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.

Purpose

The possible clinical applications which can be performed using a newly developed detector depend on the detector's characteristic performance in a number of metrics including the dynamic range, resolution, uniformity, and stability. The authors have evaluated a prototype energy resolved fast photon counting x-ray detector based on a silicon (Si) strip sensor used in an edge-on geometry with an application specific integrated circuit to record the number of x-rays and their energies at high flux and fast frame rates. The investigated detector was integrated with a dedicated breast spectral computed tomography (CT) system to make use of the detector's high spatial and energy resolution and low noise performance under conditions suitable for clinical breast imaging. The aim of this article is to investigate the intrinsic characteristics of the detector, in terms of maximum output count rate, spatial and energy resolution, and noise performance of the imaging system.

Methods

The maximum output count rate was obtained with a 50 W x-ray tube with a maximum continuous output of 50 kVp at 1.0 mA. A109Cd source, with a characteristic x-ray peak at 22 keV from Ag, was used to measure the energy resolution of the detector. The axial plane modulation transfer function (MTF) was measured using a 67 μm diameter tungsten wire. The two-dimensional (2D) noise power spectrum (NPS) was measured using flat field images and noise equivalent quanta (NEQ) were calculated using the MTF and NPS results. The image quality parameters were studied as a function of various radiation doses and reconstruction filters. The one-dimensional (1D) NPS was used to investigate the effect of electronic noise elimination by varying the minimum energy threshold.

Results

A maximum output count rate of 100 million counts per second per square millimeter (cps/mm2) has been obtained (1 million cps per 100×100 μm pixel). The electrical noise floor was less than 4 keV. The energy resolution measured with the 22 keV photons from a 109Cd source was less than 9%. A reduction of image noise was shown in all the spatial frequencies in 1D NPS as a result of the elimination of the electronic noise. The spatial resolution was measured just above 5 line pairs per mm (lp/mm) where 10% of MTF corresponded to 5.4 mm(-1). The 2D NPS and NEQ shows a low noise floor and a linear dependence on dose. The reconstruction filter choice affected both of the MTF and NPS results, but had a weak effect on the NEQ.

Conclusions

The prototype energy resolved photon counting Si strip detector can offer superior imaging performance for dedicated breast CT as compared to a conventional energy-integrating detector due to its high output count rate, high spatial and energy resolution, and low noise characteristics, which are essential characteristics for spectral breast CT imaging.

Both computer simulations and experimental phantom studies were carried out to investigate the radiation dose reduction with tensor framelet based iterative image reconstruction (TFIR) for a dedicated high-resolution spectral breast computed tomography (CT) based on a silicon strip photon-counting detector. The simulation was performed with a 10 cm-diameter water phantom including three contrast materials (polyethylene, 8 mg ml(-1) iodine and B-100 bone-equivalent plastic). In the experimental study, the data were acquired with a 1.3 cm-diameter polymethylmethacrylate (PMMA) phantom containing iodine in three concentrations (8, 16 and 32 mg ml(-1)) at various radiation doses (1.2, 2.4 and 3.6 mGy) and then CT images were reconstructed using the filtered-back-projection (FBP) technique and the TFIR technique, respectively. The image quality between these two techniques was evaluated by the quantitative analysis on contrast-to-noise ratio (CNR) and spatial resolution that was evaluated using the task-based modulation transfer function (MTF). Both the simulation and experimental results indicated that the task-based MTF obtained from TFIR reconstruction with one-third of the radiation dose was comparable to that from the FBP reconstruction for low contrast target. For high contrast target, the TFIR was substantially superior to the FBP reconstruction in terms of spatial resolution. In addition, TFIR was able to achieve a factor of 1.6-1.8 increase in CNR, depending on the target contrast level. This study demonstrates that the TFIR can reduce the required radiation dose by a factor of two-thirds for a CT image reconstruction compared to the FBP technique. It achieves much better CNR and spatial resolution for high contrast target in addition to retaining similar spatial resolution for low contrast target. This TFIR technique has been implemented with a graphic processing unit system and it takes approximately 10 s to reconstruct a single-slice CT image, which can potentially be used in a future multi-slit multi-slice spiral CT system.

Purpose

To investigate the feasibility of characterizing a Si strip photon-counting detector using x-ray fluorescence.

Methods

X-ray fluorescence was generated by using a pencil beam from a tungsten anode x-ray tube with 2 mm Al filtration. Spectra were acquired at 90° from the primary beam direction with an energy-resolved photon-counting detector based on an edge illuminated Si strip detector. The distances from the source to target and the target to detector were approximately 19 and 11 cm, respectively. Four different materials, containing silver (Ag), iodine (I), barium (Ba), and gadolinium (Gd), were placed in small plastic containers with a diameter of approximately 0.7 cm for x-ray fluorescence measurements. Linear regression analysis was performed to derive the gain and offset values for the correlation between the measured fluorescence peak center and the known fluorescence energies. The energy resolutions and charge-sharing fractions were also obtained from analytical fittings of the recorded fluorescence spectra. An analytical model, which employed four parameters that can be determined from the fluorescence calibration, was used to estimate the detector response function.

Results

Strong fluorescence signals of all four target materials were recorded with the investigated geometry for the Si strip detector. The average gain and offset of all pixels for detector energy calibration were determined to be 6.95 mV/keV and -66.33 mV, respectively. The detector's energy resolution remained at approximately 2.7 keV for low energies, and increased slightly at 45 keV. The average charge-sharing fraction was estimated to be 36% within the investigated energy range of 20-45 keV. The simulated detector output based on the proposed response function agreed well with the experimental measurement.

Conclusions

The performance of a spectral imaging system using energy-resolved photon-counting detectors is very dependent on the energy calibration of the detector. The proposed x-ray fluorescence technique offers an accurate and efficient way to calibrate the energy response of a photon-counting 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.

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.

Spinal cord injury (SCI) results in devastating motor and sensory deficits secondary to disrupted neuronal circuits and poor regenerative potential. Efforts to promote regeneration through cell extrinsic and intrinsic manipulations have met with limited success. Stem cells represent an as yet unrealized therapy in SCI. Recently, we identified novel culture methods to induce and maintain primitive neural stem cells (pNSCs) from human embryonic stem cells. We tested whether transplanted human pNSCs can integrate into the CNS of the developing chick neural tube and injured adult rat spinal cord. Following injection of pNSCs into the developing chick CNS, pNSCs integrated into the dorsal aspects of the neural tube, forming cell clusters that spontaneously differentiated into neurons. Furthermore, following transplantation of pNSCs into the lesioned rat spinal cord, grafted pNSCs survived, differentiated into neurons, and extended long distance axons through the scar tissue at the graft-host interface and into the host spinal cord to form terminal-like structures near host spinal neurons. Together, these findings suggest that pNSCs derived from human embryonic stem cells differentiate into neuronal cell types with the potential to extend axons that associate with circuits of the CNS and, more importantly, provide new insights into CNS integration and axonal regeneration, offering hope for repair in SCI.

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.

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.

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.