Prevalence of electrocardiographic abnormalities among Iranian children and adolescents and associations with blood pressure and obesity: findings from the SHED LIGHT study.

BACKGROUND: There are few studies for detecting rhythm abnormalities among healthy children and adolescents. The aim of the study was to investigate the prevalence of abnormal electrocardiographic findings in the young Iranian population and its association with blood pressure and obesity. METHODS: A total of 15084 children and adolescents were examined in a randomly selected population of Tehran city, Iran, between October 2017 and December 2018. Anthropometric values and blood pressure measurements were also assessed. A standard 12-lead electrocardiogram was recorded by a unique recorder, and those were examined by electrophysiologists. RESULTS: All students mean age was 12.3 ± 3.1 years (6-18 years), and 52% were boys. A total of 2900 students (192.2/1000 persons; 95% confidence interval 186-198.6) had electrocardiographic abnormalities. The rate of electrocardiographic abnormalities was higher in boys than girls (p < 0.001). Electrocardiographic abnormalities were significantly higher in thin than obese students (p < 0.001), and there was a trend towards hypertensive individuals to have more electrocardiographic abnormalities compared to normotensive individuals (p = 0.063). Based on the multivariable analysis, individuals with electrocardiographic abnormalities were less likely to be girls (odds ratio 0.745, 95% confidence interval 0.682-0.814) and had a lower body mass index (odds ratio 0.961, 95% confidence interval 0.944-0.979). CONCLUSIONS: In this large-scale study, there was a high prevalence of electrocardiographic abnormalities among young population. In addition, electrocardiographic findings were significantly influenced by increasing age, sex, obesity, and blood pressure levels. This community-based study revealed the implications of electrocardiographic screening to improve the care delivery by early detection.

Development of a patients' satisfaction analysis system using machine learning and lexicon-based methods.

BACKGROUND: Patients' rights are integral to medical ethics. This study aimed to perform sentiment analysis and opinion mining on patients' messages by a combination of lexicon-based and machine learning methods to identify positive or negative comments and to determine the different ward and staff names mentioned in patients' messages. METHODS: The level of satisfaction and observance of the rights of 250 service recipients of the hospital was evaluated through the related checklists by the evaluator. In total, 822 Persian messages, composed of 540 negative and 282 positive comments, were collected and labeled by the evaluator. Pre-processing was performed on the messages and followed by 2 feature vectors which were extracted from the messages, including the term frequency-inverse document frequency (TFIDF) vector and a combination of the multifeature (MF) (a lexicon-based method) and TFIDF (MF + TFIDF) vectors. Six feature selectors and 5 classifiers were used in this study. For the evaluations, 5-fold cross-validation with different metrics including area under the receiver operating characteristic curve (AUC), accuracy (ACC), F1 score, sensitivity (SEN), specificity (SPE) and Precision-Recall Curves (PRC) were reported. Message tag detection, which featured different hospital wards and identified staff names mentioned in the study patients' messages, was implemented by the lexicon-based method. RESULTS: The best classifier was Multinomial Naïve Bayes in combination with MF + TFIDF feature vector and SelectFromModel (SFM) feature selection (ACC = 0.89 ± 0.03, AUC = 0.87 ± 0.03, F1 = 0.92 ± 0.03, SEN = 0.93 ± 0.04, and SPE = 0.82 ± 0.02, PRC-AUC = 0.97). Two methods of assessment by the evaluator and artificial intelligence as well as survey systems were compared. CONCLUSION: Our results demonstrated that the lexicon-based method, in combination with machine learning classifiers, could extract sentiments in patients' comments and classify them into positive and negative categories. We also developed an online survey system to analyze patients' satisfaction in different wards and to remove conventional assessments by the evaluator.

Time-to-event overall survival prediction in glioblastoma multiforme patients using magnetic resonance imaging radiomics.

PURPOSE: Glioblastoma Multiforme (GBM) represents the predominant aggressive primary tumor of the brain with short overall survival (OS) time. We aim to assess the potential of radiomic features in predicting the time-to-event OS of patients with GBM using machine learning (ML) algorithms. MATERIALS AND METHODS: One hundred nineteen patients with GBM, who had T1-weighted contrast-enhanced and T2-FLAIR MRI sequences, along with clinical data and survival time, were enrolled. Image preprocessing methods included 64 bin discretization, Laplacian of Gaussian (LOG) filters with three Sigma values and eight variations of Wavelet Transform. Images were then segmented, followed by the extraction of 1212 radiomic features. Seven feature selection (FS) methods and six time-to-event ML algorithms were utilized. The combination of preprocessing, FS, and ML algorithms (12 × 7 × 6 = 504 models) was evaluated by multivariate analysis. RESULTS: Our multivariate analysis showed that the best prognostic FS/ML combinations are the Mutual Information (MI)/Cox Boost, MI/Generalized Linear Model Boosting (GLMB) and MI/Generalized Linear Model Network (GLMN), all of which were done via the LOG (Sigma = 1 mm) preprocessing method (C-index = 0.77). The LOG filter with Sigma = 1 mm preprocessing method, MI, GLMB and GLMN achieved significantly higher C-indices than other preprocessing, FS, and ML methods (all p values < 0.05, mean C-indices of 0.65, 0.70, and 0.64, respectively). CONCLUSION: ML algorithms are capable of predicting the time-to-event OS of patients using MRI-based radiomic and clinical features. MRI-based radiomics analysis in combination with clinical variables might appear promising in assisting clinicians in the survival prediction of patients with GBM. Further research is needed to establish the applicability of radiomics in the management of GBM in the clinic.

