3D airway geometry analysis of factors in airway navigation failure for lung nodules.

BACKGROUND: This study aimed to quantitatively reveal contributing factors to airway navigation failure during radial probe endobronchial ultrasound (R-EBUS) by using geometric analysis in a three-dimensional (3D) space and to investigate the clinical feasibility of prediction models for airway navigation failure. METHODS: We retrospectively reviewed patients who underwent R-EBUS between January 2017 and December 2018. Geometric quantification was analyzed using in-house software built with open-source python libraries including the Vascular Modeling Toolkit ( http://www.vmtk.org ), simple insight toolkit ( https://sitk.org ), and sci-kit image ( https://scikit-image.org ). We used a machine learning-based approach to explore the utility of these significant factors. RESULTS: Of the 491 patients who were eligible for analysis (mean age, 65 years +/- 11 [standard deviation]; 274 men), the target lesion was reached in 434 and was not reached in 57. Twenty-seven patients in the failure group were matched with 27 patients in the success group based on propensity scores. Bifurcation angle at the target branch, the least diameter of the last section, and the curvature of the last section are the most significant and stable factors for airway navigation failure. The support vector machine can predict airway navigation failure with an average area under the curve of 0.803. CONCLUSIONS: Geometric analysis in 3D space revealed that a large bifurcation angle and a narrow and tortuous structure of the closest bronchus from the lesion are associated with airway navigation failure during R-EBUS. The models developed using quantitative computer tomography scan imaging show the potential to predict airway navigation failure.

Predicting cerebrovascular age and its clinical relevance: Modeling using 3D morphological features of brain vessels.

Aging manifests as many phenotypes, among which age-related changes in brain vessels are important, but underexplored. Thus, in the present study, we constructed a model to predict age using cerebrovascular morphological features, further assessing their clinical relevance using a novel pipeline. Age prediction models were first developed using data from a normal cohort (n = 1181), after which their relevance was tested in two stroke cohorts (n = 564 and n = 455). Our novel pipeline adapted an existing framework to compute generic vessel features for brain vessels, resulting in 126 morphological features. We further built various machine learning models to predict age using only clinical factors, only brain vessel features, and a combination of both. We further assessed deviation from healthy aging using the age gap and explored its clinical relevance by correlating the predicted age and age gap with various risk factors. The models constructed using only brain vessel features and those combining clinical factors with vessel features were better predictors of age than the clinical factor-only model (r = 0.37, 0.48, and 0.26, respectively). Predicted age was associated with many known clinical factors, and the associations were stronger for the age gap in the normal cohort. The age gap was also associated with important factors in the pooled cohort atherosclerotic cardiovascular disease risk score and white matter hyperintensity measurements. Cerebrovascular age, computed using the morphological features of brain vessels, could serve as a potential individualized marker for the early detection of various cerebrovascular diseases.

The Current Diagnostic Performance of MRI-Based Radiomics for Glioma Grading: A Meta-Analysis.

BACKGROUND: Multiple radiomics models have been proposed for grading glioma using different algorithms, features, and sequences of magnetic resonance imaging. The research seeks to assess the present overall performance of radiomics for grading glioma. METHODS: A systematic literature review of the databases Ovid MEDLINE PubMed, and Ovid EMBASE for publications published on radiomics for glioma grading between 2012 and 2023 was performed. The systematic review was carried out following the criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analysis. RESULTS: In the meta-analysis, a total of 7654 patients from 40 articles, were assessed. R-package mada was used for modeling the joint estimates of specificity (SPE) and sensitivity (SEN). Pooled event rates across studies were performed with a random-effects meta-analysis. The heterogeneity of SPE and SEN were based on the χ2 test. Overall values for SPE and SEN in the differentiation between high-grade gliomas (HGGs) and low-grade gliomas (LGGs) were 84% and 91%, respectively. With regards to the discrimination between World Health Organization (WHO) grade 4 and WHO grade 3, the overall SPE was 81% and the SEN was 89%. The modern non-linear classifiers showed a better trend, whereas textural features tend to be the best-performing (29%) and the most used. CONCLUSIONS: Our findings confirm that present radiomics' diagnostic performance for glioma grading is superior in terms of SEN and SPE for the HGGs vs. LGGs discrimination task when compared to the WHO grade 4 vs. 3 task.

