应用速度向量成像技术评价缺血性脑血管病患者颈动脉斑块长轴力学特征
|
摘要
背景
脑卒中是缺血性脑血管疾病的重要形式,具有极高的致残率和致死率。其中,缺血性脑卒中占卒中总数约50%-60%,造成了巨大的经济负担。短暂性脑缺血发作是脑卒中的高危因素。脑卒中是目前中国人群主要的死亡原因,而其中缺血型卒中的发病率呈明显上升趋势。近年来,动脉粥样硬化作为脑卒中的重要发病因素已被大家公认。晚近一些研究发现约15%的脑梗塞与来自颈动脉分叉处的碎屑和栓子有关,至此动脉粥硬化斑块与缺血性脑血管病的关系引来更为广泛的关注。
斑块形态、形变功能对斑块的稳定性至关重要。颈动脉内膜-中层厚度(intima-media thickness, IMT)作为动脉粥样硬化的重要形态特征之一,其与心肌梗死、脑卒中的关系已被证实。此外,斑块低回声、斑块面积、斑块体积、斑块偏心指数等也与脑卒中的发生关系密切。
动脉粥样硬化斑块的力学特征近来受到重视。其中,剪切力是循环血流作用于血管壁内皮上的摩擦力,周向应力则由管壁扭转引起。剪切力不仅扮演着局部血管重构始动因子的角色,而且与动脉粥样硬化斑块的形态和易损性有关。低剪切力被认为是斑块进展的促进因素而高剪切力则与斑块破裂有关,其中低收缩期剪切力被认为是致动脉粥样硬化的危险因素,并可能与继发的脑血管事件相关。高周向应力与斑块的易损和破裂有关。此外,颈动脉扩张性也是血管壁功能的代表。我们最近的工作也证明了斑块体积压缩率(Plaque volume compression ratio, VCR)是脑卒中发生的独立危险因子。然而无创定量地研究动脉粥样硬化斑块的力学特征的研究方法相对有限,有待进一步研究。
速度向量成像技术(velocity vector imaging, VVI)以声学采集、斑点追踪、空间相干等技术为基础,可获取研究对象的运动信息,并在二维图像上表示运动信息。该技术对研究对象运动信息的测量不受角度依赖,已广泛地应用于评价心肌局部收缩和舒张功能、高血压心脏病、心力衰竭、心肌病及心脏再同步化治疗效果[23]等。
VVI技术在颈动脉粥样硬化性疾病的应用较少。国内,张蕾等应用VVI技术研究兔模型中颈动脉粥样硬化斑块的易损性。岳文胜等将该技术检应用于颈动脉粥样硬化斑块内膜旋转的发生和角度变化的检测。汪奇等使用VVI技术研究脑梗塞患者与正常人群的颈动脉血管短轴运动特征,发现ACI组颈动脉各壁的径向速度均小于正常人。目前,VVI技术对颈动脉粥样硬化的研究主要应用于血管短轴切面,而在血管长轴方向上的临床应用尚未开展。动脉粥硬化斑块沿血管长轴方向上的长期拉伸与弯曲与斑块的破裂有关。本试验首次将VVI技术应用于缺血性脑血管疾病患者颈动脉血管长轴力学特征研究,对颈动脉粥样硬化斑块长轴力学特征(拉伸与弯曲)与脑血管病之间的关系进行探讨。
研究目的
(1)探讨斑块表面力学运动参数在缺血性脑血管疾病类型间的差异。
(2)探讨斑块表面力学运动参数与斑块节段部位的关系。
(3)探讨斑块表面力学运动参数在斑块表面不同部位间的差异。
(4)探讨VVI技术测量颈动脉斑块参数对于缺血性脑血管病的诊断价值。
研究资料与方法
1.研究对象与分组：
研究对象：缺血性脑血管病患者入选59例,非脑血管病患者入选50例。缺血性脑血管病组入选标准与排除标准：具备缺血性脑血管病临床症状和颈动脉粥样硬化,符合第四届全国脑血管病学术会议修订的有关脑梗塞与短暂性脑缺血发作(TIA)的诊断标准,并经颅脑MRI/CT证实为急性脑梗塞或TIA,并排除出血后梗塞、蛛网膜下腔出血、心源性脑栓塞、颅内占位性病变等。NCD组入选标准：排除任何脑血管病病史的颈动脉粥样硬化患者。
分组方法：(1)按入选研究对象的临床诊断分组：NCD组为非脑血管组,TIA组为短暂性脑缺血发作组,ACI组为脑梗塞组。(2)按研究对象的颈动脉粥样硬化斑块的节段位置分组：AM为颈动脉起始段与中段组,BI为颈动脉分叉与颈内动脉起始部组。(3)按颈动脉粥硬化斑块长轴图像上取样部位分组：P1为近心端基底部组,P2为近心端肩部组,P3为斑块顶部组,P4为远心端斑块肩部组,P5为远心端斑块基底部组。
2.研究方法
2.1二维超声图像存储
使用Acuson Sequoia C512(Siemens)超声探测仪及10-14 MHz高频线阵探头采集颈动脉二维图像,帧频控制在60帧／秒以上。颈总动脉及颈内动脉沿血管长轴的动态图像冻结后存储。
2.2图像处理与数据分析
应用速度向量成像技术分析软件(syngo VVI)分析单心动周期内颈动脉斑块表面五个ROI部位：近心端基底部(P1)、近心端肩部(P2)、斑块顶部(P3)、远心端肩部(P4)、斑块远心端基底部(P5)。手动将参照点放置于斑块对侧管壁外的组织内。获取不同ROI部位参数,保存为全心动周期运动参数Excel表格。单心动周期运动参数表经正负极值计算后取得五个ROI部位单心动周期内速度、应变、应变率的最大正值(max)、最大负值(min)。最大变化值是max与min间差值。依据参照点所取位置,规定朝向定标的速度为正向速度。依据理论,应变的正值提示斑块舒张,负值提示斑块压缩。
3.统计学方法
应用SPSS16.0统计软件进行数据分析。统计结果以P<0.05为有显著性意义。计数资料资料以均数±标准差表示。应用单因素方差检测诊断组间均数差异显著性,符合Levene方差齐性检验采用LSD检验方法进行多重比较、方差不齐应用Dunnett's T3。斑块不同部位参数组间均数比较应用配对t检验。计量资料的显著性检验χ2检验法。单因素方差分析有显著性的参数经二分类Logistic回归建立模型。ROC曲线用于评价各模型对脑血管病的预测价值。
结果
1.按诊断分组三组间的力学参数变化
速度峰值：TIA组与NCD组相比p1-Vmax、P2-Vmax、P3-Vmax、P4-Vmin、P5-Vmin、T-Vmax、T-Vmin、T-V明显增大(P<0.05)；ACI组与NCD组相比T-Vmax、T-Vmin、T-V明显增大(P<0.05)。ACI组与TIA组相比P1-Vmax、P2-Vmax、P3-Vmax、P4-Vmin、P5-Vmin、P1-V、P2-V、P4-V、P5-V显著减小(P<0.05)。
2.按斑块节段位置分组后三组间的力学参数变化
2.1AM组与BI组低回声斑块总体力学参数的比较
AM组与BI组低回声斑块总体力学参数比较,AM-Vmin较BI-Vmin显著增大(P<0.05)。其余参数变化未见差异(P>0.05)
2.2 AM组的力学参数峰值变化：
TIA组与NCD组比较,TIA组的AM-Vmax、AM-Vmin、AM-V明显增大(P<0.05)；2与NCD组相比,AM-Vmin、AM-SRmin、AM-S明显增大(P<0.05)；ACI组与TIA组比较,ACI组的AM-Vmax、AM-V显著减小(P<0.05),AM-SRmin明显增大(P<0.05)。
2.3 B工组的力学参数峰值变化：
TIA组与NCD组比较BI-Vmax、BI-Vmin、BI-V明显增大,BI-Smin明显减小(P<0.05)。ACI组与NCD组比较BI-Vmin明显增大,BI-Smin明显减小(P<0.05),BI-SRmin明显增大(P<0.05)。2与TIA组比较BI-Vmax、BI-V明显减小(P<0.05)。
3.按斑块不同部位分组力学参数均值变化
3.1ACI组斑块不同部位力学参数变化
ACI组斑块不同部位径向速度变化：从P1至P5,Vmax、Vmin、V都出现显减小在增大的特点。P1-Vmax显著大于P2-Vmax、P3-Vmax、P4-Vmax; P5-Vmax显著大于P3-Vmax、P4-Vmax (P<0.05); P1-V显著大于P2-V、P3-V(P<0.05), P5-V显著大于P2-V、P3-V、P4-V (P<0.05); P1-Vmin显著大于P2-Vmin (P<0.05), P4-Vmin显著大于P3-Vmin (P<0.05), P5-Vmin显著大于P2-Vmin、P3-Vmin、P4-Vmin (P<0.01)。
ACI组斑块不同部位应变变化：从P1至P5,Smax、Smin、S都出现先增大再减小的变化特点。其中P2-Smin显著大于P4(P<0.05),P2-S显著大于P1-S和P5-S(P<0.05)。
ACI组斑块不同部位应变率变化：SRmax与SR从P1至P5依次增大,P1-SRmax显著小于P5-SRmax (P<0.05)。
3.2NCD组不同部位力学参数均值变化
NCD组斑块不同部位速度变化：Vmax、Vmin和V变化趋势一致,均从P1至P4依次减小,从P4至P5升高。其中,P1-V和P2-V都显著大于P4-V(P<0.05)。
NCD组斑块不同部位应变变化：Smax和S都出现先增大再减小的变化过程。各部位之间的应变差异无显著性(P>0.05)。
NCD组斑块不同部位应变率变化：SRmax、SRmin、SR的变化趋势不一致,且各部位之间的应变差异无显著性(P>0.05)。
4.斑块表面运动参数的Logistic回归分析与ROC曲线分析结果
二分类Logistic回归分析存在组间差异的各参数与缺血性脑血管病(包括急性脑梗塞与TIA)之间的关系。ROC曲线分析在单因素方差分析中存在显著差异的斑块各部位速度、斑块极值速度、斑块形态参数对缺血性脑血管病病人评价能力建立各部位速度预测、形态预测、速度极值预测、总体预测四个预测模型。
模型1：(各部位速度预测模型)包括已检测存在组间差异的PI-Vmax、P2-Vmax、P3-Vmax、P4-Vmin、P5-Vmin、P1-V、P2-V、P4-V、P5-V,曲线下面积0.713；
模型2：(形态预测模型)包括Ds、Dd、IMT、Lp,曲线下面积0.634；
模型3：(表面极值预测)包含Vmax、Vmin、V,曲线下面积0.659；
模型4：(总体预测模型)包含以上所有各部位速度、形态参数、速度极值参数,其预测能力大大提高,曲线下面积0.812,切点位置敏感性0.780,特异性0.836。
结论
1.应用VVI技术测量颈动脉粥样硬化患者斑块表面的速度、应变、应变率等力学指标,可反映斑块受力情况,辅助临床诊断。
2.依照不同颈动脉节段,分别研究节段内颈动脉斑块表面的力学特征,发现不同节段斑块径向速度不同,可能提示该指标更易受血流动力学影响。
3.颈动脉粥样硬化斑块在长轴上的受力具有不对称性。径向速度以斑块两侧基底部最大。斑块远心侧纵向应变较小,近心侧纵向应变较大,近心侧肩部在心动周期内纵向应变化最大,这一特征脑梗塞患者的颈动脉斑块上可能更为明显。
4.速度向量成像技术测量径向速度最大值、最小值、变化值可较好地反映。脑血管疾病情况,与形态学指标结合可使诊断价值进一步提高。
Background
Stroke is one of the leading causes of death worldwide. Each year, approximately 780000 people experience a new or recurrent stroke. Every 3 to 4 minutes, someone dies of a stroke on average. Patients who survived a transient ischemic attack is still at a risk of another ischemic cerebral event. Also, It is well accepted that atheromatous plaque is one of the major causes of stroke, and some researches find that up to 15% of cerebral infarctions are in association with embolic debris and thrombi at carotid bifurcation This is the reason why plaque vulnerability is drawing public attention in scientific field.
The morphology and deformation is critical to the vulnerabilty of carotid plaques, characteristics on plaque morphology has been widely investigated. IMT (intima-media thickness) and plaque stenosis were both reported to be independent indicators associated with ischemic stroke. Besides, plaque characterization, low echogenic plaque, plaque area, plaque volume, remolding index, eccentric index have also been reported to predict a subsequent stroke. Evidence support that carotid endarterectomy for severe symptomatic (70 to 99%) stenosis reduces the stroke risk compared to medical therapy alone for patients with 70 to 99% symptomatic stenosis.
Additional indicators other than morphological characteristics are needed to identify carotid artery lesions associated with a higher risk of stroke. Local mechanical environment is of great importance to plaque vulnerability. Stresses and strains mainly represent the local mechanical environment over endothelial and smooth muscle cells. Wall shear stress (WSS) is the frictional force exerted by circulating blood on endothelium and also an independent risk factor that involved with vulnerability. Low systolic WSS is identified as an atherosclerotic risk factor and may be responsible for a subsequent stroke. A higher level of tensile stress was proved to be related to plaque vulnerability and plaque rupture. The changes in the local mechanical factors further affect cellular processes such as cell proliferation, apoptosis, hypertrophy, migration, matrix synthesis and degradation, and therefore ultimately lead to observed structural and functional responses of remodeling.
