Photon-counting Spectral Mammography Research Articles

Classification of breast microcalcifications with GaAs photon-counting spectral mammography using an inverse problem approach

The purpose of this study was to investigate the use of a Gallium Arsenide (GaAs) photon-counting spectral mammography system to differentiate between Type I and Type II calcifications. Type I calcifications, consisting of calcium oxalate dihydrate (CO) or weddellite compounds are more often associated with benign lesions in the breast, and Type II calcifications containing hydroxyapatite (HA) are associated with both benign and malignant lesions in the breast. To be able to differentiate between these two calcification types, it is necessary to be able to estimate the full spectrum of the x-ray beam transmitted through the breast. We propose a novel method for estimating the energy-dependent x-ray transmission fraction of a beam using a photon counting detector with a limited number of energy bins. Using the estimated x-ray transmission through microcalcifications, it was observed that calcification type can be accurately estimated with machine learning. The study was carried out on a custom-built laboratory benchtop system using the SANTIS 0804 GaAs detector prototype system from DECTRIS Ltd with two energy thresholds enabled. Four energy thresholds detector was simulated by taking two separate acquisitions in which two energy thresholds were enabled for each acquisition and set at (12 keV, 21 keV) and then (29 keV, 36 keV). Measurements were performed using BR3D (CIRS, Norfolk, VA) breast imaging phantoms mimicking 100% adipose and 100% glandular tissues swirled together in an approximate 50/50 ratio by weight with the addition of in-house-developed synthetic microcalcifications. First, an inverse problem-based approach was used to estimate the full energy x-ray transmission fraction factor using known basis transmission factors from varying thicknesses of aluminum and polymethyl methacrylate (PMMA). Second, the classification of Type I and Type II calcifications was performed using the estimated energy-dependent transmission fraction factors for the pixels containing calcifications. The results were analyzed using receiver operating characteristic (ROC) analysis and demonstrated good discrimination performance with the area under the ROC curve greater than 84%. They indicated that GaAs photon-counting spectral mammography has potential use as a non-invasive method for discrimination between Type I and Type II calcifications. Results from this study suggested that GaAs-based spectral mammography could serve as a non-invasive measure for ruling out malignancy of calcifications found in the breast. Additional studies in more clinically realistic conditions involving breast tissues samples with smaller microcalcification specks should be performed to further explore the feasibility of this approach.

Dual energy-based quantification method for determination of breast microcalcification types

The purpose of this study is to distinguish and characterize breast microcalcification types (benign and malignant) non-invasively using photon-counting spectral mammography. In this study, a photon-counting spectral mammography system was simulated using Geant4 application for tomographic emission (GATE) tool. Based on the photon-counting detector, dual-energy images were obtained using two energy bins. Calcium oxalate and calcium hydroxyapatite were used for benign and malignant microcalcifications, respectively. As a quantitative characteristic evaluation for two types of microcalcification related to etiology, an analytical model was implemented for the determination of the calcium/phosphorus mass ratio (mCa/mP) based on the dual-energy method. In the chemical composition of each microcalcification, the calcium hydroxyapatite has a phosphate substance, and calcium oxalate has an oxalate substance. The thicknesses of the calcium oxalate corresponding to calcium hydroxyapatite were calculated to preserve equal photon beam attenuation. The results indicate a higher mass ratio value in the case of malignant microcalcifications when compared with that in the case of benign ones. Even when the breast thickness increased up to 5 cm, the difference in the mass ratio exhibited a constant tendency. By excluding the effect on x-ray attenuation properties, we confirmed that malignant and benign microcalcifications were quantitatively distinguished based only on the mineral properties of the chemical composition. In conclusion, this study provides quantitative and objective indicators, a non-invasive discrimination method of two types of microcalcifications associated with pathology. We also expect to reduce the frequency of biopsies by improving the accuracy of early diagnosis in mammography.

Discrimination of benign and malignant microcalcifications using dual-energy imaging

Screening mammography has a high detection efficiency for microcalcifications. In a mammogram, morphological characteristics are used to distinguish benign and potentially malignant changes. In this study, we propose a new method to distinguish malignant and benign microcalcifications using only mammographic images based on the dual-energy method. A photon-counting spectral mammography system was simulated using the Geant4 Application for Tomographic Emission (GATE) simulation tool. The dual-energy images were obtained using two energy bins. Microcalcifications of type I (calcium oxalate) and type II (calcium hydroxyapatite) were studied. For statistical analysis, the microcalcifications were classified as type I or type II based on a score calculated using the dual-energy images. The score values were calculated using the ratio of values at low energy and high energy because the attenuation difference was small in the high-energy region and large in the low-energy region. In other words, the classification of microcalcifications associated with pathogenesis was performed using the attenuation ratio as a discrimination criterion. For the appropriate dual-energy images, the effects on the energy spectra of microcalcifications were evaluated. We confirmed that the contrast and the noise were affected because the classification method used in this study is based on the pixel values of the images. In addition, we suggested the possibility of automatic classification for malignant microcalcifications using segmentation methods and the minimum and maximum thresholds of score values.

