【作者】 巩晓红；

【导师】 王建华；

【作者基本信息】 河北医科大学 ， 内科学， 2009， 博士

【摘要】 超声心动图因具有无创、简便、快速、经济、可床旁操作、可反复随访等优点而成为临床应用最广的影像学心功能评价方法。左心室射血分数(left ventricular ejective fraction,LVEF)从左心室容积变化的角度评价心功能,是临床最常用指标。然而超声图像相对有限的空间分辨率及操作者经验等客观与主观因素均影响其测量的准确性与可重复性。组织多普勒技术从心肌运动的角度评价心功能,其应用为心功能评价提供了新的方法。基于组织多普勒技术的超声应变与应变率成像从心肌长度变化的角度评价其功能,进一步拓展了心功能评价的视角,但由于多普勒固有的角度依赖的限制,主要用于检测与超声束平行的心肌长轴方向的纵向应变,在定量分析不同方向、不同层面的心肌应变时受到限制。超声二维斑点追踪成像(speckle tracking imaging, STI)是新的超声成像技术,可在二维灰阶动态图像中定量心肌的运动速度与应变,为临床评价心脏的整体与局部功能提供了一种全新的方法。研究证实,STI所测心肌应变值与超声微测仪及心脏磁共振(magnetic resonance imaging, MRI)所测结果高度一致,在心尖部同样能追踪位移信号,真实反映心尖部病变,为观察心肌运动、定量评价局部心肌功能提供更为准确的方法。动物实验证实,左心室心内膜层和心外膜层心肌应变及应变率存在跨壁阶差,对心内膜层和心外膜层不同室壁节段心肌应变的分析将有可能成为反映左心室局部心肌收缩和舒张功能的敏感指标。心肌应变的研究国内外已有很多报道,而对于心肌的分层应变研究,目前国内还仅限于动物实验,有关糖尿病、高血压患者的心肌分层应变的研究还未见相关报道。本研究第一部分主要应用STI技术研究正常成人左心室心内膜层及心外膜层心肌应变的特点,进一步验证STI技术无创评价心肌应变的可行性。第二、三部分分别对血糖控制良好的单纯2型糖尿病患者以及不同左心室构型的原发性高血压患者的左心室心内膜层及心外膜层心肌应变特点进行分析,观察病理情况下心肌各层不同方向应变的变化规律,以期为临床提供一种简单实用的观察心肌运动、定量评价整体和局部心肌功能的超声手段。第一部分超声二维斑点追踪成像技术评价正常人左心室收缩功能的研究目的:应用STI技术观察正常人左心室心内膜层和心外膜层心肌应变的特点。方法:选择健康志愿者75例,男46例,女29例,平均年龄(39.6±15.2)岁。所有受检者取左侧卧位,呼气末屏气,分别采集心尖左心室长轴观、心尖四腔观、心尖两腔观及二尖瓣、乳头肌和心尖水平左心室短轴二维灰阶动态图像各三个心动周期(帧频50～70帧/s),储存于光盘,将存储的二维图像导入Qlab6.0工作站进行脱机分析,系统自动将左心室壁等分为心内膜下感兴趣区和心外膜下感兴趣区,并将心尖位切面左心室后间隔、侧壁、前壁、下壁、后壁及前间隔等分为基底段、中间段及心尖段总计18节段,将二尖瓣、乳头肌、心尖水平左心室短轴等分为前间隔、前壁、侧壁、后壁、下壁及后间隔6段,总计18节段。对每一节段的心内膜层和心外膜层心肌进行斑点追踪分析,自动显示每一节段与心动周期对应的应变曲线和心动周期中各时间点的心肌应变值,从曲线图中导出数据表,可以得到心内、外膜层心肌收缩期纵向应变(longitudinal strain, LS)、径向应变(radial strain, RS)和圆周应变(circumferential strain, CS)峰值,获取连续3个心动周期峰值应变并取其均值作为各节段心肌收缩期峰值应变值,并计算长轴基底段、中间段、心尖段以及短轴二尖瓣、乳头肌及心尖水平各室壁心内膜层和心外膜层心肌平均收缩期峰值应变作为左心室各水平整体纵向、径向和圆周应变。结果:(1)左心室长轴各节段LS曲线为双峰曲线,最大LS为负值。左心室长轴各节段心内膜层心肌收缩期LS峰值均显著高于心外膜层心肌(P<0.05),从基底部到心尖部收缩期LS呈现逐步递增趋势,基底部最小,心尖部最大,但差异无统计学意义;同一水平不同节段收缩期LS峰值比较差异无统计学意义。(2)左心室短轴各节段RS曲线为正向峰值曲线,收缩期最大RS为正值。左心室短轴各节段心内膜层心肌RS峰值均高于心外膜层心肌(P<0.05)。RS在左心室短轴不同水平差异有统计学意义,乳头肌水平RS值最大,同一水平不同节段收缩期RS峰值比较差异无统计学意义;(3)左心室短轴各节段CS曲线为负向峰值曲线,最大收缩期CS为负值。左心室短轴各节段心内膜层心肌CS峰值均高于心外膜层心肌(P<0.05)。CS在各心肌节段之间存在差异,尤以前间隔和后壁节段心内膜层及心外膜层心肌间差异显著(P<0.01),二尖瓣及乳头肌水平前间隔及下壁CS值较高,侧壁与后壁较低(P<0.05),心尖水平前间隔收缩期CS峰值较高,但差异无统计学意义。结论:STI可以无创评价左心室整体及局部心肌功能,对心内膜层和心外膜层不同室壁节段心肌应变的分析有望成为反映左心室局部心肌收缩功能的敏感指标。第二部分超声二维斑点追踪成像技术评价2型糖尿病患者左心室收缩功能的研究目的:应用STI技术评价2型糖尿病患者左心室心内膜层和心外膜层心肌应变的特点,探讨STI技术评价2型糖尿病患者左心室局部及整体收缩功能的应用价值。方法:选择住院或门诊确诊的、血糖控制良好的单纯2型糖尿病患者(DM)38例,男21例,女17例,平均年龄(59.2±9.0)岁,与DM组年龄、性别相匹配的健康志愿者29例作为对照组,男18例,女11例,平均年龄(58.3±9.6)岁。用二维、M型超声和多普勒超声心动图获得一些常规左心室功能参数,包括左室内径、室壁厚度、左室射血分数(left ventricular ejective fraction, LVEF)、二尖瓣口舒张期多普勒血流速度E /A、二尖瓣环组织多普勒速度Em /Am等。每个测量数据均取三次测值的平均值。分别采集心尖左心室长轴观、心尖四腔观、心尖两腔观及二尖瓣、乳头肌和心尖水平左心室短轴二维灰阶动态图像各三个心动周期(帧频50～70帧/s),储存于光盘,应用Qlab6.0工作站进行脱机分析,分别获取心尖位切面和短轴切面各18节段心内膜层及心外膜层心肌的二维应变曲线,从中可以得到各室壁节段心内、外膜层心肌收缩期峰值LS、RS和CS值,计算长轴基底段、中间段、心尖段及短轴二尖瓣、乳头肌、心尖水平各室壁节段心内膜和心外膜层心肌收缩期峰值应变的平均值分别作为左心室长轴各节段及短轴各水平心内、外膜层心肌平均峰值应变,将左心室长轴各节段及短轴各水平心内、外膜层心肌的峰值应变平均值作为左心室心内、外膜层心肌的整体峰值LS、RS和CS值。结果:(1)两组间左室壁厚度、左室内径、LVEF差异无统计学意义;DM患者组E /A及Em / Am小于对照组(P<0.05)。(2) DM患者组左心室长轴各节段LS曲线和对照组相似,但各节段平均LS峰值及左心室整体LS峰值均显著低于对照组(心外膜层P<0.05,心内膜层P<0.01),各节段心内膜层心肌LS值高于心外膜层心肌,但差异无统计学意义。(3) DM患者组左心室短轴各节段RS曲线和对照组相似,但各水平短轴平均及整体收缩期RS峰值比对照组增高(P<0.05),且心内膜层心肌RS值高于心外膜层心肌,但差异无统计学意义。(4) DM患者左心室短轴各节段在三个心动周期中的CS曲线和对照组相似,左心室各水平短轴平均及整体收缩期CS峰值比对照组增高,但差异无统计学意义。结论:应用STI对糖尿病患者左心室心肌进行分层应变分析,能早期发现2型糖尿病患者左心室收缩功能异常,为糖尿病亚临床心肌病变的诊断提供了无创性新方法。