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 tissue characterization with photon-counting spectral CT imaging: a postmortem breast study.

PURPOSE: To investigate the feasibility of breast tissue characterization in terms of water, lipid, and protein contents with a spectral computed tomographic (CT) system based on a cadmium zinc telluride (CZT) photon-counting detector by using postmortem breasts. MATERIALS AND METHODS: Nineteen pairs of postmortem breasts were imaged with a CZT-based photon-counting spectral CT system with beam energy of 100 kVp. The mean glandular dose was estimated to be in the range of 1.8-2.2 mGy. The images were corrected for pulse pile-up and other artifacts by using spectral distortion corrections. Dual-energy decomposition was then applied to characterize each breast into water, lipid, and protein contents. The precision of the three-compartment characterization was evaluated by comparing the composition of right and left breasts, where the standard error of the estimations was determined. The results of dual-energy decomposition were compared by using averaged root mean square to chemical analysis, which was used as the reference standard. RESULTS: The standard errors of the estimations of the right-left correlations obtained from spectral CT were 7.4%, 6.7%, and 3.2% for water, lipid, and protein contents, respectively. Compared with the reference standard, the average root mean square error in breast tissue composition was 2.8%. CONCLUSION: Spectral CT can be used to accurately quantify the water, lipid, and protein contents in breast tissue in a laboratory study by using postmortem specimens.

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.

Image-based spectral distortion correction for photon-counting x-ray detectors.

PURPOSE: To investigate the feasibility of using an image-based method to correct for distortions induced by various artifacts in the x-ray spectrum recorded with photon-counting detectors for their application in breast computed tomography (CT). METHODS: The polyenergetic incident spectrum was simulated with the tungsten anode spectral model using the interpolating polynomials (TASMIP) code and carefully calibrated to match the x-ray tube in this study. Experiments were performed on a Cadmium-Zinc-Telluride (CZT) photon-counting detector with five energy thresholds. Energy bins were adjusted to evenly distribute the recorded counts above the noise floor. BR12 phantoms of various thicknesses were used for calibration. A nonlinear function was selected to fit the count correlation between the simulated and the measured spectra in the calibration process. To evaluate the proposed spectral distortion correction method, an empirical fitting derived from the calibration process was applied on the raw images recorded for polymethyl methacrylate (PMMA) phantoms of 8.7, 48.8, and 100.0 mm. Both the corrected counts and the effective attenuation coefficient were compared to the simulated values for each of the five energy bins. The feasibility of applying the proposed method to quantitative material decomposition was tested using a dual-energy imaging technique with a three-material phantom that consisted of water, lipid, and protein. The performance of the spectral distortion correction method was quantified using the relative root-mean-square (RMS) error with respect to the expected values from simulations or areal analysis of the decomposition phantom. RESULTS: The implementation of the proposed method reduced the relative RMS error of the output counts in the five energy bins with respect to the simulated incident counts from 23.0%, 33.0%, and 54.0% to 1.2%, 1.8%, and 7.7% for 8.7, 48.8, and 100.0 mm PMMA phantoms, respectively. The accuracy of the effective attenuation coefficient of PMMA estimate was also improved with the proposed spectral distortion correction. Finally, the relative RMS error of water, lipid, and protein decompositions in dual-energy imaging was significantly reduced from 53.4% to 6.8% after correction was applied. CONCLUSIONS: The study demonstrated that dramatic distortions in the recorded raw image yielded from a photon-counting detector could be expected, which presents great challenges for applying the quantitative material decomposition method in spectral CT. The proposed semi-empirical correction method can effectively reduce these errors caused by various artifacts, including pulse pileup and charge sharing effects. Furthermore, rather than detector-specific simulation packages, the method requires a relatively simple calibration process and knowledge about the incident spectrum. Therefore, it may be used as a generalized procedure for the spectral distortion correction of different photon-counting detectors in clinical breast CT systems.

