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 &lt; 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.</p

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 &lt; 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.</p

Medical Image Segmentation Review: The success of U-Net

Automatic medical image segmentation is a crucial topic in the medical domain and successively a critical counterpart in the computer-aided diagnosis paradigm. U-Net is the most widespread image segmentation architecture due to its flexibility, optimized modular design, and success in all medical image modalities. Over the years, the U-Net model achieved tremendous attention from academic and industrial researchers. Several extensions of this network have been proposed to address the scale and complexity created by medical tasks. Addressing the deficiency of the naive U-Net model is the foremost step for vendors to utilize the proper U-Net variant model for their business. Having a compendium of different variants in one place makes it easier for builders to identify the relevant research. Also, for ML researchers it will help them understand the challenges of the biological tasks that challenge the model. To address this, we discuss the practical aspects of the U-Net model and suggest a taxonomy to categorize each network variant. Moreover, to measure the performance of these strategies in a clinical application, we propose fair evaluations of some unique and famous designs on well-known datasets. We provide a comprehensive implementation library with trained models for future research. In addition, for ease of future studies, we created an online list of U-Net papers with their possible official implementation. All information is gathered in https://github.com/NITR098/Awesome-U-Net repository.Comment: Submitted to the IEEE Transactions on Pattern Analysis and Machine Intelligence Journa

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Burden of tracheal, bronchus, and lung cancer in North Africa and Middle East countries, 1990 to 2019: Results from the GBD study 2019

ObjectiveTo provide estimates on the regional and national burden of tracheal, bronchus, and lung (TBL) cancer and its attributable risk factors from 1990 to 2019 in the North Africa and Middle East (NAME) region.Methods and materialsThe Global Burden of Disease (GBD) 2019 data were used. Disability-adjusted life years (DALYs), death, incidence, and prevalence rates were categorized by sex and age groups in the NAME region, in 21 countries, from 1990 to 2019. Decomposition analysis was performed to calculate the proportion of responsible factors in the emergence of new cases. Data are presented as point estimates with their 95% uncertainty intervals (UIs).ResultsIn the NAME region, TBL cancer caused 15,396 and 57,114 deaths in women and men, respectively, in 2019. The age-standardized incidence rate (ASIR) increased by 0.7% (95% UI -20.6 to 24.1) and reached 16.8 per 100,000 (14.9 to 19.0) in 2019. All the age-standardized indices had a decreasing trend in men and an increasing trend in women from 1990 to 2019. Turkey (34.9 per 100,000 [27.6 to 43.5]) and Sudan (8.0 per 100,000 [5.2 to 12.5]) had the highest and lowest age-standardized prevalence rates (ASPRs) in 2019, respectively. The highest and lowest absolute slopes of change in ASPR, from 1990 to 2019, were seen in Bahrain (-50.0% (-63.6 to -31.7)) and the United Arab Emirates (-1.2% (-34.1 to 53.8)), respectively. The number of deaths attributable to risk factors was 58,816 (51,709 to 67,323) in 2019 and increased by 136.5%. Decomposition analysis showed that population growth and age structure change positively contributed to new incident cases. More than 80% of DALYs could be decreased by controlling risk factors, particularly tobacco use.ConclusionThe incidence, prevalence, and DALY rates of TBL cancer increased, and the death rate remained unchanged from 1990 to 2019. All the indices and contribution of risk factors decreased in men but increased in women. Tobacco is still the leading risk factor. Early diagnosis and tobacco cessation policies should be improved

Machine learning based readmission and mortality prediction in heart failure patients

Abstract This study intends to predict in-hospital and 6-month mortality, as well as 30-day and 90-day hospital readmission, using Machine Learning (ML) approach via conventional features. A total of 737 patients remained after applying the exclusion criteria to 1101 heart failure patients. Thirty-four conventional features were collected for each patient. First, the data were divided into train and test cohorts with a 70–30% ratio. Then train data were normalized using the Z-score method, and its mean and standard deviation were applied to the test data. Subsequently, Boruta, RFE, and MRMR feature selection methods were utilized to select more important features in the training set. In the next step, eight ML approaches were used for modeling. Next, hyperparameters were optimized using tenfold cross-validation and grid search in the train dataset. All model development steps (normalization, feature selection, and hyperparameter optimization) were performed on a train set without touching the hold-out test set. Then, bootstrapping was done 1000 times on the hold-out test data. Finally, the obtained results were evaluated using four metrics: area under the ROC curve (AUC), accuracy (ACC), specificity (SPE), and sensitivity (SEN). The RFE-LR (AUC: 0.91, ACC: 0.84, SPE: 0.84, SEN: 0.83) and Boruta-LR (AUC: 0.90, ACC: 0.85, SPE: 0.85, SEN: 0.83) models generated the best results in terms of in-hospital mortality. In terms of 30-day rehospitalization, Boruta-SVM (AUC: 0.73, ACC: 0.81, SPE: 0.85, SEN: 0.50) and MRMR-LR (AUC: 0.71, ACC: 0.68, SPE: 0.69, SEN: 0.63) models performed the best. The best model for 3-month rehospitalization was MRMR-KNN (AUC: 0.60, ACC: 0.63, SPE: 0.66, SEN: 0.53) and regarding 6-month mortality, the MRMR-LR (AUC: 0.61, ACC: 0.63, SPE: 0.44, SEN: 0.66) and MRMR-NB (AUC: 0.59, ACC: 0.61, SPE: 0.48, SEN: 0.63) models outperformed the others. Reliable models were developed in 30-day rehospitalization and in-hospital mortality using conventional features and ML techniques. Such models can effectively personalize treatment, decision-making, and wiser budget allocation. Obtained results in 3-month rehospitalization and 6-month mortality endpoints were not astonishing and further experiments with additional information are needed to fetch promising results in these endpoints

