Hyperia: A novel methodology of developing anthropomorphic breast phantoms for X-ray imaging modalities - Part I: Concept and initial findings.

PURPOSE: To introduce a novel methodology for developing anthropomorphic breast phantoms for use in X-ray-based imaging modalities. METHODS: "Hyperization" is a quasi-stippling mapping operation in which regions of varying grayscale values in a 2D image are transformed into regions of varying holes on a surface. The holes can be cut or engraved on the sheet of paper using a high-resolution laser cutter/engraver. In hyperization, the main parameters are the size and the distance between the holes. Here, we introduce the concept and chronicle the development and characterization of a proof-of-concept prototype. In this study, we hypothesized that a resulting "Hyperia" phantom would be a realistic representative of a patient's breast tissue: it would exhibit similar X-ray properties and show textural complexities. We used breast computed tomography (bCT) images of real patients as the input models. Using a previously developed segmentation method, the input CT images were segmented into different tissue classes (skin, adipose, and fibroglandular). The segmented images were then "Hyperized". A series of Monte Carlo simulations were conducted to find the optimal hyperization parameters. Different laser cutter/engraver systems and substrate materials were explored to find a viable option for developing an entire Hyperia breast phantom. The resulting phantom was imaged on a prototype breast CT system, and the resulting images were evaluated based on physical properties and similarity to the original patient data. RESULTS: The simulation results indicate close similarities - both in the distribution of different tissue types and the resulting CT numbers - between the patient bCT image and the bCT of the Hyperia phantom, regardless of the breast size and density: the Pearson correlation coefficient (ρ) ranged from 0.88 in a BIRADS A breast to 0.94 in BIRADS C and D breasts (ρ of 1.00 suggests perfect structural similarity), and the volumetric mean squared error ranged from 0.0033 (in BIRADS D breast) to 0.0059 (in BIRADS A), suggesting good agreement between the resulting CT numbers. For fabricating the slices, the office paper was found to be an optimal substrate material, with the Hyperization parameters of (α, ß) = (0.200 mm, 0.400 mm). CONCLUSION: A novel phantom can be used for X-ray-based breast cancer imaging systems. The main advantage is that only one material is used for creating a contrast between different tissue types in an image.

Assessment of task-based performance from five clinical DBT systems using an anthropomorphic breast phantom.

PURPOSE: Digital breast tomosynthesis (DBT) is a limited-angle tomographic breast imaging modality that can be used for breast cancer screening in conjunction with full-field digital mammography (FFDM) or synthetic mammography (SM). Currently, there are five commercial DBT systems that have been approved by the U.S. FDA for breast cancer screening, all varying greatly in design and imaging protocol. Because the systems are different in technical specifications, there is a need for a quantitative approach for assessing them. In this study, the DBT systems are assessed using a novel methodology with an inkjet-printed anthropomorphic phantom and four alternative forced choice (4AFC) study scheme. METHOD: A breast phantom was fabricated using inkjet printing and parchment paper. The phantom contained 5-mm spiculated masses fabricated with potassium iodide (KI)-doped ink and microcalcifications (MCs) made with calcium hydroxyapatite. Images of the phantom were acquired on all five systems with DBT, FFDM, and SM modalities where available using beam settings under automatic exposure control. A 4AFC study was conducted to assess reader performance with each signal under each modality. Statistical analysis was performed on the data to determine proportion correct (PC), standard deviations, and levels of significance. RESULTS: For masses, overall detection was highest with DBT. The difference in PC was statistically significant between DBT and SM for most systems. A relationship was observed between increasing PC and greater gantry span. For MCs, performance was highest with DBT and FFDM compared to SM. The difference between PC of DBT and PC of SM was statistically significant for all manufacturers. CONCLUSIONS: This methodology represents a novel approach for evaluating systems. This study is the first of its kind to use an inkjet-printed anthropomorphic phantom with realistic signals to assess performance of clinical DBT imaging systems.

Objective assessment of task performance: a comparison of two FFDM detectors using an anthropomorphic breast phantom.

