Breast arterial calcification is associated with incident atrial fibrillation among older but not younger post-menopausal women.

Aims: The goal of this study was to examine the association of breast arterial calcification (BAC) presence and quantity with incident atrial fibrillation (AF) in a large cohort of post-menopausal women. Methods and results: We conducted a longitudinal cohort study among women free of clinically overt cardiovascular disease and AF at baseline (between October 2012 and February 2015) when they attended mammography screening. Atrial fibrillation incidence was ascertained using diagnostic codes and natural language processing. Among 4908 women, 354 incident cases of AF (7%) were ascertained after a mean (standard deviation) of 7 (2) years of follow-up. In Cox regression adjusting for a propensity score for BAC, BAC presence vs. absence was not significantly associated with AF [hazard ratio (HR) = 1.12; 95% confidence interval (CI), 0.89-1.42; P = 0.34]. However, a significant (a priori hypothesized) age by BAC interaction was found (P = 0.02) such that BAC presence was not associated with incident AF in women aged 60-69 years (HR = 0.83; 95% CI, 0.63-1.15; P = 0.26) but was significantly associated with incident AF in women aged 70-79 years (HR = 1.75; 95% CI, 1.21-2.53; P = 0.003). No evidence of dose-response relationship between BAC gradation and AF was noted in the entire cohort or in age groups separately. Conclusion: Our results demonstrate, for the first time, an independent association between BAC and AF in women over age 70 years.

High-sensitivity troponin I is associated with cardiovascular outcomes but not with breast arterial calcification among postmenopausal women.

Background: Prior studies support the utility of high sensitivity troponin I (hsTnI) for cardiovascular disease (CVD) risk stratification among asymptomatic populations; however, only two prior studies examined women separately. The association between hsTnI and breast arterial calcification is unknown. Methods: Cohort study of 2896 women aged 60-79 years recruited after attending mammography screening between 10/2012 and 2/2015. BAC status (presence versus absence) and quantity (calcium mass mg) was determined using digital mammograms. Pre-specified endpoints were incident coronary heart disease (CHD), ischemic stroke, heart failure and its subtypes and all CVD. Results: After 7.4 (SD = 1.7) years of follow-up, 51 CHD, 30 ischemic stroke and 46 heart failure events were ascertained. At a limit of detection of 1.6 ng/L, 98.3 of the cohort had measurable hsTnI concentration. HsTnI in the 4-10 ng/L range were independently associated of CHD (adjusted hazard ratio[aHR] = 2.78; 95% CI, 1.48-5.22; p = 0.002) and all CVD (aHR = 2.06; 95% CI, 1.37-3.09; p = 0.0005) and hsTnI over 10 ng/L was independently associated with CHD (aHR = 4.75; 95% CI, 1.83-12.3; p = 0.001), ischemic stroke (aHR = 3.81; 95% CI, 1.22-11.9; p = 0.02), heart failure (aHR = 3.29; 95% CI, 1.33-8.13; p = 0.01) and all CVD (aHR = 4.78; 95% CI, 2.66-8.59; p < 0.0001). No significant association was found between hsTnI and BAC. Adding hsTnI to a model containing the Pooled Cohorts Equation resulted in significant and clinical important improved calibration, discrimination (Δ Cindex = 6.5; p = 0.02) and reclassification (bias-corrected clinical NRI = 0.18; 95% CI, -0.13-0.49 after adding hsTnI categories). Conclusions: Our results support the consideration of hsTnI as a risk enhancing factor for CVD in asymptomatic women that could drive preventive or therapeutic decisions.

Breast Arterial Calcification: a Novel Cardiovascular Risk Enhancer Among Postmenopausal Women.

