Maximizing microcalcification detectability in low-dose dedicated cone-beam breast CT: parallel cascades-based theoretical analysis.

Purpose: We aim to determine the combination of X-ray spectrum and detector scintillator thickness that maximizes the detectability of microcalcification clusters in dedicated cone-beam breast CT. Approach: A cascaded linear system analysis was implemented in the spatial frequency domain and was used to determine the detectability index using numerical observers for the imaging task of detecting a microcalcification cluster with 0.17 mm diameter calcium carbonate spheres. The analysis considered a thallium-doped cesium iodide scintillator coupled to a complementary metal-oxide semiconductor detector and an analytical filtered-back-projection reconstruction algorithm. Independent system parameters considered were the scintillator thickness, applied X-ray tube voltage, and X-ray beam filtration. The combination of these parameters that maximized the detectability index was considered optimal. Results: Prewhitening, nonprewhitening, and nonprewhitening with eye filter numerical observers indicate that the combination of 0.525 to 0.6 mm thick scintillator, 70 kV, and 0.25 to 0.4 mm added copper filtration maximized the detectability index at a mean glandular dose (MGD) of 4.5 mGy. Conclusion: Using parallel cascade systems' analysis, the combination of parameters that could maximize the detection of microcalcifications was identified. The analysis indicates that a harder beam than that used in current practice may be beneficial for the task of detecting microcalcifications at an MGD suitable for breast cancer screening.

An unusual artifact observed on screening mammography in a patient with an LVAD.

PURPOSE: Screening mammography and digital breast tomosynthesis consist of high-resolution x-ray images to identify findings that are potentially indicative of breast cancer, enabling early detection and reduction of breast cancer mortality. Imaging artifacts can occasionally occur, sometimes due to patient-related medical devices. Because of continuous evolution of new technologies, there is potential for novel artifacts to be encountered. In this technical note, we report an unusual artifact in the screening mammogram of a patient with an Abbott HeartMate 3 left ventricular assist device (LVAD). METHODS: A 72-year-old patient with a HeartMate 3 LVAD presented to our breast imaging facility for a standard screening exam with digital breast tomosynthesis (Selenia Dimensions, Hologic Inc., Bedford, MA) and synthetic 2D images (C-view, Hologic Inc., Bedford, MA). RESULTS: Linear artifacts oriented in the anteroposterior dimension demonstrating a spatial periodicity of ∼1.4 mm were seen on all left breast images, whereas concurrent right breast images did not demonstrate any artifacts. Repeat attempts using two identical digital breast tomosynthesis units demonstrated the same artifacts. No other exam at our imaging center that day demonstrated any such artifacts. Mammogram exams performed on this patient prior to her LVAD placement did not exhibit any similar artifacts. CONCLUSION: Findings support the patient's LVAD as the underlying source of linear artifacts observed on left breast images, particularly given the proximity of the LVAD to the left breast. With the number of patients receiving LVAD placement on the rise, as well as increasing median survival rates status post LVAD implantation, recognition of this LVAD related artifact on mammography may be important.

Dedicated Cone-Beam Breast CT: Reproducibility of Volumetric Glandular Fraction with Advanced Image Reconstruction Methods.

Dedicated cone-beam breast computed tomography (CBBCT) is an emerging modality and provides fully three-dimensional (3D) images of the uncompressed breast at an isotropic voxel resolution. In an effort to translate this modality to breast cancer screening, advanced image reconstruction methods are being pursued. Since radiographic breast density is an established risk factor for breast cancer and CBBCT provides volumetric data, this study investigates the reproducibility of the volumetric glandular fraction (VGF), defined as the proportion of fibroglandular tissue volume relative to the total breast volume excluding the skin. Four image reconstruction methods were investigated: the analytical Feldkamp-Davis-Kress (FDK), a compressed sensing-based fast, regularized, iterative statistical technique (FRIST), a fully supervised deep learning approach using a multi-scale residual dense network (MS-RDN), and a self-supervised approach based on Noise-to-Noise (N2N) learning. Projection datasets from 106 women who participated in a prior clinical trial were reconstructed using each of these algorithms at a fixed isotropic voxel size of (0.273 mm3). Each reconstructed breast volume was segmented into skin, adipose, and fibroglandular tissues, and the VGF was computed. The VGF did not differ among the four reconstruction methods (p = 0.167), and none of the three advanced image reconstruction algorithms differed from the standard FDK reconstruction (p > 0.862). Advanced reconstruction algorithms developed for low-dose CBBCT reproduce the VGF to provide quantitative breast density, which can be used for risk estimation.