第三部分超声二维斑点追踪成像技术评价原发性高血压患者左心室收缩功能的研究目的:探索采用STI技术所测的左心室心内膜层和心外膜层心肌的收缩期峰值应变评价原发性高血压左心室不同构型患者左心室收缩功能的价值。方法:住院或门诊就诊的原发性高血压患者36例,男19例,女17例,平均年龄(58.7±8.3)岁,与高血压组年龄、性别相匹配的健康志愿者33例作为对照组,男20例,女13例,平均年龄(57.9±6.5)岁。左室心肌质量指数(LVMI)=LVM/体表面积,男性LVM I> 134g/m2、女性LVMI > 110 g/m2者为左心室肥厚,根据LVMI将所有患者分成高血压A组(非左心室肥厚组,NLVH)20例,高血压B组(左心室肥厚组,LVH)16例。常规超声心动图测量舒张期左心室内径(LVEDd)、室间隔和左心室后壁厚度(LVST、LVPWT)、LVEF、E /A、Em /Am。采集心尖左心室长轴观、心尖四腔观、心尖两腔观及二尖瓣、乳头肌和心尖水平左心室短轴二维灰阶动态图像各三个心动周期(帧频50～70帧/s),储存于光盘,应用Qlab6.0工作站进行脱机分析,分析结束后将数据导出,分别计算左心室长轴各段及短轴各水平心内膜层和心外膜层心肌的平均峰值应变及左心室整体峰值应变值。结果:(1)高血压病A组与对照组比较,LVEDd、IVST、LVPWT、LVMI差异无统计学意义;高血压病B组的IVST、LVPWT、LVMI与A组和对照组比较均显著增高(P<0.01);LVEF三组间差异无统计学意义(P>0.05);A组及B组与对照组比较,E /A(分别为0.93±0.22、0.89±0.41及1.29±0.53)、Em/Am(分别为0.83±0.35、0.81±0.23及1.24±0.32)有显著性差异(P<0.05)。(2)A组和B组左心室LS曲线和对照组相似,各节段心内膜层心肌LS峰值高于心外膜层心肌,但差异无统计学意义。与对照组相比,A组基底段、中段及心尖段平均LS峰值及左心室整体LS峰值减低,但差异没有统计学意义;B组各段平均LS峰值及左心室整体LS峰值显著低于对照组(心外膜层P<0.05,心内膜层P<0.01);(3)高血压患者左心室短轴各节段的RS曲线和对照组相似,A组左心室各水平短轴及左心室整体心内膜层心肌RS峰值高于心外膜层心肌(P<0.05),且显著高于对照组(心外膜层P<0.05,心内膜层P<0.01);B组左心室各水平短轴及左心室整体心内膜层与心外膜层心肌RS峰值比较差异无统计学意义;与对照组比较,左心室二尖瓣水平短轴收缩期RS峰值高于对照组(P<0.01),乳头肌及心尖水平短轴及左心室整体RS峰值与对照组相比差异无统计学意义;除二尖瓣水平外,A组心内膜层及心外膜层心肌RS峰值均高于B组(P<0.05)。(4)高血压患者左心室短轴各节段的CS曲线和对照组相似,并且短轴各水平及左心室整体心内膜层心肌收缩期CS峰值均高于心外膜层心肌(A组P<0.01,B组P<0.05);三组间比较差异无统计学意义。结论:高血压患者径向应变的增高代偿了纵向应变的减低, STI为评价高血压不同构型患者左心室整体和局部收缩功能从而早期发现心肌病变提供了无创性的新方法。更多还原

【Abstract】 Echocardiography is now the most commonly used noninvasive tool for the assessment of cardiac anatomy and function. In addition to commonly established roles such as confirming diagnosis and disease monitoring, echocardiography plays an important clinical role in prognostic assessment. By calculating the change of left ventricular (LV) volume, LV ejective fraction (LVEF) is a clinical commonly used index, but the poor spatial resolution of ultrasound images and the operators′experience interfere with the reproducibility and accuracy. The quantification of regional myocardial function remains a challenge in clinical cardiology. Traditional methods for the evaluation of regional myocardial function using echocardiography are subjective and only partially quantitative. Tissue Doppler Imaging (TDI) is a robust and reproducible echocardiographic tool which has permitted a quantitative assessment of both global and regional function and timing of myocardial events. TDI-based strain and strain rate imaging (SRI) for LV function evaluating is a new tool for quantifying regional deformation and deformation rate by calculate the change of myocardium length. However, TDI-based strain measurements are angle dependent owing to use of the Doppler effect and simultaneous opposite deformation in the long and short axes, it can only be used to assess the longitudinal strain, but it is restricted in analyzing the myocardial strain of different directions and different levels. Speckle tracking imaging (STI) is an echocardiographic technique based on tracking of characteristic speckle patterns created by interference of ultrasound beams in the myocardium. As the tracking is based on grayscale B-mode images, it is in principle angle independent, so as a new method for quantifying global or regional LV function, it can not only evaluate the LV strain, rotation and displacement noninvasively