Impact of super-resolution and image acquisition on the detection of calcifications in digital breast tomosynthesis.

OBJECTIVES: A virtual clinical trial (VCT) method is proposed to determine the limit of calcification detection in tomosynthesis. METHODS: Breast anatomy, focal findings, image acquisition, and interpretation (n = 14 readers) were simulated using screening data (n = 660 patients). Calcifications (0.2-0.4 mm3) were inserted into virtual breast phantoms. Digital breast tomosynthesis (DBT) acquisitions were simulated assuming various acquisition geometries: source motion (continuous and step-and-shoot), detector element size (140 and 70 µm), and reconstructed voxel size (35-140 µm). VCT results were estimated using multiple-reader multiple-case analyses and d' statistics. Signal-to-noise (SNR) analyses were also performed using BR3D phantoms. RESULTS: Source motion and reconstructed voxel size demonstrated significant changes in the performance of imaging systems. Acquisition geometries that use 70 µm reconstruction voxel size and step-and-shoot motion significantly improved calcification detection. Comparing 70 with 100 µm reconstructed voxel size for step-and-shoot, the ΔAUC was 0.0558 (0.0647) and d' ratio was 1.27 (1.29) for 140 µm (70 µm) detector element size. Comparing step-and-shoot with a continuous motion for a 70 µm reconstructed voxel size, the ΔAUC was 0.0863 (0.0434) and the d' ratio was 1.40 (1.19) for 140 µm (70 µm) detector element. Small detector element sizes (e.g., 70 µm) did not significantly improve detection. The SNR results with the BR3D phantom show that calcification detection is dependent upon reconstructed voxel size and detector element size, supporting VCT results with comparable agreement (ratios: d' = 1.16 ± 0.11, SNR = 1.34 ± 0.13). CONCLUSION: DBT acquisition geometries that use super-resolution (smaller reconstructed voxels than the detector element size) combined with step-and-shoot motion have the potential to improve the detection of calcifications. CLINICAL RELEVANCE: Calcifications may not always be discernable in tomosynthesis because of differences in acquisition and reconstruction methods. VCTs can identify strategies to optimize acquisition and reconstruction parameters for calcification detection in tomosynthesis, most notably through super-resolution in the reconstruction. KEY POINTS: • Super-resolution improves calcification detection and SNR in tomosynthesis; specifically, with the use of smaller reconstruction voxels. • Calcification detection using step-and-shoot motion is superior to that using continuous tube motion. • A detector element size of 70 µm does not provide better detection than 140 µm for small calcifications at the threshold of detectability.

Fully Automated Volumetric Breast Density Estimation from Digital Breast Tomosynthesis.

Background While digital breast tomosynthesis (DBT) is rapidly replacing digital mammography (DM) in breast cancer screening, the potential of DBT density measures for breast cancer risk assessment remains largely unexplored. Purpose To compare associations of breast density estimates from DBT and DM with breast cancer. Materials and Methods This retrospective case-control study used contralateral DM/DBT studies from women with unilateral breast cancer and age- and ethnicity-matched controls (September 19, 2011-January 6, 2015). Volumetric percent density (VPD%) was estimated from DBT using previously validated software. For comparison, the publicly available Laboratory for Individualized Breast Radiodensity Assessment software package, or LIBRA, was used to estimate area-based percent density (APD%) from raw and processed DM images. The commercial Quantra and Volpara software packages were applied to raw DM images to estimate VPD% with use of physics-based models. Density measures were compared by using Spearman correlation coefficients (r), and conditional logistic regression was performed to examine density associations (odds ratios [OR]) with breast cancer, adjusting for age and body mass index. Results A total of 132 women diagnosed with breast cancer (mean age ± standard deviation [SD], 60 years ± 11) and 528 controls (mean age, 60 years ± 11) were included. Moderate correlations between DBT and DM density measures (r = 0.32-0.75; all P < .001) were observed. Volumetric density estimates calculated from DBT (OR, 2.3 [95% CI: 1.6, 3.4] per SD for VPD%DBT) were more strongly associated with breast cancer than DM-derived density for both APD% (OR, 1.3 [95% CI: 0.9, 1.9] [P < .001] and 1.7 [95% CI: 1.2, 2.3] [P = .004] per SD for LIBRA raw and processed data, respectively) and VPD% (OR, 1.6 [95% CI: 1.1, 2.4] [P = .01] and 1.7 [95% CI: 1.2, 2.6] [P = .04] per SD for Volpara and Quantra, respectively). Conclusion The associations between quantitative breast density estimates and breast cancer risk are stronger for digital breast tomosynthesis compared with digital mammography. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Yaffe in this issue.

