A Video-based Automated Tracking and Analysis System of Plaque Burden in Carotid Artery Using Deep Learning: A Comparison with Senior Sonographers.

BACKGROUND AND OBJECTIVE: The incidence of stroke is rising, and it is the second major cause of mortality and the third leading cause of disability around the globe. The goal of this study was to rapidly and accurately identify carotid plaques and automatically quantify plaque burden using our automated tracking and segmentation US-video system. METHODS: We collected 88 common carotid artery transection videos (11048 frames) with a history of atherosclerosis or risk factors for atherosclerosis, which were randomly divided into training, test, and validation sets using a 6:3:1 ratio. We first trained different segmentation models to segment the carotid intima and adventitia, and calculate the maximum plaque burden automatically. Finally, we statistically analyzed the plaque burden calculated automatically by the best model and the results of manual labeling by senior sonographers. RESULTS: Of the three Artificial Intelligence (AI) models, the Robust Video Matting (RVM) segmentation model's carotid intima and adventitia Dice Coefficients (DC) were the highest, reaching 0.93 and 0.95, respectively. Moreover, the RVM model has shown the strongest correlation coefficient (0.61±0.28) with senior sonographers, and the diagnostic effectiveness between the RVM model and experts was comparable with paired-t test and Bland-Altman analysis [P= 0.632 and ICC 0.01 (95% CI: -0.24~0.27), respectively]. CONCLUSION: Our findings have indicated that the RVM model can be used in ultrasound carotid video. The RVM model can automatically segment and quantify atherosclerotic plaque burden at the same diagnostic level as senior sonographers. The application of AI to carotid videos offers more precise and effective methods to evaluate carotid atherosclerosis in clinical practice.

A deep learning-based calculation system for plaque stenosis severity on common carotid artery of ultrasound images.

OBJECTIVES: Assessment of plaque stenosis severity allows better management of carotid source of stroke. Our objective is to create a deep learning (DL) model to segment carotid intima-media thickness and plaque and further automatically calculate plaque stenosis severity on common carotid artery (CCA) transverse section ultrasound images. METHODS: Three hundred and ninety images from 376 individuals were used to train (235/390, 60%), validate (39/390, 10%), and test (116/390, 30%) on a newly proposed CANet model. We also evaluated the model on an external test set of 115 individuals with 122 images acquired from another hospital. Comparative studies were conducted between our CANet model with four state-of-the-art DL models and two experienced sonographers to re-evaluate the present model's performance. RESULTS: On the internal test set, our CANet model outperformed the four comparative models with Dice values of 95.22% versus 90.15%, 87.48%, 90.22%, and 91.56% on lumen-intima (LI) borders and 96.27% versus 91.40%, 88.94%, 91.19%, and 92.88% on media-adventitia (MA) borders. On the external test set, our model still produced excellent results with a Dice value of 92.41%. Good consistency of stenosis severity calculation was observed between CANet model and experienced sonographers, with Intraclass Correlation Coefficient (ICC) of 0.927 and 0.702, Pearson's Correlation Coefficient of 0.928 and 0.704 on internal and external test set, respectively. CONCLUSIONS: Our CANet model achieved excellent performance in the segmentation of carotid IMT and plaques as well as automated calculation of stenosis severity.

Evaluation of Turbulence Index and Flow Pattern for Atherosclerotic Carotid Stenosis: A High-Frame-Rate Vector Flow Imaging Study.

