Artificial intelligence-based preventive, personalized and precision medicine for cardiovascular disease/stroke risk assessment in rheumatoid arthritis patients: a narrative review.

The challenges associated with diagnosing and treating cardiovascular disease (CVD)/Stroke in Rheumatoid arthritis (RA) arise from the delayed onset of symptoms. Existing clinical risk scores are inadequate in predicting cardiac events, and conventional risk factors alone do not accurately classify many individuals at risk. Several CVD biomarkers consider the multiple pathways involved in the development of atherosclerosis, which is the primary cause of CVD/Stroke in RA. To enhance the accuracy of CVD/Stroke risk assessment in the RA framework, a proposed approach involves combining genomic-based biomarkers (GBBM) derived from plasma and/or serum samples with innovative non-invasive radiomic-based biomarkers (RBBM), such as measurements of synovial fluid, plaque area, and plaque burden. This review presents two hypotheses: (i) RBBM and GBBM biomarkers exhibit a significant correlation and can precisely detect the severity of CVD/Stroke in RA patients. (ii) Artificial Intelligence (AI)-based preventive, precision, and personalized (aiP3) CVD/Stroke risk AtheroEdge™ model (AtheroPoint™, CA, USA) that utilizes deep learning (DL) to accurately classify the risk of CVD/stroke in RA framework. The authors conducted a comprehensive search using the PRISMA technique, identifying 153 studies that assessed the features/biomarkers of RBBM and GBBM for CVD/Stroke. The study demonstrates how DL models can be integrated into the AtheroEdge™-aiP3 framework to determine the risk of CVD/Stroke in RA patients. The findings of this review suggest that the combination of RBBM with GBBM introduces a new dimension to the assessment of CVD/Stroke risk in the RA framework. Synovial fluid levels that are higher than normal lead to an increase in the plaque burden. Additionally, the review provides recommendations for novel, unbiased, and pruned DL algorithms that can predict CVD/Stroke risk within a RA framework that is preventive, precise, and personalized.

Integration of cardiovascular risk assessment with COVID-19 using artificial intelligence.

Artificial Intelligence (AI), in general, refers to the machines (or computers) that mimic "cognitive" functions that we associate with our mind, such as "learning" and "solving problem". New biomarkers derived from medical imaging are being discovered and are then fused with non-imaging biomarkers (such as office, laboratory, physiological, genetic, epidemiological, and clinical-based biomarkers) in a big data framework, to develop AI systems. These systems can support risk prediction and monitoring. This perspective narrative shows the powerful methods of AI for tracking cardiovascular risks. We conclude that AI could potentially become an integral part of the COVID-19 disease management system. Countries, large and small, should join hands with the WHO in building biobanks for scientists around the world to build AI-based platforms for tracking the cardiovascular risk assessment during COVID-19 times and long-term follow-up of the survivors.

Maintenance of remission with combination etanercept-DMARD therapy versus DMARDs alone in active rheumatoid arthritis: results of an international treat-to-target study conducted in regions with limited biologic access.

In this transglobal, randomized, double-blind, placebo-controlled, treat-to-target study, the maintenance of efficacy was compared between biologic-and biologic-free-disease-modifying antirheumatic drug (DMARD) combination regimens after low disease activity (LDA) was achieved with biologic DMARD induction therapy. Patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy received open-label etanercept 50 mg subcutaneously once weekly plus methotrexate with or without other conventional synthetic (cs) DMARDs for 24 weeks. Patients achieving LDA [disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) <3.2] at week 24 were randomized to receive etanercept-methotrexate combination therapy or placebo-methotrexate combination therapy, with or without other csDMARDs, for 28 weeks. In the open-label period, 72% of patients achieved DAS28-ESR LDA at week 24. Patients enrolled in the double-blind period had long-standing rheumatoid arthritis and high disease activity at baseline (mean duration, 8.1 years; DAS28-ESR, 6.4). In the etanercept and placebo combination groups, 44% versus 17% achieved DAS28-ESR LDA and 34 versus 13% achieved DAS28-ESR remission at week 52 (p < 0.001). Adverse events were reported in 37 and 43%, serious adverse events in 0 and 4%, and serious infections in 0 and 2% in these groups, respectively, in the double-blind period. After induction of response with etanercept combination therapy following a treat-to-target approach in patients with long-standing rheumatoid arthritis and high disease activity at baseline, the etanercept combination regimen was significantly more effective in maintaining LDA and remission than a biologic-free regimen. ClinicalTrials.gov identifier. NCT01578850.