Global intracranial arterial tortuosity is associated with intracranial atherosclerotic burden.

The effect of arterial tortuosity on intracranial atherosclerosis (ICAS) is not well understood. This study aimed to evaluate the effect of global intracranial arterial tortuosity on intracranial atherosclerotic burden in patients with ischemic stroke. We included patients with acute ischemic stroke who underwent magnetic resonance angiography (MRA) and classified them into three groups according to the ICAS burden. Global tortuosity index (GTI) was defined as the standardized mean curvature of the entire intracranial arteries, measured by in-house vessel analysis software. Of the 516 patients included, 274 patients had no ICAS, 140 patients had a low ICAS burden, and 102 patients had a high ICAS burden. GTI increased with higher ICAS burden. After adjustment for age, sex, vascular risk factors, and standardized mean arterial area, GTI was independently associated with ICAS burden (adjusted odds ratio [adjusted OR] 1.33; 95% confidence interval [CI] 1.09-1.62). The degree of association increased when the arterial tortuosity was analyzed limited to the basal arteries (adjusted OR 1.48; 95% CI 1.22-1.81). We demonstrated that GTI is associated with ICAS burden in patients with ischemic stroke, suggesting a role for global arterial tortuosity in ICAS.

The effect of intensive statin therapy in non-symptomatic intracranial arteries: The STAMINA-MRI sub-study.

Background and aims: Pleiotropic effects of statins result in the stabilization of symptomatic intracranial arterial plaque. However, little is known about the effect of statins in non-symptomatic cerebral arteries. We hypothesized that intensive statin therapy could produce a change in the non-symptomatic cerebral arteries. Methods: This is a sub-study of a prospective observational study under the title of "Intensive Statin Treatment in Acute Ischemic Stroke Patients with Intracranial Atherosclerosis: a High-Resolution Magnetic Resonance Imaging (HR-MRI) study." Patients with statin-naive acute ischemic stroke who had symptomatic intracranial artery stenosis (above 50%) were recruited for this study. HR-MRI was performed to assess the patients' cerebral arterial status before and 6 months after the statin therapy. To demonstrate the effect of statins in the non-symptomatic segment of intracranial cerebral arteries, we excluded symptomatic segments from the data to be analyzed. We compared the morphological changes using cerebrovascular morphometry. Results: A total of 54 patients (mean age: 62.9 ± 14.4 years, 59.3% women) were included in this study. Intensive statin therapy produced significant morphological changes of overall cerebral arteries. Among the morphological features, the arterial luminal area showed the highest number of significant changes with a range from 5.7 and 6.7%. Systolic blood pressure (SBP) was an independent factor associated with relative changes in posterior circulation bed maximal diameter percentage change (beta -0.21, 95% confidence interval -0.36 to -0.07, p = 0.005). Conclusion: Intensive statin therapy produced a favorable morphological change in cerebral arteries of not only the target arterial segment but also non-symptomatic arterial segments. The change in cerebral arterial luminal diameter was influenced by the baseline SBP and was dependent on the topographic distribution of the cerebral arteries.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02458755.

Automated in-depth cerebral arterial labelling using cerebrovascular vasculature reframing and deep neural networks.

