Deep Learning-Enabled Quantification of 99mTc-Pyrophosphate SPECT/CT for Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR CA) is increasingly recognized as a cause of heart failure in older patients, with 99mTc-pyrophosphate imaging frequently used to establish the diagnosis. Visual interpretation of SPECT images is the gold standard for interpretation but is inherently subjective. Manual quantitation of SPECT myocardial 99mTc-pyrophosphate activity is time-consuming and not performed clinically. We evaluated a deep learning approach for fully automated volumetric quantitation of 99mTc-pyrophosphate using segmentation of coregistered anatomic structures from CT attenuation maps. Methods: Patients who underwent SPECT/CT 99mTc-pyrophosphate imaging for suspected ATTR CA were included. Diagnosis of ATTR CA was determined using standard criteria. Cardiac chambers and myocardium were segmented from CT attenuation maps using a foundational deep learning model and then applied to attenuation-corrected SPECT images to quantify radiotracer activity. We evaluated the diagnostic accuracy of target-to-background ratio (TBR), cardiac pyrophosphate activity (CPA), and volume of involvement (VOI) using the area under the receiver operating characteristic curve (AUC). We then evaluated associations with the composite outcome of cardiovascular death or heart failure hospitalization. Results: In total, 299 patients were included (median age, 76 y), with ATTR CA diagnosed in 83 (27.8%) patients. CPA (AUC, 0.989; 95% CI, 0.974-1.00) and VOI (AUC, 0.988; 95% CI, 0.973-1.00) had the highest prediction performance for ATTR CA. The next highest AUC was for TBR (AUC, 0.979; 95% CI, 0.964-0.995). The AUC for CPA was significantly higher than that for heart-to-contralateral ratio (AUC, 0.975; 95% CI, 0.952-0.998; P = 0.046). Twenty-three patients with ATTR CA experienced cardiovascular death or heart failure hospitalization. All methods for establishing TBR, CPA, and VOI were associated with an increased risk of events after adjustment for age, with hazard ratios ranging from 1.41 to 1.84 per SD increase. Conclusion: Deep learning segmentation of coregistered CT attenuation maps is not affected by the pattern of radiotracer uptake and allows for fully automatic quantification of hot-spot SPECT imaging such as 99mTc-pyrophosphate. This approach can be used to accurately identify patients with ATTR CA and may play a role in risk prediction.

Holistic AI analysis of hybrid cardiac perfusion images for mortality prediction.

Background: While low-dose computed tomography scans are traditionally used for attenuation correction in hybrid myocardial perfusion imaging (MPI), they also contain additional anatomic and pathologic information not utilized in clinical assessment. We seek to uncover the full potential of these scans utilizing a holistic artificial intelligence (AI)-driven image framework for image assessment. Methods: Patients with SPECT/CT MPI from 4 REFINE SPECT registry sites were studied. A multi-structure model segmented 33 structures and quantified 15 radiomics features for each on CT attenuation correction (CTAC) scans. Coronary artery calcium and epicardial adipose tissue scores were obtained from separate deep-learning models. Normal standard quantitative MPI features were derived by clinical software. Extreme Gradient Boosting derived all-cause mortality risk scores from SPECT, CT, stress test, and clinical features utilizing a 10-fold cross-validation regimen to separate training from testing data. The performance of the models for the prediction of all-cause mortality was evaluated using area under the receiver-operating characteristic curves (AUCs). Results: Of 10,480 patients, 5,745 (54.8%) were male, and median age was 65 (interquartile range [IQR] 57-73) years. During the median follow-up of 2.9 years (1.6-4.0), 651 (6.2%) patients died. The AUC for mortality prediction of the model (combining CTAC, MPI, and clinical data) was 0.80 (95% confidence interval [0.74-0.87]), which was higher than that of an AI CTAC model (0.78 [0.71-0.85]), and AI hybrid model (0.79 [0.72-0.86]) incorporating CTAC and MPI data (p<0.001 for all). Conclusion: In patients with normal perfusion, the comprehensive model (0.76 [0.65-0.86]) had significantly better performance than the AI CTAC (0.72 [0.61-0.83]) and AI hybrid (0.73 [0.62-0.84]) models (p<0.001, for all).CTAC significantly enhances AI risk stratification with MPI SPECT/CT beyond its primary role - attenuation correction. A comprehensive multimodality approach can significantly improve mortality prediction compared to MPI information alone in patients undergoing cardiac SPECT/CT.