A hot spot for systemic lupus erythematosus, but not for psoriatic arthritis, identified by spatial analysis suggests an interaction between ethnicity and place of residence.

OBJECTIVE: To describe the spatial distribution of incident cases of systemic lupus erythematosus (SLE) using geographic information systems (GIS). METHODS: Spatial analyses were carried out on 890 SLE patients and 541 psoriatic arthritis (PsA) patients (controls). Age- and sex-adjusted rates for SLE/PsA for each census tract were calculated using denominator population values from the Canadian census. Spatial variations in relative risk were estimated by modeling risk as the product of a time effect, an age effect, and a spatially autocorrelated risk surface to identify hot spots. Patients within the detected hot spot were compared to those outside the hot spot to identify explanatory factors. RESULTS: SLE patients were predominantly female (87.75%) and the incidence rate was highest among those 15-19 years of age (2.4 cases/100,000 person-years). In an SLE hot spot containing 59 patients, 100% of the patients were female and 49.1% (n = 29) were Caucasian, while outside of the hot spot, 86.9% (n = 722) of the patients were female and 68.4% (n = 568) were Caucasian. The proportion of cases of Chinese ethnicity was significantly greater within the hot spot. An interaction was found between Chinese ethnicity and residence within the hot spot, with the risk of SLE to the Chinese population found to be twice the risk to the non-Chinese population. CONCLUSION: GIS was used to map SLE cases and a hot spot was identified after adjustment for age and sex. Ethnicity by itself did not confer an increased risk of SLE, but the interaction of ethnicity with location of residence significantly increased the risk of SLE.

Artificial intelligence for cardiovascular disease risk assessment in personalised framework: a scoping review.

Background: The field of precision medicine endeavors to transform the healthcare industry by advancing individualised strategies for diagnosis, treatment modalities, and predictive assessments. This is achieved by utilizing extensive multidimensional biological datasets encompassing diverse components, such as an individual's genetic makeup, functional attributes, and environmental influences. Artificial intelligence (AI) systems, namely machine learning (ML) and deep learning (DL), have exhibited remarkable efficacy in predicting the potential occurrence of specific cancers and cardiovascular diseases (CVD). Methods: We conducted a comprehensive scoping review guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. Our search strategy involved combining key terms related to CVD and AI using the Boolean operator AND. In August 2023, we conducted an extensive search across reputable scholarly databases including Google Scholar, PubMed, IEEE Xplore, ScienceDirect, Web of Science, and arXiv to gather relevant academic literature on personalised medicine for CVD. Subsequently, in January 2024, we extended our search to include internet search engines such as Google and various CVD websites. These searches were further updated in March 2024. Additionally, we reviewed the reference lists of the final selected research articles to identify any additional relevant literature. Findings: A total of 2307 records were identified during the process of conducting the study, consisting of 564 entries from external sites like arXiv and 1743 records found through database searching. After 430 duplicate articles were eliminated, 1877 items that remained were screened for relevancy. In this stage, 1241 articles remained for additional review after 158 irrelevant articles and 478 articles with insufficient data were removed. 355 articles were eliminated for being inaccessible, 726 for being written in a language other than English, and 281 for not having undergone peer review. Consequently, 121 studies were deemed suitable for inclusion in the qualitative synthesis. At the intersection of CVD, AI, and precision medicine, we found important scientific findings in our scoping review. Intricate pattern extraction from large, complicated genetic datasets is a skill that AI algorithms excel at, allowing for accurate disease diagnosis and CVD risk prediction. Furthermore, these investigations have uncovered unique genetic biomarkers linked to CVD, providing insight into the workings of the disease and possible treatment avenues. The construction of more precise predictive models and personalised treatment plans based on the genetic profiles of individual patients has been made possible by the revolutionary advancement of CVD risk assessment through the integration of AI and genomics. Interpretation: The systematic methodology employed ensured the thorough examination of available literature and the inclusion of relevant studies, contributing to the robustness and reliability of the study's findings. Our analysis stresses a crucial point in terms of the adaptability and versatility of AI solutions. AI algorithms designed in non-CVD domains such as in oncology, often include ideas and tactics that might be modified to address cardiovascular problems. Funding: No funding received.