Dose Reduction in Molecular Breast Imaging With a New Image-Processing Algorithm.

OBJECTIVE. The purpose of this study was to determine whether application of a proprietary image-processing algorithm would allow a reduction in the necessary administered activity for molecular breast imaging (MBI) examinations. MATERIALS AND METHODS. Images from standard-dose MBI examinations (300 MBq 99mTc-sestamibi) of 50 subjects were analyzed. The images were acquired in dynamic mode and showed at least one breast lesion. Half-dose MBI examinations were simulated by summing one-half of the dynamic frames and were processed with the algorithm under study in both a default and a preferred filter mode. Two breast radiologists independently completed a set of two-alternative forced-choice tasks to compare lesion conspicuity on standard-dose images, half-dose images, and the algorithm-processed half-dose images in both modes. RESULTS. Relative to the standard-dose images, the half-dose images were preferred in 4, the default-filtered half-dose images in 50, and preferred-filtered half-dose images in 76 of 100 readings. Compared with standard-dose images, in terms of lesion conspicuity, the half-dose images were rated better in 2, equivalent in 6, and poorer in 92 of 100 readings. The default-filtered half-dose images were rated better, equivalent, or poorer in 13, 73, and 14 of 100 readings. The preferred-filtered half-dose images were rated as better, equivalent, or poorer in 55, 34, and 11 of 100 readings. CONCLUSION. Compared with that on standard-dose images, lesion conspicuity on images obtained with the algorithm and acquired at one-half the standard dose was equivalent or better without compromise of image quality. The algorithm can also be used to decrease imaging time with a resulting increase in patient comfort and throughput.

Imaging With Synthesized 2D Mammography: Differences, Advantages, and Pitfalls Compared With Digital Mammography.

OBJECTIVE: Synthesized 2D (s2D) mammography is rapidly replacing digital mammography in breast imaging with digital breast tomosynthesis (DBT) to reduce radiation dose and maintain screening outcomes. We illustrate variations in the appearance of s2D and digital mammograms to aid in implementation of this technology. CONCLUSION: Despite subjective differences in the appearance of s2D and digital mammograms, early outcomes of screening using s2D mammography and DBT are not inferior to those achieved with digital mammography and DBT. Understanding these variations may aid in implementing this technique and improving patient outcomes.

Implementation of Synthesized Two-dimensional Mammography in a Population-based Digital Breast Tomosynthesis Screening Program.

Purpose To evaluate the early implementation of synthesized two-dimensional (s2D) mammography in a population screened entirely with s2D and digital breast tomosynthesis (DBT) (referred to as s2D/DBT) and compare recall rates and cancer detection rates to historic outcomes of digital mammography combined with DBT (referred to as digital mammography/DBT) screening. Materials and Methods This was an institutional review board-approved and HIPAA-compliant retrospective interpretation of prospectively acquired data with waiver of informed consent. Compared were recall rates, biopsy rates, cancer detection rates, and radiation dose for 15 571 women screened with digital mammography/DBT from October 1, 2011, to February 28, 2013, and 5366 women screened with s2D/DBT from January 7, 2015, to June 30, 2015. Two-sample z tests of equal proportions were used to determine statistical significance. Results Recall rate for s2D/DBT versus digital mammography/DBT was 7.1% versus 8.8%, respectively (P < .001). Biopsy rate for s2D/DBT versus digital mammography/DBT decreased (1.3% vs 2.0%, respectively; P = .001). There was no significant difference in cancer detection rate for s2D/DBT versus digital mammography/DBT (5.03 of 1000 vs 5.45 of 1000, respectively; P = .72). The average glandular dose was 39% lower in s2D/DBT versus digital mammography/DBT (4.88 mGy vs 7.97 mGy, respectively; P < .001). Conclusion Screening with s2D/DBT in a large urban practice resulted in similar outcomes compared with digital mammography/DBT imaging. Screening with s2D/DBT allowed for the benefits of DBT with a decrease in radiation dose compared with digital mammography/DBT. © RSNA, 2016 An earlier incorrect version of this article appeared online. This article was corrected on August 11, 2016.