Myocardial Perfusion SPECT Imaging Radiomic Features and Machine Learning Algorithms for Cardiac Contractile Pattern Recognition.

A U-shaped contraction pattern was shown to be associated with a better Cardiac resynchronization therapy (CRT) response. The main goal of this study is to automatically recognize left ventricular contractile patterns using machine learning algorithms trained on conventional quantitative features (ConQuaFea) and radiomic features extracted from Gated single-photon emission computed tomography myocardial perfusion imaging (GSPECT MPI). Among 98 patients with standard resting GSPECT MPI included in this study, 29 received CRT therapy and 69 did not (also had CRT inclusion criteria but did not receive treatment yet at the time of data collection, or refused treatment). A total of 69 non-CRT patients were employed for training, and the 29 were employed for testing. The models were built utilizing features from three distinct feature sets (ConQuaFea, radiomics, and ConQuaFea + radiomics (combined)), which were chosen using Recursive feature elimination (RFE) feature selection (FS), and then trained using seven different machine learning (ML) classifiers. In addition, CRT outcome prediction was assessed by different treatment inclusion criteria as the study's final phase. The MLP classifier had the highest performance among ConQuaFea models (AUC, SEN, SPE = 0.80, 0.85, 0.76). RF achieved the best performance in terms of AUC, SEN, and SPE with values of 0.65, 0.62, and 0.68, respectively, among radiomic models. GB and RF approaches achieved the best AUC, SEN, and SPE values of 0.78, 0.92, and 0.63 and 0.74, 0.93, and 0.56, respectively, among the combined models. A promising outcome was obtained when using radiomic and ConQuaFea from GSPECT MPI to detect left ventricular contractile patterns by machine learning.

iNucs: inter-nucleosome interactions.

MOTIVATION: Deciphering nucleosome-nucleosome interactions is an important step toward mesoscale description of chromatin organization but computational tools to perform such analyses are not publicly available. RESULTS: We developed iNucs, a user-friendly and efficient Python-based bioinformatics tool to compute and visualize nucleosome-resolved interactions using standard pairs format input generated from pairtools. AVAILABILITYAND IMPLEMENTATION: https://github.com/Karimi-Lab/inucs/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Myocardial Function Prediction After Coronary Artery Bypass Grafting Using MRI Radiomic Features and Machine Learning Algorithms.

The main aim of the present study was to predict myocardial function improvement in cardiac MR (LGE-CMR) images in patients after coronary artery bypass grafting (CABG) using radiomics and machine learning algorithms. Altogether, 43 patients who had visible scars on short-axis LGE-CMR images and were candidates for CABG surgery were selected and enrolled in this study. MR imaging was performed preoperatively using a 1.5-T MRI scanner. All images were segmented by two expert radiologists (in consensus). Prior to extraction of radiomics features, all MR images were resampled to an isotropic voxel size of 1.8 × 1.8 × 1.8 mm3. Subsequently, intensities were quantized to 64 discretized gray levels and a total of 93 features were extracted. The applied algorithms included a smoothly clipped absolute deviation (SCAD)-penalized support vector machine (SVM) and the recursive partitioning (RP) algorithm as a robust classifier for binary classification in this high-dimensional and non-sparse data. All models were validated with repeated fivefold cross-validation and 10,000 bootstrapping resamples. Ten and seven features were selected with SCAD-penalized SVM and RP algorithm, respectively, for CABG responder/non-responder classification. Considering univariate analysis, the GLSZM gray-level non-uniformity-normalized feature achieved the best performance (AUC: 0.62, 95% CI: 0.53-0.76) with SCAD-penalized SVM. Regarding multivariable modeling, SCAD-penalized SVM obtained an AUC of 0.784 (95% CI: 0.64-0.92), whereas the RP algorithm achieved an AUC of 0.654 (95% CI: 0.50-0.82). In conclusion, different radiomics texture features alone or combined in multivariate analysis using machine learning algorithms provide prognostic information regarding myocardial function in patients after CABG.

Cardiac SPECT radiomic features repeatability and reproducibility: A multi-scanner phantom study.