Vector velocity imaging (VVl) is an angle-independent imaging method that uses a complicated tissue tracking algorithm and applied to conventional grayscale images to give information on myocardial velocity vectors and derive myocardial mechanic parameters. This technique is now widely used in the diagnosis of cardiac diseases, such as heart failure, cardiomyopathy, hypertension and the benefit of cardiac resynchronization therapy for its potential to quantitatively assess regional and global myocardial functions.
Limited researches have been focused on plaque deformation information derived from velocity vector imaging, by now, to our knowledge. Yue et al. investigated rotation of carotid plaques with this technique on short-axis view of carotid arteries. Wang et al. reported significantly lower radial velocities and higher circumferential strain rates of carotid artery in cerebral infarction subjects compared to those in the normals. However, research work on the longitudinal view of cartid arteries is rarely covered. Bending strain on the longitudinal view of an atherosclerotic plaque provide useful information of repetitive bending deformation of an atherosclerotic plaque and maybe responsible for plaque fatigue and rupture.
Objective
1. To investigate the local mechanical properties of carotid plaques with different types of ischemic ischemic cerebral vascular diseases using velocity vector imaging (VVl) technique.
2. To evaluate the segmental mechanical properties of atheromatous plaques.
3. To investigate the difference of local mechanical properties among different locations on atheromatous plaques.
4. To explore the diagnostic value of mechanical parameters derived from velocity vector imaging.
Methods
1. Study population and grouping
Study population:109 participants were enrolled in this study, of which 41 were diagnosed with acute ischemic infarction,17 were diagnosed with transient ischemic attack and 51 were without cerebrovascular history. All participants were with ischemic cerebrovascular diseases and carotid atherosclerosis and had gone through MRI or CT for diagnosis. Patients with hemorrhagic infarction, subarachnoid hmmorrhage, cardiac emboli, moyamoya disease were excluded in our study.
Grouping:(1)according to clinical diagnosis:0 group is representative of subjects without cerebralvascular history, TIA group and 2 are representative of patients with transient ischemic attack and ischemic infarction, separately. (2)according to plaque location on segments of carotid artery:AM group includes plaques on initial segment and middle segment of carotid artery, Bl group includes those on carotid bifurcation and initiation of interal carotid artery. (3)according to where the region of intrerest (ROI) was placed:P1 is termed as proximal base group, P2 is termed as proximal shoulder group, P3 means top of plaque group, P4 is distal shoulder group, P5 is distal base group.
2. Methods
2.1 two-dimensional echocardiography
Two-dimensional echocardiography was performed in all patients with image clips obtained after automated tissue tracking across three cardiac cycles. Visual information was acquired using a linear-array 10-14 MHz transducer (15L8W), with the frame rate controlled within 60～70 frame/sec.
2.2 Post processing of image clips
Velocity vector imaging software (syngo VVl, Siemens) was used to derive tissue velocity, strain, and strain rate, with curves obtained after automated tissue tracking. Out of the consideration that the behaviors of deformation may differ in locations, under the influence of blood flow, plaque structure, and vessel movement, we selectively tracked atheromatous plaque at five locations that include distal base (P5), distal shoulder (P4), top (P3), proximal shoulder (P2) and proximal base (P1) in each satisfactory image clip. The removable reference mark on B-mode image clips was put in the tissue across the lumen, during data analysis. Motion-related parameters such as tissue velocity, strain and strain rate were exported and later processed for the maximum, the minimum and the extreme variation values. According where the reference mark was placed, a positive value of velocity means the tracked site is moving towards the lumen center, while a negative one has the opposite meaning. Strain and strain is positive during plaque extension and negative during contraction.
3. Statistical ananlysis
SPSS 16.0 (SPSS Inc., Illinois, USA) was used for statistical analysis. Measures of grouped data are reported as mean±standard deviation. Discrete variables were analyzed by chi-square test. One-way ANOVA is used for multiple comparisons. Comparision between mechanic parameters of different locations is done with paired t test. LSD test is performed if equal variance is assumed. Dunnett's T3 is performed is if equal variance is not assumed. Binary logistic regression and ROC curve is done for diagnostic value of mechanic parameters for ischemic cerebral event. A P value of less than 0.05 is considered as significant.
Results
1. Comparisons of mechanical parameters among diagnostic groups
Peak velocity values:TIA group showed significantly higher P1-Vmax, P2-Vmax, P3-Vmax, P4-Vmin, P5-Vmin, T-Vmax, T-Vmin and T-Vcompared to NCD group. ACI group showed significantly higher T-Vmax, T-Vmin and T-V compared to NCD group. A significantly lower level of P1-Vmax, P2-Vmax, P3-Vmax, P4-Vmin, P5-Vmin, P1-V, P2-V, P4-V and P5-V were detected in ACI group in comparison to NCD group. Significance of peak strain and strain rate values was not detected among groups.
2. Segmental comparisons of mechanical parameters among each diagnostic group
2.1 Comparisons of mechanical parameters of low echogenic plaque between AM group and Bl group
AM-Vmin was significantly higher Bl-Vmin (P<0.05). No signifcance was detected in other parameters (P>0.05).
2.2 Comparisons of mechanical parameters among diagnostic groups in AM segments
TIA group showed significantly higher IM-Vmax and IM-Vmin compared to NCD group. ACI group showed significantly higher levels of IM-Vmin, M-S and IM-SRmin compared to NCD group. A significantly lower level of IM-Vmax, IM-V, IM-SRmin was detected in ACI group compared to TIA group.
