Deep Learning Paradigm for Cardiovascular Disease/Stroke Risk Stratification in Parkinson's Disease Affected by COVID-19: A Narrative Review.

Background and Motivation: Parkinson's disease (PD) is one of the most serious, non-curable, and expensive to treat. Recently, machine learning (ML) has shown to be able to predict cardiovascular/stroke risk in PD patients. The presence of COVID-19 causes the ML systems to become severely non-linear and poses challenges in cardiovascular/stroke risk stratification. Further, due to comorbidity, sample size constraints, and poor scientific and clinical validation techniques, there have been no well-explained ML paradigms. Deep neural networks are powerful learning machines that generalize non-linear conditions. This study presents a novel investigation of deep learning (DL) solutions for CVD/stroke risk prediction in PD patients affected by the COVID-19 framework. Method: The PRISMA search strategy was used for the selection of 292 studies closely associated with the effect of PD on CVD risk in the COVID-19 framework. We study the hypothesis that PD in the presence of COVID-19 can cause more harm to the heart and brain than in non-COVID-19 conditions. COVID-19 lung damage severity can be used as a covariate during DL training model designs. We, therefore, propose a DL model for the estimation of, (i) COVID-19 lesions in computed tomography (CT) scans and (ii) combining the covariates of PD, COVID-19 lesions, office and laboratory arterial atherosclerotic image-based biomarkers, and medicine usage for the PD patients for the design of DL point-based models for CVD/stroke risk stratification. Results: We validated the feasibility of CVD/stroke risk stratification in PD patients in the presence of a COVID-19 environment and this was also verified. DL architectures like long short-term memory (LSTM), and recurrent neural network (RNN) were studied for CVD/stroke risk stratification showing powerful designs. Lastly, we examined the artificial intelligence bias and provided recommendations for early detection of CVD/stroke in PD patients in the presence of COVID-19. Conclusion: The DL is a very powerful tool for predicting CVD/stroke risk in PD patients affected by COVID-19.

Cardiovascular Risk Stratification in Diabetic Retinopathy via Atherosclerotic Pathway in COVID-19/Non-COVID-19 Frameworks Using Artificial Intelligence Paradigm: A Narrative Review.

Diabetes is one of the main causes of the rising cases of blindness in adults. This microvascular complication of diabetes is termed diabetic retinopathy (DR) and is associated with an expanding risk of cardiovascular events in diabetes patients. DR, in its various forms, is seen to be a powerful indicator of atherosclerosis. Further, the macrovascular complication of diabetes leads to coronary artery disease (CAD). Thus, the timely identification of cardiovascular disease (CVD) complications in DR patients is of utmost importance. Since CAD risk assessment is expensive for low-income countries, it is important to look for surrogate biomarkers for risk stratification of CVD in DR patients. Due to the common genetic makeup between the coronary and carotid arteries, low-cost, high-resolution imaging such as carotid B-mode ultrasound (US) can be used for arterial tissue characterization and risk stratification in DR patients. The advent of artificial intelligence (AI) techniques has facilitated the handling of large cohorts in a big data framework to identify atherosclerotic plaque features in arterial ultrasound. This enables timely CVD risk assessment and risk stratification of patients with DR. Thus, this review focuses on understanding the pathophysiology of DR, retinal and CAD imaging, the role of surrogate markers for CVD, and finally, the CVD risk stratification of DR patients. The review shows a step-by-step cyclic activity of how diabetes and atherosclerotic disease cause DR, leading to the worsening of CVD. We propose a solution to how AI can help in the identification of CVD risk. Lastly, we analyze the role of DR/CVD in the COVID-19 framework.

Cardiovascular/Stroke Risk Assessment in Patients with Erectile Dysfunction-A Role of Carotid Wall Arterial Imaging and Plaque Tissue Characterization Using Artificial Intelligence Paradigm: A Narrative Review.

