Noninvasive Evaluation of the Notch Signaling Pathway via Radiomic Signatures Based on Multiparametric MRI in Association With Biological Functions of Patients With Glioma: A Multi-institutional Study.

BACKGROUND: Noninvasive determination of Notch signaling is important for prognostic evaluation and therapeutic intervention in glioma. PURPOSE: To predict Notch signaling using multiparametric (mp) MRI radiomics and correlate with biological characteristics in gliomas. STUDY TYPE: Retrospective. POPULATION: A total of 63 patients for model construction and 47 patients from two public databases for external testing. FIELD STRENGTH/SEQUENCE: A 1.5 T and 3.0 T, T1-weighted imaging (T1WI), T2WI, T2 fluid attenuated inversion recovery (FLAIR), contrast-enhanced (CE)-T1WI. ASSESSMENT: Radiomic features were extracted from CE-T1WI, T1WI, T2WI, and T2FLAIR and imaging signatures were selected using a least absolute shrinkage and selection operator. Diagnostic performance was compared between single modality and a combined mpMRI radiomics model. A radiomic-clinical nomogram was constructed incorporating the mpMRI radiomic signature and Karnofsky Performance score. The performance was validated in the test set. The radiomic signatures were correlated with immunohistochemistry (IHC) analysis of downstream Notch pathway components. STATISTICAL TESTS: Receiver operating characteristic curve, decision curve analysis (DCA), Pearson correlation, and Hosmer-Lemeshow test. A P value < 0.05 was considered statistically significant. RESULTS: The radiomic signature derived from the combination of all sequences numerically showed highest area under the curve (AUC) in both training and external test sets (AUCs of 0.857 and 0.823). The radiomics nomogram that incorporated the mpMRI radiomic signature and KPS status resulted in AUCs of 0.891 and 0.859 in the training and test sets. The calibration curves showed good agreement between prediction and observation in both sets (P= 0.279 and 0.170, respectively). DCA confirmed the clinical usefulness of the nomogram. IHC identified Notch pathway inactivation and the expression levels of Hes1 correlated with higher combined radiomic scores (r = -0.711) in Notch1 mutant tumors. DATA CONCLUSION: The mpMRI-based radiomics nomogram may reflect the intratumor heterogeneity associated with downstream biofunction that predicts Notch signaling in a noninvasive manner. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Brain Tumor Radiogenomic Classification of O6-Methylguanine-DNA Methyltransferase Promoter Methylation in Malignant Gliomas-Based Transfer Learning.

Artificial Intelligence (AI) is the subject of a challenge and attention in the field of oncology and raises many promises for preventive diagnosis, but also fears, some of which are based on highly speculative visions for the classification and detection of tumors. A brain tumor that is malignant is a life-threatening disorder. Glioblastoma is the most prevalent kind of adult brain cancer and the 1 with the poorest prognosis, with a median survival time of less than a year. The presence of O6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation, a particular genetic sequence seen in tumors, has been proven to be a positive prognostic indicator and a significant predictor of recurrence.This strong revival of interest in AI is modeled in particular to major technological advances which have significantly increased the performance of the predicted model for medical decision support. Establishing reliable forecasts remains a significant challenge for electronic health records (EHRs). By enhancing clinical practice, precision medicine promises to improve healthcare delivery. The goal is to produce improved prognosis, diagnosis, and therapy through evidence-based sub stratification of patients, transforming established clinical pathways to optimize care for each patient's individual requirements. The abundance of today's healthcare data, dubbed "big data," provides great resources for new knowledge discovery, potentially advancing precision treatment. The latter necessitates multidisciplinary initiatives that will use the knowledge, skills, and medical data of newly established organizations with diverse backgrounds and expertise.The aim of this paper is to use magnetic resonance imaging (MRI) images to train and evaluate your model to detect the presence of MGMT promoter methylation in this competition to predict the genetic subtype of glioblastoma based transfer learning. Our objective is to emphasize the basic problems in the developing disciplines of radiomics and radiogenomics, as well as to illustrate the computational challenges from the perspective of big data analytics.

