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BackgroundWe sought to evaluate the association of metabolic syndrome (MetS) and computed tomography (CT)-derived cardiometabolic biomarkers (non-alcoholic fatty liver disease [NAFLD] and epicardial adipose tissue [EAT] measures) with long-term risk of major adverse cardiovascular events (MACE) in asymptomatic individuals.MethodsThis was a post-hoc analysis of the prospective EISNER (Early-Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study of participants who underwent baseline coronary artery calcium (CAC) scoring CT and 14-year follow-up for MACE (myocardial infarction, late revascularization, or cardiac death). EAT volume (cm3) and attenuation (Hounsfield units [HU]) were quantified from CT using fully automated deep learning software (

Background and aimsWe sought to assess the performance of a comprehensive machine learning (ML) risk score integrating circulating biomarkers and computed tomography (CT) measures for the long-term prediction of hard cardiac events in asymptomatic subjects.MethodsWe studied 1069 subjects (age 58.2 ± 8.2 years, 54.0% males) from the prospective EISNER trial who underwent coronary artery calcium (CAC) scoring CT, serum biomarker assessment, and long-term follow-up. Epicardial adipose tissue (EAT) was quantified from CT using fully automated deep learning software. Forty-eight serum biomarkers, both established and novel, were assayed. An ML algorithm (XGBoost) was trained using clinical risk factors, CT measures (CAC score, number of coronary lesions, aortic valve calcium score, EAT volume and attenuation), and circulating biomarkers, and validated using repeated 10-fold cross validation.ResultsAt 14.5 ± 2.0 years, there were 50 hard cardiac events (myocardial infarction or cardiac death). The ML risk score (area under the receiver operator characteristic curve [AUC] 0.81) outperformed the CAC score (0.75) and ASCVD risk score (0.74; both p = 0.02) for the prediction of hard cardiac events. Serum biomarkers provided incremental prognostic value beyond clinical data and CT measures in the ML model (net reclassification index 0.53 [95% CI: 0.23-0.81], p

BackgroundEpicardial adipose tissue (EAT) volume (cm3) and attenuation (Hounsfield units) may predict major adverse cardiovascular events (MACE). We aimed to evaluate the prognostic value of fully automated deep learning-based EAT volume and attenuation measurements quantified from noncontrast cardiac computed tomography.MethodsOur study included 2068 asymptomatic subjects (56±9 years, 59% male) from the EISNER trial (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) with long-term follow-up after coronary artery calcium measurement. EAT volume and mean attenuation were quantified using automated deep learning software from noncontrast cardiac computed tomography. MACE was defined as myocardial infarction, late (>180 days) revascularization, and cardiac death. EAT measures were compared to coronary artery calcium score and atherosclerotic cardiovascular disease risk score for MACE prediction.ResultsAt 14±3 years, 223 subjects suffered MACE. Increased EAT volume and decreased EAT attenuation were both independently associated with MACE. Atherosclerotic cardiovascular disease risk score, coronary artery calcium, and EAT volume were associated with increased risk of MACE (hazard ratio [95%CI]: 1.03 [1.01-1.04]; 1.25 [1.19-1.30]; and 1.35 [1.07-1.68], P