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

High-dimensional multinomial multiclass severity scoring of COVID-19 pneumonia using CT radiomics features and machine learning algorithms

We aimed to construct a prediction model based on computed tomography (CT) radiomics features to classify COVID-19 patients into severe-, moderate-, mild-, and non-pneumonic. A total of 1110 patients were studied from a publicly available dataset with 4-class severity scoring performed by a radiologist (based on CT images and clinical features). The entire lungs were segmented and followed by resizing, bin discretization and radiomic features extraction. We utilized two feature selection algorithms, namely bagging random forest (BRF) and multivariate adaptive regression splines (MARS), each coupled to a classifier, namely multinomial logistic regression (MLR), to construct multiclass classification models. The dataset was divided into 50% (555 samples), 20% (223 samples), and 30% (332 samples) for training, validation, and untouched test datasets, respectively. Subsequently, nested cross-validation was performed on train/validation to select the features and tune the models. All predictive power indices were reported based on the testing set. The performance of multi-class models was assessed using precision, recall, F1-score, and accuracy based on the 4 × 4 confusion matrices. In addition, the areas under the receiver operating characteristic curves (AUCs) for multi-class classifications were calculated and compared for both models. Using BRF, 23 radiomic features were selected, 11 from first-order, 9 from GLCM, 1 GLRLM, 1 from GLDM, and 1 from shape. Ten features were selected using the MARS algorithm, namely 3 from first-order, 1 from GLDM, 1 from GLRLM, 1 from GLSZM, 1 from shape, and 3 from GLCM features. The mean absolute deviation, skewness, and variance from first-order and flatness from shape, and cluster prominence from GLCM features and Gray Level Non Uniformity Normalize from GLRLM were selected by both BRF and MARS algorithms. All selected features by BRF or MARS were significantly associated with four-class outcomes as assessed within MLR (All p values &lt; 0.05). BRF + MLR and MARS + MLR resulted in pseudo-R 2 prediction performances of 0.305 and 0.253, respectively. Meanwhile, there was a significant difference between the feature selection models when using a likelihood ratio test ( p value = 0.046). Based on confusion matrices for BRF + MLR and MARS + MLR algorithms, the precision was 0.856 and 0.728, the recall was 0.852 and 0.722, whereas the accuracy was 0.921 and 0.861, respectively. AUCs (95% CI) for multi-class classification were 0.846 (0.805–0.887) and 0.807 (0.752–0.861) for BRF + MLR and MARS + MLR algorithms, respectively. Our models based on the utilization of radiomic features, coupled with machine learning were able to accurately classify patients according to the severity of pneumonia, thus highlighting the potential of this emerging paradigm in the prognostication and management of COVID-19 patients

The effect of harmonization on the variability of PET radiomic features extracted using various segmentation methods

Purpose This study aimed to examine the robustness of positron emission tomography (PET) radiomic features extracted via different segmentation methods before and after ComBat harmonization in patients with non-small cell lung cancer (NSCLC). Methods We included 120 patients (positive recurrence = 46 and negative recurrence = 74) referred for PET scanning as a routine part of their care. All patients had a biopsy-proven NSCLC. Nine segmentation methods were applied to each image, including manual delineation, K-means (KM), watershed, fuzzy-C-mean, region-growing, local active contour (LAC), and iterative thresholding (IT) with 40, 45, and 50% thresholds. Diverse image discretizations, both without a filter and with different wavelet decompositions, were applied to PET images. Overall, 6741 radiomic features were extracted from each image (749 radiomic features from each segmented area). Non-parametric empirical Bayes (NPEB) ComBat harmonization was used to harmonize the features. Linear Support Vector Classifier (LinearSVC) with L1 regularization For feature selection and Support Vector Machine classifier (SVM) with fivefold nested cross-validation was performed using StratifiedKFold with ‘n_splits’ set to 5 to predict recurrence in NSCLC patients and assess the impact of ComBat harmonization on the outcome. Results From 749 extracted radiomic features, 206 (27%) and 389 (51%) features showed excellent reliability (ICC ≥ 0.90) against segmentation method variation before and after NPEB ComBat harmonization, respectively. Among all, 39 features demonstrated poor reliability, which declined to 10 after ComBat harmonization. The 64 fixed bin widths (without any filter) and wavelets (LLL)-based radiomic features set achieved the best performance in terms of robustness against diverse segmentation techniques before and after ComBat harmonization. The first-order and GLRLM and also first-order and NGTDM feature families showed the largest number of robust features before and after ComBat harmonization, respectively. In terms of predicting recurrence in NSCLC, our findings indicate that using ComBat harmonization can significantly enhance machine learning outcomes, particularly improving the accuracy of watershed segmentation, which initially had fewer reliable features than manual contouring. Following the application of ComBat harmonization, the majority of cases saw substantial increase in sensitivity and specificity. Conclusion Radiomic features are vulnerable to different segmentation methods. ComBat harmonization might be considered a solution to overcome the poor reliability of radiomic features.</p

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