CT-based radiogenomic analysis dissects intratumor heterogeneity and predicts prognosis of colorectal cancer: a multi-institutional retrospective study.

BACKGROUND: This study aimed to develop a radiogenomic prognostic prediction model for colorectal cancer (CRC) by investigating the biological and clinical relevance of intratumoural heterogeneity. METHODS: This retrospective multi-cohort study was conducted in three steps. First, we identified genomic subclones using unsupervised deconvolution analysis. Second, we established radiogenomic signatures to link radiomic features with prognostic subclone compositions in an independent radiogenomic dataset containing matched imaging and gene expression data. Finally, the prognostic value of the identified radiogenomic signatures was validated using two testing datasets containing imaging and survival information collected from separate medical centres. RESULTS: This multi-institutional retrospective study included 1601 patients (714 females and 887 males; mean age, 65 years ± 14 [standard deviation]) with CRC from 5 datasets. Molecular heterogeneity was identified using unsupervised deconvolution analysis of gene expression data. The relative prevalence of the two subclones associated with cell cycle and extracellular matrix pathways identified patients with significantly different survival outcomes. A radiogenomic signature-based predictive model significantly stratified patients into high- and low-risk groups with disparate disease-free survival (HR = 1.74, P = 0.003). Radiogenomic signatures were revealed as an independent predictive factor for CRC by multivariable analysis (HR = 1.59, 95% CI:1.03-2.45, P = 0.034). Functional analysis demonstrated that the 11 radiogenomic signatures were predominantly associated with extracellular matrix and immune-related pathways. CONCLUSIONS: The identified radiogenomic signatures might be a surrogate for genomic signatures and could complement the current prognostic strategies.

A Comparison of the Efficiency of Using a Deep CNN Approach with Other Common Regression Methods for the Prediction of EGFR Expression in Glioblastoma Patients.

To estimate epithermal growth factor receptor (EGFR) expression level in glioblastoma (GBM) patients using radiogenomic analysis of magnetic resonance images (MRI). A comparative study using a deep convolutional neural network (CNN)-based regression, deep neural network, least absolute shrinkage and selection operator (LASSO) regression, elastic net regression, and linear regression with no regularization was carried out to estimate EGFR expression of 166 GBM patients. Except for the deep CNN case, overfitting was prevented by using feature selection, and loss values for each method were compared. The loss values in the training phase for deep CNN, deep neural network, Elastic net, LASSO, and the linear regression with no regularization were 2.90, 8.69, 7.13, 14.63, and 21.76, respectively, while in the test phase, the loss values were 5.94, 10.28, 13.61, 17.32, and 24.19 respectively. These results illustrate that the efficiency of the deep CNN approach is better than that of the other methods, including Lasso regression, which is a regression method known for its advantage in high-dimension cases. A comparison between deep CNN, deep neural network, and three other common regression methods was carried out, and the efficiency of the CNN deep learning approach, in comparison with other regression models, was demonstrated.

IMAGGS: a radiogenomic framework for identifying multi-way associations in breast cancer subtypes.

Investigating correlations between radiomic and genomic profiling in breast cancer (BC) molecular subtypes is crucial for understanding disease mechanisms and providing personalized treatment. We present a well-designed radiogenomic framework image-gene-gene set (IMAGGS), which detects multi-way associations in BC subtypes by integrating radiomic and genomic features. Our dataset consists of 721 patients, each of whom has 12 ultrasound (US) images captured from different angles and gene mutation data. To better characterize tumor traits, 12 multi-angle US images are fused using two distinct strategies. Then, we analyze complex many-to-many associations between phenotypic and genotypic features using a machine learning algorithm, deviating from the prevalent one-to-one relationship pattern observed in previous studies. Key radiomic and genomic features are screened using these associations. In addition, gene set enrichment analysis is performed to investigate the joint effects of gene sets and delve deeper into the biological functions of BC subtypes. We further validate the feasibility of IMAGGS in a glioblastoma multiforme dataset to demonstrate the scalability of IMAGGS across different modalities and diseases. Taken together, IMAGGS provides a comprehensive characterization for diseases by associating imaging, genes, and gene sets, paving the way for biological interpretation of radiomics and development of targeted therapy.