Combined analysis of SPECT myocardial perfusion imaging (MPI) performed with a solid-state camera on patients in 2 positions (semiupright, supine) is routinely used to mitigate attenuation artifacts. We evaluated the prediction of obstructive disease from combined analysis of semiupright and supine stress MPI by deep learning (DL) as compared with standard combined total perfusion deficit (TPD). Methods: 1,160 patients without known coronary artery disease (64% male) were studied. Patients underwent stress 99mTc-sestamibi MPI with new-generation solid-state SPECT scanners in 4 different centers. All patients had on-site clinical reads and invasive coronary angiography correlations within 6 mo of MPI. Obstructive disease was defined as at least 70% narrowing of the 3 major coronary arteries and at least 50% for the left main coronary artery. Images were quantified at Cedars-Sinai. The left ventricular myocardium was segmented using standard clinical nuclear cardiology software. The contour placement was verified by an experienced technologist. Combined stress TPD was computed using sex- and camera-specific normal limits. DL was trained using polar distributions of normalized radiotracer counts, hypoperfusion defects, and hypoperfusion severities and was evaluated for prediction of obstructive disease in a novel leave-one-center-out cross-validation procedure equivalent to external validation. During the validation procedure, 4 DL models were trained using data from 3 centers and then evaluated on the 1 center left aside. Predictions for each center were merged to have an overall estimation of the multicenter performance. Results: 718 (62%) patients and 1,272 of 3,480 (37%) arteries had obstructive disease. The area under the receiver operating characteristics curve for prediction of disease on a per-patient and per-vessel basis by DL was higher than for combined TPD (per-patient, 0.81 vs. 0.78; per-vessel, 0.77 vs. 0.73; P < 0.001). With the DL cutoff set to exhibit the same specificity as the standard cutoff for combined TPD, per-patient sensitivity improved from 61.8% (TPD) to 65.6% (DL) (P < 0.05), and per-vessel sensitivity improved from 54.6% (TPD) to 59.1% (DL) (P < 0.01). With the threshold matched to the specificity of a normal clinical read (56.3%), DL had a sensitivity of 84.8%, versus 82.6% for an on-site clinical read (P = 0.3). Conclusion: DL improves automatic interpretation of MPI as compared with current quantitative methods.

OBJECTIVES:The study evaluated the automatic prediction of obstructive disease from myocardial perfusion imaging (MPI) by deep learning as compared with total perfusion deficit (TPD). BACKGROUND:Deep convolutional neural networks trained with a large multicenter population may provide improved prediction of per-patient and per-vessel coronary artery disease from single-photon emission computed tomography MPI. METHODS:A total of 1,638 patients (67% men) without known coronary artery disease, undergoing stress 99mTc-sestamibi or tetrofosmin MPI with new generation solid-state scanners in 9 different sites, with invasive coronary angiography performed within 6 months of MPI, were studied. Obstructive disease was defined as ≥70% narrowing of coronary arteries (≥50% for left main artery). Left ventricular myocardium was segmented using clinical nuclear cardiology software and verified by an expert reader. Stress TPD was computed using sex- and camera-specific normal limits. Deep learning was trained using raw and quantitative polar maps and evaluated for prediction of obstructive stenosis in a stratified 10-fold cross-validation procedure. RESULTS:A total of 1,018 (62%) patients and 1,797 of 4,914 (37%) arteries had obstructive disease. Area under the receiver-operating characteristic curve for disease prediction by deep learning was higher than for TPD (per patient: 0.80 vs. 0.78; per vessel: 0.76 vs. 0.73: p < 0.01). With deep learning threshold set to the same specificity as TPD, per-patient sensitivity improved from 79.8% (TPD) to 82.3% (deep learning) (p < 0.05), and per-vessel sensitivity improved from 64.4% (TPD) to 69.8% (deep learning) (p < 0.01). CONCLUSIONS:Deep learning has the potential to improve automatic interpretation of MPI as compared with current clinical methods.

BackgroundWe investigated whether epicardial adipose tissue (EAT) volume and density are related to early atherosclerosis, plaque inflammation and major adverse cardiac events (MACE, cardiac death and myocardial infarction) in asymptomatic subjects.MethodsEAT volume and density were quantified from non-contrast cardiac CT in 456 asymptomatic individuals (age 60.3 ± 8.3; 68% with CCS>0) from the prospective EISNER trial. EAT volume and density were examined in relation to coronary calcium score (CCS), inflammatory biomarkers and MACE.ResultsEAT volume was higher and EAT density lower in subjects with coronary calcium compared to subjects without [89 vs 74 cm3, p

