Characterization of Molecular Chaperone GroEL as a Potential Virulence Factor in Cronobacter sakazakii.

The molecular chaperone GroEL of C. sakazakii, a highly conserved protein encoded by the gene grol, has the basic function of responding to heat shock, thus enhancing the bacterium's adaptation to dry and high-temperature environments, which poses a threat to food safety and human health. Our previous study demonstrated that GroEL was found in the bacterial membrane fraction and caused a strong immune response in C. sakazakii. In this study, we tried to elucidate the subcellular location and virulent effects of GroEL. In live C. sakazakii cells, GroEL existed in both the soluble and insoluble fractions. To study the secretory mechanism of GroEL protein, a non-reduced Western immunoblot was used to analyze the form of the protein, and the result showed that the exported GroEL protein was mainly in monomeric form. The exported GroEL could also be located on bacterial surface. To further research the virulent effect of C. sakazakii GroEL, an indirect immunofluorescence assay was used to detect the adhesion of recombinant GroEL protein to HCT-8 cells. The results indicated that the recombinant GroEL protein could adhere to HCT-8 cells in a short period of time. The recombinant GroEL protein could activate the NF-κB signaling pathway to release more pro-inflammatory cytokines (TNF-α, IL-6 and IL-8), downregulating the expression of tight-junction proteins (claudin-1, occluding, ZO-1 and ZO-2), which collectively resulted in dose-dependent virulent effects on host cells. Inhibition of the grol gene expression resulted in a significant decrease in bacterial adhesion to and invasion of HCT-8 cells. Moreover, the deficient GroEL also caused slow growth, decreased biofilm formation, defective motility and abnormal filamentation of the bacteria. In brief, C. sakazakii GroEL was an important virulence factor. This protein was not only crucial for the physiological activity of C. sakazakii but could also be secreted to enhance the bacterium's adhesion and invasion capabilities.

Integrated multifunctional nanoplatform for fluorescence detection and inactivation of Staphylococcus aureus.

Foodborne illness caused by Staphylococcus aureus (S. aureus) has posed a significant threat to human health. Herein, an integrated multifunctional nanoplatform was developed for fluorescence detection and inactivation of S. aureus based on cascade signal amplification coupled with single strand DNA-template copper nanoparticles (ssDNA-Cu NPs). Benefiting from reasonable design, one-step cascade signal amplification was achieved through strand displacement amplification combined with rolling circle amplification, followed by in-situ generation of copper nanoparticles. S. aureus detection could be performed through naked eye observation and microplate reader measurement of the red fluorescence signal. The multifunctional nanoplatform had satisfactory specificity and sensitivity, achieving 5.2 CFU mL-1 detection limit and successful detection of 7.3 CFU of S. aureus in spiked egg after < 5 h of enrichment. Moreover, ssDNA-Cu NPs could eliminate S. aureus to avoid secondary bacterial contamination without further treatment. Therefore, this multifunctional nanoplatform has potential application in food safety dtection.

Effects of ESA_00986 Gene on Adhesion/Invasion and Virulence of Cronobacter sakazakii and Its Molecular Mechanism.

Cronobacter sakazakii is an opportunistic Gram-negative pathogen that has been identified as a causative agent of severe foodborne infections with a higher risk of mortality in neonates, premature infants, the elderly, and immunocompromised populations. The specific pathogenesis mechanisms of C. sakazakii, such as adhesion and colonization, remain unclear. Previously, we conducted comparative proteomic studies on the two strains with the stronger and weaker infection ability, respectively, and found an interesting protein, ESA_00986, which was more highly expressed in the strain with the stronger ability. This unknown protein, predicted to be a type of invasitin related to invasion, may be a critical factor contributing to its virulence. This study aimed to elucidate the precise roles of the ESA_00986 gene in C. sakazakii by generating gene knockout mutants and complementary strains. The mutant and complementary strains were assessed for their biofilm formation, mobility, cell adhesion and invasion, and virulence in a rat model. Compared with the wild-type strain, the mutant strain exhibited a decrease in motility, whereas the complementary strain showed comparable motility to the wild-type. The biofilm-forming ability of the mutant was weakened, and the mutant also exhibited attenuated adhesion to/invasion of intestinal epithelial cells (HCT-8, HICE-6) and virulence in a rat model. This indicated that ESA_00986 plays a positive role in adhesion/invasion and virulence. This study proves that the ESA_00986 gene encodes a novel virulence factor and advances our understanding of the pathogenic mechanism of C. sakazakii.