Impact of cardiac size on SPECT myocardial perfusion imaging performance: Insights from the REFINE-SPECT registry.

AIMS: Variation in diagnostic performance of SPECT myocardial perfusion imaging (MPI) has been observed, yet the impact of cardiac size has not been well characterized. We assessed whether low left ventricular volume influences SPECT MPI's ability to detect obstructive coronary artery disease (CAD), and its interaction with age and sex. METHODS AND RESULTS: A total of 2,066 patients without known CAD (67% male, 64.7 ± 11.2 years) across 9 institutions underwent SPECT MPI with solid-state scanners followed by coronary angiography as part of the REgistry of Fast Myocardial Perfusion Imaging with NExt Generation SPECT. Area under receiver-operating characteristic curve (AUC) analyses evaluated performance of quantitative and visual assessments according to cardiac size (end- diastolic volume [EDV]; < 20th vs. ≥ 20th population or sex-specific percentiles), age (<75 vs. ≥ 75 years), and sex. Significantly decreased performance was observed in patients with low EDV compared to those without (AUC: population 0.72 vs. 0.78, p = 0.03; sex-specific 0.72 vs. 0.79, p = 0.01) and elderly patients compared to younger patients (AUC 0.72 vs. 0.78, p = 0.03), whereas males and females demonstrated similar AUC (0.77 vs. 0.76, p = 0.67). The reduction in accuracy attributed to lower volumes was primarily observed in males (sex-specific threshold: EDV 0.69 vs. 0.79, p = 0.01). Accordingly, a significant decrease in AUC, sensitivity, specificity, and negative predictive value for quantitative and visual assessments was noted in patients with at least two characteristics of low EDV, elderly age, or male sex. CONCLUSIONS: Detection of CAD with SPECT MPI is negatively impacted by small cardiac size, most notably in elderly and male patients.

AI-Defined Cardiac Anatomy Improves Risk Stratification of Hybrid Perfusion Imaging.

BACKGROUND: Computed tomography attenuation correction (CTAC) improves perfusion quantification of hybrid myocardial perfusion imaging by correcting for attenuation artifacts. Artificial intelligence (AI) can automatically measure coronary artery calcium (CAC) from CTAC to improve risk prediction but could potentially derive additional anatomic features. OBJECTIVES: The authors evaluated AI-based derivation of cardiac anatomy from CTAC and assessed its added prognostic utility. METHODS: The authors considered consecutive patients without known coronary artery disease who underwent single-photon emission computed tomography/computed tomography (CT) myocardial perfusion imaging at 3 separate centers. Previously validated AI models were used to segment CAC and cardiac structures (left atrium, left ventricle, right atrium, right ventricular volume, and left ventricular [LV] mass) from CTAC. They evaluated associations with major adverse cardiovascular events (MACEs), which included death, myocardial infarction, unstable angina, or revascularization. RESULTS: In total, 7,613 patients were included with a median age of 64 years. During a median follow-up of 2.4 years (IQR: 1.3-3.4 years), MACEs occurred in 1,045 (13.7%) patients. Fully automated AI processing took an average of 6.2 ± 0.2 seconds for CAC and 15.8 ± 3.2 seconds for cardiac volumes and LV mass. Patients in the highest quartile of LV mass and left atrium, LV, right atrium, and right ventricular volume were at significantly increased risk of MACEs compared to patients in the lowest quartile, with HR ranging from 1.46 to 3.31. The addition of all CT-based volumes and CT-based LV mass improved the continuous net reclassification index by 23.1%. CONCLUSIONS: AI can automatically derive LV mass and cardiac chamber volumes from CT attenuation imaging, significantly improving cardiovascular risk assessment for hybrid perfusion imaging.

Predicting mortality from AI cardiac volumes mass and coronary calcium on chest computed tomography.

Chest computed tomography is one of the most common diagnostic tests, with 15 million scans performed annually in the United States. Coronary calcium can be visualized on these scans, but other measures of cardiac risk such as atrial and ventricular volumes have classically required administration of contrast. Here we show that a fully automated pipeline, incorporating two artificial intelligence models, automatically quantifies coronary calcium, left atrial volume, left ventricular mass, and other cardiac chamber volumes in 29,687 patients from three cohorts. The model processes chamber volumes and coronary artery calcium with an end-to-end time of ~18 s, while failing to segment only 0.1% of cases. Coronary calcium, left atrial volume, and left ventricular mass index are independently associated with all-cause and cardiovascular mortality and significantly improve risk classification compared to identification of abnormalities by a radiologist. This automated approach can be integrated into clinical workflows to improve identification of abnormalities and risk stratification, allowing physicians to improve clinical decision-making.