Development of silica-encapsulated silver nanoparticles as contrast agents intended for dual-energy mammography.

OBJECTIVE: Dual-energy (DE) mammography has recently entered the clinic. Previous theoretical and phantom studies demonstrated that silver provides greater contrast than iodine for this technique. Our objective was to characterize and evaluate in vivo a prototype silver contrast agent ultimately intended for DE mammography. METHODS: The prototype silver contrast agent was synthesized using a three-step process: synthesis of a silver core, silica encapsulation and PEG coating. The nanoparticles were then injected into mice to determine their accumulation in various organs, blood half-life and dual-energy contrast. All animal procedures were approved by the institutional animal care and use committee. RESULTS: The final diameter of the nanoparticles was measured to be 102 (±9) nm. The particles were removed from the vascular circulation with a half-life of 15 min, and accumulated in macrophage-rich organs such as the liver, spleen and lymph nodes. Dual-energy subtraction techniques increased the signal difference-to-noise ratio of the particles by as much as a factor of 15.2 compared to the single-energy images. These nanoparticles produced no adverse effects in mice. CONCLUSION: Silver nanoparticles are an effective contrast agent for dual-energy x-ray imaging. With further design improvements, silver nanoparticles may prove valuable in breast cancer screening and diagnosis. KEY POINTS: • Silver has potential as a contrast agent for DE mammography. • Silica-coated silver nanoparticles are biocompatible and suited for in vivo use. • Silver nanoparticles produce strong contrast in vivo using DE mammography imaging systems.

Digital breast tomosynthesis: lessons learned from early clinical implementation.

The limitations of mammography are well known and are partly related to the fact that with conventional imaging, the three-dimensional volume of the breast is imaged and presented in a two-dimensional format. Because normal breast tissue is similar in x-ray attenuation to some breast cancers, clinically relevant malignancies may be obscured by normal overlapping tissue. In addition, complex areas of normal tissue may be perceived as suspicious. The limitations of two-dimensional breast imaging lead to low sensitivity in detecting some cancers and high false-positive recall rates. Although mammographic screening has been shown to reduce breast cancer deaths by approximately 30%, controversy exists over when and how often screening mammography should occur. Digital breast tomosynthesis (DBT) is rapidly being implemented in breast imaging clinics around the world as early clinical data demonstrate that it may address some of the limitations of conventional mammography. With DBT, multiple low-dose x-ray images are acquired in an arc and reconstructed to create a three-dimensional image, thus minimizing the impact of overlapping breast tissue and improving lesion conspicuity. Early studies of screening DBT have shown decreased false-positive callback rates and increased rates of cancer detection (particularly for invasive cancers), resulting in increased sensitivity and specificity. In our clinical practice, we have completed more than 2 years of using two-view digital mammography combined with two-view DBT for all screening and select diagnostic imaging examinations (over 25,000 patients). Our experience, combined with previously published data, demonstrates that the combined use of DBT and digital mammography is associated with improved outcomes for screening and diagnostic imaging. Online supplemental material is available for this article.

Line-based iterative geometric calibration method for a tomosynthesis system.

