PURPOSE:To investigate whether biologic image composition of mammographic lesions can improve upon existing mammographic quantitative image analysis (QIA) in estimating the probability of malignancy.METHODS:The study population consisted of 45 breast lesions imaged with dual-energy mammography prior to breast biopsy with final diagnosis resulting in 10 invasive ductal carcinomas, 5 ductal carcinomain situ, 11 fibroadenomas, and 19 other benign diagnoses. Analysis was threefold: (1) The raw low-energy mammographic images were analyzed with an established in-house QIA method, "QIA alone," (2) the three-compartment breast (3CB) composition measure-derived from the dual-energy mammography-of water, lipid, and protein thickness were assessed, "3CB alone", and (3) information from QIA and 3CB was combined, "QIA + 3CB." Analysis was initiated from radiologist-indicated lesion centers and was otherwise fully automated. Steps of the QIA and 3CB methods were lesion segmentation, characterization, and subsequent classification for malignancy in leave-one-case-out cross-validation. Performance assessment included box plots, Bland-Altman plots, and Receiver Operating Characteristic (ROC) analysis.RESULTS:The area under the ROC curve (AUC) for distinguishing between benign and malignant lesions (invasive and DCIS) was 0.81 (standard error 0.07) for the "QIA alone" method, 0.72 (0.07) for "3CB alone" method, and 0.86 (0.04) for "QIA+3CB" combined. The difference in AUC was 0.043 between "QIA + 3CB" and "QIA alone" but failed to reach statistical significance (95% confidence interval [-0.17 to + 0.26]).CONCLUSIONS:In this pilot study analyzing the new 3CB imaging modality, knowledge of the composition of breast lesions and their periphery appeared additive in combination with existing mammographic QIA methods for the distinction between different benign and malignant lesion types.

Purpose: To investigate the lesion discrimination ability of compositional 3-component breast imaging technique (3CB) of patients with suspicious breast lesions (BIRADS 4 or greater). Materials and Methods: A novel dual-energy 3CB imaging technique concludes in quantifying of the lipid, protein, and water thicknesses. The protocol was designed to be performed on a standard full-field digital mammography system by imaging additional high-energy image using a 3-mm Al filter. A pilot study of 43 abnormal breast findings on diagnostic mammography was performed using the 3CB protocol. The lesion groups include fibroadenoma (FA), invasive (IDC), DCIS and benign tissues. The lesions were delineated by the radiologist on CC and MLO views, and the compositional measures of the whole breasts, local areas within lesions and their peripheries were derived. Univariate logistic regression statistics was applied to analyze lesion different group separation. The variable statistical significance of MLO, CC views and their average was also compared. Results: We found for FA/rest group discrimination that water and lipid difference between lesion and periphery are significant for CC and MLO views. In addition, the breast fibroglandular dense volume are also significant for both views. Lesion to background water difference predicted FA with an odds ratio = 4.4 , ROC area of 0.8. For cancer/non cancer groups there were no variables showing the significance for both views. However, for IDC/rest groups lipid thicknesses within breast and at the periphery normalized by total thicknesses become significant for both views. Conclusion: Our pilot set data demonstrates that the technique provides biologically meaningful compositional components of lesion, its periphery and breast which are statistically significant for FA/rest and invasive cancers/rest group separation.

Purpose. Investigate whether knowledge of the biologic image composition of mammographic lesions provides imagebased biomarkers above and beyond those obtainable from quantitative image analysis (QIA) of X-ray mammography. Methods. The dataset consisted of 45 in vivo breast lesions imaged with the novel 3-component breast (3CB) imaging technique based on dual-energy mammography (15 malignant, 30 benign diagnoses). The 3CB composition measures of water, lipid, and protein thicknesses were assessed and mathematical descriptors, ‘3CB features’, were obtained for the lesions and their periphery. The raw low-energy mammographic images were analyzed with an established in-house QIA method obtaining ‘QIA features’ describing morphology and texture. We investigated the correlation within the ‘3CB features’, within the ‘QIA features’, and between the two. In addition, the merit of individual features in the distinction between malignant and benign lesions was assessed. Results. Whereas many descriptors within the ‘3CB features’ and ‘QIA features’ were, often by design, highly correlated, correlation between descriptors of the two feature groups was much weaker (maximum absolute correlation coefficient 0.58, p<0.001) indicating that 3CB and QIA-based biomarkers provided potentially complementary information. Single descriptors from 3CB and QIA appeared equally well-suited for the distinction between malignant and benign lesions, with maximum area under the ROC curve 0.71 for a protein feature (3CB) and 0.71 for a texture feature (QIA). Conclusions. In this pilot study analyzing the new 3CB imaging modality, knowledge of breast tissue composition appeared additive in combination with existing mammographic QIA methods for the distinction between benign and malignant lesions.