AI-derived epicardial fat measurements improve cardiovascular risk prediction from myocardial perfusion imaging.

Epicardial adipose tissue (EAT) volume and attenuation are associated with cardiovascular risk, but manual annotation is time-consuming. We evaluated whether automated deep learning-based EAT measurements from ungated computed tomography (CT) are associated with death or myocardial infarction (MI). We included 8781 patients from 4 sites without known coronary artery disease who underwent hybrid myocardial perfusion imaging. Of those, 500 patients from one site were used for model training and validation, with the remaining patients held out for testing (n = 3511 internal testing, n = 4770 external testing). We modified an existing deep learning model to first identify the cardiac silhouette, then automatically segment EAT based on attenuation thresholds. Deep learning EAT measurements were obtained in <2 s compared to 15 min for expert annotations. There was excellent agreement between EAT attenuation (Spearman correlation 0.90 internal, 0.82 external) and volume (Spearman correlation 0.90 internal, 0.91 external) by deep learning and expert segmentation in all 3 sites (Spearman correlation 0.90-0.98). During median follow-up of 2.7 years (IQR 1.6-4.9), 565 patients experienced death or MI. Elevated EAT volume and attenuation were independently associated with an increased risk of death or MI after adjustment for relevant confounders. Deep learning can automatically measure EAT volume and attenuation from low-dose, ungated CT with excellent correlation with expert annotations, but in a fraction of the time. EAT measurements offer additional prognostic insights within the context of hybrid perfusion imaging.

Clinical phenotypes among patients with normal cardiac perfusion using unsupervised learning: a retrospective observational study.

BACKGROUND: Myocardial perfusion imaging (MPI) is one of the most common cardiac scans and is used for diagnosis of coronary artery disease and assessment of cardiovascular risk. However, the large majority of MPI patients have normal results. We evaluated whether unsupervised machine learning could identify unique phenotypes among patients with normal scans and whether those phenotypes were associated with risk of death or myocardial infarction. METHODS: Patients from a large international multicenter MPI registry (10 sites) with normal perfusion by expert visual interpretation were included in this cohort analysis. The training population included 9849 patients, and external testing population 12,528 patients. Unsupervised cluster analysis was performed, with separate training and external testing cohorts, to identify clusters, with four distinct phenotypes. We evaluated the clinical and imaging features of clusters and their associations with death or myocardial infarction. FINDINGS: Patients in Clusters 1 and 2 almost exclusively underwent exercise stress, while patients in Clusters 3 and 4 mostly required pharmacologic stress. In external testing, the risk for Cluster 4 patients (20.2% of population, unadjusted hazard ratio [HR] 6.17, 95% confidence interval [CI] 4.64-8.20) was higher than the risk associated with pharmacologic stress (HR 3.03, 95% CI 2.53-3.63), or previous myocardial infarction (HR 1.82, 95% CI 1.40-2.36). INTERPRETATION: Unsupervised learning identified four distinct phenotypes of patients with normal perfusion scans, with a significant proportion of patients at very high risk of myocardial infarction or death. Our results suggest a potential role for patient phenotyping to improve risk stratification of patients with normal imaging results. FUNDING: This work was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health [R35HL161195 to PS]. The REFINE SPECT database was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health [R01HL089765 to PS]. MCW was supported by the British Heart Foundation [FS/ICRF/20/26002].

Time and event-specific deep learning for personalized risk assessment after cardiac perfusion imaging.

Standard clinical interpretation of myocardial perfusion imaging (MPI) has proven prognostic value for predicting major adverse cardiovascular events (MACE). However, personalizing predictions to a specific event type and time interval is more challenging. We demonstrate an explainable deep learning model that predicts the time-specific risk separately for all-cause death, acute coronary syndrome (ACS), and revascularization directly from MPI and 15 clinical features. We train and test the model internally using 10-fold hold-out cross-validation (n = 20,418) and externally validate it in three separate sites (n = 13,988) with MACE follow-ups for a median of 3.1 years (interquartile range [IQR]: 1.6, 3.6). We evaluate the model using the cumulative dynamic area under receiver operating curve (cAUC). The best model performance in the external cohort is observed for short-term prediction - in the first six months after the scan, mean cAUC for ACS and all-cause death reaches 0.76 (95% confidence interval [CI]: 0.75, 0.77) and 0.78 (95% CI: 0.78, 0.79), respectively. The model outperforms conventional perfusion abnormality measures at all time points for the prediction of death in both internal and external validations, with improvement increasing gradually over time. Individualized patient explanations are visualized using waterfall plots, which highlight the contribution degree and direction for each feature. This approach allows the derivation of individual event probability as a function of time as well as patient- and event-specific risk explanations that may help draw attention to modifiable risk factors. Such a method could help present post-scan risk assessments to the patient and foster shared decision-making.