Savi-Scout Radar Localization: Transitioning From the Traditional Wire Localization to Wireless Technology for Surgical Guidance at Lumpectomies.

Breast-conserving surgery or lumpectomy requires localization of the lesion prior to surgery, which is traditionally accomplished by imaging-guided wire localization. Over the last decade, alternatives to wire localization have emerged. This work reviews the literature on one such wireless technology, SaviScout radar (SSR) system, and shares our experience with using this technology for presurgical tumor localization. The SSR surgical guidance system is non-radioactive. The radiologist implants a reflector device in the breast under mammography or ultrasound guidance at any time prior to surgery. The placement of this reflector can be confirmed from the cadence of a handheld percutaneous probe of a handpiece and console system. Results from several studies show that the surgical outcomes from SSR and wire-localization are similar. SSR provides operational advantages as the scheduling for reflector placement by radiologists is decoupled from surgery, but at an increased cost compared to wire-localization.

Artificial Intelligence in Breast X-Ray Imaging.

This topical review is focused on the clinical breast x-ray imaging applications of the rapidly evolving field of artificial intelligence (AI). The range of AI applications is broad. AI can be used for breast cancer risk estimation that could allow for tailoring the screening interval and the protocol that are woman-specific and for triaging the screening exams. It also can serve as a tool to aid in the detection and diagnosis for improved sensitivity and specificity and as a tool to reduce radiologists' reading time. AI can also serve as a potential second 'reader' during screening interpretation. During the last decade, numerous studies have shown the potential of AI-assisted interpretation of mammography and to a lesser extent digital breast tomosynthesis; however, most of these studies are retrospective in nature. There is a need for prospective clinical studies to evaluate these technologies to better understand their real-world efficacy. Further, there are ethical, medicolegal, and liability concerns that need to be considered prior to the routine use of AI in the breast imaging clinic.

Audit of Prior Screening Mammograms of Screen-Detected Cancers: Implications for the Delay in Breast Cancer Detection.

When cancer is detected in a screening mammogram, on occasion retrospective review of prior screening (pre-index) mammograms indicates a likely presence of cancer. These missed cancers during pre-index screens constitute a delay in detection and diagnosis. This study was undertaken to quantify the missed cancer rate by auditing pre-index screens to improve the quality of mammography screening practice. From a cohort of 135 screen-detected cancers, 120 pre-index screening mammograms could be retrieved and served as the study sample. A consensus read by 2 radiologists who interpreted the pre-index screens in an unblinded manner with full knowledge of cancer location, cancer type, lesion type, and pathology served as the truth or reference standard. Five radiologists interpreted the pre-index screens in a blinded manner. Established performance metrics such as sensitivity and specificity were quantified for each reader in interpreting these pre-index screens in a blinded manner. All five radiologists detected lesions in 8/120 (6.7%) screens. Excluding the 2 readers whose performance was close to random, all the 3 remaining readers detected lesions in 13 pre-index screens. This indicates that there is a delay in diagnosis by at least one cycle from 8/120 (6.7%) to 13/120 (10.8%). There were no observable trends in terms of either the cancer type or the lesion type. Auditing prior screening mammograms in screen-detected cancers can help in identifying the proportion of cases that were missed during interpretation and help in quantifying the delay in breast cancer detection.

The Current State of Timeliness in the Breast Cancer Diagnosis Journey: Abnormal Screening to Biopsy.

