Robust radiogenomics approach to the identification of EGFR mutations among patients with NSCLC from three different countries using topologically invariant Betti numbers

Abstract Objectives: To propose a novel robust radiogenomics approach to the identification of epidermal growth factor receptor (EGFR) mutations among patients with non-small cell lung cancer (NSCLC) using Betti numbers (BNs). Materials and methods: Contrast enhanced computed tomography (CT) images of 194 multi-racial NSCLC patients (79 EGFR mutants and 115 wildtypes) were collected from three different countries using 5 manufacturers' scanners with a variety of scanning parameters. Ninety-nine cases obtained from the University of Malaya Medical Centre (UMMC) in Malaysia were used for training and validation procedures. Forty-one cases collected from the Kyushu University Hospital (KUH) in Japan and fifty-four cases obtained from The Cancer Imaging Archive (TCIA) in America were used for a test procedure. Radiomic features were obtained from BN maps, which represent topologically invariant heterogeneous characteristics of lung cancer on CT images, by applying histogram- and texture-based feature computations. A BN-based signature was determined using support vector machine (SVM) models with the best combination of features that maximized a robustness index (RI) which defined a higher total area under receiver operating characteristics curves (AUCs) and lower difference of AUCs between the training and the validation. The SVM model was built using the signature and optimized in a five-fold cross validation. The BN-based model was compared to conventional original image (OI)- and wavelet-decomposition (WD)-based models with respect to the RI between the validation and the test. Results: The BN-based model showed a higher RI of 1.51 compared with the models based on the OI (RI: 1.33) and the WD (RI: 1.29). Conclusion: The proposed model showed higher robustness than the conventional models in the identification of EGFR mutations among NSCLC patients. The results suggested the robustness of the BN-based approach against variations in image scanner/scanning parameters

Three-dimensional topological radiogenomics of epidermal growth factor receptor Del19 and L858R mutation subtypes on computed tomography images of lung cancer patients

Objectives : To elucidate a novel radiogenomics approach using three-dimensional (3D) topologically invariant Betti numbers (BNs) for topological characterization of epidermal growth factor receptor (EGFR) Del19 and L858R mutation subtypes. Methods : In total, 154 patients (wild-type EGFR, 72 patients; Del19 mutation, 45 patients; and L858R mutation, 37 patients) were retrospectively enrolled and randomly divided into 92 training and 62 test cases. Two support vector machine (SVM) models to distinguish between wild-type and mutant EGFR (mutation [M] classification) as well as between the Del19 and L858R subtypes (subtype [S] classification) were trained using 3DBN features. These features were computed from 3DBN maps by using histogram and texture analyses. The 3DBN maps were generated using computed tomography (CT) images based on the Čech complex constructed on sets of points in the images. These points were defined by coordinates of voxels with CT values higher than several threshold values. The M classification model was built using image features and demographic parameters of sex and smoking status. The SVM models were evaluated by determining their classification accuracies. The feasibility of the 3DBN model was compared with those of conventional radiomic models based on pseudo-3D BN (p3DBN), two-dimensional BN (2DBN), and CT and wavelet-decomposition (WD) images. The validation of the model was repeated with 100 times random sampling. Results : The mean test accuracies for M classification with 3DBN, p3DBN, 2DBN, CT, and WD images were 0.810, 0.733, 0.838, 0.782, and 0.799, respectively. The mean test accuracies for S classification with 3DBN, p3DBN, 2DBN, CT, and WD images were 0.773, 0.694, 0.657, 0.581, and 0.696, respectively. Conclusion : 3DBN features, which showed a radiogenomic association with the characteristics of the EGFR Del19/L858R mutation subtypes, yielded higher accuracy for subtype classifications in comparison with conventional features

Prediction of Intracranial Aneurysm Rupture Risk Using Non-Invasive Radiomics Analysis Based on Follow-Up Magnetic Resonance Angiography Images: A Preliminary Study

This is the first preliminary study to develop prediction models for aneurysm rupture risk using radiomics analysis based on follow-up magnetic resonance angiography (MRA) images. We selected 103 follow-up images from 18 unruptured aneurysm (UA) cases and 10 follow-up images from 10 ruptured aneurysm (RA) cases to build the prediction models. A total of 486 image features were calculated, including 54 original features and 432 wavelet-based features, within each aneurysm region in the MRA images for the texture patterns. We randomly divided the 103 UA data into 50 training and 53 testing data and separated the 10 RA data into 1 test and 9 training data to be increased to 54 using a synthetic minority oversampling technique. We selected 11 image features associated with UAs and RAs from 486 image features using the least absolute shrinkage and the selection operator logistic regression and input them into a support vector machine to build the rupture prediction models. An imbalanced adjustment training and test strategy was developed. The area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity were 0.971, 0.948, 0.700, and 0.953, respectively. This prediction model with non-invasive MRA images could predict aneurysm rupture risk for SAH prevention