DermAI 1.0: A Robust, Generalized, and Novel Attention-Enabled Ensemble-Based Transfer Learning Paradigm for Multiclass Classification of Skin Lesion Images.

Skin lesion classification plays a crucial role in dermatology, aiding in the early detection, diagnosis, and management of life-threatening malignant lesions. However, standalone transfer learning (TL) models failed to deliver optimal performance. In this study, we present an attention-enabled ensemble-based deep learning technique, a powerful, novel, and generalized method for extracting features for the classification of skin lesions. This technique holds significant promise in enhancing diagnostic accuracy by using seven pre-trained TL models for classification. Six ensemble-based DL (EBDL) models were created using stacking, softmax voting, and weighted average techniques. Furthermore, we investigated the attention mechanism as an effective paradigm and created seven attention-enabled transfer learning (aeTL) models before branching out to construct three attention-enabled ensemble-based DL (aeEBDL) models to create a reliable, adaptive, and generalized paradigm. The mean accuracy of the TL models is 95.30%, and the use of an ensemble-based paradigm increased it by 4.22%, to 99.52%. The aeTL models' performance was superior to the TL models in accuracy by 3.01%, and aeEBDL models outperformed aeTL models by 1.29%. Statistical tests show significant p-value and Kappa coefficient along with a 99.6% reliability index for the aeEBDL models. The approach is highly effective and generalized for the classification of skin lesions.

A Pharmaceutical Paradigm for Cardiovascular Composite Risk Assessment Using Novel Radiogenomics Risk Predictors in Precision Explainable Artificial Intelligence Framework: Clinical Trial Tool.

BACKGROUND: Cardiovascular disease (CVD) is challenging to diagnose and treat since symptoms appear late during the progression of atherosclerosis. Conventional risk factors alone are not always sufficient to properly categorize at-risk patients, and clinical risk scores are inadequate in predicting cardiac events. Integrating genomic-based biomarkers (GBBM) found in plasma/serum samples with novel non-invasive radiomics-based biomarkers (RBBM) such as plaque area, plaque burden, and maximum plaque height can improve composite CVD risk prediction in the pharmaceutical paradigm. These biomarkers consider several pathways involved in the pathophysiology of atherosclerosis disease leading to CVD. OBJECTIVE: This review proposes two hypotheses: (i) The composite biomarkers are strongly correlated and can be used to detect the severity of CVD/Stroke precisely, and (ii) an explainable artificial intelligence (XAI)-based composite risk CVD/Stroke model with survival analysis using deep learning (DL) can predict in preventive, precision, and personalized (aiP3) framework benefiting the pharmaceutical paradigm. METHOD: The PRISMA search technique resulted in 214 studies assessing composite biomarkers using radiogenomics for CVD/Stroke. The study presents a XAI model using AtheroEdgeTM 4.0 to determine the risk of CVD/Stroke in the pharmaceutical framework using the radiogenomics biomarkers. CONCLUSIONS: Our observations suggest that the composite CVD risk biomarkers using radiogenomics provide a new dimension to CVD/Stroke risk assessment. The proposed review suggests a unique, unbiased, and XAI model based on AtheroEdgeTM 4.0 that can predict the composite risk of CVD/Stroke using radiogenomics in the pharmaceutical paradigm.