Identifying radiogenomic associations of breast cancer based on DCE-MRI by using Siamese Neural Network with manufacturer bias normalization.

BACKGROUND AND PURPOSE: The immunohistochemical test (IHC) for Human Epidermal Growth Factor Receptor 2 (HER2) and hormone receptors (HR) provides prognostic information and guides treatment for patients with invasive breast cancer. The objective of this paper is to establish a non-invasive system for identifying HER2 and HR in breast cancer using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: In light of the absence of high-performance algorithms and external validation in previously published methods, this study utilizes 3D deep features and radiomics features to represent the information of the Region of Interest (ROI). A Siamese Neural Network was employed as the classifier, with 3D deep features and radiomics features serving as the network input. To neutralize manufacturer bias, a batch effect normalization method, ComBat, was introduced. To enhance the reliability of the study, two datasets, Predict Your Therapeutic Response with Imaging and moLecular Analysis (I-SPY 1) and I-SPY 2, were incorporated. I-SPY 2 was utilized for model training and validation, while I-SPY 1 was exclusively employed for external validation. Additionally, a breast tumor segmentation network was trained to improve radiomic feature extraction. RESULTS: The results indicate that our approach achieved an average Area Under the Curve (AUC) of 0.632, with a Standard Error of the Mean (SEM) of 0.042 for HER2 prediction in the I-SPY 2 dataset. For HR prediction, our method attained an AUC of 0.635 (SEM 0.041), surpassing other published methods in the AUC metric. Moreover, the proposed method yielded competitive results in other metrics. In external validation using the I-SPY 1 dataset, our approach achieved an AUC of 0.567 (SEM 0.032) for HR prediction and 0.563 (SEM 0.033) for HER2 prediction. CONCLUSION: This study proposes a non-invasive system for identifying HER2 and HR in breast cancer. Although the results do not conclusively demonstrate superiority in both tasks, they indicate that the proposed method achieved good performance and is a competitive classifier compared to other reference methods. Ablation studies demonstrate that both radiomics features and deep features for the Siamese Neural Network are beneficial for the model. The introduced manufacturer bias normalization method has been shown to enhance the method's performance. Furthermore, the external validation of the method enhances the reliability of this research. Source code, pre-trained segmentation network, Radiomics and deep features, data for statistical analysis, and Supporting Information of this article are online at: https://github.com/FORRESTHUACHEN/Siamese_Neural_Network_based_Brest_cancer_Radiogenomic.

Multi-Parametric Radiomic Model to Predict 1p/19q Co-Deletion in Patients with IDH-1 Mutant Glioma: Added Value to the T2-FLAIR Mismatch Sign.

PURPOSE: The T2-FLAIR mismatch sign has shown promise in determining IDH mutant 1p/19q non-co-deleted gliomas with a high specificity and modest sensitivity. To develop a multi-parametric radiomic model using MRI to predict 1p/19q co-deletion status in patients with newly diagnosed IDH1 mutant glioma and to perform a comparative analysis to T2-FLAIR mismatch sign+. METHODS: In this retrospective study, patients with diagnosis of IDH1 mutant gliomas with known 1p/19q status who had preoperative MRI were included. T2-FLAIR mismatch was evaluated independently by two board-certified neuroradiologists. Texture features were extracted from glioma segmentation of FLAIR images. eXtremeGradient Boosting (XGboost) classifiers were used for model development. Leave-one-out-cross-validation (LOOCV) and external validation performances were reported for both the training and external validation sets. RESULTS: A total of 103 patients were included for model development and 18 patients for external testing validation. The diagnostic performance (sensitivity/specificity/accuracy) in the determination of the 1p/19q co-deletion status was 59%/83%/67% (training) and 62.5%/70.0%/66.3% (testing) for the T2-FLAIR mismatch sign. This was significantly improved (p = 0.04) using the radiomics model to 77.9%/82.8%/80.3% (training) and 87.5%/89.9%/88.8% (testing), respectively. The addition of radiomics as a computer-assisted tool resulted in significant (p = 0.02) improvement in the performance of the neuroradiologist with 13 additional corrected cases in comparison to just using the T2-FLAIR mismatch sign. CONCLUSION: The proposed radiomic model provides much needed sensitivity to the highly specific T2-FLAIR mismatch sign in the determination of the 1p/19q non-co-deletion status and improves the overall diagnostic performance of neuroradiologists when used as an assistive tool.

