Aimilia Gastounioti

Beyond breast density: a review on the advancing role of parenchymal texture analysis in breast cancer risk assessment

BackgroundThe 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.Main textThe 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.ConclusionsThe 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.

Cancer imaging phenomics toolkit: quantitative imaging analytics for precision diagnostics and predictive modeling of clinical outcome

Abstract. 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.

Volumetric versus area-based density assessment: comparisons using automated quantitative measurements from a large screening cohort.

Mammographic density is an established risk factor for breast cancer. However, area-based density (ABD) measured in 2D mammograms consider the projection, rather than the actual volume of dense tissue which may be an important limitation. With the increasing utilization of digital breast tomosynthesis (DBT) in screening, there’s an opportunity to routinely estimate volumetric breast density (VBD). In this study, we investigate associations between DBT-VBD and ABD extracted from standard-dose mammography (DM) and synthetic 2D digital mammography (sDM) increasingly replacing DM. We retrospectively analyzed bilateral imaging data from a random sample of 1000 women, acquired over a transitional period at our institution when all women had DBT, sDM and DM acquired as part of their routine breast screening. For each exam, ABD was measured in DM and sDM images with the publicly available “LIBRA” software, while DBT-VBD was measured using a previously validated, fully-automated computer algorithm. Spearman correlation (r) was used to compare VBD to ABD measurements. For each density measure, we also estimated the within woman intraclass correlation (ICC) and finally, to compare to clinical assessments, we performed analysis of variance (ANOVA) to evaluate the variation to the assigned clinical BI-RADS breast density category for each woman. DBT-VBD was moderately correlated to ABD from DM (r=0.70) and sDM (r=0.66). All density measures had strong bilateral symmetry (ICC = [0.85, 0.95]), but were significantly different across BI-RADS density categories (ANOVA, p<0.001). Our results contribute to further elaborating the clinical implications of breast density measures estimated with DBT which may better capture the volumetric amount of dense tissue within the breast than area-based measures and visual assessment.

Validation of the textural realism of a 3D anthropomorphic phantom for digital breast tomosynthesis.

In this paper, texture calculations are used to validate the realism of a physical anthropomorphic phantom for digital breast tomosynthesis. The texture features were compared against clinical mammography data. Three groups of features (grey-level histogram, co-occurrence, and run-length) were considered. The features were analyzed over a broad range of technique settings (kV and mAs). These calculations were done in the central slice of the reconstruction as well as the synthetic 2D mammogram. For each feature, the clinical data were binned into strata based on the compressed breast thickness. It was demonstrated that the clinical features vary by thickness. To evaluate the realism of the phantom, each feature was compared against clinical data in the same thickness stratum. For the purpose of this paper, a feature was considered to be realistic if it was within the middle 95% of the statistical distribution of clinical values. In the reconstruction, most features were found to exhibit realism; specifically, all 12 grey-level histogram features, four out of seven co-occurrence features, and three out of seven run-length features. The realism of most features was robust to changes in the technique settings. However, in the synthetic 2D mammogram, fewer features were found to exhibit realism. In conclusion, this paper provides a validation of the textural realism of the phantom in the reconstruction, and shows that there is less realism in the synthetic 2D mammogram. We identify the features that should be considered to refine the design of the phantom in future work.

Convolutional neural network approach for enhanced capture of breast parenchymal complexity patterns associated with breast cancer risk

We assess the feasibility of a parenchymal texture feature fusion approach, utilizing a convolutional neural network (ConvNet) architecture, to benefit breast cancer risk assessment. Hypothesizing that by capturing sparse, subtle interactions between localized motifs present in two-dimensional texture feature maps derived from mammographic images, a multitude of texture feature descriptors can be optimally reduced to five meta-features capable of serving as a basis on which a linear classifier, such as logistic regression, can efficiently assess breast cancer risk. We combine this methodology with our previously validated lattice-based strategy for parenchymal texture analysis and we evaluate the feasibility of this approach in a case-control study with 424 digital mammograms. In a randomized split-sample setting, we optimize our framework in training/validation sets (N=300) and evaluate its descriminatory performance in an independent test set (N=124). The discriminatory capacity is assessed in terms of the the area under the curve (AUC) of the receiver operator characteristic (ROC). The resulting meta-features exhibited strong classification capability in the test dataset (AUC = 0.90), outperforming conventional, non-fused, texture analysis which previously resulted in an AUC=0.85 on the same case-control dataset. Our results suggest that informative interactions between localized motifs exist and can be extracted and summarized via a fairly simple ConvNet architecture.

