Search

The current study aimed to predict lymphovascular invasion (LVI) using multiple machine learning algorithms and multi-segmentation positron emission tomography (PET) radiomics in non-small cell lung cancer (NSCLC) patients, offering new avenues for personalized treatment strategies and improving patient outcomes. One hundred and twenty-six patients with NSCLC were enrolled in this study. Various automated and semi-automated PET image segmentation methods were applied, including Local Active Contour (LAC), Fuzzy-C-mean (FCM), K-means (KM), Watershed, Region Growing (RG), and Iterative thresholding (IT) with different percentages of the threshold. One hundred five radiomic features were extracted from each region of interest (ROI). Multiple feature selection methods, including Minimum Redundancy Maximum Relevance (MRMR), Recursive Feature Elimination (RFE), and Boruta, and multiple classifiers, including Multilayer Perceptron (MLP), Logistic Regression (LR), XGBoost (XGB), Naive Bayes (NB), and Random Forest (RF), were employed. Synthetic Minority Oversampling Technique (SMOTE) was also used to determine if it boosts the area under the ROC curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE). Our results indicated that the combination of SMOTE, IT (with 45% threshold), RFE feature selection and LR classifier showed the best performance (AUC = 0.93, ACC = 0.84, SEN = 0.85, SPE = 0.84) followed by SMOTE, FCM segmentation, MRMR feature selection, and LR classifier (AUC = 0.92, ACC = 0.87, SEN = 1, SPE = 0.84). The highest ACC belonged to the IT segmentation (with 45 and 50% thresholds) alongside Boruta feature selection and the NB classifier without SMOTE (ACC = 0.9, AUC = 0.78 and 0.76, SEN = 0.7, and SPE = 0.94, respectively). Our results indicate that selection of appropriate segmentation method and machine learning algorithm may be helpful in successful prediction of LVI in patients with NSCLC with high accuracy using PET radiomics analysis., Competing Interests: Declarations. Ethics approval: This retrospective study was approved by the Institutional Review Board (IRB) of Tehran University of Medical Sciences (approval ID IR.TUMS.MEDICINE.REC.1397.733). Due to the retrospective nature of the study, the requirement for obtaining written informed consent from patients was waived by the IRB. Conflict of interest: The authors have no conflicts to disclose., (© 2024. The Author(s).)

Purpose: Non-small cell lung cancer is the most common subtype of lung cancer. Patient survival prediction using machine learning (ML) and radiomics analysis proved to provide promising outcomes. However, most studies reported in the literature focused on information extracted from malignant lesions. This study aims to explore the relevance and additional value of information extracted from healthy organs in addition to tumoral tissue using ML algorithms., Patients and Methods: This study included PET/CT images of 154 patients collected from available online databases. The gross tumor volume and 33 volumes of interest defined on healthy organs were segmented using nnU-Net deep learning-based segmentation. Subsequently, 107 radiomic features were extracted from PET and CT images (Organomics). Clinical information was combined with PET and CT radiomics from organs and gross tumor volumes considering 19 different combinations of inputs. Finally, different feature selection (FS; 5 methods) and ML (6 algorithms) algorithms were tested in a 3-fold data split cross-validation scheme. The performance of the models was quantified in terms of the concordance index (C-index) metric., Results: For an input combination of all radiomics information, most of the selected features belonged to PET Organomics and CT Organomics. The highest C-index (0.68) was achieved using univariate C-index FS method and random survival forest ML model using CT Organomics + PET Organomics as input as well as minimum depth FS method and CoxPH ML model using PET Organomics as input. Considering all 17 combinations with C-index higher than 0.65, Organomics from PET or CT images were used as input in 16 of them., Conclusions: The selected features and C-indices demonstrated that the additional information extracted from healthy organs of both PET and CT imaging modalities improved the ML performance. Organomics could be a step toward exploiting the whole information available from multimodality medical images, contributing to the emerging field of digital twins in health care., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., (© 2024. The Author(s).)

