【作者】 刘茵；

【导师】 张梅； 姚桂华；

【作者基本信息】 山东大学 ， 内科学， 2010， 硕士

【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。更多还原

【Abstract】 BackgroundStroke 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.Objective1. 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.Methods1. Study population and groupingStudy 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. Methods2.1 two-dimensional echocardiographyTwo-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 clipsVelocity 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 ananlysisSPSS 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.Results1. Comparisons of mechanical parameters among diagnostic groupsPeak 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 group2.1 Comparisons of mechanical parameters of low echogenic plaque between AM group and Bl groupAM-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 segmentsTIA 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 segmentsTIA 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 locations3.1 Comparisons of mechanical parameters among different locations in symptomatic patientsPeak 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 plaquesPeak 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 eventIn 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.Conclusion1. 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.更多还原