Tumor radiogenomics in gliomas with Bayesian layered variable selection.

We propose a statistical framework to analyze radiological magnetic resonance imaging (MRI) and genomic data to identify the underlying radiogenomic associations in lower grade gliomas (LGG). We devise a novel imaging phenotype by dividing the tumor region into concentric spherical layers that mimics the tumor evolution process. MRI data within each layer is represented by voxel-intensity-based probability density functions which capture the complete information about tumor heterogeneity. Under a Riemannian-geometric framework these densities are mapped to a vector of principal component scores which act as imaging phenotypes. Subsequently, we build Bayesian variable selection models for each layer with the imaging phenotypes as the response and the genomic markers as predictors. Our novel hierarchical prior formulation incorporates the interior-to-exterior structure of the layers, and the correlation between the genomic markers. We employ a computationally-efficient Expectation-Maximization-based strategy for estimation. Simulation studies demonstrate the superior performance of our approach compared to other approaches. With a focus on the cancer driver genes in LGG, we discuss some biologically relevant findings. Genes implicated with survival and oncogenesis are identified as being associated with the spherical layers, which could potentially serve as early-stage diagnostic markers for disease monitoring, prior to routine invasive approaches. We provide a R package that can be used to deploy our framework to identify radiogenomic associations.

Robustness of Radiomics in Pre-Surgical Computer Tomography of Non-Small-Cell Lung Cancer.

Background: Radiomic features are increasingly used in CT of NSCLC. However, their robustness with respect to segmentation variability has not yet been demonstrated. The aim of this study was to assess radiomic features agreement across three kinds of segmentation. Methods: We retrospectively included 48 patients suffering from NSCLC who underwent pre-surgery CT. Two expert radiologists in consensus manually delineated three 3D-ROIs on each patient. To assess robustness for each feature, the intra-class correlation coefficient (ICC) across segmentations was evaluated. The 'sensitivity' of ICC upon some parameters affecting features computation (such as bin-width for first-order features and pixel-distances for second-order features) was also evaluated. Moreover, an assessment with respect to interpolator and isotropic resolution was also performed. Results: Our results indicate that 'shape' features tend to have excellent agreement (ICC > 0.9) across segmentations; moreover, they have approximately zero sensitivity to other parameters. 'First-order' features are in general sensitive to parameters variation; however, a few of them showed excellent agreement and low sensitivity (below 0.1) with respect to bin-width and pixel-distance. Similarly, a few second-order features showed excellent agreement and low sensitivity. Conclusions: Our results suggest that a limited number of radiomic features can achieve a high level of reproducibility in CT of NSCLC.

Radiogenomics, Breast Cancer Diagnosis and Characterization: Current Status and Future Directions.

Breast cancer (BC) is a heterogeneous disease, affecting millions of women every year. Early diagnosis is crucial to increasing survival. The clinical workup of BC diagnosis involves diagnostic imaging and bioptic characterization. In recent years, technical advances in image processing allowed for the application of advanced image analysis (radiomics) to clinical data. Furthermore, -omics technologies showed their potential in the characterization of BC. Combining information provided by radiomics with -omics data can be important to personalize diagnostic and therapeutic work up in a clinical context for the benefit of the patient. In this review, we analyzed the recent literature, highlighting innovative approaches to combine imaging and biochemical/biological data, with the aim of identifying recent advances in radiogenomics applied to BC. The results of radiogenomic studies are encouraging approaches in a clinical setting. Despite this, as radiogenomics is an emerging area, the optimal approach has to face technical limitations and needs to be applied to large cohorts including all the expression profiles currently available for BC subtypes (e.g., besides markers from transcriptomics, proteomics and miRNomics, also other non-coding RNA profiles).

