Coronary artery calcium is an accurate predictor of cardiovascular events. While it is visible on all computed tomography (CT) scans of the chest, this information is not routinely quantified as it ...requires expertise, time, and specialized equipment. Here, we show a robust and time-efficient deep learning system to automatically quantify coronary calcium on routine cardiac-gated and non-gated CT. As we evaluate in 20,084 individuals from distinct asymptomatic (Framingham Heart Study, NLST) and stable and acute chest pain (PROMISE, ROMICAT-II) cohorts, the automated score is a strong predictor of cardiovascular events, independent of risk factors (multivariable-adjusted hazard ratios up to 4.3), shows high correlation with manual quantification, and robust test-retest reliability. Our results demonstrate the clinical value of a deep learning system for the automated prediction of cardiovascular events. Implementation into clinical practice would address the unmet need of automating proven imaging biomarkers to guide management and improve population health.
Artificial intelligence (AI), especially deep learning, has the potential to fundamentally alter clinical radiology. AI algorithms, which excel in quantifying complex patterns in data, have shown ...remarkable progress in applications ranging from self-driving cars to speech recognition. The AI application within radiology, known as radiomics, can provide detailed quantifications of the radiographic characteristics of underlying tissues. This information can be used throughout the clinical care path to improve diagnosis and treatment planning, as well as assess treatment response. This tremendous potential for clinical translation has led to a vast increase in the number of research studies being conducted in the field, a number that is expected to rise sharply in the future. Many studies have reported robust and meaningful findings; however, a growing number also suffer from flawed experimental or analytic designs. Such errors could not only result in invalid discoveries, but also may lead others to perpetuate similar flaws in their own work. This perspective article aims to increase awareness of the issue, identify potential reasons why this is happening, and provide a path forward.
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Two CT features were developed to quantitatively describe lung adenocarcinomas by scoring tumor shape complexity (feature 1: convexity) and intratumor density variation (feature 2: entropy ratio) in ...routinely obtained diagnostic CT scans. The developed quantitative features were analyzed in two independent cohorts (cohort 1: n = 61; cohort 2: n = 47) of patients diagnosed with primary lung adenocarcinoma, retrospectively curated to include imaging and clinical data. Preoperative chest CTs were segmented semi-automatically. Segmented tumor regions were further subdivided into core and boundary sub-regions, to quantify intensity variations across the tumor. Reproducibility of the features was evaluated in an independent test-retest dataset of 32 patients. The proposed metrics showed high degree of reproducibility in a repeated experiment (concordance, CCC≥0.897; dynamic range, DR≥0.92). Association with overall survival was evaluated by Cox proportional hazard regression, Kaplan-Meier survival curves, and the log-rank test. Both features were associated with overall survival (convexity: p = 0.008; entropy ratio: p = 0.04) in Cohort 1 but not in Cohort 2 (convexity: p = 0.7; entropy ratio: p = 0.8). In both cohorts, these features were found to be descriptive and demonstrated the link between imaging characteristics and patient survival in lung adenocarcinoma.
Tumors are characterized by somatic mutations that drive biological processes ultimately reflected in tumor phenotype. With regard to radiographic phenotypes, generally unconnected through present ...understanding to the presence of specific mutations, artificial intelligence methods can automatically quantify phenotypic characters by using predefined, engineered algorithms or automatic deep-learning methods, a process also known as radiomics. Here we demonstrate how imaging phenotypes can be connected to somatic mutations through an integrated analysis of independent datasets of 763 lung adenocarcinoma patients with somatic mutation testing and engineered CT image analytics. We developed radiomic signatures capable of distinguishing between tumor genotypes in a discovery cohort (
= 353) and verified them in an independent validation cohort (
= 352). All radiomic signatures significantly outperformed conventional radiographic predictors (tumor volume and maximum diameter). We found a radiomic signature related to radiographic heterogeneity that successfully discriminated between EGFR
and EGFR
cases (AUC = 0.69). Combining this signature with a clinical model of EGFR status (AUC = 0.70) significantly improved prediction accuracy (AUC = 0.75). The highest performing signature was capable of distinguishing between EGFR
and KRAS
tumors (AUC = 0.80) and, when combined with a clinical model (AUC = 0.81), substantially improved its performance (AUC = 0.86). A KRAS
/KRAS
radiomic signature also showed significant albeit lower performance (AUC = 0.63) and did not improve the accuracy of a clinical predictor of KRAS status. Our results argue that somatic mutations drive distinct radiographic phenotypes that can be predicted by radiomics. This work has implications for the use of imaging-based biomarkers in the clinic, as applied noninvasively, repeatedly, and at low cost.