BACKGROUND: Breast arterial calcification (BAC), a common incidental finding in mammography, has been shown to be associated with angiographic coronary artery disease and cardiovascular disease (CVD) outcomes. We aimed to (1) examine the association of BAC presence and quantity with hard atherosclerotic CVD (ASCVD) and global CVD; (2) ascertain model calibration, discrimination and reclassification of ASCVD risk; (3) assess the joint effect of BAC presence and 10-year pooled cohorts equations risk on ASCVD. METHODS: A cohort study of 5059 women aged 60-79 years recruited after attending mammography screening between October 2012 and February 2015 was conducted in a large health plan in Northern California, United States. BAC status (presence versus absence) and quantity (calcium mass mg) was determined using digital mammograms. Prespecified end points were incident hard ASCVD and a composite of global CVD. RESULTS: Twenty-six percent of women had BAC >0 mg. After a mean (SD) follow-up of 6.5 (1.6) years, we ascertained 155 (3.0%) ASCVD events and 427 (8.4%) global CVD events. In Cox regression adjusted for traditional CVD risk factors, BAC presence was associated with a 1.51 (95% CI, 1.08-2.11; P=0.02) increased hazard of ASCVD and a 1.23 (95% CI, 1.002-1.52; P=0.04) increased hazard of global CVD. While there was no evidence of dose-response association with ASCVD, a threshold effect was found for global CVD at very high BAC burden (95th percentile when BAC present). BAC status provided additional risk stratification of the pooled cohorts equations risk. We noted improvements in model calibration and reclassification of ASCVD: the overall net reclassification improvement was 0.12 (95% CI, 0.03-0.14; P=0.01) and the bias-corrected clinical-net reclassification improvement was 0.11 (95% CI, 0.01-0.22; P=0.04) after adding BAC status. CONCLUSIONS: Our results indicate that BAC has potential utility for primary CVD prevention and, therefore, support the notion that BAC ought to be considered a risk-enhancing factor for ASCVD among postmenopausal women.

Characterization of arterial plaque composition with dual energy computed tomography: a simulation study.

To investigate the feasibility of quantifying the chemical composition of coronary artery plaque in terms of water, lipid, protein, and calcium contents using dual-energy computed tomography (CT) in a simulation study. A CT simulation package was developed based on physical parameters of a clinical CT scanner. A digital thorax phantom was designed to simulate coronary arterial plaques in the range of 2-5 mm in diameter. Both non-calcified and calcified plaques were studied. The non-calcified plaques were simulated as a mixture of water, lipid, and protein, while the calcified plaques also contained calcium. The water, lipid, protein, and calcium compositions of the plaques were selected to be within the expected clinical range. A total of 95 plaques for each lesion size were simulated using the CT simulation package at 80 and 135 kVp. Half-value layer measurements were made to make sure the simulated dose was within the range of clinical dual energy scanning protocols. Dual-energy material decomposition using a previously developed technique was performed to determine the volumetric fraction of water, lipid, protein, and calcium contents in each plaque. For non-calcified plaque, the total volume conservation provides the third constrain for three-material decomposition with dual energy CT. For calcified plaque, a fourth criterion was introduced from a previous report suggesting a linear correlation between water and protein contents in soft tissue. For non-calcified plaque, the root mean-squared error (RMSE) of the image-based decomposition was estimated to be 0.7%, 1.5%, and 0.3% for water, lipid, and protein contents, respectively. As for the calcified plaques, the RMSE of the 5 mm plaques were estimated to be 5.6%, 5.7%, 0.2%, and 3.1%, for water, lipid, calcium, and protein contents, respectively. The RMSE increases as the plaque size reduces. The simulation results indicate that chemical composition of coronary arterial plaques can be quantified using dual-energy CT. By accurately quantifying the content of a coronary plaque lesion, our decomposition method may provide valuable insight for the assessment and stratification of coronary artery disease.

Quantification of water and lipid density with dual-energy mammography: validation in postmortem breasts.

OBJECTIVES: Breast cancer is the most common cancer in women and the second leading cause of cancer death. It is well known that breast density is an important risk factor for breast cancer and also can be used to personalize screening and for assessment of treatment response. Breast density has previously been correlated to volumetric water density. The purpose of this study is to validate the accuracy and precision of dual-energy mammography in measuring water density in postmortem breasts. METHODS: Twenty pairs of postmortem breasts were imaged using dual-energy mammography with energy-sensitive photon-counting detectors. Chemical analysis was used as the reference standard to assess the accuracy of dual-energy mammography in measuring volumetric water and lipid density. Images from different views and contralateral breasts were used to assess estimate of precision for water and lipid volumetric density measurements. RESULTS: The measured volumetric water and lipid density from dual-energy mammography and chemical analysis were in good agreement, where the standard errors of estimates (SEE) of both were calculated to be 2.1%. Volumetric water and lipid density measurements from different views were also in good agreement, with a SEE of 1.3% and 1.1%, respectively. CONCLUSIONS: The results indicate that dual-energy mammography can be used to accurately measure volumetric water and lipid density in breast tissue. Accurate quantification of volumetric water density is expected to enhance its utility as a risk factor for breast cancer and for assessment of response to therapy. KEY POINTS: • Dual-energy mammography can be used to accurately measure water and lipid volumetric density in breast tissue. • Improved quantification of volumetric water density is expected to enhance its utility for assessment of response to therapy and as a risk factor for breast cancer.