PURPOSE: The role of erectile dysfunction (ED) has recently shown an association with the risk of stroke and coronary heart disease (CHD) via the atherosclerotic pathway. Cardiovascular disease (CVD)/stroke risk has been widely understood with the help of carotid artery disease (CTAD), a surrogate biomarker for CHD. The proposed study emphasizes artificial intelligence-based frameworks such as machine learning (ML) and deep learning (DL) that can accurately predict the severity of CVD/stroke risk using carotid wall arterial imaging in ED patients. METHODS: Using the PRISMA model, 231 of the best studies were selected. The proposed study mainly consists of two components: (i) the pathophysiology of ED and its link with coronary artery disease (COAD) and CHD in the ED framework and (ii) the ultrasonic-image morphological changes in the carotid arterial walls by quantifying the wall parameters and the characterization of the wall tissue by adapting the ML/DL-based methods, both for the prediction of the severity of CVD risk. The proposed study analyzes the hypothesis that ML/DL can lead to an accurate and early diagnosis of the CVD/stroke risk in ED patients. Our finding suggests that the routine ED patient practice can be amended for ML/DL-based CVD/stroke risk assessment using carotid wall arterial imaging leading to fast, reliable, and accurate CVD/stroke risk stratification. SUMMARY: We conclude that ML and DL methods are very powerful tools for the characterization of CVD/stroke in patients with varying ED conditions. We anticipate a rapid growth of these tools for early and better CVD/stroke risk management in ED patients.

Nutrition, atherosclerosis, arterial imaging, cardiovascular risk stratification, and manifestations in COVID-19 framework: a narrative review.

Background: Atherosclerosis is the primary cause of the cardiovascular disease (CVD). Several risk factors lead to atherosclerosis, and altered nutrition is one among those. Nutrition has been ignored quite often in the process of CVD risk assessment. Altered nutrition along with carotid ultrasound imaging-driven atherosclerotic plaque features can help in understanding and banishing the problems associated with the late diagnosis of CVD. Artificial intelligence (AI) is another promisingly adopted technology for CVD risk assessment and management. Therefore, we hypothesize that the risk of atherosclerotic CVD can be accurately monitored using carotid ultrasound imaging, predicted using AI-based algorithms, and reduced with the help of proper nutrition. Layout: The review presents a pathophysiological link between nutrition and atherosclerosis by gaining a deep insight into the processes involved at each stage of plaque development. After targeting the causes and finding out results by low-cost, user-friendly, ultrasound-based arterial imaging, it is important to (i) stratify the risks and (ii) monitor them by measuring plaque burden and computing risk score as part of the preventive framework. Artificial intelligence (AI)-based strategies are used to provide efficient CVD risk assessments. Finally, the review presents the role of AI for CVD risk assessment during COVID-19. Conclusions: By studying the mechanism of low-density lipoprotein formation, saturated and trans fat, and other dietary components that lead to plaque formation, we demonstrate the use of CVD risk assessment due to nutrition and atherosclerosis disease formation during normal and COVID times. Further, nutrition if included, as a part of the associated risk factors can benefit from atherosclerotic disease progression and its management using AI-based CVD risk assessment.

A Review on Joint Carotid Intima-Media Thickness and Plaque Area Measurement in Ultrasound for Cardiovascular/Stroke Risk Monitoring: Artificial Intelligence Framework.

Cardiovascular diseases (CVDs) are the top ten leading causes of death worldwide. Atherosclerosis disease in the arteries is the main cause of the CVD, leading to myocardial infarction and stroke. The two primary image-based phenotypes used for monitoring the atherosclerosis burden is carotid intima-media thickness (cIMT) and plaque area (PA). Earlier segmentation and measurement methods were based on ad hoc conventional and semi-automated digital imaging solutions, which are unreliable, tedious, slow, and not robust. This study reviews the modern and automated methods such as artificial intelligence (AI)-based. Machine learning (ML) and deep learning (DL) can provide automated techniques in the detection and measurement of cIMT and PA from carotid vascular images. Both ML and DL techniques are examples of supervised learning, i.e., learn from "ground truth" images and transformation of test images that are not part of the training. This review summarizes (1) the evolution and impact of the fast-changing AI technology on cIMT/PA measurement, (2) the mathematical representations of ML/DL methods, and (3) segmentation approaches for cIMT/PA regions in carotid scans based for (a) region-of-interest detection and (b) lumen-intima and media-adventitia interface detection using ML/DL frameworks. AI-based methods for cIMT/PA segmentation have emerged for CVD/stroke risk monitoring and may expand to the recommended parameters for atherosclerosis assessment by carotid ultrasound.