Current digital mammography systems primarily employ one of two types of detectors: indirect conversion, typically using a cesium-iodine scintillator integrated with an amorphous silicon photodiode matrix, or direct conversion, using a photoconductive layer of amorphous selenium (a-Se) combined with thin-film transistor array. The goal of this study was to evaluate a methodology for objectively assessing image quality to compare human observer task performance in detecting microcalcification clusters and extended mass-like lesions achieved with different detector types. The proposed assessment methodology uses a novel anthropomorphic breast phantom fabricated with ink-jet printing. In addition to human observer detection performance, standard linear metrics such as modulation transfer function, noise power spectrum, and detective quantum efficiency (DQE) were also measured to assess image quality. An Analogic Anrad AXS-2430 a-Se detector used in a commercial FFDM/DBT system and a Teledyne Dalsa Xineos-2329 with CMOS pixel readout were evaluated and compared. The DQE of each detector was similar over a range of exposures. Similar task performance in detecting microcalcifications and masses was observed between the two detectors over a range of clinically applicable dose levels, with some perplexing differences in the detection of microcalcifications at the lowest dose measurement. The evaluation approach presented seems promising as a new technique for objective assessment of breast imaging technology.

A four-alternative forced choice (4AFC) methodology for evaluating microcalcification detection in clinical full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) systems using an inkjet-printed anthropomorphic phantom.

PURPOSE: The advent of three-dimensional breast imaging systems such as digital breast tomosynthesis (DBT) has great promise for improving the detection and diagnosis of breast cancer. With these new technologies comes an essential need for testing methods to assess the resultant image quality. Although randomized clinical trials are the gold standard for assessing image quality, phantom-based studies can provide a simpler and less burdensome approach. In this work, a complete framework is presented for task-based evaluation of microcalcification (MCs) detection performance for DBT imaging systems. METHODS: The framework consists of three parts. The first part is a realistic anthropomorphic physical breast phantom created through inkjet printing, with parchment paper and iodine-doped ink. The second is a method for inserting realistic MCs fabricated from calcium hydroxyapatite. The reproducibility and stability of the phantom materials were investigated through multiple samples of parchment and ink over 6 months. The final part is an analysis using a four-alternative forced choice (4AFC) reader study. To demonstrate the framework, a task-based 4AFC study was conducted using a clinical system to compare performance from DBT, synthetic mammography (SM), and full-field digital mammography (FFDM). Nine human observers read images containing MC clusters imaged with all three modalities and tried to correctly locate the MCs. The proportion correct (PC) was measured as the number of correctly detected clusters out of all trials. RESULTS: Overall, readers scored the highest with FFDM, (PC = 0.95 ± 0.03) then DBT (0.85 ± 0.04), and finally SM (0.44 ± 0.06). For the parchment and ink samples, the linear attenuation properties were very stable over 6 months. In addition, little difference was found between the various parchment and ink samples, indicating good reproducibility. CONCLUSIONS: This framework presents a promising methodology for evaluating diagnostic task performance of clinical breast DBT systems.

Advances in digital and physical anthropomorphic breast phantoms for x-ray imaging.

PURPOSE: With the advent of three-dimensional (3D) breast imaging modalities such as digital breast tomosynthesis (DBT) and dedicated breast CT (bCT), research into new anthropomorphic breast phantoms has accelerated. These breast phantoms are important for the optimization of new breast imaging systems, assessing new regulatory submissions to prove safety and effectiveness, and for developing new approaches to acceptance and constancy testing of 3D breast imaging systems. This paper provides a review of current research investigating both digital and physical breast phantom development for use in x-ray based imaging. METHODS: Two approaches for designing anthropomorphic, digital breast phantoms are discussed, procedural model-based phantom generation, where breast features are expressed using mathematical models, and patient-based generation, where breast structures from tissue specimens or patient-based breast MR or CT volumes are segmented. Following this discussion, a review of physical anthropomorphic phantoms is given, with emphasis on the advantages and disadvantages present with each approach. CONCLUSIONS: This paper provides a summary of the state-of-the-art in anthropomorphic breast phantom development for x-ray breast imaging. The primary advantage of model-based digital phantoms is that an unlimited number of phantoms with varying size, shape, and density can be generated. Current research on model-based breast phantoms is producing more and more realistic breast models; however, they probably are not yet able to pass the so-called "fool the radiologist" visualization test. Empirical patient-based breast phantoms are typically based on clinical breast CT data and look more realistic. However, clinical breast CT images have limited spatial resolution and thus do not always portray the finer details in the breast. A number of innovative solutions have been proposed for fabricating physical anthropomorphic breast phantoms based on digital phantom models; however, a number of challenges remain, including realistic modeling of x-ray attenuation properties and accurately representing high-frequency structures within breast.

Report of AAPM Task Group 162: Software for planar image quality metrology.