OBJECTIVE: The emerging high-frame-rate vector flow imaging provides a new way of hemodynamic evaluation for complex blood flow. This study was aimed at exploring quantitatively the characteristics of complex flow with turbulence (Tur) index and analyzing flow patterns in atherosclerotic internal carotid artery stenosis (ICAS) using high-frame-rate vector flow imaging. METHODS: This study prospectively included 60 patients with ICAS. Tur values in different segments of stenosis and cardiac phases were compared. Spearman correlation analysis was performed between clinical plaque characteristics with turbulence grading by ln(Tur). Three complex flow patterns were qualitatively drawn on vector flow mode, and the rates of detection of flow patterns in different stenosis groups and ulceration groups were compared. RESULTS: Highly disordered blood flow was observed in the stenotic (Tur [M, QR] = 12.5%, 21.5%) and distal segment (15.4%, 27.2%), particularly during systole (21.0%, 30.7%, 33.3%, 38.7%, p < 0.05). Spearman correlation analysis revealed that stenosis rate was correlated with turbulence grading in the stenotic (ρ = 0.65, p < 0.05) and distal segment (ρ = 0.79, p < 0.05), and ulcer formation was correlated with turbulence grading in the stenotic segment (ρ = 0.58, p < 0.05). The overall rate of detection of three flow patterns was higher in the severe stenosis group (22/22) versus the mild to moderate stenosis group (21/38) (p < 0.001) and in the ulcer group (21/23) versus the non-ulcer group (23/37) (p < 0.001). CONCLUSION: High-frame-rate vector flow imaging was helpful in assessing the severity and characteristics of flow turbulence. Lumen geometric factors could affect flow turbulence and blood flow patterns around the plaque. This would provide important hemodynamic information for the detection of high-risk plaque.

Characteristics and Correlations of Wall Shear Stress and Flow Turbulence in the Carotid Bifurcation Evaluated Using an Ultrasound Vector Flow Imaging.

INTRODUCTION: The aim of the study was to evaluate characteristics and provide the normal values of wall shear stress (WSS) and flow turbulence (Tur), and the relationship between them in the carotid bifurcation based on an ultrasound vector flow imaging (V Flow) in healthy adults. METHODS: Max and mean WSS and Tur values at three segments (initial segments of internal and external carotid arteries [IICA and IECA]; distal segment of common carotid artery [DCCA]), both in anterior and posterior walls, were successfully obtained in 56 healthy adults, using ultrasound V Flow function. Relationship between mean WSS and Tur was further explored. RESULTS: The mean WSS value was 0.71 Pa, 0.86 Pa, and 0.96 Pa at IICA, IECA, and DCCA, respectively (IICA < IECA < DCCA, p < 0.05). The mean Tur value was 13.85%, 5.46%, and 4.17% at IICA, IECA, and DCCA, respectively (IICA > IECA > DCCA, p < 0.05). A cutoff value (WSS = 0.4 Pa) was selected and Tur values were significantly higher in group with WSS cutoff value <0.4 Pa than group with WSS cutoff value ≥0.4 Pa (p < 0.01). CONCLUSION: WSS and Tur are moderately negatively correlated, which can be used in the quantitative evaluation of carotid bifurcation and could be a potential dual-parameter tool in the clinical research for early detection of carotid atherosclerosis.

Precise evaluation of blood flow patterns in human carotid bifurcation based on high-frame-rate vector flow imaging.

PURPOSE: To investigate the feasibility of high-frame-rate vector flow imaging (HiFR-VFI) compared to ultrasound color Doppler flow imaging (CDFI) for precisely evaluating flow characteristics in the carotid bifurcation (CB) of presumed healthy adults. METHODS: Forty-three volunteers were assessed for flow characteristics and their extensions using HiFR-VFI and CDFI in CBs. The flow patterns were classified according to the streamlines in HiFR-VFI and quantitatively measured using an innovative turbulence index (Tur-value). Interobserver agreement was also assessed. RESULTS: HiFR-VFI was consistent with CDFI in detecting laminar and nonlaminar flow in 81.4% of the cases; however, in 18.6% of the cases, only HiFR-VFI identified the nonlaminar flow. HiFR-VFI showed a larger extension of complex flow (0.37 ± 0.26 cm2 ) compared to CDFI (0.22 ± 0.21 cm2 ; p < 0.05). The flow patterns were classified into four types: 3 type-I (laminar flow), 35 type-II (rotational flow), 27 type-III (reversed flow), and 5 type-IV (complex flow). The Tur-value of type-IV (50.03 ± 14.97)% is larger than type-III (44.57 ± 8.89)%, type-II (16.30 ± 8.16)%, and type-I (1.48 ± 1.43)% (p < 0.05). Two radiologists demonstrated almost perfect interobserver agreement on recognizing the change of streamlines (κ = 0.81, p < 0.001). The intraclass correlation coefficient of the Tur-value was 0.98. CONCLUSION: HiFR-VFI can reliably characterize complex hemodynamics with quantitative turbulence measurement and may be an auxiliary diagnostic tool for assessing atherosclerotic arterial disease.