There are several steps involved in a breast cancer diagnosis, starting from the initial abnormal screening mammogram. Each step from the additional imaging to a biopsy provokes anxiety. Timely attention to these appointments will not only help allay anxiety but also provide better care. While breast facilities routinely audit their performance, currently timeliness is not one of the audit parameters. The role of timeliness as a robust quality tool is gaining attention. In this study, we review the timeline of care at our facility over a 1-year period (October 2021- September 2022) and compare them with those reported by National Quality Measures for Breast Centers (NQMBC). Race, ethnicity, location, and type of facility affect the outcome of care and contribute to delays in providing care. In this manuscript, we outline some of the major factors. Societal guidelines outlining some metrics for timeliness may be a useful first step.

Dedicated cone-beam breast CT: Data acquisition strategies based on projection angle-dependent normalized glandular dose coefficients.

BACKGROUND: Dedicated cone-beam breast computed tomography (CBBCT) using short-scan acquisition is being actively investigated to potentially reduce the radiation dose to the breast. This would require determining the optimal x-ray source trajectory for such short-scan acquisition. PURPOSE: To quantify the projection angle-dependent normalized glandular dose coefficient ( D g N C T $Dg{N^{CT}}$ ) in CBBCT, referred to as angular D g N C T $Dg{N^{CT}}$ , so that the x-ray ray source trajectory that minimizes the radiation dose to the breast for short-scan acquisition can be determined. MATERIALS AND METHODS: A cohort of 75 CBBCT clinical datasets was segmented and used to generate three breast models - (I) patient-specific breast with heterogeneous fibroglandular tissue distribution and real breast shape, (II) patient-specific breast shape with homogeneous tissue distribution and matched fibroglandular weight fraction, and (III) homogeneous semi-ellipsoidal breast with patient-specific breast dimensions and matched fibroglandular weight fraction, which corresponds to the breast model used in current radiation dosimetry protocols. For each clinical dataset, the angular D g N C T $Dg{N^{CT}}$ was obtained at 10 discrete angles, spaced 36° apart, for full-scan, circular, x-ray source trajectory from Monte Carlo simulations. Model III is used for validating the Monte Carlo simulation results. Models II and III are used to determine if breast shape contributes to the observed trends in angular D g N C T $Dg{N^{CT}}$ . A geometry-based theory in conjunction with center-of-mass ( C O M $COM$ ) based distribution analysis is used to explain the projection angle-dependent variation in angular D g N C T $Dg{N^{CT}}$ . RESULTS: The theoretical model predicted that the angular D g N C T $Dg{N^{CT}}$ will follow a sinusoidal pattern and the amplitude of the sinusoid increases when the center-of-mass of fibroglandular tissue ( C O M f $CO{M_f}$ ) is farther from the center-of-mass of the breast ( C O M b $CO{M_b}$ ). It also predicted that the angular D g N C T $Dg{N^{CT}}$ will be minimized at x-ray source positions complementary to the C O M f $CO{M_f}$ . The C O M f $CO{M_f}$ was superior to the C O M b $CO{M_b}$ in 80% (60/75) of the breasts. From Monte Carlo simulations and for homogeneous breasts (models II and III), the deviation in breast shape from a semi-ellipsoid had minimal effect on angular D g N C T $Dg{N^{CT}}$ and showed less than 4% variation. From Monte Carlo simulations and for model I, as predicted by our theory, the angular D g N C T $Dg{N^{CT}}$ followed a sinusoidal pattern with maxima and minima at x-ray source positions superior and inferior to the breast, respectively. For model I, the projection angle-dependent variation in angular D g N C T $Dg{N^{CT}}$ was 16.4%. CONCLUSION: The heterogeneous tissue distribution affected the angular D g N C T $Dg{N^{CT}}$ more than the breast shape. For model I, the angular D g N C T $Dg{N^{CT}}$ was lowest when the x-ray source was inferior to the breast. Hence, for short-scan CBBCT acquisition with C O M b $CO{M_b}$ aligned with axis-of-rotation, an x-ray source trajectory inferior to the breast is preferable and such an acquisition spanning 205° can potentially reduce the mean glandular dose by up to 52%.