Ensemble Deep Learning Derived from Transfer Learning for Classification of COVID-19 Patients on Hybrid Deep-Learning-Based Lung Segmentation: A Data Augmentation and Balancing Framework.

BACKGROUND AND MOTIVATION: Lung computed tomography (CT) techniques are high-resolution and are well adopted in the intensive care unit (ICU) for COVID-19 disease control classification. Most artificial intelligence (AI) systems do not undergo generalization and are typically overfitted. Such trained AI systems are not practical for clinical settings and therefore do not give accurate results when executed on unseen data sets. We hypothesize that ensemble deep learning (EDL) is superior to deep transfer learning (TL) in both non-augmented and augmented frameworks. METHODOLOGY: The system consists of a cascade of quality control, ResNet-UNet-based hybrid deep learning for lung segmentation, and seven models using TL-based classification followed by five types of EDL's. To prove our hypothesis, five different kinds of data combinations (DC) were designed using a combination of two multicenter cohorts-Croatia (80 COVID) and Italy (72 COVID and 30 controls)-leading to 12,000 CT slices. As part of generalization, the system was tested on unseen data and statistically tested for reliability/stability. RESULTS: Using the K5 (80:20) cross-validation protocol on the balanced and augmented dataset, the five DC datasets improved TL mean accuracy by 3.32%, 6.56%, 12.96%, 47.1%, and 2.78%, respectively. The five EDL systems showed improvements in accuracy of 2.12%, 5.78%, 6.72%, 32.05%, and 2.40%, thus validating our hypothesis. All statistical tests proved positive for reliability and stability. CONCLUSION: EDL showed superior performance to TL systems for both (a) unbalanced and unaugmented and (b) balanced and augmented datasets for both (i) seen and (ii) unseen paradigms, validating both our hypotheses.

Clinical and laboratory characteristics of patients with sickle-cell and autoimmune/connective tissue diseases.

Patients with sickle-cell disease who develop autoimmune connective tissue disorders can present with similar clinical manifestations and/or complications making them indistinguishable. We report here a single-institution study on a cohort of 24 patients, with the above combination. The results suggest that there is often a significant delay in making the second diagnosis because of the overlapping clinical profile. It is emphasized that the clinician should be aware of and vigilant about such cases and should diligently follow up such cases to make an early diagnosis and start the appropriate treatment.

Economics of Artificial Intelligence in Healthcare: Diagnosis vs. Treatment.

Motivation: The price of medical treatment continues to rise due to (i) an increasing population; (ii) an aging human growth; (iii) disease prevalence; (iv) a rise in the frequency of patients that utilize health care services; and (v) increase in the price. Objective: Artificial Intelligence (AI) is already well-known for its superiority in various healthcare applications, including the segmentation of lesions in images, speech recognition, smartphone personal assistants, navigation, ride-sharing apps, and many more. Our study is based on two hypotheses: (i) AI offers more economic solutions compared to conventional methods; (ii) AI treatment offers stronger economics compared to AI diagnosis. This novel study aims to evaluate AI technology in the context of healthcare costs, namely in the areas of diagnosis and treatment, and then compare it to the traditional or non-AI-based approaches. Methodology: PRISMA was used to select the best 200 studies for AI in healthcare with a primary focus on cost reduction, especially towards diagnosis and treatment. We defined the diagnosis and treatment architectures, investigated their characteristics, and categorized the roles that AI plays in the diagnostic and therapeutic paradigms. We experimented with various combinations of different assumptions by integrating AI and then comparing it against conventional costs. Lastly, we dwell on three powerful future concepts of AI, namely, pruning, bias, explainability, and regulatory approvals of AI systems. Conclusions: The model shows tremendous cost savings using AI tools in diagnosis and treatment. The economics of AI can be improved by incorporating pruning, reduction in AI bias, explainability, and regulatory approvals.

