Measurement of breast-tissue x-ray attenuation by spectral imaging: fresh and fixed normal and malignant tissue.

Knowledge of x-ray attenuation is essential for developing and evaluating x-ray imaging technologies. In mammography, measurement of breast density, dose estimation, and differentiation between cysts and solid tumours are example applications requiring accurate data on tissue attenuation. Published attenuation data are, however, sparse and cover a relatively wide range. To supplement available data we have previously measured the attenuation of cyst fluid and solid lesions using photon-counting spectral mammography. The present study aims to measure the attenuation of normal adipose and glandular tissue, and to measure the effect of formalin fixation, a major uncertainty in published data. A total of 27 tumour specimens, seven fibro-glandular tissue specimens, and 15 adipose tissue specimens were included. Spectral (energy-resolved) images of the samples were acquired and the image signal was mapped to equivalent thicknesses of two known reference materials, from which x-ray attenuation as a function of energy can be derived. The spread in attenuation between samples was relatively large, partly because of natural variation. The variation of malignant and glandular tissue was similar, whereas that of adipose tissue was lower. Formalin fixation slightly altered the attenuation of malignant and glandular tissue, whereas the attenuation of adipose tissue was not significantly affected. The difference in attenuation between fresh tumour tissue and cyst fluid was smaller than has previously been measured for fixed tissue, but the difference was still significant and discrimination of these two tissue types is still possible. The difference between glandular and malignant tissue was close-to significant; it is reasonable to expect a significant difference with a larger set of samples. We believe that our studies have contributed to lower the overall uncertainty of breast tissue attenuation in the literature due to the relatively large sample sets, the novel measurement method, and by clarifying the difference between fresh and fixed tissue.

Mammographic density and breast cancer risk in breast screening assessment cases and women with a family history of breast cancer.

BACKGROUND: Mammographic density has been shown to be a strong independent predictor of breast cancer and a causative factor in reducing the sensitivity of mammography. There remain questions as to the use of mammographic density information in the context of screening and risk management, and of the association with cancer in populations known to be at increased risk of breast cancer. AIM: To assess the association of breast density with presence of cancer by measuring mammographic density visually as a percentage, and with two automated volumetric methods, Quantra™ and VolparaDensity™. METHODS: The TOMosynthesis with digital MammographY (TOMMY) study of digital breast tomosynthesis in the Breast Screening Programme of the National Health Service (NHS) of the United Kingdom (UK) included 6020 breast screening assessment cases (of whom 1158 had breast cancer) and 1040 screened women with a family history of breast cancer (of whom two had breast cancer). We assessed the association of each measure with breast cancer risk in these populations at enhanced risk, using logistic regression adjusted for age and total breast volume as a surrogate for body mass index (BMI). RESULTS: All density measures showed a positive association with presence of cancer and all declined with age. The strongest effect was seen with Volpara absolute density, with a significant 3% (95% CI 1-5%) increase in risk per 10 cm3 of dense tissue. The effect of Volpara volumetric density on risk was stronger for large and grade 3 tumours. CONCLUSIONS: Automated absolute breast density is a predictor of breast cancer risk in populations at enhanced risk due to either positive mammographic findings or family history. In the screening context, density could be a trigger for more intensive imaging.

Measurement of breast-tissue x-ray attenuation by spectral mammography: solid lesions.