Breast Arterial Calcification Is Not Associated with Mild Cognitive Impairment or Incident All-Cause Dementia Among Postmenopausal Women: The MINERVA Study.

Background: Since vascular risk factors are implicated in cognitive decline, and breast arterial calcification (BAC) is related to vascular risk, we postulated that BAC may be associated with cognitive impairment and dementia. Methods: We used a multiethnic cohort of 3,913 asymptomatic women 60-79 years of age recruited after mammography screening at a large health plan in 2012-2015. A BAC mass score (mg) was derived from digital mammograms. Cognitive function was measured at baseline using the Montreal Cognitive Assessment (MoCA) and incident all-cause dementia (n = 49 events; median follow-up = 5.6 years) were ascertained with validated ICD-9 and ICD-10 codes. We used cross-sectional linear regression of MoCA scores on BAC, then multinomial logistic regression predicting mild cognitive impairment not progressing to dementia and incident all-cause dementia and, finally, Cox regression of incident all-cause dementia. Results: No association by linear regression was found between MoCA scores and BAC presence in unadjusted or adjusted analysis. Women with severe (upper tertile) BAC had a MoCA score lower by 0.58 points (standard error [SE] = 0.18) relative to women with no BAC. However, this difference disappeared after multivariate adjustment. No significant associations were found in multinomial logistic regression for either BAC presence or gradation in unadjusted or adjusted analysis. No significant associations were found between BAC presence with incident all-cause dementia (fully adjusted hazard ratio = 0.74; 95% confidence interval: 0.39-1.39). Likewise, no significant association with incident all-cause dementia was noted for BAC gradation. Conclusions: Our results do not support the hypothesis that BAC presence or gradation may contribute to cognitive impairment or development of all-cause dementia.

LEGO-compatible modular mapping phantom for magnetic resonance imaging.

Physical phantoms have been widely used for performance evaluation of magnetic resonance imaging (MRI). Although there are many kinds of physical phantoms, most MRI phantoms use fixed configurations with specific sizes that may fit one or a few different types of radio frequency (RF) coils. Therefore, it has limitations for various image quality assessments of scanning areas. In this article, we report a novel design for a truly customizable MRI phantom called the LEGO-compatible Modular Mapping (MOMA) phantom, which not only serves as a general quality assurance phantom for a wide range of RF coils, but also a flexible calibration phantom for quantitative imaging. The MOMA phantom has a modular architecture which includes individual assessment functionality of the modules and LEGO-type assembly compatibility. We demonstrated the feasibility of the MOMA phantom for quantitative evaluation of image quality using customized module assembly compatible with head, breast, spine, knee, and body coil features. This unique approach allows comprehensive image quality evaluation with wide versatility. In addition, we provide detailed MOMA phantom development and imaging characteristics of the modules.

No Association Between Bone Mineral Density and Breast Arterial Calcification Among Postmenopausal Women.

CONTEXT: The association between bone mineral density (BMD) and breast arterial calcification (BAC) remains poorly understood and controversial. OBJECTIVE: The objective of this article is to examine the association between BMD and BAC in a large cohort of postmenopausal women undergoing routine mammography. DESIGN: A cross-sectional analysis of baseline data from a multiethnic cohort was performed. SETTING: The setting for this analysis is an integrated health care delivery system in Northern California in the United States. PATIENTS: A total of 1273 women age 60 to 79 years (mean age, 67 years) were recruited within 12 months of screening mammography. MAIN OUTCOME MEASURE: A BAC score (mg) was obtained from digital mammograms using a novel densitometry method. BAC presence was defined as a BAC score greater than 0 mg, and severe BAC as a BAC score greater than 20 mg. RESULTS: Overall, 53% of women had osteopenia and 21% had osteoporosis. The prevalence of BAC greater than 0 mg was 29%, 30%, and 29% among women with normal BMD, osteopenia, and osteoporosis, respectively (P = 0.98). The prevalence of BAC greater than 20 mg was 5%, 3%, and 5% among women with normal BMD, osteopenia and osteoporosis, respectively (P = .65). The odds ratios (ORs) of BAC greater than 0 mg vs BAC = 0 mg after multivariable adjustment were 1.09 (95% CI, 0.81-1.48; P = .54) for osteopenia and 0.99 (95% CI, 0.69-1.48; P = .98) for osteoporosis. The adjusted ORs for BAC greater than 20 mg vs BAC 20 mg or less were 1.03 (95% CI, 0.52-2.01; P = .93) for osteopenia and 1.89 (95 CI, 0.81-4.47; P = .14) for osteoporosis. CONCLUSION: Our findings do not support an association of either osteopenia or osteoporosis with BAC presence or severity among postmenopausal women.

