Primary Study Of Carotid Plaque Biomechanics With Strain And Strain Rate Imaging In Patients With Acute Cerebral Infarction

1. IntroductionMore than half of ischemic strokes are related to extra cranial athermanous disease in the developed world. In present clinical practice, selection for surgery or revascularization is based on the degree of luminal stenosis as measured by angiography such as ultrasound or magnetic resonance angiography (MRI). Carotid endarterectomy is well known to be beneficial in patients with symptomatic and asymptomatic severe carotid stenosis [1-4]. However, increasing evidences suggested that the severely luminal stenosis alone might not be sufficient to detect patients at high risk to develop ischemic stroke [5 6]. Instead, the identification of plaque factors other than degree of stenosis may improve risk stratification and help to decrease the opportunity of stroke in the carotid territory [7]"Vulnerable plaque" has been used to describe rupture-prone plaques. Histological data suggests that vulnerable plaque is characterized by a large necrotic lipid pool(>40% of the plaque's total volume), a thin overlying fibrous cap<100um, and inflammatory infiltrate within the plaque [8-11]. Thus, to evaluate plaque vulnerability, an ideal approach would provide information containing both plaques'anatomic characteristics (morphology) and its functional properties (activity) [8 9 12 13]Once atherosclerotic plaques are formed, there should be a great change of the distribution of stress and strain in the wall [14 15].It has been hypothesized that mechanics play an important role in plaque rupture and should be considered in an incorporated way with plaque morphology and composition for possible improvement of plaque assessment schemes [16]. Several studies was carried out to analyze stress in atherosclerotic wall [14 15 17]. They primarily focused on the biomechanical properties in atherosclerotic plaques. Previously, such biomechanical profiling has been based on finite element analyses that use ex vivo histology or imaging data to create stress maps of vessel wall [9-13], which may alter the morphology and geometric relationships, that calling into question of the simulation validity.In recent years, the advent of high-resolution imaging techniques such as intravascular ultrasound has allowed detailed morphologic and structural characterization of carotid plaques to be performed in vivo, which can avoid the problem of possible structural alterations in the vessel wall. MRI technique has shown its ability to non-invasively quantify plaque size, shape and component [18-20]. Attempts of using ultrasound and IVUS techniques have been made to determine vessel motion, mechanical properties and vessel wall structure, even to predict rupture locations [21 22]Two-dimensional (2D) strain, which is based on speckle tracking in gray-scale B-mode images, has been implemented in numerous experimental and clinical studies for exploration of cardiac function different clinical setting [23 24]. This method enables simultaneous evaluation of radial, longitudinal and circumferential myocardial deformation. However, little data has been reported for its usability in plaque biomechanics assessment.In this study, we examined carotid plaque morphology and biomechanics properties by high-resolution B-mode ultrasonography combined with strain and strain rate imaging, for evaluated carotid plaque elasticity and investigated the association between ACI and carotid plaque biomechanics.2. Materials and Methods2.1. SubjectsOne hundred patients(Ages between 34-89 years, male and female) were enrolled for this cross-sectional study in the Department of Neurology at Qilu hospital. Fifty patients with ACI of anterior circulation according to the result of CT or MRI within 24 hours of the onset of symptoms were selected as ACI group. In addition, Age and gender matched fifty patients without ACI, were taken as control group. The following patients were excluded from the study:(1) patients with lacuna infarcts, silence infarcts, or posterior circulation infarcts; (2) patients with aerial fibrillation, cardiac valve abnormalities, recent myocardial infarction, or heart failure; (3) patients with concurrent diseases which influence the expression of inflammatory mediators, such as ischemic events, trauma, or surgery during the previous 3 months, sever liver disease, renal failure, hematologic, or malignant diseases, chronic inflammatory diseases, autoimmune diseases, as well as fever or infectious conditions. General data including age, sex, hypertension, coronary heart disease, smoking state were derived. And venous blood was obtained between 7 and 8 am after 12 hours of fasting. Laboratory parameters contained red blood cell count, plasma fibrinogen, serum levels of total cholesterol, triglycerides, high density cholesterol, low density cholesterol, apolipoprotein