Explore the value of carotid ultrasound radiomics nomogram in predicting ischemic stroke risk in patients with type 2 diabetes mellitus.

Background and objective: Type 2 Diabetes Mellitus (T2DM) with insulin resistance (IR) is prone to damage the vascular endothelial, leading to the formation of vulnerable carotid plaques and increasing ischemic stroke (IS) risk. The purpose of this study is to develop a nomogram model based on carotid ultrasound radiomics for predicting IS risk in T2DM patients. Methods: 198 T2DM patients were enrolled and separated into study and control groups based on IS history. After manually delineating carotid plaque region of interest (ROI) from images, radiomics features were identified and selected using the least absolute shrinkage and selection operator (LASSO) regression to calculate the radiomics score (RS). A combinatorial logistic machine learning model and nomograms were created using RS and clinical features like the triglyceride-glucose index. The three models were assessed using area under curve (AUC) and decision curve analysis (DCA). Results: Patients were divided into the training set and the testing set by the ratio of 0.7. 4 radiomics features were selected. RS and clinical variables were all statically significant in the training set and were used to create a combination model and a prediction nomogram. The combination model (radiomics + clinical nomogram) had the largest AUC in both the training set and the testing set (0.898 and 0.857), and DCA analysis showed that it had a higher overall net benefit compared to the other models. Conclusions: This study created a carotid ultrasound radiomics machine-learning-based IS risk nomogram for T2DM patients with carotid plaques. Its diagnostic performance and clinical prediction capabilities enable accurate, convenient, and customized medical care.

Comparison of IMD and ICG videoangiography in combined bypass surgery: a single-center study.

BACKGROUND: Superficial temporal artery-middle cerebral artery (STA-MCA) bypass combined with an encephaloduromyosynangiosis (EDMS) had gained significant role in treating chronic cerebral ischemia. Invasiveness and costs of intraoperative digital subtraction angiography (DSA) limited its application in operations. OBJECTIVE: To find the reliable parameters for determining bypass patency with intraoperative micro-Doppler (IMD) sonography and compare the diagnostic accuracy of indocyanine green (ICG) videoangiography with IMD in combined bypass. METHOD: One hundred fifty bypass procedures were included and divided into patent and non-patent groups according to postoperative computed tomography angiography (CTA) within 72 h. The surgical process was divided into four phases in the following order: preparation phase (phase 1), anastomosis phase (phase 2), the temporalis muscle closure phase (phase 3), and the bone flap closure phase (phase 4). The IMD parameters were compared between patent and non-patent groups, and then compared with the patency on CTA by statistical analyses. IMD with CTA, ICG videoangiography with CTA, IMD with ICG videoangiography were performed to assess bypass patency. The agreement between methods was evaluated using kappa statistics. RESULTS: No significant differences of baseline characteristics were found between patent and non-patent group. Parameters in the STA were different between patent and non-patent groups in phases 2, 3, and 4. In patent group, Vm was apparently higher and PI was lower in phases 2, 3, and 4 compared with phase 1 (P < .001). In non-patent group, no differences of Vm and PI were found within inter-group. The best cutoff value of IMD in the STA to distinguish patent from non-patent bypasses was Vm in phase 4 > 17.5 cm/s (sensitivity 94.2%, specificity 100%). In addition, the agreement for accessing bypass patency was moderate between ICG videoangiography and CTA (kappa = 0.67), IMD and ICG videoangiography (kappa = 0.73), and good between IMD and CTA (kappa = 0.86). CONCLUSION: ICG videoangiography could directly display morphology changes of bypass. IMD could be used for providing half-quantitative parameters to assess bypass patency. Vm in phase 4 > 17.5 cm/s suggesting the patency of bypass on CTA would be good. Also, compared with ICG videoangiography, IMD had more accuracy.

Systemic immune-inflammation index is associated with ulcerative plaque in patients with acute ischemic stroke: A single center exploratory study.

PURPOSE: This study explored the correlation between inflammatory markers and ulcerative plaques based on carotid doppler ultrasound (CDU) in individuals with acute ischemic stroke (AIS). METHODS: A total of 202 cases diagnosed with AIS associated with atherosclerotic plaque (AP) in the carotid artery were enrolled in this research. Collecting clinical baseline data, laboratory data (such as the complete blood count) and imaging data (CDU and Brain magnetic resonance imaging [MRI]). Then the correlation between Systemic immune-inflammation index (SII, SII = P N/L, where P, N, and L were the peripheral blood platelet, neutrophil and lymphocyte counts, respectively), the shape and position of AP, the degree of carotid artery stenosis, and the presence of ulcerative plaques. Cutoff values were determined accordingly. RESULTS: SII and high sensitivity CRP (hs-CRP) were independent risk factors for the presence of vulnerable carotid plaques. SII, type A plaque, plaque above carotid bifurcation, and severe carotid stenosis were independent risk factors for the presence of ulcerative plaque. The AUC value, the sensitivity, specificity, the best cutoff value of SII in predicting the presence of ulcerative plaque was 0.895, 93.3%, 89.2%, and 537.4 (109 /L), respectively. CONCLUSION: SII at admission was found to be independently associated with the presence of AIS with vulnerable plaque, especially ulcerative plaques. Moreover, plaque ulceration was more likely to form when the area of higher plaque thickness was located in the upstream arterial wall of maximum plaque thickness (WTmax), plaque was above the carotid bifurcation and severe carotid stenosis.