Value of BI-RADS 3 Audits.

Objectives: BI-RADS 3 is an established assessment category in which the probability of malignancy is equal to or less than 2%. However, monitoring adherence to imaging criteria can be challenging and there are few established benchmarks for auditing BI-RADS 3 assignments. In this study, we explore some parameters that could serve as useful tools for quality control and clinical practice management. Materials and Methods: This retrospective study covered a 4-year period (Jan 2014-Dec 2017) and included all women over 40 years who were recalled from a screening exam and had an initial assignment of BI-RADS 3 (probably benign) category after diagnostic workup. A follow-up period of 2 years following the assignment of BI-RADS 3 was used for quantitative quality control metrics. Results: Among 135,765 screening exams, 13,453 were recalled and 1,037 BI-RADS 3 cases met inclusion criteria. The follow-up rate at 24 months was 86.7%. The upgrade rate was 7.4% (77/1,037) [CI: 5.9-9.2%] and the PPV3 was 33.8% (26/77) [CI: 23.4-45.5%]. The cancer yield was 2.51% (26/1,037) [CI: 1.64-3.65%] and did not differ (p=0. 243) from the 2% probability of malignancy. The initial BI-RADS3 per screening exam and per recall from screening were 0.76% (1,037/135,765) [CI: 0.72-0.81%] and 7.7% (1,037/13,453) [CI: 7.26-8.17%], respectively. Conclusion: Regular audit of BIRADS 3 metrics has the potential to provide additional insights for clinical practice management. Data from varied clinical settings with input from an expert committee could help establish benchmarks for these metrics.

Ultrasound Imaging Morphology is Associated with Biological Behavior in Invasive Ductal Carcinoma of the Breast.

OBJECTIVES: Ultrasound (US) is commonly used for diagnostic evaluation of breast lesions. The objective of this study was to investigate the association between US imaging morphology from routine radiologists' interpretation and biological behavior such as receptor status and tumor grade determined from histopathology in invasive ductal carcinoma (IDC). MATERIAL AND METHODS: This retrospective study included 453 patients with pathology-verified diagnosis of IDC who had undergone US imaging and had surgery over a 5-year period. US and surgical pathology reports were reviewed and compiled. Correlation analyses and age-adjusted multivariable models were used to determine the association between US imaging morphology and receptor status, tumor grade, and germ line mutation of the breast cancer genes (BRCA1 and BRCA2). The odds ratio (OR), area under receiver operating characteristic curve (AUC), and 95% confidence intervals (CI) were obtained. RESULTS: The likelihood for high-grade cancer increased with size (OR: 1.066; CI: 1.042-1.091) and hypo-echogenicity (OR: 2.044; CI: 1.337-3.126), and decreased with angular or spiculated margins (OR: 0.605; CI: 0.393-0.931) and posterior acoustic shadowing (OR: 0.352; CI: 0.238-0.523). These features achieved an AUC of 0.799 (CI: 0.752-0.845) for predicting high-grade tumors. The likelihood for Estrogen Receptor-positive tumors increased with posterior acoustic shadowing (OR: 3.818; CI: 2.206-6.607), angulated or spiculated margins (OR: 2.596; CI: 1.159-5.815) and decreased with US measured tumor size (OR: 0.959; CI: 0.933-0.986) and hypoechoic features (OR: 0.399; CI: 0.198- 0.801), and achieved an AUC of 0.787 (CI: 0.733-0.841). The likelihood for Progesterone Receptor-positive tumors increased with posterior acoustic shadowing (OR: 2.732; CI: 1.744-4.28) and angulated or spiculated margins (OR: 2.618; CI: 1.412-4.852), and decreased with US measured tumor size (OR: 0.961; CI: 0.937-0.985) and hypoechoic features (OR: 0.571; CI: 0.335-0.975), and achieved an AUC of 0.739 (CI: 0.689-0.790). The likelihood for Human epidermal growth factor receptor 2-positive tumors increased with heterogeneous echo texture (OR: 2.141; CI: 1.17- 3.919) and decreased with angulated or spiculated margins (OR: 0.408; CI: 0.177-0.944), and was marginally associated with hypoechoic features (OR: 2.101; CI: 0.98-4.505) and circumscribed margins (OR: 4.225; CI: 0.919-19.4). The model with the aforementioned four US morphological features and achieved an AUC of 0.686 (CI: 0.614-0.758). The likelihood for triple-negative breast cancers increased with hypo-echogenicity (OR: 2.671; CI: 1.249-5.712) and decreased with posterior acoustic shadowing (OR: 0.287; CI: 0.161-0.513), and achieved an AUC of 0.739 (CI: 0.671- 0.806). No statistical association was observed between US imaging morphology and BRCA mutation. CONCLUSION: In this study of over 450 IDCs, significant statistical associations between tumor grade and receptor status with US imaging morphology were observed and could serve as a surrogate imaging marker for the biological behavior of the tumor.