Changes in breast density during hormone treatment with transdermal estrogens alone or in combination with progesterone

A retrospective observational study to assess whether hormonal treatment (HT) with transdermal estrogens alone or in combination with micronized progesterone increases breast density and to compare these changes to those of a control group of 4120 patients were not given HT. We included 150 patients whose baseline breast density was assessed with photon-counting spectral mammography and 1 year after hormone treatment. The reduction in breast density was compared using an analysis of covariance. The difference in breast density between mammographies in the HT group was −0.40 ± 5.5 and −0.85 ± 4.2 in the control group. The changes in density according to the type of HT, we found that women on treatment with estrogen alone presented a difference of 0.44 ± 5.8, and −1.35 ± 5 (p = 0.13) in women on combined treatment. After adjusting changes in density for age and average number of days between mammographies, we observed a difference of −0.36 95% confidence intervals (CI) [−1.04 to −0.31] in the women on HT and −0.71 95% CI [−1.65 to −0.21] in the control group. No increased breast density was observed in women on HT treatment, nor did we observe an increase according to HT type. The difference in breast density loss was smaller in the HT group versus the control group.

Evaluation of photon-counting spectral mammography for classification of breast microcalcifications

The purpose of this study was to evaluate the feasibility of spectral mammography using a dual-energy method to non-invasively distinguish between type I (calcium oxalate) and type II (calcium hydroxyapatite) microcalcifications. These two types of microcalcifications are difficult to differentiate owing to their similar linear attenuation coefficients. To improve the detection efficiency regarding microcalcifications, a photon-counting detector with energy discrimination capability was used, and the microcalcifications were classified using the optimal dual-energy spectrum. Two energy bins were used to obtain dual-energy images. In this study, a photon-counting spectral mammography system was simulated using Geant4 Application for Tomographic Emission (GATE) simulation tools. A cadmium zinc telluride detector with a high quantum efficiency was used in this study. The effects of classification on the density and thickness of the breast phantom were investigated. Microcalcifications of various sizes, ranging from 130 to 550 μm, were embedded in the phantom. For statistical analysis, the microcalcifications were classified as calcium hydroxyapatite or calcium oxalate based on a score calculation using the dual-energy images. According to the results, the measured contrast-to-noise ratio (CNR) of the calcium hydroxyapatite was higher than that of calcium oxalate in a single-energy image. The calcium hydroxyapatite had a higher attenuation coefficient and slightly higher contrast compared with calcium oxalate. In addition, the microcalcifications were classified into the optimal energy bin in the dual-energy images. This classification showed better performance with a high energy of 50 kVp and an energy threshold of 30 keV. This study demonstrated that using the dual-energy method could improve classification performance because the microcalcifications are affected by the density and thickness of the breast phantom. These results indicate that the classification accuracy was improved when the difference between the low-energy image and high-energy image was used. The dual-energy method can reduce the frequency of the need for biopsies and discriminate between different types of microcalcifications in mammography. These results can improve the efficiency of early breast cancer diagnosis.

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.

Feasibility of estimating volumetric breast density from mammographic x-ray spectra using a cadmium telluride photon-counting detector.

Mammographic density of glandular breast tissue has a masking effect that can reduce lesion detection accuracy and is also a strong risk factor for breast cancer. Therefore, accurate quantitative estimation of breast density is clinically important. In this study, we investigate experimentally the feasibility of quantifying volumetric breast density with spectral mammography using a CdTe-based photon-counting detector. To demonstrate proof-of-principle, this study was carried out using the single pixel Amptek XR-100T-CdTe detector. The total number of x rays recorded by the detector from a single pencil-beam projection through 50%/50% of adipose/glandular mass fraction-equivalent phantoms was measured. Material decomposition assuming two, four, and eight energy bins was then applied to characterize the inspected phantom into adipose and glandular using log-likelihood estimation, taking into account the polychromatic source, the detector response function, and the energy-dependent attenuation. Measurement tests were carried out for different doses, kVp settings, and different breast sizes. For dose of 1 mGy and above, the percent relative root mean square (RMS) errors of the estimated breast density was measured below 7% for all three phantom studies. It was also observed that some decrease in RMS errors was achieved using eight energy bins. For 3 and 4 cm thick phantoms, performance at 40 and 45 kVp showed similar performance. However, it was observed that 45 kVp showed better performance for a phantom thickness of 6 cm at low dose levels due to increased statistical variation at lower photon count levels with 40 kVp. The results of the current study suggest that photon-counting spectral mammography systems using CdTe detectors have the potential to be used for accurate quantification of volumetric breast density on a pixel-to-pixel basis, with an RMS error of less than 7%.