Corrigendum: The correlation between collagen types and ultrasound feature score in evaluating the vulnerability of carotid artery plaque.

[This corrects the article DOI: 10.3389/fcvm.2021.756424.].

Effects of plaque characteristics and artery hemodynamics on the residual stenosis after carotid artery stenting.

OBJECTIVE: Carotid artery stenting (CAS) has become an alternative strategy to carotid endarterectomy for carotid artery stenosis. Residual stenosis was an independent risk factor for restenosis, with the latter affecting the long-term outcomes of CAS. This multicenter study aimed to evaluate the echogenicity of plaques and hemodynamic alteration by color duplex ultrasound (CDU) examination and investigate their effects on the residual stenosis after CAS. METHODS: From June 2018 to June 2020, 454 patients (386 males and 68 females) with a mean age of 67.2 ± 7.9 years, who underwent CAS from 11 advanced stroke centers in China were enrolled. One week before recanalization, CDU was used to evaluate the responsible plaques, including the morphology (regular or irregular), echogenicity of the plaques (iso-, hypo-, or hyperechoic) and calcification characteristics (without calcification, superficial calcification, inner calcification, and basal calcification). One week after CAS, the alteration of diameter and hemodynamic parameters were evaluated by CDU, and the occurrence and degree of residual stenosis were determined. In addition, magnetic resonance imaging was performed before and during the 30-day postprocedural period to identify new ischemic cerebral lesions. RESULTS: The rate of composite complications, including cerebral hemorrhage, symptomatic new ischemic cerebral lesions, and death after CAS, was 1.54% (7/454 cases). The rate of residual stenosis after CAS was 16.3% (74/454 cases). After CAS, both the diameter and peak systolic velocity (PSV) improved in the preprocedural 50% to 69% and 70% to 99% stenosis groups (P < .05). Compared with the groups without residual stenosis and with <50% residual stenosis, the PSV of all three segments of stent in the 50% to 69% residual stenosis group were the highest, and the difference in the midsegment of stent PSV was the largest (P < .05). Logistic regression analysis showed that preprocedural severe (70% to 99%) stenosis (odds ratio [OR], 9.421; P = .032), hyperechoic plaques (OR, 3.060; P = .006) and plaques with basal calcification (OR, 1.885; P = .049) were independent risk factors for residual stenosis after CAS. CONCLUSIONS: Patients with hyperechoic and calcified plaques of the carotid stenosis are at a high risk of residual stenosis after CAS. CDU is an optimal, simple and noninvasive imaging method to evaluate plaque echogenicity and hemodynamic alterations during the perioperative period of CAS, which can help surgeons to select the optimal strategies and prevent the occurrence of residual stenosis.

Intracranial hemorrhage in large vessel occlusion patients receiving endovascular thrombectomy with or without intravenous alteplase: a secondary analysis of the DIRECT-MT trial.

BACKGROUND: Alteplase before thrombectomy for patients with large vessel occlusion stroke raises concerns regarding an increased risk of intracranial hemorrhage (ICH), but the details of this relationship are not well understood. METHODS: This was a secondary analysis of the DIRECT-MT trial. ICH and its subtypes were independently reviewed and classified according to the Heidelberg Bleeding Classification. The effects of alteplase before thrombectomy on ICH and ICH subtypes occurrence were evaluated using logistic regression. Clinical and imaging characteristics that may modify these effects were exploratorily tested. RESULTS: Among 591 patients, any ICH occurred in 254 (43.0%), including hemorrhagic infarction type 1 in 12 (2.1%), hemorrhagic infarction type 2 in 127 (21.7%), parenchymal hematoma type 1 in 34 (5.8%), parenchymal hematoma type 2 in 50 (8.6%), and other hemorrhage types (3a-3c) in 24 (4.1%). Similar ICH frequencies were observed with combined alteplase and thrombectomy versus thrombectomy only (134/292 (45.9%) vs 120/299 (40.1%); OR 1.27, 95% CI 0.91 to 1.75, P=0.16), but patients treated with alteplase had a higher parenchymal hematoma rate (51/287 (17.8%) vs 33/297 (11.1%); OR 1.75, 95% CI 1.08 to 2.85, P=0.024). In the adjusted model, difference in parenchymal hematoma occurrence between groups remained significant (adjusted OR 1.71, 95% CI 1.00 to 2.92, P=0.049). Patients with history of diabetes (Pinteraction=0.048), hypertension (Pinteraction=0.02), antiplatelet therapy (Pinteraction=0.02), anticoagulation therapy (Pinteraction=0.04), and statin administration (Pinteraction=0.02) harbored a higher ICH rate when they received combination therapy. CONCLUSIONS: Our data showed that in the DIRECT-MT trial, alteplase did not increase overall ICH for large vessel occlusion patients treated with thrombectomy, but it increased the parenchymal hematoma rate.

