Machine learning-based diagnosis and risk classification of coronary artery disease using myocardial perfusion imaging SPECT: A radiomics study.

This study aimed to investigate the diagnostic performance of machine learning-based radiomics analysis to diagnose coronary artery disease status and risk from rest/stress Myocardial Perfusion Imaging (MPI) single-photon emission computed tomography (SPECT). A total of 395 patients suspicious of coronary artery disease who underwent 2-day stress-rest protocol MPI SPECT were enrolled in this study. The left ventricle myocardium, excluding the cardiac cavity, was manually delineated on rest and stress images to define a volume of interest. Added to clinical features (age, sex, family history, diabetes status, smoking, and ejection fraction), a total of 118 radiomics features, were extracted from rest and stress MPI SPECT images to establish different feature sets, including Rest-, Stress-, Delta-, and Combined-radiomics (all together) feature sets. The data were randomly divided into 80% and 20% subsets for training and testing, respectively. The performance of classifiers built from combinations of three feature selections, and nine machine learning algorithms was evaluated for two different diagnostic tasks, including 1) normal/abnormal (no CAD vs. CAD) classification, and 2) low-risk/high-risk CAD classification. Different metrics, including the area under the ROC curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE), were reported for models' evaluation. Overall, models built on the Stress feature set (compared to other feature sets), and models to diagnose the second task (compared to task 1 models) revealed better performance. The Stress-mRMR-KNN (feature set-feature selection-classifier) reached the highest performance for task 1 with AUC, ACC, SEN, and SPE equal to 0.61, 0.63, 0.64, and 0.6, respectively. The Stress-Boruta-GB model achieved the highest performance for task 2 with AUC, ACC, SEN, and SPE of 0.79, 0.76, 0.75, and 0.76, respectively. Diabetes status from the clinical feature family, and dependence count non-uniformity normalized, from the NGLDM family, which is representative of non-uniformity in the region of interest were the most frequently selected features from stress feature set for CAD risk classification. This study revealed promising results for CAD risk classification using machine learning models built on MPI SPECT radiomics. The proposed models are helpful to alleviate the labor-intensive MPI SPECT interpretation process regarding CAD status and can potentially expedite the diagnostic process.

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.

A machine learning-based sonomics for prediction of thyroid nodule malignancies.

OBJECTIVES: This study aims to use ultrasound derived features as biomarkers to assess the malignancy of thyroid nodules in patients who were candidates for FNA according to the ACR TI-RADS guidelines. METHODS: Two hundred and ten patients who met the selection criteria were enrolled in the study and subjected to ultrasound-guided FNA of thyroid nodules. Different radiomics features were extracted from sonographic images, including intensity, shape, and texture feature sets. Least Absolute Shrinkage and Selection Operator (LASSO), Minimum Redundancy Maximum Relevance (MRMR), and Random Forests/Extreme Gradient Boosting Machine (XGBoost) algorithms were used for feature selection and classification of the univariate and multivariate modeling, respectively. Evaluation of models performed using accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). RESULTS: In the univariate analysis, Gray Level Run Length Matrix - Run-Length Non-Uniformity (GLRLM-RLNU) and gray-level zone length matrix - Run-Length Non-Uniformity (GLZLM-GLNU) (both with an AUC of 0.67) were top-performing for predicting nodules malignancy. In the multivariate analysis of the training dataset, the AUC of all combinations of feature selection algorithms and classifiers was 0.99, and the highest sensitivity was for XGBoost classifier and MRMR feature selection algorithms (0.99). Finally, the test dataset was used to evaluate our model in which XGBoost classifier with MRMR and LASSO feature selection algorithms had the highest performance (AUC = 0.95). CONCLUSIONS: Ultrasound-extracted features can be used as non-invasive biomarkers for thyroid nodules' malignancy prediction.

Effects of 3D electrodes arrangement in a novel AC electroosmotic micropump: Numerical modeling and experimental validation.