2.3 Comparisons of mechanical parameters among diagnostic groups in Bl segments
TIA group showed significantly higher Bl-Vmax, Bl-Vmin and Bl-V (P<0.05)and a significantly lower BI-Smin(P<0.05)compared to NCD group. ACI group showed a significantly higher level of Bl-Vmin,and BI-SRmin and a significantly lower Bl-Smin (P<0.05) compared to NCD group. A significantly lower level of Bl-Vmax and Bl-Vwas detected in ACI group compared to TIA group.
3. Comparisons of mechanical parameters among different locations
3.1 Comparisons of mechanical parameters among different locations in symptomatic patients
Peak velocity values:Vmax, Vmin, V all showed a trend of first increase and then decrease. P1-Vmax is significantly higher than P2-Vmax, P3-Vmax and P4-Vmax (P<0.05). P5-Vmax is significantly higher than P3-Vmax and P4-Vmax (P<0.05). P1-V is significantly higher than P2-V and P3-V. P5-V is significantly higher than P2-V, P3-V and P4-V. P1-Vmin is significantly higher than P2-Vmin (P<0.05), P4-Vmin is significantly higher than P3-Vmin, P5-Vmin is significantly higher than P2-Vmin, P3-Vmin and P4-Vmin(P<0.05).
Peak strain values:Smax, Smin, S all showed a trend of first increase and then decrease. P2-Smin is significantly higher than P4-Smin (P<0.05), P2-S is significantly higher than P1-Sand P5-S (P<0.05).
Peak strain rate values:SRmax showed a increasing intendancy from P1 to P5, P5-SRmax is significantly higher than P1-SRmax (P<0.05).
3.2 Comparisons of mechanical parameters among different locations on asymptomatic plaques
Peak velocity values:A decreasing trend was detected in Vmax, Vmin and V from P1 to P4. Both P1-V and P2-V are significantly higher than P4-V (P<0.05).
Peak strain values:A trend of first increase and then decrease was detected in Smax, Smin and S. However no significance was detected among different locations.
Peak strain rate values:No agreement on trend was detected in SRmax, SRmin and SR. Besides, no significance of strain rate was detected among different locations.
4. Predictors of a subsequent ischemic cerebral event
In order to test if mechanical parameters are indicative of a ischemic cerebralvascular event (both acute ischemic stroke and TIA), we used four binary logistic regression models in which peak velocity values, morphological parameters, extreme velocity parameters and total parameters were included.
Model 1 (model of peak velocity values):includes P1-Vmax, P2-Vmax, P3-Vmax, P4-Vmin, P5-Vmin, P1-V, P2-V, P4-V and P5-V. An AUC of 0.713 was detected in this model.
Model 2 (model of morphological parameters):include Ds, Dd, IMT, Lp. AUC was 0.634 in model 2.
Model 3 (model of extreme velocity parameters):Vmax, Vmin and V were included in this model, an AUC of 0.659 was detected.
Model 4(model of total parameters):Model 4 includes both morphological and mechanical parameters. AUC for this model is 0.812, which means the abiblity for predication is highly elevated. The sensitivity and specificity were 0.780 and 0.836 at the cut-off point.
Conclusion
1. Vector velocity imaging is an angle-independent visual and quantitative method for the quantitatively assessment of carotid atheromatious plaque vulnerability.
2. Result of segmental analysis of velocity, strain and strain rate showed that radial velocity varies in segments. Therefore, this parameter might be more susceptible to hemodynamic states.
3. A characteristic of asymmetry was detected among different locations on carotid plaques, the asymmetrical properties may be more detectabl in symptomatic plaques.
4. A model that combines the morphological and mechanical parameters may better diagnosis patients with ischemic cerebralvascular diseases.
脑卒中是缺血性脑血管疾病的重要形式,具有极高的致残率和致死率。其中,缺血性脑卒中占卒中总数约50%-60%,造成了巨大的经济负担。短暂性脑缺血发作是脑卒中的高危因素。脑卒中是目前中国人群主要的死亡原因,而其中缺血型卒中的发病率呈明显上升趋势。近年来,动脉粥样硬化作为脑卒中的重要发病因素已被大家公认。晚近一些研究发现约15%的脑梗塞与来自颈动脉分叉处的碎屑和栓子有关,至此动脉粥硬化斑块与缺血性脑血管病的关系引来更为广泛的关注。
斑块形态、形变功能对斑块的稳定性至关重要。颈动脉内膜-中层厚度(intima-media thickness, IMT)作为动脉粥样硬化的重要形态特征之一,其与心肌梗死、脑卒中的关系已被证实。此外,斑块低回声、斑块面积、斑块体积、斑块偏心指数等也与脑卒中的发生关系密切。
动脉粥样硬化斑块的力学特征近来受到重视。其中,剪切力是循环血流作用于血管壁内皮上的摩擦力,周向应力则由管壁扭转引起。剪切力不仅扮演着局部血管重构始动因子的角色,而且与动脉粥样硬化斑块的形态和易损性有关。低剪切力被认为是斑块进展的促进因素而高剪切力则与斑块破裂有关,其中低收缩期剪切力被认为是致动脉粥样硬化的危险因素,并可能与继发的脑血管事件相关。高周向应力与斑块的易损和破裂有关。此外,颈动脉扩张性也是血管壁功能的代表。我们最近的工作也证明了斑块体积压缩率(Plaque volume compression ratio, VCR)是脑卒中发生的独立危险因子。然而无创定量地研究动脉粥样硬化斑块的力学特征的研究方法相对有限,有待进一步研究。
速度向量成像技术(velocity vector imaging, VVI)以声学采集、斑点追踪、空间相干等技术为基础,可获取研究对象的运动信息,并在二维图像上表示运动信息。该技术对研究对象运动信息的测量不受角度依赖,已广泛地应用于评价心肌局部收缩和舒张功能、高血压心脏病、心力衰竭、心肌病及心脏再同步化治疗效果[23]等。
VVI技术在颈动脉粥样硬化性疾病的应用较少。国内,张蕾等应用VVI技术研究兔模型中颈动脉粥样硬化斑块的易损性。岳文胜等将该技术检应用于颈动脉粥样硬化斑块内膜旋转的发生和角度变化的检测。汪奇等使用VVI技术研究脑梗塞患者与正常人群的颈动脉血管短轴运动特征,发现ACI组颈动脉各壁的径向速度均小于正常人。目前,VVI技术对颈动脉粥样硬化的研究主要应用于血管短轴切面,而在血管长轴方向上的临床应用尚未开展。动脉粥硬化斑块沿血管长轴方向上的长期拉伸与弯曲与斑块的破裂有关。本试验首次将VVI技术应用于缺血性脑血管疾病患者颈动脉血管长轴力学特征研究,对颈动脉粥样硬化斑块长轴力学特征(拉伸与弯曲)与脑血管病之间的关系进行探讨。
研究目的
(1)探讨斑块表面力学运动参数在缺血性脑血管疾病类型间的差异。
(2)探讨斑块表面力学运动参数与斑块节段部位的关系。
(3)探讨斑块表面力学运动参数在斑块表面不同部位间的差异。
(4)探讨VVI技术测量颈动脉斑块参数对于缺血性脑血管病的诊断价值。
研究资料与方法
1.研究对象与分组：
研究对象：缺血性脑血管病患者入选59例,非脑血管病患者入选50例。缺血性脑血管病组入选标准与排除标准：具备缺血性脑血管病临床症状和颈动脉粥样硬化,符合第四届全国脑血管病学术会议修订的有关脑梗塞与短暂性脑缺血发作(TIA)的诊断标准,并经颅脑MRI/CT证实为急性脑梗塞或TIA,并排除出血后梗塞、蛛网膜下腔出血、心源性脑栓塞、颅内占位性病变等。NCD组入选标准：排除任何脑血管病病史的颈动脉粥样硬化患者。
分组方法：(1)按入选研究对象的临床诊断分组：NCD组为非脑血管组,TIA组为短暂性脑缺血发作组,ACI组为脑梗塞组。(2)按研究对象的颈动脉粥样硬化斑块的节段位置分组：AM为颈动脉起始段与中段组,BI为颈动脉分叉与颈内动脉起始部组。(3)按颈动脉粥硬化斑块长轴图像上取样部位分组：P1为近心端基底部组,P2为近心端肩部组,P3为斑块顶部组,P4为远心端斑块肩部组,P5为远心端斑块基底部组。
2.研究方法
2.1二维超声图像存储
使用Acuson Sequoia C512(Siemens)超声探测仪及10-14 MHz高频线阵探头采集颈动脉二维图像,帧频控制在60帧／秒以上。颈总动脉及颈内动脉沿血管长轴的动态图像冻结后存储。
2.2图像处理与数据分析
应用速度向量成像技术分析软件(syngo VVI)分析单心动周期内颈动脉斑块表面五个ROI部位：近心端基底部(P1)、近心端肩部(P2)、斑块顶部(P3)、远心端肩部(P4)、斑块远心端基底部(P5)。手动将参照点放置于斑块对侧管壁外的组织内。获取不同ROI部位参数,保存为全心动周期运动参数Excel表格。单心动周期运动参数表经正负极值计算后取得五个ROI部位单心动周期内速度、应变、应变率的最大正值(max)、最大负值(min)。最大变化值是max与min间差值。依据参照点所取位置,规定朝向定标的速度为正向速度。依据理论,应变的正值提示斑块舒张,负值提示斑块压缩。
3.统计学方法
应用SPSS16.0统计软件进行数据分析。统计结果以P<0.05为有显著性意义。计数资料资料以均数±标准差表示。应用单因素方差检测诊断组间均数差异显著性,符合Levene方差齐性检验采用LSD检验方法进行多重比较、方差不齐应用Dunnett's T3。斑块不同部位参数组间均数比较应用配对t检验。计量资料的显著性检验χ2检验法。单因素方差分析有显著性的参数经二分类Logistic回归建立模型。ROC曲线用于评价各模型对脑血管病的预测价值。
结果
1.按诊断分组三组间的力学参数变化
速度峰值：TIA组与NCD组相比p1-Vmax、P2-Vmax、P3-Vmax、P4-Vmin、P5-Vmin、T-Vmax、T-Vmin、T-V明显增大(P<0.05)；ACI组与NCD组相比T-Vmax、T-Vmin、T-V明显增大(P<0.05)。ACI组与TIA组相比P1-Vmax、P2-Vmax、P3-Vmax、P4-Vmin、P5-Vmin、P1-V、P2-V、P4-V、P5-V显著减小(P<0.05)。
2.按斑块节段位置分组后三组间的力学参数变化
2.1AM组与BI组低回声斑块总体力学参数的比较