Predictors of ischemic events in patients with unilateral extracranial vertebral artery dissection: A single-center exploratory study.

Objective: Extracranial vertebral artery dissection (EVAD) is one of the main causes of stroke in young and middle-aged patients. However, the diagnosis is challenging. This study aimed to identify the characteristics of EVAD on color duplex ultrasonography (CDU) and high-resolution magnetic resonance imaging (hrMRI), hoping to improve the accuracy and determine the relative contribution of vessel findings and clinical factors to acute ischemic events. Methods: Patients with unilateral EVAD were recruited and divided into ischemia and non-ischemia groups. Clinical features of patients and the lesion location; a variety of signs which indicate dissection, including the presence of an intimal flap, double lumen, intramural hematoma, dissecting aneurysm, intraluminal thrombus, and irregular lumen; and other quantitative parameters of each dissected segment on CDU and hrMRI were reviewed, respectively. Multiple logistic regression was performed to explore the association between clinical, imaging characteristics, and ischemic events in patients with unilateral EVAD. Results: Ninety-six patients with unilateral EVAD who met the inclusion criteria were enrolled during a six-year period. Overall, 41 cases (42.7%) were confirmed as ischemic stroke (n = 40) or transient ischemic attack (n = 1) during the 48 h after the onset of symptoms. Men, infections during the last week, and smoking were more common in the ischemia group. Intraluminal thrombus and occlusion on CDU were more prevalent in patients with cerebral ischemia than in those without (36.6 vs. 5.5%; p < 0.001, and 39.0 vs. 9.1%; p = 0.001, respectively). On hrMRI, intraluminal thrombus and occlusion were also more frequent in the ischemia group than in the non-ischemia group (34.1 vs. 5.5%; p < 0.001, and 34.1 vs. 9.1%; p = 0.003, respectively). In addition, lesion length on hrMRI was significantly longer for patients with ischemia (81.5 ± 41.7 vs. 64.7 ± 30.8 mm; p = 0.025). In multivariable logistic regression analysis, male gender, infections during the last week, and the presence of intraluminal thrombus on CDU and hrMRI were independently associated with acute ischemic events. Conclusion: Male sex, infections during the last week, and the presence of intraluminal thrombus due to dissection are associated with an increased risk of ischemic events in patients with unilateral EVAD.

Segmented carotid endarterectomy for treatment of Riles type 1A common carotid artery occlusion.

OBJECTIVE: Common carotid artery occlusion (CCAO) is a rare cause of cerebrovascular events. Symptomatic lesions are resistant to medical treatment and revascularization is often required, but there is no consensus on the treatment of CCAO at present. Riles type 1A CCAO is most likely to benefit from revascularization because it has patent outflow tract (internal carotid artery) which was supplied by patent external carotid artery (ECA) from collateral circulation. We described a novel surgical technique improved on the basis of the carotid endarterectomy (CEA) for treatment of Riles type 1A CCAO. METHODS: We rigorously screened ten patients with symptomatic Riles type1A CCAO for surgery from January 2017 to May 2019 and performed a full preoperative assessment of the inadequate collateral circulation compensation. Moreover, we retrospectively reviewed our experience of the segmented CEA in the treatment of them in our single center. RESULTS: Segmented CEA was performed on the left side in four cases and on the right side in six cases. The technical success rate of the procedure was 100%. Primary suture was used in nine cases. Only one patient (right CCAO) who had a history of neck radiotherapy was treated by the patch CEA. The mean temporary blocking time during surgery was 52.8 ± 9.15 min. The mean temporary blocking time for treating the upper segment of the common carotid artery (CCA) was 11.1 ± 2.64 min. In the postoperative period, cerebral perfusion on the ipsilateral site improved in all patients, myocardial infarction occurred in one patient, and recurrent laryngeal nerve damage occurred in another. No ischemic events or re-occlusion or restenosis (> 50%) of the treated CCA occurred during the mean follow-up of 32.6 ± 9.3 months. The preoperative mean modified Rankin Scale (mRS) score was 1.9 (range, 1-3; median, 2). At last follow-up for all patients, the mRS score was 1 (range, 0-3; median, 1). CONCLUSION: Segmented CEA, which utilizes the compensatory effect of collateral circulation, is an effective and safe technique to treat patients suffering from Riles type 1A CCAO with hemodynamic cerebrovascular compromise.

