Radiomics aims to quantify phenotypic characteristics on medical imaging through the use of automated algorithms. Radiomic artificial intelligence (AI) technology, either based on engineered ...hard-coded algorithms or deep learning methods, can be used to develop noninvasive imaging-based biomarkers. However, lack of standardized algorithm definitions and image processing severely hampers reproducibility and comparability of results. To address this issue, we developed
, a flexible open-source platform capable of extracting a large panel of engineered features from medical images.
is implemented in Python and can be used standalone or using 3D Slicer. Here, we discuss the workflow and architecture of
and demonstrate its application in characterizing lung lesions. Source code, documentation, and examples are publicly available at www.radiomics.io With this platform, we aim to establish a reference standard for radiomic analyses, provide a tested and maintained resource, and to grow the community of radiomic developers addressing critical needs in cancer research.
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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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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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Radiomics extracts and mines large number of medical imaging features quantifying tumor phenotypic characteristics. Highly accurate and reliable machine-learning approaches can drive the success of ...radiomic applications in clinical care. In this radiomic study, fourteen feature selection methods and twelve classification methods were examined in terms of their performance and stability for predicting overall survival. A total of 440 radiomic features were extracted from pre-treatment computed tomography (CT) images of 464 lung cancer patients. To ensure the unbiased evaluation of different machine-learning methods, publicly available implementations along with reported parameter configurations were used. Furthermore, we used two independent radiomic cohorts for training (n = 310 patients) and validation (n = 154 patients). We identified that Wilcoxon test based feature selection method WLCX (stability = 0.84 ± 0.05, AUC = 0.65 ± 0.02) and a classification method random forest RF (RSD = 3.52%, AUC = 0.66 ± 0.03) had highest prognostic performance with high stability against data perturbation. Our variability analysis indicated that the choice of classification method is the most dominant source of performance variation (34.21% of total variance). Identification of optimal machine-learning methods for radiomic applications is a crucial step towards stable and clinically relevant radiomic biomarkers, providing a non-invasive way of quantifying and monitoring tumor-phenotypic characteristics in clinical practice.
Medical imaging can visualize characteristics of human cancer noninvasively. Radiomics is an emerging field that translates these medical images into quantitative data to enable phenotypic profiling ...of tumors. While radiomics has been associated with several clinical endpoints, the complex relationships of radiomics, clinical factors, and tumor biology are largely unknown. To this end, we analyzed two independent cohorts of respectively 262 North American and 89 European patients with lung cancer, and consistently identified previously undescribed associations between radiomic imaging features, molecular pathways, and clinical factors. In particular, we found a relationship between imaging features, immune response, inflammation, and survival, which was further validated by immunohistochemical staining. Moreover, a number of imaging features showed predictive value for specific pathways; for example, intra-tumor heterogeneity features predicted activity of RNA polymerase transcription (AUC = 0.62, p=0.03) and intensity dispersion was predictive of the autodegration pathway of a ubiquitin ligase (AUC = 0.69, p
10
). Finally, we observed that prognostic biomarkers performed highest when combining radiomic, genetic, and clinical information (CI = 0.73, p<10
) indicating complementary value of these data. In conclusion, we demonstrate that radiomic approaches permit noninvasive assessment of both molecular and clinical characteristics of tumors, and therefore have the potential to advance clinical decision-making by systematically analyzing standard-of-care medical images.
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.
Non-small-cell lung cancer (NSCLC) patients often demonstrate varying clinical courses and outcomes, even within the same tumor stage. This study explores deep learning applications in medical ...imaging allowing for the automated quantification of radiographic characteristics and potentially improving patient stratification.
We performed an integrative analysis on 7 independent datasets across 5 institutions totaling 1,194 NSCLC patients (age median = 68.3 years range 32.5-93.3, survival median = 1.7 years range 0.0-11.7). Using external validation in computed tomography (CT) data, we identified prognostic signatures using a 3D convolutional neural network (CNN) for patients treated with radiotherapy (n = 771, age median = 68.0 years range 32.5-93.3, survival median = 1.3 years range 0.0-11.7). We then employed a transfer learning approach to achieve the same for surgery patients (n = 391, age median = 69.1 years range 37.2-88.0, survival median = 3.1 years range 0.0-8.8). We found that the CNN predictions were significantly associated with 2-year overall survival from the start of respective treatment for radiotherapy (area under the receiver operating characteristic curve AUC = 0.70 95% CI 0.63-0.78, p < 0.001) and surgery (AUC = 0.71 95% CI 0.60-0.82, p < 0.001) patients. The CNN was also able to significantly stratify patients into low and high mortality risk groups in both the radiotherapy (p < 0.001) and surgery (p = 0.03) datasets. Additionally, the CNN was found to significantly outperform random forest models built on clinical parameters-including age, sex, and tumor node metastasis stage-as well as demonstrate high robustness against test-retest (intraclass correlation coefficient = 0.91) and inter-reader (Spearman's rank-order correlation = 0.88) variations. To gain a better understanding of the characteristics captured by the CNN, we identified regions with the most contribution towards predictions and highlighted the importance of tumor-surrounding tissue in patient stratification. We also present preliminary findings on the biological basis of the captured phenotypes as being linked to cell cycle and transcriptional processes. Limitations include the retrospective nature of this study as well as the opaque black box nature of deep learning networks.