AM组与BI组低回声斑块总体力学参数比较,AM-Vmin较BI-Vmin显著增大(P<0.05)。其余参数变化未见差异(P>0.05)
2.2 AM组的力学参数峰值变化：
TIA组与NCD组比较,TIA组的AM-Vmax、AM-Vmin、AM-V明显增大(P<0.05)；2与NCD组相比,AM-Vmin、AM-SRmin、AM-S明显增大(P<0.05)；ACI组与TIA组比较,ACI组的AM-Vmax、AM-V显著减小(P<0.05),AM-SRmin明显增大(P<0.05)。
2.3 B工组的力学参数峰值变化：
TIA组与NCD组比较BI-Vmax、BI-Vmin、BI-V明显增大,BI-Smin明显减小(P<0.05)。ACI组与NCD组比较BI-Vmin明显增大,BI-Smin明显减小(P<0.05),BI-SRmin明显增大(P<0.05)。2与TIA组比较BI-Vmax、BI-V明显减小(P<0.05)。
3.按斑块不同部位分组力学参数均值变化
3.1ACI组斑块不同部位力学参数变化
ACI组斑块不同部位径向速度变化：从P1至P5,Vmax、Vmin、V都出现显减小在增大的特点。P1-Vmax显著大于P2-Vmax、P3-Vmax、P4-Vmax; P5-Vmax显著大于P3-Vmax、P4-Vmax (P<0.05); P1-V显著大于P2-V、P3-V(P<0.05), P5-V显著大于P2-V、P3-V、P4-V (P<0.05); P1-Vmin显著大于P2-Vmin (P<0.05), P4-Vmin显著大于P3-Vmin (P<0.05), P5-Vmin显著大于P2-Vmin、P3-Vmin、P4-Vmin (P<0.01)。
ACI组斑块不同部位应变变化：从P1至P5,Smax、Smin、S都出现先增大再减小的变化特点。其中P2-Smin显著大于P4(P<0.05),P2-S显著大于P1-S和P5-S(P<0.05)。
ACI组斑块不同部位应变率变化：SRmax与SR从P1至P5依次增大,P1-SRmax显著小于P5-SRmax (P<0.05)。
3.2NCD组不同部位力学参数均值变化
NCD组斑块不同部位速度变化：Vmax、Vmin和V变化趋势一致,均从P1至P4依次减小,从P4至P5升高。其中,P1-V和P2-V都显著大于P4-V(P<0.05)。
NCD组斑块不同部位应变变化：Smax和S都出现先增大再减小的变化过程。各部位之间的应变差异无显著性(P>0.05)。
NCD组斑块不同部位应变率变化：SRmax、SRmin、SR的变化趋势不一致,且各部位之间的应变差异无显著性(P>0.05)。
4.斑块表面运动参数的Logistic回归分析与ROC曲线分析结果
二分类Logistic回归分析存在组间差异的各参数与缺血性脑血管病(包括急性脑梗塞与TIA)之间的关系。ROC曲线分析在单因素方差分析中存在显著差异的斑块各部位速度、斑块极值速度、斑块形态参数对缺血性脑血管病病人评价能力建立各部位速度预测、形态预测、速度极值预测、总体预测四个预测模型。
模型1：(各部位速度预测模型)包括已检测存在组间差异的PI-Vmax、P2-Vmax、P3-Vmax、P4-Vmin、P5-Vmin、P1-V、P2-V、P4-V、P5-V,曲线下面积0.713；
模型2：(形态预测模型)包括Ds、Dd、IMT、Lp,曲线下面积0.634；
模型3：(表面极值预测)包含Vmax、Vmin、V,曲线下面积0.659；
模型4：(总体预测模型)包含以上所有各部位速度、形态参数、速度极值参数,其预测能力大大提高,曲线下面积0.812,切点位置敏感性0.780,特异性0.836。
结论
1.应用VVI技术测量颈动脉粥样硬化患者斑块表面的速度、应变、应变率等力学指标,可反映斑块受力情况,辅助临床诊断。
2.依照不同颈动脉节段,分别研究节段内颈动脉斑块表面的力学特征,发现不同节段斑块径向速度不同,可能提示该指标更易受血流动力学影响。
3.颈动脉粥样硬化斑块在长轴上的受力具有不对称性。径向速度以斑块两侧基底部最大。斑块远心侧纵向应变较小,近心侧纵向应变较大,近心侧肩部在心动周期内纵向应变化最大,这一特征脑梗塞患者的颈动脉斑块上可能更为明显。
4.速度向量成像技术测量径向速度最大值、最小值、变化值可较好地反映。脑血管疾病情况,与形态学指标结合可使诊断价值进一步提高。
Background
Stroke is one of the leading causes of death worldwide. Each year, approximately 780000 people experience a new or recurrent stroke. Every 3 to 4 minutes, someone dies of a stroke on average. Patients who survived a transient ischemic attack is still at a risk of another ischemic cerebral event. Also, It is well accepted that atheromatous plaque is one of the major causes of stroke, and some researches find that up to 15% of cerebral infarctions are in association with embolic debris and thrombi at carotid bifurcation This is the reason why plaque vulnerability is drawing public attention in scientific field.
The morphology and deformation is critical to the vulnerabilty of carotid plaques, characteristics on plaque morphology has been widely investigated. IMT (intima-media thickness) and plaque stenosis were both reported to be independent indicators associated with ischemic stroke. Besides, plaque characterization, low echogenic plaque, plaque area, plaque volume, remolding index, eccentric index have also been reported to predict a subsequent stroke. Evidence support that carotid endarterectomy for severe symptomatic (70 to 99%) stenosis reduces the stroke risk compared to medical therapy alone for patients with 70 to 99% symptomatic stenosis.
Additional indicators other than morphological characteristics are needed to identify carotid artery lesions associated with a higher risk of stroke. Local mechanical environment is of great importance to plaque vulnerability. Stresses and strains mainly represent the local mechanical environment over endothelial and smooth muscle cells. Wall shear stress (WSS) is the frictional force exerted by circulating blood on endothelium and also an independent risk factor that involved with vulnerability. Low systolic WSS is identified as an atherosclerotic risk factor and may be responsible for a subsequent stroke. A higher level of tensile stress was proved to be related to plaque vulnerability and plaque rupture. The changes in the local mechanical factors further affect cellular processes such as cell proliferation, apoptosis, hypertrophy, migration, matrix synthesis and degradation, and therefore ultimately lead to observed structural and functional responses of remodeling.
Vector velocity imaging (VVl) is an angle-independent imaging method that uses a complicated tissue tracking algorithm and applied to conventional grayscale images to give information on myocardial velocity vectors and derive myocardial mechanic parameters. This technique is now widely used in the diagnosis of cardiac diseases, such as heart failure, cardiomyopathy, hypertension and the benefit of cardiac resynchronization therapy for its potential to quantitatively assess regional and global myocardial functions.
Limited researches have been focused on plaque deformation information derived from velocity vector imaging, by now, to our knowledge. Yue et al. investigated rotation of carotid plaques with this technique on short-axis view of carotid arteries. Wang et al. reported significantly lower radial velocities and higher circumferential strain rates of carotid artery in cerebral infarction subjects compared to those in the normals. However, research work on the longitudinal view of cartid arteries is rarely covered. Bending strain on the longitudinal view of an atherosclerotic plaque provide useful information of repetitive bending deformation of an atherosclerotic plaque and maybe responsible for plaque fatigue and rupture.
Objective
1. To investigate the local mechanical properties of carotid plaques with different types of ischemic ischemic cerebral vascular diseases using velocity vector imaging (VVl) technique.
2. To evaluate the segmental mechanical properties of atheromatous plaques.
3. To investigate the difference of local mechanical properties among different locations on atheromatous plaques.
4. To explore the diagnostic value of mechanical parameters derived from velocity vector imaging.
Methods
1. Study population and grouping
Study population:109 participants were enrolled in this study, of which 41 were diagnosed with acute ischemic infarction,17 were diagnosed with transient ischemic attack and 51 were without cerebrovascular history. All participants were with ischemic cerebrovascular diseases and carotid atherosclerosis and had gone through MRI or CT for diagnosis. Patients with hemorrhagic infarction, subarachnoid hmmorrhage, cardiac emboli, moyamoya disease were excluded in our study.