Contrast-Enhanced Computed Tomography-Based Radiogenomics Analysis for Predicting Prognosis in Gastric Cancer.

Objective: The aim of this study is to identify prognostic imaging biomarkers and create a radiogenomics nomogram to predict overall survival (OS) in gastric cancer (GC). Material: RNA sequencing data from 407 patients with GC and contrast-enhanced computed tomography (CECT) imaging data from 46 patients obtained from The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA) were utilized to identify radiogenomics biomarkers. A total of 392 patients with CECT images from the Nanfang Hospital database were obtained to create and validate a radiogenomics nomogram based on the biomarkers. Methods: The prognostic imaging features that correlated with the prognostic gene modules (selected by weighted gene coexpression network analysis) were identified as imaging biomarkers. A nomogram that integrated the radiomics score and clinicopathological factors was created and validated in the Nanfang Hospital database. Nomogram discrimination, calibration, and clinical usefulness were evaluated. Results: Three prognostic imaging biomarkers were identified and had a strong correlation with four prognostic gene modules (P < 0.05, FDR < 0.05). The radiogenomics nomogram (AUC = 0.838) resulted in better performance of the survival prediction than that of the TNM staging system (AUC = 0.765, P = 0.011; Delong et al.). In addition, the radiogenomics nomogram exhibited good discrimination, calibration, and clinical usefulness in both the training and validation cohorts. Conclusions: The novel prognostic radiogenomics nomogram that was constructed achieved excellent correlation with prognosis in both the training and validation cohort of Nanfang Hospital patients with GC. It is anticipated that this work may assist in clinical preferential treatment decisions and promote the process of precision theranostics in the future.

U-Net Based Segmentation and Characterization of Gliomas.

(1) Background: Gliomas are the most common primary brain neoplasms accounting for roughly 40−50% of all malignant primary central nervous system tumors. We aim to develop a deep learning-based framework for automated segmentation and prediction of biomarkers and prognosis in patients with gliomas. (2) Methods: In this retrospective two center study, patients were included if they (1) had a diagnosis of glioma with known surgical histopathology and (2) had preoperative MRI with FLAIR sequence. The entire tumor volume including FLAIR hyperintense infiltrative component and necrotic and cystic components was segmented. Deep learning-based U-Net framework was developed based on symmetric architecture from the 512 × 512 segmented maps from FLAIR as the ground truth mask. (3) Results: The final cohort consisted of 208 patients with mean ± standard deviation of age (years) of 56 ± 15 with M/F of 130/78. DSC of the generated mask was 0.93. Prediction for IDH-1 and MGMT status had a performance of AUC 0.88 and 0.62, respectively. Survival prediction of <18 months demonstrated AUC of 0.75. (4) Conclusions: Our deep learning-based framework can detect and segment gliomas with excellent performance for the prediction of IDH-1 biomarker status and survival.

MRI- and Histologic-Molecular-Based Radio-Genomics Nomogram for Preoperative Assessment of Risk Classes in Endometrial Cancer.