Texture Analysis Based on Vascular Ultrasound to Identify the Vulnerable Carotid Plaques.

Vulnerable carotid plaques are closely related to the occurrence of ischemic stroke. Therefore, accurate and rapid identification of the nature of carotid plaques is essential. This study aimed to determine whether texture analysis based on a vascular ultrasound can be applied to identify vulnerable plaques. Data from a total of 150 patients diagnosed with atherosclerotic plaque (AP) by carotid ultrasound (CDU) and high-resolution magnetic resonance imaging (HRMRI) were collected. HRMRI is the in vivo reference to assess the nature of AP. MaZda software was used to delineate the region of interest and extract 303 texture features from ultrasonic images of plaques. Following regression analysis using the least absolute shrinkage and selection operator (LASSO) algorithm, the overall cohort was randomized 7:3 into the training (n = 105) and testing (n = 45) sets. In the training set, the conventional ultrasound model, the texture feature model, and the conventional ultrasound-texture feature combined model were constructed. The testing set was used to validate the model's effectiveness by calculating the area under the curve (AUC), accuracy, sensitivity, and specificity. Based on the combined model, a nomogram risk prediction model was established, and the consistency index (C-index) and the calibration curve were obtained. In the training and testing sets, the AUC of the prediction performance of the conventional ultrasonic-texture feature combined model was higher than that of the conventional ultrasonic model and the texture feature model. In the training set, the AUC of the combined model was 0.88, while in the testing set, AUC was 0.87. In addition, the C-index results were also favorable (0.89 in the training set and 0.84 in the testing set). Furthermore, the calibration curve was close to the ideal curve, indicating the accuracy of the nomogram. This study proves the performance of vascular ultrasound-based texture analysis in identifying the vulnerable carotid plaques. Texture feature extraction combined with CDU sonogram features can accurately predict the vulnerability of AP.

Percutaneous Patent Foramen Ovale Closure in Patients with Cryptogenic Stroke or Transient Ischemic Attack: A Retrospective Study.

BACKGROUND: Patent foramen ovale (PFO) is associated with cryptogenic stroke (CS). Transcatheter closure of PFO is superior to pharmacotherapy for patients with CS or transient ischemic attack (TIA). More evidence is needed to evaluate the efficacy and safety of PFO closure in Chinese patients. METHODS: This study enrolled ten CS patients and two TIA patients (mean age of 40.8 ± 9.7 y), including seven males (58%) and five females (42%) who underwent PFO closure in our center from January 2017 to July 2019. Baseline data, imaging data, and RoPE (Risk of Paradoxical Embolism) score were collected retrospectively. The preprocedural assessment and percutaneous transcatheter PFO closure were described in detail. The perioperative complications and follow-ups were recorded from all patients. RESULTS: Among ten patients with CS, eight patients had a RoPE score of >6 and two patients had a RoPE score of 6. MRI confirmed multiple infarcts in seven cases, and infarct involving the cortex in nine cases. Abnormal ECG was found in three patients and abnormal Echo in four patients. Right-to-left shunt (RLS) was detected in all the patients by cTCD or cTTE. To be specific, RLS was observed in nine of the ten TEE-detected patients. No case had PFO complicated with atrial septal aneurysm (ASA). The success rate of PFO closure was 91.6%. No serious perioperative complications were observed. During a mean time of 26.5 ± 8 months (15-41 months) of follow-up, no recurrent cerebral infarction, TIA, or thromboembolism were detected in postoperative patients. CONCLUSIONS: PFO closure is safe and effective in the treatment of Chinese patients with CS or TIA.

Evaluation of right-to-left shunt on contrast-enhanced transcranial Doppler in patent foramen ovale-related cryptogenic stroke: Research based on imaging.