Objective Image Quality Optimization in Augmented Reality Using Spatial Frequency Domain Models.

Augmented reality (AR) blends the digital and physical worlds by overlapping a virtual image onto the see-through physical environment. However, contrast reduction and noise superposition in an AR head-mounted display (HMD) can substantially limit image quality and human perceptual performance in both the digital and physical spaces. To assess image quality in AR, we performed human and model observer studies for various imaging tasks with targets placed in the digital and physical worlds. A target detection model was developed for the complete AR system including the optical see-through. Target detection performance using different observer models developed in the spatial frequency domain was compared with the human observer results. The non-prewhitening model with eye filter and internal noise results closely track human perception performance as measured by the area under the receiver operating characteristic curve (AUC), especially for tasks with high image noise. The AR HMD non-uniformity limits the low-contrast target (less than 0.02) observer performance for low image noise. In augmented reality conditions, the detectability of a target in the physical world is reduced due to the contrast reduction by the overlaid AR display image (AUC less than 0.87 for all the contrast levels evaluated). We propose an image quality optimization scheme to optimize the AR display configurations to match observer detection performance for targets in both the digital and physical worlds. The image quality optimization procedure is validated using both simulation and bench measurements of a chest radiography image with digital and physical targets for various imaging configurations.

Spatiotemporal image quality of virtual reality head mounted displays.

Virtual reality (VR) head mounted displays (HMDs) require both high spatial resolution and fast temporal response. However, methods to quantify the VR image quality in the spatiotemporal domain when motion exists are not yet standardized. In this study, we characterize the spatiotemporal capabilities of three VR devices: the HTC VIVE, VIVE Pro, and VIVE Pro 2 during smooth pursuit. A spatiotemporal model for VR HMDs is presented using measured spatial and temporal characteristics. Among the three evaluated headsets, the VIVE Pro 2 improves the display temporal performance using a fast 120 Hz refresh rate and pulsed emission with a small duty cycle of 5%. In combination with a high pixel resolution beyond 2 k [Formula: see text] 2 k per eye, the VIVE Pro 2 achieves an improved spatiotemporal performance compared to the VIVE and VIVE Pro in the high spatial frequency range above 8 cycles per degree during smooth pursuit. The result demonstrates that reducing the display emission duty cycle to less than 20% is beneficial to mitigate motion blur in VR HMDs. Frame rate reduction (e.g., to below 60 Hz) of the input signal compared to the display refresh rate of 120 Hz yields replicated shadow images that can affect the image quality under motion. This work supports the regulatory science research efforts in development of testing methods to characterize the spatiotemporal performance of VR devices for medical use.

Red yeast rice dietary intervention reduces oxidative stress-related inflammation and improves intestinal microbiota.

Inflammation and oxidative stress play key roles in the aging process, while red yeast rice (RYR), a traditional Chinese fermented food, has anti-oxidant and anti-inflammatory effects. To understand the anti-aging function of RYR in vivo, this study established a D-galactose-induced aging mouse model to verify the positive effects of RYR dietary intervention on aging and explore the related underlying mechanism. Eight weeks of RYR dietary intervention was shown to have a significant inhibitory effect on cognitive decline and hippocampal damage. The molecular mechanistic studies showed that the anti-aging effects of RYR were achieved by (i) improving the oxidative stress-related damage (increasing SOD, CAT, and GSH, and reducing MDA), (ii) regulating the NF-κB inflammation pathway induced by oxidative stress (decreasing the pro-inflammatory cytokines IL-6, TNF-α, IFN-γ, iNOs, and IL-1ß, increasing the anti-inflammatory cytokine IL-10, and decreasing the expression of the NF-κB protein), (iii) slowing down apoptosis caused by oxidative stress (reducing the expression of P21 and P53), (iv) restoring the abundance of Lactobacillus, Lachnospiraceae and Rikenellaceae downregulated by D-galactose, and (v) reducing the abundance of Akkermansia and Helicobacter enriched by D-galactose. Mass spectrometry revealed orange pigments (rubropunctatin and monascorubrin) as the main antioxidant components in RYR, which might play key roles in aging inhibition. This study provides theoretical support for the wide application of orange pigments as an antioxidant dietary supplement.