PURPOSE: The AAPM Task Group 162 aimed to provide a standardized approach for the assessment of image quality in planar imaging systems. This report offers a description of the approach as well as the details of the resultant software bundle to measure detective quantum efficiency (DQE) as well as its basis components and derivatives. METHODS: The methodology and the associated software include the characterization of the noise power spectrum (NPS) from planar images acquired under specific acquisition conditions, modulation transfer function (MTF) using an edge test object, the DQE, and effective DQE (eDQE). First, a methodological framework is provided to highlight the theoretical basis of the work. Then, a step-by-step guide is included to assist in proper execution of each component of the code. Lastly, an evaluation of the method is included to validate its accuracy against model-based and experimental data. RESULTS: The code was built using a Macintosh OSX operating system. The software package contains all the source codes to permit an experienced user to build the suite on a Linux or other *nix type system. The package further includes manuals and sample images and scripts to demonstrate use of the software for new users. The results of the code are in close alignment with theoretical expectations and published results of experimental data. CONCLUSIONS: The methodology and the software package offered in AAPM TG162 can be used as baseline for characterization of inherent image quality attributes of planar imaging systems.

A novel physical anthropomorphic breast phantom for 2D and 3D x-ray imaging.

PURPOSE: Physical phantoms are central to the evaluation of 2D and 3D breast-imaging systems. Currently, available physical phantoms have limitations including unrealistic uniform background structure, large expense, or excessive fabrication time. The purpose of this work is to outline a method for rapidly creating realistic, inexpensive physical anthropomorphic phantoms for use in full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT). METHODS: The phantom was first modeled using analytical expressions and then discretized into voxels of a specified size. The interior of the breast was divided into glandular and adipose tissue classes using Voronoi segmentation, and additional structures like blood vessels, chest muscle, and ligaments were added. The physical phantom was then fabricated from the virtual model in a slice by slice fashion through inkjet printing, using parchment paper and a radiopaque ink containing 33% (I33% ) or 25% (I25% ) iohexol by volume. Three types of parchment paper (P1, P2, and P3) were examined. The phantom materials were characterized in terms of their effective linear attenuation coefficients (µeff ) using full-field digital mammography (FFDM) and their energy-dependent linear attenuation coefficients (µ(E)) using a spectroscopic energy discriminating detector system. The printing method was further validated on the basis of accuracy, print consistency, and the reproducibility of ink batches. RESULTS: The µeff of two types of parchment paper were close to that of adipose tissue, with µeff = 0.61 ± 0.05 cm-1 for P1, 0.61 ± 0.04 cm-1 for P2, and 0.57 ± 0.03 cm-1 for adipose tissue. The addition of the iodinated ink increased the effective attenuation to that of glandular tissue, with µeff = 0.89 ± 0.06 cm-1 for P1 + I25% and 0.94 ± 0.06 cm-1 for P1 + I33% compared to 0.90 ± 0.03 cm-1 for glandular tissue. Spectroscopic measurements showed a good match between the parchment paper and reference values for adipose and glandular tissues across photon energies. Good accuracy was found between the model and the printed phantom by comparing a FFDM of the virtual model simulated through Monte Carlo with a real FFDM of the fully printed phantom. High consistency was found over multiple prints, with 3% variability in mean ink signal across various samples. Reproducibility of ink consistency was very high with <1% variation signal from multiple batches of ink. Imaging of the phantom using FFDM and DBT systems showed promising utility for 2D and 3D imaging. CONCLUSIONS: A novel, realistic breast phantom can be created using an analytically defined breast model and readily available materials. The work provides a method to fabricate any virtual phantom in a manner that is accurate, inexpensive, easily accessible, and can be made with different materials or breast models.

Assessing task performance in FFDM, DBT, and synthetic mammography using uniform and anthropomorphic physical phantoms.