BACKGROUND: A next generation tomosynthesis (NGT) system, capable of two-dimensional source motion, detector motion in the perpendicular direction, and magnification tomosynthesis, was constructed to investigate different acquisition geometries. Existing position-based geometric calibration methods proved ineffective when applied to the NGT geometries. PURPOSE: A line-based iterative calibration method is developed to perform accurate geometric calibration for the NGT system. METHODS: The proposed method calculates the system geometry through virtual line segments created by pairs of fiducials within a calibration phantom, by minimizing the error between the line equations computed from the true and estimated fiducial projection pairs. It further attempts to correct the 3D fiducial locations based on the initial geometric calibration. The method's performance was assessed via simulation and experimental setups with four distinct NGT geometries: X, T, XZ, and TZ. The X geometry resembles a conventional DBT acquisition along the chest wall. The T geometry forms a "T"-shaped source path in mediolateral (ML) and posteroanterior (PA) directions. A descending detector motion is added to both X and T geometries to form the XZ and TZ geometries, respectively. Simulation studies were conducted to assess the robustness of the method to geometric perturbations and inaccuracies in fiducial locations. Experimental studies were performed to assess the impact of phantom magnification and the performance of the proposed method for various geometries, compared to the traditional position-based method. Star patterns were evaluated for both qualitative and quantitative analyses; the Fourier spectral distortions (FSDs) graphs and the contrast transfer function (CTF) were extracted. The limit of spatial resolution (LSR) was measured at 5% modulation of the CTF. RESULTS: The proposed method presented is highly robust to geometric perturbation and fiducial inaccuracies. After the line-based iterative method, the mean distance between the true and estimated fiducial projections was [X, T, XZ, TZ]: [0.01, 0.01, 0.02, 0.01] mm. The impact of phantom magnification was observed; a contact-mode acquisition of a calibration phantom successfully provided an accurate geometry for 1.85× magnification images of a star pattern, with the X geometry. The FSD graphs for the contact-mode T geometry acquisition presented evidence of super-resolution, with the LSR of [0°-quadrant: 8.57, 90°-quadrant: 8.47] lp/mm. Finally, a contact-mode XZ geometry acquisition and a 1.50× magnification TZ geometry acquisition were reconstructed with three calibration methods-position-based, line-based, and iterative line-based. As more advanced methods are applied, the CTF becomes more isotropic, the FSD graphs demonstrate less spectral leakage as super-resolution is achieved, and the degree of blurring artifacts reduces significantly. CONCLUSIONS: This study introduces a robust calibration method tailored to the unique requirements of advanced tomosynthesis systems. By employing virtual line segments and iterative techniques, we ensure accurate geometric calibration while mitigating the limitations posed by the complex acquisition geometries of the NGT system. Our method's ability to handle various NGT configurations and its tolerance to fiducial misalignment make it a superior choice compared to traditional calibration techniques.

Non-Isocentric Geometry for Next-Generation Tomosynthesis With Super-Resolution.

Our lab at the University of Pennsylvania (UPenn) is investigating novel designs for digital breast tomosynthesis. We built a next-generation tomosynthesis system with a non-isocentric geometry (superior-to-inferior detector motion). This paper examines four metrics of image quality affected by this design. First, aliasing was analyzed in reconstructions prepared with smaller pixelation than the detector. Aliasing was assessed with a theoretical model of r -factor, a metric calculating amplitudes of alias signal relative to input signal in the Fourier transform of the reconstruction of a sinusoidal object. Aliasing was also assessed experimentally with a bar pattern (illustrating spatial variations in aliasing) and 360°-star pattern (illustrating directional anisotropies in aliasing). Second, the point spread function (PSF) was modeled in the direction perpendicular to the detector to assess out-of-plane blurring. Third, power spectra were analyzed in an anthropomorphic phantom developed by UPenn and manufactured by Computerized Imaging Reference Systems (CIRS), Inc. (Norfolk, VA). Finally, calcifications were analyzed in the CIRS Model 020 BR3D Breast Imaging Phantom in terms of signal-to-noise ratio (SNR); i.e., mean calcification signal relative to background-tissue noise. Image quality was generally superior in the non-isocentric geometry: Aliasing artifacts were suppressed in both theoretical and experimental reconstructions prepared with smaller pixelation than the detector. PSF width was also reduced at most positions. Anatomic noise was reduced. Finally, SNR in calcification detection was improved. (A potential trade-off of smaller-pixel reconstructions was reduced SNR; however, SNR was still improved by the detector-motion acquisition.) In conclusion, the non-isocentric geometry improved image quality in several ways.