Grouping:(1)according to clinical diagnosis:0 group is representative of subjects without cerebralvascular history, TIA group and 2 are representative of patients with transient ischemic attack and ischemic infarction, separately. (2)according to plaque location on segments of carotid artery:AM group includes plaques on initial segment and middle segment of carotid artery, Bl group includes those on carotid bifurcation and initiation of interal carotid artery. (3)according to where the region of intrerest (ROI) was placed:P1 is termed as proximal base group, P2 is termed as proximal shoulder group, P3 means top of plaque group, P4 is distal shoulder group, P5 is distal base group.
2. Methods
2.1 two-dimensional echocardiography
Two-dimensional echocardiography was performed in all patients with image clips obtained after automated tissue tracking across three cardiac cycles. Visual information was acquired using a linear-array 10-14 MHz transducer (15L8W), with the frame rate controlled within 60～70 frame/sec.
2.2 Post processing of image clips
Velocity vector imaging software (syngo VVl, Siemens) was used to derive tissue velocity, strain, and strain rate, with curves obtained after automated tissue tracking. Out of the consideration that the behaviors of deformation may differ in locations, under the influence of blood flow, plaque structure, and vessel movement, we selectively tracked atheromatous plaque at five locations that include distal base (P5), distal shoulder (P4), top (P3), proximal shoulder (P2) and proximal base (P1) in each satisfactory image clip. The removable reference mark on B-mode image clips was put in the tissue across the lumen, during data analysis. Motion-related parameters such as tissue velocity, strain and strain rate were exported and later processed for the maximum, the minimum and the extreme variation values. According where the reference mark was placed, a positive value of velocity means the tracked site is moving towards the lumen center, while a negative one has the opposite meaning. Strain and strain is positive during plaque extension and negative during contraction.
3. Statistical ananlysis
SPSS 16.0 (SPSS Inc., Illinois, USA) was used for statistical analysis. Measures of grouped data are reported as mean±standard deviation. Discrete variables were analyzed by chi-square test. One-way ANOVA is used for multiple comparisons. Comparision between mechanic parameters of different locations is done with paired t test. LSD test is performed if equal variance is assumed. Dunnett's T3 is performed is if equal variance is not assumed. Binary logistic regression and ROC curve is done for diagnostic value of mechanic parameters for ischemic cerebral event. A P value of less than 0.05 is considered as significant.
Results
1. Comparisons of mechanical parameters among diagnostic groups
Peak velocity values:TIA group showed significantly higher P1-Vmax, P2-Vmax, P3-Vmax, P4-Vmin, P5-Vmin, T-Vmax, T-Vmin and T-Vcompared to NCD group. ACI group showed significantly higher T-Vmax, T-Vmin and T-V compared to NCD group. A significantly lower level of P1-Vmax, P2-Vmax, P3-Vmax, P4-Vmin, P5-Vmin, P1-V, P2-V, P4-V and P5-V were detected in ACI group in comparison to NCD group. Significance of peak strain and strain rate values was not detected among groups.
2. Segmental comparisons of mechanical parameters among each diagnostic group
2.1 Comparisons of mechanical parameters of low echogenic plaque between AM group and Bl group
AM-Vmin was significantly higher Bl-Vmin (P<0.05). No signifcance was detected in other parameters (P>0.05).
2.2 Comparisons of mechanical parameters among diagnostic groups in AM segments
TIA group showed significantly higher IM-Vmax and IM-Vmin compared to NCD group. ACI group showed significantly higher levels of IM-Vmin, M-S and IM-SRmin compared to NCD group. A significantly lower level of IM-Vmax, IM-V, IM-SRmin was detected in ACI group compared to TIA group.
2.3 Comparisons of mechanical parameters among diagnostic groups in Bl segments
TIA group showed significantly higher Bl-Vmax, Bl-Vmin and Bl-V (P<0.05)and a significantly lower BI-Smin(P<0.05)compared to NCD group. ACI group showed a significantly higher level of Bl-Vmin,and BI-SRmin and a significantly lower Bl-Smin (P<0.05) compared to NCD group. A significantly lower level of Bl-Vmax and Bl-Vwas detected in ACI group compared to TIA group.
3. Comparisons of mechanical parameters among different locations
3.1 Comparisons of mechanical parameters among different locations in symptomatic patients
Peak velocity values:Vmax, Vmin, V all showed a trend of first increase and then decrease. P1-Vmax is significantly higher than P2-Vmax, P3-Vmax and P4-Vmax (P<0.05). P5-Vmax is significantly higher than P3-Vmax and P4-Vmax (P<0.05). P1-V is significantly higher than P2-V and P3-V. P5-V is significantly higher than P2-V, P3-V and P4-V. P1-Vmin is significantly higher than P2-Vmin (P<0.05), P4-Vmin is significantly higher than P3-Vmin, P5-Vmin is significantly higher than P2-Vmin, P3-Vmin and P4-Vmin(P<0.05).
Peak strain values:Smax, Smin, S all showed a trend of first increase and then decrease. P2-Smin is significantly higher than P4-Smin (P<0.05), P2-S is significantly higher than P1-Sand P5-S (P<0.05).
Peak strain rate values:SRmax showed a increasing intendancy from P1 to P5, P5-SRmax is significantly higher than P1-SRmax (P<0.05).
3.2 Comparisons of mechanical parameters among different locations on asymptomatic plaques
Peak velocity values:A decreasing trend was detected in Vmax, Vmin and V from P1 to P4. Both P1-V and P2-V are significantly higher than P4-V (P<0.05).
Peak strain values:A trend of first increase and then decrease was detected in Smax, Smin and S. However no significance was detected among different locations.
Peak strain rate values:No agreement on trend was detected in SRmax, SRmin and SR. Besides, no significance of strain rate was detected among different locations.
4. Predictors of a subsequent ischemic cerebral event
In order to test if mechanical parameters are indicative of a ischemic cerebralvascular event (both acute ischemic stroke and TIA), we used four binary logistic regression models in which peak velocity values, morphological parameters, extreme velocity parameters and total parameters were included.
Model 1 (model of peak velocity values):includes P1-Vmax, P2-Vmax, P3-Vmax, P4-Vmin, P5-Vmin, P1-V, P2-V, P4-V and P5-V. An AUC of 0.713 was detected in this model.
Model 2 (model of morphological parameters):include Ds, Dd, IMT, Lp. AUC was 0.634 in model 2.
Model 3 (model of extreme velocity parameters):Vmax, Vmin and V were included in this model, an AUC of 0.659 was detected.
Model 4(model of total parameters):Model 4 includes both morphological and mechanical parameters. AUC for this model is 0.812, which means the abiblity for predication is highly elevated. The sensitivity and specificity were 0.780 and 0.836 at the cut-off point.
Conclusion
1. Vector velocity imaging is an angle-independent visual and quantitative method for the quantitatively assessment of carotid atheromatious plaque vulnerability.
2. Result of segmental analysis of velocity, strain and strain rate showed that radial velocity varies in segments. Therefore, this parameter might be more susceptible to hemodynamic states.
3. A characteristic of asymmetry was detected among different locations on carotid plaques, the asymmetrical properties may be more detectabl in symptomatic plaques.
4. A model that combines the morphological and mechanical parameters may better diagnosis patients with ischemic cerebralvascular diseases.