Unsupervised learning to characterize patients with known coronary artery disease undergoing myocardial perfusion imaging.

PURPOSE: Patients with known coronary artery disease (CAD) comprise a heterogenous population with varied clinical and imaging characteristics. Unsupervised machine learning can identify new risk phenotypes in an unbiased fashion. We use cluster analysis to risk-stratify patients with known CAD undergoing single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). METHODS: From 37,298 patients in the REFINE SPECT registry, we identified 9221 patients with known coronary artery disease. Unsupervised machine learning was performed using clinical (23), acquisition (17), and image analysis (24) parameters from 4774 patients (internal cohort) and validated with 4447 patients (external cohort). Risk stratification for all-cause mortality was compared to stress total perfusion deficit (< 5%, 5-10%, ≥10%). RESULTS: Three clusters were identified, with patients in Cluster 3 having a higher body mass index, more diabetes mellitus and hypertension, and less likely to be male, have dyslipidemia, or undergo exercise stress imaging (p < 0.001 for all). In the external cohort, during median follow-up of 2.6 [0.14, 3.3] years, all-cause mortality occurred in 312 patients (7%). Cluster analysis provided better risk stratification for all-cause mortality (Cluster 3: hazard ratio (HR) 5.9, 95% confidence interval (CI) 4.0, 8.6, p < 0.001; Cluster 2: HR 3.3, 95% CI 2.5, 4.5, p < 0.001; Cluster 1, reference) compared to stress total perfusion deficit (≥10%: HR 1.9, 95% CI 1.5, 2.5 p < 0.001; < 5%: reference). CONCLUSIONS: Our unsupervised cluster analysis in patients with known CAD undergoing SPECT MPI identified three distinct phenotypic clusters and predicted all-cause mortality better than ischemia alone.

Deep Learning of Coronary Calcium Scores From PET/CT Attenuation Maps Accurately Predicts Adverse Cardiovascular Events.

BACKGROUND: Assessment of coronary artery calcium (CAC) by computed tomographic (CT) imaging provides an accurate measure of atherosclerotic burden. CAC is also visible in computed tomographic attenuation correction (CTAC) scans, always acquired with cardiac positron emission tomographic (PET) imaging. OBJECTIVES: The aim of this study was to develop a deep-learning (DL) model capable of fully automated CAC definition from PET CTAC scans. METHODS: The novel DL model, originally developed for video applications, was adapted to rapidly quantify CAC. The model was trained using 9,543 expert-annotated CT scans and was tested in 4,331 patients from an external cohort undergoing PET/CT imaging with major adverse cardiac events (MACEs) (follow-up 4.3 years), including same-day paired electrocardiographically gated CAC scans available in 2,737 patients. MACE risk stratification in 4 CAC score categories (0, 1-100, 101-400, and >400) was analyzed and CAC scores derived from electrocardiographically gated CT scans (standard scores) by expert observers were compared with automatic DL scores from CTAC scans. RESULTS: Automatic DL scoring required <6 seconds per scan. DL CTAC scores provided stepwise increase in the risk for MACE across the CAC score categories (HR up to 3.2; P < 0.001). Net reclassification improvement of standard CAC scores over DL CTAC scores was nonsignificant (-0.02; 95% CI: -0.11 to 0.07). The negative predictive values for MACE of zero CAC with standard (85%) and DL CTAC (83%) CAC scores were similar (P = 0.19). CONCLUSIONS: DL CTAC scores predict cardiovascular risk similarly to standard CAC scores quantified manually by experienced operators from dedicated electrocardiographically gated CAC scans and can be obtained almost instantly, with no changes to PET/CT scanning protocol.

Direct Risk Assessment From Myocardial Perfusion Imaging Using Explainable Deep Learning.