but also analyze the characters of the cardiac movement mechanics. Previous studies indicated that STI results consist with sonomicrometry and magnetic resonance imaging (MRI) for systolic strain in the long axis and in the short axis. Moreover, STI can assess apical function which TDI difficultly to deal with. Animal experiments confirmed that there is an endocardial-epicardial gradient in both peak strain and SR values. Study to the endocardial-epicardial gradient of LV will be sensitive to objectively quantify regional and global myocardial function.The studies were divided into three parts. In the first part, the peak systolic strain of the inner and outer layers of myocardium in healthy adults were evaluated by two-dimensional ultrasound STI. The research further confirmed the feasibility of STI in assessing the LV myocardium strain. In the next two parts, we explored the strain of the inner and outer layers of LV myocardium in patients with type 2 diabetes mellitus and essential hypertension with different patterns of left hypertrophic geometric models respectively, hoping to find the abnormity of LV systolic function, providing an easy and practical ultrasonic mean for clinical diagnosis, treatment and prognostic assessment for heart disease with regional myocardial ischemia.Part I Evaluation of left ventricular systolic function in healthy subjects using two-dimensional speckle tracking imagingObjective: To explore the characters of the peak systolic strain of the inner and outer layers of myocardium and to confirm the endocardial-epicardial gradients of LV in healthy adults using STI.Methods: Study population consisted of 75 healthy volunteers (male 46, female 29, average age 39.6±15.2 years). High frame rate two-dimensional (2D)images of three consecutive cardiac cycles were recorded from the LV apical four-chamber view, two-chamber view, long-axis view and the short-axis views at the levels of mitral annulus, papillary muscle and apex of the LV respectively. 2D images were transferred to Qlab6.0 work station for offline strain analysis. The software algorithm segmented the LV wall into two equidistant layers(the inner and outer layers), moreover, the software algorithm segmented the LV long axis and short axis into 18 equidistant segments respectively(anteroseptal, anterior, lateral, posterior, inferior and interventricular). The longitudinal strain(LS) values in the inner and outer layers of myocardium were measured in the left ventricular apical views. Radial strain(RS) and circumferential strain(CS) values in the inner and outer layers of myocardium were measured in the left ventricular short-axis views using two-dimensional strain software. Acquired the peak systolic strain of each segment, calculated the average strain value of three consecutive cardiac cycles as the peak systolic strain. The average strain values of the basal segment, the middle segment, the apical segment of the LV long axis and mitral annulus, papillary muscle and apex of the LV short axis in the inner and outer layers were calculated as the LV global LS, RS and CS of each level.Results: (1) The LV longitudinal strain curve had two peaks, the peak systolic LS values were negative. In the inner layers of