To date, a comprehensive systematic optimization framework, capable of accurately predicting an efficient electrode geometry, is not available. Here, different geometries, including 3D step electrodes, have been designed in order to fabricate AC electroosmosis micropumps. It is essential to optimize both geometrical parameters of electrode, such as width and height of steps on each base electrode and their location in one pair, the size of each base electrode (symmetric or asymmetric), the gap of electrode pairs, and nongeometrical parameters such as fluid flow in a channel and electrical characteristics (e.g., frequency and voltage). The governing equations comprising of electric domain and fluid domain have been coupled using finite element method. The developed model was employed to investigate the effect of electrode geometric parameters on electroosmotic slip velocity and its subsequent effect on pressure and flow rate. Numerical simulation indicates that the optimal performance can be achieved using a design with varying step height and displacement, at a given voltage (2.5 V) and frequency (1 kHz). Finally, in order to validate the numerical simulation, the optimal microchip was fabricated using a combination of photolithography, electroplating, and a polydimethylsiloxane microchannel. Our results indicate that our micropump is capable of generating a pressure, velocity, and flow rate of 74.2 Pa, 1.76 mm/s, and 14.8 µl/min, respectively. This result reveals that our proposed geometry outperforms the state-of-the-art micropumps previously reported in the literature by improving the fluid velocity by 32%, with 80% less electrodes per unit length, and whereas the channel length is ∼80% shorter.

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.

Multi-level multi-modality (PET and CT) fusion radiomics: prognostic modeling for non-small cell lung carcinoma.

We developed multi-modality radiomic models by integrating information extracted from18F-FDG PET and CT images using feature- and image-level fusions, toward improved prognosis for non-small cell lung carcinoma (NSCLC) patients. Two independent cohorts of NSCLC patients from two institutions (87 and 95 patients) were cycled as training and testing datasets. Fusion approaches were applied at two levels, namely feature- and image-levels. For feature-level fusion, radiomic features were extracted individually from CT and PET images and concatenated. Alternatively, radiomic features extracted separately from CT and PET images were averaged. For image-level fusion, wavelet fusion was utilized and tuned with two parameters, namely CT weight and Wavelet Band Pass Filtering Ratio. Clinical and combined clinical + radiomic models were developed. Gray level discretization was performed at 3 different levels (16, 32 and 64) and 225 radiomics features were extracted. Overall survival (OS) was considered as the endpoint. For feature reduction, correlated (redundant) features were excluded using Spearman's correlation, and best combination of top ten features with highest concordance-indices (via univariate Cox model) were selected in each model for further multivariate Cox model. Moreover, prognostic score's median, obtained from the training cohort, was used intact in the testing cohort as a threshold to classify patients into low- versus high-risk groups, and log-rank test was applied to assess differences between the Kaplan-Meier curves. Overall, while models based on feature-level fusion strategy showed limited superiority over single-modalities, image-level fusion strategy significantly outperformed both single-modality and feature-level fusion strategies. As such, the clinical model (C-index = 0.656) outperformed all models from single-modality and feature-level strategies, but was outperformed by certain models from image-level fusion strategy. Our findings indicated that image-level fusion multi-modality radiomics models outperformed single-modality, feature-level fusion, and clinical models for OS prediction of NSCLC patients.

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.

Treatment response prediction using MRI-based pre-, post-, and delta-radiomic features and machine learning algorithms in colorectal cancer.

