Abstract"Radiomics" refers to the extraction and analysis of large amounts of advanced quantitative imaging features with high throughput from medical images obtained with computed tomography (CT), positron emission tomography (PET) or magnetic resonance imaging (MRI). Importantly, these data are designed to be extracted from standard-of-care images, leading to a very large potential subject pool. Radiomic data are in a mineable form that can be used to build descriptive and predictive models relating image features to phenotypes or gene-protein signatures. The core hypothesis of radiomics is that these models, which can include biological or medical data, can provide valuable diagnostic, prognostic or predictive information. The radiomics enterprise can be divided into distinct processes, each with its own challenges that need to be overcome: (i) image acquisition and reconstruction (ii) image segmentation and rendering (iii) feature extraction and feature qualification (iv) databases and data sharing for eventual (v) ad hoc informatic analyses.Each of these individual processes poses unique challenges. For example, optimum protocols for image acquisition and reconstruction have to be identified and harmonized. Also, segmentations have to be robust and involve minimal operator input. Features have to be generated that robustly reflect the complexity of the individual volumes, but cannot be overly complex or redundant. Furthermore, informatics databases that allow incorporation of image features and image annotations, along with medical and genetic data have to be generated. Finally, the statistical approaches to analyze these data have to be optimized, as radiomics is not a mature field of study. Each of these processes will be discussed in turn, as well as some of their unique challenges and

We study the reproducibility of quantitative imaging features that are used to describe tumor shape, size, and texture from computed tomography (CT) scans of non-small cell lung cancer (NSCLC). CT images are dependent on various scanning factors. We focus on characterizing image features that are reproducible in the presence of variations due to patient factors and segmentation methods. Thirty-two NSCLC nonenhanced lung CT scans were obtained from the Reference Image Database to Evaluate Response data set. The tumors were segmented using both manual (radiologist expert) and ensemble (software-automated) methods. A set of features (219 three-dimensional and 110 two-dimensional) was computed, and quantitative image features were statistically filtered to identify a subset of reproducible and nonredundant features. The variability in the repeated experiment was measured by the test-retest concordance correlation coefficient (CCCTreT). The natural range in the features, normalized to variance, was measured by the dynamic range (DR). In this study, there were 29 features across segmentation methods found with CCCTreT and DR ≥ 0.9 and R(2) Bet ≥ 0.95. These reproducible features were tested for predicting radiologist prognostic score; some texture features (run-length and Laws kernels) had an area under the curve of 0.9. The representative features were tested for their prognostic capabilities using an independent NSCLC data set (59 lung adenocarcinomas), where one of the texture features, run-length gray-level nonuniformity, was statistically significant in separating the samples into survival groups (P ≤ .046).

Image reconstruction for magnetic resonance spectroscopic imaging (MRSI) requires specialized spatial and spectral data processing methods and benefits from the use of several sources of prior information that are not commonly available, including MRI-derived tissue segmentation, morphological analysis and spectral characteristics of the observed metabolites. In addition, incorporating information obtained from MRI data can enhance the display of low-resolution metabolite images and multiparametric and regional statistical analysis methods can improve detection of altered metabolite distributions. As a result, full MRSI processing and analysis can involve multiple processing steps and several different data types. In this paper, a processing environment is described that integrates and automates these data processing and analysis functions for imaging of proton metabolite distributions in the normal human brain. The capabilities include normalization of metabolite signal intensities and transformation into a common spatial reference frame, thereby allowing the formation of a database of MR-measured human metabolite values as a function of acquisition, spatial and subject parameters. This development is carried out under the MIDAS project (Metabolite Imaging and Data Analysis System), which provides an integrated set of MRI and MRSI processing functions. It is anticipated that further development and distribution of these capabilities will facilitate more widespread use of MRSI for diagnostic imaging, encourage the development of standardized MRSI acquisition, processing and analysis methods and enable improved mapping of metabolite distributions in the human brain.

Quantitative size, shape, and texture features derived from computed tomographic (CT) images may be useful as predictive, prognostic, or response biomarkers in non-small cell lung cancer (NSCLC). However, to be useful, such features must be reproducible, non-redundant, and have a large dynamic range. We developed a set of quantitative three-dimensional (3D) features to describe segmented tumors and evaluated their reproducibility to select features with high potential to have prognostic utility. Thirty-two patients with NSCLC were subjected to unenhanced thoracic CT scans acquired within 15 min of each other under an approved protocol. Primary lung cancer lesions were segmented using semi-automatic 3D region growing algorithms. Following segmentation, 219 quantitative 3D features were extracted from each lesion, corresponding to size, shape, and texture, including features in transformed spaces (laws, wavelets). The most informative features were selected using the concordance correlation coefficient across test-retest, the biological range and a feature independence measure. There were 66 (30.14%) features with concordance correlation coefficient ≥ 0.90 across test-retest and acceptable dynamic range. Of these, 42 features were non-redundant after grouping features with R (2) Bet ≥ 0.95. These reproducible features were found to be predictive of radiological prognosis. The area under the curve (AUC) was 91% for a size-based feature and 92% for the texture features (runlength, laws). We tested the ability of image features to predict a radiological prognostic score on an independent NSCLC (39 adenocarcinoma) samples, the AUC for texture features (runlength emphasis, energy) was 0.84 while the conventional size-based features (volume, longest diameter) was 0.80. Test-retest and correlation analyses have identified non-redundant CT image features with both high intra-patient reproducibility and inter-patient biological range. Thus making the case that quantitative image features are informative and prognostic biomarkers for NSCLC.

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.