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.

COVLIAS 1.0Lesion vs. MedSeg: An Artificial Intelligence Framework for Automated Lesion Segmentation in COVID-19 Lung Computed Tomography Scans.

Background: COVID-19 is a disease with multiple variants, and is quickly spreading throughout the world. It is crucial to identify patients who are suspected of having COVID-19 early, because the vaccine is not readily available in certain parts of the world. Methodology: Lung computed tomography (CT) imaging can be used to diagnose COVID-19 as an alternative to the RT-PCR test in some cases. The occurrence of ground-glass opacities in the lung region is a characteristic of COVID-19 in chest CT scans, and these are daunting to locate and segment manually. The proposed study consists of a combination of solo deep learning (DL) and hybrid DL (HDL) models to tackle the lesion location and segmentation more quickly. One DL and four HDL models­namely, PSPNet, VGG-SegNet, ResNet-SegNet, VGG-UNet, and ResNet-UNet­were trained by an expert radiologist. The training scheme adopted a fivefold cross-validation strategy on a cohort of 3000 images selected from a set of 40 COVID-19-positive individuals. Results: The proposed variability study uses tracings from two trained radiologists as part of the validation. Five artificial intelligence (AI) models were benchmarked against MedSeg. The best AI model, ResNet-UNet, was superior to MedSeg by 9% and 15% for Dice and Jaccard, respectively, when compared against MD 1, and by 4% and 8%, respectively, when compared against MD 2. Statistical tests­namely, the Mann−Whitney test, paired t-test, and Wilcoxon test­demonstrated its stability and reliability, with p < 0.0001. The online system for each slice was <1 s. Conclusions: The AI models reliably located and segmented COVID-19 lesions in CT scans. The COVLIAS 1.0Lesion lesion locator passed the intervariability test.

COVLIAS 2.0-cXAI: Cloud-Based Explainable Deep Learning System for COVID-19 Lesion Localization in Computed Tomography Scans.

Background: The previous COVID-19 lung diagnosis system lacks both scientific validation and the role of explainable artificial intelligence (AI) for understanding lesion localization. This study presents a cloud-based explainable AI, the "COVLIAS 2.0-cXAI" system using four kinds of class activation maps (CAM) models. Methodology: Our cohort consisted of ~6000 CT slices from two sources (Croatia, 80 COVID-19 patients and Italy, 15 control patients). COVLIAS 2.0-cXAI design consisted of three stages: (i) automated lung segmentation using hybrid deep learning ResNet-UNet model by automatic adjustment of Hounsfield units, hyperparameter optimization, and parallel and distributed training, (ii) classification using three kinds of DenseNet (DN) models (DN-121, DN-169, DN-201), and (iii) validation using four kinds of CAM visualization techniques: gradient-weighted class activation mapping (Grad-CAM), Grad-CAM++, score-weighted CAM (Score-CAM), and FasterScore-CAM. The COVLIAS 2.0-cXAI was validated by three trained senior radiologists for its stability and reliability. The Friedman test was also performed on the scores of the three radiologists. Results: The ResNet-UNet segmentation model resulted in dice similarity of 0.96, Jaccard index of 0.93, a correlation coefficient of 0.99, with a figure-of-merit of 95.99%, while the classifier accuracies for the three DN nets (DN-121, DN-169, and DN-201) were 98%, 98%, and 99% with a loss of ~0.003, ~0.0025, and ~0.002 using 50 epochs, respectively. The mean AUC for all three DN models was 0.99 (p < 0.0001). The COVLIAS 2.0-cXAI showed 80% scans for mean alignment index (MAI) between heatmaps and gold standard, a score of four out of five, establishing the system for clinical settings. Conclusions: The COVLIAS 2.0-cXAI successfully showed a cloud-based explainable AI system for lesion localization in lung CT scans.