引文
1. Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics-2008 update-A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008;117:E25-E146
2. Rosamond W, Flegal K, Friday G, et al. Heart disease and stroke statistics-2007 update-A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2007;115:E69-E171
3. Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack A statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke Co-sponsored by the Council on Cardiovascular Radiology and Intervention-The American Academy of Neurology affirms the value of this guideline. Circulation 2006;113:E409-E449
4. Easton JD, Saver JL, Albers GW, et al. Definition and Evaluation of Transient Ischemic Attack A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke 2009;40:2276-2293
5. 赵冬.我国人群脑卒中发病率、死亡率的流行病学研究.中华流行病学杂
志2003；3
6. 王文化.北京市1984～1999年人群脑卒中发病率变化趋势分析.中华流行病学杂志2001;4
7. Fairhead JF, Mehta Z, Rothwell PM. Population-based study of delays in carotid imaging and surgery and the risk of recurrent stroke. Neurology 2005:65:371-375
8. Prati P, Tosetto A, Vanuzzo D, et al. Carotid intima media thickness and plaques can predict the occurrence of ischemic cerebrovascular events. Stroke 2008:39:2470-2476
9. Chaturvedi S, Bruno A, Feasby T, et al. Carotid endarterectomy-An evidence-based review-Report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology. Neurology 2005:65:794-801
10. Heliopoulos J, Vadikolias K, Mitsias P, et al. A three-dimensional ultrasonographic quantitative analysis of non-ulcerated carotid plaque morphology in symptomatic and asymptomatic carotid stenosis. Atherosclerosis 2008:198:129-135
11. Ohara T, Toyoda K, Otsubo R, et al. Eccentric Stenosis of the Carotid Artery Associated with Ipsilateral Cerebrovascular Events. AJNR Am J Neuroradiol 2008;29:1200-1203
12. Cunningham KS, Gotlieb AI. The role of shear stress in the pathogenesis of atherosclerosis. Laboratory Investigation 2005:85:9-23
13. Cheng C, Tempel D, van Haperen R, et al. Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress. Circulation 2006:113:2744-2753
14. Groen HC, Gijsen FJH, van der Lugt A, et al. Plaque rupture in the carotid artery is localized at the high shear stress region-A case report. Stroke 2007:38:2379-2381
15. Carallo C, Lucca LF, Ciamei M, Tucci S, de Franceschi MS. Wall shear stress is lower in the carotid artery responsible for a unilateral ischemic stroke. Atherosclerosis 2006;185:108-113
16. Lee RT, Schoen FJ, Loree HM, Lark MW, Libby P. Circumferential stress and matrix metalloproteinasel in human coronary atherosclerosis. Implications for plaque rupture. Arterioscler Thromb Vasc Biol 1996:16:1070-1073
17. 岳文胜,尹立雪,王珊,et al.孤立性颈动脉粥样硬化斑块内膜旋转角度的超声评价.中国医学科学院学报2007;30：63-68
18. Hare JL, Brown JK, Marwick TH. Association of Myocardial Strain With Left Ventricular Geometry and Progression of Hypertensive Heart Disease. The American Journal of Cardiology 2008:102:87-91
19. Chen JH, Cao TS, Duan YY, Yuan LJ, Wang ZJ. Velocity vector imaging in assessing myocardial systolic function of hypertensive patients with left ventricular hypertrophy. Canadian Journal of Cardiology 2007:23:957-961
20. 国建萍,王玉堂,单兆亮,et al.速度向量成像技术在心力衰竭患者同步化治疗中的应用.中国心脏起搏与心电生理杂志2009;23：309-312
21. Burri MV, Nanda NC, Lloyd SG, et al. Assessment of Systolic and Diastolic Left Ventricular and Left Atrial Function Using Vector Velocity Imaging in Takotsubo Cardiomyopathy. Echocardiography 2008:25:1138-1144
22. Carasso S, Yang H, Woo A, et al. Systolic Myocardial Mechanics in Hypertrophic Cardiomyopathy:Novel Concepts and Implications for Clinical Status. Journal of the American Society of Echocardiography 2008:21:675-683
23. Jansen AHM, van Dantzig JM, Bracke F, et al. Qualitative observation of left ventricular multiphasic septal motion and septal-to-latelal apical shuffle predicts left ventricular reverse remodeling after cardiac resynchronization therapy. American Journal of Cardiology 2007;99:966-969
24. 王志蕴,张梅,刘晓玲,et al.速度向量成像技术早期无创性评价动脉硬化的临床研究.中华医学超声杂志(电子版)2009；6：252-258
25. Zhang L, Liu Y, Zhang PF, et al. Peak radial and circumferential strain measured by velocity vector imaging is a novel index for detecting vulnerable plaques in a rabbit model of atherosclerosis. Atherosclerosis;In Press, Corrected Proof
26. 汪奇,钱蕴秋,刘丽文,et al.速度向量成像技术评价脑梗死患者颈总动脉管壁运动的初步研究.中国超声医学杂志2007；23：32-35
27. Fagerberg B, Ryndel M, Kjelldahl J, et al. Differences in lesion severity and cellular composition between in vivo assessed upstream and downstream sides of human symptomatic carotid atherosclerotic plaques. Journal of vascular Research 2010:47:221-230
28. Ding SF, Zhang M, Zhao YX, et al. The role of carotid plaque vulnerability and inflammation in the pathogenesis of acute ischemic stroke. Am J Med Sci 2008:336:27-31
29. Zhang PF, Su HJ, Yao GH, et al. Plaque volume compression ratio, a novel biomechanical index, is independently associated with ischemic cerebrovascular events. Journal of Hypertension 2009;27:348-356
30. 脑血管疾病分类(1995)(中、英文)中华神经科杂志1996；29：376-377
31. 张梅,张运,高月花,et al.超声检查对颈动脉粥样硬化血管重构的研究.中华超声影像学杂志2002；4：229-231
32. Adams HP, Bendixen BH, Kappelle LJ, et al. CLASSIFICATION OF SUBTYPE OF ACUTE ISCHEMIC STROKE-DEFINITIONS FOR USE IN A MULTICENTER CLINICAL-TRIAL. Stroke 1993;24:35-41
33. 吴江,贾建平,崔丽英.神经病学.2005：155-159
34. Lusis AJ. Atherosclerosis. Nature 2000;407:233-241
35. Kalogeropoulos A, Terzis G, Chrysanthopoulou A, et al. Risk for transient ischemic attacks is mainly determined by intima-media thickness and carotid plaque echogenicity. Atherosclerosis 2007;192:190-196
36. Cao JJ, Arnold AM, Manolio TA, et al. Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality-The cardiovascular health study. Circulation 2007;116:32-38
37. DeMaria AN, Narula J, Mahmud E, Tsimikas S. Imaging vulnerable plaque by ultrasound. J Am Coll Cardiol 2006;47:C32-39
38. Fuster V, Moreno PR, Fayad ZA, Corti R, Badimon JJ. Atherothrombosis and High-Risk Plaque:Part I:Evolving Concepts. Journal of the American College of Cardiology 2005:46:937-954
39. Huang H, Virmani R, Younis H, et al. The impact of calcification on the biomechanical stability of atherosclerotic plaques. Circulation 2001:103:1051-1056
40. Schoenhagen P, Ziada KM, Kapadia SR, et al. Extent and direction of arterial remodeling in stable versus unstable coronary syndromes an intravascular ultrasound study. Circulation 2000:101:598-603
41. Fisher M, Paganini-Hill A, Martin A, et al. Carotid plaque pathology: thrombosis, ulceration, and stroke pathogenesis. Stroke 2005:36:253-257
42. Nikic P, Savic M, Jakovljevic V, Djuric D. Intima-media thickness of common carotid artery, carotid atherosclerosis and subtypes of ischemic cerebral disease. Rom J Intern Med 2004;42:149-160
43. Nikic P, Savic M, Jakovljevic V, Djuric D. Carotid atherosclerosis, coronary atherosclerosis and carotid intima-media thickness in patients with ischemic cerebral disease:Is there any link? Exp Clin Cardiol 2006:11:102-106
44. Ouhlous M, Flach HZ, de Weert TT, et al. Carotid plaque composition and cerebral infarction:MR imaging study. AJNR Am J Neuroradiol 2005;26:1044-1049
45. Heuten H, Claeys M, Goovaerts I, et al. Can measurement of the intima-media thickness of the carotid artery improve the diagnostic value of exercise stress tests? Acta Cardiol 2006;61:501-505
46. 周鹏,陈荔川,高雪梅.数字减影在脑血管造影中的临床应用.实用医学影像学杂志2004;5：64-66
47. 王颖颖.数字减影血管造影技术.中国医疗器械信息2004;6
48. 李运军.MRA、 CTA、 DSA在出血性脑血管病诊断中的应用.中国微侵袭神经外科杂志2008;2：81
49. 王大明.CTA、 MRA与DSA在脑血管病诊断与治疗中的地位.中国现代神经疾病杂志2007;7：413
50. 张天义,冼惠珍.速度向量成像技术及其定量评价.中华临床医师杂志(电子版) 2007;1：433-437
51. Langeland S, D'Hooge J, Wouters PF, et al. Experimental validation of a new ultrasound method for the simultaneous assessment of radial and longitudinal myocardial deformation independent of insonation angle. Circulation 2005:112:2157-2162
52. Cinthio M, Ahlgren AR, Bergkvist J, et al. Longitudinal movements and resulting shear strain of the arterial wall. Am J Physiol Heart Circ Physiol 2006:291:H394-402
53. Cinthio M, Ahlgren AR. Intra-Observer Variability of Longitudinal Displacement and Intramural Shear Strain Measurements of the Arterial Wall Using Ultrasound Noninvasively in vivo. Ultrasound in Medicine & Biology;36:697-704
54. Hansen HHG, Lopata RGP, de Korte CL. Noninvasive Carotid Strain Imaging Using Angular Compounding at Large Beam Steered Angles: Validation in Vessel Phantoms. Ieee Transactions on Medical Imaging 2009:28:872-880