Identifying the cerebral arterial branches is essential for undertaking a computational approach to cerebrovascular imaging. However, the complexity and inter-individual differences involved in this process have not been thoroughly studied. We used machine learning to examine the anatomical profile of the cerebral arterial tree. The method is less sensitive to inter-subject and cohort-wise anatomical variations and exhibits robust performance with an unprecedented in-depth vessel range. We applied machine learning algorithms to disease-free healthy control subjects (n = 42), patients with stroke with intracranial atherosclerosis (ICAS) (n = 46), and patients with stroke mixed with the existing controls (n = 69). We trained and tested 70% and 30% of each study cohort, respectively, incorporating spatial coordinates and geometric vessel feature vectors. Cerebral arterial images were analyzed based on the 'segmentation-stacking' method using magnetic resonance angiography. We precisely classified the cerebral arteries across the exhaustive scope of vessel components using advanced geometric characterization, redefinition of vessel unit conception, and post-processing algorithms. We verified that the neural network ensemble, with multiple joint models as the combined predictor, classified all vessel component types independent of inter-subject variations in cerebral arterial anatomy. The validity of the categorization performance of the model was tested, considering the control, ICAS, and control-blended stroke cohorts, using the area under the receiver operating characteristic (ROC) curve and precision-recall curve. The classification accuracy rarely fell outside each image's 90-99% scope, independent of cohort-dependent cerebrovascular structural variations. The classification ensemble was calibrated with high overall area rates under the ROC curve of 0.99-1.00 [0.97-1.00] in the test set across various study cohorts. Identifying an all-inclusive range of vessel components across controls, ICAS, and stroke patients, the accuracy rates of the prediction were: internal carotid arteries, 91-100%; middle cerebral arteries, 82-98%; anterior cerebral arteries, 88-100%; posterior cerebral arteries, 87-100%; and collections of superior, anterior inferior, and posterior inferior cerebellar arteries, 90-99% in the chunk-level classification. Using a voting algorithm on the queued classified vessel factors and anatomically post-processing the automatically classified results intensified quantitative prediction performance. We employed stochastic clustering and deep neural network ensembles. Ma-chine intelligence-assisted prediction of vessel structure allowed us to personalize quantitative predictions of various types of cerebral arterial structures, contributing to precise and efficient decisions regarding the cerebrovascular disease.

Tumor-Attentive Segmentation-Guided GAN for Synthesizing Breast Contrast-Enhanced MRI Without Contrast Agents.

OBJECTIVE: Breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a sensitive imaging technique critical for breast cancer diagnosis. However, the administration of contrast agents poses a potential risk. This can be avoided if contrast-enhanced MRI can be obtained without using contrast agents. Thus, we aimed to generate T1-weighted contrast-enhanced MRI (ceT1) images from pre-contrast T1 weighted MRI (preT1) images in the breast. METHODS: We proposed a generative adversarial network to synthesize ceT1 from preT1 breast images that adopted a local discriminator and segmentation task network to focus specifically on the tumor region in addition to the whole breast. The segmentation network performed a related task of segmentation of the tumor region, which allowed important tumor-related information to be enhanced. In addition, edge maps were included to provide explicit shape and structural information. Our approach was evaluated and compared with other methods in the local (n = 306) and external validation (n = 140) cohorts. Four evaluation metrics of normalized mean squared error (NRMSE), Pearson cross-correlation coefficients (CC), peak signal-to-noise ratio (PSNR), and structural similarity index map (SSIM) for the whole breast and tumor region were measured. An ablation study was performed to evaluate the incremental benefits of various components in our approach. RESULTS: Our approach performed the best with an NRMSE 25.65, PSNR 54.80 dB, SSIM 0.91, and CC 0.88 on average, in the local test set. CONCLUSION: Performance gains were replicated in the validation cohort. SIGNIFICANCE: We hope that our method will help patients avoid potentially harmful contrast agents. Clinical and Translational Impact Statement-Contrast agents are necessary to obtain DCE-MRI which is essential in breast cancer diagnosis. However, administration of contrast agents may cause side effects such as nephrogenic systemic fibrosis and risk of toxic residue deposits. Our approach can generate DCE-MRI without contrast agents using a generative deep neural network. Thus, our approach could help patients avoid potentially harmful contrast agents resulting in an improved diagnosis and treatment workflow for breast cancer.

Robust multimodal fusion network using adversarial learning for brain tumor grading.

BACKGROUND AND OBJECTIVE: Gliomas are graded using multimodal magnetic resonance imaging, which provides important information for treatment and prognosis. When modalities are missing, the grading is degraded. We propose a robust brain tumor grading model that can handle missing modalities. METHODS: Our method was developed and tested on Brain Tumor Segmentation Challenge 2017 dataset (n = 285) via nested five-fold cross-validation. Our method adopts adversarial learning to generate the features of missing modalities relative to the features obtained from a full set of modalities in the latent space. An attention-based fusion block across modalities fuses the features of each available modality into a shared representation. Our method's results are compared to those of two other models where 15 missing-modality scenarios are explicitly considered and a joint training approach with random dropouts is used. RESULTS: Our method outperforms the two competing methods in classifying high-grade gliomas (HGGs) and low-grade gliomas (LGGs), achieving an area under the curve of 87.76% on average for all missing-modality scenarios. The activation maps derived with our method confirm that it focuses on the enhancing portion of the tumor in HGGs and on the edema and non-enhancing portions of the tumor in LGGs, which is consistent with prior expertise. An ablation study shows the added benefits of a fusion block and adversarial learning for handling missing modalities. CONCLUSION: Our method shows robust grading of gliomas in all cases of missing modalities. Our proposed network might have positive implications in glioma care by learning features robust to missing modalities.

