Automatic Diagnosis of Carotid Atherosclerosis Using a Portable Freehand 3-D Ultrasound Imaging System.

The objective of this study is to develop a deep-learning-based detection and diagnosis technique for carotid atherosclerosis (CA) using a portable freehand 3-D ultrasound (US) imaging system. A total of 127 3-D carotid artery scans were acquired using a portable 3-D US system, which consisted of a handheld US scanner and an electromagnetic (EM) tracking system. A U-Net segmentation network was first applied to extract the carotid artery on 2-D transverse frame, and then, a novel 3-D reconstruction algorithm using fast dot projection (FDP) method with position regularization was proposed to reconstruct the carotid artery volume. Furthermore, a convolutional neural network (CNN) was used to classify healthy and diseased cases qualitatively. Three-dimensional volume analysis methods, including longitudinal image acquisition and stenosis grade measurement, were developed to obtain the clinical metrics quantitatively. The proposed system achieved a sensitivity of 0.71, a specificity of 0.85, and an accuracy of 0.80 for diagnosis of CA. The automatically measured stenosis grade illustrated a good correlation ( r = 0.76) with the experienced expert measurement. The developed technique based on 3-D US imaging can be applied to the automatic diagnosis of CA. The proposed deep-learning-based technique was specially designed for a portable 3-D freehand US system, which can provide a more convenient CA examination and decrease the dependence on the clinician's experience.

The association between metabolic dysfunction-associated steatotic liver disease, cardiovascular and cerebrovascular diseases and the thickness of carotid plaque.

BACKGROUND: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and atherosclerosis has been controversial, which has become a hit of recent research. The study aimed to explore the association between MASLD, cardiovascular and cerebrovascular diseases (CCVD), and the thickness of carotid plaque which was assessed by ultrasound. METHODS: From September 2018 to June 2019, 3543 patients were enrolled. We asked participants to complete questionnaires to obtain information. All patients underwent liver ultrasound and bilateral carotid ultrasound to obtain carotid intima-media thickness (IMT) and maximum carotid plaque thickness (CPT). Hepatic steatosis was quantified during examination according to Hamaguchi's ultrasonographic score, from 0 to 6 points. A score < 2 was defined as without fatty liver, and a score ≥ 2 was defined as fatty liver. Information about blood lipids was collected based on the medical records. RESULTS: We found common risk factors for CCVD events, MASLD, and atherosclerosis. There was a significant correlation between MASLD and carotid plaque, but not with CPT. No association was found between MASLD and CCVD events. CPT and IMT were thicker in CCVD patients than in non-CCVD patients. No significant difference was found between IMT and CPT in MASLD patients and non-MASLD patients. CCVD was independently and consistently associated with higher IMT, and free fatty acid (FFA). CONCLUSIONS: According to our results, we recommend carotid ultrasound examination of the patients when FFA is increased, regardless of the presence of risk factors and MASLD. Due to the distribution of CPT of both CCVD and MASLD patients in the CPT 2-4 mm group, contrast-enhanced ultrasound is necessary to assess the vulnerability of the plaque when CPT ≥ 2 mm. Timely treatment of vulnerable plaques may reduce the incidence of future CCVD events.

The clinical value of carotid plaque score in patients with metabolic syndrome and cardiovascular diseases.

OBJECTIVE: To investigate the relationship between carotid plaque load score (CPS) and metabolic syndrome (MS) and cardiovascular diseases (CVD), in order to provide theoretical basis for the precaution and control of MS and CVD. METHODS: A total of 1962 patients were incorporated into the study and divided into MS group and non-MS group, CVD group and non-CVD group. CPS and CIMT were obtained by carotid artery ultrasound, and the data of each group were statistically analyzed. RESULTS: Age, BMI, basal metabolic rate, body fat rate, gender, and the incidence of central obesity, hypertension, diabetes and dyslipidemia are statistical different between MS group and non-MS group (P < 0.05). CIMT between CVD group and non-CVD group are statistical different (1.040 ± 0.239 VS 0.972 ± 0.297, P < 0.001). CPS was statistically significant between MS group and non-MS group(2.254 ± 2.728 VS 1.548 ± 2.219, P = 0.003) and between CVD group and non-CVD group (2.322 ± 2.760 VS 1.688 ± 2.347, P = 0.004). CONCLUSION: Patients in MS group and CVD group have higher carotid plaque burden than those in non-MS group and non-CVD group. The higher the CPS was, the higher the incidence of MS and CVD was, and the distribution of CPS in MS and CVD population was consistent.

