第一部分  他汀类药物对颅内动脉粥样硬化斑块疗效及影响因素的VWI研究

目的：磁共振血管壁成像（Magnetic resonance vessel wall imaging，VWI）技术是一种可靠且无创的新型磁共振检查技术，其可以在评估动脉粥样硬化斑块引起的血管狭窄的同时评估斑块特征。本研究应用VWI评估他汀类药物对颅内动脉粥样硬化斑块的疗效，探讨与颅内动脉斑块他汀类药物疗效相关的患者临床特征。

材料与方法：选取颅内动脉VWI影像数据库中2017年7月至2021年8月期间VWI检出颅内动脉粥样硬化斑块、并接受他汀类药物治疗的患者。收集患者的临床信息，包括性别、年龄、体重指数（Body mass index, BMI）、高血压史、糖尿病史、吸烟史、基线期及随访期血脂指标。在PACS系统及Vessel Explorer软件对斑块特征进行测量，包括斑块长度、斑块厚度、斑块负荷、血管狭窄程度、斑块强化程度、血管重构及斑块位置。利用配对样本t检验及Wilcoxon秩和检验评估治疗前后患者血脂及斑块特征的变化。根据他汀治疗后血脂及斑块的变化，分为效果良好组及效果不佳组，使用独立样本t检验、Mann-Whitney U检验及卡方检验比较两组患者基线期临床特征之间的差异，并使用多元线性回归探究患者基线期临床特征与颅内动脉斑块他汀类药物疗效之间的关系。

结果：共53例患者纳入本研究。与基线期相比，他汀类药物治疗后斑块厚度（1.30 (IQR, 1.05-1.50) mm vs. 1.30 (IQR, 1.20-1.50) mm, P=0.016），斑块负荷（51.42 (IQR, 33.47-76.98) % vs. 61.39 (IQR, 38.81-83.74) %, P=0.001），血管狭窄程度（30.00 (IQR, 18.00-54.50) % vs.39.39 (IQR, 21.00-63.04) %, P=0.001）及斑块强化程度（122.3±49.7% vs. 148.8±43.1%，P<0.001）均明显减低，以治疗时长＞6个月的患者尤为显著。与降脂效果不佳组相比，降脂效果良好组患者治疗后斑块负荷明显降低（-24.0±23.3% vs. -4.1±23.8%, P=0.026）。多因素线性回归分析发现，在诸多的临床因素中，年龄（B=0.009, P=0.008），高血压史（B=0.147, P=0.037）及基线期BMI（B=0.024, P=0.03）与斑块负荷减低率呈负相关；高血压史（B=0.188, P=0.034）及基线期BMI（B=0.043, P=0.002）与斑块强化程度减低率呈负相关，用药时长（B=-0.03, P=0.008）及基线期斑块强化程度（B=-0.215, P=0.043）与斑块强化程度减低率呈正相关。

结论：本研究利用VWI证实了他汀类药物具有稳定颅内动脉粥样硬化斑块、降低斑块负荷的作用，尤以他汀药物治疗时间长、低密度脂蛋白胆固醇（Low-density lipoprotein cholesterol, LDL-C）水平控制好的人群为著。他汀类药物的治疗时长、患者基线期的年龄、血压、BMI等因素可能会影响他汀类药物对颅内动脉斑块的治疗效果。

关键词：磁共振血管壁成像；颅内动脉粥样硬化；他汀类药物；疗效

第二部分  颅内动脉粥样硬化斑块基线期VWI影像特征与他汀药物疗效的相关性研究

目的：本研究应用磁共振血管壁成像（Magnetic resonance vessel wall imaging，VWI）评估他汀类药物对颅内动脉粥样硬化斑块的疗效，并探讨基线期斑块特征与药物疗效之间的关系。