PURPOSE: The purpose of this study is to quantify the differences in detectability between full field digital mammography (FFDM), digital breast tomosynthesis (DBT), and synthetic mammography (SM) for challenging, low contrast signals, in the context of both a uniform and an anthropomorphic, textured phantom. METHODS: Images of the phantoms were acquired using a Hologic Selenia Dimensions system. Images were taken at 50%, 100%, and 200% of the dose delivered under automatic exposure control (AEC). Low-contrast disks, created using an inkjet printer with iodine-doped ink, were inserted into the phantom. The disks varied in diameter from 210 to 630 µm, and in local contrast from 1.1% to 2.8% in regular increments. Human observers located the disks in a 4 alternative forced choice experiment. Proportion correct (PC) was computed as the number of correct localizations out of the total number of tries. RESULTS: Overall, scores from FFDM and DBT were consistently greater than scores from SM. At an exposure corresponding to the AEC setting, mean PC scores for the largest disks with the uniform phantom were 0.80 for FFDM, 0.83 for DBT, and 0.66 for SM, with the same rank ordering at other doses. Scores were similar but lower for the nonuniform background. At an exposure twice the AEC setting, however, the difference between uniform and nonuniform scores was most pronounced for DBT alone. Differences between scores for FFDM and SM were statistically significant, while those between FFDM and DBT were not. Scores were used to compute the minimum contrast level needed to reach 62.5% detection rate. The minimum contrast for SM was 36%-81% higher compared to FFDM or DBT, in either background. CONCLUSIONS: This study shows that an anthropomorphic phantom and lesions inserts may be used to conduct a reader study. Detectability was significantly lower for synthetic mammography than for FFDM or DBT, for all conditions. Additionally, observer performance was consistently lower for the anthropomorphic phantom, indicating the greater challenge due to anatomical background. Because of this, it may be important to use realistic phantoms in observer studies in order to draw conclusions that are more clinically relevant.

A quantitative metrology for performance characterization of five breast tomosynthesis systems based on an anthropomorphic phantom.

PURPOSE: In medical imaging systems, proper rendition of anatomy is essential in discerning normal tissue from disease. Currently, digital breast tomosynthesis (DBT) systems are evaluated using subjective evaluation of lesion visibility in uniform phantoms. This study involved the development of a new methodology to objectively measure the rendition of a 3D breast model by an anthropomorphic breast phantom, and its implementation on five clinical DBT systems of different makes and models. METHODS: A 3D, patient-based breast phantom was fabricated based on XCAT breast models. This phantom was imaged on representative breast tomosynthesis systems. The ability of tomosynthesis systems to accurately reproduce the 3D structure of the breast was assessed by computational analysis of the resultant images in terms of three groups of indices: contrast index (CI), reflective of local difference between adipose and glandular material; adipose variability index (AVI), reflective of contributions of noise and artifacts within uniform adipose regions; and contrast detectability, which describes contrast against local background variability and is described by contrast variability index (CVI), coefficient of variation (COV), contrast to adipose variability index (CAVI), and contrast to noise ratio index (CNRI). The indices were obtained by comparing the image data to the gold standard 3D distribution of breast tissue in the model. Corresponding indices were measured within variable region of interest (ROI) sizes ranging from 10 to 37 mm. The characterization was performed on five tomosynthesis systems: Fuji Aspire Crystal, GE Essential, Hologic Dimension, IMS Giotto, and Siemens Inspiration, all evaluated at a fixed dose of 1.5 mGy average glandular dose, anonymized in random order from A to E. RESULTS: Results are provided as a function of ROI size. The systems ranked orders in terms of CI with values of 7.4%, 7.0%, 6.9%, 6.4%, and 5.2% for systems A-E, respectively. This system ranking was identical for CNRI. Both CI and CNRI were constant over ROI size. The ranking was similar for CVI. The COV also changed little with ROI size and was similar across systems. For 10 mm ROIs, the average system COV was 0.7, which reduced to 0.5 with 37 mm ROIs. Two systems (A and B) exhibited highest AVI values when measured in 10 mm ROIs. This, however, was ROI-size-dependent with the three other systems (C-E) yielding higher AVI values when measured with 37 mm ROIs. Two systems (B and E) showed inferior CAVI compared to others. CONCLUSIONS: The quality of rendition tracked with differences in image appearance across systems. The findings illustrate that the anthropomorphic phantom can be used as a basis to extract quantitative values of image attributes in DBT.

Task-based strategy for optimized contrast enhanced breast imaging: analysis of six imaging techniques for mammography and tomosynthesis.