Subclinical atherosclerosis in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis is an inflammatory disorder of the central nervous system. Inflammation may create high susceptibility to subclinical atherosclerosis. The purpose of this study was to compare subclinical atherosclerosis and the role of inflammatory cytokines between the group of patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls matched for age and sex. METHODS: The study group consisted of 112 non-diabetic and non-hypertensive RRMS patients treated with disease modifying drugs (DMD) and the control group was composed of 51 healthy subjects. The common carotid artery (CCA) intima media thickness (IMT) was investigated. Serum levels of risk factors for atherosclerosis and inflammatory cytokines were also determined. RESULTS: The mean CCA IMT (0.572 ± 0.131 mm vs. 0.571 ± 0.114 mm) did not differ (p > 0.05) between patients and controls. The RRMS patients' CCA IMT was significantly correlated with serum interleukin 6 (IL-6) (p = 0.027), high-sensitivity C-reactive protein (hs-CRP) (p = 0.027), cystatin C (p < 0.0005), glucose (p = 0.031), cholesterol (p = 0.008), LDL (p = 0.021), erythrocyte sedimentation rate (p = 0.001) and triglyceride (p = 0.018) level. We fitted generalized linear models in order to assess the relationship between CCA IMT and IL­6 with adjustment for sex and age. The obtained results showed that adjusted for age (p < 0.001) and sex (p = 0.048) IL­6 serum levels statistically significantly (p = 0.009) predict CCA IMT only in the RRMS group. CONCLUSION: The findings of the present study suggest that when treated with DMD RRMS might not be an independent risk factor for early atherosclerosis presenting with arterial wall thickening; however, the results suggest a significant association of IL­6 serum levels with CCA IMT only in the RRMS group.

A Special Report on Changing Trends in Preventive Stroke/Cardiovascular Risk Assessment Via B-Mode Ultrasonography.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) and stroke risk assessment have been largely based on the success of traditional statistically derived risk calculators such as Pooled Cohort Risk Score or Framingham Risk Score. However, over the last decade, automated computational paradigms such as machine learning (ML) and deep learning (DL) techniques have penetrated into a variety of medical domains including CVD/stroke risk assessment. This review is mainly focused on the changing trends in CVD/stroke risk assessment and its stratification from statistical-based models to ML-based paradigms using non-invasive carotid ultrasonography. RECENT FINDINGS: In this review, ML-based strategies are categorized into two types: non-image (or conventional ML-based) and image-based (or integrated ML-based). The success of conventional (non-image-based) ML-based algorithms lies in the different data-driven patterns or features which are used to train the ML systems. Typically these features are the patients' demographics, serum biomarkers, and multiple clinical parameters. The integrated (image-based) ML-based algorithms integrate the features derived from the ultrasound scans of the arterial walls (such as morphological measurements) with conventional risk factors in ML frameworks. Even though the review covers ML-based system designs for carotid and coronary ultrasonography, the main focus of the review is on CVD/stroke risk scores based on carotid ultrasound. There are two key conclusions from this review: (i) fusion of image-based features with conventional cardiovascular risk factors can lead to more accurate CVD/stroke risk stratification; (ii) the ability to handle multiple sources of information in big data framework using artificial intelligence-based paradigms (such as ML and DL) is likely to be the future in preventive CVD/stroke risk assessment.

The present and future of deep learning in radiology.

The advent of Deep Learning (DL) is poised to dramatically change the delivery of healthcare in the near future. Not only has DL profoundly affected the healthcare industry it has also influenced global businesses. Within a span of very few years, advances such as self-driving cars, robots performing jobs that are hazardous to human, and chat bots talking with human operators have proved that DL has already made large impact on our lives. The open source nature of DL and decreasing prices of computer hardware will further propel such changes. In healthcare, the potential is immense due to the need to automate the processes and evolve error free paradigms. The sheer quantum of DL publications in healthcare has surpassed other domains growing at a very fast pace, particular in radiology. It is therefore imperative for the radiologists to learn about DL and how it differs from other approaches of Artificial Intelligence (AI). The next generation of radiology will see a significant role of DL and will likely serve as the base for augmented radiology (AR). Better clinical judgement by AR will help in improving the quality of life and help in life saving decisions, while lowering healthcare costs. A comprehensive review of DL as well as its implications upon the healthcare is presented in this review. We had analysed 150 articles of DL in healthcare domain from PubMed, Google Scholar, and IEEE EXPLORE focused in medical imagery only. We have further examined the ethic, moral and legal issues surrounding the use of DL in medical imaging.