BACKGROUND: The aim of this work was to assess the robustness of cardiac SPECT radiomic features against changes in imaging settings, including acquisition, and reconstruction parameters. METHODS: Four commercial SPECT and SPECT/CT cameras were used to acquire images of a static cardiac phantom mimicking typical myorcardial perfusion imaging using 185 MBq of 99mTc. The effects of different image acquisition and reconstruction parameters, including number of views, view matrix size, attenuation correction, as well as image reconstruction related parameters (algorithm, number of iterations, number of subsets, type of post-reconstruction filter, and its associated parameters, including filter order and cut-off frequency) were studied. In total, 5,063 transverse views were reconstructed by varying the aforementioned factors. Eighty-seven radiomic features including first-, second-, and high-order textures were extracted from these images. To assess reproducibility and repeatability, the coefficient of variation (COV), as a widely adopted metric, was measured for each of the radiomic features over the different imaging settings. RESULTS: The Inverse Difference Moment Normalized (IDMN) and Inverse Difference Normalized (IDN) features from the Gray Level Co-occurrence Matrix (GLCM), Run Percentage (RP) from the Gray Level Co-occurrence Matrix (GLRLM), Zone Entropy (ZE) from the Gray Level Size Zone Matrix (GLSZM), and Dependence Entropy (DE) from the Gray Level Dependence Matrix (GLDM) feature sets were the only features that exhibited high reproducibility (COV ≤ 5%) against changes in all imaging settings. In addition, Large Area Low Gray Level Emphasis (LALGLE), Small Area Low Gray Level Emphasis (SALGLE) and Low Gray Level Zone Emphasis (LGLZE) from GLSZM, and Small Dependence Low Gray Level Emphasis (SDLGLE) from GLDM feature sets turned out to be less reproducible (COV > 20%) against changes in imaging settings. The GLRLM (31.88%) and GLDM feature set (54.2%) had the highest (COV < 5%) and lowest (COV > 20%) number of the reproducible features, respectively. Matrix size had the largest impact on feature variability as most of the features were not repeatable when matrix size was modified with 82.8% of them having a COV > 20%. CONCLUSION: The repeatability and reproducibility of SPECT/CT cardiac radiomic features under different imaging settings is feature-dependent. Different image acquisition and reconstruction protocols have variable effects on radiomic features. The radiomic features exhibiting low COV are potential candidates for future clinical studies.

Overall Survival Prediction in Renal Cell Carcinoma Patients Using Computed Tomography Radiomic and Clinical Information.

The aim of this work is to investigate the applicability of radiomic features alone and in combination with clinical information for the prediction of renal cell carcinoma (RCC) patients' overall survival after partial or radical nephrectomy. Clinical studies of 210 RCC patients from The Cancer Imaging Archive (TCIA) who underwent either partial or radical nephrectomy were included in this study. Regions of interest (ROIs) were manually defined on CT images. A total of 225 radiomic features were extracted and analyzed along with the 59 clinical features. An elastic net penalized Cox regression was used for feature selection. Accelerated failure time (AFT) with the shared frailty model was used to determine the effects of the selected features on the overall survival time. Eleven radiomic and twelve clinical features were selected based on their non-zero coefficients. Tumor grade, tumor malignancy, and pathology t-stage were the most significant predictors of overall survival (OS) among the clinical features (p < 0.002, < 0.02, and < 0.018, respectively). The most significant predictors of OS among the selected radiomic features were flatness, area density, and median (p < 0.02, < 0.02, and < 0.05, respectively). Along with important clinical features, such as tumor heterogeneity and tumor grade, imaging biomarkers such as tumor flatness, area density, and median are significantly correlated with OS of RCC patients.

Noninvasive Fuhrman grading of clear cell renal cell carcinoma using computed tomography radiomic features and machine learning.

PURPOSE: To identify optimal classification methods for computed tomography (CT) radiomics-based preoperative prediction of clear cell renal cell carcinoma (ccRCC) grade. MATERIALS AND METHODS: Seventy-one ccRCC patients (31 low grade and 40 high grade) were included in this study. Tumors were manually segmented on CT images followed by the application of three image preprocessing techniques (Laplacian of Gaussian, wavelet filter, and discretization of the intensity values) on delineated tumor volumes. Overall, 2530 radiomics features (tumor shape and size, intensity statistics, and texture) were extracted from each segmented tumor volume. Univariate analysis was performed to assess the association between each feature and the histological condition. Multivariate analysis involved the use of machine learning (ML) algorithms and the following three feature selection algorithms: the least absolute shrinkage and selection operator, Student's t test, and minimum Redundancy Maximum Relevance. These selected features were then used to construct three classification models (SVM, random forest, and logistic regression) to discriminate high from low-grade ccRCC at nephrectomy. Lastly, multivariate model performance was evaluated on the bootstrapped validation cohort using the area under the receiver operating characteristic curve (AUC) metric. RESULTS: The univariate analysis demonstrated that among the different image sets, 128 bin-discretized images have statistically significant different texture parameters with a mean AUC of 0.74 ± 3 (q value < 0.05). The three ML-based classifiers showed proficient discrimination between high and low-grade ccRCC. The AUC was 0.78 for logistic regression, 0.62 for random forest, and 0.83 for the SVM model, respectively. CONCLUSION: CT radiomic features can be considered as a useful and promising noninvasive methodology for preoperative evaluation of ccRCC Fuhrman grades.