BP-Net: Boundary and perfusion feature guided dual-modality ultrasound video analysis network for fibrous cap integrity assessment.

Ultrasonography is one of the main imaging methods for monitoring and diagnosing atherosclerosis due to its non-invasiveness and low-cost. Automatic differentiation of carotid plaque fibrous cap integrity by using multi-modal ultrasound videos has significant diagnostic and prognostic value for cardiovascular and cerebrovascular disease patients. However, the task faces several challenges, including high variation in plaque location and shape, the absence of analysis mechanism focusing on fibrous cap, the lack of effective mechanism to capture the relevance among multi-modal data for feature fusion and selection, etc. To overcome these challenges, we propose a new target boundary and perfusion feature guided video analysis network (BP-Net) based on conventional B-mode ultrasound and contrast-enhanced ultrasound videos for assessing the integrity of fibrous cap. Based on our previously proposed plaque auto-tracking network, in our BP-Net, we further introduce the plaque edge attention module and reverse mechanism to focus the dual video analysis on the fiber cap of plaques. Moreover, to fully explore the rich information on the fibrous cap and inside/outside of the plaque, we propose a feature fusion module for B-mode and contrast video to filter out the most valuable features for fibrous cap integrity assessment. Finally, multi-head convolution attention is proposed and embedded into transformer-based network, which captures semantic features and global context information to obtain accurate evaluation of fibrous caps integrity. The experimental results demonstrate that the proposed method has high accuracy and generalizability with an accuracy of 92.35% and an AUC of 0.935, which outperforms than the state-of-the-art deep learning based methods. A series of comprehensive ablation studies suggest the effectiveness of each proposed component and show great potential in clinical application.

Voacamine is a novel inhibitor of EGFR exerting oncogenic activity against colorectal cancer through the mitochondrial pathway.

Colorectal cancer (CRC), among the most aggressive and prevailing neoplasms, is primarily treated with chemotherapy. Voacamine (VOA), a novel bisindole natural product, possesses a variety of conspicuous pharmacological activities. Within the current research, we evaluated in vitro and in vivo the anticancer efficacy of VOA against CRC and its potential mechanisms. Our results illustrated that VOA concentrationdependently suppressed the proliferation and migration of CT26 and HCT116 cells as correspondingly indicated by IC50 values of 1.38 ± 0.09 µM and 4.10 ± 0.14 µM. Furthermore, treatment of VOA also suppressed tumor cell colony formation, escalated the late-stage apoptosis rate of tumor cells, and evoked cell cycle of CT26 and HCT116 cells arrest inhibition in G2-M and G0-G1 phases, respectively. Meanwhile, VOA markedly disrupted the mitochondrial membrane potential eliciting mitochondrial dysfunction, decreased ATP production, and intermediated an enhanced accumulation of intracellular reactive oxygen species with a concentration-dependent pattern, accompanied by elevated expression levels of pro-apoptotic related protein Bax, Cyt-C, cleaved caspases 3/8/9 and by diminished Bcl-2, Bid, PRAP and caspases 3/8/9 expression. Further mechanistic studies revealed VOA treatment suppressed the EGFR/PI3K/Akt pathway with the evidence of the decreased phosphorylation proteins of EGFR, PI3K, Akt, and downstream proteins of p-mTOR, p-NF-kB, and p-P70S6. Additionally, molecular dynamics simulations further displayed VOA could enter the EGFR pocket followed by multiple mutual interaction effects. Interestingly, the EGFR activator (NSC228155) could slack the inhibitory capability of VOA on the EGFR/PI3K/Akt pathway as well as VOA-induced impairment of mitochondrial function. Finally, administration of VOA (15, 30 mg/kg every 2 days, i.p., for 16 days) in CT26 syngeneic mice dose-dependently suppressed the neoplastic development without appreciable organ toxicities. Taken together, our study demonstrated that VOA may be a prospective therapeutic agent for the treatment of CRC.

Carotid artery vulnerable plaque model for cerebrovascular events by conventional ultrasound & contrast-enhanced ultrasound: A preliminary study.