High- and low-risk endometrial carcinoma (EC) differ in whether or not a lymphadenectomy is performed. We aimed to develop MRI-based radio-genomic models able to preoperatively assess lymph-vascular space invasion (LVSI) and discriminate between low- and high-risk EC according to the ESMO-ESGO-ESTRO 2020 guidelines, which include molecular risk classification proposed by "ProMisE". This is a retrospective, multicentric study that included 64 women with EC who underwent 3T-MRI before a hysterectomy. Radiomics features were extracted from T2WI images and apparent diffusion coefficient maps (ADC) after manual segmentation of the gross tumor volume. We constructed a multiple logistic regression approach from the most relevant radiomic features to distinguish between low- and high-risk classes under the ESMO-ESGO-ESTRO 2020 guidelines. A similar approach was taken to assess LVSI. Model diagnostic performance was assessed via ROC curves, accuracy, sensitivity and specificity on training and test sets. The LVSI predictive model used a single feature from ADC as a predictor; the risk class model used two features as predictors from both ADC and T2WI. The low-risk predictive model showed an AUC of 0.74 with an accuracy, sensitivity, and specificity of 0.74, 0.76, 0.94; the LVSI model showed an AUC of 0.59 with an accuracy, sensitivity, and specificity of 0.60, 0.50, 0.61. MRI-based radio-genomic models are useful for preoperative EC risk stratification and may facilitate therapeutic management.

Racial/ancestral diversity in 174 toxicity-related radiogenomic studies: A systematic review.

PURPOSE: This study systematically reviews the distribution of racial/ancestral features and their inclusion as covariates in genetic-toxicity association studies following radiation therapy. MATERIALS AND METHODS: Original research studies associating genetic features and normal tissue complications following radiation therapy were identified from PubMed. The distribution of radiogenomic studies was determined by mining the statement of country of origin and racial/ancestrial distribution and the inclusion in analyses. Descriptive analyses were performed to determine the distribution of studies across races/ancestries, countries, and continents and the inclusion in analyses. RESULTS: Among 174 studies, only 23 with a population of more one race/ancestry which were predominantly conducted in the United States. Across the continents, most studies were performed in Europe (77 studies averaging at 30.6 patients/million population [pt/mil]), North America (46 studies, 20.8 pt/mil), Asia (46 studies, 2.4 pt/mil), South America (3 studies, 0.4 pt/mil), Oceania (2 studies, 2.1 pt/mil), and none from Africa. All 23 studies with more than one race/ancestry considered race/ancestry as a covariate, and three studies showed race/ancestry to be significantly associated with endpoints. CONCLUSION: Most toxicity-related radiogenomic studies involved a single race/ancestry. Individual Participant Data meta-analyses or multinational studies need to be encouraged.

Using Genomics Feature Selection Method in Radiomics Pipeline Improves Prognostication Performance in Locally Advanced Esophageal Squamous Cell Carcinoma-A Pilot Study.

PURPOSE: To evaluate the prognostic value of baseline and restaging CT-based radiomics with features associated with gene expression in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiation (nCRT) plus surgery. METHODS: We enrolled 106 ESCC patients receiving nCRT from two institutions. Gene expression profiles of 28 patients in the training set were used to detect differentially expressed (DE) genes between patients with and without relapse. Radiomic features that were correlated to DE genes were selected, followed by additional machine learning selection. A radiomic nomogram for disease-free survival (DFS) prediction incorporating the radiomic signature and prognostic clinical characteristics was established for DFS estimation and validated. RESULTS: The radiomic signature with DE genes feature selection achieved better performance for DFS prediction than without. The nomogram incorporating the radiomic signature and lymph nodal status significantly stratified patients into high and low-risk groups for DFS (p < 0.001). The areas under the curve (AUCs) for predicting 5-year DFS were 0.912 in the training set, 0.852 in the internal test set, 0.769 in the external test set. CONCLUSIONS: Genomics association was useful for radiomic feature selection. The established radiomic signature was prognostic for DFS. The radiomic nomogram could provide a valuable prediction for individualized long-term survival.

Radiogenomic Analysis of Papillary Thyroid Carcinoma for Prediction of Cervical Lymph Node Metastasis: A Preliminary Study.