BACKGROUND: Myocardial perfusion imaging (MPI) is frequently used to provide risk stratification, but methods to improve the accuracy of these predictions are needed. OBJECTIVES: The authors developed an explainable deep learning (DL) model (HARD MACE [major adverse cardiac events]-DL) for the prediction of death or nonfatal myocardial infarction (MI) and validated its performance in large internal and external testing groups. METHODS: Patients undergoing single-photon emission computed tomography MPI were included, with 20,401 patients in the training and internal testing group (5 sites) and 9,019 in the external testing group (2 different sites). HARD MACE-DL uses myocardial perfusion, motion, thickening, and phase polar maps combined with age, sex, and cardiac volumes. The primary outcome was all-cause mortality or nonfatal MI. Prognostic accuracy was evaluated using area under the receiver-operating characteristic curve (AUC). RESULTS: During internal testing, patients with normal perfusion and elevated HARD MACE-DL risk were at higher risk than patients with abnormal perfusion and low HARD MACE-DL risk (annualized event rate, 2.9% vs 1.2%; P < 0.001). Patients in the highest quartile of HARD MACE-DL score had an annual rate of death or MI (4.8%) 10-fold higher than patients in the lowest quartile (0.48% per year). In external testing, the AUC for HARD MACE-DL (0.73; 95% CI: 0.71-0.75) was higher than a logistic regression model (AUC: 0.70), stress total perfusion deficit (TPD) (AUC: 0.65), and ischemic TPD (AUC: 0.63; all P < 0.01). Calibration, a measure of how well predicted risk matches actual risk, was excellent in both groups (Brier score, 0.079 for internal and 0.070 for external). CONCLUSIONS: The DL model predicts death or MI directly from MPI, by estimating patient-level risk with good calibration and improved accuracy compared with traditional quantitative approaches. The model incorporates mechanisms to explain to the physician which image regions contribute to the adverse event prediction.

Deep Learning Coronary Artery Calcium Scores from SPECT/CT Attenuation Maps Improve Prediction of Major Adverse Cardiac Events.

Low-dose ungated CT attenuation correction (CTAC) scans are commonly obtained with SPECT/CT myocardial perfusion imaging. Despite the characteristically low image quality of CTAC, deep learning (DL) can potentially quantify coronary artery calcium (CAC) from these scans in an automatic manner. We evaluated CAC quantification derived with a DL model, including correlation with expert annotations and associations with major adverse cardiovascular events (MACE). Methods: We trained a convolutional long short-term memory DL model to automatically quantify CAC on CTAC scans using 6,608 studies (2 centers) and evaluated the model in an external cohort of patients without known coronary artery disease (n = 2,271) obtained in a separate center. We assessed agreement between DL and expert annotated CAC scores. We also assessed associations between MACE (death, revascularization, myocardial infarction, or unstable angina) and CAC categories (0, 1-100, 101-400, or >400) for scores manually derived by experienced readers and scores obtained fully automatically by DL using multivariable Cox models (adjusted for age, sex, past medical history, perfusion, and ejection fraction) and net reclassification index. Results: In the external testing population, DL CAC was 0 in 908 patients (40.0%), 1-100 in 596 (26.2%), 100-400 in 354 (15.6%), and >400 in 413 (18.2%). Agreement in CAC category by DL CAC and expert annotation was excellent (linear weighted κ, 0.80), but DL CAC was obtained automatically in less than 2 s compared with about 2.5 min for expert CAC. DL CAC category was an independent risk factor for MACE with hazard ratios in comparison to a CAC of zero: CAC of 1-100 (2.20; 95% CI, 1.54-3.14; P < 0.001), CAC of 101-400 (4.58; 95% CI, 3.23-6.48; P < 0.001), and CAC of more than 400 (5.92; 95% CI, 4.27-8.22; P < 0.001). Overall, the net reclassification index was 0.494 for DL CAC, which was similar to expert annotated CAC (0.503). Conclusion: DL CAC from SPECT/CT attenuation maps agrees well with expert CAC annotations and provides a similar risk stratification but can be obtained automatically. DL CAC scores improved classification of a significant proportion of patients as compared with SPECT myocardial perfusion alone.

Mitigating bias in deep learning for diagnosis of coronary artery disease from myocardial perfusion SPECT images.

