The growth of multiparametric imaging protocols has paved the way for quantitative imaging phenotypes that predict treatment response and clinical outcome, reflect underlying cancer molecular characteristics and spatiotemporal heterogeneity, and can guide personalized treatment planning. This growth has underlined the need for efficient quantitative analytics to derive high-dimensional imaging signatures of diagnostic and predictive value in this emerging era of integrated precision diagnostics. This paper presents cancer imaging phenomics toolkit (CaPTk), a new and dynamically growing software platform for analysis of radiographic images of cancer, currently focusing on brain, breast, and lung cancer. CaPTk leverages the value of quantitative imaging analytics along with machine learning to derive phenotypic imaging signatures, based on two-level functionality. First, image analysis algorithms are used to extract comprehensive panels of diverse and complementary features, such as multiparametric intensity histogram distributions, texture, shape, kinetics, connectomics, and spatial patterns. At the second level, these quantitative imaging signatures are fed into multivariate machine learning models to produce diagnostic, prognostic, and predictive biomarkers. Results from clinical studies in three areas are shown: (i) computational neuro-oncology of brain gliomas for precision diagnostics, prediction of outcome, and treatment planning; (ii) prediction of treatment response for breast and lung cancer, and (iii) risk assessment for breast cancer.

The assessment of a woman’s risk for developing breast cancer has become increasingly important for establishing personalized screening recommendations and forming preventive strategies. Studies have consistently shown a strong relationship between breast cancer risk and mammographic parenchymal patterns, typically assessed by percent mammographic density. This paper will review the advancing role of mammographic texture analysis as a potential novel approach to characterize the breast parenchymal tissue to augment conventional density assessment in breast cancer risk estimation. The analysis of mammographic texture provides refined, localized descriptors of parenchymal tissue complexity. Currently, there is growing evidence in support of textural features having the potential to augment the typically dichotomized descriptors (dense or not dense) of area or volumetric measures of breast density in breast cancer risk assessment. Therefore, a substantial research effort has been devoted to automate mammographic texture analysis, with the aim of ultimately incorporating such quantitative measures into breast cancer risk assessment models. In this paper, we review current and emerging approaches in this field, summarizing key methodological details and related studies using novel computerized approaches. We also discuss research challenges for advancing the role of parenchymal texture analysis in breast cancer risk stratification and accelerating its clinical translation. The objective is to provide a comprehensive reference for researchers in the field of parenchymal pattern analysis in breast cancer risk assessment, while indicating key directions for future research.

Purpose: Identifying imaging phenotypes and understanding their relationship with prognostic markers and patient outcomes can allow for a noninvasive assessment of cancer. The purpose of this study was to identify and validate intrinsic imaging phenotypes of breast cancer heterogeneity in preoperative breast dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) scans and evaluate their prognostic performance in predicting 10 years recurrence. Experimental Design: Pretreatment DCE-MRI scans of 95 women with primary invasive breast cancer with at least 10 years of follow-up from a clinical trial at our institution (2002–2006) were retrospectively analyzed. For each woman, a signal enhancement ratio (SER) map was generated for the entire segmented primary lesion volume from which 60 radiomic features of texture and morphology were extracted. Intrinsic phenotypes of tumor heterogeneity were identified via unsupervised hierarchical clustering of the extracted features. An independent sample of 163 women diagnosed with primary invasive breast cancer (2002–2006), publicly available via The Cancer Imaging Archive, was used to validate phenotype reproducibility. Results: Three significant phenotypes of low, medium, and high heterogeneity were identified in the discovery cohort and reproduced in the validation cohort (P < 0.01). Kaplan–Meier curves showed statistically significant differences (P < 0.05) in recurrence-free survival (RFS) across phenotypes. Radiomic phenotypes demonstrated added prognostic value (c = 0.73) predicting RFS. Conclusions: Intrinsic imaging phenotypes of breast cancer tumor heterogeneity at primary diagnosis can predict 10-year recurrence. The independent and additional prognostic value of imaging heterogeneity phenotypes suggests that radiomic phenotypes can provide a noninvasive characterization of tumor heterogeneity to augment personalized prognosis and treatment.

Purpose To identify phenotypes of mammographic parenchymal complexity by using radiomic features and to evaluate their associations with breast density and other breast cancer risk factors. Materials and Methods Computerized image analysis was used to quantify breast density and extract parenchymal texture features in a cross-sectional sample of women screened with digital mammography from September 1, 2012, to February 28, 2013 (n = 2029; age range, 35-75 years; mean age, 55.9 years). Unsupervised clustering was applied to identify and reproduce phenotypes of parenchymal complexity in separate training (n = 1339) and test sets (n = 690). Differences across phenotypes by age, body mass index, breast density, and estimated breast cancer risk were assessed by using Fisher exact, χ2, and Kruskal-Wallis tests. Conditional logistic regression was used to evaluate preliminary associations between the detected phenotypes and breast cancer in an independent case-control sample (76 women diagnosed with breast cancer and 158 control participants) matched on age. Results Unsupervised clustering in the screening sample identified four phenotypes with increasing parenchymal complexity that were reproducible between training and test sets (P = .001). Breast density was not strongly correlated with phenotype category (R2 = 0.24 for linear trend). The low- to intermediate-complexity phenotype (prevalence, 390 of 2029 [19%]) had the lowest proportion of dense breasts (eight of 390 [2.1%]), whereas similar proportions were observed across other phenotypes (from 140 of 291 [48.1%] in the high-complexity phenotype to 275 of 511 [53.8%] in the low-complexity phenotype). In the independent case-control sample, phenotypes showed a significant association with breast cancer (P = .001), resulting in higher discriminatory capacity when added to a model with breast density and body mass index (area under the curve, 0.84 vs 0.80; P = .03 for comparison). Conclusion Radiomic phenotypes capture mammographic parenchymal complexity beyond conventional breast density measures and established breast cancer risk factors. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Pinker in this issue.

Deep Learning (DL) has the potential to optimize machine learning in both the scientific and clinical communities. However, greater expertise is required to develop DL algorithms, and the variability of implementations hinders their reproducibility, translation, and deployment. Here we present the community-driven Generally Nuanced Deep Learning Framework (GaNDLF), with the goal of lowering these barriers. GaNDLF makes the mechanism of DL development, training, and inference more stable, reproducible, interpretable, and scalable, without requiring an extensive technical background. GaNDLF aims to provide an end-to-end solution for all DL-related tasks in computational precision medicine. We demonstrate the ability of GaNDLF to analyze both radiology and histology images, with built-in support for k-fold cross-validation, data augmentation, multiple modalities and output classes. Our quantitative performance evaluation on numerous use cases, anatomies, and computational tasks supports GaNDLF as a robust application framework for deployment in clinical workflows.