BACKGROUND: Papillary thyroid carcinoma (PTC) is characterized by frequent metastases to cervical lymph nodes (CLNs), and the presence of lymph node metastasis at diagnosis has a significant impact on the surgical approach. Therefore, we established a radiomic signature to predict the CLN status of PTC patients using preoperative thyroid ultrasound, and investigated the association between the radiomic features and underlying molecular characteristics of PTC tumors. METHODS: In total, 270 patients were enrolled in this prospective study, and radiomic features were extracted according to multiple guidelines. A radiomic signature was built with selected features in the training cohort and validated in the validation cohort. The total protein extracted from tumor samples was analyzed with LC/MS and iTRAQ technology. Gene modules acquired by clustering were chosen for their diagnostic significance. A radiogenomic map linking radiomic features to gene modules was constructed with the Spearman correlation matrix. Genes in modules related to metastasis were extracted for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and a protein-protein interaction (PPI) network was built to identify the hub genes in the modules. Finally, the screened hub genes were validated by immunohistochemistry analysis. RESULTS: The radiomic signature showed good performance for predicting CLN status in training and validation cohorts, with area under curve of 0.873 and 0.831 respectively. A radiogenomic map was created with nine significant correlations between radiomic features and gene modules, and two of them had higher correlation coefficient. Among these, MEmeganta representing the upregulation of telomere maintenance via telomerase and cell-cell adhesion was correlated with 'Rectlike' and 'deviation ratio of tumor tissue and normal thyroid gland' which reflect the margin and the internal echogenicity of the tumor, respectively. MEblue capturing cell-cell adhesion and glycolysis was associated with feature 'minimum calcification area' which measures the punctate calcification. The hub genes of the two modules were identified by protein-protein interaction network. Immunohistochemistry validated that LAMC1 and THBS1 were differently expressed in metastatic and non-metastatic tissues (p=0.003; p=0.002). And LAMC1 was associated with feature 'Rectlike' and 'deviation ratio of tumor and normal thyroid gland' (p<0.001; p<0.001); THBS1 was correlated with 'minimum calcification area' (p<0.001). CONCLUSIONS: The radiomic signature proposed here has the potential to noninvasively predict the CLN status in PTC patients. Merging imaging phenotypes with genomic data could allow noninvasive identification of the molecular properties of PTC tumors, which might support clinical decision making and personalized management.

Prediction of breast cancer molecular subtypes using DCE-MRI based on CNNs combined with ensemble learning.

To design an ensemble learning based prediction model using different breast DCE-MR post-contrast sequence images to distinguish two kinds of breast cancer subtypes (luminal and non-luminal). We retrospectively studied preoperative dynamic contrast enhanced-magnetic resonance imaging and molecular information of 266 breast cancer cases with either luminal subtype (luminal A and luminal B) or non-luminal subtype (human epidermal growth factor receptor 2 and triple negative). Then, multiple bounding boxes covering tumor lesions were acquired from three series of post-contrast DCE-MR sequence images which were determined by radiologists. Afterwards, three baseline convolutional neural networks (CNNs) with same architecture were concurrently trained, followed by preliminary prediction of probabilities from the testing database. Finally, the classification and evaluation of breast subtypes were realized by means of fusing predicted results from three CNNs employed via ensemble learning based on weighted voting. Taking advantage of 5-fold cross validation CV, the average prediction specificity, accuracy, precision and area under the ROC curve on testing dataset for the luminal versus non-luminal are 0.958, 0.852, 0.961, and 0.867, respectively, which empirically demonstrate that our proposed ensemble model has highly reliability and robustness. The breast DCE-MR post-contrast sequence image analysis utilizing the ensemble CNN model based on deep learning could show a valuable and extendible practical application on breast molecular subtype identification.

Glioblastoma multiforme prognosis: MRI missing modality generation, segmentation and radiogenomic survival prediction.