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.

Eight pruning deep learning models for low storage and high-speed COVID-19 computed tomography lung segmentation and heatmap-based lesion localization: A multicenter study using COVLIAS 2.0.

BACKGROUND: COVLIAS 1.0: an automated lung segmentation was designed for COVID-19 diagnosis. It has issues related to storage space and speed. This study shows that COVLIAS 2.0 uses pruned AI (PAI) networks for improving both storage and speed, wiliest high performance on lung segmentation and lesion localization. METHOD: ology: The proposed study uses multicenter ∼9,000 CT slices from two different nations, namely, CroMed from Croatia (80 patients, experimental data), and NovMed from Italy (72 patients, validation data). We hypothesize that by using pruning and evolutionary optimization algorithms, the size of the AI models can be reduced significantly, ensuring optimal performance. Eight different pruning techniques (i) differential evolution (DE), (ii) genetic algorithm (GA), (iii) particle swarm optimization algorithm (PSO), and (iv) whale optimization algorithm (WO) in two deep learning frameworks (i) Fully connected network (FCN) and (ii) SegNet were designed. COVLIAS 2.0 was validated using "Unseen NovMed" and benchmarked against MedSeg. Statistical tests for stability and reliability were also conducted. RESULTS: Pruning algorithms (i) FCN-DE, (ii) FCN-GA, (iii) FCN-PSO, and (iv) FCN-WO showed improvement in storage by 92.4%, 95.3%, 98.7%, and 99.8% respectively when compared against solo FCN, and (v) SegNet-DE, (vi) SegNet-GA, (vii) SegNet-PSO, and (viii) SegNet-WO showed improvement by 97.1%, 97.9%, 98.8%, and 99.2% respectively when compared against solo SegNet. AUC > 0.94 (p < 0.0001) on CroMed and > 0.86 (p < 0.0001) on NovMed data set for all eight EA model. PAI <0.25 s per image. DenseNet-121-based Grad-CAM heatmaps showed validation on glass ground opacity lesions. CONCLUSIONS: Eight PAI networks that were successfully validated are five times faster, storage efficient, and could be used in clinical settings.

Cardiovascular/Stroke Risk Stratification in Diabetic Foot Infection Patients Using Deep Learning-Based Artificial Intelligence: An Investigative Study.

A diabetic foot infection (DFI) is among the most serious, incurable, and costly to treat conditions. The presence of a DFI renders machine learning (ML) systems extremely nonlinear, posing difficulties in CVD/stroke risk stratification. In addition, there is a limited number of well-explained ML paradigms due to comorbidity, sample size limits, and weak scientific and clinical validation methodologies. Deep neural networks (DNN) are potent machines for learning that generalize nonlinear situations. The objective of this article is to propose a novel investigation of deep learning (DL) solutions for predicting CVD/stroke risk in DFI patients. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) search strategy was used for the selection of 207 studies. We hypothesize that a DFI is responsible for increased morbidity and mortality due to the worsening of atherosclerotic disease and affecting coronary artery disease (CAD). Since surrogate biomarkers for CAD, such as carotid artery disease, can be used for monitoring CVD, we can thus use a DL-based model, namely, Long Short-Term Memory (LSTM) and Recurrent Neural Networks (RNN) for CVD/stroke risk prediction in DFI patients, which combines covariates such as office and laboratory-based biomarkers, carotid ultrasound image phenotype (CUSIP) lesions, along with the DFI severity. We confirmed the viability of CVD/stroke risk stratification in the DFI patients. Strong designs were found in the research of the DL architectures for CVD/stroke risk stratification. Finally, we analyzed the AI bias and proposed strategies for the early diagnosis of CVD/stroke in DFI patients. Since DFI patients have an aggressive atherosclerotic disease, leading to prominent CVD/stroke risk, we, therefore, conclude that the DL paradigm is very effective for predicting the risk of CVD/stroke in DFI patients.