Direct attenuation correction of brain PET images using only emission data via a deep convolutional encoder-decoder (Deep-DAC).

OBJECTIVE: To obtain attenuation-corrected PET images directly from non-attenuation-corrected images using a convolutional encoder-decoder network. METHODS: Brain PET images from 129 patients were evaluated. The network was designed to map non-attenuation-corrected (NAC) images to pixel-wise continuously valued measured attenuation-corrected (MAC) PET images via an encoder-decoder architecture. Image quality was evaluated using various evaluation metrics. Image quantification was assessed for 19 radiomic features in 83 brain regions as delineated using the Hammersmith atlas (n30r83). Reliability of measurements was determined using pixel-wise relative errors (RE; %) for radiomic feature values in reference MAC PET images. RESULTS: Peak signal-to-noise ratio (PSNR) and structural similarity index metric (SSIM) values were 39.2 ± 3.65 and 0.989 ± 0.006 for the external validation set, respectively. RE (%) of SUVmean was - 0.10 ± 2.14 for all regions, and only 3 of 83 regions depicted significant differences. However, the mean RE (%) of this region was 0.02 (range, - 0.83 to 1.18). SUVmax had mean RE (%) of - 3.87 ± 2.84 for all brain regions, and 17 regions in the brain depicted significant differences with respect to MAC images with a mean RE of - 3.99 ± 2.11 (range, - 8.46 to 0.76). Homogeneity amongst Haralick-based radiomic features had the highest number (20) of regions with significant differences with a mean RE (%) of 7.22 ± 2.99. CONCLUSIONS: Direct AC of PET images using deep convolutional encoder-decoder networks is a promising technique for brain PET images. The proposed deep learning method shows significant potential for emission-based AC in PET images with applications in PET/MRI and dedicated brain PET scanners. KEY POINTS: • We demonstrate direct emission-based attenuation correction of PET images without using anatomical information. • We performed radiomics analysis of 83 brain regions to show robustness of direct attenuation correction of PET images. • Deep learning methods have significant promise for emission-based attenuation correction in PET images with potential applications in PET/MRI and dedicated brain PET scanners.

Development and validation of survival prognostic models for head and neck cancer patients using machine learning and dosiomics and CT radiomics features: a multicentric study.

BACKGROUND: This study aimed to investigate the value of clinical, radiomic features extracted from gross tumor volumes (GTVs) delineated on CT images, dose distributions (Dosiomics), and fusion of CT and dose distributions to predict outcomes in head and neck cancer (HNC) patients. METHODS: A cohort of 240 HNC patients from five different centers was obtained from The Cancer Imaging Archive. Seven strategies, including four non-fusion (Clinical, CT, Dose, DualCT-Dose), and three fusion algorithms (latent low-rank representation referred (LLRR),Wavelet, weighted least square (WLS)) were applied. The fusion algorithms were used to fuse the pre-treatment CT images and 3-dimensional dose maps. Overall, 215 radiomics and Dosiomics features were extracted from the GTVs, alongside with seven clinical features incorporated. Five feature selection (FS) methods in combination with six machine learning (ML) models were implemented. The performance of the models was quantified using the concordance index (CI) in one-center-leave-out 5-fold cross-validation for overall survival (OS) prediction considering the time-to-event. RESULTS: The mean CI and Kaplan-Meier curves were used for further comparisons. The CoxBoost ML model using the Minimal Depth (MD) FS method and the glmnet model using the Variable hunting (VH) FS method showed the best performance with CI = 0.73 ± 0.15 for features extracted from LLRR fused images. In addition, both glmnet-Cindex and Coxph-Cindex classifiers achieved a CI of 0.72 ± 0.14 by employing the dose images (+ incorporated clinical features) only. CONCLUSION: Our results demonstrated that clinical features, Dosiomics and fusion of dose and CT images by specific ML-FS models could predict the overall survival of HNC patients with acceptable accuracy. Besides, the performance of ML methods among the three different strategies was almost comparable.

Impact of harmonization on the reproducibility of MRI radiomic features when using different scanners, acquisition parameters, and image pre-processing techniques: a phantom study.