A1, apolipoprotein B, cystatin-C (Cys-C), fasting blood glucose (GLU) were acquired.2.2. Carotid artery ultrasound examinationUltrasound images of the carotid artery were achieved with a high-resolution ultrasound scanner, Mylab90 equipped with a linear array 5-8MHZ transducer. Patients with ACI were underwent the examination within 24 hours after onset of symptoms. All ultrasound examinations were performed by the same experienced ultrasonographer who was unaware of history and physical signs of the patient. Patients were examined in the supine position. Each carotid artery scan started above the clavicle, and the transducer moved along the common carotid, internal and outer carotid arteries in order. Transverse views and three different longitudinal views (anterior, posterior and lateral) were scanned for the presence of atherosclerotic plaques. The intimae-media thickness (IMT) and blood flow index were all evaluated in the position 1-1.5 centimeters (cm) distal to the common carotid artery proximal to the bifurcation. The intimae-media thickness (IMT) was measured with quality intimae-media thickness (QIMT), software in the ultrasound scanner, automatically. And blood flow index including blood flow velocity integral, end-diastolic velocity, resistance index, systolic and diastolic end speed ratios were all measured automatically. Dynamic state images in three cardiac cycles of the longitude and transverse views in the plaques'position were saved. Left and right carotid arteries were all examined by turns for each patient. In arteries with multiple plaques, only the thickest plaque was selected.2.3. Carotid plaque analysisThe plaque biomechanics parameters were analyzed by strain and strain rate imaging software within the ultrasound scanner. The saved dynamic state images were imported into strain and train rate imaging mode. All the analyses were done in systolic phase monitored by electrocardiogram. In the transverse views, the outer members were traced. However, the fibrous cap and outer member were traced in the longitude view. Eight regions of interest (ROT) of plaque longitude axis were separated:the half part near the heart(na),the half part far away the heart(fa), shoulder near the heart(ns), middle near the heart(nm), top (t), shoulder far away the heart(fs),middle far away the heart(fm). Data was exported into computer, positive peak of circ strain (Sc) and negative peak of radial displacement (Dr) in the outer member of plaque short axis images, as well as positive peak of fibrous cap long strain (Si1), negative peak of fibrous cap long strain (Si2), positive peak of outer member long strain (Se1), negative peak of outer member long strain (Se2) were measured correspondingly. Positive peak of shear stress (SS1), negative peak of shear stress (SS2) were calculated with fibrous cap and outer member long strains. Then difference of sheer stress and fibrous cap strain between two regions of interest was calculated one by one.Plaque morphology in terms of echogenicity was divided into fibrous type and lipid type. The plaque thickest position (PT) and the thinnest IMT beyond the plaque were measured, and then the eccentric index (EI) was calculated. A second observer reviewed each plaque to determine the reproducibility of ultrasonic characterization of plaque morphology.2.4. Statistical analysisData were analyzed with SPSS software version 17.0. Continuous variables were demonstrated as means±standard error (SEM). Measurement features between patients with ACI and control group were evaluated with Independent-samples t test, while Chi-square test was used for the categorical comparisons. Independent-samples t test was also used for the comparisons of plaque biochemists parameters between fibrous type plaques and lipid type plaques. The comparisons of biomechanics parameters between the different regions of interest were evaluated with One-way ANOVA. Binary logistic regression was performed to assess the association between ACI and plaque biomechanics index or morphology data or carotid artery parameters. Model 1 included the general variables with age and sex adjusted. Then variables with significant association were added into model 1 subsequently to determine the final regression model. For each model, a receiver operating characteristic curve was plotted to describe the sensitivity and specificity according to the area under the curve (AUC) and 95% confidence interval (CI). For p<0.05, results were considered as statistically significant.3. ResultsAs illustrated from the general and laboratory data, there is no statistical significant difference between patients with ACI and control group in terms of age, gender, Hypertension, CHD and smoking state. Blood parameters included red blood cell count, plasma fibrinogen, serum levels of total cholesterol, triglycerides, high density cholesterol, low density cholesterol, apolipoprotein A1, apolipoprotein