Proceedings Virtual Imaging Trials in Medicine 2024.

This submission comprises the proceedings of the 1st Virtual Imaging Trials in Medicine conference, organized by Duke University on April 22-24, 2024. The listed authors serve as the program directors for this conference. The VITM conference is a pioneering summit uniting experts from academia, industry and government in the fields of medical imaging and therapy to explore the transformative potential of in silico virtual trials and digital twins in revolutionizing healthcare. The proceedings are categorized by the respective days of the conference: Monday presentations, Tuesday presentations, Wednesday presentations, followed by the abstracts for the posters presented on Monday and Tuesday.

Spatial dependency of multiplanar reconstruction in digital breast tomosynthesis.

Tomosynthesis acquires projections over a limited angular range, resulting in anisotropic sampling in the Fourier domain. The volume of the sampled space is therefore spatially dependent; different Fourier components are sampled for the same object, depending upon where the object is located relative to the system origin. A next-generation tomosynthesis (NGT) system was developed at the University of Pennsylvania to increase the spatial isotropy in DBT, by incorporating additional system motions. In this work, we investigate the spatial dependency of image quality in tomosynthesis and compare conventional and NGT tomosynthesis in terms of multiplanar reconstruction (MPR). Two test objects, a high-frequency star pattern and a low-frequency octagon phantom, were placed throughout the detector field of view at various obliquities to analyze the anisotropic nature of tomosynthesis. Reconstructions of the star pattern were analyzed both qualitatively and quantitatively using the Fourier distortion metric (FSD). Reconstructions of the octagon phantom were analyzed qualitatively. In a separate experiment, a container filled with water and acrylic beads of various diameters were imaged at various locations to simulate low-contrast objects mimicking breast tissue. We show that the spatial dependency of MPR is unique to the tilt angle, orientation, and frequency of the input. The NGT geometry benefitted the visualization of objects by reducing the out-of-plane artifacts in MPR.

Impact of Tomosynthesis Acquisition on 3D Segmentations of Breast Outline and Adipose/Dense Tissue with AI: A Simulation-Based Study.

Digital breast tomosynthesis (DBT) reconstructions introduce out-of-plane artifacts and false-tissue boundaries impacting the dense/adipose and breast outline (convex hull) segmentations. A virtual clinical trial method was proposed to segment both the breast tissues and the breast outline in DBT reconstructions. The DBT images of a representative population were simulated using three acquisition geometries: a left-right scan (conventional, I), a two-directional scan in the shape of a "T" (II), and an extra-wide range (XWR, III) left-right scan at a six-times higher dose than I. The nnU-Net was modified including two losses for segmentation: (1) tissues and (2) breast outline. The impact of loss (1) and the combination of loss (1) and (2) was evaluated using models trained with data simulating geometry I. The impact of the geometry was evaluated using the combined loss (1&2). The loss (1&2) improved the convex hull estimates, resolving 22.2% of the false classification of air voxels. Geometry II was superior to I and III, resolving 99.1% and 96.8% of the false classification of air voxels. Geometry III (Dice = (0.98, 0.94)) was superior to I (0.92, 0.78) and II (0.93, 0.74) for the tissue segmentation (adipose, dense, respectively). Thus, the loss (1&2) provided better segmentation, and geometries T and XWR improved the dense/adipose and breast outline segmentations relative to the conventional scan.

Multiclass Segmentation of Breast Tissue and Suspicious Findings: A Simulation-Based Study for the Development of Self-Steering Tomosynthesis.