Computer-Aided Diagnosis Systems for Brain Diseases in Magnetic Resonance Images

This paper reviews the basics and recent researches of computer-aided diagnosis (CAD) systems for assisting neuroradiologists in detection of brain diseases, e.g., asymptomatic unruptured aneurysms, Alzheimer's disease, vascular dementia, and multiple sclerosis (MS), in magnetic resonance (MR) images. The CAD systems consist of image feature extraction based on image processing techniques and machine learning classifiers such as linear discriminant analysis, artificial neural networks, and support vector machines. We introduce useful examples of the CAD systems in the neuroradiology, and conclude with possibilities in the future of the CAD systems for brain diseases in MR images

Can Persistent Homology Features Capture More Intrinsic Information about Tumors from ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Images of Head and Neck Cancer Patients?

This study hypothesized that persistent homology (PH) features could capture more intrinsic information about the metabolism and morphology of tumors from 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) images of patients with head and neck (HN) cancer than other conventional features. PET/CT images and clinical variables of 207 patients were selected from the publicly available dataset of the Cancer Imaging Archive. PH images were generated from persistent diagrams obtained from PET/CT images. The PH features were derived from the PH PET/CT images. The signatures were constructed in a training cohort from features from CT, PET, PH-CT, and PH-PET images; clinical variables; and the combination of features and clinical variables. Signatures were evaluated using statistically significant differences (p-value, log-rank test) between survival curves for low- and high-risk groups and the C-index. In an independent test cohort, the signature consisting of PH-PET features and clinical variables exhibited the lowest log-rank p-value of 3.30 × 10−5 and C-index of 0.80, compared with log-rank p-values from 3.52 × 10−2 to 1.15 × 10−4 and C-indices from 0.34 to 0.79 for other signatures. This result suggests that PH features can capture the intrinsic information of tumors and predict prognosis in patients with HN cancer

Similar-Case-Based Optimization of Beam Arrangements in Stereotactic Body Radiotherapy for Assisting Treatment Planners

Objective. To develop a similar-case-based optimization method for beam arrangements in lung stereotactic body radiotherapy (SBRT) to assist treatment planners. Methods. First, cases that are similar to an objective case were automatically selected based on geometrical features related to a planning target volume (PTV) location, PTV shape, lung size, and spinal cord position. Second, initial beam arrangements were determined by registration of similar cases with the objective case using a linear registration technique. Finally, beam directions of the objective case were locally optimized based on the cost function, which takes into account the radiation absorption in normal tissues and organs at risk. The proposed method was evaluated with 10 test cases and a treatment planning database including 81 cases, by using 11 planning evaluation indices such as tumor control probability and normal tissue complication probability (NTCP). Results. The procedure for the local optimization of beam arrangements improved the quality of treatment plans with significant differences (P<0.05) in the homogeneity index and conformity index for the PTV, V10, V20, mean dose, and NTCP for the lung. Conclusion. The proposed method could be usable as a computer-aided treatment planning tool for the determination of beam arrangements in SBRT

CT Image-Based Biopsy to Aid Prediction of HOPX Expression Status and Prognosis for Non-Small Cell Lung Cancer Patients

This study aimed to elucidate a computed tomography (CT) image-based biopsy with a radiogenomic signature to predict homeodomain-only protein homeobox (HOPX) gene expression status and prognosis in patients with non-small cell lung cancer (NSCLC). Patients were labeled as HOPX-negative or positive based on HOPX expression and were separated into training (n = 92) and testing (n = 24) datasets. In correlation analysis between genes and image features extracted by Pyradiomics for 116 patients, eight significant features associated with HOPX expression were selected as radiogenomic signature candidates from the 1218 image features. The final signature was constructed from eight candidates using the least absolute shrinkage and selection operator. An imaging biopsy model with radiogenomic signature was built by a stacking ensemble learning model to predict HOPX expression status and prognosis. The model exhibited predictive power for HOPX expression with an area under the receiver operating characteristic curve of 0.873 and prognostic power in Kaplan–Meier curves (p = 0.0066) in the test dataset. This study’s findings implied that the CT image-based biopsy with a radiogenomic signature could aid physicians in predicting HOPX expression status and prognosis in NSCLC