Incremental benefits of size-zone matrix-based radiomics features for the prognosis of lung adenocarcinoma: advantage of spatial partitioning on tumor evaluation.

OBJECTIVES: Prognostic models of lung adenocarcinoma (ADC) can be built using radiomics features from various categories. The size-zone matrix (SZM) features have a strong biological basis related to tumor partitioning, but their incremental benefits have not been fully explored. In our study, we aimed to evaluate the incremental benefits of SZM features for the prognosis of lung ADC. METHODS: A total of 298 patients were included and their pretreatment computed tomography images were analyzed in fivefold cross-validation. We built a risk model of overall survival using SZM features and compared it with a conventional radiomics risk model and a clinical variable-based risk model. We also compared it with other models incorporating various combinations of SZM features, other radiomics features, and clinical variables. A total of seven risk models were compared and evaluated using the hazard ratio (HR) on the left-out test fold. RESULTS: As a baseline, the clinical variable risk model showed an HR of 2.739. Combining the radiomics signature with SZM feature was better (HR 4.034) than using radiomics signature alone (HR 3.439). Combining radiomics signature, SZM feature, and clinical variable (HR 6.524) fared better than just combining radiomics signature and clinical variables (HR 4.202). These results confirmed the added benefits of SZM features for prognosis in lung ADC. CONCLUSION: Combining SZM feature with the radiomics signature was better than using the radiomics signature alone and the benefits of SZM features were maintained when clinical variables were added confirming the incremental benefits of SZM features for lung ADC prognosis. KEY POINTS: • Size-zone matrix (SZM) features provide incremental benefits for the prognosis of lung adenocarcinoma. • Combining the radiomics signature with SZM features performed better than using a radiomics signature alone.

Measurement of Perfusion Heterogeneity within Tumor Habitats on Magnetic Resonance Imaging and Its Association with Prognosis in Breast Cancer Patients.

The purpose of this study was to identify perfusional subregions sharing similar kinetic characteristics from dynamic contrast-enhanced magnetic resonance imaging (MRI) using data-driven clustering, and to evaluate the effect of perfusional heterogeneity based on those subregions on patients' survival outcomes in various risk models. From two hospitals, 308 and 147 women with invasive breast cancer who underwent preoperative MRI between October 2011 and July 2012 were retrospectively enrolled as development and validation cohorts, respectively. Using the Cox-least absolute shrinkage and selection operator model, a habitat risk score (HRS) was constructed from the radiomics features from the derived habitat map. An HRS-only, clinical, combined habitat, and two conventional radiomics risk models to predict patients' disease-free survival (DFS) were built. Patients were classified into low-risk or high-risk groups using the median cutoff values of each risk score. Five habitats with distinct perfusion patterns were identified. An HRS was an independent risk factor for predicting worse DFS outcomes in the HRS-only risk model (hazard ratio = 3.274 [95% CI = 1.378-7.782]; p = 0.014) and combined habitat risk model (hazard ratio = 4.128 [95% CI = 1.744-9.769]; p = 0.003) in the validation cohort. In the validation cohort, the combined habitat risk model (hazard ratio = 4.128, p = 0.003, C-index = 0.760) showed the best performance among five different risk models. The quantification of perfusion heterogeneity is a potential approach for predicting prognosis and may facilitate personalized, tailored treatment strategies for breast cancer.

Overview of radiomics in prostate imaging and future directions.

Recent advancements in imaging technology and analysis methods have led to an analytic framework known as radiomics. This framework extracts comprehensive high-dimensional features from imaging data and performs data mining to build analytical models for improved decision-support. Its features include many categories spanning texture and shape; thus, it can provide abundant information for precision medicine. Many studies of prostate radiomics have shown promising results in the assessment of pathological features, prediction of treatment response, and stratification of risk groups. Herein, we aimed to provide a general overview of radiomics procedures, discuss technical issues, explain various clinical applications, and suggest future research directions, especially for prostate imaging.