In breast tomosynthesis, multiple low-dose projections are acquired in a single scanning direction over a limited angular range to produce cross-sectional planes through the breast for three-dimensional imaging interpretation. We built a next-generation tomosynthesis system capable of multidirectional source motion with the intent to customize scanning motions around "suspicious findings". Customized acquisitions can improve the image quality in areas that require increased scrutiny, such as breast cancers, architectural distortions, and dense clusters. In this paper, virtual clinical trial techniques were used to analyze whether a finding or area at high risk of masking cancers can be detected in a single low-dose projection and thus be used for motion planning. This represents a step towards customizing the subsequent low-dose projection acquisitions autonomously, guided by the first low-dose projection; we call this technique "self-steering tomosynthesis." A U-Net was used to classify the low-dose projections into "risk classes" in simulated breasts with soft-tissue lesions; class probabilities were modified using post hoc Dirichlet calibration (DC). DC improved the multiclass segmentation (Dice = 0.43 vs. 0.28 before DC) and significantly reduced false positives (FPs) from the class of the highest risk of masking (sensitivity = 81.3% at 2 FPs per image vs. 76.0%). This simulation-based study demonstrated the feasibility of identifying suspicious areas using a single low-dose projection for self-steering tomosynthesis.

Observation of super-resolution in digital breast tomosynthesis.

PURPOSE: Digital breast tomosynthesis (DBT) is a 3D x-ray imaging modality in which tomographic sections of the breast are generated from a limited range of tube angles. Because oblique x-ray incidence shifts the image of an object in subpixel detector element increments with each increasing projection angle, it is demonstrated that DBT is capable of super-resolution (i.e., subpixel resolution). METHODS: By convention, DBT reconstructions are performed on planes parallel to the breast support at various depths of the breast volume. In order for resolution in each reconstructed slice to be comparable to the detector, the pixel size should match that of the detector elements; hence, the highest frequency that can be resolved in the plane of reconstruction is the alias frequency of the detector. This study considers reconstruction grids with much smaller pixelation to visualize higher frequencies. For analytical proof of super-resolution, a theoretical framework is developed in which the reconstruction of a high frequency sinusoidal input is calculated using both simple backprojection (SBP) and filtered backprojection. To study the frequency spectrum of the reconstruction, its Fourier transform is also determined. The experimental feasibility of super-resolution was investigated by acquiring images of a bar pattern phantom with frequencies higher than the detector alias frequency. RESULTS: Using analytical modeling, it is shown that the central projection cannot resolve frequencies exceeding the detector alias frequency. The Fourier transform of the central projection is maximized at a lower frequency than the input as evidence of aliasing. By contrast, SBP reconstruction can resolve the input, and its Fourier transform is correctly maximized at the input frequency. Incorporating filters into the reconstruction smoothens pixelation artifacts in the spatial domain and reduces spectral leakage in the Fourier domain. It is also demonstrated that the existence of super-resolution is dependent on position in the reconstruction and on the directionality of the input frequency. Consistent with the analytical results, experimental reconstructions of bar patterns showed visibility of frequencies greater than the detector alias frequency. Super-resolution was present at positions predicted from analytical modeling. CONCLUSIONS: This work demonstrates the existence of super-resolution in DBT. Super-resolution has the potential to impact the visualization of fine structural details in the breast, such as microcalcifications and other subtle signs of cancer.

Optimized generation of high resolution breast anthropomorphic software phantoms.

PURPOSE: The authors present an efficient method for generating anthropomorphic software breast phantoms with high spatial resolution. Employing the same region growing principles as in their previous algorithm for breast anatomy simulation, the present method has been optimized for computational complexity to allow for fast generation of the large number of phantoms required in virtual clinical trials of breast imaging. METHODS: The new breast anatomy simulation method performs a direct calculation of the Cooper's ligaments (i.e., the borders between simulated adipose compartments). The calculation corresponds to quadratic decision boundaries of a maximum a posteriori classifier. The method is multiscale due to the use of octree-based recursive partitioning of the phantom volume. The method also provides user-control of the thickness of the simulated Cooper's ligaments and skin. RESULTS: Using the proposed method, the authors have generated phantoms with voxel size in the range of (25-1000 µm)(3)∕voxel. The power regression of the simulation time as a function of the reciprocal voxel size yielded a log-log slope of 1.95 (compared to a slope of 4.53 of our previous region growing algorithm). CONCLUSIONS: A new algorithm for computer simulation of breast anatomy has been proposed that allows for fast generation of high resolution anthropomorphic software phantoms.