Quantitative contrast-enhanced spectral mammography based on photon-counting detectors: A feasibility study.

To investigate the feasibility of accurate quantification of iodine mass thickness in contrast-enhanced spectral mammography. A computer simulation model was developed to evaluate the performance of a photon-counting spectral mammography system in the application of contrast-enhanced spectral mammography. A figure-of-merit (FOM), which was defined as the decomposed iodine signal-to-noise ratio (SNR) with respect to the square root of the mean glandular dose (MGD), was chosen to optimize the imaging parameters, in terms of beam energy, splitting energy, and prefiltrations for breasts of various thicknesses and densities. Experimental phantom studies were also performed using a beam energy of 40 kVp and a splitting energy of 34 keV with 3 mm Al prefiltration. A two-step calibration method was investigated to quantify the iodine mass thickness, and was validated using phantoms composed of a mixture of glandular and adipose materials, for various breast thicknesses and densities. Finally, the traditional dual-energy log-weighted subtraction method was also studied as a comparison. The measured iodine signal from both methods was compared to the known value to characterize the quantification accuracy and precision. The optimal imaging parameters, which lead to the highest FOM, were found at a beam energy between 42 and 46 kVp with a splitting energy at 34 keV. The optimal tube voltage decreased as the breast thickness or the Al prefiltration increased. The proposed quantification method was able to measure iodine mass thickness on phantoms of various thicknesses and densities with high accuracy. The root-mean-square (RMS) error for cm-scale lesion phantoms was estimated to be 0.20 mg/cm2 . The precision of the technique, characterized by the standard deviation of the measurements, was estimated to be 0.18 mg/cm2 . The traditional weighted subtraction method also predicted a linear correlation between the measured signal and the known iodine mass thickness. However, the correlation slope and offset values were strongly dependent on the total breast thickness and density. The results of this study suggest that iodine mass thickness for cm-scale lesions can be accurately quantified with contrast-enhanced spectral mammography. The quantitative information can potentially improve the differential power for malignancy.

Breast-density measurement using photon-counting spectral mammography.

To evaluate a method for measuring breast density using photon-counting spectral mammography. Breast density is an indicator of breast cancer risk and diagnostic accuracy in mammography, and can be used as input to personalized screening, treatment monitoring and dose estimation. The measurement method employs the spectral difference in x-ray attenuation between adipose and fibro-glandular tissue, and does not rely on any a priori information. The method was evaluated using phantom measurements on tissue-equivalent material (slabs and breast-shaped phantoms) and using clinical data from a screening population (n=1329). A state-of-the-art nonspectral method for breast-density assessment was used for benchmarking. The precision of the spectral method was estimated to be 1.5-1.8 percentage points (pp) breast density. Expected correlations were observed in the screening population for thickness versus breast density, dense volume, breast volume, and compression height. Densities ranged between 4.5% and 99.6%, and exhibited a skewed distribution with a mode of 12.5%, a median of 18.3%, and a mean of 23.7%. The precision of the nonspectral method was estimated to be 2.7-2.8 pp. The major uncertainty of the nonspectral method originated from the thickness estimate, and in particular thin/dense breasts posed problems compared to the spectral method. The spectral method yielded reasonable results in a screening population with a precision approximately two times that of the nonspectral method, which may improve or enable applications of breast-density measurement on an individual basis such as treatment monitoring and personalized screening.

Investigating the feasibility of classifying breast microcalcifications using photon-counting spectral mammography: A simulation study.