Radiomics-guided deep neural networks stratify lung adenocarcinoma prognosis from CT scans.

Deep learning (DL) is a breakthrough technology for medical imaging with high sample size requirements and interpretability issues. Using a pretrained DL model through a radiomics-guided approach, we propose a methodology for stratifying the prognosis of lung adenocarcinomas based on pretreatment CT. Our approach allows us to apply DL with smaller sample size requirements and enhanced interpretability. Baseline radiomics and DL models for the prognosis of lung adenocarcinomas were developed and tested using local (n = 617) cohort. The DL models were further tested in an external validation (n = 70) cohort. The local cohort was divided into training and test cohorts. A radiomics risk score (RRS) was developed using Cox-LASSO. Three pretrained DL networks derived from natural images were used to extract the DL features. The features were further guided using radiomics by retaining those DL features whose correlations with the radiomics features were high and Bonferroni-corrected p-values were low. The retained DL features were subject to a Cox-LASSO when constructing DL risk scores (DRS). The risk groups stratified by the RRS and DRS showed a significant difference in training, testing, and validation cohorts. The DL features were interpreted using existing radiomics features, and the texture features explained the DL features well.

A Cascaded Neural Network for Staging in Non-Small Cell Lung Cancer Using Pre-Treatment CT.

BACKGROUND AND AIM: Tumor staging in non-small cell lung cancer (NSCLC) is important for treatment and prognosis. Staging involves expert interpretation of imaging, which we aim to automate with deep learning (DL). We proposed a cascaded DL method comprised of two steps to classification between early- and advanced-stage NSCLC using pretreatment computed tomography. METHODS: We developed and tested a DL model to classify between early- and advanced-stage using training (n = 90), validation (n = 8), and two test (n = 37, n = 26) cohorts obtained from the public domain. The first step adopted an autoencoder network to compress the imaging data into latent variables and the second step used the latent variable to classify the stages using the convolutional neural network (CNN). Other DL and machine learning-based approaches were compared. RESULTS: Our model was tested in two test cohorts of CPTAC and TCGA. In CPTAC, our model achieved accuracy of 0.8649, sensitivity of 0.8000, specificity of 0.9412, and area under the curve (AUC) of 0.8206 compared to other approaches (AUC 0.6824-0.7206) for classifying between early- and advanced-stages. In TCGA, our model achieved accuracy of 0.8077, sensitivity of 0.7692, specificity of 0.8462, and AUC of 0.8343. CONCLUSION: Our cascaded DL model for classification NSCLC patients into early-stage and advanced-stage showed promising results and could help future NSCLC research.

Pleomorphic carcinoma of the lung: Prognostic models of semantic, radiomics and combined features from CT and PET/CT in 85 patients.

INTRODUCTION: To demonstrate semantic, radiomics, and the combined risk models related to the prognoses of pulmonary pleomorphic carcinomas (PCs). METHODS: We included 85 patients (M:F = 71:14; age, 35-88 [mean, 63 years]) whose imaging features were divided into training (n = 60) and test (n = 25) sets. Nineteen semantic and 142 radiomics features related to tumors were computed. Semantic risk score (SRS) model was built using the Cox-least absolute shrinkage and selection operator (LASSO) approach. Radiomics risk score (RRS) from CT and PET features and combined risk score (CRS) adopting both semantic and radiomics features were also constructed. Risk groups were stratified by the median of the risk scores of the training set. Survival analysis was conducted with the Kaplan-Meier plots. RESULTS: Of 85 PCs, adenocarcinoma was the most common epithelial component found in 63 (73 %) tumors. In SRS model, four features were stratified into high- and low-risk groups (HR, 4.119; concordance index ([C-index], 0.664) in the test set. In RRS model, five features helped improve the stratification (HR, 3.716; C-index, 0.591) and in CRS model, three features helped perform the best stratification (HR, 4.795; C-index, 0.617). The two significant features of CRS models were the SUVmax and the histogram feature of energy ([CT Firstorder Energy]). CONCLUSION: In PCs of the lungs, the combined model leveraging semantic and radiomics features provides a better prognosis compared to using semantic and radiomics features separately. The high SUVmax of solid portion (CT Firstorder Energy) of tumors is associated with poor prognosis in lung PCs.

Are radiomics features universally applicable to different organs?