Kidney function, proteinuria and breast arterial calcification in women without clinical cardiovascular disease: The MINERVA study.

BACKGROUND: Breast arterial calcification (BAC) may be a predictor of cardiovascular events and is highly prevalent in persons with end-stage kidney disease. However, few studies to date have examined the association between mild-to-moderate kidney function and proteinuria with BAC. METHODS: We prospectively enrolled women with no prior cardiovascular disease aged 60 to 79 years undergoing mammography screening at Kaiser Permanente Northern California between 10/24/2012 and 2/13/2015. Urine albumin-to-creatinine ratio (uACR), along with specific laboratory, demographic, and medical data, were measured at the baseline visit. Baseline estimated glomerular filtration rate (eGFR), medication history, and other comorbidities were identified from self-report and/or electronic medical records. BAC presence and gradation (mass) was measured by digital quantification of full-field mammograms. RESULTS: Among 3,507 participants, 24.5% were aged ≥70 years, 63.5% were white, 7.5% had eGFR <60 ml/min/1.73m2, with 85.7% having uACR ≥30 mg/g and 3.3% having uACR ≥300 mg/g. The prevalence of any measured BAC (>0 mg) was 27.9%. Neither uACR ≥30 mg/g nor uACR ≥300 were significantly associated with BAC in crude or multivariable analyses. Reduced eGFR was associated with BAC in univariate analyses (odds ratio 1.53, 95% CI: 1.18-2.00), but the association was no longer significant after adjustment for potential confounders. Results were similar in various sensitivity analyses that used different BAC thresholds or analytic approaches. CONCLUSIONS: Among women without cardiovascular disease undergoing mammography screening, reduced eGFR and albuminuria were not significantly associated with BAC.

A phantom based evaluation of vessel lumen area quantification for coronary CT angiography.

Coronary computed tomography (CT) angiography is a noninvasive method for visualizing coronary artery disease. However, coronary CT angiography is limited in assessment of stenosis severity by the partial volume effect and calcification. Therefore, an accurate method for assessment of stenosis severity is needed. A 10 cm diameter cylindrical Lucite phantom with holes in the range of 0.4-4.5 mm diameter was fitted in a chest phantom. The holes were filled with an iodine solution of 8 mg/mL. To simulate coronary artery disease, different levels of stenosis were created by inserting Lucite rods into the holes with diameter range of 2-4.5 mm. The resulting lumen cross sectional areas ranged from 1.4 to 12.3 mm2. To simulate arterial calcification, calcium hydroxyapatite rods were inserted into the holes with diameter range of 2-4.5 mm. Images of the phantoms were acquired at 100 kVp using a 320-slice CT scanner. A maual and a semi-automated technique based on integrated Hounsfield units was used to calculate vessel cross-sectional area. There was an excellent correlation between the measured and the known cross-sectional area for both normal and stenotic vessels using the manual and the semi-automated techniques. However, the overall measurement error for the manual method was more than twice as compared with the integrated HU technique. Determination of vessel lumen area using the semi-automated integrated Hounsfield unit technique yields more than a factor of two improvement in precision and accuracy as compared to the existing manual technique for vessels with and without stenosis. This technique can also be used to accurately measure arterial cross-sectional area in the presence of coronary calcification.

MultIethNic Study of BrEast ARterial Calcium Gradation and CardioVAscular Disease: cohort recruitment and baseline characteristics.