55. Humphrey JD, Eberth JF, Dye WW, Gleason RL. Fundamental role of axial stress in compensatory adaptations by arteries. J Biomech 2009;42:1-8
56. Huang X, Yang C, Yuan C, et al. Patient-specific artery shrinkage and 3D zero-stress state in multi-component 3D FSI models for carotid atherosclerotic plaques based on in vivo MRI data. Mol Cell Biomech 2009:6:121-134
57. Gao H, Long Q, Graves M, Gillard JH, Li Z-Y. Carotid arterial plaque stress analysis using fluid-structure interactive simulation based on in-vivo magnetic resonance images of four patients. Journal of Biomechanics 2009:42:1416-1423
58. Pirat B, Khoury DS, Hartley CJ, et al. A novel feature-tracking echocardiographic method for the quantitation of regional myocardial function-Validation in an animal model of ischemia-reperfusion. Journal of the American College of Cardiology 2008:51:651-659
59. Gao H, Long Q. Effects of varied lipid core volume and fibrous cap thickness on stress distribution in carotid arterial plaques. Journal of Biomechanics 2008:41:3053-3059
60. Thrysoe SA, Oikawa M, Yuan C, et al. Longitudinal Distribution of Mechanical Stresses in Carotid Plaques of Symptomatic Patients. Stroke:STROKEAHA.109.571588
61. Li Z-Y, Howarth SPS, Tang T, et al. Structural analysis and magnetic resonance imaging predict plaque vulnerability:A study comparing symptomatic and asymptomatic individuals. Journal of Vascular Surgery 2007:45:768-775
62. Lee RT, Schoen FJ, Loree HM, Lark MW, Libby P. Circumferential Stress and Matrix Metalloproteinase 1 in Human Coronary Atherosclerosis: Implications for Plaque Rupture. Arteriosclerosis, Thrombosis, and Vascular Biology 1996;16:1070-1073
63. Cheng C, Tempel D, van Haperen R, et al. Activation of MMP8 and MMP13 by angiotensin II correlates to severe intra-plaque hemorrhages and collagen breakdown in atherosclerotic lesions with a vulnerable phenotype. Atherosclerosis 2009:204:26-33
64. 岳文胜,尹立雪,王志刚,et al.颈动脉粥样硬化斑块上中下游短轴切面内膜位点的超声径向力学研究.中国医学影像技术2008；24：1389-1393
65. 张鹏飞,张运,张梅,姚桂华,王荣.颈动脉粥样斑块应变及应变率分布的初步探讨.中华超声影像学杂志2004；13:573-576
66. LaDisa JF, Jr., Bowers M, Harmann L, et al. Time-efficient patient-specific quantification of regional carotid artery fluid dynamics and spatial correlation with plaque burden. Med Phys;37:784-792
67. Boyd J, Buick JM. Three-dimensional modelling of the human carotid artery using the lattice Boltzmann method:Ⅱ. Shear analysis Physics in Medicine and Biology 2008;53
68. Poepping TL, Rankin RN, Holdsworth DW. Flow Patterns in Carotid Bifurcation Models Using Pulsed Doppler Ultrasound:Effect of Concentric vs. Eccentric Stenosis on Turbulence and Recirculation. Ultrasound in Medicine & Biology;In Press, Corrected Proof
69. Zhao SZ, Ariff B, Long Q, et al. Inter-individual variations in wall shear stress and mechanical stress distributions at the carotid artery bifurcation of healthy humans. J Biomech 2002;35:1367-1377
70. Marfella R, D'Amico M, Di Filippo C, et al. Increased Activity of the Ubiquitin-Proteasome System in Patients With Symptomatic Carotid Disease Is Associated With Enhanced Inflammation and May Destabilize the Atherosclerotic Plaque:Effects of Rosiglitazone
Treatment. Journal of the American College of Cardiology 2006;47:2444-2455
71. Redgrave JNE, Lovett JK, Gallagher PJ, Rothwell PM. Histological Assessment of 526 Symptomatic Carotid Plaques in Relation to the Nature and Timing of Ischemic Symptoms:The Oxford Plaque Study. Circulation 2006;113:2320-2328
72. Mannheim D, Herrmann J, Versari D, et al. Enhanced Expression of Lp-PLA2 and Lysophosphatidylcholine in Symptomatic Carotid Atherosclerotic Plaques. Stroke 2008:39:1448-1455
73. Richardson PD, Davies MJ, Born GV. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet 1989:2:941-944
74. Li Z-Y, Howarth S, Trivedi RA, et al. Stress analysis of carotid plaque rupture based on in vivo high resolution MRI. Journal of Biomechanics 2006;39:2611-2622
75. Li Z-Y, Howarth SPS, Tang T, Gillard JH. How Critical Is Fibrous Cap Thickness to Carotid Plaque Stability?:A Flow-Plaque Interaction Model. Stroke 2006;37:1195-1199
76. Salzar RS, Thubrikar MJ, Eppink RT. Pressure-induced mechanical stress in the carotid artery bifurcation:a possible correlation to atherosclerosis. J Biomech 1995:28:1333-1340
2. Rosamond W, Flegal K, Friday G, et al. Heart disease and stroke statistics-2007 update-A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2007;115:E69-E171
3. Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack A statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke Co-sponsored by the Council on Cardiovascular Radiology and Intervention-The American Academy of Neurology affirms the value of this guideline. Circulation 2006;113:E409-E449
4. Easton JD, Saver JL, Albers GW, et al. Definition and Evaluation of Transient Ischemic Attack A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke 2009;40:2276-2293
5. 赵冬.我国人群脑卒中发病率、死亡率的流行病学研究.中华流行病学杂
志2003；3
6. 王文化.北京市1984～1999年人群脑卒中发病率变化趋势分析.中华流行病学杂志2001;4
7. Fairhead JF, Mehta Z, Rothwell PM. Population-based study of delays in carotid imaging and surgery and the risk of recurrent stroke. Neurology 2005:65:371-375
8. Prati P, Tosetto A, Vanuzzo D, et al. Carotid intima media thickness and plaques can predict the occurrence of ischemic cerebrovascular events. Stroke 2008:39:2470-2476
9. Chaturvedi S, Bruno A, Feasby T, et al. Carotid endarterectomy-An evidence-based review-Report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology. Neurology 2005:65:794-801
10. Heliopoulos J, Vadikolias K, Mitsias P, et al. A three-dimensional ultrasonographic quantitative analysis of non-ulcerated carotid plaque morphology in symptomatic and asymptomatic carotid stenosis. Atherosclerosis 2008:198:129-135
11. Ohara T, Toyoda K, Otsubo R, et al. Eccentric Stenosis of the Carotid Artery Associated with Ipsilateral Cerebrovascular Events. AJNR Am J Neuroradiol 2008;29:1200-1203
12. Cunningham KS, Gotlieb AI. The role of shear stress in the pathogenesis of atherosclerosis. Laboratory Investigation 2005:85:9-23
13. Cheng C, Tempel D, van Haperen R, et al. Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress. Circulation 2006:113:2744-2753
14. Groen HC, Gijsen FJH, van der Lugt A, et al. Plaque rupture in the carotid artery is localized at the high shear stress region-A case report. Stroke 2007:38:2379-2381
15. Carallo C, Lucca LF, Ciamei M, Tucci S, de Franceschi MS. Wall shear stress is lower in the carotid artery responsible for a unilateral ischemic stroke. Atherosclerosis 2006;185:108-113
16. Lee RT, Schoen FJ, Loree HM, Lark MW, Libby P. Circumferential stress and matrix metalloproteinasel in human coronary atherosclerosis. Implications for plaque rupture. Arterioscler Thromb Vasc Biol 1996:16:1070-1073
17. 岳文胜,尹立雪,王珊,et al.孤立性颈动脉粥样硬化斑块内膜旋转角度的超声评价.中国医学科学院学报2007;30：63-68
18. Hare JL, Brown JK, Marwick TH. Association of Myocardial Strain With Left Ventricular Geometry and Progression of Hypertensive Heart Disease. The American Journal of Cardiology 2008:102:87-91
19. Chen JH, Cao TS, Duan YY, Yuan LJ, Wang ZJ. Velocity vector imaging in assessing myocardial systolic function of hypertensive patients with left ventricular hypertrophy. Canadian Journal of Cardiology 2007:23:957-961
20. 国建萍,王玉堂,单兆亮,et al.速度向量成像技术在心力衰竭患者同步化治疗中的应用.中国心脏起搏与心电生理杂志2009;23：309-312
21. Burri MV, Nanda NC, Lloyd SG, et al. Assessment of Systolic and Diastolic Left Ventricular and Left Atrial Function Using Vector Velocity Imaging in Takotsubo Cardiomyopathy. Echocardiography 2008:25:1138-1144
22. Carasso S, Yang H, Woo A, et al. Systolic Myocardial Mechanics in Hypertrophic Cardiomyopathy:Novel Concepts and Implications for Clinical Status. Journal of the American Society of Echocardiography 2008:21:675-683
23. Jansen AHM, van Dantzig JM, Bracke F, et al. Qualitative observation of left ventricular multiphasic septal motion and septal-to-latelal apical shuffle predicts left ventricular reverse remodeling after cardiac resynchronization therapy. American Journal of Cardiology 2007;99:966-969
24. 王志蕴,张梅,刘晓玲,et al.速度向量成像技术早期无创性评价动脉硬化的临床研究.中华医学超声杂志(电子版)2009；6：252-258
25. Zhang L, Liu Y, Zhang PF, et al. Peak radial and circumferential strain measured by velocity vector imaging is a novel index for detecting vulnerable plaques in a rabbit model of atherosclerosis. Atherosclerosis;In Press, Corrected Proof
26. 汪奇,钱蕴秋,刘丽文,et al.速度向量成像技术评价脑梗死患者颈总动脉管壁运动的初步研究.中国超声医学杂志2007；23：32-35