BACKGROUND: Many studies have successfully identified radiomics features reflecting macroscale tumor features and tumor microenvironment for various organs. There is an increased interest in applying these radiomics features found in a given organ to other organs. Here, we explored whether common radiomics features could be identified over target organs in vastly different environments. METHODS: Four datasets of three organs were analyzed. One radiomics model was constructed from the training set (lungs, n = 401), and was further evaluated in three independent test sets spanning three organs (lungs, n = 59; kidneys, n = 48; and brains, n = 43). Intensity histograms derived from the whole organ were compared to establish organ-level differences. We constructed a radiomics score based on selected features using training lung data over the tumor region. A total of 143 features were computed for each tumor. We adopted a feature selection approach that favored stable features, which can also capture survival. The radiomics score was applied to three independent test data from lung, kidney, and brain tumors, and whether the score could be used to separate high- and low-risk groups, was evaluated. RESULTS: Each organ showed a distinct pattern in the histogram and the derived parameters (mean and median) at the organ-level. The radiomics score trained from the lung data of the tumor region included seven features, and the score was only effective in stratifying survival for other lung data, not in other organs such as the kidney and brain. Eliminating the lung-specific feature (2.5 percentile) from the radiomics score led to similar results. There were no common features between training and test sets, but a common category of features (texture category) was identified. CONCLUSION: Although the possibility of a generally applicable model cannot be excluded, we suggest that radiomics score models for survival were mostly specific for a given organ; applying them to other organs would require careful consideration of organ-specific properties.

The Tumor-Fat Interface Volume of Breast Cancer on Pretreatment MRI Is Associated with a Pathologic Response to Neoadjuvant Chemotherapy.

Adipocytes are active sources of numerous adipokines that work in both a paracrine and endocrine manner. It is not known that the direct contact between tumor and neighboring fat measured by pretreatment breast magnetic resonance imaging (MRI) affects treatment outcomes to neoadjuvant chemotherapy (NAC) in breast cancer patients. A biomarker quantifying the tumor-fat interface volume from pretreatment MRI was proposed and used to predict pathologic complete response (pCR) in breast cancer patients treated with NAC. The tumor-fat interface volume was computed with data-driven clustering using multiphasic MRI. Our approach was developed and validated in two cohorts consisting of 1140 patients. A high tumor-fat interface volume was significantly associated with a non-pCR in both the development and validation cohorts (p = 0.030 and p = 0.037, respectively). Quantitative measurement of the tumor-fat interface volume based on pretreatment MRI may be useful for precision medicine and subsequently influence the treatment strategy of patients.

Radiomics Based on Thyroid Ultrasound Can Predict Distant Metastasis of Follicular Thyroid Carcinoma.

We aimed to evaluate whether radiomics analysis based on gray-scale ultrasound (US) can predict distant metastasis of follicular thyroid cancer (FTC). We retrospectively included 35 consecutive FTCs with distant metastases and 134 FTCs without distant metastasis. We extracted a total of 60 radiomics features derived from the first order, shape, gray-level cooccurrence matrix, and gray-level size zone matrix features using US imaging. A radiomics signature was generated using the least absolute shrinkage and selection operator and was used to train a support vector machine (SVM) classifier in five-fold cross-validation. The SVM classifier showed an area under the curve (AUC) of 0.90 on average on the test folds. Age, size, widely invasive histology, extrathyroidal extension, lymph node metastases on pathology, nodule-in-nodule appearance, marked hypoechogenicity, and rim calcification on the US were significantly more frequent among FTCs with distant metastasis compared to those without metastasis (p < 0.05). Radiomics signature and widely invasive histology were significantly associated with distant metastasis on multivariate analysis (p < 0.01 and p = 0.003). The classifier using the results of the multivariate analysis showed an AUC of 0.93. The radiomics signature from thyroid ultrasound is an independent biomarker for noninvasively predicting distant metastasis of FTC.

Multi-Habitat Radiomics Unravels Distinct Phenotypic Subtypes of Glioblastoma with Clinical and Genomic Significance.