PURPOSE: MultIethNic Study of BrEast ARterial Calcium Gradation and CardioVAscular Disease (MINERVA) was designed to answer the question of whether a novel continuous breast arterial calcification (BAC) mass score improves cardiovascular risk stratification among asymptomatic postmenopausal women. This article describes recruitment and baseline characteristics. METHODS: MINERVA is a multiethnic longitudinal cohort study. The phenotype data include BAC mass by densitometry applied to digital mammograms, sociodemographic factors, self-reported medical history, medications, parental history, reproductive history, smoking, alcohol consumption, physical activity, anthropometry, ankle-brachial index, blood pressure, laboratory panel, breast volumes, cognitive function, bioelectrical impedance, habitual diet, dietary supplements, sleep, psychosocial factors, and sun exposure. RESULTS: A total of 5145 women aged 60 to 79 years with available digital, uncompressed mammograms were recruited from the membership of Kaiser Permanente of Northern California between October 24, 2012 and February 13, 2015 and completed a baseline clinic visit or an abbreviated phone questionnaire. Of those, 4153 underwent phlebotomy and have blood biomarkers. Overall prevalence of BAC was 26%, and it varied by age and race. The mean (SD) BAC mass was 12 (23) mg and the range 0-342 mg. CONCLUSIONS: MINERVA is the first cohort with a continuous measure of BAC. The cohort is large, ethnically diverse, and deeply phenotyped in terms of socioeconomic, behavioral, and clinical factors, and blood biomarkers.

Association of Breast Arterial Calcification Presence and Gradation with the Ankle-Brachial Index among Postmenopausal Women.

OBJECTIVE: To examine the association of breast arterial calcification (BAC) with the ankle brachial index (ABI), a sensitive metric of peripheral arterial disease (PAD), among postmenopausal women. Background: BAC is an emerging risk marker of cardiovascular disease (CVD). METHODS: MINERVA (MultIethNic study of brEast aRterial calcium gradation and cardioVAscular disease) is a cohort of women aged 60 to 79 at baseline (10/24/2012 - 2/13/2015) who were free of symptomatic CVD at baseline. The analytical sample comprised 3,800 women with available ABI, BAC assessment and covariates. We performed cross-sectional logistic regression analysis. RESULTS: 203 women (5.3%) had an ABI < 0.90 indicative of PAD, 26 (0.7%) had an ABI > 1.3 and 94% (n=3,571) had an ABI within normal limits. After adjustment for age, race/ethnicity, body mass index, smoking status, diabetes, hypertension, LDL-C, HDL-C, hs-CRP, estimated-GFR, urinary albumin/creatinine ratio, serum calcium, serum vitamin D and serum PTH, BAC presence remained significantly associated with ABI < 0.90 (OR=1.37; 95% CI, 1.01-1.87; p=0.04). After further adjustment for menopausal hormone therapy, parity and history of breast feeding, the association became marginally significant (OR=1.36; 95% CI, 0.99-1.85; p=0.05). No clear pattern of association was observed for increased gradation of BAC and ABI<0.9, and no significant associations were noted between BAC presence vs. absence or BAC gradation with ABI > 1.3. CONCLUSIONS: Among asymptomatic postmenopausal women, presence of BAC was associated with PAD independently of traditional risk factors. Additional prospective studies are required to establish the value of BAC for prediction of incident PAD in the general population.

Breast-density measurement using photon-counting spectral mammography.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

PURPOSE: To investigate the feasibility of accurate quantification of iodine mass thickness in contrast-enhanced spectral mammography. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Detecting Cardiovascular Disease from Mammograms With Deep Learning.

Coronary artery disease is a major cause of death in women. Breast arterial calcifications (BACs), detected inmammograms, can be useful riskmarkers associated with the disease. We investigate the feasibility of automated and accurate detection ofBACsinmammograms for risk assessment of coronary artery disease. We develop a 12-layer convolutional neural network to discriminate BAC from non-BAC and apply a pixelwise, patch-based procedure for BAC detection. To assess the performance of the system, we conduct a reader study to provide ground-truth information using the consensus of human expert radiologists. We evaluate the performance using a set of 840 full-field digital mammograms from 210 cases, using both free-responsereceiveroperatingcharacteristic (FROC) analysis and calcium mass quantification analysis. The FROC analysis shows that the deep learning approach achieves a level of detection similar to the human experts. The calcium mass quantification analysis shows that the inferred calcium mass is close to the ground truth, with a linear regression between them yielding a coefficient of determination of 96.24%. Taken together, these results suggest that deep learning can be used effectively to develop an automated system for BAC detection inmammograms to help identify and assess patients with cardiovascular risks.

Accurate quantification of vessel cross-sectional area using CT angiography: a simulation study.