Our results provide evidence that deep learning networks may be used for mortality risk stratification based on standard-of-care CT images from NSCLC patients. This evidence motivates future research into better deciphering the clinical and biological basis of deep learning networks as well as validation in prospective data.
Radiomics can quantify tumor phenotypic characteristics non-invasively by applying feature algorithms to medical imaging data. In this study of lung cancer patients, we investigated the association ...between radiomic features and the tumor histologic subtypes (adenocarcinoma and squamous cell carcinoma). Furthermore, in order to predict histologic subtypes, we employed machine-learning methods and independently evaluated their prediction performance.
Two independent radiomic cohorts with a combined size of 350 patients were included in our analysis. A total of 440 radiomic features were extracted from the segmented tumor volumes of pretreatment CT images. These radiomic features quantify tumor phenotypic characteristics on medical images using tumor shape and size, intensity statistics, and texture. Univariate analysis was performed to assess each feature's association with the histological subtypes. In our multivariate analysis, we investigated 24 feature selection methods and 3 classification methods for histology prediction. Multivariate models were trained on the training cohort and their performance was evaluated on the independent validation cohort using the area under ROC curve (AUC). Histology was determined from surgical specimen.
In our univariate analysis, we observed that fifty-three radiomic features were significantly associated with tumor histology. In multivariate analysis, feature selection methods ReliefF and its variants showed higher prediction accuracy as compared to other methods. We found that Naive Baye's classifier outperforms other classifiers and achieved the highest AUC (0.72; p-value = 2.3 × 10(-7)) with five features: Stats_min, Wavelet_HLL_rlgl_lowGrayLevelRunEmphasis, Wavelet_HHL_stats_median, Wavelet_HLL_stats_skewness, and Wavelet_HLH_glcm_clusShade.
Histological subtypes can influence the choice of a treatment/therapy for lung cancer patients. We observed that radiomic features show significant association with the lung tumor histology. Moreover, radiomics-based multivariate classifiers were independently validated for the prediction of histological subtypes. Despite achieving lower than optimal prediction accuracy (AUC 0.72), our analysis highlights the impressive potential of non-invasive and cost-effective radiomics for precision medicine. Further research in this direction could lead us to optimal performance and therefore to clinical applicability, which could enhance the efficiency and efficacy of cancer care.
"Radiomics" extracts and mines a large number of medical imaging features in a non-invasive and cost-effective way. The underlying assumption of radiomics is that these imaging features quantify ...phenotypic characteristics of an entire tumor. In order to enhance applicability of radiomics in clinical oncology, highly accurate and reliable machine-learning approaches are required. In this radiomic study, 13 feature selection methods and 11 machine-learning classification methods were evaluated in terms of their performance and stability for predicting overall survival in head and neck cancer patients.
Two independent head and neck cancer cohorts were investigated. Training cohort HN1 consisted of 101 head and neck cancer patients. Cohort HN2 (n = 95) was used for validation. A total of 440 radiomic features were extracted from the segmented tumor regions in CT images. Feature selection and classification methods were compared using an unbiased evaluation framework.
We observed that the three feature selection methods minimum redundancy maximum relevance (AUC = 0.69, Stability = 0.66), mutual information feature selection (AUC = 0.66, Stability = 0.69), and conditional infomax feature extraction (AUC = 0.68, Stability = 0.7) had high prognostic performance and stability. The three classifiers BY (AUC = 0.67, RSD = 11.28), RF (AUC = 0.61, RSD = 7.36), and NN (AUC = 0.62, RSD = 10.52) also showed high prognostic performance and stability. Analysis investigating performance variability indicated that the choice of classification method is the major factor driving the performance variation (29.02% of total variance).
Our study identified prognostic and reliable machine-learning methods for the prediction of overall survival of head and neck cancer patients. Identification of optimal machine-learning methods for radiomics-based prognostic analyses could broaden the scope of radiomics in precision oncology and cancer care.
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