Feasibility study of combining wall shear stress and elastography to assess the vascular status of carotid artery.

INTRODUCTION: At present, early detection of the potential risk of atherosclerosis and prevention is of great significance to reduce the occurrence of stroke. AIM: This study aims to explore the value of combining the wall shear stress measured by ultrasound vector flow imaging technique and sound touch elastography of common carotid artery in normal adults using the Mindray Resona 7 ultrasound system. METHODS: Forty volunteers (mean age 39.5 y, 23 females, 17 males) were divided into four groups according to their age. All volunteers underwent ultrasound carotid artery examination, and the values of wall shear stress and elasticity on the posterior wall of the common carotid artery were measured using advanced imaging functions, vector flow imaging technique, and sound touch elastography. RESULTS: Different cut-off values of wall shear stress were used to investigate the significance between two groups with corresponding sound touch elastography values. It can be seen that the statistical difference could be found when the mean wall shear stress was larger than 1.5 Pa approximately (statistical significance was defined when P < 0.05), and the sound touch elastography value was positively correlated with the wall shear stress value. CONCLUSION: This study reveals that the combination of wall shear stress and sound touch elastography is an effective and feasible method for assessing carotid artery health. When the mean wall shear stress value is over 1.5 Pa, the corresponding sound touch elastography value increases significantly. The risk of atherosclerosis increases with the stiffness of blood vessel walls.

Blood Flow Turbulence Quantification of Carotid Artery With a High-Frame Rate Vector Flow Imaging.

OBJECTIVES: To assess the feasibility and performance of Turbulence (Tur) index as a quantitative tool for carotid artery flow turbulence; to detect and compare the blood flow patterns of common carotid artery (CCA) and carotid bulb (CB) at different ages and cardiac phases in healthy adults, and thus interpret the evolvement of etiology difference between CCA and CB. METHODS: Carotid flow characteristics of 40 healthy volunteers were evaluated quantitatively by a high-frame rate vector flow imaging. Three types of flow patterns were defined depending on the distributive range of complex flow during systole in CB. Comparison of mean Tur value in CCA and CB at different age groups and cardiac phases was performed. And the correlation between Tur value and the diameter ratio of proximal internal carotid artery to common carotid artery (DRpro-ica/cca) was tested. RESULTS: Mean Tur values in CB were remarkably higher than that in CCA, whether during systole or diastole (P < .001). Meanwhile Tur values in CB during systole were significantly higher than that during diastole (P < .001). Flow complexity of CB showed variations among 40 participants especially in systole, whereas the flow pattern of CCA was relatively consistent. Mean Tur values were positively correlated with DRpro-ica/cca in CB (ρ = 0.69, P < .05). CONCLUSIONS: V Flow imaging provided a reliable method-Tur, for quantitative analysis of carotid blood flow. It had potential to be further applied in distinguishing complex hemodynamic characteristics in high-risk people of carotid diseases for the risk stratification of cardiovascular events.

Investigation on the differences of hemodynamics in normal common carotid, subclavian, and common femoral arteries using the vector flow technique.