Coronary computed tomography (CT) angiography is a noninvasive method for visualizing coronary atherosclerosis. However, CT angiography is limited in assessment of stenosis severity by the partial volume effect and calcification. Therefore, a quantitative method for assessment of stenosis severity is needed. Polyenergetic fan beam CT simulations were performed to match the geometry of a 320-slice CT scanner. Contrast-enhanced vessel lumens were modeled as 8 mg/ml Iodine solution against a lipid background. Normal vessels were simulated by circles with diameters in the range of 0.1-3 mm. To simulate lesions, 2, 3, and 4 mm diameter vessels were simulated with area stenoses in a range of 10-90 %. The occlusion was created by a circular region of lipid placed within the lumen resulting in a crescent shaped lumen. Each vessel was simulated three times to obtain multiple noise realizations for a total of 126 vessels. Two trained readers performed manual cross-sectional area measurements in simulated normal and stenotic vessels. A new, semi-automated technique based on integrated Hounsfield units was also used to calculate vessel cross-sectional area. There was an excellent correlation between the measured and the known cross-sectional area for both normal and stenotic vessels using the manual and the semi-automated techniques. However, the overall measurement error for the manual method was more than twice as compared with the integrated HU technique. Determination of vessel cross-sectional area using the semi-automated integrated Hounsfield unit technique yields more than a factor of two improvement in accuracy as compared to the existing manual technique for vessels with and without stenosis. This technique can also be used to correct for the effect of coronary calcification.

Quantification of breast lesion compositions using low-dose spectral mammography: A feasibility study.

PURPOSE: The positive predictive power for malignancy can potentially be improved, if the chemical compositions of suspicious breast lesions can be reliably measured in screening mammography. The purpose of this study is to investigate the feasibility of quantifying breast lesion composition, in terms of water and lipid contents, with spectral mammography. METHODS: Phantom and tissue samples were imaged with a spectral mammography system based on silicon-strip photon-counting detectors. Dual-energy calibration was performed for material decomposition, using plastic water and adipose-equivalent phantoms as the basis materials. The step wedge calibration phantom consisted of 20 calibration configurations, which ranged from 2 to 8 cm in thickness and from 0% to 100% in plastic water density. A nonlinear rational fitting function was used in dual-energy calibration of the imaging system. Breast lesion phantoms, made from various combinations of plastic water and adipose-equivalent disks, were embedded in a breast mammography phantom with a heterogeneous background pattern. Lesion phantoms with water densities ranging from 0% to 100% were placed at different locations of the heterogeneous background phantom. The water density in the lesion phantoms was measured using dual-energy material decomposition. The thickness and density of the background phantom were varied to test the accuracy of the decomposition technique in different configurations. In addition, an in vitro study was also performed using mixtures of lean and fat bovine tissue of 25%, 50%, and 80% lean weight percentages as the background. Lesions were simulated by using breast lesion phantoms, as well as small bovine tissue samples, composed of carefully weighed lean and fat bovine tissues. The water densities in tissue samples were measured using spectral mammography and compared to measurement using chemical decomposition of the tissue. RESULTS: The thickness of measured and known water contents was compared for various lesion configurations. There was a good linear correlation between the measured and the known values. The root-mean-square errors in water thickness measurements were 0.3 and 0.2 mm for the plastic phantom and bovine tissue backgrounds, respectively. CONCLUSIONS: The results indicate that spectral mammography can be used to accurately characterize breast lesion composition in terms of their equivalent water and lipid contents.

TICMR: Total Image Constrained Material Reconstruction via Nonlocal Total Variation Regularization for Spectral CT.

This work develops a material reconstruction method for spectral CT, namely Total Image Constrained Material Reconstruction (TICMR), to maximize the utility of projection data in terms of both spectral information and high signal-to-noise ratio (SNR). This is motivated by the following fact: when viewed as a spectrally-integrated measurement, the projection data can be used to reconstruct a total image without spectral information, which however has a relatively high SNR; when viewed as a spectrally-resolved measurement, the projection data can be utilized to reconstruct the material composition, which however has a relatively low SNR. The material reconstruction synergizes material decomposition and image reconstruction, i.e., the direct reconstruction of material compositions instead of a two-step procedure that first reconstructs images and then decomposes images. For material reconstruction with high SNR, we propose TICMR with nonlocal total variation (NLTV) regularization. That is, first we reconstruct a total image using spectrally-integrated measurement without spectral binning, and build the NLTV weights from this image that characterize nonlocal image features; then the NLTV weights are incorporated into a NLTV-based iterative material reconstruction scheme using spectrally-binned projection data, so that these weights serve as a high-SNR reference to regularize material reconstruction. Note that the nonlocal property of NLTV is essential for material reconstruction, since material compositions may have significant local intensity variations although their structural information is often similar. In terms of solution algorithm, TICMR is formulated as an iterative reconstruction method with the NLTV regularization, in which the nonlocal divergence is utilized based on the adjoint relationship. The alternating direction method of multipliers is developed to solve this sparsity optimization problem. The proposed TICMR method was validated using both simulated and experimental data. In comparison with FBP and total-variation-based iterative method, TICMR had improved image quality, e.g., contrast-to-noise ratio and spatial resolution.