Aims Our aim was to evaluate the performance of machine learning (ML), integrating clinical parameters with coronary artery calcium (CAC), and automated epicardial adipose tissue (EAT) quantification, for the prediction of long-term risk of myocardial infarction (MI) and cardiac death in asymptomatic subjects. Methods and results Our study included 1912 asymptomatic subjects [1117 (58.4%) male, age: 55.8  ±  9.1 years] from the prospective EISNER trial with long-term follow-up after CAC scoring. EAT volume and density were quantified using a fully automated deep learning method. ML extreme gradient boosting was trained using clinical co-variates, plasma lipid panel measurements, risk factors, CAC, aortic calcium, and automated EAT measures, and validated using repeated 10-fold cross validation. During mean follow-up of 14.5  ±  2 years, 76 events of MI and/or cardiac death occurred. ML obtained a significantly higher AUC than atherosclerotic cardiovascular disease (ASCVD) risk and CAC score for predicting events (ML: 0.82; ASCVD: 0.77; CAC: 0.77, P  < 0.05 for all). Subjects with a higher ML score (by Youden's index) had high hazard of suffering events (HR: 10.38, P  < 0.001); the relationships persisted in multivariable analysis including ASCVD-risk and CAC measures (HR: 2.94, P  = 0.005). Age, ASCVD-risk, and CAC were prognostically important for both genders. Systolic blood pressure was more important than cholesterol in women, and the opposite in men. Conclusions In this prospective study, machine learning used to integrate clinical and quantitative imaging-based variables significantly improves prediction of MI and cardiac death compared with standard clinical risk assessment. Following further validation, such a personalized paradigm could potentially be used to improve cardiovascular risk assessment. [ABSTRACT FROM AUTHOR]

Aims To optimize per-vessel prediction of early coronary revascularization (ECR) within 90 days after fast single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) using machine learning (ML) and introduce a method for a patient-specific explanation of ML results in a clinical setting. Methods and results A total of 1980 patients with suspected coronary artery disease (CAD) underwent stress/rest 99mTc-sestamibi/tetrofosmin MPI with new-generation SPECT scanners were included. All patients had invasive coronary angiography within 6 months after SPECT MPI. ML utilized 18 clinical, 9 stress test, and 28 imaging variables to predict per-vessel and per-patient ECR with 10-fold cross-validation. Area under the receiver operator characteristics curve (AUC) of ML was compared with standard quantitative analysis [total perfusion deficit (TPD)] and expert interpretation. ECR was performed in 958 patients (48%). Per-vessel, the AUC of ECR prediction by ML (AUC 0.79, 95% confidence interval (CI) [0.77, 0.80]) was higher than by regional stress TPD (0.71, [0.70, 0.73]), combined-view stress TPD (AUC 0.71, 95% CI [0.69, 0.72]), or ischaemic TPD (AUC 0.72, 95% CI [0.71, 0.74]), all P  <   0.001. Per-patient, the AUC of ECR prediction by ML (AUC 0.81, 95% CI [0.79, 0.83]) was higher than that of stress TPD, combined-view TPD, and ischaemic TPD, all P  <   0.001. ML also outperformed nuclear cardiologists' expert interpretation of MPI for the prediction of early revascularization performance. A method to explain ML prediction for an individual patient was also developed. Conclusion In patients with suspected CAD, the prediction of ECR by ML outperformed automatic MPI quantitation by TPDs (per-vessel and per-patient) or nuclear cardiologists' expert interpretation (per-patient). [ABSTRACT FROM AUTHOR]