OBJECTIVES: We evaluate the feasibility of treatment response prediction using MRI-based pre-, post-, and delta-radiomic features for locally advanced rectal cancer (LARC) patients treated by neoadjuvant chemoradiation therapy (nCRT). MATERIALS AND METHODS: This retrospective study included 53 LARC patients divided into a training set (Center#1, n = 36) and external validation set (Center#2, n = 17). T2-weighted (T2W) MRI was acquired for all patients, 2 weeks before and 4 weeks after nCRT. Ninety-six radiomic features, including intensity, morphological and second- and high-order texture features were extracted from segmented 3D volumes from T2W MRI. All features were harmonized using ComBat algorithm. Max-Relevance-Min-Redundancy (MRMR) algorithm was used as feature selector and k-nearest neighbors (KNN), Naïve Bayes (NB), Random forests (RF), and eXtreme Gradient Boosting (XGB) algorithms were used as classifiers. The evaluation was performed using the area under the receiver operator characteristic (ROC) curve (AUC), sensitivity, specificity and accuracy. RESULTS: In univariate analysis, the highest AUC in pre-, post-, and delta-radiomic features were 0.78, 0.70, and 0.71, for GLCM_IMC1, shape (surface area and volume) and GLSZM_GLNU features, respectively. In multivariate analysis, RF and KNN achieved the highest AUC (0.85 ± 0.04 and 0.81 ± 0.14, respectively) among pre- and post-treatment features. The highest AUC was achieved for the delta-radiomic-based RF model (0.96 ± 0.01) followed by NB (0.96 ± 0.04). Overall. Delta-radiomics model, outperformed both pre- and post-treatment features (P-value <0.05). CONCLUSION: Multivariate analysis of delta-radiomic T2W MRI features using machine learning algorithms could potentially be used for response prediction in LARC patients undergoing nCRT. We also observed that multivariate analysis of delta-radiomic features using RF classifiers can be used as powerful biomarkers for response prediction in LARC.

Machine learning-based prognostic modeling using clinical data and quantitative radiomic features from chest CT images in COVID-19 patients.

OBJECTIVE: To develop prognostic models for survival (alive or deceased status) prediction of COVID-19 patients using clinical data (demographics and history, laboratory tests, visual scoring by radiologists) and lung/lesion radiomic features extracted from chest CT images. METHODS: Overall, 152 patients were enrolled in this study protocol. These were divided into 106 training/validation and 46 test datasets (untouched during training), respectively. Radiomic features were extracted from the segmented lungs and infectious lesions separately from chest CT images. Clinical data, including patients' history and demographics, laboratory tests and radiological scores were also collected. Univariate analysis was first performed (q-value reported after false discovery rate (FDR) correction) to determine the most predictive features among all imaging and clinical data. Prognostic modeling of survival was performed using radiomic features and clinical data, separately or in combination. Maximum relevance minimum redundancy (MRMR) and XGBoost were used for feature selection and classification. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC), sensitivity, specificity, and accuracy were used to assess the prognostic performance of the models on the test datasets. RESULTS: For clinical data, cancer comorbidity (q-value < 0.01), consciousness level (q-value < 0.05) and radiological score involved zone (q-value < 0.02) were found to have high correlated features with outcome. Oxygen saturation (AUC = 0.73, q-value < 0.01) and Blood Urea Nitrogen (AUC = 0.72, q-value = 0.72) were identified as high clinical features. For lung radiomic features, SAHGLE (AUC = 0.70) and HGLZE (AUC = 0.67) from GLSZM were identified as most prognostic features. Amongst lesion radiomic features, RLNU from GLRLM (AUC = 0.73), HGLZE from GLSZM (AUC = 0.73) had the highest performance. In multivariate analysis, combining lung, lesion and clinical features was determined to provide the most accurate prognostic model (AUC = 0.95 ± 0.029 (95%CI: 0.95-0.96), accuracy = 0.88 ± 0.046 (95% CI: 0.88-0.89), sensitivity = 0.88 ± 0.066 (95% CI = 0.87-0.9) and specificity = 0.89 ± 0.07 (95% CI = 0.87-0.9)). CONCLUSION: Combination of radiomic features and clinical data can effectively predict outcome in COVID-19 patients. The developed model has significant potential for improved management of COVID-19 patients.