Vascular Implications of COVID-19: Role of Radiological Imaging, Artificial Intelligence, and Tissue Characterization: A Special Report.

The SARS-CoV-2 virus has caused a pandemic, infecting nearly 80 million people worldwide, with mortality exceeding six million. The average survival span is just 14 days from the time the symptoms become aggressive. The present study delineates the deep-driven vascular damage in the pulmonary, renal, coronary, and carotid vessels due to SARS-CoV-2. This special report addresses an important gap in the literature in understanding (i) the pathophysiology of vascular damage and the role of medical imaging in the visualization of the damage caused by SARS-CoV-2, and (ii) further understanding the severity of COVID-19 using artificial intelligence (AI)-based tissue characterization (TC). PRISMA was used to select 296 studies for AI-based TC. Radiological imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound were selected for imaging of the vasculature infected by COVID-19. Four kinds of hypotheses are presented for showing the vascular damage in radiological images due to COVID-19. Three kinds of AI models, namely, machine learning, deep learning, and transfer learning, are used for TC. Further, the study presents recommendations for improving AI-based architectures for vascular studies. We conclude that the process of vascular damage due to COVID-19 has similarities across vessel types, even though it results in multi-organ dysfunction. Although the mortality rate is ~2% of those infected, the long-term effect of COVID-19 needs monitoring to avoid deaths. AI seems to be penetrating the health care industry at warp speed, and we expect to see an emerging role in patient care, reduce the mortality and morbidity rate.

A narrative review on characterization of acute respiratory distress syndrome in COVID-19-infected lungs using artificial intelligence.

COVID-19 has infected 77.4 million people worldwide and has caused 1.7 million fatalities as of December 21, 2020. The primary cause of death due to COVID-19 is Acute Respiratory Distress Syndrome (ARDS). According to the World Health Organization (WHO), people who are at least 60 years old or have comorbidities that have primarily been targeted are at the highest risk from SARS-CoV-2. Medical imaging provides a non-invasive, touch-free, and relatively safer alternative tool for diagnosis during the current ongoing pandemic. Artificial intelligence (AI) scientists are developing several intelligent computer-aided diagnosis (CAD) tools in multiple imaging modalities, i.e., lung computed tomography (CT), chest X-rays, and lung ultrasounds. These AI tools assist the pulmonary and critical care clinicians through (a) faster detection of the presence of a virus, (b) classifying pneumonia types, and (c) measuring the severity of viral damage in COVID-19-infected patients. Thus, it is of the utmost importance to fully understand the requirements of for a fast and successful, and timely lung scans analysis. This narrative review first presents the pathological layout of the lungs in the COVID-19 scenario, followed by understanding and then explains the comorbid statistical distributions in the ARDS framework. The novelty of this review is the approach to classifying the AI models as per the by school of thought (SoTs), exhibiting based on segregation of techniques and their characteristics. The study also discusses the identification of AI models and its extension from non-ARDS lungs (pre-COVID-19) to ARDS lungs (post-COVID-19). Furthermore, it also presents AI workflow considerations of for medical imaging modalities in the COVID-19 framework. Finally, clinical AI design considerations will be discussed. We conclude that the design of the current existing AI models can be improved by considering comorbidity as an independent factor. Furthermore, ARDS post-processing clinical systems must involve include (i) the clinical validation and verification of AI-models, (ii) reliability and stability criteria, and (iii) easily adaptable, and (iv) generalization assessments of AI systems for their use in pulmonary, critical care, and radiological settings.

COVLIAS 1.0 vs. MedSeg: Artificial Intelligence-Based Comparative Study for Automated COVID-19 Computed Tomography Lung Segmentation in Italian and Croatian Cohorts.