PURPOSE: Artificial intelligence (AI) has high diagnostic accuracy for coronary artery disease (CAD) from myocardial perfusion imaging (MPI). However, when trained using high-risk populations (such as patients with correlating invasive testing), the disease probability can be overestimated due to selection bias. We evaluated different strategies for training AI models to improve the calibration (accurate estimate of disease probability), using external testing. METHODS: Deep learning was trained using 828 patients from 3 sites, with MPI and invasive angiography within 6 months. Perfusion was assessed using upright (U-TPD) and supine total perfusion deficit (S-TPD). AI training without data augmentation (model 1) was compared to training with augmentation (increased sampling) of patients without obstructive CAD (model 2), and patients without CAD and TPD < 2% (model 3). All models were tested in an external population of patients with invasive angiography within 6 months (n = 332) or low likelihood of CAD (n = 179). RESULTS: Model 3 achieved the best calibration (Brier score 0.104 vs 0.121, p < 0.01). Improvement in calibration was particularly evident in women (Brier score 0.084 vs 0.124, p < 0.01). In external testing (n = 511), the area under the receiver operating characteristic curve (AUC) was higher for model 3 (0.930), compared to U-TPD (AUC 0.897) and S-TPD (AUC 0.900, p < 0.01 for both). CONCLUSION: Training AI models with augmentation of low-risk patients can improve calibration of AI models developed to identify patients with CAD, allowing more accurate assignment of disease probability. This is particularly important in lower-risk populations and in women, where overestimation of disease probability could significantly influence down-stream patient management.

Deep Learning-Based Attenuation Correction Improves Diagnostic Accuracy of Cardiac SPECT.

To improve diagnostic accuracy, myocardial perfusion imaging (MPI) SPECT studies can use CT-based attenuation correction (AC). However, CT-based AC is not available for most SPECT systems in clinical use, increases radiation exposure, and is impacted by misregistration. We developed and externally validated a deep-learning model to generate simulated AC images directly from non-AC (NC) SPECT, without the need for CT. Methods: SPECT myocardial perfusion imaging was performed using 99mTc-sestamibi or 99mTc-tetrofosmin on contemporary scanners with solid-state detectors. We developed a conditional generative adversarial neural network that applies a deep learning model (DeepAC) to generate simulated AC SPECT images. The model was trained with short-axis NC and AC images performed at 1 site (n = 4,886) and was tested on patients from 2 separate external sites (n = 604). We assessed the diagnostic accuracy of the stress total perfusion deficit (TPD) obtained from NC, AC, and DeepAC images for obstructive coronary artery disease (CAD) with area under the receiver-operating-characteristic curve. We also quantified the direct count change among AC, NC, and DeepAC images on a per-voxel basis. Results: DeepAC could be obtained in less than 1 s from NC images; area under the receiver-operating-characteristic curve for obstructive CAD was higher for DeepAC TPD (0.79; 95% CI, 0.72-0.85) than for NC TPD (0.70; 95% CI, 0.63-0.78; P < 0.001) and similar to AC TPD (0.81; 95% CI, 0.75-0.87; P = 0.196). The normalcy rate in the low-likelihood-of-coronary-disease population was higher for DeepAC TPD (70.4%) and AC TPD (75.0%) than for NC TPD (54.6%, P < 0.001 for both). The positive count change (increase in counts) was significantly higher for AC versus NC (median, 9.4; interquartile range, 6.0-14.2; P < 0.001) than for AC versus DeepAC (median, 2.4; interquartile range, 1.3-4.2). Conclusion: In an independent external dataset, DeepAC provided improved diagnostic accuracy for obstructive CAD, as compared with NC images, and this accuracy was similar to that of actual AC. DeepAC simplifies the task of artifact identification for physicians, avoids misregistration artifacts, and can be performed rapidly without the need for CT hardware and additional acquisitions.

Deep Learning for Explainable Estimation of Mortality Risk From Myocardial Positron Emission Tomography Images.