Radiation dosimetry of a clinical prototype dedicated cone-beam breast CT system with offset detector.

PURPOSE: A clinical-prototype, dedicated, cone-beam breast computed tomography (CBBCT) system with offset detector is undergoing clinical evaluation at our institution. This study is to estimate the normalized glandular dose coefficients ( DgN CT ) that provide air kerma-to-mean glandular dose conversion factors using Monte Carlo simulations. MATERIALS AND METHODS: The clinical prototype CBBCT system uses 49 kV x-ray spectrum with 1.39 mm 1st half-value layer thickness. Monte Carlo simulations (GATE, version 8) were performed with semi-ellipsoidal, homogeneous breasts of various fibroglandular weight fractions ( f g = 0.01 , 0.15 , 0.5 , 1 ) , chest wall diameters ( d = 8 , 10 , 14 , 18 , 20  cm), and chest wall to nipple length ( l = 0.75 d ), aligned with the axis of rotation (AOR) located at 65 cm from the focal spot to determine the DgN CT . Three geometries were considered - 40 × 30 -cm detector with no offset that served as reference and corresponds to a clinical CBBCT system, 30 × 30 -cm detector with 5 cm offset, and a 30 × 30 -cm detector with 10 cm offset. RESULTS: For 5 cm lateral offset, the DgN CT ranged 0.177 - 0.574  mGy/mGy and reduction in DgN CT with respect to reference geometry was observed only for 18 cm ( 6.4 % ± 0.23 % ) and 20 cm ( 9.6 % ± 0.22 % ) diameter breasts. For the 10 cm lateral offset, the DgN CT ranged 0.221 - 0.581  mGy/mGy and reduction in DgN CT was observed for all breast diameters. The reduction in DgN CT was 1.4 % ± 0.48 % , 7.1 % ± 0.13 % , 17.5 % ± 0.19 % , 25.1 % ± 0.15 % , and 27.7 % ± 0.08 % for 8, 10, 14, 18, and 20 cm diameter breasts, respectively. For a given breast diameter, the reduction in DgN CT with offset-detector geometries was not dependent on f g . Numerical fits of DgN CT d , l , f g were generated for each geometry. CONCLUSION: The DgN CT and the numerical fit, D g N CT d , l , f g would be of benefit for current CBBCT systems using the reference geometry and for future generations using offset-detector geometry. There exists a potential for radiation dose reduction with offset-detector geometry, provided the same technique factors as the reference geometry are used, and the image quality is clinically acceptable.

Quantitative metric for assessment of pancreatic ductal adenocarcinoma treatment response in T1-weighted gadolinium-enhanced magnetic resonance imaging.