Ranking of stroke and cardiovascular risk factors for an optimal risk calculator design: Logistic regression approach.

PURPOSE: Conventional cardiovascular risk factors (CCVRFs) and carotid ultrasound image-based phenotypes (CUSIP) are independently associated with long-term risk of cardiovascular (CV) disease. In this study, 26 cardiovascular risk (CVR) factors which consisted of a combination of CCVRFs and CUSIP together were ranked. Further, an optimal risk calculator using AtheroEdge composite risk score (AECRS1.0) was designed and benchmarked against seven conventional CV risk (CVR) calculators. METHODS: Two types of ranking were performed: (i) ranking of 26 CVR factors and (ii) ranking of eight types of 10-year risk calculators. In the first case, multivariate logistic regression was used to compute the odds ratio (OR) and in the second, receiver operating characteristic curves were used to evaluate the performance of eight types of CVR calculators using SPSS23.0 and MEDCALC12.0 with validation against STATA15.0. RESULTS: The left and right common carotid arteries (CCA) of 202 Japanese patients were examined to obtain 404 ultrasound scans. CUSIP ranked in the top 50% of the 26 covariates. Intima-media thickness variability (IMTV) and IMTV10yr were the most influential carotid phenotypes for left CCA (OR = 250, P < 0.0001 and OR = 207, P < 0.0001 respectively) and right CCA (OR = 1614, P < 0.0001 and OR = 626, P < 0.0001 respectively). However, for the mean CCA, AECRS1.0 and AECRS1.010yr reported the most highly significant OR among all the CVR factors (OR = 1.073, P < 0.0001 and OR = 1.104, P < 0.0001). AECRS1.010yr also reported highest area-under-the-curve (AUC = 0.904, P < 0.0001) compared to seven types of conventional calculators. Age and glycated haemoglobin reported highest OR (1.96, P < 0.0001 and 1.05, P = 0.012) among all other CCVRFs. CONCLUSION: AECRS1.010yr demonstrated the best performance due to presence of CUSIP and ranked at the first place with highest AUC.

Performance evaluation of 10-year ultrasound image-based stroke/cardiovascular (CV) risk calculator by comparing against ten conventional CV risk calculators: A diabetic study.

MOTIVATION: AtheroEdge Composite Risk Score (AECRS1.010yr) is an integrated stroke/cardiovascular risk calculator that was recently developed and computes the 10-year risk of carotid image phenotypes by integrating conventional cardiovascular risk factors (CCVRFs). It is therefore important to understand how closely AECRS1.010yr is associated with the ten other currently available conventional cardiovascular risk calculators (CCVRCs). METHODS: The Institutional Review Board of Toho University approved the examination of the left/right common carotid arteries of 202 Japanese patients. Step 1 consists of measurement of AECRS1.010yr, given current image phenotypes and CCVRFs. Step 2 consists of computing the risk score using ten different CCVRCs given CCVR factors: QRISK3, Framingham Risk Score (FRS), United Kingdom Prospective Diabetes Study (UKPDS) 56, UKPDS60, Reynolds Risk Score (RRS), Pooled cohort Risk Score (PCRS or ASCVD), Systematic Coronary Risk Evaluation (SCORE), Prospective Cardiovascular Munster Study (PROCAM) calculator, NIPPON, and World Health Organization (WHO) risk. Step 3 consists of computing the closeness factor between AECRS1.010yr and ten CCVRCs using cumulative ranking index derived using eight different statistically derived metrics. RESULTS: AECRS1.010yr reported the highest area-under-the-curve (0.927;P < 0.001) among all the risk calculators. The top three CCVRCs closest to AECRS1.010yr were QRISK3, FRS, and UKPDS60 with cumulative ranking scores of 2.1, 3.0, and 3.8, respectively. CONCLUSION: AECRS1.010yr produced the largest AUC due to the integration of image-based phenotypes with CCVR factors, and ranked at first place with the highest AUC. Cumulative ranking of ten CCVRCs demonstrated that QRISK3 was the closest calculator to AECRS1.010yr, which is also consistent with the industry trend.