材料与方法：选取颅内动脉VWI影像数据库中2017年7月至2021年8月期间VWI检出颅内动脉粥样硬化斑块、并接受他汀类药物治疗的患者。在PACS系统及Vessel Explorer软件对斑块特征进行测量，包括斑块长度、斑块厚度、斑块负荷、血管狭窄程度、斑块强化程度、血管重构及斑块位置。使用配对样本t检验及Wilcoxon秩和检验评估他汀类药物治疗前后斑块特征的变化。分别以斑块长度变化率、斑块厚度变化率、斑块负荷变化率、斑块强化程度变化率及血管狭窄程度变化率总体数据分布的三分位数分为疗效良好组和疗效不佳组，使用独立样本t检验、Mann-Whitney U检验及卡方检验分析各组患者基线期斑块特征的差异，并使用线性回归探讨基线期斑块特征与他汀类药物治疗后斑块疗效间的关系。

结果： 共计107个斑块纳入本研究。与基线期相比，随访期的斑块厚度（1.33±0.46mm vs. 1.38±0.41mm, P=0.049），斑块负荷（41.29 (IQR, 28.64-63.19) % vs. 48.08 (IQR, 31.50-71.88) %, P=0.002），血管狭窄程度（23.00 (IQR, 12.00-42.86) % vs. 24.00 (IQR, 14.29-50.00) %, P=0.005）及斑块强化程度（110.87 (IQR, 86.46-149.24) % vs. 143.62 (IQR, 110.03-171.62) %, P<0.001）均明显减低。多因素线性回归发现，基线期斑块负荷与斑块负荷减低率（B=-0.385, P=0.01）及狭窄程度减低率（B=-0.503, P=0.013）呈正相关；斑块位于前循环与斑块负荷减低率（B=0.142, P=0.048）及强化程度减低率（B=0.16, P=0.015）呈正相关；基线期斑块强化程度（B=-0.219, P=0.007）与强化程度减低率呈正相关。

结论： 本研究利用VWI证实了他汀类药物可以有效增强颅内动脉粥样硬化斑块的稳定性，发现基线期斑块特征与斑块的他汀药物疗效具有一定的相关性，表现为位于前循环、较大的、明显强化的斑块可能得到的治疗收益更大。

关键词：磁共振血管壁成像；颅内动脉粥样硬化；他汀类药物；疗效

PART ONE. The statin medication efficacy on intracranial atherosclerotic plaque and its influencing factors: a magnetic resonance vessel wall imaging study

Purpose: Magnetic resonance vessel wall imaging (VWI), a new non-invasive imaging technique, can reliably evaluate the characteristics of plaque and vascular stenosis which caused by atherosclerotic plaque in the same time. In this study, VWI were used to explore the efficacy of statins on intracranial atherosclerotic plaque, and analyze the clinical and plaque characteristics that may be related with the treatment efficacy.

Materials and methods: Patients with intracranial atherosclerotic plaques confirmed by VWI and treated with statins from July 2017 to August 2021 in the intracranial artery VWI image database were selected. The clinical information of the patients, including gender, age, body mass index (BMI), history of hypertension, history of diabetes, history of smoking, blood lipid indicators at baseline was collected from the clinical database. Plaque characteristics including plaque length, plaque thickness, plaque burden, degree of vascular stenosis, degree of plaque enhancement, vascular remodeling and plaque location were measured using PACS system and vessel Explorer software. Paired sample t-test and Wilcoxon rank sum test were used to evaluate the changes of blood lipid and plaque characteristics before and after statin treatment. Patients were divided into good responder group and poor responder group according to the changes of blood lipid and plaque characteristics. Independent sample t-test, Mann Whitney U-test and Chi-square test were used to investigate the differences in the baseline clinical and plaque characteristics between two groups, and multiple linear regression was used to explore the relationship between the clinical and plaque characteristics at baseline and the efficacy of statin treatment.