BACKGROUND:Muscle wasting is a consequence of many primary conditions including sarcopenia, cachexia, osteoporosis, HIV/AIDS, and chronic kidney disease. Unfortunately, there is not a clinically accessible method to measure total body protein, which is the functional mass of muscle.OBJECTIVE:We sought to derive a simple method to measure total body protein by using dual-energy X-ray absorptiometry (DXA) and bioimpedance analysis (BIA).DESIGN:We retrospectively analyzed a clinical convenience sample of individuals with numerous metabolic conditions from the Monash Medical Centre, Melbourne, Australia, who had a concurrent protein measure by using neutron activation analysis-derived protein (NAA-TBPro), water measure by using BIA, and whole-body DXA scan. The study was split into calibration and validation data sets by using simple random sampling stratified by sex, BMI category, and age decade. We generated a protein estimate direct-calibration protein (DC-TBPro) derived from BIA water, bone mass, and body volume. We compared NAA-TBPro with DC-TBPro and 2 protein estimates from the literature, one that used the DC-TBPro equation with fixed coefficients [4-compartment Lohman method for analysis of total body protein (4CL-TBPro)] and another that used fat-free mass, age, and sex [Wang equation-derived protein (W-TBPro)].RESULTS:A total of 187 participants [119 women; mean (±SD) age: 37.0 ± 15.4 y; mean (±SD) BMI (in kg/m(2)) 24.5 ± 7.7] were included. When plotted against NAA-TBPro, DC-TBPro had the highest correlation [coefficient of determination (R(2)) = 0.87], lowest root mean squared error (RMSE; 0.87 kg), and fewest outliers compared with 4CL-TBPro (R(2) = 0.75; RMSE = 1.22 kg) and W-TBPro (R(2) = 0.80; RMSE = 1.10 kg).CONCLUSIONS:A simple method to measure total body protein by using a DXA system and BIA unit was developed and compared with NAA as proof of principle. With additional validation, this method could provide a clinically useful way to monitor muscle-wasting conditions.

We report on development of a new calibration approach for the Single-Energy X-ray Absorptiometry method (SXA) to provide absolute breast tissue composition accuracy in clinical conditions for the long term and realize cross-calibration between machines, sites and manufacturers. The proposed method takes into account both geometric and image related factors that impact the calibration of grayscale image into absolute tissue composition. A specially designed phantom (GEN III) is imaged in place of the breast and analyzed as if it were a breast. An automatic algorithm was developed to extract all necessary parameters for recalibration. Subsequently, the thickness correction factors and recalibration procedures were applied during calculations of density. A breakpoint stepwise approach was used to correct the thickness variations. It provides the thickness measurement variations over time with a typical standard deviation of 0.2-0.3 mm. After recalibration, the recalculated

Determine whether or not improvements to the calibration procedure for a novel dual-energy x-ray mammography technique improve the uniformity, accuracy, and/or reproducibility of the measured breast composition. The long-term goal of this project is to develop a technique that will improve the specificity of mammography diagnosis. Energy dependent corrections for light-field, dark-field, and Heel effect were made for each measurement. A total of 20 women who were scheduled for additional imaging prior to biopsy underwent an additional dual-energy/low dose full-field digital mammography scan as part of a pilot study investigating the use of breast composition measures in mammography. The estimated water/lipid/protein content of suspicious lesions were measured. The modified x-ray calibration procedure resulted in over a 3-fold improvement in the uniformity of a flat-field calibration phantom with known breast density. Some preliminary results from women are available and show that different types of breast lesions have different compositions.