BACKGROUND: We theoretically derived a new quantitative metric reflecting the product of T1 signal intensity and contrast media concentration (T1C) using first principles for the signal provided by the gradient echo sequence. This metric can be used with conventional gadolinium contrast-enhanced magnetic resonance imaging (CE-MRI) exams. We used this metric to test our hypothesis that gadolinium enhancement changes with pancreatic ductal adenocarcinoma (PDA) treatment response, and that this metric may differentiate responders from non-responders. METHODS: Out of 264 initially identified patients, a final total of 35 patients with PDA were included in a retrospective study of responders (n=24) and non-responders (n=11), which used changes in cancer antigen 19-9 (CA 19-9) and tumor size as reference standards. T1C was computed for the pancreatic mass in the arterial, portal venous, and delayed phases in pre-treatment and post-treatment MRIs. Changes in measurements and correlations with treatment response were assessed by repeated measures analysis of variance and paired t-tests. RESULTS: In the treatment responder group, T1C significantly increased in the arterial, portal venous, and delayed phases (P=7.57e-5, P=3.25e-4, P=1.75e-4). In the non-responder group, T1C did not significantly change in any phase (P>0.58). Post-treatment T1C significantly differed between responders and non-responders (P=0.044) by repeated measures analysis of variance. CONCLUSIONS: T1C significantly increases in all phases of CE-MRI in responders to treatment, but does not change in non-responders. T1C correlates with treatment response, can be computed from clinical MRI exams, and may be useful as an additional metric to stratify patients undergoing treatment.

Sparse-view, short-scan, dedicated cone-beam breast computed tomography: image quality assessment.

The purpose of this study is to quantify the impact of sparse-view acquisition in short-scan trajectories, compared to 360-degrees full-scan acquisition, on image quality measures in dedicated cone-beam breast computed tomography (BCT). Projection data from 30 full-scan (360-degrees; 300 views) BCT exams with calcified lesions were selected from an existing clinical research database. Feldkamp-Davis-Kress (FDK) reconstruction of the full-scan data served as the reference. Projection data corresponding to two short-scan trajectories, 204 and 270-degrees, which correspond to the minimum and maximum angular range achievable in a cone-beam BCT system were selected. Projection data were retrospectively sampled to provide 225, 180, and 168 views for 270-degrees short-scan, and 170 views for 204-degrees short-scan. Short-scans with 180 and 168 views in 270-degrees used non-uniform angular sampling. A fast, iterative, total variation-regularized, statistical reconstruction technique (FIRST) was used for short-scan image reconstruction. Image quality was quantified by variance, signal-difference to noise ratio (SDNR) between adipose and fibroglandular tissues, full-width at half-maximum (FWHM) of calcifications in two orthogonal directions, as well as, bias and root-mean-squared-error (RMSE) computed with respect to the reference full-scan FDK reconstruction. The median values of bias (8.6 × 10-4-10.3 × 10-4cm-1) and RMSE (6.8 × 10-6-9.8 × 10-6cm-1) in the short-scan reconstructions, computed with the full-scan FDK as the reference were close to, but not zero (P < 0.0001, one-sample median test). The FWHM of the calcifications in the short-scan reconstructions did not differ significantly from the reference FDK reconstruction (P > 0.118), except along the superior-inferior direction for the short-scan reconstruction with 168 views in 270-degrees (P = 0.046). The variance and SDNR from short-scan reconstructions were significantly improved compared to the full-scan FDK reconstruction (P < 0.0001). This study demonstrates the feasibility of the short-scan, sparse-view, compressed sensing-based iterative reconstruction. This study indicates that shorter scan times and reduced radiation dose without sacrificing image quality are potentially feasible.

Dedicated cone-beam breast CT using laterally-shifted detector geometry: Quantitative analysis of feasibility for clinical translation.