BACKGROUND: We aim to develop an explainable deep learning (DL) network for the prediction of all-cause mortality directly from positron emission tomography myocardial perfusion imaging flow and perfusion polar map data and evaluate it using prospective testing. METHODS: A total of 4735 consecutive patients referred for stress and rest 82Rb positron emission tomography between 2010 and 2018 were followed up for all-cause mortality for 4.15 (2.24-6.3) years. DL network utilized polar maps of stress and rest perfusion, myocardial blood flow, myocardial flow reserve, and spill-over fraction combined with cardiac volumes, singular indices, and sex. Patients scanned from 2010 to 2016 were used for training and validation. The network was tested in a set of 1135 patients scanned from 2017 to 2018 to simulate prospective clinical implementation. RESULTS: In prospective testing, the area under the receiver operating characteristic curve for all-cause mortality prediction by DL (0.82 [95% CI, 0.77-0.86]) was higher than ischemia (0.60 [95% CI, 0.54-0.66]; P <0.001), myocardial flow reserve (0.70 [95% CI, 0.64-0.76], P <0.001) or a comprehensive logistic regression model (0.75 [95% CI, 0.69-0.80], P <0.05). The highest quartile of patients by DL had an annual all-cause mortality rate of 11.87% and had a 16.8 ([95% CI, 6.12%-46.3%]; P <0.001)-fold increase in the risk of death compared with the lowest quartile patients. DL showed a 21.6% overall reclassification improvement as compared with established measures of ischemia. CONCLUSIONS: The DL model trained directly on polar maps allows improved patient risk stratification in comparison with established methods for positron emission tomography flow or perfusion assessments.

Machine learning to predict abnormal myocardial perfusion from pre-test features.

BACKGROUND: Accurately predicting which patients will have abnormal perfusion on MPI based on pre-test clinical information may help physicians make test selection decisions. We developed and validated a machine learning (ML) model for predicting abnormal perfusion using pre-test features. METHODS: We included consecutive patients who underwent SPECT MPI, with 20,418 patients from a multi-center (5 sites) international registry in the training population and 9019 patients (from 2 separate sites) in the external testing population. The ML (extreme gradient boosting) model utilized 30 pre-test features to predict the presence of abnormal myocardial perfusion by expert visual interpretation. RESULTS: In external testing, the ML model had higher prediction performance for abnormal perfusion (area under receiver-operating characteristic curve [AUC] 0.762, 95% CI 0.750-0.774) compared to the clinical CAD consortium (AUC 0.689) basic CAD consortium (AUC 0.657), and updated Diamond-Forrester models (AUC 0.658, p < 0.001 for all). Calibration (validation of the continuous risk prediction) was superior for the ML model (Brier score 0.149) compared to the other models (Brier score 0.165 to 0.198, all p < 0.001). CONCLUSION: ML can predict abnormal myocardial perfusion using readily available pre-test information. This model could be used to help guide physician decisions regarding non-invasive test selection.

Differences in Prognostic Value of Myocardial Perfusion Single-Photon Emission Computed Tomography Using High-Efficiency Solid-State Detector Between Men and Women in a Large International Multicenter Study.

BACKGROUND: Semiquantitative assessment of stress myocardial perfusion defect has been shown to have greater prognostic value for prediction of major adverse cardiac events (MACE) in women compared with men in single-center studies with conventional single-photon emission computed tomography (SPECT) cameras. We evaluated sex-specific difference in the prognostic value of automated quantification of ischemic total perfusion defect (ITPD) and the interaction between sex and ITPD using high-efficiency SPECT cameras with solid-state detectors in an international multicenter imaging registry (REFINE SPECT [Registry of Fast Myocardial Perfusion Imaging With Next-Generation SPECT]). METHODS: Rest and exercise or pharmacological stress SPECT myocardial perfusion imaging were performed in 17 833 patients from 5 centers. MACE was defined as the first occurrence of death or myocardial infarction. Total perfusion defect (TPD) at rest, stress, and ejection fraction were quantified automatically by software. ITPD was given by stressTPD-restTPD. Cox proportional hazards model was used to evaluate the association between ITPD versus MACE-free survival and expressed as a hazard ratio. RESULTS: In 10614 men and 7219 women, with a median follow-up of 4.75 years (interquartile range, 3.7-6.1), there were 1709 MACE. In a multivariable Cox model, after adjusting for revascularization and other confounding variables, ITPD was associated with MACE (hazard ratio, 1.08 [95% CI, 1.05-1.1]; P<0.001). There was an interaction between ITPD and sex (P<0.001); predicted survival for ITPD<5% was worse among men compared to women, whereas survival among women was worse than men for ITPD≥5%, P<0.001. CONCLUSIONS: In the international, multicenter REFINE SPECT registry, moderate and severe ischemia as quantified by ITPD from high-efficiency SPECT is associated with a worse prognosis in women compared with men.

Reproducibility of quantitative coronary calcium scoring from PET/CT attenuation maps: comparison to ECG-gated CT scans.