Radiomics-based machine learning model to predict risk of death within 5-years in clear cell renal cell carcinoma patients.

PURPOSE: The aim of this study was to develop radiomics-based machine learning models based on extracted radiomic features and clinical information to predict the risk of death within 5 years for prognosis of clear cell renal cell carcinoma (ccRCC) patients. METHODS: According to image quality and clinical data availability, we eventually selected 70 ccRCC patients that underwent CT scans. Manual volume-of-interest (VOI) segmentation of each image was performed by an experienced radiologist using the 3D slicer software package. Prior to feature extraction, image pre-processing was performed on CT images to extract different image features, including wavelet, Laplacian of Gaussian, and resampling of the intensity values to 32, 64 and 128 bin levels. Overall, 2544 3D radiomics features were extracted from each VOI for each patient. Minimum Redundancy Maximum Relevance (MRMR) algorithm was used as feature selector. Four classification algorithms were used, including Generalized Linear Model (GLM), Support Vector Machine (SVM), K-nearest Neighbor (KNN) and XGBoost. We used the Bootstrap resampling method to create validation sets. Area under the receiver operating characteristic (ROC) curve (AUROC), accuracy, sensitivity, and specificity were used to assess the performance of the classification models. RESULTS: The best single performance among 8 different models was achieved by the XGBoost model using a combination of radiomic features and clinical information (AUROC, accuracy, sensitivity, and specificity with 95% confidence interval were 0.95-0.98, 0.93-0.98, 0.93-0.96 and ~1.0, respectively). CONCLUSIONS: We developed a robust radiomics-based classifier that is capable of accurately predicting overall survival of RCC patients for prognosis of ccRCC patients. This signature may help identifying high-risk patients who require additional treatment and follow up regimens.

Pseudo-spectral method for controlling the drug dosage in cancer.

A mixed chemotherapy-immunotherapy treatment protocol is developed for cancer treatment. Chemotherapy pushes the trajectory of the system towards the desired equilibrium point, and then immunotherapy alters the dynamics of the system by affecting the parameters of the system. A co-existing cancerous equilibrium point is considered as the desired equilibrium point instead of the tumour-free equilibrium. Chemotherapy protocol is derived using the pseudo-spectral (PS) controller due to its high convergence rate and simple implementation structure. Thus, one of the contributions of this study is simplifying the design procedure and reducing the controller computational load in comparison with Lyapunov-based controllers. In this method, an infinite-horizon optimal control problem is proposed for a non-linear cancer model. Then, the infinite-horizon optimal control of cancer is transformed into a non-linear programming problem. The efficient Legendre PS scheme is suggested to solve the proposed problem. Then, the dynamics of the system is modified by immunotherapy is another contribution. To restrict the upper limit of the chemo-drug dose based on the age of the patients, a Mamdani fuzzy system is designed, which is not present yet. Simulation results on four different dynamics cases how the efficiency of the proposed treatment strategy.

Droplet size prediction in a microfluidic flow focusing device using an adaptive network based fuzzy inference system.

Microfluidics has wide applications in different technologies such as biomedical engineering, chemistry engineering, and medicine. Generating droplets with desired size for special applications needs costly and time-consuming iterations due to the nonlinear behavior of multiphase flow in a microfluidic device and the effect of several parameters on it. Hence, designing a flexible way to predict the droplet size is necessary. In this paper, we use the Adaptive Neural Fuzzy Inference System (ANFIS), by mixing the artificial neural network (ANN) and fuzzy inference system (FIS), to study the parameters which have effects on droplet size. The four main dimensionless parameters, i.e. the Capillary number, the Reynolds number, the flow ratio and the viscosity ratio are regarded as the inputs and the droplet diameter as the output of the ANFIS. Using dimensionless groups cause to extract more comprehensive results and avoiding more experimental tests. With the ANFIS, droplet sizes could be predicted with the coefficient of determination of 0.92.

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.