BACKGROUND: Cardiogenic embolism caused by patent foramen ovale (PFO) is a common etiology of cryptogenic stroke (CS), particularly in young and middle-aged patients. Studies about right-to-left shunt (RLS) detection using contrast-enhanced transcranial Doppler (c-TCD) are numerous. According to the time phase and number of microbubbles detected on c-TCD, RLS can be classified and graded. We hypothesized that the characteristics of an infarction lesion on diffusion-weighted imaging differs when combining the type and grade of RLS on c-TCD in patients with PFO-related CS. AIM: To explore the characteristics of infarction lesions on diffusion-weighted imaging when combining the RLS type and grade determined by c-TCD. METHODS: We retrospectively evaluated CS patients from August 2015 to December 2019 at a tertiary hospital. In total, 111 PFO-related CS patients were divided according to whether RLS was permanent (microbubbles detected both at resting state and after the Valsalva maneuver) or latent (microbubbles detected only after the Valsalva maneuver) on c-TCD. Each group was subdivided into small, mild and large RLS according to the grade of shunt on c-TCD. A normal control group was composed of 33 patients who suffered from simple dizziness. Intragroup and intergroup differences were analyzed in terms of clinical, laboratory and diffusion-weighted imaging lesion characteristics. The correlation between RLS grade evaluated by c-TCD and size of PFO determined by transesophageal echocardiography were also analyzed. RESULTS: In 111 patients with PFO-related CS, 68 had permanent RLS and 43 had latent RLS. Clinical characteristics and laboratory tests were not significantly different among the permanent RLS, latent RLS and normal control groups. The proportion of patients with multiple territory lesions in the permanent RLS group (50%) was larger than that in the latent RLS group (27.91%; P = 0.021). Posterior circulation was more likely to be affected in the latent RLS group than in the permanent RLS group (30.23% vs 8.82%, P = 0.004). Permanent-large and latent-large RLS were both more likely to be related to multiple (P trend = 0.017 and 0.009, respectively), small (P trend = 0.035 and 0.006, respectively) and cortical (P trend = 0.031 and 0.033, respectively) lesions. The grade of RLS evaluated by c-TCD was correlated to the size of PFO determined by transesophageal echocardiography (r = 0.758, P < 0.001). CONCLUSION: Distribution of the infarct suggested the possible type of RLS. Multiple, small and cortical infarcts suggest large RLS induced by a large PFO.

Association of Carotid Plaque Vulnerability and Cardiovascular Risk Factors in Patients Undergoing Carotid Endarterectomy.

BACKGROUND: The association between high-risk cardiovascular factors and atherosclerotic is well established. However, whether plaque vulnerability is related to specific cardiovascular risk factors remains unknown. The association between plaque vulnerability and cardiovascular risk factors was evaluated in plaques removed in a carotid endarterectomy. METHODS: Consecutive subjects scheduled for a carotid endarterectomy were recruited. All patients' baseline characteristics, risk factors, laboratory results, cardiovascular disease history, and medication use history were collected preoperatively. Histopathologic features within the vulnerable plaques were analyzed postoperatively. Risk factors for plaque vulnerability were assessed by univariate and multivariate analyses with adjustment for potential confounders. RESULTS: A total of 128 carotid plaques were removed during the carotid endarterectomy. On multivariate analysis, hypertension (odds ratio [OR] 5.971, 95% confidence interval [CI] 1.959-18.203, P = 0.002) and dyslipidemia (OR 3.822, 95% CI 1.317-11.089, P = 0.014) were independently associated with plaque vulnerability. Hypertension was independently associated with the presence of a ruptured fibrous cap (OR 6.122, 95% CI 2.318-16.166, P < 0.001), intraplaque hemorrhage (OR 3.535, 95% CI 1.551-8.055, P = 0.003), and a large lipid core (OR 2.335, 95% CI 1.053-5.180, P = 0.037). The incidence of having a large lipid core was increased by 3.216-fold in patients with dyslipidemia (95% CI 1.409-7.340, P = 0.006). When the multivariate analysis was restricted to symptomatic patients, hypertension (OR 5.005, 95% CI 1.294-19.350, P = 0.020) was the most significant risk factor associated with vulnerable plaque. CONCLUSION: The composition heterogeneity in the atherosclerotic plaque was significantly correlated to specific cardiovascular risk factors.

The Correlation Between Collagen Types and Ultrasound Feature Score in Evaluating the Vulnerability of Carotid Artery Plaque.

Objectives: To investigate whether ultrasound score has clinical value in identifying carotid artery-vulnerable plaque and the impacts of collagen distribution on the stability of plaque. Materials and Methods: Standard carotid artery ultrasound examinations were performed in 51 patients with carotid artery plaques before carotid endarterectomy. Hematoxylin-eosin staining and Sirius red-picric acid staining of plaque sections were performed to analyze the pathological features and collagen distribution. All plaques were classified into vulnerable and stable groups by pathological features. Ultrasound scores, cap thickness, and the ratios of different collagen types were recorded and analyzed between two groups and different parts of plaques. Results: Ultrasound scores of the vulnerable group were higher than those of the stable group (4.35 ± 1.23 vs. 2.09 ± 1.04, P = 0.001). AUC was 0.894 (best cutoff point three) in differentiating vulnerable and stable plaques. Compared with the stable group, the fibrous caps of the vulnerable group were thinner (P = 0.012); the area ratios of collagen type I to all collagen in the vulnerable group were lower (P = 0.033); however, the area ratios of collagen type IV to all collagen were higher (P = 0.026). Compared with downstream shoulders, the ultrasound scores of upstream shoulders of plaque were higher (P = 0.001), the fibrous caps of upstream shoulders were thinner (P = 0.001), and the area ratios of collagen type I to all collagen were lower (P = 0.022). Conclusion: Ultrasound score could have a clinical value in identifying vulnerable carotid artery plaque, and the collagen distribution could impact the stability of plaques, especially collagen type I and type IV. The results also prompted that the upstream shoulders were more vulnerable than the downstream shoulders.