This study investigated the impact of ComBat harmonization on the reproducibility of radiomic features extracted from magnetic resonance images (MRI) acquired on different scanners, using various data acquisition parameters and multiple image pre-processing techniques using a dedicated MRI phantom. Four scanners were used to acquire an MRI of a nonanatomic phantom as part of the TCIA RIDER database. In fast spin-echo inversion recovery (IR) sequences, several inversion durations were employed, including 50, 100, 250, 500, 750, 1000, 1500, 2000, 2500, and 3000 ms. In addition, a 3D fast spoiled gradient recalled echo (FSPGR) sequence was used to investigate several flip angles (FA): 2, 5, 10, 15, 20, 25, and 30 degrees. Nineteen phantom compartments were manually segmented. Different approaches were used to pre-process each image: Bin discretization, Wavelet filter, Laplacian of Gaussian, logarithm, square, square root, and gradient. Overall, 92 first-, second-, and higher-order statistical radiomic features were extracted. ComBat harmonization was also applied to the extracted radiomic features. Finally, the Intraclass Correlation Coefficient (ICC) and Kruskal-Wallis's (KW) tests were implemented to assess the robustness of radiomic features. The number of non-significant features in the KW test ranged between 0-5 and 29-74 for various scanners, 31-91 and 37-92 for three times tests, 0-33 to 34-90 for FAs, and 3-68 to 65-89 for IRs before and after ComBat harmonization, with different image pre-processing techniques, respectively. The number of features with ICC over 90% ranged between 0-8 and 6-60 for various scanners, 11-75 and 17-80 for three times tests, 3-83 to 9-84 for FAs, and 3-49 to 3-63 for IRs before and after ComBat harmonization, with different image pre-processing techniques, respectively. The use of various scanners, IRs, and FAs has a great impact on radiomic features. However, the majority of scanner-robust features is also robust to IR and FA. Among the effective parameters in MR images, several tests in one scanner have a negligible impact on radiomic features. Different scanners and acquisition parameters using various image pre-processing might affect radiomic features to a large extent. ComBat harmonization might significantly impact the reproducibility of MRI radiomic features.

Differential privacy preserved federated learning for prognostic modeling in COVID-19 patients using large multi-institutional chest CT dataset.

BACKGROUND: Notwithstanding the encouraging results of previous studies reporting on the efficiency of deep learning (DL) in COVID-19 prognostication, clinical adoption of the developed methodology still needs to be improved. To overcome this limitation, we set out to predict the prognosis of a large multi-institutional cohort of patients with COVID-19 using a DL-based model. PURPOSE: This study aimed to evaluate the performance of deep privacy-preserving federated learning (DPFL) in predicting COVID-19 outcomes using chest CT images. METHODS: After applying inclusion and exclusion criteria, 3055 patients from 19 centers, including 1599 alive and 1456 deceased, were enrolled in this study. Data from all centers were split (randomly with stratification respective to each center and class) into a training/validation set (70%/10%) and a hold-out test set (20%). For the DL model, feature extraction was performed on 2D slices, and averaging was performed at the final layer to construct a 3D model for each scan. The DensNet model was used for feature extraction. The model was developed using centralized and FL approaches. For FL, we employed DPFL approaches. Membership inference attack was also evaluated in the FL strategy. For model evaluation, different metrics were reported in the hold-out test sets. In addition, models trained in two scenarios, centralized and FL, were compared using the DeLong test for statistical differences. RESULTS: The centralized model achieved an accuracy of 0.76, while the DPFL model had an accuracy of 0.75. Both the centralized and DPFL models achieved a specificity of 0.77. The centralized model achieved a sensitivity of 0.74, while the DPFL model had a sensitivity of 0.73. A mean AUC of 0.82 and 0.81 with 95% confidence intervals of (95% CI: 0.79-0.85) and (95% CI: 0.77-0.84) were achieved by the centralized model and the DPFL model, respectively. The DeLong test did not prove statistically significant differences between the two models (p-value = 0.98). The AUC values for the inference attacks fluctuate between 0.49 and 0.51, with an average of 0.50 ± 0.003 and 95% CI for the mean AUC of 0.500 to 0.501. CONCLUSION: The performance of the proposed model was comparable to centralized models while operating on large and heterogeneous multi-institutional datasets. In addition, the model was resistant to inference attacks, ensuring the privacy of shared data during the training process.

Comparison of Machine Learning Algorithms Using Manual/Automated Features on 12-Lead Signal Electrocardiogram Classification: A Large Cohort Study on Students Aged Between 6 to 18 Years Old.

