Impact of breast structure on lesion detection in breast tomosynthesis, a simulation study.

This study aims to characterize the effect of background tissue density and heterogeneity on the detection of irregular masses in breast tomosynthesis, while demonstrating the capability of the sophisticated tools that can be used in the design, implementation, and performance analysis of virtual clinical trials (VCTs). Twenty breast phantoms from the extended cardiac-torso (XCAT) family, generated based on dedicated breast computed tomography of human subjects, were used to extract a total of 2173 volumes of interest (VOIs) from simulated tomosynthesis images. Five different lesions, modeled after human subject tomosynthesis images, were embedded in the breasts and combined with the lesion absent condition yielded a total of [Formula: see text] VOIs. Effects of background tissue density and heterogeneity on the detection of the lesions were studied by implementing a composite hypothesis signal detection paradigm with location known exactly, lesion known exactly or statistically, and background known statistically. Using the area under the receiver operating characteristic curve, detection performance deteriorated as density was increased, yielding findings consistent with clinical studies. A human observer study was performed on a subset of the simulated tomosynthesis images, confirming the detection performance trends with respect to density and serving as a validation of the implemented detector. Performance of the implemented detector varied substantially across the 20 breasts. Furthermore, background tissue density and heterogeneity affected the log-likelihood ratio test statistic differently under lesion absent and lesion present conditions. Therefore, considering background tissue variability in tissue models can change the outcomes of a VCT and is hence of crucial importance. The XCAT breast phantoms have the potential to address this concern by offering realistic modeling of background tissue variability based on a wide range of human subjects, comprising various breast shapes, sizes, and densities.

Development of realistic physical breast phantoms matched to virtual breast phantoms based on human subject data.

PURPOSE: Physical phantoms are essential for the development, optimization, and evaluation of x-ray breast imaging systems. Recognizing the major effect of anatomy on image quality and clinical performance, such phantoms should ideally reflect the three-dimensional structure of the human breast. Currently, there is no commercially available three-dimensional physical breast phantom that is anthropomorphic. The authors present the development of a new suite of physical breast phantoms based on human data. METHODS: The phantoms were designed to match the extended cardiac-torso virtual breast phantoms that were based on dedicated breast computed tomography images of human subjects. The phantoms were fabricated by high-resolution multimaterial additive manufacturing (3D printing) technology. The glandular equivalency of the photopolymer materials was measured relative to breast tissue-equivalent plastic materials. Based on the current state-of-the-art in the technology and available materials, two variations were fabricated. The first was a dual-material phantom, the Doublet. Fibroglandular tissue and skin were represented by the most radiographically dense material available; adipose tissue was represented by the least radiographically dense material. The second variation, the Singlet, was fabricated with a single material to represent fibroglandular tissue and skin. It was subsequently filled with adipose-equivalent materials including oil, beeswax, and permanent urethane-based polymer. Simulated microcalcification clusters were further included in the phantoms via crushed eggshells. The phantoms were imaged and characterized visually and quantitatively. RESULTS: The mammographic projections and tomosynthesis reconstructed images of the fabricated phantoms yielded realistic breast background. The mammograms of the phantoms demonstrated close correlation with simulated mammographic projection images of the corresponding virtual phantoms. Furthermore, power-law descriptions of the phantom images were in general agreement with real human images. The Singlet approach offered more realistic contrast as compared to the Doublet approach, but at the expense of air bubbles and air pockets that formed during the filling process. CONCLUSIONS: The presented physical breast phantoms and their matching virtual breast phantoms offer realistic breast anatomy, patient variability, and ease of use, making them a potential candidate for performing both system quality control testing and virtual clinical trials.

Development and application of a suite of 4-D virtual breast phantoms for optimization and evaluation of breast imaging systems.