Objectives: To investigate the feasibility of the vector flow imaging (V Flow) technique to measure peripheral arterial hemodynamic parameters, including wall shear stress (WSS) and turbulence index (Tur) in healthy adults, and compare the results in different arteries. Materials and methods: Fifty-two healthy adult volunteers were recruited in this study. The maximum and mean values of WSS, and the Tur values at early-systole, mid-systole, late-systole, and early diastole for total 156 normal peripheral arteries [common carotid arteries (CCA), subclavian arteries (SCA), and common femoral arteries (CFA)] were assessed using the V Flow technique. Results: The mean WSS values for CCA, SCA, and CFA were (1.66 ± 0.68) Pa, (0.62 ± 0.30) Pa, and (0.56 ± 0.27) Pa, respectively. The mean Tur values for CCA, SCA, and CFA were (0.46 ± 1.09%), (20.7 ± 9.06%), and (24.63 ± 17.66%), respectively. The CCA and SCA, as well as the CCA and CFA, showed statistically significant differences in the mean WSS and the mean Tur (P < 0.01). The mean Tur values had a negative correlation with the mean WSS; the correlation coefficient between log(Tur) and WSS is -0.69 (P < 0.05). Conclusion: V Flow technique is a simple, practical, and feasible quantitative imaging approach for assessing WSS and Tur in peripheral arteries. It has the potential to be a useful tool for evaluating atherosclerotic plaques in peripheral arteries. The results provide a new quantitative foundation for future investigations into diverse arterial hemodynamic parameters.

Diagnostic performance of elastography for breast non-mass lesions: A systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the diagnostic performance of ultrasound elastography in the differentiation of benign and malignant breast non-mass lesions (NMLs). METHODS: PubMed, Cochrane Library, and Embase databases were searched for eligible studies up to end of June 2021. The diagnostic performance of elastography for NMLs was investigated using pooled sensitivity and specificity, likelihood ratio, diagnostic odds ratio (DOR), post-test probability, and the area under hierarchical summary receiver operating characteristic curve (HSROC). RESULTS: Eleven studies involving 812 NMLs (malignant 414) were included. The pooled sensitivity, specificity, DOR, positive likelihood ratio, and negative likelihood of elastography for the differentiation of benign and malignant breast NMLs were 79% (95 %CI: 71-85), 86% (95 %CI: 79-91), 23.32 (95 %CI: 13.38-40.66), 5.67 (95 %CI: 3.79-8.47), and 0.24 (95 %CI: 0.17-0.34), respectively. No significant publication bias existed. The area under the HSROC curve was 90% (95 %CI: 87-92). Fagan plots demonstrated good clinical utility. However, substantial heterogeneity existed. Country, measurement index, and number of lesions served as potential sources of heterogeneity. CONCLUSIONS: The results of this study suggest that elastography has high diagnostic accuracy in differentiating between malignant and benign NMLs. Elastography can be a feasible and non-invasive tool for breast NMLs.

Synergistic effects of negative-charged nanoparticles assisted by ultrasound on the reversal multidrug resistance phenotype in breast cancer cells.

We have fabricated a negative-charged nanoparticle (Heparin-Folate-Tat-Taxol NP, H-F-Tat-T NP) with dual ligands, tumor targeting ligand folate and cell-penetrating peptide Tat, to deliver taxol presenting great anticancer activity for sensitive cancer cells, while it fails to overcome multidrug resistance (MDR) in MCF-7/T cells (taxol-resistant breast cancer cells). Ultrasound (US) can increase the sensitivity of positive-charged NPs thereby making it possible to reverse MDR through inducing NPs' drug release. However, compared with the negative-charged NPs, positive-charged NPs may cause higher toxic effect. Hence, the combination of negative-charged NPs and US may be an efficient strategy for overcoming MDR. The conventional procedure to treat with NPs followed by US exposure possibly destruct multifunctional NPs resulting in its bioactivity inhibition. Herein, we have further improved the operating approach to eliminate US mechanical damage and keep the integrity of negative-charged NPs: cells are exposed to US with microbubbles (MBs) prior to the treatment of H-F-Tat-T NPs. Superior to the conventional method, US sonoporation affects the physiological property of cancer cells while preventing direct promotion of drug release from NPs. The results of the present study displayed that US in condition (1MHz, 10% duty cycle, duration of 80s, US intensity of 0.6W/cm2 and volume ratio of medium to MBs 20:1) combined with H-F-T-Tat-T NPs can achieve optimal reversal MDR effect in MCF-7/T cells. Mechanism study further disclosed that the individual effect of US was responsible for the enhancement of cell membrane permeability, inhibition of cell proliferation rate and down-regulation of MDR-related genes and proteins. Simultaneously, US sonoporation on resistant cancer cells indirectly increased the accumulation of NPs by inducing endosomal escape of negative-charged NPs. Taken together, the overcoming MDR ability for the combined strategy was achieved by the synergistic effect from individual function of NPs, physiological changes of resistant cancer cells and behavior changes of NPs caused by US.