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Abstract Solid cancers are spatially and temporally heterogeneous. This limits the use of invasive biopsy based molecular assays but gives huge potential for medical imaging, which has the ability to ...capture intra-tumoural heterogeneity in a non-invasive way. During the past decades, medical imaging innovations with new hardware, new imaging agents and standardised protocols, allows the field to move towards quantitative imaging. Therefore, also the development of automated and reproducible analysis methodologies to extract more information from image-based features is a requirement. Radiomics – the high-throughput extraction of large amounts of image features from radiographic images – addresses this problem and is one of the approaches that hold great promises but need further validation in multi-centric settings and in the laboratory.
In this study we assessed the repeatability of radiomics features on small prostate tumors using test-retest Multiparametric Magnetic Resonance Imaging (mpMRI). The premise of radiomics is that ...quantitative image-based features can serve as biomarkers for detecting and characterizing disease. For such biomarkers to be useful, repeatability is a basic requirement, meaning its value must remain stable between two scans, if the conditions remain stable. We investigated repeatability of radiomics features under various preprocessing and extraction configurations including various image normalization schemes, different image pre-filtering, and different bin widths for image discretization. Although we found many radiomics features and preprocessing combinations with high repeatability (Intraclass Correlation Coefficient > 0.85), our results indicate that overall the repeatability is highly sensitive to the processing parameters. Neither image normalization, using a variety of approaches, nor the use of pre-filtering options resulted in consistent improvements in repeatability. We urge caution when interpreting radiomics features and advise paying close attention to the processing configuration details of reported results. Furthermore, we advocate reporting all processing details in radiomics studies and strongly recommend the use of open source implementations.
Abstract Background and purpose Radiomics provides opportunities to quantify the tumor phenotype non-invasively by applying a large number of quantitative imaging features. This study evaluates ...computed-tomography (CT) radiomic features for their capability to predict distant metastasis (DM) for lung adenocarcinoma patients. Material and methods We included two datasets: 98 patients for discovery and 84 for validation. The phenotype of the primary tumor was quantified on pre-treatment CT-scans using 635 radiomic features. Univariate and multivariate analysis was performed to evaluate radiomics performance using the concordance index (CI). Results Thirty-five radiomic features were found to be prognostic (CI > 0.60, FDR < 5%) for DM and twelve for survival. It is noteworthy that tumor volume was only moderately prognostic for DM (CI = 0.55, p -value = 2.77 × 10−5 ) in the discovery cohort. A radiomic-signature had strong power for predicting DM in the independent validation dataset (CI = 0.61, p -value = 1.79 × 10−17 ). Adding this radiomic-signature to a clinical model resulted in a significant improvement of predicting DM in the validation dataset ( p -value = 1.56 × 10−11 ). Conclusions Although only basic metrics are routinely quantified, this study shows that radiomic features capturing detailed information of the tumor phenotype can be used as a prognostic biomarker for clinically-relevant factors such as DM. Moreover, the radiomic-signature provided additional information to clinical data.