B, cystatin-C (Cys-C), fasting blood glucose (GLU) did not differ between the two groups.For carotid artery, the two groups differed significantly in carotid blood flow velocity integral, end-diastolic velocity (p=0.001 and p=0.018 respectively). As well intimae-media thickness, resistance index, systolic and diastolic end velocity did not differ between the two groups.The ratio of fibrous plaque in patients with ACI and control group were 62% and 55% respectively (p=0.291). Eccentric index (EI) in patients with ACI was lower than control group (p=0.057). The plaque thickness (PT) in longitudinal view in ACIs was significantly higher than patients without ACI (p=0.012).3.1. Plaque biomechanics between the two groupsCompared with control group, negative peak of sheer stress(SS2) in the half part far away the heart (fa) and middle far away the heart (fm) were significantly higher (p=0.044, p=0.020 respectively) in ACIs. And, negative peak of fibrous cap strain(Si2) and sheer stress(SS2) in the regions of interest contained half part near heart, top and shoulder far away heart with ACIs were no significantly higher than NACIs. However in ACIs, other plaque biomechanics indexes contained positive peak of fibrous cap strain (Si1) and sheer stress (SS1) in the half part near heart, top and shoulder far away heart were on significantly lower than patients without ACI. Other biomechanics parameters were all no significantly different between two groups.3.2. Plaque biomechanics distribution in ACIsIn one way ANOVA, plaque biomechanics contained positive and negative peak of fibrous cap strain (Sil and Si2) among regions of interest in patients with ACI were all significant different (p=0.020 and p=0.009 respectively). And the concentrated region for positive peak of strain and sheer stress was in shoulder near away heart (ns), while the concentrated region for negative peak of strain and sheer stress was in shoulder far away heart (FS). However plaque biomechanics index among different regions in control group all had insignificant differences. The next pairwise comparison was performed among different regions in ACIs. Figure 2 shows plaque strain and sheer stress distribution in ACIs.3.3. Plaque biomechanics difference among regions of interestDifference of plaque fibrous cap strain and sheer stress between two regions of interest was collected by turn. Compared with NACIs, strain difference between fm and shoulder far away heart (d10-Si1) was significantly lower (p=0.03) in ACIs. And strain difference between top and middle far away heart (d6-Si1) was significantly lower (p=0.021) too. Meanwhile in patients with ACI, sheer stress difference between top and far away shoulder (d9-SS1) were significantly lower (p=0.034) than patients without ACI.3.4. Correlation between acute cerebral infarction events and plaque biomechanicsBinary logistic regression model was used to choose the significant correlation between ACI and the carotid artery data, plaque morphology and biomechanics index. General data included age, sex, hypertension, coronary heart disease, smoking state, serum level of total cholesterol and triglycerides, high density cholesterol, low density cholesterol, fasting blood glucose were added into the model firstly. Then index with significant differ was added into the model independently by turn. Strain difference (d6-Si1) and sheer stress (SS2-fa and SS2-fm) were all significantly associated with ACI.General data included age, sex, hypertension, coronary heart disease, smoking state, serum level of total cholesterol and triglycerides, high density cholesterol, low density cholesterol, fasting blood glucose were constituted Model 1, which the receiver operating characteristic (ROC) AUC was 0.825 (95%CI= 0.687-0.962, P=0.002). And indexes with significantly associated with ACI in logistic analysis were added into model 1 respectively. The AUC with peak positive strain difference between top and middle far away heart (d6-Si1) added into Model 1 was 0.890 (95%CI= 0.777-1.000, P=0.000). And when added negative peak of sheer stress of half part far away heart (SS2-fa) into Model 1, the AUC was 0.870 (95%CI=0.743-0.997,P＝0.000). Similarly, the AUC with peak negative sheer stress of middle far away heart (SS2-fm) added into Model 1 was 0.903 (95%CI=0.797-1.000, P=0.000).4. ConclusionsThe peak values of shear stress and long strain in plaque different regions were significant different in patients with ACI. High sheer stress of middle far away heart(SS2-fm) and half part far away heart(SS2-fa) in plaque longitudinal views were significantly associated with ACI. Plaque biomechanics in the longitudinal view could be calculated by strain and strain rate imaging, which may provide a more useful quantitative assessment of plaque biomechanics. Therefore, the reliability and clinical importance of these quantitative parameters will be specified by further investigations.