Laser acupuncture attenuates oxaliplatin-induced peripheral neuropathy in patients with gastrointestinal cancer: a pilot prospective cohort study.

BACKGROUND: Oxaliplatin is a platinum compound that is widely used in the treatment of some solid tumours. Oxaliplatin-induced peripheral neuropathy (OIPN) in the upper and lower extremities is the major adverse side effect and represents the main dose-limiting factor of this drug. The aim of this single-arm study was to evaluate the feasibility and effects of laser acupuncture (LA) in the treatment of OIPN in patients with advanced gastrointestinal cancers. METHODS: 17 gastrointestinal cancer survivors (14 colorectal and 3 gastric cancers), who had been treated with oxaliplatin-based chemotherapies, were recruited. Low-level laser stimulation (50 mW) bilaterally at PC6, PC7, PC8, P9, LU11, SP6, KI3, BL60, KI1, and KI2 was administered for 20 min/point for 12 sessions over 4 weeks. The pain quality assessment scale (PQAS), chemotherapy-induced neurotoxicity questionnaire (CINQ), oxaliplatin-specific neurotoxicity scale (OSNS), quantitative touch-detection threshold (using von Frey filaments), and cold-triggered pain withdrawal latency (using the cold-water immersion test) were measured before and after completion of the 12 treatment sessions. RESULTS: PQAS, CINQ, and OSNS scores, as well as touch-detection threshold and cold-trigger pain withdrawal latency all improved significantly after LA in the cancer patients with OIPN (p<0.05). LA significantly relieved both oxaliplatin-induced cold and mechanical allodynia and also decreased the incidence and severity of neurotoxicity symptoms in the patients' upper and lower extremities and impact on their daily activities (all p<0.05). CONCLUSIONS: Following treatment with LA, neurotoxicity symptoms were significantly improved in cancer patients with OIPN. Further randomised controlled trials are needed to evaluate the role of LA as a therapeutic option in the management of OIPN.

Response of heterogeneous cancer cells on targeted nanoparticles.

Heterogenous cancer cells possess cancer multidrug resistance (MDR) due to their relative quiescence and ABC-transporter expression. Heterogenous cancer cells can be detected by an Rh123 exclusion assay for identifying Rh123low population. In the present study, we fabricated targeted nanoparticles entrapped with Rh123 (Rh123 NPs) to investigate the effect of these targeted nanoparticles on an Rh123low population. The Rh123low population stained by Rh123 NPs exhibited similar heterogeneity to that stained by Rh123. In addition, the ABC-transporters did not contribute to the uptake of Rh123 or Rh123 NPs. Interestingly, ABC-transporters in the Rh123low population stained by Rh123 were possibly responsible for Rh123 efflux, while Rh123 NPs were not susceptible to ABC-transporters in the Rh123low population. It is plausible that the synergistic effect of NPs caused a targeted and endocytic effect which promoted the cellular uptake of Rh123 NPs, and the targeted effect played a more important role.