Mammography is currently the most widely utilized tool for detection and diagnosis of breast cancer. However, in women with dense breast tissue, tissue overlap may obscure lesions. Digital breast tomosynthesis can reduce tissue overlap. Furthermore, imaging with contrast enhancement can provide additional functional information about lesions, such as morphology and kinetics, which in turn may improve lesion identification and characterization. The performance of these imaging techniques is strongly dependent on the structural composition of the breast, which varies significantly among patients. Therefore, imaging system and imaging technique optimization should take patient variability into consideration. Furthermore, optimization of imaging techniques that employ contrast agents should include the temporally varying breast composition with respect to the contrast agent uptake kinetics. To these ends, we have developed a suite of 4-D virtual breast phantoms, which are incorporated with the kinetics of contrast agent propagation in different tissues and can realistically model normal breast parenchyma as well as benign and malignant lesions. This development presents a new approach in performing simulation studies using truly anthropomorphic models. To demonstrate the utility of the proposed 4-D phantoms, we present a simplified example study to compare the performance of 14 imaging paradigms qualitatively and quantitatively.

An anthropomorphic breast model for breast imaging simulation and optimization.

RATIONALE AND OBJECTIVES: Optimization studies for x-ray-based breast imaging systems using computer simulation can greatly benefit from a phantom capable of modeling varying anatomical variability across different patients. This study aimed to develop a three-dimensional phantom model with realistic and randomizable anatomical features. MATERIALS AND METHODS: A voxelized breast model was developed consisting of an outer layer of skin and subcutaneous fat, a mixture of glandular and adipose, stochastically generated ductal trees, masses, and microcalcifications. Randomized realization of the breast morphology provided a range of patient models. Compression models were included to represent the breast under various compression levels along different orientations. A Monte Carlo (MC) simulation code was adapted to simulate x-ray based imaging systems for the breast phantom. Simulated projections of the phantom at different angles were generated and reconstructed with iterative methods, simulating mammography, breast tomosynthesis, and computed tomography (CT) systems. Phantom dose maps were further generated for dosimetric evaluation. RESULTS: Region of interest comparisons of simulated and real mammograms showed strong similarities in terms of appearance and features. Noise-power spectra of simulated mammographic images demonstrated that the phantom provided target properties for anatomical backgrounds. Reconstructed tomosynthesis and CT images and dose maps provided corresponding data from a single breast enabling optimization studies. Dosimetry result provided insight into the dose distribution difference between modalities and compression levels. CONCLUSION: The anthropomorphic breast phantom, combined with the MC simulation platform, generated a realistic model for a breast imaging system. The developed platform is expected to provide a versatile and powerful framework for optimizing volumetric breast imaging systems.

Bayesian quantitative electrophysiology and its multiple applications in bioengineering.

Bayesian interpretation of observations began in the early 1700s, and scientific electrophysiology began in the late 1700s. For two centuries these two fields developed mostly separately. In part that was because quantitative Bayesian interpretation, in principle a powerful method of relating measurements to their underlying sources, often required too many steps to be feasible with hand calculation in real applications. As computer power became widespread in the later 1900s, Bayesian models and interpretation moved rapidly but unevenly from the domain of mathematical statistics into applications. Use of Bayesian models now is growing rapidly in electrophysiology. Bayesian models are well suited to the electrophysiological environment, allowing a direct and natural way to express what is known (and unknown) and to evaluate which one of many alternatives is most likely the source of the observations, and the closely related receiver operating characteristic (ROC) curve is a powerful tool in making decisions. Yet, in general, many people would ask what such models are for, in electrophysiology, and what particular advantages such models provide. So to examine this question in particular, this review identifies a number of electrophysiological papers in bioengineering arising from questions in several organ systems to see where Bayesian electrophysiological models or ROC curves were important to the results that were achieved.

Decision-level fusion of EEG and pupil features for single-trial visual detection analysis.

Several recent studies have reported success in applying EEG-based signal analysis to achieve accurate single-trial classification of responses to visual target detection. Pupil responses are proposed as a complementary modality that can support improved accuracy of single-trial signal analysis. We develop a pupillary response feature-extraction and -selection procedure that helps to improve the classification performance of a system based only on EEG signal analysis. We apply a two-level linear classifier to obtain cognitive-task-related analysis of EEG and pupil responses. The classification results based on the two modalities are then fused at the decision level. Here, the goal is to support increased classification confidence through the inherent modality complementarities. The fusion results show significant improvement over classification performance based on a single modality.