PROPOSE: An electrocardiogram (ECG) has been extensively used to detect rhythm disturbances. We sought to determine the accuracy of different machine learning in distinguishing abnormal ECGs from normal ones in children who were examined using a resting 12-Lead ECG machine, and we also compared the manual and automated measurement using the modular ECG Analysis System (MEANS) algorithm of ECG features. METHODS: Altogether, 10745 ECGs were recorded for students aged 6 to 18. Manual and automatic ECG features were extracted for each participant. Features were normalized using Z-score normalization and went through the student's t-test and chi-squared test to measure their relevance. We applied the Boruta algorithm for feature selection and then implemented eight classifier algorithms. The dataset was split into training (80%) and test (20%) partitions. The performance of the classifiers was evaluated on the test data (unseen data) by 1000 bootstrap, and sensitivity (SEN), specificity (SPE), AUC, and accuracy (ACC) were reported. RESULTS: In univariate analysis, the highest performance was heart rate and RR interval in the manual dataset and heart rate in an automated dataset with AUC of 0.72 and 0.71, respectively. The best classifiers in the manual dataset were random forest (RF) and quadratic-discriminant-analysis (QDA) with AUC, ACC, SEN, and SPE equal to 0.93, 0.98, 0.69, 0.99, and 0.90, 0.95, 0.75, 0.96, respectively. In the automated dataset, QDA (AUC: 0.89, ACC:0.92, SEN:0.71, SPE:0.93) and stack learning (SL) (AUC:0.89, ACC:0.96, SEN:0.61, SPE:0.99) reached best performances. CONCLUSION: This study demonstrated that the manual measurement of 12-Lead ECG features had better performance than the automated measurement (MEANS algorithm), but some classifiers had promising results in discriminating between normal and abnormal cases. Further studies can help us evaluate the applicability and efficacy of machine-learning approaches for distinguishing abnormal ECGs in community-based investigations in both adults and children.

Artificial intelligence-based analysis of whole-body bone scintigraphy: The quest for the optimal deep learning algorithm and comparison with human observer performance.

PURPOSE: Whole-body bone scintigraphy (WBS) is one of the most widely used modalities in diagnosing malignant bone diseases during the early stages. However, the procedure is time-consuming and requires vigour and experience. Moreover, interpretation of WBS scans in the early stages of the disorders might be challenging because the patterns often reflect normal appearance that is prone to subjective interpretation. To simplify the gruelling, subjective, and prone-to-error task of interpreting WBS scans, we developed deep learning (DL) models to automate two major analyses, namely (i) classification of scans into normal and abnormal and (ii) discrimination between malignant and non-neoplastic bone diseases, and compared their performance with human observers. MATERIALS AND METHODS: After applying our exclusion criteria on 7188 patients from three different centers, 3772 and 2248 patients were enrolled for the first and second analyses, respectively. Data were split into two parts, including training and testing, while a fraction of training data were considered for validation. Ten different CNN models were applied to single- and dual-view input (posterior and anterior views) modes to find the optimal model for each analysis. In addition, three different methods, including squeeze-and-excitation (SE), spatial pyramid pooling (SPP), and attention-augmented (AA), were used to aggregate the features for dual-view input models. Model performance was reported through area under the receiver operating characteristic (ROC) curve (AUC), accuracy, sensitivity, and specificity and was compared with the DeLong test applied to ROC curves. The test dataset was evaluated by three nuclear medicine physicians (NMPs) with different levels of experience to compare the performance of AI and human observers. RESULTS: DenseNet121_AA (DensNet121, with dual-view input aggregated by AA) and InceptionResNetV2_SPP achieved the highest performance (AUC = 0.72) for the first and second analyses, respectively. Moreover, on average, in the first analysis, Inception V3 and InceptionResNetV2 CNN models and dual-view input with AA aggregating method had superior performance. In addition, in the second analysis, DenseNet121 and InceptionResNetV2 as CNN methods and dual-view input with AA aggregating method achieved the best results. Conversely, the performance of AI models was significantly higher than human observers for the first analysis, whereas their performance was comparable in the second analysis, although the AI model assessed the scans in a drastically lower time. CONCLUSION: Using the models designed in this study, a positive step can be taken toward improving and optimizing WBS interpretation. By training DL models with larger and more diverse cohorts, AI could potentially be used to assist physicians in the assessment of WBS images.

Impact of feature harmonization on radiogenomics analysis: Prediction of EGFR and KRAS mutations from non-small cell lung cancer PET/CT images.