27. Fagerberg B, Ryndel M, Kjelldahl J, et al. Differences in lesion severity and cellular composition between in vivo assessed upstream and downstream sides of human symptomatic carotid atherosclerotic plaques. Journal of vascular Research 2010:47:221-230
28. Ding SF, Zhang M, Zhao YX, et al. The role of carotid plaque vulnerability and inflammation in the pathogenesis of acute ischemic stroke. Am J Med Sci 2008:336:27-31
29. Zhang PF, Su HJ, Yao GH, et al. Plaque volume compression ratio, a novel biomechanical index, is independently associated with ischemic cerebrovascular events. Journal of Hypertension 2009;27:348-356
30. 脑血管疾病分类(1995)(中、英文)中华神经科杂志1996；29：376-377
31. 张梅,张运,高月花,et al.超声检查对颈动脉粥样硬化血管重构的研究.中华超声影像学杂志2002；4：229-231
32. Adams HP, Bendixen BH, Kappelle LJ, et al. CLASSIFICATION OF SUBTYPE OF ACUTE ISCHEMIC STROKE-DEFINITIONS FOR USE IN A MULTICENTER CLINICAL-TRIAL. Stroke 1993;24:35-41
33. 吴江,贾建平,崔丽英.神经病学.2005：155-159
34. Lusis AJ. Atherosclerosis. Nature 2000;407:233-241
35. Kalogeropoulos A, Terzis G, Chrysanthopoulou A, et al. Risk for transient ischemic attacks is mainly determined by intima-media thickness and carotid plaque echogenicity. Atherosclerosis 2007;192:190-196
36. Cao JJ, Arnold AM, Manolio TA, et al. Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality-The cardiovascular health study. Circulation 2007;116:32-38
37. DeMaria AN, Narula J, Mahmud E, Tsimikas S. Imaging vulnerable plaque by ultrasound. J Am Coll Cardiol 2006;47:C32-39
38. Fuster V, Moreno PR, Fayad ZA, Corti R, Badimon JJ. Atherothrombosis and High-Risk Plaque:Part I:Evolving Concepts. Journal of the American College of Cardiology 2005:46:937-954
39. Huang H, Virmani R, Younis H, et al. The impact of calcification on the biomechanical stability of atherosclerotic plaques. Circulation 2001:103:1051-1056
40. Schoenhagen P, Ziada KM, Kapadia SR, et al. Extent and direction of arterial remodeling in stable versus unstable coronary syndromes an intravascular ultrasound study. Circulation 2000:101:598-603
41. Fisher M, Paganini-Hill A, Martin A, et al. Carotid plaque pathology: thrombosis, ulceration, and stroke pathogenesis. Stroke 2005:36:253-257
42. Nikic P, Savic M, Jakovljevic V, Djuric D. Intima-media thickness of common carotid artery, carotid atherosclerosis and subtypes of ischemic cerebral disease. Rom J Intern Med 2004;42:149-160
43. Nikic P, Savic M, Jakovljevic V, Djuric D. Carotid atherosclerosis, coronary atherosclerosis and carotid intima-media thickness in patients with ischemic cerebral disease:Is there any link? Exp Clin Cardiol 2006:11:102-106
44. Ouhlous M, Flach HZ, de Weert TT, et al. Carotid plaque composition and cerebral infarction:MR imaging study. AJNR Am J Neuroradiol 2005;26:1044-1049
45. Heuten H, Claeys M, Goovaerts I, et al. Can measurement of the intima-media thickness of the carotid artery improve the diagnostic value of exercise stress tests? Acta Cardiol 2006;61:501-505
46. 周鹏,陈荔川,高雪梅.数字减影在脑血管造影中的临床应用.实用医学影像学杂志2004;5：64-66
47. 王颖颖.数字减影血管造影技术.中国医疗器械信息2004;6
48. 李运军.MRA、 CTA、 DSA在出血性脑血管病诊断中的应用.中国微侵袭神经外科杂志2008;2：81
49. 王大明.CTA、 MRA与DSA在脑血管病诊断与治疗中的地位.中国现代神经疾病杂志2007;7：413
50. 张天义,冼惠珍.速度向量成像技术及其定量评价.中华临床医师杂志(电子版) 2007;1：433-437
51. Langeland S, D'Hooge J, Wouters PF, et al. Experimental validation of a new ultrasound method for the simultaneous assessment of radial and longitudinal myocardial deformation independent of insonation angle. Circulation 2005:112:2157-2162
52. Cinthio M, Ahlgren AR, Bergkvist J, et al. Longitudinal movements and resulting shear strain of the arterial wall. Am J Physiol Heart Circ Physiol 2006:291:H394-402
53. Cinthio M, Ahlgren AR. Intra-Observer Variability of Longitudinal Displacement and Intramural Shear Strain Measurements of the Arterial Wall Using Ultrasound Noninvasively in vivo. Ultrasound in Medicine & Biology;36:697-704
54. Hansen HHG, Lopata RGP, de Korte CL. Noninvasive Carotid Strain Imaging Using Angular Compounding at Large Beam Steered Angles: Validation in Vessel Phantoms. Ieee Transactions on Medical Imaging 2009:28:872-880
55. Humphrey JD, Eberth JF, Dye WW, Gleason RL. Fundamental role of axial stress in compensatory adaptations by arteries. J Biomech 2009;42:1-8
56. Huang X, Yang C, Yuan C, et al. Patient-specific artery shrinkage and 3D zero-stress state in multi-component 3D FSI models for carotid atherosclerotic plaques based on in vivo MRI data. Mol Cell Biomech 2009:6:121-134
57. Gao H, Long Q, Graves M, Gillard JH, Li Z-Y. Carotid arterial plaque stress analysis using fluid-structure interactive simulation based on in-vivo magnetic resonance images of four patients. Journal of Biomechanics 2009:42:1416-1423
58. Pirat B, Khoury DS, Hartley CJ, et al. A novel feature-tracking echocardiographic method for the quantitation of regional myocardial function-Validation in an animal model of ischemia-reperfusion. Journal of the American College of Cardiology 2008:51:651-659
59. Gao H, Long Q. Effects of varied lipid core volume and fibrous cap thickness on stress distribution in carotid arterial plaques. Journal of Biomechanics 2008:41:3053-3059
60. Thrysoe SA, Oikawa M, Yuan C, et al. Longitudinal Distribution of Mechanical Stresses in Carotid Plaques of Symptomatic Patients. Stroke:STROKEAHA.109.571588
61. Li Z-Y, Howarth SPS, Tang T, et al. Structural analysis and magnetic resonance imaging predict plaque vulnerability:A study comparing symptomatic and asymptomatic individuals. Journal of Vascular Surgery 2007:45:768-775
62. Lee RT, Schoen FJ, Loree HM, Lark MW, Libby P. Circumferential Stress and Matrix Metalloproteinase 1 in Human Coronary Atherosclerosis: Implications for Plaque Rupture. Arteriosclerosis, Thrombosis, and Vascular Biology 1996;16:1070-1073
63. Cheng C, Tempel D, van Haperen R, et al. Activation of MMP8 and MMP13 by angiotensin II correlates to severe intra-plaque hemorrhages and collagen breakdown in atherosclerotic lesions with a vulnerable phenotype. Atherosclerosis 2009:204:26-33
64. 岳文胜,尹立雪,王志刚,et al.颈动脉粥样硬化斑块上中下游短轴切面内膜位点的超声径向力学研究.中国医学影像技术2008；24：1389-1393
65. 张鹏飞,张运,张梅,姚桂华,王荣.颈动脉粥样斑块应变及应变率分布的初步探讨.中华超声影像学杂志2004；13:573-576
66. LaDisa JF, Jr., Bowers M, Harmann L, et al. Time-efficient patient-specific quantification of regional carotid artery fluid dynamics and spatial correlation with plaque burden. Med Phys;37:784-792
67. Boyd J, Buick JM. Three-dimensional modelling of the human carotid artery using the lattice Boltzmann method:Ⅱ. Shear analysis Physics in Medicine and Biology 2008;53
68. Poepping TL, Rankin RN, Holdsworth DW. Flow Patterns in Carotid Bifurcation Models Using Pulsed Doppler Ultrasound:Effect of Concentric vs. Eccentric Stenosis on Turbulence and Recirculation. Ultrasound in Medicine & Biology;In Press, Corrected Proof
69. Zhao SZ, Ariff B, Long Q, et al. Inter-individual variations in wall shear stress and mechanical stress distributions at the carotid artery bifurcation of healthy humans. J Biomech 2002;35:1367-1377
70. Marfella R, D'Amico M, Di Filippo C, et al. Increased Activity of the Ubiquitin-Proteasome System in Patients With Symptomatic Carotid Disease Is Associated With Enhanced Inflammation and May Destabilize the Atherosclerotic Plaque:Effects of Rosiglitazone
Treatment. Journal of the American College of Cardiology 2006;47:2444-2455
71. Redgrave JNE, Lovett JK, Gallagher PJ, Rothwell PM. Histological Assessment of 526 Symptomatic Carotid Plaques in Relation to the Nature and Timing of Ischemic Symptoms:The Oxford Plaque Study. Circulation 2006;113:2320-2328
72. Mannheim D, Herrmann J, Versari D, et al. Enhanced Expression of Lp-PLA2 and Lysophosphatidylcholine in Symptomatic Carotid Atherosclerotic Plaques. Stroke 2008:39:1448-1455
73. Richardson PD, Davies MJ, Born GV. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet 1989:2:941-944
74. Li Z-Y, Howarth S, Trivedi RA, et al. Stress analysis of carotid plaque rupture based on in vivo high resolution MRI. Journal of Biomechanics 2006;39:2611-2622
75. Li Z-Y, Howarth SPS, Tang T, Gillard JH. How Critical Is Fibrous Cap Thickness to Carotid Plaque Stability?:A Flow-Plaque Interaction Model. Stroke 2006;37:1195-1199
76. Salzar RS, Thubrikar MJ, Eppink RT. Pressure-induced mechanical stress in the carotid artery bifurcation:a possible correlation to atherosclerosis. J Biomech 1995:28:1333-1340
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |