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Abstract: We have investigated a pre-breast collimator able to operate at variable heights for a photon-counting scanned multi-slit mammography system. A prototype system was built and used to evaluate how different collimator heights combined with optimized collimator slit widths affect dose efficiency and scan time. Moreover, new image construction software which takes into account the sub-pixel shift of each detector line was implemented and evaluated. With maintained scan time a collimator 79mm above patient support improved dose efficiency for a disc by 12% and by 22% for a scan time extended by 10%. For image reconstruction and the same disc size a dose efficiency improvement of 32%±9% was measured indicating a higher gain than expected. [Copyright &y& Elsevier]

Purpose: Digital breast tomosynthesis (DBT) is becoming an important part of breast cancer screening and diagnosis. Compared to two-dimensional mammography, tomosynthesis introduces limited three-dimensional (3D) resolution, but maintains high in-plane resolution, low dose, and allows for similar clinical protocols. The scanning motion and oblique projections of tomosynthesis acquisitions introduce shift-variance to the image quality, in addition to effects such as source blurring and geometric magnification. Shift-variant detector response caused by oblique incidence has been extensively studied previously and is most easily mitigated by letting the source and detector move in sync. In addition, conical reconstruction grids, that is, a grid aligned with the central tomosynthesis projection, have been proposed to compensate for magnification effects. This paper introduces a shift-variant cascaded systems model for tomosynthesis and validates it against measurements. As an example, the model was used to investigate the shift-variance of a tomosynthesis system., Methods: The shift-variant cascaded systems model was validated on a slit-scanning photon-counting DBT system, with synchronous source-detector movement, using simple back-projection in a conical reconstruction volume. The modulation transfer function (MTF), normalized noise-power spectrum (NNPS), and detective quantum efficiency (DQE) were used as figures of merit. Simulations were performed for single points while measurements were done over a finite volume, assuming local shift invariance. To investigate the full extent of shift-variance, 80 locations across the volume were simulated, and the MTF and DQE at 2.5 lp/mm were calculated as a function of position., Results: The simulated metrics generally agreed well with their corresponding measurements. The frequency at 50% MTF along the scan direction showed a relatively small variation, ranging from 2.1 to 2.4 lp/mm for the different locations. The frequency at 50% MTF along the chest-mammilla direction showed a larger variation, ranging from 2.9 to 3.8 lp/mm. All points exhibited a similarly shaped NNPS but the noise magnitude varied with slice height. The zero-frequency DQE in reconstructed slices was lower than that of the projections, an effect likely caused by noise-aliasing increasing the zero-frequency noise., Conclusions: A shift-variant cascaded systems model has been developed for slit-scanning tomosynthesis using simple back-projection. The model was successfully validated against measurements. Even though the study was performed on a slit-scanning system, several parts of the framework can be applied and extended to other tomosynthesis geometries. The conical reconstruction grid has low variation in image quality in the scan direction where the 3D information is acquired, but source and geometric magnification still dominate in the slit direction, causing a larger variation in image quality. We conclude that image quality is close to shift-invariant in the scan direction, but not in the height and chest-mammilla directions, and we recommend that small measurement volumes are used when measuring image quality in these directions to minimize the effects of shift variance., (© 2018 American Association of Physicists in Medicine.)

Purpose: Digital breast tomosynthesis (DBT) is an emerging tool for breast-cancer screening and diagnostics. The purpose of this study is to present a second-generation photon-counting slit-scanning DBT system and compare it to the first-generation system in terms of geometry and image quality. The study presents the first image-quality measurements on the second-generation system., Method: The geometry of the new system is based on a combined rotational and linear motion, in contrast to a purely rotational scan motion in the first generation. In addition, the calibration routines have been updated. Image quality was measured in the center of the image field in terms of in-slice modulation transfer function (MTF), artifact spread function (ASF), and in-slice detective quantum efficiency (DQE). Images were acquired using a W/Al 29 kVp spectrum at 13 mAs with 2 mm Al additional filtration and reconstructed using simple back-projection., Result: The in-slice 50% MTF was improved in the chest-mammilla direction, going from 3.2 to 3.5 lp/mm, and the zero-frequency DQE increased from 0.71 to 0.77. The MTF and ASF were otherwise found to be on par for the two systems. The new system has reduced in-slice variation of the tomographic angle., Conclusions: The new geometry is less curved, which reduces in-slice tomographic-angle variation, and increases the maximum compression height, making the system accessible for a larger population. The improvements in MTF and DQE were attributed to the updated calibration procedures. We conclude that the second-generation system maintains the key features of the photon-counting system while maintaining or improving image quality and improving the maximum compression height., (© 2017 American Association of Physicists in Medicine.)

Purpose: It has been shown that breast tomosynthesis may improve sensitivity and specificity compared to two-dimensional mammography, resulting in increased detection-rate of cancers or lowered call-back rates. The purpose of this study is to characterize a spectral photon-counting multislit breast tomosynthesis system that is able to do single-scan spectral imaging with multiple collimated x-ray beams. The system differs in many aspects compared to conventional tomosynthesis using energy-integrating flat-panel detectors., Methods: The investigated system was a prototype consisting of a dual-threshold photon-counting detector with 21 collimated line detectors scanning across the compressed breast. A review of the system is done in terms of detector, acquisition geometry, and reconstruction methods. Three reconstruction methods were used, simple back-projection, filtered back-projection and an iterative algebraic reconstruction technique. The image quality was evaluated by measuring the modulation transfer-function (MTF), normalized noise-power spectrum, detective quantum-efficiency (DQE), and artifact spread-function (ASF) on reconstructed spectral tomosynthesis images for a total-energy bin (defined by a low-energy threshold calibrated to remove electronic noise) and for a high-energy bin (with a threshold calibrated to split the spectrum in roughly equal parts). Acquisition was performed using a 29 kVp W/Al x-ray spectrum at a 0.24 mGy exposure., Results: The difference in MTF between the two energy bins was negligible, that is, there was no energy dependence on resolution. The MTF dropped to 50% at 1.5 lp/mm to 2.3 lp/mm in the scan direction and 2.4 lp/mm to 3.3 lp/mm in the slit direction, depending on the reconstruction method. The full width at half maximum of the ASF was found to range from 13.8 mm to 18.0 mm for the different reconstruction methods. The zero-frequency DQE of the system was found to be 0.72. The fraction of counts in the high-energy bin was measured to be 59% of the total detected spectrum. Scantimes ranged from 4 s to 16.5 s depending on voltage and current settings., Conclusions: The characterized system generates spectral tomosynthesis images with a dual-energy photon-counting detector. Measurements show a high DQE, enabling high image quality at a low dose, which is beneficial for low-dose applications such as screening. The single-scan spectral images open up for applications such as quantitative material decomposition and contrast-enhanced tomosynthesis., (© 2017 American Association of Physicists in Medicine.)

