Meng-Kang Hsieh

Automatic segmentation of fibroglandular tissue in breast MRI using anatomy-driven three-dimensional spatial context

The relative amount of fibroglandular tissue (FGT) in the breast has been shown to be a risk factor for breast cancer. However, automatic segmentation of FGT in breast MRI is challenging due mainly to its wide variation in anatomy (e.g., amount, location and pattern, etc.), and various imaging artifacts especially the prevalent bias-field artifact. Motivated by a previous work demonstrating improved FGT segmentation with 2-D a priori likelihood atlas, we propose a machine learning-based framework using 3-D FGT context. The framework uses features specifically defined with respect to the breast anatomy to capture spatially varying likelihood of FGT, and allows (a) intuitive standardization across breasts of different sizes and shapes, and (b) easy incorporation of additional information helpful to the segmentation (e.g., texture). Extended from the concept of 2-D atlas, our framework not only captures spatial likelihood of FGT in 3-D context, but also broadens its applicability to both sagittal and axial breast MRI rather than being limited to the plane in which the 2-D atlas is constructed. Experimental results showed improved segmentation accuracy over the 2-D atlas method, and demonstrated further improvement by incorporating well-established texture descriptors.

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.

Deformable image registration as a tool to improve survival prediction after neoadjuvant chemotherapy for breast cancer: results from the ACRIN 6657/I-SPY-1 trial.

We examined the ability of DCE-MRI longitudinal features to give early prediction of recurrence-free survival (RFS) in women undergoing neoadjuvant chemotherapy for breast cancer, in a retrospective analysis of 106 women from the ISPY 1 cohort. These features were based on the voxel-wise changes seen in registered images taken before treatment and after the first round of chemotherapy. We computed the transformation field using a robust deformable image registration technique to match breast images from these two visits. Using the deformation field, parametric response maps (PRM) — a voxel-based feature analysis of longitudinal changes in images between visits — was computed for maps of four kinetic features (signal enhancement ratio, peak enhancement, and wash-in/wash-out slopes). A two-level discrete wavelet transform was applied to these PRMs to extract heterogeneity information about tumor change between visits. To estimate survival, a Cox proportional hazard model was applied with the C statistic as the measure of success in predicting RFS. The best PRM feature (as determined by C statistic in univariable analysis) was determined for each of the four kinetic features. The baseline model, incorporating functional tumor volume, age, race, and hormone response status, had a C statistic of 0.70 in predicting RFS. The model augmented with the four PRM features had a C statistic of 0.76. Thus, our results suggest that adding information on the texture of voxel-level changes in tumor kinetic response between registered images of first and second visits could improve early RFS prediction in breast cancer after neoadjuvant chemotherapy.

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.

Three-dimensional whole breast segmentation in sagittal MR images with dense depth field modeling and localized self-adaptation

Whole breast segmentation is the first step in quantitative analysis of breast MR images. This task is challenging due mainly to the chest-wall line’s (CWL) spatially varying appearance and nearby distracting structures, both being complex. In this paper, we propose an automatic three-dimensional (3-D) segmentation method of whole breast in sagittal MR images. This method distinguishes itself from others in two main aspects. First, it reformulates the challenging problem of CWL localization into an equivalence that searches for an optimal smooth depth field and so fully utilizes the 3-D continuity of the CWLs. Second, it employs a localized self- adapting algorithm to adjust to the CWL’s spatial variation. Experimental results on real patient data with expert-outlined ground truth show that the proposed method can segment breasts accurately and reliably, and that its segmentation is superior to that of previously established methods.

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.

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.