Feasibility of Dual-Energy Cone-Beam CT of Bone Marrow Edema Using Dual-Layer Flat Panel Detectors.

Purpose: We investigated the feasibility of detection and quantification of bone marrow edema (BME) using dual-energy (DE) Cone-Beam CT (CBCT) with a dual-layer flat panel detector (FPD) and three-material decomposition. Methods: A realistic CBCT system simulator was applied to study the impact of detector quantization, scatter, and spectral calibration errors on the accuracy of fat-water-bone decompositions of dual-layer projections. The CBCT system featured 975 mm source-axis distance, 1,362 mm source-detector distance and a 430 × 430 mm2 dual-layer FPD (top layer: 0.20 mm CsI:Tl, bottom layer: 0.55 mm CsI:Tl; a 1 mm Cu filter between the layers to improve spectral separation). Tube settings were 120 kV (+2 mm Al, +0.2 mm Cu) and 10 mAs per exposure. The digital phantom consisted of a 160 mm water cylinder with inserts containing mixtures of water (volume fraction ranging 0.18 to 0.46) - fat (0.5 to 0.7) - Ca (0.04 to 0.12); decreasing fractions of fat indicated increasing degrees of BME. A two-stage three-material DE decomposition was applied to DE CBCT projections: first, projection-domain decomposition (PDD) into fat-aluminum basis, followed by CBCT reconstruction of intermediate base images, followed by image-domain change of basis into fat, water and bone. Sensitivity to scatter was evaluated by i) adjusting source collimation (12 to 400 mm width) and ii) subtracting various fractions of the true scatter from the projections at 400 mm collimation. The impact of spectral calibration was studied by shifting the effective beam energy (± 2 keV) when creating the PDD lookup table. We further simulated a realistic BME imaging framework, where the scatter was estimated using a fast Monte Carlo (MC) simulation from a preliminary decomposition of the object; the object was a realistic wrist phantom with an 0.85 mL BME stimulus in the radius. Results: The decomposition is sensitive to scatter: approx. <20 mm collimation width or <10% error of scatter correction in a full field-of-view setting is needed to resolve BME. A mismatch in PDD decomposition calibration of ± 1 keV results in ~25% error in fat fraction estimates. In the wrist phantom study with MC scatter corrections, we were able to achieve ~0.79 mL true positive and ~0.06 mL false positive BME detection (compared to 0.85 mL true BME volume). Conclusions: Detection of BME using DE CBCT with dual-layer FPD is feasible, but requires scatter mitigation, accurate scatter estimation, and robust spectral calibration.

Slot-scan dual-energy bone densitometry using motorized X-ray systems.