BACKGROUND: Conventional ultrasound and contrast-enhanced ultrasound play an important role in the application of carotid plaque. AIMS: To establish carotid artery vulnerable plaques model by conventional ultrasound combined with contrast-enhanced ultrasound, identify high-risk plaques that may lead to cerebrovascular events, and provide clinical risk warning of high-risk plaques of stroke. METHODS: 205 cases of patients selected in 5053 patients with symptoms from 2018 to 2019 who were verified carotid plaques by conventional ultrasound and contrast-enhanced ultrasound image characteristics, 147 cases as a training set, establishing the carotid artery plaque model, analyzing the characteristic of the plaques and the relationship between cerebrovascular event, with 58 cases as a test set, verify the model. Routine carotid ultrasound and contrast-enhanced carotid ultrasound were performed in all enrolled patients. RESULTS: The gray-level characteristics of conventional ultrasound in the training concentration showed statistical differences in plaque morphology, fibrous cap morphology, uniformity and calcification degree in cerebrovascular events. The contrast enhanced ultrasound characteristics of plaques showed statistical differences in neovascularization and perfusion mode in cerebrovascular events. In the test set, there were statistical differences in the above conventional gray scale features and CEUS features. CONCLUSION: The vulnerable plaque model established by conventional ultrasound combined with contrast-enhanced ultrasound has good diagnostic value for the characteristic plaque of carotid artery with cerebrovascular events.

Automatic multi-plaque tracking and segmentation in ultrasonic videos.

Carotid plaque tracking and segmentation in ultrasound videos is the premise for subsequent plaque property evaluation and treatment plan development. However, the task is quite challenging, as it needs to address the problems of poor image quality, plaque shape variations among frames, the existence of multiple plaques, etc. To overcome these challenges, we propose a new automatic multi-plaque tracking and segmentation (AMPTS) framework. AMPTS consists of three modules. The first module is a multi-object detector, in which a Dual Attention U-Net is proposed to detect multiple plaques and vessels simultaneously. The second module is a set of single-object trackers that can utilize the previous tracking results efficiently and achieve stable tracking of the current target by using channel attention and a ranking strategy. To make the first module and the second module work together, a parallel tracking module based on a simplified 'tracking-by-detection' mechanism is proposed to solve the challenge of tracking object variation. Extensive experiments are conducted to compare the proposed method with several state-of-the-art deep learning based methods. The experimental results demonstrate that the proposed method has high accuracy and generalizability with a Dice similarity coefficient of 0.83 which is 0.16, 0.06 and 0.27 greater than MAST (Lai et al., 2020), Track R-CNN (Voigtlaender et al., 2019) and VSD (Yang et al., 2019) respectively and has made significant improvements on seven other indicators. In the additional Testing set 2, our method achieved a Dice similarity coefficient of 0.80, an accuracy of 0.79, a precision of 0.91, a Recall 0.70, a F1 score of 0.79, an AP@0.5 of 0.92, an AP@0.7 of 0.74, and an expected average overlap of 0.79. Numerous ablation studies suggest the effectiveness of each proposed component and the great potential for multiple carotid plaques tracking and segmentation in clinical practice.

Contrast-enhanced ultrasound perfusion patterns and serum lipid signatures of vulnerable carotid artery plaque in predicting stroke: A cohort study of carotid stenosis in Chinese patients.

BACKGROUND: Early identification of vulnerable plaques at risk of rupture could help prevent cerebral ischemic stroke in patients with carotid artery disease. OBJECTIVE: To investigate the correlation between contrast-enhanced ultrasound (CEUS) perfusion patterns and serum lipid signatures of carotid artery plaques with the degree of carotid stenosis. METHODS: A total of 80 patients with carotid artery plaques who underwent CEUS were included. All patients underwent CEUS, computed tomography angiography or digital subtraction angiography, and serum lipid testing. RESULTS: The contrast agent enhancement levels and the CEUS perfusion patterns in the plaques were associated with the degree of carotid stenosis (P < 0.05). Serum free fatty acid (FFA) was associated with the contrast agent enhancement levels (P < 0.05), but did not correlate with the degree of stenosis (P > 0.05). There was no significant difference in total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides with respect to contrast agent enhancement levels (P > 0.05) or the degree of stenosis (P > 0.05). CONCLUSION: A high level of CEUS perfusion and increased serum FFA levels are indicative of vulnerable carotid plaques, which may be useful for the prediction of stroke in patients with carotid artery disease.