Evaluation of Carotid Plaque Rupture and Neovascularization by Contrast-Enhanced Ultrasound Imaging: an Exploratory Study Based on Histopathology.

A significant portion of ischemic stroke is on account of emboli caused by fibrous cap rupture of vulnerable plaque with intraplaque neovascularization as a significant triggering factor to plaque vulnerability. Contrast-enhanced ultrasound (CEUS) could offer detailed information on plaque surface and intraplaque microvascular. This study aims to comprehensively assess the value of CEUS for the detection of plaque rupture and neovascularization in histologically verified plaques that had been removed from the patients who had undergone carotid endarterectomy (CEA). Fifty-one consecutive subjects (mean age, 67.0 ± 6.5 years; 43 [84.3%] men) scheduled for CEA were recruited. Standard ultrasound and CEUS were performed prior to surgery. Based on the direction of the contrast agents that diffuse within the plaques, plaques were divided as "inside-out" direction (contrast agents diffuse from the artery lumen towards the inside of the plaque) and non-inside-out direction. Plaque enhancement was assessed by using a semi-quantitative grading scale (grade 1: no enhancement; grade 2: moderate enhancement; grade 3: extensive enhancement). Plaques were evaluated for histopathologic characteristics according to Oxford Plaque Study (OPS) standard postoperative. Intraplaque neovascularization as manifested by the appearance of CD34-positive microvessels was characterized in terms of microvessel density (MVD), microvessel area (MVA), and microvessel shape (MVS). In 51 plaques, the sensitivity, specificity, positive, and negative predictive values of contrast agent inside-out direction diffusion for the detection of plaque fibrous cap rupture were 87.5%, 92.6%, 91.3%, and 89.3%, respectively. The incidence of cap rupture was significantly higher in contrast agent inside-out direction diffusion than non-inside-out direction diffusion (73.9% vs 25.0%, p < 0.001), and inside-out direction diffusion did exhibit higher frequency of vulnerable plaques (OPS grades 3-4) (95.7% vs 53.6%, p = 0.001). Multivariate logistic regression analysis revealed the contrast agent inside-out direction diffusion as an independent correlate to plaque rupture (OR 8.5, 95% CI 2.4-30.1, p = 0.001). With increasing plaque enhancement, plaque MVD (p < 0.001), plaque MVA (p = 0.012), and percentage of highly irregular-shaped microvessels increased (p < 0.001). Contrast agent inside-out direction diffusion could indicate plaque rupture. The increase in plaque enhancement paralleled increased, larger, and more irregular-shaped microvessels, which may suggest an increased risk of plaque vulnerability.

Decreased cortical perfusion in areas with blood-brain barrier dysfunction in Moyamoya disease.

BACKGROUND: Recently, several studies have focused on the relationship between blood-brain barrier (BBB) impairment and the etiology of Moyamoya disease (MMD). However, in vivo studies investigating about BBB impairment and cortical perfusion in MMD patients were really rare. METHODS: This study included 16 patients diagnosed with MMD and 9 patients with atherosclerotic cerebrovascular disease (ACVD); all of who were treated with superficial temporal artery-middle cerebral artery (STA-MCA) bypass. Cortical perfusion was assessed using intraoperative indocyanine green (ICG) videoangiography by calculating the blood flow index (BFI). In addition, we used sodium fluorescein (NaFl) to evaluate the permeability of BBB in vivo during operation. RESULTS: The results showed that BBB impairment in MMD patients was more significant than that in ACVD patients, whereas, the cortical perfusion was comparable between two groups. BFI was significantly improved after STA-MCA bypass both in the MMD group (post-operation vs pre-operation: 109.2 ± 67.7 vs 64.3 ± 35.0, p = 0.004) and the ACVD group (post-operation vs pre-operation: 137.6 ± 89.6 vs 90.8 ± 58.3, p = 0.015). Moreover, BFI was significantly decreased in the cortex with BBB impairment as compared with that in the cortex with intact BBB (impaired BBB vs intact BBB: 55.7 ± 26.5 vs 87.6 ± 55.1, p = 0.025). Following bypass, the cortical perfusion significantly improved in the area of BBB impairment (post-operation vs pre-operation: 93.8 ± 75.2 vs 55.7 ± 26.5, p = 0.004), which was not observed in the BBB intact area (post-operation vs pre-operation: 92.4 ± 50.4 vs 87.6 ± 55.1, p = 0.58). CONCLUSION: In summary, we observed that BBB impairment in MMD patients was more significant than that in ACVD patients. This study also demonstrated for the first time that cortical perfusion was significantly decreased in the cortex with BBB impairment as compared with that in the cortex with intact BBB in MMD patients. We also observed that After STA-MCA bypass, the cortical perfusion was significantly improved in the cortex with BBB impairment. These results may provide a new insight for BBB impairment and cortical perfusion in the etiology of MMD.