OBJECTIVE: To investigate the impact of harmonization on the performance of CT, PET, and fused PET/CT radiomic features toward the prediction of mutations status, for epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) genes in non-small cell lung cancer (NSCLC) patients. METHODS: Radiomic features were extracted from tumors delineated on CT, PET, and wavelet fused PET/CT images obtained from 136 histologically proven NSCLC patients. Univariate and multivariate predictive models were developed using radiomic features before and after ComBat harmonization to predict EGFR and KRAS mutation statuses. Multivariate models were built using minimum redundancy maximum relevance feature selection and random forest classifier. We utilized 70/30% splitting patient datasets for training/testing, respectively, and repeated the procedure 10 times. The area under the receiver operator characteristic curve (AUC), accuracy, sensitivity, and specificity were used to assess model performance. The performance of the models (univariate and multivariate), before and after ComBat harmonization was compared using statistical analyses. RESULTS: While the performance of most features in univariate modeling was significantly improved for EGFR prediction, most features did not show any significant difference in performance after harmonization in KRAS prediction. Average AUCs of all multivariate predictive models for both EGFR and KRAS were significantly improved (q-value < 0.05) following ComBat harmonization. The mean ranges of AUCs increased following harmonization from 0.87-0.90 to 0.92-0.94 for EGFR, and from 0.85-0.90 to 0.91-0.94 for KRAS. The highest performance was achieved by harmonized F_R0.66_W0.75 model with AUC of 0.94, and 0.93 for EGFR and KRAS, respectively. CONCLUSION: Our results demonstrated that regarding univariate modelling, while ComBat harmonization had generally a better impact on features for EGFR compared to KRAS status prediction, its effect is feature-dependent. Hence, no systematic effect was observed. Regarding the multivariate models, ComBat harmonization significantly improved the performance of all radiomics models toward more successful prediction of EGFR and KRAS mutation statuses in lung cancer patients. Thus, by eliminating the batch effect in multi-centric radiomic feature sets, harmonization is a promising tool for developing robust and reproducible radiomics using vast and variant datasets.

Overall Survival Prognostic Modelling of Non-small Cell Lung Cancer Patients Using Positron Emission Tomography/Computed Tomography Harmonised Radiomics Features: The Quest for the Optimal Machine Learning Algorithm.

AIMS: Despite the promising results achieved by radiomics prognostic models for various clinical applications, multiple challenges still need to be addressed. The two main limitations of radiomics prognostic models include information limitation owing to single imaging modalities and the selection of optimum machine learning and feature selection methods for the considered modality and clinical outcome. In this work, we applied several feature selection and machine learning methods to single-modality positron emission tomography (PET) and computed tomography (CT) and multimodality PET/CT fusion to identify the best combinations for different radiomics modalities towards overall survival prediction in non-small cell lung cancer patients. MATERIALS AND METHODS: A PET/CT dataset from The Cancer Imaging Archive, including subjects from two independent institutions (87 and 95 patients), was used in this study. Each cohort was used once as training and once as a test, followed by averaging of the results. ComBat harmonisation was used to address the centre effect. In our proposed radiomics framework, apart from single-modality PET and CT models, multimodality radiomics models were developed using multilevel (feature and image levels) fusion. Two different methods were considered for the feature-level strategy, including concatenating PET and CT features into a single feature set and alternatively averaging them. For image-level fusion, we used three different fusion methods, namely wavelet fusion, guided filtering-based fusion and latent low-rank representation fusion. In the proposed prognostic modelling framework, combinations of four feature selection and seven machine learning methods were applied to all radiomics modalities (two single and five multimodalities), machine learning hyper-parameters were optimised and finally the models were evaluated in the test cohort with 1000 repetitions via bootstrapping. Feature selection and machine learning methods were selected as popular techniques in the literature, supported by open source software in the public domain and their ability to cope with continuous time-to-event survival data. Multifactor ANOVA was used to carry out variability analysis and the proportion of total variance explained by radiomics modality, feature selection and machine learning methods was calculated by a bias-corrected effect size estimate known as ω2. RESULTS: Optimum feature selection and machine learning methods differed owing to the applied radiomics modality. However, minimum depth (MD) as feature selection and Lasso and Elastic-Net regularized generalized linear model (glmnet) as machine learning method had the highest average results. Results from the ANOVA test indicated that the variability that each factor (radiomics modality, feature selection and machine learning methods) introduces to the performance of models is case specific, i.e. variances differ regarding different radiomics modalities and fusion strategies. Overall, the greatest proportion of variance was explained by machine learning, except for models in feature-level fusion strategy. CONCLUSION: The identification of optimal feature selection and machine learning methods is a crucial step in developing sound and accurate radiomics risk models. Furthermore, optimum methods are case specific, differing due to the radiomics modality and fusion strategy used.

Non-contrast Cine Cardiac Magnetic Resonance image radiomics features and machine learning algorithms for myocardial infarction detection.