PURPOSE: We investigate the feasibility of slot-scan dual-energy (DE) bone densitometry on motorized radiographic equipment. This approach will enable fast quantitative measurements of areal bone mineral density (aBMD) for opportunistic evaluation of osteoporosis. METHODS: We investigated DE slot-scan protocols to obtain aBMD measurements at the lumbar spine (L-spine) and hip using a motorized x-ray platform capable of synchronized translation of the x-ray source and flat-panel detector (FPD). The slot dimension was 5 × 20 cm2 . The DE slot views were processed as follows: (1) convolution kernel-based scatter correction, (2) unfiltered backprojection to tile the slots into long-length radiographs, and (3) projection-domain DE decomposition, consisting of an initial adipose-water decomposition in a bone-free region followed by water-CaHA decomposition with adjustment for adipose content. The accuracy and reproducibility of slot-scan aBMD measurements were investigated using a high-fidelity simulator of a robotic x-ray system (Siemens Multitom Rax) in a total of 48 body phantom realizations: four average bone density settings (cortical bone mass fraction: 10-40%), four body sizes (waist circumference, WC = 70-106 cm), and three lateral shifts of the body within the slot field of view (FOV) (centered and ±1 cm off-center). Experimental validations included: (1) x-ray test-bench feasibility study of adipose-water decomposition and (2) initial demonstration of slot-scan DE bone densitometry on the robotic x-ray system using the European Spine Phantom (ESP) with added attenuation (polymethyl methacrylate [PMMA] slabs) ranging 2 to 6 cm thick. RESULTS: For the L-spine, the mean aBMD error across all WC settings ranged from 0.08 g/cm2 for phantoms with average cortical bone fraction wcortical  = 10% to ∼0.01 g/cm2 for phantoms with wcortical  = 40%. The L-spine aBMD measurements were fairly robust to changes in body size and positioning, e.g., coefficient of variation (CV) for L1 with wcortical  = 30% was ∼0.034 for various WC and ∼0.02 for an obese patient (WC = 106 cm) changing lateral shift. For the hip, the mean aBMD error across all phantom configurations was about 0.07 g/cm2 for a centered patient. The reproducibility of hip aBMD was slightly worse than in the L-spine (e.g., in the femoral neck, the CV with respect to changing WC was ∼0.13 for phantom realizations with wcortical  = 30%) due to more challenging scatter estimation in the presence of an air-tissue interface within the slot FOV. The aBMD of the hip was therefore sensitive to lateral positioning of the patient, especially for obese patients: e.g., the CV with respect to patient lateral shift for femoral neck with WC = 106 cm and wcortical  = 30% was 0.14. Empirical evaluations confirmed substantial reduction in aBMD errors with the proposed adipose estimation procedure and demonstrated robust aBMD measurements on the robotic x-ray system, with aBMD errors of ∼0.1 g/cm2 across all three simulated ESP vertebrae and all added PMMA attenuator settings. CONCLUSIONS: We demonstrated that accurate aBMD measurements can be obtained on a motorized FPD-based x-ray system using DE slot-scans with kernel-based scatter correction, backprojection-based slot view tiling, and DE decomposition with adipose correction.

Production and Characterization of a Novel Low-Sugar Beverage from Red Jujube Fruits and Bamboo Shoots Fermented with Selected Lactiplantibacillus plantarum.

Red jujube fruits and bamboo shoots are rich in many nutrients and have the advantage of high yield in China. However, the storage of fresh fruits is difficult, and there are no fermented products using both as raw materials. In order to develop the two raw materials into novel products and improve their nutritional value, this study reports the production and characterization of a beverage via fermentation of red jujube fruits and bamboo shoots with Lactiplantibacillus plantarum. L. plantarum TUST-232 was selected as the starter from several different strains by comparing pH value and the number of viable cells, which reached 8.91 log CFU/mL in the beverage fermented for 14 h at 37 °C with 0.3% inoculation. After fermentation, the beverage showed improvement in the contents of several nutrients and antioxidant indices, with a decrease of 44.10% in sucrose content, along with increases of 11.09%, 12.30%, and 59.80% in total phenolic content, total antioxidant capacity, and superoxide anion scavenging ability, respectively. These results indicate that L. plantarum fermentation of red jujube fruits and bamboo shoots could be an effective way to develop a new beverage with high nutritional value, high antioxidant capacity, and high dietary fiber content. This research provided experimental support for the development of new fermentation products with the functions of improving health and body functions.

Cone-beam imaging with tilted rotation axis: Method and performance evaluation.