Novel x-ray medical imaging sensors, such as photon counting detectors (PCDs) and large area CCD and CMOS cameras can involve irregular and/or sparse sampling of the detector plane. Application of such detectors to CT involves undersampling that is markedly different from the commonly considered case of sparse angular sampling. This work investigates volumetric sampling in CT systems incorporating sparsely sampled detectors with axial and helical scan orbits and evaluates performance of model-based image reconstruction (MBIR) with spatially varying regularization in mitigating artifacts due to sparse detector sampling. Volumetric metrics of sampling density and uniformity were introduced. Penalized-likelihood MBIR with a spatially varying penalty that homogenized resolution by accounting for variations in local sampling density (i.e. detector gaps) was evaluated. The proposed methodology was tested in simulations and on an imaging bench based on a Si-strip PCD (total area 5 cm  ×  25 cm) consisting of an arrangement of line sensors separated by gaps of up to 2.5 mm. The bench was equipped with translation/rotation stages allowing a variety of scanning trajectories, ranging from a simple axial acquisition to helical scans with variable pitch. Statistical (spherical clutter) and anthropomorphic (hand) phantoms were considered. Image quality was compared to that obtained with a conventional uniform penalty in terms of structural similarity index (SSIM), image uniformity, spatial resolution, contrast, and noise. Scan trajectories with intermediate helical width (~10 mm longitudinal distance per 360° rotation) demonstrated optimal tradeoff between the average sampling density and the homogeneity of sampling throughout the volume. For a scan trajectory with 10.8 mm helical width, the spatially varying penalty resulted in significant visual reduction of sampling artifacts, confirmed by a 10% reduction in minimum SSIM (from 0.88 to 0.8) and a 40% reduction in the dispersion of SSIM in the volume compared to the constant penalty (both penalties applied at optimal regularization strength). Images of the spherical clutter and wrist phantoms confirmed the advantages of the spatially varying penalty, showing a 25% improvement in image uniformity and 1.8  ×  higher CNR (at matched spatial resolution) compared to the constant penalty. The studies elucidate the relationship between sampling in the detector plane, acquisition orbit, sampling of the reconstructed volume, and the resulting image quality. They also demonstrate the benefit of spatially varying regularization in MBIR for scenarios with irregular sampling patterns. Such findings are important and integral to the incorporation of a sparsely sampled Si-strip PCD in CT imaging.

Rationale and Objectives: The purpose of this study was to assess the performance of a MicroDose photon-counting full-field digital mammography (PCM) system in comparison to full-field digital mammography (FFDM) for area under the receiver-operating characteristic (ROC) curve (AUC), sensitivity, specificity, and feature analysis of standard-view mammography for women presenting for screening mammography, diagnostic mammography, or breast biopsy., Materials and Methods: A total of 133 women were enrolled in this study at two European medical centers, with 67 women who had a pre-existing 10-36 months FFDM enrolled prospectively into the study and 66 women who underwent breast biopsy and had screening PCM and diagnostic FFDM, including standard craniocaudal and mediolateral oblique views of the breast with the lesion, enrolled retrospectively. The case mix consisted of 49 cancers, 17 biopsy-benign cases, and 67 normal cases. Sixteen radiologists participated in the reader study and interpreted all 133 cases in both conditions, separated by washout period of ≥4 weeks. ROC curve and free-response ROC curve analyses were performed for noninferiority of PCM compared to FFDM using a noninferiority margin Δ value of 0.10. Feature analysis of the 66 cases with lesions was conducted with all 16 readers at the conclusion of the blinded reads. Mean glandular dose was recorded for all cases., Results: The AUC for PCM was 0.947 (95% confidence interval [CI], 0.920-0.974) and for FFDM was 0.931 (95% CI, 0.898-0.964). Sensitivity per case for PCM was 0.936 (95% CI, 0.897-0.976) and for FFDM was 0.908 (95% CI, 0.856-0.960). Specificity per case for PCM was 0.764 (95% CI, 0.688-0.841) and for FFDM was 0.749 (95% CI, 0.668-0.830). Free-response ROC curve figures of merit were 0.920 (95% CI, 0.881-0.959) and 0.903 (95% CI, 0.858-0.948) for PCM and FFDM, respectively. Sensitivity per lesion was 0.903 (95% CI, 0.846-0.960) and 0.883 (95% CI, 0.823-0.944) for PCM and FFDM, respectively. The average false-positive marks per image of noncancer cases were 0.265 (95% CI, 0.171-0.359) and 0.281 (95% CI, 0.188-0.374) for PCM and FFDM, respectively. Noninferiority P values for AUC, sensitivity (per case and per lesion), specificity, and average false-positive marks per image were all statistically significant (P < .001). The noninferiority P value for free-response ROC was <.025, from the 95% CI for the difference. Feature analysis resulted in PCM being preferred to FFDM by the readers for ≥70% of the cases. The average mean glandular dose for PCM was 0.74 mGy (95% CI, 0.722-0.759 mGy) and for FFDM was 1.23 mGy (95% CI, 1.199-1.262 mGy)., Conclusions: In this study, radiologist performance with PCM was not inferior to that with conventional FFDM at an average 40% lower mean glandular dose., (Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.)