OBJECTIVE: Robust differentiation between infarcted and normal tissue is important for clinical diagnosis and precision medicine. The aim of this work is to investigate the radiomic features and to develop a machine learning algorithm for the differentiation of myocardial infarction (MI) and viable tissues/normal cases in the left ventricular myocardium on non-contrast Cine Cardiac Magnetic Resonance (Cine-CMR) images. METHODS: Seventy-two patients (52 with MI and 20 healthy control patients) were enrolled in this study. MR imaging was performed on a 1.5 T MRI using the following parameters: TR = 43.35 ms, TE = 1.22 ms, flip angle = 65°, temporal resolution of 30-40 ms. N4 bias field correction algorithm was applied to correct the inhomogeneity of images. All images were segmented and verified simultaneously by two cardiac imaging experts in consensus. Subsequently, features extraction was performed within the whole left ventricular myocardium (3D volume) in end-diastolic volume phase. Re-sampling to 1 × 1 × 1 mm3 voxels was performed for MR images. All intensities within the VOI of MR images were discretized to 64 bins. Radiomic features were normalized to obtain Z-scores, followed by Student's t-test statistical analysis for comparison. A p-value < 0.05 was used as a threshold for statistically significant differences and false discovery rate (FDR) correction performed to report q-value (FDR adjusted p-value). The extracted features were ranked using the MSVM-RFE algorithm, then Spearman correlation between features was performed to eliminate highly correlated features (R2 > 0.80). Ten different machine learning algorithms were used for classification and different metrics used for evaluation and various parameters used for models' evaluation. RESULTS: In univariate analysis, the highest area under the curve (AUC) of receiver operating characteristic (ROC) value was achieved for the Maximum 2D diameter slice (M2DS) shape feature (AUC = 0.88, q-value = 1.02E-7), while the average of univariate AUCs was 0.62 ± 0.08. In multivariate analysis, Logistic Regression (AUC = 0.93 ± 0.03, Accuracy = 0.86 ± 0.05, Recall = 0.87 ± 0.1, Precision = 0.93 ± 0.03 and F1 Score = 0.90 ± 0.04) and SVM (AUC = 0.92 ± 0.05, Accuracy = 0.85 ± 0.04, Recall = 0.92 ± 0.01, Precision = 0.88 ± 0.04 and F1 Score = 0.90 ± 0.02) yielded optimal performance as the best machine learning algorithm for this radiomics analysis. CONCLUSION: This study demonstrated that using radiomics analysis on non-contrast Cine-CMR images enables to accurately detect MI, which could potentially be used as an alternative diagnostic method for Late Gadolinium Enhancement Cardiac Magnetic Resonance (LGE-CMR).

COVID-19 prognostic modeling using CT radiomic features and machine learning algorithms: Analysis of a multi-institutional dataset of 14,339 patients.

BACKGROUND: We aimed to analyze the prognostic power of CT-based radiomics models using data of 14,339 COVID-19 patients. METHODS: Whole lung segmentations were performed automatically using a deep learning-based model to extract 107 intensity and texture radiomics features. We used four feature selection algorithms and seven classifiers. We evaluated the models using ten different splitting and cross-validation strategies, including non-harmonized and ComBat-harmonized datasets. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were reported. RESULTS: In the test dataset (4,301) consisting of CT and/or RT-PCR positive cases, AUC, sensitivity, and specificity of 0.83 ± 0.01 (CI95%: 0.81-0.85), 0.81, and 0.72, respectively, were obtained by ANOVA feature selector + Random Forest (RF) classifier. Similar results were achieved in RT-PCR-only positive test sets (3,644). In ComBat harmonized dataset, Relief feature selector + RF classifier resulted in the highest performance of AUC, reaching 0.83 ± 0.01 (CI95%: 0.81-0.85), with a sensitivity and specificity of 0.77 and 0.74, respectively. ComBat harmonization did not depict statistically significant improvement compared to a non-harmonized dataset. In leave-one-center-out, the combination of ANOVA feature selector and RF classifier resulted in the highest performance. CONCLUSION: Lung CT radiomics features can be used for robust prognostic modeling of COVID-19. The predictive power of the proposed CT radiomics model is more reliable when using a large multicentric heterogeneous dataset, and may be used prospectively in clinical setting to manage COVID-19 patients.

Non-small cell lung carcinoma histopathological subtype phenotyping using high-dimensional multinomial multiclass CT radiomics signature.

OBJECTIVE: The aim of this study was to identify the most important features and assess their discriminative power in the classification of the subtypes of NSCLC. METHODS: This study involved 354 pathologically proven NSCLC patients including 134 squamous cell carcinoma (SCC), 110 large cell carcinoma (LCC), 62 not other specified (NOS), and 48 adenocarcinoma (ADC). In total, 1433 radiomics features were extracted from 3D volumes of interest drawn on the malignant lesion identified on CT images. Wrapper algorithm and multivariate adaptive regression splines were implemented to identify the most relevant/discriminative features. A multivariable multinomial logistic regression was employed with 1000 bootstrapping samples based on the selected features to classify four main subtypes of NSCLC. RESULTS: The results revealed that the texture features, specifically gray level size zone matrix features (GLSZM), were the significant indicators of NSCLC subtypes. The optimized classifier achieved an average precision, recall, F1-score, and accuracy of 0.710, 0.703, 0.706, and 0.865, respectively, based on the selected features by the wrapper algorithm. CONCLUSIONS: Our CT radiomics approach demonstrated impressive potential for the classification of the four main histological subtypes of NSCLC, It is anticipated that CT radiomics could be useful in treatment planning and precision medicine.