PURPOSE: The recently introduced robotic x-ray systems provide the flexibility to acquire cone-beam computed tomography (CBCT) data using customized, application-specific source-detector trajectories. We exploit this capability to mitigate the effects of x-ray scatter and noise in CBCT imaging of weight-bearing foot and cervical spine (C-spine) using scan orbits with a tilted rotation axis. METHODS: We used an advanced CBCT simulator implementing accurate models of x-ray scatter, primary attenuation, and noise to investigate the effects of the orbital tilt angle in upright foot and C-spine imaging. The system model was parameterized using a laboratory version of a three-dimensional (3D) robotic x-ray system (Multitom RAX, Siemens Healthineers). We considered a generalized tilted axis scan configuration, where the detector remained parallel to patient's long body axis during the acquisition, but the elevation of source and detector was changing. A modified Feldkamp-Davis-Kress (FDK) algorithm was developed for reconstruction in this configuration, which departs from the FDK assumption of a detector that is perpendicular to the scan plane. The simulated foot scans involved source-detector distance (SDD) of 1386 mm, orbital tilt angles ranging 10° to 40°, and 400 views at 1 mAs/view and 0.5° increment; the C-spine scans involved -25° to -45° tilt angles, SDD of 1090 mm, and 202 views at 1.3 mAs and 1° increment The imaging performance was assessed by projection-domain measurements of the scatter-to-primary ratio (SPR) and by reconstruction-domain measurements of contrast, noise and generalized contrast-to-noise ratio (gCNR, accounting for both image noise and background nonuniformity) of the metatarsals (foot imaging) and cervical vertebrae (spine imaging). The effects of scatter correction were also compared for horizontal and tilted scans using an ideal Monte Carlo (MC)-based scatter correction and a frame-by-frame mean scatter correction. RESULTS: The proposed modified FDK, involving projection resampling, mitigated streak artifacts caused by the misalignment between the filtering direction and the detector rows. For foot imaging (no grids), an optimized 20° tilted orbit reduced the maximum SPR from ~1.5 in a horizontal scan to <0.5. The gCNR of the second metatarsal was enhanced twofold compared to a horizontal orbit. For the C-spine (with vertical grids), imaging with a tilted orbit avoided highly attenuating x-ray paths through the lower cervical vertebrae and shoulders. A -35° tilted orbit yielded improved image quality and visualization of the lower cervical spine: the SPR of lower cervical vertebrae was reduced from ~10 (horizontal orbit) to <6 (tilted orbit), and the gCNR for C5-C7 increased by a factor of 2. Furthermore, tilted orbits showed potential benefits over horizontal orbits by enabling scatter correction with a simple frame-by-frame mean correction without substantial increase in noise-induced artifacts after the correction. CONCLUSIONS: Tilted scan trajectories, enabled by the emerging robotic x-ray system technology, were optimized for CBCT imaging of foot and cervical spine using an advanced simulation framework. The results demonstrated the potential advantages of tilted axis orbits in mitigation of scatter artifacts and improving contrast-to-noise ratio in CBCT reconstructions.

Cascaded systems analysis of a-Se/a-Si and a-InGaZnO TFT passive and active pixel sensors for tomosynthesis.

Medical imaging systems like full field digital mammography (FFDM) and digital breast tomosynthesis (DBT) commonly use amorphous selenium (a-Se) based passive pixel sensor (PPS) direct conversion x-ray detectors. On one hand, direct conversion detectors inherently offer better resolution characteristics in terms of a higher modulation transfer function (MTF), in comparison to the indirect CsI:Tl PPS x-ray imager. On the other hand, especially at lower doses, this superior performance of the direct imager is seldom retained in its detective quantum efficiency (DQE) curves. It is well known that a-Se PPS x-ray imagers suffer from high additive electronic noise originating from the from the amorphous silicon (a-Si) thin film transistor (TFT) array that is being used in the current back-plane technology. This degrades the noise power spectrum (NPS) and subsequently the overall DQE. To address this deficiency, we propose to replace the PPS back-plane by active pixel sensor (APS) back-plane technology, which has the potential to reduce the back-plane electronic noise by amplifying the input signal, especially at low doses. The proposed APS is based on amorphous In-Ga-Zn-O (a-IGZO) TFT technology, which can offer high mobility (5-20 cm2 V-1 s-1), low leakage current (<10-13 A) and low flicker noise (Hooge's parameter α H ~ 1.5 [Formula: see text] 10-3), leading to better imager noise performance. To test our hypothesis, we used linear cascaded systems analysis to model the imaging performance (MTF, NPS and DQE) of the PPS and APS a-Se direct imagers. This model was first validated using experimentally measured data obtained for a 85 µm pixel pitch a-Se/a-Si TFT PPS imager. Using this model, we analyzed the noise performance of the direct a-Se and indirect CsI:Tl x-ray a-IGZO APS imagers at different dose and electronic noise levels. Obtained results clearly showed that lowering back-plane electronic noise can significantly improve the performance of the a-Se/a-IGZO TFT APS imager. Our simulated results showed that a higher DQE at lower radiation doses (maximum DQE of 0.6 can be achieved at an exposure level of 1 µGy) can be achieved with the a-Se detector, thereby making this combination a promising candidate for low dose applications like DBT.

Association of systolic blood pressure with cardiovascular outcomes in elderly patients with hypertension in Northern China.