Result: A total of 53 patients were included in this study. Compared with the baseline, the plaque thickness (1.30 (IQR, 1.05-1.50) mm vs. 1.30 (IQR, 1.20-1.50) mm, P=0.016), plaque burden (51.42 (IQR, 33.47-76.98) % vs. 61.39 (IQR, 38.81-83.74) %, P=0.001), vessel stenosis (30.00 (IQR, 18.00-54.50) % vs. 39.39 (IQR, 21.00-63.04) %, P=0.001) and plaque enhancement (122.3±49.7% vs. 148.8±43.1%, P<0.001) were significantly reduced in patients after treated with statins, especially in patients treated with statins for more than 6 months. When grouped by lipid-lowering effect, it was found that compared with the group with poor lipid-lowering responder, the plaque burden in the group with good lipid-lowering responder decreased significantly (-24.0 ±23.3% vs. -4.1±23.8%, P=0.026). The history of hypertension (B=0.188, SE=0.086, P=0.034) and baseline BMI (kg/m2, B=0.043, SE=0.013, P=0.002) were negatively correlated with the reduction of plaque enhancement, while the medication duration (month, B=-0.03, SE=0.011, P=0.008) and baseline plaque enhancement (B=-0.215, SE=0.103, P=0.043) were positively correlated with the reduction of plaque enhancement.

Conclusion: Statins can stabilize intracranial atherosclerotic plaques and reduce plaque burden, and the treatment effect is positively correlated with the treatment time and reduction of Low-density lipoprotein cholesterol (LDL-C) level. It was further found that the therapeutic effect of statins on intracranial arterial plaque may have relationship with the treatment time of statins, the age of patients, blood pressure, BMI and other factors at baseline.

Key words: Magnetic resonance vessel wall imaging; Intracranial atherosclerosis; Statins; Treatment outcome

PART TWO. The relationship between baseline intracranial atherosclerotic plaque features on VWI and efficacy of statin treatment

Purpose: Magnetic resonance vessel wall imaging (VWI) can be used to evaluate the vascular stenosis caused by intracranial atherosclerotic plaque and estimate the stability of plaque by analyzing plaque characteristics. In this study, VWI was used to evaluate the efficacy of statin treatment on intracranial atherosclerotic plaque, and investigate the relationship between the baseline plaque characteristics and the treatment efficacy.

Materials and methods: Patients with intracranial atherosclerotic plaques who received statin treatment were selected from the intracranial artery VWI image database between July 2017 and August 2021. The characteristics of plaque were measured in PACS system and vessel Explorer software, including plaque length, plaque thickness, plaque burden, degree of vascular stenosis, degree of plaque enhancement, vascular remodeling and plaque location. Paired sample t-test and Wilcoxon rank sum test were used to evaluate the changes of plaque characteristics before and after treatment. The patients were respectively divided into two groups according to the tri-sectional quantiles of rate change of every plaque characteristic (good responder and poor responder), and the differences of plaque characteristics between the groups at baseline were analyzed using independent samples t-test, Mann Whitney U test and chi square test. Multiple linear regression was used to investigate the relationship between plaque characteristics at baseline and efficacy of statin therapy.

Result: A total of 107 plaques were included in this study. Compared with the baseline, the plaque thickness (1.33±0.46mm vs. 1.38±0.41mm, P=0.049), plaque burden (41.29 (IQR, 28.64-63.19) % vs. 48.08 (IQR, 31.50-71.88) %, P=0.002), vessel stenosis (23.00 (IQR, 12.00-42.86) % vs. 24.00 (IQR, 14.29-50.00) %, P=0.005) and plaque enhancement (110.87 (IQR, 86.46-149.24) % vs. 143.62 (IQR, 110.03-171.62) %, P＜0.001) were significantly reduced in patients after treated with statins. Multivariate linear regression found that plaque burden at baseline was positively correlated with the rate of plaque burden reduction (%, B=-0.385, SE=0.147, P=0.01) and vessel stenosis reduction (%, B=-0.503, SE=0.198, P=0.013); plaque location in the anterior circulation was positively correlated with the rate of plaque burden reduction(B=0.142, SE=0.071, P=0.048) and plaque enhancement reduction (B=0.16, SE=0.064, P=0.015); and plaque enhancement at baseline (%, B=-0.219, SE=0.079, P=0.007) was positively correlated with the rate of plaque enhancement reduction.

Conclusion: Statins can effectively improve the stability of intracranial atherosclerotic plaque, and there was a relationship between plaque characteristics at baseline and the treatment efficacy of statins, the larger plaques and those located in the anterior circulation may receive greater therapeutic benefit.

Key words: Magnetic resonance vessel wall imaging; Intracranial atherosclerosis; Statins; Treatment outcome