As an initial step in defining the transcriptome of the North Atlantic right whale (Eubalaena glacialis) and developing functional genomic tools to study right whale health at the molecular physiological level, a cDNA library has been constructed from a skin biopsy. 2496 randomly selected clones (expressed sequence tags, ESTs) have been sequenced, and genes identified as important in the response to stress and immune challenges have been cloned by targeted RT-PCR from skin cDNA. The analysis of the EST collection (archived at www.marinegenomics.org and GenBank) showed a 34.79% redundancy, yielding 1578 unigenes and 27 potential microsatellite markers. 96 genes were cloned by targeted PCR; moreover, 52 of these genes are stress and immune function related. A Gene Ontology analysis of the unigene collection indicates that the skin is a rich source of expressed genes with diverse functions, suggesting an important role in multiple physiological processes including those related to immunity and stress response.

Teleosts and tetrapods have evolved different splice patterns to generate their membrane-bound IgM. In the tetrapod lineage, the first transmembrane exon is spliced to an internal cryptic site located close to the end of the fourth constant exon. Because teleosts lack this site they use the regular 3'-splice site of the CH3 exon instead. We characterized the mum splicing patterns in a Chondrostean, the Siberian sturgeon. We observed a surprising diversity of splice patterns, the TM1 exon being spliced to a cryptic site at the end of CH4, to a cryptic site in CH3 or to the 3'-end of CH1. These different pathways lead to mIGHM transcripts encoding four, two or one complete C-domain(s), respectively. The short variant CH1-TM1 was found only in VH2 positive transcripts, while the two other variants were observed for IgHM transcripts expressing all VH families. These results shed light on the evolution of IgM splicing pathways.

A transcriptional enhancer, Emu, was defined in the IGH locus of the Pekin duck, Anas platyrhynchos. Regions of DNA from the JH to IGHM intron were cloned into reporter constructs containing the SV40 promoter and transiently transfected into chicken B and T lymphocytes. A strong transcriptional activity, of several hundred-fold greater than that of a reporter construct with the promoter alone, was localized to a 281bp region that contains 2 E-box motifs, CAGCTG. This fragment showed enhancer activity in both orientations and was active in chicken B cells but not in T cells. When the activity of the enhancer was tested in constructs without a promoter, it showed high transcriptional activity in the forward orientation, but much less activity (by two orders of magnitude) when tested in the reverse orientation. This suggests that the fragment contains not only enhancer activity but may contain promoter activity analogous to that of the Imu promoter described in mammals. Thus it appears that the location, but not the fine structure, of the Emu enhancer was established before the evolutionary divergence of the avian and mammalian lineages some 300Myr ago.

A microarray focused on stress response and immune function genes of the bottlenosed dolphin has been developed. Random expressed sequence tags (ESTs) were isolated and sequenced from two dolphin peripheral blood leukocyte (PBL) cDNA libraries biased towards T- and B-cell gene expression by stimulation with IL-2 and LPS, respectively. A total of 2784 clones were sequenced and contig analysis yielded 1343 unigenes (archived and annotated at ). In addition, 52 dolphin genes known to be important in innate and adaptive immune function and stress responses of terrestrial mammals were specifically targeted, cloned and added to the unigene collection. The set of dolphin sequences printed on a cDNA microarray comprised the 1343 unigenes, the 52 targeted genes and 2305 randomly selected (but unsequenced) EST clones. This set was printed in duplicate spots, side by side, and in two replicates per slide, such that the total number of features per microarray slide was 19,200, including controls. The dolphin arrays were validated and transcriptomic profiles were generated using PBL from a wild dolphin, a captive dolphin and dolphin skin cells. The results demonstrate that the array is a reproducible and informative tool for assessing differential gene expression in dolphin PBL and in other tissues.