Aims: We aimed to build radiomic models for classifying non-small cell lung cancer (NSCLC) histopathological subtypes through a dual-centre dataset and comprehensively evaluate the effect of ComBat harmonisation on the performance of single- and multimodality radiomic models., Materials and Methods: A public dataset of NSCLC patients from two independent centres was used. Two image fusion methods, namely guided filtering-based fusion and image fusion based on visual saliency map and weighted least square optimisation, were used. Radiomic features were extracted from each scan, including first-order, texture and moment-invariant features. Subsequently, ComBat harmonisation was applied to the extracted features from computed tomography (CT), positron emission tomography (PET) and fused images to correct the centre effect. For feature selection, least absolute shrinkage and selection operator (Lasso) and recursive feature elimination (RFE) were investigated. For machine learning, logistic regression (LR), support vector machine (SVM) and AdaBoost were evaluated for classifying NSCLC subtypes. Training and evaluation of the models were carried out in a robust framework to offset plausible errors and performance was reported using area under the curve, balanced accuracy, sensitivity and specificity before and after harmonisation. N-way ANOVA was used to assess the effect of different factors on the performance of the models., Results: Support vector machine fed with selected features by recursive feature elimination from a harmonised PET feature set achieved the highest performance (area under the curve = 0.82) in classifying NSCLC histopathological subtypes. Although the performance of the models did not significantly improve for CT images after harmonisation, the performance of PET and guided filtering-based fusion feature signatures significantly improved for almost all models. Although the selection of the image modality and feature selection methods was effective on the performance of the model (ANOVA P-values <0.001), machine learning and harmonisation did not change the performance significantly (ANOVA P-values = 0.839 and 0.292, respectively)., Conclusion: This study confirmed the potential of radiomic analysis on PET, CT and hybrid images for histopathological classification of NSCLC subtypes., (Copyright © 2023. Published by Elsevier Ltd.)

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., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study is aimed at examining the synergistic impact of motion and acquisition/reconstruction parameters on 18 F-FDG PET image radiomic features in non-small cell lung cancer (NSCLC) patients, and investigating the robustness of features performance in differentiating NSCLC histopathology subtypes., Methods: An in-house developed thoracic phantom incorporating lesions with different sizes was used with different reconstruction settings, including various reconstruction algorithms, number of subsets and iterations, full-width at half-maximum of post-reconstruction smoothing filter and acquisition parameters, including injected activity and test-retest with and without motion simulation. To simulate motion, a special motor was manufactured to simulate respiratory motion based on a normal patient in two directions. The lesions were delineated semi-automatically to extract 174 radiomic features. All radiomic features were categorized according to the coefficient of variation (COV) to select robust features. A cohort consisting of 40 NSCLC patients with adenocarcinoma (n = 20) and squamous cell carcinoma (n = 20) was retrospectively analyzed. Statistical analysis was performed to discriminate robust features in differentiating histopathology subtypes of NSCLC lesions., Results: Overall, 29% of radiomic features showed a COV ≤5% against motion. Forty-five percent and 76% of the features showed a COV ≤ 5% against the test-retest with and without motion in large lesions, respectively. Thirty-three percent and 45% of the features showed a COV ≤ 5% against different reconstruction parameters with and without motion, respectively. For NSCLC histopathological subtype differentiation, statistical analysis showed that 31 features were significant (p-value < 0.05). Two out of the 31 significant features, namely, the joint entropy of GLCM (AUC = 0.71, COV = 0.019) and median absolute deviation of intensity histogram (AUC = 0.7, COV = 0.046), were robust against the motion (same reconstruction setting)., Conclusions: Motion, acquisition, and reconstruction parameters significantly impact radiomic features, just as their synergies. Radiomic features with high predictive performance (statistically significant) in differentiating histopathological subtype of NSCLC may be eliminated due to non-reproducibility., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

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&#95;R0.66&#95;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., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 ω 2 ., 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., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We developed multi-modality radiomic models by integrating information extracted from 18 F-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., (© 2021 Institute of Physics and Engineering in Medicine.)