Hepatic dual-contrast CT imaging: slow triple kVp switching CT with CNN-based sinogram completion and material decomposition.

Purpose: Dual-contrast protocols are a promising clinical multienergy computed tomography (CT) application for focal liver lesion detection and characterization. One avenue to enable multienergy CT is the introduction of photon-counting detectors (PCD). Although clinical translation is highly desired because of the diagnostic benefits of PCDs, it will still be a decade or more before they are broadly available. In our work, we investigated an alternative solution that can be implemented on widely used conventional CT systems (single source and integrating detector) to perform multimaterial spectral decomposition for dual-contrast imaging. Approach: We propose to slowly alternate the x-ray tube voltage between 3 kVp levels so each kVp level covers a few degrees of gantry rotation. This leads to the challenge of sparsely sampled projection data in each energy level. Performing the material decomposition (MD) in the sinogram domain is not directly possible as the projection images of the three energy levels are not angularly aligned. In order to overcome this challenge, we developed a convolutional neural network (CNN) framework for sparse sinogram completion (SC) and MD. To evaluate the feasibility of the slow kVp switching scheme, simulation studies of an abdominal phantom, which included liver lesions, were conducted. Results: The line-integral SC network yielded sinograms with a pixel-wise RMSE < 0.05 of the line-integrals compared to the ground truth. This provided acceptable image quality up to a switching angle of 9 deg per kVp. The MD network we developed allowed us to differentiate iodine and gadolinium in the sinogram domain. The average relative quantification errors for iodine and gadolinium were below 10%. Conclusions: We developed a slow triple kVp switching data acquisition scheme and a CNN-based data processing pipeline. Results from a digital phantom validation illustrate the potential for future applications of dual-contrast agent protocols on practically available single-energy CT systems.

Computer simulations of case difficulty in digital breast tomosynthesis using virtual clinical trials.

PURPOSE: Virtual clinical trials (VCTs) require computer simulations of representative patients and images to evaluate and compare changes in performance of imaging technologies. The simulated images are usually interpreted by model observers whose performance depends upon the selection of imaging cases used in training evaluation models. This work proposes an efficient method to simulate and calibrate soft tissue lesions, which matches the detectability threshold of virtual and human readings. METHODS: Anthropomorphic breast phantoms were used to evaluate the simulation of four mass models (I-IV) that vary in shape and composition of soft tissue. Ellipsoidal (I) and spiculated (II-IV) masses were simulated using composite voxels with partial volumes. Digital breast tomosynthesis projections and reconstructions of a clinical system were simulated. Channelized Hotelling observers (CHOs) were evaluated using reconstructed slices of masses that varied in shape, composition, and density of surrounded tissue. The detectability threshold of each mass model was evaluated using receiver operating characteristic (ROC) curves calculated with the CHO's scores. RESULTS: The area under the curve (AUC) of each calibrated mass model were within the 95% confidence interval (mean AUC [95% CI]) reported in a previous reader study (0.93 [0.89, 0.97]). The mean AUC [95% CI] obtained were 0.94 [0.93, 0.96], 0.92 [0.90, 0.93], 0.92 [0.90, 0.94], 0.93 [0.92, 0.95] for models I to IV, respectively. The mean AUC results varied substantially as a function of shape, composition, and density of surrounded tissue. CONCLUSIONS: For successful VCTs, lesions composed of soft tissue should be calibrated to simulate imaging cases that match the case difficulty predicted by human readers. Lesion composition, shape, and size are parameters that should be carefully selected to calibrate VCTs.