PURPOSE: We sought to evaluate inter-scan and inter-reader agreement of coronary calcium (CAC) scores obtained from dedicated, ECG-gated CAC scans (standard CAC scan) and ultra-low-dose, ungated computed tomography attenuation correction (CTAC) scans obtained routinely during cardiac PET/CT imaging. METHODS: From 2928 consecutive patients who underwent same-day 82Rb cardiac PET/CT and gated CAC scan in the same hybrid PET/CT scanning session, we have randomly selected 200 cases with no history of revascularization. Standard CAC scans and ungated CTAC scans were scored by two readers using quantitative clinical software. We assessed the agreement between readers and between two scan protocols in 5 CAC categories (0, 1-10, 11-100, 101-400, and > 400) using Cohen's Kappa and concordance. RESULTS: Median age of patients was 70 (inter-quartile range: 63-77), and 46% were male. The inter-scan concordance index and Cohen's Kappa for readers 1 and 2 were 0.69; 0.75 (0.69, 0.81) and 0.72; 0.8 (0.75, 0.85) respectively. The inter-reader concordance index and Cohen's Kappa (95% confidence interval [CI]) was higher for standard CAC scans: 0.9 and 0.92 (0.89, 0.96), respectively, vs. for CTAC scans: 0.83 and 0.85 (0.79, 0.9) for CTAC scans (p = 0.02 for difference in Kappa). Most discordant readings between two protocols occurred for scans with low extent of calcification (CAC score < 100). CONCLUSION: CAC can be quantitatively assessed on PET CTAC maps with good agreement with standard scans, however with limited sensitivity for small lesions. CAC scoring of CTAC can be performed routinely without modification of PET protocol and added radiation dose.

Artificial intelligence for disease diagnosis and risk prediction in nuclear cardiology.

Artificial intelligence (AI) techniques have emerged as a highly efficient approach to accurately and rapidly interpret diagnostic imaging and may play a vital role in nuclear cardiology. In nuclear cardiology, there are many clinical, stress, and imaging variables potentially available, which need to be optimally integrated to predict the presence of obstructive coronary artery disease (CAD) or predict the risk of cardiovascular events. In spite of clinical awareness of a large number of potential variables, it is difficult for physicians to integrate multiple features consistently and objectively. Machine learning (ML) is particularly well suited to integrating this vast array of information to provide patient-specific predictions. Deep learning (DL), a branch of ML characterized by a multi-layered convolutional model architecture, can extract information directly from images and identify latent image features associated with a specific prediction. This review will discuss the latest AI applications to disease diagnosis and risk prediction in nuclear cardiology with a focus on potential clinical applications.

Explainable Deep Learning Improves Physician Interpretation of Myocardial Perfusion Imaging.

Artificial intelligence may improve accuracy of myocardial perfusion imaging (MPI) but will likely be implemented as an aid to physician interpretation rather than an autonomous tool. Deep learning (DL) has high standalone diagnostic accuracy for obstructive coronary artery disease (CAD), but its influence on physician interpretation is unknown. We assessed whether access to explainable DL predictions improves physician interpretation of MPI. Methods: We selected a representative cohort of patients who underwent MPI with reference invasive coronary angiography. Obstructive CAD, defined as stenosis ≥50% in the left main artery or ≥70% in other coronary segments, was present in half of the patients. We used an explainable DL model (CAD-DL), which was previously developed in a separate population from different sites. Three physicians interpreted studies first with clinical history, stress, and quantitative perfusion, then with all the data plus the DL results. Diagnostic accuracy was assessed using area under the receiver-operating-characteristic curve (AUC). Results: In total, 240 patients with a median age of 65 y (interquartile range 58-73) were included. The diagnostic accuracy of physician interpretation with CAD-DL (AUC 0.779) was significantly higher than that of physician interpretation without CAD-DL (AUC 0.747, P = 0.003) and stress total perfusion deficit (AUC 0.718, P < 0.001). With matched specificity, CAD-DL had higher sensitivity when operating autonomously compared with readers without DL results (P < 0.001), but not compared with readers interpreting with DL results (P = 0.122). All readers had numerically higher accuracy with CAD-DL, with AUC improvement 0.02-0.05, and interpretation with DL resulted in overall net reclassification improvement of 17.2% (95% CI 9.2%-24.4%, P < 0.001). Conclusion: Explainable DL predictions lead to meaningful improvements in physician interpretation; however, the improvement varied across the readers, reflecting the acceptance of this new technology. This technique could be implemented as an aid to physician diagnosis, improving the diagnostic accuracy of MPI.