Purpose: Investigate the relationship between pathology diagnosis, biopsy composition, and breast texture measured in digital mammogram in women who have had previous benign findings in their breast. The long-term goal of this project is to determine whether or not global breast texture is associated with tissue composition and biopsy results. Such a finding would be of interest because it would provide evidence that mammography images contain information related to breast biology beyond average density. Materials and Methods: A total of 124 women who had previously received benign biopsies underwent an additional dual-energy/low dose full-field digital mammography (DXA) scan of the unaffected breast. Three measures of breast density (percent dense area (PD), percent fibroglandular volume (%FGV), absolute fibroglandular volume (FGV) from mammogram, 15 biopsy types including apocrine metaplasia and non-secretory pituitary adenoma, and four tissue compositions (collagen percent area, fat percent area, ductal percent area, epithelial percent area) were estimated from biopsies for each participant. In addition 45 breast texture features were measured on each screening image taken during the dual-energy mammography using custom software. Tissue composition at the biopsy location was estimated based on the average percent area of stained collagen, fat, ductal, and epithelial from up to 3 slides taken from the biopsy. Pathology results from the three slides were taken to indicate the tissue type. Results: Neither mammographic percent density, %FGV, nor FGV showed significant association with either biopsy type or tissue composition. However, some of breast texture features were significantly associated with tissue type and tissue composition. The strongest associations were found between collagen percent area and the neighborhood gray tone difference matrix texture strength (R=0.26, P=0.005) and ductal percent area and the gray level contrast matrix homogeneity (GLCM HOM) (R=-0.30, P=0.001). When classified according to biopsy type, the univariate association between ductal percent area and GLCM HOM for apocrine metaplasia increased. (R=-0.55, P=0.007) Conclusion: 10 breast texture features of the unaffected breast were significantly associated with local tissue composition and biopsy type. Further study will be required to determine whether this association is related to masking effects related to breast complexity or changes in breast biology driving changes in breast morphology. CLINICAL RELEVANCE The use of texture measures as biomarkers of variations in breast biology is potentially clinically significant. This work indicates that texture measures are associated with some biological outcomes. It is possible that this work could be used to improve diagnostic utility of computer-aided diagnosis by weighting the probability of various benign outcomes according to the measured breast texture. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-08-02.

Background: Assessing the volume of mammographic density might more accurately reflect the amount of breast volume at risk of malignant transformation and provide a stronger indication of risk of breast cancer than methods based on qualitative scores or dense breast area. Methods: We prospectively collected mammograms for women undergoing screening mammography. We determined the diagnosis of subsequent invasive or ductal carcinoma in situ for 275 cases, selected 825 controls matched for age, ethnicity, and mammography system, and assessed three measures of breast density: percent dense area, fibroglandular volume, and percent fibroglandular volume. Results: After adjustment for familial breast cancer history, body mass index, history of breast biopsy, and age at first live birth, the ORs for breast cancer risk in the highest versus lowest measurement quintiles were 2.5 (95% CI: 1.5–4.3) for percent dense area, 2.9 (95% CI: 1.7–4.9) for fibroglandular volume, and 4.1 (95% CI: 2.3–7.2) for percent fibroglandular volume. Net reclassification indexes for density measures plus risk factors versus risk factors alone were 9.6% (P = 0.07) for percent dense area, 21.1% (P = 0.0001) for fibroglandular volume, and 14.8% (P = 0.004) for percent fibroglandular volume. Fibroglandular volume improved the categorical risk classification of 1 in 5 women for both women with and without breast cancer. Conclusion: Volumetric measures of breast density are more accurate predictors of breast cancer risk than risk factors alone and than percent dense area. Impact: Risk models including dense fibroglandular volume may more accurately predict breast cancer risk than current risk models. Cancer Epidemiol Biomarkers Prev; 20(7); 1473–82. ©2011 AACR.