Large-insert genomic bacterial artificial chromosome (BAC) libraries of two culturally and economically important oyster species, Crassostrea virginica and C. gigas, have been developed as part of an international effort to develop tools and reagents that will advance our ability to conduct genetic and genomic research. A total of 73,728 C. gigas clones with an average insert size of 152 kb were picked and arrayed representing an 11.8-fold genome coverage. A total of 55,296 clones with an average insert size of 150 kb were picked and arrayed for C. virginica, also representing an 11.8-fold genome coverage. The C. gigas and C. virginica libraries were screened with probes derived from selected oyster genes using high-density BAC colony filter arrays. The probes identified 4 to 25 clones per gene for C. virginica and 5 to 50 clones per gene for C. gigas. We conducted a preliminary analysis of genetic polymorphism represented in the C. gigas library. The results suggest that the degree of divergence among similar sequences is highly variable and concentrated in intronic regions. Evidence supporting allelic polymorphism is reported for two genes and allelic and/or locus specific polymorphism for several others. Classical inheritance studies are needed to confirm the nature of these polymorphisms. The oyster BAC libraries are publicly available to the research community on a cost-recovery basis at (www.genome.clemson.edu).

Galliform and non-galliform birds express three immunoglobulin isotypes, IgM, IgA and IgY. Beyond this we should not generalize because differences in gene organization may have functional consequences reflected in the immune response. At present, studies on non-galliform birds are largely restricted to ducks. Ducks express an alternatively spliced form of their IgY heavy chain (upsilon) gene, the IgY(DeltaFc), that lacks the Fc region and Fc-associated secondary effector functions. It is not known how common the expression of the IgY(DeltaFc) is among birds, nor the functional consequences. It is also not known whether the unusual organization of the duck IgH locus, also shared with the chicken, having the gene order of mu, alpha and upsilon, with alpha inverted in the locus, is unique to the galloanseriform lineage. Ducks, like chickens, have a single immunoglobulin light chain of the lambda (lambda) type. Evidence suggests that ducks, like chickens, generate their immunoglobulin repertoire through a single functional rearrangement of the variable (V) region, and generate diversity through gene conversion from a pool of pseudogenes. In Southern blots of germline and rearranged bursal DNA, both the heavy and light chain loci of ducks appear to each undergo one major rearrangement event. For both heavy and light chains, the functional V region element and the pseudogenes appear to consist of a single gene family. Further analysis of 26 heavy chain joining (JH) and 27 light chain JL segments shows there is use of a single J segment in ducks, which is diversified presumably through somatic mutations and gene conversion events. Despite this limitation on the rearrangement of immunoglobulin genes, analysis of 26 DH and 122 VL sequences suggests that extensive sequence diversity is generated.

A theoretical evaluation of nonuniform x-ray field distributions in mammography was conducted. An automatic exposure control (AEC) is proposed for a scanning full field digital mammography system. It uses information from the leading part of the detector to vary the scan velocity dynamically, thus creating a nonuniform x-ray field in the scan direction. Nonuniform radiation fields were also created by numerically optimizing the scan velocity profile to each breast's transmission distribution, with constraints on velocity and acceleration. The goal of the proposed AEC is to produce constant pixel signal-to-noise ratio throughout the image. The target pixel SNR for each image could be set based on the breast thickness, breast composition, and the beam quality as to achieve the same contrast-to-noise ratio between images for structures of interest. The results are quantified in terms of reduction in entrance surface air kerma (ESAK) and scan time relative to a uniform x-ray field. The theoretical evaluation was performed on a set of 266 mammograms. The performance of the different methods to create nonuniform fields decreased with increased detector width, from 18% to 11% in terms of ESAK reduction and from 30% to 25% in terms of scan time reduction for the proposed AEC and detector widths from 10 to 60 mm. Some correlation was found between compressed breast thickness and the projected breast area onto the image field. This translated into an increase of the ESAK and decrease of the scan time reduction with breast thickness. Ideally a nonuniform field in two dimensions could reduce the entrance dose by 39% on average, whereas a field nonuniform in only the scanning dimension ideally yields a 20% reduction. A benefit with the proposed AEC is that the risk of underexposing the densest region of the breast can be virtually eliminated.