Knowledge of x-ray attenuation is essential for developing and evaluating x-ray imaging technologies. For instance, techniques to distinguish between cysts and solid tumours at mammography screening would be highly desirable to reduce recalls, but the development requires knowledge of the x-ray attenuation for cysts and tumours. We have previously measured the attenuation of cyst fluid using photon-counting spectral mammography. Data on x-ray attenuation for solid breast lesions are available in the literature, but cover a relatively wide range, likely caused by natural spread between samples, random measurement errors, and different experimental conditions. In this study, we have adapted a previously developed spectral method to measure the linear attenuation of solid breast lesions. A total of 56 malignant and 5 benign lesions were included in the study. The samples were placed in a holder that allowed for thickness measurement. Spectral (energy-resolved) images of the samples were acquired and the image signal was mapped to equivalent thicknesses of two known reference materials, which can be used to derive the x-ray attenuation as a function of energy. The spread in equivalent material thicknesses was relatively large between samples, which is likely to be caused mainly by natural variation and only to a minor extent by random measurement errors and sample inhomogeneity. No significant difference in attenuation was found between benign and malignant solid lesions. The separation between cyst-fluid and tumour attenuation was, however, significant, which suggests it may be possible to distinguish cystic from solid breast lesions, and the results lay the groundwork for a clinical trial. In addition, the study adds a relatively large sample set to the published data and may contribute to a reduction in the overall uncertainty in the literature.

Characterization of Cystic Lesions by Spectral Mammography: Results of a Clinical Pilot Study.

OBJECTIVES: Round lesions are a common mammographic finding, which can contribute more than 20% of overall recalls at screening. Discrimination of cystic fluid from solid tissue by spectral x-ray imaging has been demonstrated in specimen experiments. This work translates these results into a clinical pilot study to investigate the feasibility of discriminating cystic from solid lesions using spectral mammography. MATERIALS AND METHODS: Women undergoing mammography as part of their routine diagnostic workup were consented for analysis of spectral information obtained from a photon-counting mammography system. Images were analyzed retrospectively after diagnosis was confirmed with ultrasound and pathology. Well-defined solitary lesions were delineated independently by 3 expert radiologists. A breast lesion model is generated from the spectral mammography data using the energy-dependent x-ray attenuation of cyst fluid, carcinoma, and adipose and glandular tissue. From the breast lesion model, 2 spectral features are computed and combined in a 2-feature discrimination algorithm, which is evaluated in an analysis of the receiver operating characteristic curve for the task of identifying solid lesions ("positive result"). Expected outcomes on a screening population are extrapolated from this pilot study by cross-validation with bootstrapping using a 95% confidence interval (CI). RESULTS: The 2-feature discrimination algorithm was evaluated on the set of 119 eligible lesions (62 solids, 57 cysts) of diameter greater than 10 mm. The area under the receiver operating characteristic curve (AUC) was 0.88 with a specificity of 61% at the 99% sensitivity level on average over all expert radiologists. Cross-validation with bootstrapping of the clinical data revealed an AUC of 0.89 (95% CI, 0.79-0.96) and a specificity of 56% (95% CI, 33%-78%) when operating the algorithm at the 99% sensitivity level. CONCLUSIONS: Discriminating cystic from solid lesions with spectral mammography demonstrates promising results with the potential to reduce mammographic recalls. It is estimated that for each missed cancer at least 625 cystic lesions would have been correctly identified and hence would not have been needed to be recalled. Our results justify undertaking a larger reader study to refine the algorithm and determine clinically relevant thresholds to allow safe classification of cystic lesions by spectral mammography.

Accuracy of Digital Breast Tomosynthesis for Depicting Breast Cancer Subgroups in a UK Retrospective Reading Study (TOMMY Trial).