PURPOSE: The use of contrast agents in breast imaging has the capability of enhancing nodule detectability and providing physiological information. Accordingly, there has been a growing trend toward using iodine as a contrast medium in digital mammography (DM) and digital breast tomosynthesis (DBT). Widespread use raises concerns about the best way to use iodine in DM and DBT, and thus a comparison is necessary to evaluate typical iodine-enhanced imaging methods. This study used a task-based observer model to determine the optimal imaging approach by analyzing six imaging paradigms in terms of their ability to resolve iodine at a given dose: unsubtracted mammography and tomosynthesis, temporal subtraction mammography and tomosynthesis, and dual energy subtraction mammography and tomosynthesis. METHODS: Imaging performance was characterized using a detectability index d', derived from the system task transfer function (TTF), an imaging task, iodine signal difference, and the noise power spectrum (NPS). The task modeled a 10 mm diameter lesion containing iodine concentrations between 2.1 mg/cc and 8.6 mg/cc. TTF was obtained using an edge phantom, and the NPS was measured over several exposure levels, energies, and target-filter combinations. Using a structured CIRS phantom, d' was generated as a function of dose and iodine concentration. RESULTS: For all iodine concentrations and dose, temporal subtraction techniques for mammography and tomosynthesis yielded the highest d', while dual energy techniques for both modalities demonstrated the next best performance. Unsubtracted imaging resulted in the lowest d' values for both modalities, with unsubtracted mammography performing the worst out of all six paradigms. CONCLUSIONS: At any dose, temporal subtraction imaging provides the greatest detectability, with temporally subtracted DBT performing the highest. The authors attribute the successful performance to excellent cancellation of inplane structures and improved signal difference in the lesion.

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.

The vanadyl chelate bis(acetylacetonato)oxovanadium(IV) increases the fractional uptake of 2-(fluorine-18)-2-deoxy-D-glucose by cultured human breast carcinoma cells.

Detection of breast cancer by positron emission tomography (PET) imaging with 2-(fluorine-18)-2-deoxy-D-glucose (FDG) as the tracer molecule is limited in part by both tumor dimension and metabolic activity. While some types of aggressive breast cancers are associated with a high capacity for FDG uptake, more indolent breast cancers are characterized by low FDG uptake. Moreover, detection of malignant lesions in most clinical settings requires tumor dimensions ≥10 mm. Development of a method to increase the fractional uptake of FDG by cancer tissue would provide a means to detect smaller tumors. However, there is no clinically available pharmacologic reagent known to enhance the preferential uptake of FDG by cancer tissue. Because the vanadyl (VO(2+)) chelate bis(acetylacetonato)oxovanadium(IV) [VO(acac)2] is known to enhance cellular uptake of glucose, we have investigated whether VO(acac)2 facilitates enhanced uptake of FDG by cultured human breast carcinoma cells. We observed that the fractional uptake of FDG by cultured human MDA-MB-231 carcinoma cells is increased in the presence of VO(acac)2 in a dose dependent manner. Preliminary results with xenograft tumors generated in severely compromised, immunodeficient (SCID) female mice showed that VO(acac)2 treatment of mice 3-4 h prior to FDG injection enhanced FDG uptake by the malignant tissue by a factor >2.0 compared with that by normal surrounding tissue.

Analysis of parenchymal texture with digital breast tomosynthesis: comparison with digital mammography and implications for cancer risk assessment.

PURPOSE: To correlate the parenchymal texture features at digital breast tomosynthesis (DBT) and digital mammography with breast percent density (PD), an established breast cancer risk factor, in a screening population of women. MATERIALS AND METHODS: This HIPAA-compliant study was approved by the institutional review board. Bilateral DBT images and digital mammograms from 71 women (mean age, 54 years; age range, 34-75 years) with negative or benign findings at screening mammography were retrospectively collected from a separate institutional review board-approved DBT screening trial (performed from July 2007 to March 2008) in which all women had given written informed consent. Parenchymal texture features of skewness, coarseness, contrast, energy, homogeneity, and fractal dimension were computed from the retroareolar region. Principal component analysis (PCA) was applied to obtain orthogonal texture components. Mammographic PD was estimated with software. Correlation analysis and multiple linear regression with generalized estimating equations were performed to determine the association between texture features and breast PD. Regression was adjusted for age to determine the independent association of texture to breast PD when age was also considered as a predictor variable. RESULTS: Texture feature correlations to breast PD were stronger with DBT than with digital mammography. Statistically significant correlations (P < .001) were observed for contrast (r = 0.48), energy (r = -0.47), and homogeneity (r = -0.56) at DBT and for contrast (r = 0.26), energy (r = -0.26), and homogeneity (r = -0.33) at digital mammography. Multiple linear regression analysis of PCA texture components as predictors of PD also demonstrated significantly stronger associations with DBT. The association was strongest when age was also considered as a predictor of PD (R² = 0.41 for DBT and 0.28 for digital mammography; P < .001). CONCLUSION: Parenchymal texture features are more strongly correlated to breast PD in DBT than in digital mammography. The authors' long-term hypothesis is that parenchymal texture analysis with DBT will result in quantitative imaging biomarkers that can improve the estimation of breast cancer risk.