OBJECTIVE: The aim of this study was to investigate the association of systolic blood pressure (SBP) with cardiovascular disease and all-cause mortality among elderly hypertensive patients in northern China. PARTICIPANTS AND METHODS: In this prospective cohort study, 9655 elderly hypertensive patients from Kailuan study were followed up with the incidence of primary outcomes (composite outcomes including myocardial infarction, stroke, and all-cause death) and the incidence of secondary outcomes (stroke, myocardial infarction, and all-cause death). Patients were categorized into five groups on the basis of SBP levels: Q1 (SBP<130 mmHg), Q2 (130≤SBP<140 mmHg), Q3 (140≤SBP<150 mmHg), Q4 (150≤SBP<160 mmHg), and Q5 (SBP≥160 mmHg). RESULTS: During an average of 7.2±1.6 years of follow-up, patients in the group Q2 had the lowest incidence rates of composite outcomes. Q1 was not associated with a decreased risk of composite outcomes. Interestingly, compared with reference group Q2, the risk of composite outcomes [hazard ratio (HR): 1.36; 95% confidence interval (CI): 1.06-1.75] was significantly increased in the Q3 subgroup with high risk+very high risk for the incidence of ischemic cardiovascular disease (ICVD). Similarly, the risk of composite outcomes (HR: 1.25; 95% CI: 1.01-1.53 and HR: 1.35; 95% CI: 1.04-1.75) was significantly increased in Q4 subgroups, with both intermediate risk and high risk+very high risk for 10-year ICVD. CONCLUSION: Elderly hypertensive patients with a high risk of 10-year ICVD were still at a higher risk of developing adverse outcomes even with 140≤SBP<150 mmHg. SBP of less than 130 mmHg was not associated significantly with a reduced risk of developing adverse outcomes.

Task-Based Modeling of a 5k Ultra-High-Resolution Medical Imaging System for Digital Breast Tomosynthesis.

High-resolution, low-noise X-ray detectors based on CMOS active pixel sensor (APS) technology have demonstrated superior imaging performance for digital breast tomosynthesis (DBT). This paper presents a task-based model for a high-resolution medical imaging system to evaluate its ability to detect simulated microcalcifications and masses as lesions for breast cancer. A 3-D cascaded system analysis for a 50- [Formula: see text] pixel pitch CMOS APS X-ray detector was integrated with an object task function, a medical imaging display model, and the human eye contrast sensitivity function to calculate the detectability index and area under the ROC curve (AUC). It was demonstrated that the display pixel pitch and zoom factor should be optimized to improve the AUC for detecting small microcalcifications. In addition, detector electronic noise of smaller than 300 e- and a high display maximum luminance (>1000 cd/cm 2) are desirable to distinguish microcalcifications of [Formula: see text] in size. For low contrast mass detection, a medical imaging display with a minimum of 12-bit gray levels is recommended to realize accurate luminance levels. A wide projection angle range of greater than ±30° in combination with the image gray level magnification could improve the mass detectability especially when the anatomical background noise is high. On the other hand, a narrower projection angle range below ±20° can improve the small, high contrast object detection. Due to the low mass contrast and luminance, the ambient luminance should be controlled below 5 cd/ [Formula: see text]. Task-based modeling provides important firsthand imaging performance of the high-resolution CMOS-based medical imaging system that is still at early stage development for DBT. The modeling results could guide the prototype design and clinical studies in the future.

Large area CMOS active pixel sensor x-ray imager for digital breast tomosynthesis: Analysis, modeling, and characterization.