Radiomics provides a comprehensive quantification of tumor phenotypes by extracting and mining large number of quantitative image features. To reduce the redundancy and compare the prognostic ...characteristics of radiomic features across cancer types, we investigated cancer-specific radiomic feature clusters in four independent Lung and Head &Neck (H) cancer cohorts (in total 878 patients). Radiomic features were extracted from the pre-treatment computed tomography (CT) images. Consensus clustering resulted in eleven and thirteen stable radiomic feature clusters for Lung and H cancer, respectively. These clusters were validated in independent external validation cohorts using rand statistic (Lung RS = 0.92, p < 0.001, H RS = 0.92, p < 0.001). Our analysis indicated both common as well as cancer-specific clustering and clinical associations of radiomic features. Strongest associations with clinical parameters: Prognosis Lung CI = 0.60 ± 0.01, Prognosis H CI = 0.68 ± 0.01; Lung histology AUC = 0.56 ± 0.03, Lung stage AUC = 0.61 ± 0.01, H HPV AUC = 0.58 ± 0.03, H stage AUC = 0.77 ± 0.02. Full utilization of these cancer-specific characteristics of image features may further improve radiomic biomarkers, providing a non-invasive way of quantifying and monitoring tumor phenotypic characteristics in clinical practice.
PET-based texture features have been used to quantify tumor heterogeneity due to their predictive power in treatment outcome. We investigated the sensitivity of texture features to tumor motion by ...comparing static (3D) and respiratory-gated (4D) PET imaging.
Twenty-six patients (34 lesions) received 3D and 4D 18FFDG-PET scans before the chemo-radiotherapy. The acquired 4D data were retrospectively binned into five breathing phases to create the 4D image sequence. Texture features, including Maximal correlation coefficient (MCC), Long run low gray (LRLG), Coarseness, Contrast, and Busyness, were computed within the physician-defined tumor volume. The relative difference (δ3D-4D) in each texture between the 3D- and 4D-PET imaging was calculated. Coefficient of variation (CV) was used to determine the variability in the textures between all 4D-PET phases. Correlations between tumor volume, motion amplitude, and δ3D-4D were also assessed.
4D-PET increased LRLG ( = 1%-2%, p < 0.02), Busyness ( = 7%-19%, p < 0.01), and decreased MCC ( = 1%-2%, p < 7.5 × 10(-3)), Coarseness ( = 5%-10%, p < 0.05) and Contrast ( = 4%-6%, p > 0.08) compared to 3D-PET. Nearly negligible variability was found between the 4D phase bins with CV < 5% for MCC, LRLG, and Coarseness. For Contrast and Busyness, moderate variability was found with CV = 9% and 10%, respectively. No strong correlation was found between the tumor volume and δ3D-4D for the texture features. Motion amplitude had moderate impact on δ for MCC and Busyness and no impact for LRLG, Coarseness, and Contrast.
Significant differences were found in MCC, LRLG, Coarseness, and Busyness between 3D and 4D PET imaging. The variability between phase bins for MCC, LRLG, and Coarseness was negligible, suggesting that similar quantification can be obtained from all phases. Texture features, blurred out by respiratory motion during 3D-PET acquisition, can be better resolved by 4D-PET imaging. 4D-PET textures may have better prognostic value as they are less susceptible to tumor motion.
Radiographic imaging continues to be one of the most effective and clinically useful tools within oncology. Sophistication of artificial intelligence has allowed for detailed quantification of ...radiographic characteristics of tissues using predefined engineered algorithms or deep learning methods. Precedents in radiology as well as a wealth of research studies hint at the clinical relevance of these characteristics. However, critical challenges are associated with the analysis of medical imaging data. Although some of these challenges are specific to the imaging field, many others like reproducibility and batch effects are generic and have already been addressed in other quantitative fields such as genomics. Here, we identify these pitfalls and provide recommendations for analysis strategies of medical imaging data, including data normalization, development of robust models, and rigorous statistical analyses. Adhering to these recommendations will not only improve analysis quality but also enhance precision medicine by allowing better integration of imaging data with other biomedical data sources.
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