient and proxy reporting ranged from fair to perfect (ICC: 0.31 to 0.87). Better agreement was observed in more objective domains while worse agreement was reported in more subjective domains. Proxy education was tested to be a significant predictor of the overall patient-proxy score difference, which indicated that higher proxy education level was associated with greater agreement. It was shown that higher overall patient-reported or proxy-reported SS-QoL score was associated with less stroke impairments. Factors of stroke impairments, patient/proxy education level, patient/proxy gender, and stroke type separately have significant impacts on the agreement between patient and proxy in different domains of QoL. Conclusion: Our findings indicate that proxies may provide reliable information for assessments about stroke patients’ quality of life in China. And the outcomes are more appropriate for mind to moderate stroke patients. For further studies, the reliability of proxy information about severe stroke patients should be paid attention to. Research about changes of agreement between patient and proxy along with the disease development process would be focused on. / published_or_final_version / Public Health / Master / Master of Public Health

Background: Cardio-and Cerebrovascular Disease Event Surveillance System (CDESS) was established in Guangzhou in 2013. It provided important information of the stroke hospitalization and set up a platform for further research on stroke. Objective: To describe the characteristics of stroke hospitalizations in Class 2 and 3 hospitals, examine crude and standardized hospitalization rates by age, sex and stroke subtypes, identify problems in the first year database through the analysis and make recommendations for further improvements Design: Case-series study Setting: Guangzhou, China Subjects: 32324 stroke hospitalizations in Class 2 and 3 hospitals Methods: Descriptive statistics were used to describe the distributions of stroke hospitalizations by age, sex and subtypes. Chi-square test, One-way ANOVA and two-independent sample t-test were conducted to compare differences in sex and age in total strokes and 3 main subtypes. Crude rates, age- and sex-specific hospitalization rates were calculated using the 2010 Guangzhou Census population. Age-standardized rates were calculated by direct standardization method using the WHO world population. Results: The mean age±SD for total strokes was 70.33±12.26 for all subjects, 68.95±12.56 for men and 72.19±11.59 for women. CBI and the 75-79 year age group accounted for the largest proportions in total strokes. The mean age of women was significantly greater than men for total stroke. The crude hospitalization rate of total strokes was 275.22 for men, 224.16 for women and 250.85 for all. The age-standardized rate of total strokes was 308.2 in men, 202.2 in women and 253.5 in all. Conclusion: Because the stroke hospitalization data combined first-ever and recurrent strokes, incident hospitalization rates could not be calculated. The present study also could not distinguish fatal hospitalizations from nonfatal ones. Hence, bed days and hospital charges analysis would not yield meaningful results. The CDESS needs to be improved by collecting information to clarify whether the hospitalization is first-ever or recurrent, and the survival status at discharge. The mortality data from death registration in CDC should be used to check with CDESS data for stroke death outside the hospitals Community based studies are needed to identify strokes not admitted into Class 2 and 3 hospitals. The problems identified in CDESS or WHO STEP Stroke should be discussed with other hospitals in China, such as Hangzhou and Shanghai so that the problems can be tackled together. / published_or_final_version / Public Health / Master / Master of Public Health

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