PURPOSE: Large area x-ray imagers based on complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology have been proposed for various medical imaging applications including digital breast tomosynthesis (DBT). The low electronic noise (50-300 e-) of CMOS APS x-ray imagers provides a possible route to shrink the pixel pitch to smaller than 75 µm for microcalcification detection and possible reduction of the DBT mean glandular dose (MGD). METHODS: In this study, imaging performance of a large area (29×23 cm2) CMOS APS x-ray imager [Dexela 2923 MAM (PerkinElmer, London)] with a pixel pitch of 75 µm was characterized and modeled. The authors developed a cascaded system model for CMOS APS x-ray imagers using both a broadband x-ray radiation and monochromatic synchrotron radiation. The experimental data including modulation transfer function, noise power spectrum, and detective quantum efficiency (DQE) were theoretically described using the proposed cascaded system model with satisfactory consistency to experimental results. Both high full well and low full well (LFW) modes of the Dexela 2923 MAM CMOS APS x-ray imager were characterized and modeled. The cascaded system analysis results were further used to extract the contrast-to-noise ratio (CNR) for microcalcifications with sizes of 165-400 µm at various MGDs. The impact of electronic noise on CNR was also evaluated. RESULTS: The LFW mode shows better DQE at low air kerma (Ka<10 µGy) and should be used for DBT. At current DBT applications, air kerma (Ka∼10 µGy, broadband radiation of 28 kVp), DQE of more than 0.7 and ∼0.3 was achieved using the LFW mode at spatial frequency of 0.5 line pairs per millimeter (lp/mm) and Nyquist frequency ∼6.7 lp/mm, respectively. It is shown that microcalcifications of 165-400 µm in size can be resolved using a MGD range of 0.3-1 mGy, respectively. In comparison to a General Electric GEN2 prototype DBT system (at MGD of 2.5 mGy), an increased CNR (by ∼10) for microcalcifications was observed using the Dexela 2923 MAM CMOS APS x-ray imager at a lower MGD (2.0 mGy). CONCLUSIONS: The Dexela 2923 MAM CMOS APS x-ray imager is capable to achieve a high imaging performance at spatial frequencies up to 6.7 lp/mm. Microcalcifications of 165 µm are distinguishable based on reported data and their modeling results due to the small pixel pitch of 75 µm. At the same time, potential dose reduction is expected using the studied CMOS APS x-ray imager.

Amorphous In-Ga-Zn-O thin-film transistor active pixel sensor x-ray imager for digital breast tomosynthesis.

PURPOSE: The breast cancer detection rate for digital breast tomosynthesis (DBT) is limited by the x-ray image quality. The limiting Nyquist frequency for current DBT systems is around 5 lp/mm, while the fine image details contained in the high spatial frequency region (>5 lp/mm) are lost. Also today the tomosynthesis patient dose is high (0.67-3.52 mGy). To address current issues, in this paper, for the first time, a high-resolution low-dose organic photodetector/amorphous In-Ga-Zn-O thin-film transistor (a-IGZO TFT) active pixel sensor (APS) x-ray imager is proposed for next generation DBT systems. METHODS: The indirect x-ray detector is based on a combination of a novel low-cost organic photodiode (OPD) and a cesium iodide-based (CsI:Tl) scintillator. The proposed APS x-ray imager overcomes the difficulty of weak signal detection, when small pixel size and low exposure conditions are used, by an on-pixel signal amplification with a significant charge gain. The electrical performance of a-IGZO TFT APS pixel circuit is investigated by SPICE simulation using modified Rensselaer Polytechnic Institute amorphous silicon (a-Si:H) TFT model. Finally, the noise, detective quantum efficiency (DQE), and resolvability of the complete system are modeled using the cascaded system formalism. RESULTS: The result demonstrates that a large charge gain of 31-122 is achieved for the proposed high-mobility (5-20 cm2/V s) amorphous metal-oxide TFT APS. The charge gain is sufficient to eliminate the TFT thermal noise, flicker noise as well as the external readout circuit noise. Moreover, the low TFT (<10(-13) A) and OPD (<10(-8) A/cm2) leakage currents can further reduce the APS noise. Cascaded system analysis shows that the proposed APS imager with a 75 µm pixel pitch can effectively resolve the Nyquist frequency of 6.67 lp/mm, which can be further improved to ∼10 lp/mm if the pixel pitch is reduced to 50 µm. Moreover, the detector entrance exposure per projection can be reduced from 1 to 0.3 mR without a significant reduction of DQE. The signal-to-noise ratio of the a-IGZO APS imager under 0.3 mR x-ray exposure is comparable to that of a-Si:H passive pixel sensor imager under 1 mR, indicating good image quality under low dose. A threefold reduction of current tomosynthesis dose is expected if proposed technology is combined with an advanced DBT image reconstruction method. CONCLUSIONS: The proposed a-IGZO APS x-ray imager with a pixel pitch<75 µm is capable to achieve a high spatial frequency (>6.67 lp/mm) and a low dose (<0.4 mGy) in next generation DBT systems.