Bayesian analysis of fiber impedance measurements.

The resistivities of microscale components of excitable tissue include the longitudinal intracellular and interstitial resistivities and the membrane resistivity. Measurements of these tissue micro impedances have rarely been obtained, mainly because of the lack of a satisfactory measurement system. Here we evaluate a possible strategy for obtaining such measurements, and begin with a simulation. In the model, a one-dimensional fiber was stimulated with closely space interstitial electrodes at four frequencies, and the voltage differences that occurred in response were recorded. We then considered the inverse question, asking if tissue micro impedances could be found from the voltage measurements plus additive noise. In so doing, we used a Bayesian interpretation of the measured data to find the probability that each of the longitudinal and transmembrane resistivity sets was their origin. The Bayesian procedure proved better suited for interpreting the measurements than was conventional least-squares analysis. It was better because all known data, including realistic noise specifications and a priori probabilities, were included in the defined procedure. The results show that the micro impedances were found satisfactorily using realistic parameters and noise levels. The overall quantitative evaluation is promising for future experimental measurements.

Optimized approach to decision fusion of heterogeneous data for breast cancer diagnosis.

As more diagnostic testing options become available to physicians, it becomes more difficult to combine various types of medical information together in order to optimize the overall diagnosis. To improve diagnostic performance, here we introduce an approach to optimize a decision-fusion technique to combine heterogeneous information, such as from different modalities, feature categories, or institutions. For classifier comparison we used two performance metrics: The receiving operator characteristic (ROC) area under the curve [area under the ROC curve (AUC)] and the normalized partial area under the curve (pAUC). This study used four classifiers: Linear discriminant analysis (LDA), artificial neural network (ANN), and two variants of our decision-fusion technique, AUC-optimized (DF-A) and pAUC-optimized (DF-P) decision fusion. We applied each of these classifiers with 100-fold cross-validation to two heterogeneous breast cancer data sets: One of mass lesion features and a much more challenging one of microcalcification lesion features. For the calcification data set, DF-A outperformed the other classifiers in terms of AUC (p < 0.02) and achieved AUC=0.85 +/- 0.01. The DF-P surpassed the other classifiers in terms of pAUC (p < 0.01) and reached pAUC=0.38 +/- 0.02. For the mass data set, DF-A outperformed both the ANN and the LDA (p < 0.04) and achieved AUC=0.94 +/- 0.01. Although for this data set there were no statistically significant differences among the classifiers' pAUC values (pAUC=0.57 +/- 0.07 to 0.67 +/- 0.05, p > 0.10), the DF-P did significantly improve specificity versus the LDA at both 98% and 100% sensitivity (p < 0.04). In conclusion, decision fusion directly optimized clinically significant performance measures, such as AUC and pAUC, and sometimes outperformed two well-known machine-learning techniques when applied to two different breast cancer data sets.

Effects of environmental uncertainties on sonar detection performance prediction.

The development of effective passive sonar systems depends upon the ability to accurately predict the performance of sonar detection algorithms in realistic ocean environments. Such environments are typically characterized by a high degree of uncertainty, thus limiting the usefulness of performance prediction approaches that assume a deterministic environment. Here we derive closed-form receiver operating characteristic (ROC) expressions for an optimal Bayesian detector and for several typical suboptimal detectors, based on a statistical model of environmental uncertainty. Various scenarios extended from an NRL benchmark shallow-water model were used to check the analytical ROC expressions and to illustrate the effect of environmental uncertainty on detection performance. The results showed that (1) optimal detection performance in an uncertain environment in diffuse noise depends primarily on the signal-to-noise ratio at the receivers and the rank of the signal matrix, where the rank is an effective representation of the scale of environmental uncertainty; (2) the ROC expression for the optimal Bayesian detector provides a more realistic performance upper bound than that obtained from conventional sonar equations that do not incorporate environmental uncertainty; and (3) detection performance predictions can be performed much faster than with commonly used numerical methods such as Monte Carlo performance evaluations.