myocardium, the peak systolic LS values of different segments and the peak global LS values at different levels showed higher than those of the outer layers(P<0.05), and the LS values gradually increased from base to apex(P>0.05). At the same level, the LS values of different segments had no significant difference in the inner or outer layers. (2) LV radial strain curve of each segment was a positive peak curve, the peak systolic RS values were positive. The peak systolic RS values of different segments and the peak global RS values at different levels of the inner layers showed higher than those of the outer layers(P<0.05). The RS values at different levels had significant difference, the value at the level of papillary muscle was the largest, the peak systolic RS values of different segments at the same level had no significant difference. (3) LV circumferential strain curve of each segment was a negative peak curve, the peak systolic CS values were negative. The peak systolic CS values of different segments and the peak global CS values at different levels of the inner layers showed higher than those of the outer layers(P<0.05), especially in anteroseptal and posterior segments(P<0.01). At levels of mitral annulus and papillary muscle, the CS values of anteroseptal and inferior were relatively high, the CS values of lateral and posterior were relatively low (P< 0.05). The peak systolic CS value of anteroseptal at level of apex showed higher than those of the other segments, but there were no significant difference.Conclusions: Independent of insonation angle for assessing myocardial strain, STI has the potentiality to be used clinically to evaluate the regional and global myocardial function of LV, study to the endocardial-epicardial gradient of LV will be sensitive to objectively quantify regional myocardial systolic function.Part II Evaluation of left ventricular systolic function in patients with type 2 diabetes mellitus using two-dimensional speckle tracking imagingObjective: To evaluate the characters of the peak systolic strain of the inner and outer layers of myocardium and to explore the application value in assessing the long-axis and short axis systolic function of LV by STI in patients with type 2 diabetes mellitus.Methods: 38 patients with type 2 diabetes mellitus (male 21, female 17, average age 59.2±9.0 years) as DM group, 29 age- and gender- matched healthy volunteers (male 18, female 11, average age 58.3±9.6 years) as the control group. The patients′blood glucose was well controlled within normal level. Two-dimensional, M-mode and Doppler echocardiographic examination were performed and some parameters were acquired, including LV end-diastolic diameter (LVDd), LV end-systolic diameter (LVDs), diastolic interventricular septal thickness (IVST), diastolic posterior wall thickness (PWT), left ventricular ejective fraction (LVEF), the early rapid filling velocity of mitral valve (E), peak velocity of the late filling wave due to atrial contraction (A), E /A velocity ratio, peak myocardial early diastolic velocity at the mitral annulus (Em), late diastolic velocity (Am), Em /Am ratio. High frame rate two-dimensional (2D) images of three consecutive cardiac cycles were recorded from the LV apical four-chamber view, two-chamber view, long-axis view and the short-axis views at the levels of mitral annulus, papillary muscle and apex of the LV respectively. 