BACKGROUND: High-resolution, low-noise detectors with minimal dead-space at chest-wall could improve posterior coverage and microcalcification visibility in the dedicated cone-beam breast CT (CBBCT). However, the smaller field-of-view necessitates laterally-shifted detector geometry to enable optimizing the air-gap for x-ray scatter rejection. OBJECTIVE: To evaluate laterally-shifted detector geometry for CBBCT with clinical projection datasets that provide for anatomical structures and lesions. METHODS: CBBCT projection datasets (n = 17 breasts) acquired with a 40×30 cm detector (1024×768-pixels, 0.388-mm pixels) were truncated along the fan-angle to emulate 20.3×30 cm, 22.2×30 cm and 24.1×30 cm detector formats and correspond to 20, 120, 220 pixels overlap in conjugate views, respectively. Feldkamp-Davis-Kress (FDK) algorithm with 3 different weighting schemes were used for reconstruction. Visual analysis for artifacts and quantitative analysis of root-mean-squared-error (RMSE), absolute difference between truncated and 40×30 cm reconstructions (Diff), and its power spectrum (PSDiff) were performed. RESULTS: Artifacts were observed for 20.3×30 cm, but not for other formats. The 24.1×30 cm provided the best quantitative results with RMSE and Diff (both in units of µ, cm-1) of 4.39×10-3±1.98×10-3 and 4.95×10-4±1.34×10-4, respectively. The PSDiff (>0.3 cycles/mm) was in the order of 10-14µ2mm3 and was spatial-frequency independent. CONCLUSIONS: Laterally-shifted detector CBBCT with at least 220 pixels overlap in conjugate views (24.1×30 cm detector format) provides quantitatively accurate and artifact-free image reconstruction.

Positive Predictive Value of Tomosynthesis-guided Biopsies of Architectural Distortions Seen on Digital Breast Tomosynthesis and without an Ultrasound Correlate.

OBJECTIVE: The objective of the study was to determine the positive predictive value (PPV) of architectural distortions (AD) observed on digital breast tomosynthesis (DBT) and without an ultrasound (US) correlate. MATERIALS AND METHODS: In this single-institution, retrospective study, patients who underwent DBT-guided biopsies of AD without any associated findings on digital mammography (DM) or DBT, and without a correlate on targeted US exam, over a 14-month period were included in this study. All patients had DM and DBT and targeted US exams. The PPV was computed along with the exact 95% confidence limits (CL) using simple binomial proportions, with histopathology as the reference standard. RESULTS: A total of 45 ADs in 45 patients met the inclusion criteria. Histopathology indicated 6/45 (PPV: 13.3%, CL: 5.1-26.8%), ADs were malignant, including one high-risk lesion that was upgraded at surgery. ADs were appreciated only on DBT in 12/45 (26.7%) patients, and on both DBT and DM in 33/45 (73.3%) patients, and the corresponding PPV was 25% (3/12, CL: 5.5-57.2%) and 9.1% (3/33, CL: 1.9-24.3%), respectively. In all analyses, the observed PPV significantly exceeded the 2% probability of malignancy for Breast Imaging Reporting and Data System-3 diagnostic categories (P < 0.004). CONCLUSIONS: The PPV of malignancy in DBT detected AD without an US correlate in our series of 45 cases was 6/45 (13.3%). In the absence of an US correlate, the PPV of AD is lower than that mentioned in prior literature but exceeds the 2% threshold to justify DBT-guided biopsy.

Role of VEGF165b/VEGFTOTAL ratio in gestational diabetes mellitus.