Aims: Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) stress-only protocols reduce radiation exposure and cost but require clinicians to make immediate decisions regarding rest scan cancellation. We developed a machine learning (ML) approach for automatic rest scan cancellation and evaluated its prognostic safety., Methods and Results: In total, 20 414 patients from a solid-state SPECT MPI international multicentre registry with clinical data and follow-up for major adverse cardiac events (MACE) were used to train ML for MACE prediction as a continuous probability (ML score), using 10-fold repeated hold-out testing to separate test from training data. Three ML score thresholds (ML1, ML2, and ML3) were derived by matching the cancellation rates achieved by physician interpretation and two clinical selection rules. Annual MACE rates were compared in patients selected for rest scan cancellation between approaches. Patients selected for rest scan cancellation with ML had lower annualized MACE rates than those selected by physician interpretation or clinical selection rules (ML1 vs. physician interpretation: 1.4 ± 0.1% vs. 2.1 ± 0.1%; ML2 vs. clinical selection: 1.5 ± 0.1% vs. 2.0 ± 0.1%; ML3 vs. stringent clinical selection: 0.6 ± 0.1% vs. 1.7 ± 0.1%, all P < 0.0001) at matched cancellation rates (60 ± 0.7, 64 ± 0.7, and 30 ± 0.6%). Annualized all-cause mortality rates in populations recommended for rest cancellation by physician interpretation, clinical selection approaches were higher (1.3%, 1.2%, and 1.0%, respectively) compared with corresponding ML thresholds (0.6%, 0.6%, and 0.2%)., Conclusion: ML, using clinical and stress imaging data, can be used to automatically recommend cancellation of rest SPECT MPI scans, while ensuring higher prognostic safety than current clinical approaches., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: To optimize per-vessel prediction of early coronary revascularization (ECR) within 90 days after fast single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) using machine learning (ML) and introduce a method for a patient-specific explanation of ML results in a clinical setting., Methods and Results: A total of 1980 patients with suspected coronary artery disease (CAD) underwent stress/rest 99mTc-sestamibi/tetrofosmin MPI with new-generation SPECT scanners were included. All patients had invasive coronary angiography within 6 months after SPECT MPI. ML utilized 18 clinical, 9 stress test, and 28 imaging variables to predict per-vessel and per-patient ECR with 10-fold cross-validation. Area under the receiver operator characteristics curve (AUC) of ML was compared with standard quantitative analysis [total perfusion deficit (TPD)] and expert interpretation. ECR was performed in 958 patients (48%). Per-vessel, the AUC of ECR prediction by ML (AUC 0.79, 95% confidence interval (CI) [0.77, 0.80]) was higher than by regional stress TPD (0.71, [0.70, 0.73]), combined-view stress TPD (AUC 0.71, 95% CI [0.69, 0.72]), or ischaemic TPD (AUC 0.72, 95% CI [0.71, 0.74]), all P < 0.001. Per-patient, the AUC of ECR prediction by ML (AUC 0.81, 95% CI [0.79, 0.83]) was higher than that of stress TPD, combined-view TPD, and ischaemic TPD, all P < 0.001. ML also outperformed nuclear cardiologists' expert interpretation of MPI for the prediction of early revascularization performance. A method to explain ML prediction for an individual patient was also developed., Conclusion: In patients with suspected CAD, the prediction of ECR by ML outperformed automatic MPI quantitation by TPDs (per-vessel and per-patient) or nuclear cardiologists' expert interpretation (per-patient)., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: Increased attenuation of pericoronary adipose tissue (PCAT) around the proximal right coronary artery (RCA) from coronary computed tomography angiography (CTA) has been shown to be associated with coronary inflammation and improved prediction of cardiac death over plaque features. Our aim was to investigate whether PCAT CT attenuation is related to progression of coronary plaque burden., Methods and Results: We analysed CTA studies of 111 stable patients (age 59.2 ± 9.8 years, 77% male) who underwent sequential CTA (3.4 ± 1.6 years between scans) with identical acquisition protocols. Total plaque (TP), calcified plaque (CP), non-calcified plaque (NCP), and low-density non-calcified plaque (LD-NCP) volumes and corresponding burden (plaque volume × 100%/vessel volume) were quantified using semi-automated software. PCAT CT attenuation (HU) was measured around the proximal RCA, the most standardized method for PCAT analysis. Patients with an increase in NCP burden (n = 51) showed an increase in PCAT attenuation, whereas patients with a decrease in NCP burden (n = 60) showed a decrease {4.4 [95% confidence interval (CI) 2.6-6.2] vs. -2.78 (95% CI -4.6 to -1.0) HU, P < 0.0001}. Changes in PCAT attenuation correlated with changes in the burden of NCP (r = 0.55, P < 0.001) and LD-NCP (r = 0.24, P = 0.01); but not CP burden (P = 0.3). Increased baseline PCAT attenuation ≥-75 HU was independently associated with increase in NCP (odds ratio 3.07, 95% CI 1.4-7.0; P < 0.008) and TP burden on follow-up CTA., Conclusion: PCAT attenuation measured from routine CTA is related to the progression of NCP and TP burden. This imaging biomarker may help to identify patients at increased risk of high-risk plaque progression and allow monitoring of beneficial changes from medical therapy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Coronary computed tomography angiography (CTA) allows quantification of stenosis. However, such quantitative analysis is not part of clinical routine. We evaluated the feasibility of utilizing deep learning for quantifying coronary artery disease from CTA., Methods: A total of 716 diseased segments in 156 patients (66 ± 10 years) who underwent CTA were analyzed. Minimal luminal area (MLA), percent diameter stenosis (DS), and percent contrast density difference (CDD) were measured using semi-automated software (Autoplaque) by an expert reader. Using the expert annotations, deep learning was performed with convolutional neural networks using 10-fold cross-validation to segment CTA lumen and calcified plaque. MLA, DS and CDD computed using deep-learning-based approach was compared to expert reader measurements., Results: There was excellent correlation between the expert reader and deep learning for all quantitative measures (r=0.984 for MLA; r=0.957 for DS; and r=0.975 for CDD, p<0.001 for all). The expert reader and deep learning method was not significantly different for MLA (median 4.3 mm 2 for both, p=0.68) and CDD (11.6 vs 11.1%, p=0.30), and was significantly different for DS (26.0 vs 26.6%, p<0.05); however, the ranges of all the quantitative measures were within inter-observer variability between 2 expert readers., Conclusions: Our deep learning-based method allows quantitative measurement of coronary artery disease segments accurately from CTA and may enhance clinical reporting.