Morphologic TPA (mTPA) and composite risk score for moderate carotid atherosclerotic plaque is strongly associated with HbA1c in diabetes cohort.

BACKGROUND: This study examines the association between six types of carotid artery disease image-based phenotypes and HbA1c in diabetes patients. Six phenotypes (intima-media thickness measurements (cIMT (ave.), cIMT (max.), cIMT (min.)), bidirectional wall variability (cIMTV), morphology-based total plaque area (mTPA), and composite risk score (CRS)) were measured in an automated setting using AtheroEdge™ (AtheroPoint, CA, USA). METHOD: Consecutive 199 patients (157 M, age: 68.96 ±â€¯10.98 years), L/R common carotid artery (CCA; 398 US scans) who underwent a carotid ultrasound (L/R) were retrospectively analyzed using AtheroEdge™ system. Two operators (novice and experienced) manually calibrated all the US scans using AtheroEdge™. Logistic regression (LR) and Odds ratio (OR) was computed and phenotypes were ranked. RESULTS: The baseline results showed 150 low-risk patients (HbA1c < 6.50 mg/dl) and 49 high-risk patients (HbA1c ≥ 6.50 mg/dl). The fasting blood sugar (FBS) was highly associated with HbA1c (P < 0.001). Except for cIMTV, all phenotypes showed an OR > 1.0 (P < 0.001) for left common carotid artery (LCCA), right carotid artery (RCCA), and mean of left and right common carotid artery (MCCA). After adjusting the FBS, the OR for mTPA showed a higher risk for LCCA, RCCA, and MCCA. The coefficient of correlation (CC) between phenotypes and HbA1c were strong and inter-CC between cIMT and mTPA/CRS was above 0.9 (P < 0.001). The statistical tests showed that phenotypes were significantly associated with diabetes (P-value<0.0001). CONCLUSIONS: All phenotypes using AtheroEdge™, except cIMTV, showed a strong association with HbA1c. mTPA and CRS were equally strong phenotypes as cIMT. The CRS phenotype showed the strongest relationship to HbA1c.

Deep learning strategy for accurate carotid intima-media thickness measurement: An ultrasound study on Japanese diabetic cohort.

MOTIVATION: The carotid intima-media thickness (cIMT) is an important biomarker for cardiovascular diseases and stroke monitoring. This study presents an intelligence-based, novel, robust, and clinically-strong strategy that uses a combination of deep-learning (DL) and machine-learning (ML) paradigms. METHODOLOGY: A two-stage DL-based system (a class of AtheroEdge™ systems) was proposed for cIMT measurements. Stage I consisted of a convolution layer-based encoder for feature extraction and a fully convolutional network-based decoder for image segmentation. This stage generated the raw inner lumen borders and raw outer interadventitial borders. To smooth these borders, the DL system used a cascaded stage II that consisted of ML-based regression. The final outputs were the far wall lumen-intima (LI) and media-adventitia (MA) borders which were used for cIMT measurements. There were two sets of gold standards during the DL design, therefore two sets of DL systems (DL1 and DL2) were derived. RESULTS: A total of 396 B-mode ultrasound images of the right and left common carotid artery were used from 203 patients (Institutional Review Board approved, Toho University, Japan). For the test set, the cIMT error for the DL1 and DL2 systems with respect to the gold standard was 0.126 ±â€¯0.134 and 0.124 ±â€¯0.100 mm, respectively. The corresponding LI error for the DL1 and DL2 systems was 0.077 ±â€¯0.057 and 0.077 ±â€¯0.049 mm, respectively, while the corresponding MA error for DL1 and DL2 was 0.113 ±â€¯0.105 and 0.109 ±â€¯0.088 mm, respectively. The results showed up to 20% improvement in cIMT readings for the DL system compared to the sonographer's readings. Four statistical tests were conducted to evaluate reliability, stability, and statistical significance. CONCLUSION: The results showed that the performance of the DL-based approach was superior to the nonintelligence-based conventional methods that use spatial intensities alone. The DL system can be used for stroke risk assessment during routine or clinical trial modes.