Distribution Pattern of Atherosclerotic Stenosis in Chinese Patients with Stroke: A Multicenter Registry Study.

The aim of this multicenter study was to demonstrate the distribution pattern of atherosclerotic stenosis and its trend with aging between extracranial and intracranial arteries and its distribution between the anterior and posterior circulations in Chinese patients hospitalized with ischemic stroke. In addition, the risk factors for the distribution pattern were illustrated. From June 2015 to May 2016, 9,346 patients with ischemic stroke from 20 hospitals were enrolled. Carotid artery ultrasonography and transcranial color-coded sonography/transcranial Doppler were used to evaluate the extracranial and intracranial arteries. The distribution pattern of atherosclerotic stenosis and its trend with aging were analyzed. Logistic regression was used to analyze the risk factors for the distribution pattern. Among the 9,346 patients, 2,882 patients (30.8%) had at least one artery with a degree of stenosis ≥50%. Among patients with arterial stenosis, the proportion of patients with intracranial artery stenosis was higher than those with extracranial artery stenosis (52.6% vs. 27.6%), and the proportion of anterior circulation artery stenosis was higher than that in the posterior circulation (52.2% vs.26.2%). With aging, the proportion of intracranial artery stenosis alone decreased; at the same time, the proportion of extracranial artery stenosis and extracranial plus intracranial artery stenosis increased (trend χ2=6.698, P=0.001). Hypertension (OR 1.416, P=0.008) and family history of stroke (OR 1.479, P=0.014) were risk factors for intracranial artery stenosis. Male, aging, and smoking were factors more related to extracranial artery stenosis. Aging (OR 1.022, P<0.001) and hypertension (OR 1.392, P=0.019) were related to posterior circulation artery stenosis. Intracranial arteries and anterior circulation arteries were susceptible to stenosis in Chinese patients with ischemic stroke. However, the distribution pattern of atherosclerotic stenosis was dynamic and varied with aging. Aging and different risk factors contribute to this distribution pattern.

Specific matrix metalloproteinases and calcification factors are associated with the vulnerability of human carotid plaque.

The rupture of atherosclerotic plaque provokes the majority of acute cerebrovascular events. Studies have demonstrated that various matrix metalloproteinases (MMPs) may promote atherosclerotic plaque progression and rupture. However, results have been incongruous and the mechanisms of this remain obscured. Therefore, in the current study, carotid plaques were characterized by assessing the levels of MMPs and calcification factors, and evaluating their association with plaque vulnerability. Human carotid plaques were obtained from carotid endarterectomies, and classified into stable and vulnerable groups by ultrasonography and histological analyses. The mRNA and protein levels of MMPs, vascular endothelial growth factor (VEGF), bone sialoprotein 2 (BSP) and osteopontin were investigated by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. Immunohistochemistry was used to localize MMP-2 and MMP-14 in stable and vulnerable plaques. The activation of various associated signaling pathways was also investigated using western blotting. The mRNA levels of MMP-2, -7, -9 and -14 were elevated in vulnerable plaques, among which expression of MMP-2 and -14 were the highest. Consistent with the mRNA levels, the protein levels of MMP-2 and -14 were also elevated. Immunohistochemistry also demonstrated positive staining of MMP-2 and MMP-14 in vulnerable plaques. Factors that indicate neovascularization and calcification, including VEGF and BSP, were concurrently elevated in vulnerable plaques. In addition, the protein levels of extracellular regulated kinase (ERK) and protein kinase C (PKC) were upregulated in vulnerable plaques. The current study provides novel insights into the MMP profiles of vulnerability plaques, and may assist in the development of novel methods for the diagnosis of plaque vulnerability and the prevention of plaque rupture.

Superficial and multiple calcifications and ulceration associate with intraplaque hemorrhage in the carotid atherosclerotic plaque.