Microcalcification detectability using a bench-top prototype photon-counting breast CT based on a Si strip detector.

PURPOSE: To investigate the feasibility of detecting breast microcalcification (µCa) with a dedicated breast computed tomography (CT) system based on energy-resolved photon-counting silicon (Si) strip detectors. METHODS: The proposed photon-counting breast CT system and a bench-top prototype photon-counting breast CT system were simulated using a simulation package written in matlab to determine the smallest detectable µCa. A 14 cm diameter cylindrical phantom made of breast tissue with 20% glandularity was used to simulate an average-sized breast. Five different size groups of calcium carbonate grains, from 100 to 180 µm in diameter, were simulated inside of the cylindrical phantom. The images were acquired with a mean glandular dose (MGD) in the range of 0.7-8 mGy. A total of 400 images was used to perform a reader study. Another simulation study was performed using a 1.6 cm diameter cylindrical phantom to validate the experimental results from a bench-top prototype breast CT system. In the experimental study, a bench-top prototype CT system was constructed using a tungsten anode x-ray source and a single line 256-pixels Si strip photon-counting detector with a pixel pitch of 100 µm. Calcium carbonate grains, with diameter in the range of 105-215 µm, were embedded in a cylindrical plastic resin phantom to simulate µCas. The physical phantoms were imaged at 65 kVp with an entrance exposure in the range of 0.6-8 mGy. A total of 500 images was used to perform another reader study. The images were displayed in random order to three blinded observers, who were asked to give a 4-point confidence rating on each image regarding the presence of µCa. The µCa detectability for each image was evaluated by using the average area under the receiver operating characteristic curve (AUC) across the readers. RESULTS: The simulation results using a 14 cm diameter breast phantom showed that the proposed photon-counting breast CT system can achieve high detection accuracy with an average AUC greater than 0.89 ± 0.07 for µCas larger than 120 µm in diameter at a MGD of 3 mGy. The experimental results using a 1.6 cm diameter breast phantom showed that the prototype system can achieve an average AUC greater than 0.98 ± 0.01 for µCas larger than 140 µm in diameter using an entrance exposure of 1.2 mGy. CONCLUSIONS: The proposed photon-counting breast CT system based on a Si strip detector can potentially offer superior image quality to detect µCa with a lower dose level than a standard two-view mammography.

Breast density evaluation using spectral mammography, radiologist reader assessment, and segmentation techniques: a retrospective study based on left and right breast comparison.

RATIONALE AND OBJECTIVES: The purpose of this study was to compare the precision of mammographic breast density measurement using radiologist reader assessment, histogram threshold segmentation, fuzzy C-mean segmentation, and spectral material decomposition. MATERIALS AND METHODS: Spectral mammography images from a total of 92 consecutive asymptomatic women (aged 50-69 years) who presented for annual screening mammography were retrospectively analyzed for this study. Breast density was estimated using 10 radiologist reader assessment, standard histogram thresholding, fuzzy C-mean algorithm, and spectral material decomposition. The breast density correlation between left and right breasts was used to assess the precision of these techniques to measure breast composition relative to dual-energy material decomposition. RESULTS: In comparison to the other techniques, the results of breast density measurements using dual-energy material decomposition showed the highest correlation. The relative standard error of estimate for breast density measurements from left and right breasts using radiologist reader assessment, standard histogram thresholding, fuzzy C-mean algorithm, and dual-energy material decomposition was calculated to be 1.95, 2.87, 2.07, and 1.00, respectively. CONCLUSIONS: The results indicate that the precision of dual-energy material decomposition was approximately factor of two higher than the other techniques with regard to better correlation of breast density measurements from right and left breasts.