A dual-energy material decomposition method using photon-counting spectral mammography was investigated as a non-invasive diagnostic approach to differentiate between Type I calcifications, consisting of calcium oxalate dihydrate or weddellite compounds that are more often associated with benign lesions, and Type II calcifications containing hydroxyapatite that are predominantly associated with malignant tumors. The study was carried out by numerical simulation to assess the feasibility of the proposed approach. A pencil-beam geometry was modeled, and the total number of x-rays transported through a breast embedded with microcalcifications of different types and sizes were simulated by a one-pixel detector. Material decomposition using two energy bins was then applied to characterize the simulated calcifications into hydroxyapatite and weddellite using maximum-likelihood estimation, taking into account the polychromatic source, and the energy dependent attenuation. Simulation tests were carried out for different dose levels, energy windows and calcification sizes for multiple noise realizations. The results were analyzed using receiver operating characteristic (ROC) analysis. Classification between Type I and Type II calcifications achieved by analyzing a single microcalcification showed moderate accuracy. However, simultaneously analyzing several calcifications within the cluster provided area under the ROC curve of greater than 99% for radiation dose greater than 4.8 mGy mean glandular dose. Simulation results indicated that photon-counting spectral mammography with dual energy material decomposition has the potential to be used as a non-invasive method for discrimination between Type I and Type II microcalcifications that can potentially improve early breast cancer diagnosis and reduce the number of negative breast biopsies. Additional studies using breast specimens and clinical data should be performed to further explore the feasibility of this approach.

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.

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.

Quantification of breast density with spectral mammography based on a scanned multi-slit photon-counting detector: a feasibility study

A simple and accurate measurement of breast density is crucial for the understanding of its impact in breast cancer risk models. The feasibility to quantify volumetric breast density with a photon-counting spectral mammography system has been investigated using both computer simulations and physical phantom studies. A computer simulation model involved polyenergetic spectra from a tungsten anode x-ray tube and a Si-based photon-counting detector has been evaluated for breast density quantification. The figure-of-merit (FOM), which was defined as the signal-to-noise ratio of the dual energy image with respect to the square root of mean glandular dose, was chosen to optimize the imaging protocols, in terms of tube voltage and splitting energy. A scanning multi-slit photon-counting spectral mammography system has been employed in the experimental study to quantitatively measure breast density using dual energy decomposition with glandular and adipose equivalent phantoms of uniform thickness. Four different phantom studies were designed to evaluate the accuracy of the technique, each of which addressed one specific variable in the phantom configurations, including thickness, density, area and shape. In addition to the standard calibration fitting function used for dual energy decomposition, a modified fitting function has been proposed, which brought the tube voltages used in the imaging tasks as the third variable in dual energy decomposition. For an average sized 4.5 cm thick breast, the FOM was maximized with a tube voltage of 46 kVp and a splitting energy of 24 keV. To be consistent with the tube voltage used in current clinical screening exam (∼32 kVp), the optimal splitting energy was proposed to be 22 keV, which offered a FOM greater than 90% of the optimal value. In the experimental investigation, the root-mean-square (RMS) error in breast density quantification for all four phantom studies was estimated to be approximately 1.54% using standard calibration function. The results from the modified fitting function, which integrated the tube voltage as a variable in the calibration, indicated a RMS error of approximately 1.35% for all four studies. The results of the current study suggest that photon-counting spectral mammography systems may potentially be implemented for an accurate quantification of volumetric breast density, with an RMS error of less than 2%, using the proposed dual energy imaging technique.

TH-A-217BCD-08: BEST IN PHYSICS (IMAGING) - Quantification of Breast Density with Spectral Mammography

Purpose: To investigate the feasibility of quantification of volumetric breast density using photon-counting spectral mammography. Methods: A computer simulation model using polyenergetic spectra from a tungsten anode x-ray tube and a Si-based photon-counting detector has been evaluated for breast density quantification. The figure-of-merit (FOM), which was defined as the signal-to-noise ratio (SNR) of the dual energy image with respect to the square root of the mean glandular dose (MGD), was chosen to optimize the imaging protocols, in terms of beam energy and splitting energy. A scanning multi-slit photon-counting spectral mammography system was used in the experimental study to quantitatively measure breast density using dual energy decomposition with glandular and adipose equivalent phantoms of uniform thickness. Four phantom studies were designed, which covered various thicknesses ranged from 2.0 to 8.5 cm and densities ranged from 0% to 100%. In addition to the standard calibration fitting function used for dual energy decomposition, a modified third order fitting function was also investigated. Results: The optimal splitting energies for breast density quantification with clinically relevant beam energies were suggested from the FOM simulation for various breast thicknesses. In the physical phantom studies, the RMS errors in breast density quantification were approximately 1.54% and 1.35% for measurements using the standard and the modified calibration fitting function, respectively. Conclusions: The results of the current study suggest that photon-counting spectral mammography can be implemented in screening exam to measure volumetric breast density with high accuracy, which can potentially have a high impact in the assessment of breast cancer risk.