(1) Background: COVID-19 computed tomography (CT) lung segmentation is critical for COVID lung severity diagnosis. Earlier proposed approaches during 2020-2021 were semiautomated or automated but not accurate, user-friendly, and industry-standard benchmarked. The proposed study compared the COVID Lung Image Analysis System, COVLIAS 1.0 (GBTI, Inc., and AtheroPointTM, Roseville, CA, USA, referred to as COVLIAS), against MedSeg, a web-based Artificial Intelligence (AI) segmentation tool, where COVLIAS uses hybrid deep learning (HDL) models for CT lung segmentation. (2) Materials and Methods: The proposed study used 5000 ITALIAN COVID-19 positive CT lung images collected from 72 patients (experimental data) that confirmed the reverse transcription-polymerase chain reaction (RT-PCR) test. Two hybrid AI models from the COVLIAS system, namely, VGG-SegNet (HDL 1) and ResNet-SegNet (HDL 2), were used to segment the CT lungs. As part of the results, we compared both COVLIAS and MedSeg against two manual delineations (MD 1 and MD 2) using (i) Bland-Altman plots, (ii) Correlation coefficient (CC) plots, (iii) Receiver operating characteristic curve, and (iv) Figure of Merit and (v) visual overlays. A cohort of 500 CROATIA COVID-19 positive CT lung images (validation data) was used. A previously trained COVLIAS model was directly applied to the validation data (as part of Unseen-AI) to segment the CT lungs and compare them against MedSeg. (3) Result: For the experimental data, the four CCs between COVLIAS (HDL 1) vs. MD 1, COVLIAS (HDL 1) vs. MD 2, COVLIAS (HDL 2) vs. MD 1, and COVLIAS (HDL 2) vs. MD 2 were 0.96, 0.96, 0.96, and 0.96, respectively. The mean value of the COVLIAS system for the above four readings was 0.96. CC between MedSeg vs. MD 1 and MedSeg vs. MD 2 was 0.98 and 0.98, respectively. Both had a mean value of 0.98. On the validation data, the CC between COVLIAS (HDL 1) vs. MedSeg and COVLIAS (HDL 2) vs. MedSeg was 0.98 and 0.99, respectively. For the experimental data, the difference between the mean values for COVLIAS and MedSeg showed a difference of <2.5%, meeting the standard of equivalence. The average running times for COVLIAS and MedSeg on a single lung CT slice were ~4 s and ~10 s, respectively. (4) Conclusions: The performances of COVLIAS and MedSeg were similar. However, COVLIAS showed improved computing time over MedSeg.

Inter-Variability Study of COVLIAS 1.0: Hybrid Deep Learning Models for COVID-19 Lung Segmentation in Computed Tomography.

Background: For COVID-19 lung severity, segmentation of lungs on computed tomography (CT) is the first crucial step. Current deep learning (DL)-based Artificial Intelligence (AI) models have a bias in the training stage of segmentation because only one set of ground truth (GT) annotations are evaluated. We propose a robust and stable inter-variability analysis of CT lung segmentation in COVID-19 to avoid the effect of bias. Methodology: The proposed inter-variability study consists of two GT tracers for lung segmentation on chest CT. Three AI models, PSP Net, VGG-SegNet, and ResNet-SegNet, were trained using GT annotations. We hypothesized that if AI models are trained on the GT tracings from multiple experience levels, and if the AI performance on the test data between these AI models is within the 5% range, one can consider such an AI model robust and unbiased. The K5 protocol (training to testing: 80%:20%) was adapted. Ten kinds of metrics were used for performance evaluation. Results: The database consisted of 5000 CT chest images from 72 COVID-19-infected patients. By computing the coefficient of correlations (CC) between the output of the two AI models trained corresponding to the two GT tracers, computing their differences in their CC, and repeating the process for all three AI-models, we show the differences as 0%, 0.51%, and 2.04% (all < 5%), thereby validating the hypothesis. The performance was comparable; however, it had the following order: ResNet-SegNet > PSP Net > VGG-SegNet. Conclusions: The AI models were clinically robust and stable during the inter-variability analysis on the CT lung segmentation on COVID-19 patients.