Registration of histopathology volumes to Magnetic Resonance Images(MRI) is a crucial step for finding correlations in Prostate Cancer (PCa) and assessing tumor agressivity. This paper proposes a two-stage framework aimed at registering both modalities. Firstly, Speeded-Up Robust Features (SURF) algorithm and a context-based search is used to automatically determine slice correspondences between MRI and histology volumes. This step initializes a multimodal nonrigid registration strategy, which allows to propagate histology slices to MRI. Evaluation was performed on 5 prospective studies using a slice index score and landmark distances. With respect to a manual ground truth, the first stage of the framework exhibited an average error of 1,54 slice index and 3,51 mm in the prostate specimen. The reconstruction of a three-dimensional Whole-Mount Histology (WMH) shows promising results aimed to perform later PCa pattern detection and staging.

Multi-parametric magnetic resonance imaging (mMRI) is the standard exam for prostate cancer diagnosis, staging and risk assessment in current clinical routine. Correlating mMRI in-vivo observations with biological findings from radical prostatectomy specimen would improve the optimal therapy selection. Thus, we proposed a method for reconstructing and registering the prostate whole-mount histology (WMH) to the MRI, considering a thin slicing of the prostatectomy specimen. The method was evaluated on 3 patients, included in a prospective study, for which hematein-eosinsafran and immunohistochemistry stainings were performed. The registration error was assessed by measuring the Euclidean distance between landmarks, previously identified by an expert on both mMRI and histological slices. The mean error was 4:90α1:34 mm. Our method demonstrated promising results for registering prostate WMH to in-vivo mMRI, thus allowing for spatial accurate correlation between radiologic observations and biological information.