Achieving Isotropic Super-Resolution with a Non-Isocentric Acquisition Geometry in a Next-Generation Tomosynthesis System.

We have constructed a prototype next-generation tomosynthesis (NGT) system that supports a non-isocentric acquisition geometry for digital breast tomosynthesis (DBT). In this geometry, the detector gradually descends in the superior-to-inferior direction. The aim of this work is to demonstrate that this geometry offers isotropic super-resolution (SR), unlike clinical DBT systems which are characterized by anisotropies in SR. To this end, a theoretical model of a sinusoidal test object was developed with frequency exceeding the alias frequency of the detector. We simulated two geometries: (1) a conventional geometry with a stationary detector, and (2) a non-isocentric geometry. The input frequency was varied over the full 360° range of angles in the plane of the object. To investigate whether SR was achieved, we calculated the Fourier transform of the reconstruction. The amplitude of the tallest peak below the alias frequency was measured relative to the peak at the input frequency. This ratio (termed the r-factor) should approach zero to achieve high-quality SR. In the conventional geometry, the r-factor was minimized (approaching zero) if the orientation of the frequency was parallel with the source motion, yet exceeded unity (prohibiting SR) in the orientation perpendicular to the source motion. However, in the non-isocentric geometry, the r-factor was minimized (approaching zero) for all orientations of the frequency, meaning SR was achieved isotropically. In summary, isotropic SR in DBT can be achieved using the non-isocentric acquisition geometry supported by the NGT system.

Renally Excretable Silver Telluride Nanoparticles as Contrast Agents for X-ray Imaging.

The use of nanoparticles in the biomedical field has gained much attention due to their applications in biomedical imaging, drug delivery, and therapeutics. Silver telluride nanoparticles (Ag2Te NPs) have been recently shown to be highly effective computed tomography (CT) and dual-energy mammography contrast agents with good stability and biocompatibility, as well as to have potential for many other biomedical purposes. Despite their numerous advantageous properties for diagnosis and treatment of disease, the clinical translation of Ag2Te NPs is dependent on achieving high levels of excretion, a limitation for many nanoparticle types. In this work, we have synthesized and characterized a library of Ag2Te NPs and identified conditions that led to 3 nm core size and were renally excretable. We found that these nanoparticles have good biocompatibility, strong X-ray contrast generation, and rapid renal clearance. Our CT data suggest that renal elimination of nanoparticles occurred within 2 h of administration. Moreover, biodistribution data indicate that 93% of the injected dose (%ID) has been excreted from the main organs in 24 h, 95% ID in 7 days, and 97% ID in 28 days with no signs of acute toxicity in the tissues studied under histological analysis. To our knowledge, this renal clearance is the best reported for Ag2Te NP, while being comparable to the highest renal clearance reported for any type of nanoparticle. Together, the results herein presented suggest the use of GSH-Ag2Te NPs as an X-ray contrast agent with the potential to be clinically translated in the future.

MaasPenn Radiomics Reproducibility Score: A Novel Quantitative Measure for Evaluating the Reproducibility of CT-Based Handcrafted Radiomic Features.

The reproducibility of handcrafted radiomic features (HRFs) has been reported to be affected by variations in imaging parameters, which significantly affect the generalizability of developed signatures and translation to clinical practice. However, the collective effect of the variations in imaging parameters on the reproducibility of HRFs remains unclear, with no objective measure to assess it in the absence of reproducibility analysis. We assessed these effects of variations in a large number of scenarios and developed the first quantitative score to assess the reproducibility of CT-based HRFs without the need for phantom or reproducibility studies. We further assessed the potential of image resampling and ComBat harmonization for removing these effects. Our findings suggest a need for radiomics-specific harmonization methods. Our developed score should be considered as a first attempt to introduce comprehensive metrics to quantify the reproducibility of CT-based handcrafted radiomic features. More research is warranted to demonstrate its validity in clinical contexts and to further improve it, possibly by the incorporation of more realistic situations, which better reflect real patients' situations.