We aimed to evaluate the potential of radiomics as an imaging biomarker for glioblastoma (GBM) patients and explore the molecular rationale behind radiomics using a radio-genomics approach. A total of 144 primary GBM patients were included in this study (training cohort). Using multi-parametric MR images, radiomics features were extracted from multi-habitats of the tumor. We applied Cox-LASSO algorithm to build a survival prediction model, which we validated using an independent validation cohort. GBM patients were consensus clustered to reveal inherent phenotypic subtypes. GBM patients were successfully stratified by the radiomics risk score, a weighted sum of radiomics features, corroborating the potential of radiomics as a prognostic biomarker. Using consensus clustering, we identified three distinct subtypes which significantly differed in the prognosis ("heterogenous enhancing", "rim-enhancing necrotic", and "cystic" subtypes). Transcriptomic traits enriched in individual subtypes were in accordance with imaging phenotypes summarized by radiomics. For example, rim-enhancing necrotic subtype was well described by radiomics profiling (T2 autocorrelation and flat shape) and highlighted by the inflammatory genomic signatures, which well correlated to its phenotypic peculiarity (necrosis). This study showed that imaging subtypes derived from radiomics successfully recapitulated the genomic underpinnings of GBMs and thereby confirmed the feasibility of radiomics as an imaging biomarker for GBM patients with comprehensible biologic annotation.

Integrative Radiogenomics Approach for Risk Assessment of Post-Operative Metastasis in Pathological T1 Renal Cell Carcinoma: A Pilot Retrospective Cohort Study.

Despite the increasing incidence of pathological stage T1 renal cell carcinoma (pT1 RCC), postoperative distant metastases develop in many surgically treated patients, causing death in certain cases. Therefore, this study aimed to create a radiomics model using imaging features from multiphase computed tomography (CT) to more accurately predict the postoperative metastasis of pT1 RCC and further investigate the possible link between radiomics parameters and gene expression profiles generated by whole transcriptome sequencing (WTS). Four radiomic features, including the minimum value of a histogram feature from inner regions of interest (ROIs) (INNER_Min_hist), the histogram of the energy feature from outer ROIs (OUTER_Energy_Hist), the maximum probability of gray-level co-occurrence matrix (GLCM) feature from inner ROIs (INNER_MaxProb_GLCM), and the ratio of voxels under 80 Hounsfield units (Hus) in the nephrographic phase of postcontrast CT (Under80HURatio), were detected to predict the postsurgical metastasis of patients with pathological stage T1 RCC, and the clinical outcomes of patients could be successfully stratified based on their radiomic risk scores. Furthermore, we identified heterogenous-trait-associated gene signatures correlated with these four radiomic features, which captured clinically relevant molecular pathways, tumor immune microenvironment, and potential treatment strategies. Our results of accurate surrogates using radiogenomics could lead to additional benefit from adjuvant therapy or postsurgical metastases in pT1 RCC.

Marginal radiomics features as imaging biomarkers for pathological invasion in lung adenocarcinoma.

OBJECTIVES: Lung adenocarcinomas which manifest as ground-glass nodules (GGNs) have different degrees of pathological invasion and differentiating among them is critical for treatment. Our goal was to evaluate the addition of marginal features to a baseline radiomics model on computed tomography (CT) images to predict the degree of pathologic invasiveness. METHODS: We identified 236 patients from two cohorts (training, n = 189; validation, n = 47) who underwent surgery for GGNs. All GGNs were pathologically confirmed as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IA). The regions of interest were semi-automatically annotated and 40 radiomics features were computed. We selected features using L1-norm regularization to build the baseline radiomics model. Additional marginal features were developed using the cumulative distribution function (CDF) of intratumoral intensities. An improved model was built combining the baseline model with CDF features. Three classifiers were tested for both models. RESULTS: The baseline radiomics model included five features and resulted in an average area under the curve (AUC) of 0.8419 (training) and 0.9142 (validation) for the three classifiers. The second model, with the additional marginal features, resulted in AUCs of 0.8560 (training) and 0.9581 (validation). All three classifiers performed better with the added features. The support vector machine showed the most performance improvement (AUC improvement = 0.0790) and the best performance was achieved by the logistic classifier (validation AUC = 0.9825). CONCLUSION: Our novel marginal features, when combined with a baseline radiomics model, can help differentiate IA from AIS and MIA on preoperative CT scans. KEY POINTS: • Our novel marginal features could improve the existing radiomics model to predict the degree of pathologic invasiveness in lung adenocarcinoma.