Proper vascular function is important for well-being of mother and growing fetus. VEGFTOTAL, and VEGF165b levels and its vascular endothelial complications in gestational diabetes mellitus (GDM) together with the association of inflammation and advanced glycation end products (AGEs) are less studied. VEGF165b/VEGFTOTAL (VEGF RATIO) in GDM pregnant women was investigated in this study. Plasma VEGFTOTAL was lower in GDM (17.68 ± 1.30 pg/mL) compared to non-GDM (25.69 ± 1.40 pg/mL). VEGF165b, ICAM-1, and AGEs were higher in GDM (9.9 ± 1.4 pg/mL, 201.04 ± 7.85 µg/mL, and 10.40 ± 0.98 µg/mL, respectively) and lower in non-GDM (6.47 ± 0.70 pg/mL, 174.1 ± 7.11 µg/mL, and 4.71 ± 0.39 µg/mL, respectively). Compared to non GDM (0.25 ± 0.02), VEGF RATIO was higher in GDM (0.45 ± 0.04) and correlated with -ICAM-1 (r = 0.375, p < .001) and AGEs (r = 0.199, p < .05). Tertile stratification of VEGF RATIO implied that frequency of GDM increases with increasing tertiles of VEGF RATIO (p for trend <.001). Association of VEGF RATIO with GDM was significant even after adjusting for AGEs (OR = 1.279, CI = 1.118-1.462, p < .0010) but it lost its significance when adjusted for ICAM-1 (OR = 1.006, CI = 0.995-1.017, p = .308). VEGF RATIO plays an important role in GDM in association with vascular inflammation.

Hyperglycaemia cause vascular inflammation through advanced glycation end products/early growth response-1 axis in gestational diabetes mellitus.

Hyperglycaemia during pregnancy is the main reason for developing diabetes mediated vascular complications. Advanced glycation end products (AGEs) are formed due to non-enzymatic glycation of proteins, lipids and nucleic acids during hyperglycaemia. It has the potential to damage vasculature by modifying the substrate or by means of AGEs and receptor of AGE (RAGE) interaction. It has been linked with the pathogenesis of various vascular diseases including coronary heart disease, atherosclerosis, restenosis etc. This study was carried out to investigate the role of AGEs-EGR-1 pathway in gestational diabetes mellitus (GDM) vascular inflammation. Human umbilical vein endothelial cells (HuVECs) isolated from normal glucose tolerant mothers were subjected to various treatments including high glucose, silencing of early growth response (EGR)-1, blockade of protein kinase C (PKC) ß, blocking extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), and treatment with AGEs and assayed for EGR-1, tissue factor (TF) and soluble intercellular adhesion molecule (sICAM)-1. Similarly, umbilical vein endothelial cells isolated from normal and GDM mothers were assayed for EGR-1, TF, and sICAM-1. There was a significant increase in EGR-1 and TF levels in HuVECs isolated form GDM mother's umbilical cord and normal HuVECs treated with high glucose condition. This was accompanied by elevated levels of sICAM-1 in high glucose treated cells. Our results revealed AGE-mediated activation of EGR-1 and its downstream genes via PKC ßII and ERK1/2 signaling pathway. The present study demonstrated a novel mechanism of AGEs/ PKC ßII/ ERK1/2/EGR-1 pathway in inducing vascular inflammation in GDM.

Digital breast tomosynthesis: Image acquisition principles and artifacts.

Digital breast tomosynthesis (DBT) is a new technology that is being used more frequently for both breast cancer screening and diagnostic purposes and its utilization is likely to continue to increase over time. The major benefit of tomosynthesis over 2D-mammography is that it allows radiologists to view breast tissue using a three-dimensional dataset and improves diagnostic accuracy by facilitating differentiation of potentially malignant lesions from overlap of normal tissue. In addition, image processing techniques allow reconstruction of two dimensional synthesized mammograms (SM) from DBT data, which eliminates the need for acquiring two dimensional full field digital mammography (FFDM) in addition to tomosynthesis and thereby reduces the radiation dose. DBT systems incorporate a moveable x-ray tube, which moves in a prescribed way over a limited angular range to obtain three-dimensional data of patients' breasts, and utilize reconstruction algorithms. The limited angular range for DBT leads to incomplete sampling of the object, and a movable x-ray tube prolongs the imaging time, both of which make DBT and SM susceptible to artifacts. Understanding the etiology of these artifacts should help radiologists in reducing the number of artifacts and in differentiating a true finding from one related to an artifact, thus potentially decreasing recall rates and false positive rates. This is becoming especially important with increased incorporation of DBT in practices around the world. The goal of this article is to review the physics principles behind DBT systems and use these principles to explain the origin of artifacts that can limit diagnostic evaluation.