Bayesian sonar detection performance prediction in the presence of interference in uncertain environments.

The detection performance of sonar systems can be greatly limited by the presence of interference and environmental uncertainty. The classic sonar equation does not take into account these two limiting factors and is inaccurate in predicting sonar detection performance. Here we have developed closed-form receiver operating characteristic (ROC) performance expressions for the Bayesian detector in the presence of interference in uncertain environments. Various scenarios extended from a NRL benchmark shallow-water model were used to test the analytical ROC expressions and to analyze the effects of interference and environmental uncertainty on detection performance. The results show that (1) the degradation on detection performance due to interference is greatly magnified by the presence of environmental uncertainty; (2) Bayesian sonar detection performance depends on the following fundamental parameters: the signal-to-noise ratio, the rank of the signal matrix, and the signal-to-interference coefficient; (3) the proposed analytical ROC performance predictions can be computed much faster than performance evaluations with commonly used Monte Carlo techniques.

Application of likelihood ratio to classification of mammographic masses; performance comparison to case-based reasoning.

The likelihood ratio (LR) is an optimal approach for deciding which of two alternate hypotheses best describes a given situation. We adopted this formalism for predicting whether biopsy results of mammographic masses will be benign or malignant, aiming to reduce the number of biopsies performed on benign lesions. We compared the performance of this LR-based algorithm (LRb) to a case-based reasoning (CBR) classifier, which provides a solution to a new problem using past similiar cases. Each classifier used mammographers' BI-RADS descriptions of mammographic masses as input. The database consisted of 646 biopsy-proven mammography cases. Performance was evaluated using Receiver Operating Characteristic (ROC) analysis, Round Robin sampling, and bootstrap. The ROC areas (AUC) for the LRb and CBR were 0.91+/- 0.01 and 0.92 +/- 0.01, respectively. The partial ROC area index (0.90AUC) was the same for both classifiers, 0.59 +/- 0.05. At a sensitivity of 98%, the CBR would spare 204 (49%) of benign lesions from biopsy; the LRb would spare 209 (51%) benign lesions. The performance of the two classifiers was very similar, with no statistical differences in AUC or 0.90AUC. Although the CBR and LRb originate from different fields of study, their implementations differ only in the estimation of the probability density functions (PDFs) of the feature distributions. The CBR performs this estimation implicitly, while using various similarity metrics. On the other hand, the estimation of the PDFs is specified explicitly in the LRb implementation. This difference in the estimation of the PDFs results in the very small difference in performance, and at 98% sensitivity, both classifiers would spare about half of the benign mammographic masses from biopsy. The CBR and LRb are equivalent methods in implementation and performance.

The performance of matched-field track-before-detect methods using shallow-water Pacific data.

Matched-field track-before-detect processing, which extends the concept of matched-field processing to include modeling of the source dynamics, has recently emerged as a promising approach for maintaining the track of a moving source. In this paper, optimal Bayesian and minimum variance beamforming track-before-detect algorithms which incorporate a priori knowledge of the source dynamics in addition to the underlying uncertainties in the ocean environment are presented. A Markov model is utilized for the source motion as a means of capturing the stochastic nature of the source dynamics without assuming uniform motion. In addition, the relationship between optimal Bayesian track-before-detect processing and minimum variance track-before-detect beamforming is examined, revealing how an optimal tracking philosophy may be used to guide the modification of existing beamforming techniques to incorporate track-before-detect capabilities. Further, the benefits of implementing an optimal approach over conventional methods are illustrated through application of these methods to shallow-water Pacific data collected as part of the SWellEX-1 experiment. The results show that incorporating Markovian dynamics for the source motion provides marked improvement in the ability to maintain target track without the use of a uniform velocity hypothesis.