Breast composition measurement with a cadmium-zinc-telluride based spectral computed tomography system.

PURPOSE: To investigate the feasibility of breast tissue composition in terms of water, lipid, and protein with a cadmium-zinc-telluride (CZT) based computed tomography (CT) system to help better characterize suspicious lesions. METHODS: Simulations and experimental studies were performed using a spectral CT system equipped with a CZT-based photon-counting detector with energy resolution. Simulations of the figure-of-merit (FOM), the signal-to-noise ratio (SNR) of the dual energy image with respect to the square root of mean glandular dose (MGD), were performed to find the optimal configuration of the experimental acquisition parameters. A calibration phantom 3.175 cm in diameter was constructed from polyoxymethylene plastic with cylindrical holes that were filled with water and oil. Similarly, sized samples of pure adipose and pure lean bovine tissues were used for the three-material decomposition. Tissue composition results computed from the images were compared to the chemical analysis data of the tissue samples. RESULTS: The beam energy was selected to be 100 kVp with a splitting energy of 40 keV. The tissue samples were successfully decomposed into water, lipid, and protein contents. The RMS error of the volumetric percentage for the three-material decomposition, as compared to data from the chemical analysis, was estimated to be approximately 5.7%. CONCLUSIONS: The results of this study suggest that the CZT-based photon-counting detector may be employed in the CT system to quantify the water, lipid, and protein mass densities in tissue with a relatively good agreement.

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.

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.

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.

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.

Fullerene/thiol-terminated molecules.

A series of fullerene-terminated oligo(phenylene ethynylene) (OPEs) have been synthesized for potential use in electronic or optoelectronic device monolayers. Electronic properties such as the energy levels and the distribution of HOMOs and LUMOs of fullerene-terminated OPEs have been calculated using the ab initio method at the B3LYP/6-31G(d) level. The calculations have revealed the concentration of frontier orbitals on the fullerene cage and a narrow distribution of HOMO-LUMO energy gaps. Ultraviolet photoelectron spectroscopy and inverse photoemission spectroscopy studies have been performed to further examine the electronic properties of the fullerene-terminated OPEs on gold surfaces. The obtained broad photoelectron spectra suggest that there are strong intermolecular interactions in the fullerene self-assembled monolayers, and the small bandgap (approximately 1.5 eV), determined by the photoelectron spectroscopy, indicates the unique nature of the fullerene-terminated OPEs in which the C(60) moiety can be connected to the Au surface through the conjugated OPE backbone.

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.

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.

Silicon/molecule interfacial electronic modifications.

Electronic structures at the silicon/molecule interface were studied by X-ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy, inverse photoemission spectroscopy, and Kelvin probe techniques. The heterojunctions were fabricated by direct covalent grafting of a series of molecules (-C6H4-X, with X = NMe2, NH2, NO2, and Mo6 oxide cluster) onto the surface of four types of silicon substrates (both n- and p-type with different dopant densities). The electronic structures at the interfaces were thus systematically tuned in accordance with the electron-donating ability, redox capability, and/or dipole moment of the grafted molecules. The work function of each grafted surface is determined by a combination of the surface band bending and electron affinity. The surface band bending is dependent on the charge transfer between the silicon substrate and the grafted molecules, whereas electron affinity is dependent on the dipole moment of the grafted molecules. The contribution of each to the work function can be separated by a combination of the aforementioned analytical techniques. In addition, because of the relatively low molecular coverage on the surface, the contribution from the unreacted H-terminated surface to the work function was considered. The charge-transfer barrier of silicon substrates attached to different molecules exhibits a trend analogous to surface band bending effects, whereas the surface potential step exhibits properties analogous to electron affinity effects. These results provide a foundation for the utilization of organic molecule surface grafting as a means to tune the electronic properties of semiconductors and, consequently, to achieve controllable modulation of electronic characteristics in small semiconductor devices at future technology nodes.

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.

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.

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.

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.

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.