Mammographic phenotypes of breast cancer risk driven by breast anatomy

Image-derived features of breast parenchymal texture patterns have emerged as promising risk factors for breast cancer, paving the way towards personalized recommendations regarding women’s cancer risk evaluation and screening. The main steps to extract texture features of the breast parenchyma are the selection of regions of interest (ROIs) where texture analysis is performed, the texture feature calculation and the texture feature summarization in case of multiple ROIs. In this study, we incorporate breast anatomy in these three key steps by (a) introducing breast anatomical sampling for the definition of ROIs, (b) texture feature calculation aligned with the structure of the breast and (c) weighted texture feature summarization considering the spatial position and the underlying tissue composition of each ROI. We systematically optimize this novel framework for parenchymal tissue characterization in a case-control study with digital mammograms from 424 women. We also compare the proposed approach with a conventional methodology, not considering breast anatomy, recently shown to enhance the case-control discriminatory capacity of parenchymal texture analysis. The case-control classification performance is assessed using elastic-net regression with 5-fold cross validation, where the evaluation measure is the area under the curve (AUC) of the receiver operating characteristic. Upon optimization, the proposed breast-anatomy-driven approach demonstrated a promising case-control classification performance (AUC=0.87). In the same dataset, the performance of conventional texture characterization was found to be significantly lower (AUC=0.80, DeLongs test p-value<0.05). Our results suggest that breast anatomy may further leverage the associations of parenchymal texture features with breast cancer, and may therefore be a valuable addition in pipelines aiming to elucidate quantitative mammographic phenotypes of breast cancer risk.

Preliminary evaluation of a fully automated quantitative framework for characterizing general breast tissue histology via color histogram and color texture analysis

Visual characterization of histologic specimens is known to suffer from intra- and inter-observer variability. To help address this, we developed an automated framework for characterizing digitized histology specimens based on a novel application of color histogram and color texture analysis. We perform a preliminary evaluation of this framework using a set of 73 trichrome-stained, digitized slides of normal breast tissue which were visually assessed by an expert pathologist in terms of the percentage of collagenous stroma, stromal collagen density, duct-lobular unit density and the presence of elastosis. For each slide, our algorithm automatically segments the tissue region based on the lightness channel in CIELAB colorspace. Within each tissue region, a color histogram feature vector is extracted using a common color palette for trichrome images generated with a previously described method. Then, using a whole-slide, lattice-based methodology, color texture maps are generated using a set of color co-occurrence matrix statistics: contrast, correlation, energy and homogeneity. The extracted features sets are compared to the visually assessed tissue characteristics. Overall, the extracted texture features have high correlations to both the percentage of collagenous stroma (r=0.95, p<0.001) and duct-lobular unit density (r=0.71, p<0.001) seen in the tissue samples, and several individual features were associated with either collagen density and/or the presence of elastosis (p≤0.05). This suggests that the proposed framework has promise as a means to quantitatively extract descriptors reflecting tissue-level characteristics and thus could be useful in detecting and characterizing histological processes in digitized histology specimens.

Parenchymal texture measures weighted by breast anatomy: preliminary optimization in a case-control study

Growing evidence suggests that quantitative descriptors of the parenchymal texture patterns hold a valuable role in assessing an individual woman’s risk for breast cancer. In this work, we assess the hypothesis that breast cancer risk factors are not uniformly expressed in the breast parenchymal tissue and, therefore, breast-anatomy-weighted parenchymal texture descriptors, where different breasts ROIs have non uniform contributions, may enhance breast cancer risk assessment. To this end, we introduce an automated breast-anatomy-driven methodology which generates a breast atlas, which is then used to produce a weight map that reinforces the contributions of the central and upper-outer breast areas. We incorporate this methodology to our previously validated lattice-based strategy for parenchymal texture analysis. In the framework of a pilot case-control study, including digital mammograms from 424 women, our proposed breast-anatomy-weighted texture descriptors are optimized and evaluated against non weighted texture features, using regression analysis with leave-one-out cross validation. The classification performance is assessed in terms of the area under the curve (AUC) of the receiver operating characteristic. The collective discriminatory capacity of the weighted texture features was maximized (AUC=0.87) when the central breast area was considered more important than the upperouter area, with significant performance improvement (DeLongs test, p-value<0.05) against the non-weighted texture features (AUC=0.82). Our results suggest that breast-anatomy-driven methodologies have the potential to further upgrade the promising role of parenchymal texture analysis in breast cancer risk assessment and may serve as a reference in the design of future studies towards image-driven personalized recommendations regarding women’s cancer risk evaluation.