Abstract BACKGROUND: Mammographic percent dense area, the percent ratio of dense to total breast area in a mammogram, is one of the strongest measures of a woman's risk of breast cancer. However, systematic differences have been observed between readers and mammography technologies (film and digital) that could cause clinically inconsistent associations with risk. The purpose of this study was to evaluate inter- and intra-reproducibility of percent dense area between readers and between film and digital technologies. METHODS: One hundred digitized film mammograms were randomly selected with 25 films in each of quartile of percent density and read by two readers at two different sites (Mayo Clinic and UCSF). The readers had extensive experience and were also jointly trained at university of Toronto using Cumulus software. After training, all films were read twice with at least one year between duplicate readings. The Mayo clinic reading used Cumulus while UCSF used custom semiautomatic software to estimate total and dense tissue area. In addition, digitized films and unprocessed full field digital mammograms of the same women were assessed by one reader. The time between the film and digital acquisitions ranged from nine to twenty-four months. Interclass correlation coefficient (ICC) was calculated for each comparison. RESULTS: The intra- and inter-observer ICCs, consistency for film images, were 0.96 (UCSF) and 0.97 (Mayo), and 0.96 (UCSF vs. Mayo). We found ICC between film and digital mammograms for percent dense area was 0.88. The digital mammogram had 9% significantly higher total breast area and 5% significantly lower percent density area compared to film. CONCLUSIONS: Similarly trained readers had a high reproducibility regardless of the software used. Our results suggest centralized reader training should enable pooling of film breast density results from different clinics. However, pooling film and digital results would need careful calibration due to lower measured percent dense areas than on film. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-08-03.

An absolute efficiency measurement technique for Fresnel zone plates using an electron impact micro-focus laboratory X-ray source (Lα line of Tungsten at 8.4 KeV) is demonstrated. A quasi-monochromatic x-ray image of a zone plate was obtained employing a pair of copper and cobalt filters. Applying this method to zone plates optimizes the zone plate fabrication process and provides the ability to explore zone geometry to achieve the best possible efficiency. Several zone plate parameters were tested with first order efficiency measuring from 1% to 29%.

Single-bounce ellipsoidal and paraboloidal glass capillary focusing optics have been fabricated for use as condenser lenses for both synchrotron and tabletop x-ray microscopes in the x-ray energy range of 2.5-18 keV. The condenser numerical apertures (NAs) of these devices are designed to match the NA of x-ray zone plate objectives, which gives them a great advantage over zone plate condensers in laboratory microscopes. The fabricated condensers have slope errors as low as 20 mu rad rms. These capillaries provide a uniform hollow-cone illumination with almost full focusing efficiency, which is much higher than what is available with zone plate condensers. Sub-50 nm resolution at 8 keV x-ray energy was achieved by utilizing this high-efficiency condenser in a laboratory microscope based on a rotating anode generator. (C) 2008 Optical Society of America.

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Many modern industrial processes and research applications place increasingly higher demands on x-ray computed tomography (CT) imaging resolution and sensitivity for low-contrast specimens with a low atomic number. The three approaches to increasing imaging resolution are (1) reduction in the x-ray spot size, (2) use of higher resolution detectors or (3) employment of x-ray optical elements. Systems that pursue one or more of these approaches are available and under continued development. The Xradia MicroXCT™ projection-type microscope described in this paper has been optimized for high-resolution x-ray CT by employing a high-resolution detector paired with a microfocus x-ray source. Large working distances in this CT system enable full tomographic data collection at micrometre resolution of large samples, such as flip-chip packages. X-ray CT instruments using x-ray optical elements for condenser optics and imaging objective lenses are a new development capable of reaching sub-50 nm resolution. These instruments find various applications, including die-level imaging in the semiconductor industry as well as the process development for fuel cells, which we describe here as one application. Sub-micron resolution CT instruments without x-ray optical elements have a large application base already; however, new instruments optimized for soft materials and low-contrast specimens, such as the Xradia nanoXCT™, offer completely new capabilities and open new applications. New developments in the area of phase contrast imaging enable unprecedented image contrast for specimens with very low absorption, which for research applications enables for the first time the imaging of many specimens in their natural state (e.g., arteries to examine calcification). Zernike phase contrast for sub-50 nm x-ray CT even enables the imaging of single cell or thin tissue slices for biological or medical applications.