The accurate prognosis of glioblastoma multiforme (GBM) plays an essential role in planning correlated surgeries and treatments. The conventional models of survival prediction rely on radiomic features using magnetic resonance imaging (MRI). In this paper, we propose a radiogenomic overall survival (OS) prediction approach by incorporating gene expression data with radiomic features such as shape, geometry, and clinical information. We exploit TCGA (The Cancer Genomic Atlas) dataset and synthesize the missing MRI modalities using a fully convolutional network (FCN) in a conditional generative adversarial network (cGAN). Meanwhile, the same FCN architecture enables the tumor segmentation from the available and the synthesized MRI modalities. The proposed FCN architecture comprises octave convolution (OctConv) and a novel decoder, with skip connections in spatial and channel squeeze & excitation (skip-scSE) block. The OctConv can process low and high-frequency features individually and improve model efficiency by reducing channel-wise redundancy. Skip-scSE applies spatial and channel-wise excitation to signify the essential features and reduces the sparsity in deeper layers learning parameters using skip connections. The proposed approaches are evaluated by comparative experiments with state-of-the-art models in synthesis, segmentation, and overall survival (OS) prediction. We observe that adding missing MRI modality improves the segmentation prediction, and expression levels of gene markers have a high contribution in the GBM prognosis prediction, and fused radiogenomic features boost the OS estimation.

Deep learning for identifying radiogenomic associations in breast cancer.

RATIONALE AND OBJECTIVES: To determine whether deep learning models can distinguish between breast cancer molecular subtypes based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: In this institutional review board-approved single-center study, we analyzed DCE-MR images of 270 patients at our institution. Lesions of interest were identified by radiologists. The task was to automatically determine whether the tumor is of the Luminal A subtype or of another subtype based on the MR image patches representing the tumor. Three different deep learning approaches were used to classify the tumor according to their molecular subtypes: learning from scratch where only tumor patches were used for training, transfer learning where networks pre-trained on natural images were fine-tuned using tumor patches, and off-the-shelf deep features where the features extracted by neural networks trained on natural images were used for classification with a support vector machine. Network architectures utilized in our experiments were GoogleNet, VGG, and CIFAR. We used 10-fold crossvalidation method for validation and area under the receiver operating characteristic (AUC) as the measure of performance. RESULTS: The best AUC performance for distinguishing molecular subtypes was 0.65 (95% CI:[0.57,0.71]) and was achieved by the off-the-shelf deep features approach. The highest AUC performance for training from scratch was 0.58 (95% CI:[0.51,0.64]) and the best AUC performance for transfer learning was 0.60 (95% CI:[0.52,0.65]) respectively. For the off-the-shelf approach, the features extracted from the fully connected layer performed the best. CONCLUSION: Deep learning may play a role in discovering radiogenomic associations in breast cancer.

Molecular profiles of tumor contrast enhancement: A radiogenomic analysis in anaplastic gliomas.

The presence of contrast enhancement (CE) on magnetic resonance (MR) imaging is conventionally regarded as an indicator for tumor malignancy. However, the biological behaviors and molecular mechanism of enhanced tumor are not well illustrated. The aim of this study was to investigate the molecular profiles associated with anaplastic gliomas (AGs) presenting CE on postcontrast T1-weighted MR imaging. In this retrospective database study, RNA sequencing and MR imaging data of 91 AGs from the Cancer Genome Atlas (TCGA) and 64 from the Chinese Glioma Genome Atlas (CGGA) were collected. Gene set enrichment analysis (GSEA), significant analysis of microarray, generalized linear models, and Least absolute shrinkage and selection operator algorithm were used to explore radiogenomic and prognostic signatures of AG patients. GSEA indicated that angiogenesis and epithelial-mesenchymal transition were significantly associated with post-CE. Genes driving immune system response, cell proliferation, and focal adhesions were also significantly enriched. Gene ontology of 237 differential genes indicated consistent results. A 48-gene signature for CE was identified in TCGA and validated in CGGA dataset (area under the curve = 0.9787). Furthermore, seven genes derived from the CE-specific signature could stratify AG patients into two subgroups based on overall survival time according to corresponding risk score. Comprehensive analysis of post-CE and genomic characteristics leads to a better understanding of radiology-pathology correlations. Our gene signature helps interpret the occurrence of radiological traits and predict clinical outcomes. Additionally, we found nine prognostic quantitative radiomic features of CE and investigated the underlying biological processes of them.