PURPOSE: To compare the diagnostic performance of two-dimensional (2D) mammography, 2D mammography plus digital breast tomosynthesis (DBT), and synthetic 2D mammography plus DBT in depicting malignant radiographic features. MATERIALS AND METHODS: In this multicenter, multireader, retrospective reading study (the TOMMY trial), after written informed consent was obtained, 8869 women (age range, 29-85 years; mean, 56 years) were recruited from July 2011 to March 2013 in an ethically approved study. From these women, a reading dataset of 7060 cases was randomly allocated for independent blinded review of (a) 2D mammography images, (b) 2D mammography plus DBT images, and (c) synthetic 2D mammography plus DBT images. Reviewers had no access to results of previous examinations. Overall sensitivities and specificities were calculated for younger women and those with dense breasts. RESULTS: Overall sensitivity was 87% for 2D mammography, 89% for 2D mammography plus DBT, and 88% for synthetic 2D mammography plus DBT. The addition of DBT was associated with a 34% increase in the odds of depicting cancer (odds ratio [OR] = 1.34, P = .06); however, this level did not achieve significance. For patients aged 50-59 years old, sensitivity was significantly higher (P = .01) for 2D mammography plus DBT than it was for 2D mammography. For those with breast density of 50% or more, sensitivity was 86% for 2D mammography compared with 93% for 2D mammography plus DBT (P = .03). Specificity was 57% for 2D mammography, 70% for 2D mammography plus DBT, and 72% for synthetic 2D mammography plusmDBT. Specificity was significantly higher than 2D mammography (P < .001in both cases) and was observed for all subgroups (P < .001 for all cases). CONCLUSION: The addition of DBT increased the sensitivity of 2D mammography in patients with dense breasts and the specificity of 2D mammography for all subgroups. The use of synthetic 2D DBT demonstrated performance similar to that of standard 2D mammography with DBT. DBT is of potential benefit to screening programs, particularly in younger women with dense breasts. (©) RSNA, 2015.

The TOMMY trial: a comparison of TOMosynthesis with digital MammographY in the UK NHS Breast Screening Programme--a multicentre retrospective reading study comparing the diagnostic performance of digital breast tomosynthesis and digital mammography with digital mammography alone.

BACKGROUND: Digital breast tomosynthesis (DBT) is a three-dimensional mammography technique with the potential to improve accuracy by improving differentiation between malignant and non-malignant lesions. OBJECTIVES: The objectives of the study were to compare the diagnostic accuracy of DBT in conjunction with two-dimensional (2D) mammography or synthetic 2D mammography, against standard 2D mammography and to determine if DBT improves the accuracy of detection of different types of lesions. STUDY POPULATION: Women (aged 47-73 years) recalled for further assessment after routine breast screening and women (aged 40-49 years) with moderate/high of risk of developing breast cancer attending annual mammography screening were recruited after giving written informed consent. INTERVENTION: All participants underwent a two-view 2D mammography of both breasts and two-view DBT imaging. Image-processing software generated a synthetic 2D mammogram from the DBT data sets. RETROSPECTIVE READING STUDY: In an independent blinded retrospective study, readers reviewed (1) 2D or (2) 2D + DBT or (3) synthetic 2D + DBT images for each case without access to original screening mammograms or prior examinations. Sensitivities and specificities were calculated for each reading arm and by subgroup analyses. RESULTS: Data were available for 7060 subjects comprising 6020 (1158 cancers) assessment cases and 1040 (two cancers) family history screening cases. Overall sensitivity was 87% [95% confidence interval (CI) 85% to 89%] for 2D only, 89% (95% CI 87% to 91%) for 2D + DBT and 88% (95% CI 86% to 90%) for synthetic 2D + DBT. The difference in sensitivity between 2D and 2D + DBT was of borderline significance (p = 0.07) and for synthetic 2D + DBT there was no significant difference (p = 0.6). Specificity was 58% (95% CI 56% to 60%) for 2D, 69% (95% CI 67% to 71%) for 2D + DBT and 71% (95% CI 69% to 73%) for synthetic 2D + DBT. Specificity was significantly higher in both DBT reading arms for all subgroups of age, density and dominant radiological feature (p < 0.001 all cases). In all reading arms, specificity tended to be lower for microcalcifications and higher for distortion/asymmetry. Comparing 2D + DBT to 2D alone, sensitivity was significantly higher: 93% versus 86% (p < 0.001) for invasive tumours of size 11-20 mm. Similarly, for breast density 50% or more, sensitivities were 93% versus 86% (p = 0.03); for grade 2 invasive tumours, sensitivities were 91% versus 87% (p = 0.01); where the dominant radiological feature was a mass, sensitivities were 92% and 89% (p = 0.04) For synthetic 2D + DBT, there was significantly (p = 0.006) higher sensitivity than 2D alone in invasive cancers of size 11-20 mm, with a sensitivity of 91%. CONCLUSIONS: The specificity of DBT and 2D was better than 2D alone but there was only marginal improvement in sensitivity. The performance of synthetic 2D appeared to be comparable to standard 2D. If these results were observed with screening cases, DBT and 2D mammography could benefit to the screening programme by reducing the number of women recalled unnecessarily, especially if a synthetic 2D mammogram were used to minimise radiation exposure. Further research is required into the feasibility of implementing DBT in a screening setting, prognostic modelling on outcomes and mortality, and comparison of 2D and synthetic 2D for different lesion types. STUDY REGISTRATION: Current Controlled Trials ISRCTN73467396. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 4. See the HTA programme website for further project information.