2D images were transferred to Qlab6.0 work station for offline strain analysis, acquired the peak systolic strain of each segment and calculated the average value of three consecutive cardiac cycles as the peak systolic strain. The average strain values of the basal segment, the middle segment, the apical segment of the LV long axis and mitral annulus, papillary muscle and apex of the LV short axis in the inner and outer layers were calculated as the LV strain of each level in the inner and outer layers respectively. The LV global LS, RS and CS were the average values of the LV strain of each level in the inner and outer layers respectively.Results: (1) The LV wall thickness, LV diameter and LVEF had no significant difference between two groups; E /A and Em /Am in DM group showed lower than those in the control group (P<0.05). (2) LV longitudinal strain curve in DM group was similar to that in the control group, but the average LS values of the basal segment, the middle segment, the apical segment and the LV global LS value in DM group were lower than those in the control group (outer layer: P<0.05, inner layer: P<0.01). In DM group, the peak systolic LS values of different segments of the inner layers showed higher than those of the outer layers (P>0.05). (3) LV radial strain curve in DM group was similar to that in the control group, but the average RS values at each short axis level and the peak global RS values were higher than those in the control group ( P<0.05), and the peak systolic RS values of different segments of the inner layers showed higher than those of the outer layers( P>0.05). (4) LV circumferential strain curve in DM group was similar to that in the control group, the average CS values of each short axis level and the peak global CS values were higher than those in the control group( P>0.05).Conclusions: Analysis of the strain of the inner and outer layers of LV myocardium with STI in patients with type 2 diabetes mellitus can help to identify LV systolic dysfunction and to provide a new noninvasive method for the diagnosis of sub-clinical cardiomyopathy.Part III Evaluation of left ventricular systolic function in patients with essential hypertension using two-dimensional speckle tracking imagingObjective: To evaluate the characters of the peak systolic strain of the inner and outer layers of myocardium and to explore the application value of STI in evaluating LV systolic function in hypertension patients with different patterns of left ventricular hypertrophic (LVH) geometric models.Methods: 36 patients with essential hypertension (male 19, female 17, average age 58.7±8.3 years), 33 age- and gender- matched healthy volunteers (male 20, female 13, average age 57.9±6.5 years) as the control group. All patients were divided into two groups according to left ventricular mass index (LVMI)(group A 20 patients: NLVH,group B 16 patients: LVH), male LVMI>134 g/m2, female LVMI>110 g/m2 defined as LVH. Echocardiographic examination were performed and some paremeters were acquired, including LVDd, LVDs, IVST, LVPWT, LVEF, E /A and Em /Am. High frame rate two-dimensional images of three consecutive cardiac cycles were recorded from the LV apical four-chamber view, two-chamber view, long-axis view and the short-axis views at the levels of mitral annulus, papillary muscle and apex of the LV respectively. LS, RS and CS in the inner and outer layers of myocardium were measured in the left ventricular long-axis and short-axis views using two-dimensional strain software. The LV strain values at each level of the long axis and the short axis in the inner and outer layers were calculated, the LV global strain values of the long axis and the short axis were the averages of the LV strain value of each level.Results: (1) There were no significant difference in IVST, LVPWT, LVMI between group A and the control group; IVST, LVPWT, LVMI in group B were significantly higher than those in group A and the control group (P<0.01); There were no significant difference in LVEF among three groups; Compared with the control group, the LV global diastolic function in group A and group B was significantly decreased (E /A: 1.29±0.53 vs 0.93±0.22 and 0.89±0.41; Em /Am: 1.24±0.32 vs 0.83±0.35 and 0.81±0.23) (P<0.05). (2) LV longitudinal strain curves in group A and group B were similar to that in the control group, the peak systolic LS values of different segments of the inner layers were higher than those of the outer layers (P>0.05). Compared with the control group, the average LS values of the basal segment, the middle segment and the apical segment of the LV long axis were decreased in group A (P>0.05); The average LS values at each level and the LV global LS values in group B were significantly decreased than those in the control group (outer layer: P<0.05, inner layer: P<0.01); (3) LV radial strain curve in hypertension patients was similar to that in the control group. In group A, the average RS values of short axis levels and the LV peak global RS values of the inner layers were higher than those of the outer layers (P<0.05), and the peak systolic RS values were higher than those in the control group (outer layer: P<0.05, inner layer: P<0.01); In group B, there was no significant difference in the peak systolic RS values between the inner and outer layers, compared with the control group, the peak systolic RS value at level of the mitral annulus was higher than that in the control group (P<0.01); The peak systolic RS values of the inner and outer layers in group A were significantly increased than those in group B (P<0.05). (4) LV circumferential strain curve in hypertension patients was similar to that in the control group, the peak systolic CS values of short axis levels and the LV peak global CS values of the inner layers were higher than those of the outer layers (group A P<0.01; group B P<0.05); There were no significant difference among three groups.Conclusions: Radial contractility appears to compensate for reduced longitudinal contractility in subclinical LV dysfunction occurring in the absence of ischemia or LV hypertrophy. STI has the potentiality to be used clinically to evaluate the LV systolic function in hypertension patients with different patterns of left ventricular hypertrophic geometric models.更多还原