OBJECTIVE: Intraplaque hemorrhage (IPH) and ulceration of carotid atherosclerotic plaques have been associated with vulnerability while calcification has been conventionally thought protective. However, studies suggested calcification size and location may increase plaque vulnerability. This study explored the association between calcium configurations and ulceration with IPH. METHODS: One hundred thirty-seven consecutive symptomatic patients scheduled for carotid endarterectomy were recruited. CTA and CTP were performed prior to surgery. Plaque samples were collected for histology. According to the location, calcifications were categorized into superficial, deep and mixed types; according to the size and number, calcifications were classified as thick and thin, multiple and single. RESULTS: Seventy-one plaques had IPH (51.8%) and 83 had ulceration (60.6%). The appearance of IPH and ulceration was correlated (r = 0.49; p < 0.001). The incidence of multiple, superficial and thin calcifications was significantly higher in lesions with IPH and ulceration compared with those without. After adjusting factors including age, stenosis and ulceration, the presence of calcification [OR (95% CI), 3.0 (1.1-8.2), p = 0.035], multiple calcification [3.9 (1.4-10.9), p = 0.009] and superficial calcification [3.4 (1.1-10.8), p = 0.001] were all associated with IPH. ROC analysis showed that the AUC of superficial and multiple calcifications in detecting IPH was 0.63 and 0.66, respectively (p < 0.05). When the ulceration was combined, AUC increased significantly to 0.82 and 0.83, respectively. Results also showed that patients with lesions of both ulceration and IPH have significantly reduced brain perfusion in the area ipsilateral to the infarction. CONCLUSIONS: Superficial and multiple calcifications and ulceration were associated with carotid IPH, and they may be a surrogate for higher risk lesions. KEY POINTS: • CTA-defined superficial and multiple calcifications in carotid atherosclerotic plaques are independently associated with the presence of intraplaque hemorrhage. • The combination of superficial and multiple calcifications and ulceration is highly predictive of carotid intraplaque hemorrhage. • Patients with lesions of both ulceration and intraplaque hemorrhage have significantly reduced brain perfusion in the area ipsilateral to the infarction.

Expression of MMP14 in invasive pituitary adenomas: relationship to invasion and angiogenesis.

Pituitary adenomas (PAs) are noncancerous tumors, and about 35% of those reported to be invasive have been classified as "invasive pituitary adenomas (IPAs)". In clinical, operative complications, total resection failures, and high relapse rates result from invasive features during the therapeutic process. Invasive mechanism is a complex process, including metalloproteases, inhibitors and tumor microenvironment factors etc. Thus, studying invasive mechanism of PAs might contribute to understanding its biological behavior. In our research, three type tissue samples of human, pituitaries, PAs, IPAs, their mRNA expression of MMP1, MMP2, MMP9, MMP14 and MMP15 were measured using real-time PCR. MMP2 and MMP14 protein levels also were measured with immunohistochemistry in same samples. We confirmed that elevated matrix metalloproteinase-14 expression correlates with invasive characteristics of IPAs. To investigate molecular mechanism of how MMP14 contributes to invasiveness, an ATT20 cell was used in this study. After transient-transfection of the MMP14-shRNA expression vector into ATT20 cells, we observed that mRNA expression of PTTG, VEGF, and TGFß was significantly suppressed in interference groups. Meanwhile, ATT20 cells in high concentration TIMP-1 environment exhibit reduced PTTG, VEGF, and TGFß expression accompanied with the down-regulation of MMP14. Thus, we propose that MMP14 plays an important role in tumor invasion and angiogenesis and that a novel regulatory pathway for MMP14 may exist through VEGF and PTTG. In brief, MMP14 may be a target for therapeutic treatment.

Intraoperative microvascular Doppler monitoring in intracranial aneurysm surgery.

BACKGROUND: Surgical treatment of intracranial aneurysms is often compromised by incomplete exclusion of the aneurysm or stenosis of parent vessels. Intraoperative microvascular Doppler (IMD) is an attractive, noninvasive, and inexpensive tool. The present study aimed to evaluate the usefulness and reliability of IMD for guiding clip placement in aneurysm surgery. METHODS: A total of 92 patients with 101 intracranial aneurysms were included in the study. IMD with a 1.5-mm diameter, 20-MHz microprobe was used before and after clip application to confirm aneurysm obliteration and patency of parent vessels and branching arteries. IMD findings were verified postoperatively with digital subtraction angiography (DSA) or dual energy computed tomography angiography (DE-CTA). Ninety consecutive patients, harboring 108 aneurysms, who underwent surgery without IMD was considered as the control group. RESULTS: The microprobe detected all vessels of the Circle of Willis and their major branches. Clips were repositioned in 24 (23.8%) aneurysms on the basis of the IMD findings consistent with incomplete exclusion and/or stenosis. IMD identified persistent weak blood flow through the aneurismal sac of 11 of the 101 (10.9%) aneurysms requiring clip adjustment. Stenosis or occlusion of the parent or branching arteries as indicated by IMD necessitated immediate clip adjustment in 19 aneurysms (18.8%). The mean duration of the IMD procedure was 4.8 minutes. The frequency of clip adjustment (mean: 1.8 times per case) was associated with the size and location of the aneurysm. There were no complications related to the use of IMD, and postoperative angiograms confirmed complete aneurysm exclusion and parent vessel patency. About 8.3% (9/108) aneurysms were unexpectedly incompletely occluded, and 10.2% (11/108) aneurysms and parent vessel stenosis without IMD were detected by postoperative DSA or DE-CTA. IMD could reduce the rate of residual aneurysm and unanticipated vessel stenosis which demonstrated statistically significant advantages compared with aneurysm surgery without IMD. CONCLUSION: IMD is a safe, easily performed, reliable, and valuable tool that is suitable for routine use in intracranial surgery, especially in complicated, large, and giant aneurysms with wide neck or without neck.