Mammographic breast density: comparison of methods for quantitative evaluation.

PURPOSE: To evaluate the results from two software tools for measurement of mammographic breast density and compare them with observer-based scores in a large cohort of women. MATERIALS AND METHODS: Following written informed consent, a data set of 36 281 mammograms from 8867 women were collected from six United Kingdom centers in an ethically approved trial. Breast density was assessed by one of 26 readers on a visual analog scale and with two automated density tools. Mean differences were calculated as the mean of all the individual percentage differences between each measurement for each case (woman). Agreement in total breast volume, fibroglandular volume, and percentage density was assessed with the Bland-Altman method. Association with observer's scores was calculated by using the Pearson correlation coefficient (r). RESULTS: Correlation between the Quantra and Volpara outputs for total breast volume was r = 0.97 (P < .001), with a mean difference of 43.5 cm(3) for all cases representing 5.0% of the mean total breast volume. Correlation of the two measures was lower for fibroglandular volume (r = 0.86, P < .001). The mean difference was 30.3 cm(3) for all cases representing 21.2% of the mean fibroglandular tissue volume result. Quantra gave the larger value and the difference tended to increase with volume. For the two measures of percentage volume density, the mean difference was 1.61 percentage points (r = 0.78, P < .001). Comparison of observer's scores with the area-based density given by Quantra yielded a low correlation (r = 0.55, P < .001). Correlations of observer's scores with the volumetric density results gave r values of 0.60 (P < .001) and 0.63 (P < .001) for Quantra and Volpara, respectively. CONCLUSION: Automated techniques for measuring breast density show good correlation, but these are poorly correlated with observer's scores. However automated techniques do give different results that should be considered when informing patient personalized imaging. (©) RSNA, 2015 Clinical trial registration no. ISRCTN 73467396.

Measurement of breast-tissue x-ray attenuation by spectral mammography: first results on cyst fluid.

Knowledge of x-ray attenuation is essential for developing and evaluating x-ray imaging technologies. For instance, techniques to better characterize cysts at mammography screening would be highly desirable to reduce recalls, but the development is hampered by the lack of attenuation data for cysts. We have developed a method to measure x-ray attenuation of tissue samples using a prototype photon-counting spectral mammography unit. The method was applied to measure the attenuation of 50 samples of breast cyst fluid and 50 samples of water. Spectral (energy-resolved) images of the samples were acquired and the image signal was mapped to equivalent thicknesses of two known reference materials, which can be used to derive the x-ray attenuation as a function of energy. The attenuation of cyst fluid was found to be significantly different from water. There was a relatively large natural spread between different samples of cyst fluid, whereas the homogeneity of each individual sample was found to be good; the variation within samples did not reach above the quantum noise floor. The spectral method proved stable between several measurements on the same sample. Further, chemical analysis and elemental attenuation calculation were used to validate the spectral measurement on a subset of the samples. The two methods agreed within the precision of the elemental attenuation calculation over the mammographic energy range.