INTRODUCTION:Due to the increasing use of dynamic breast MRI and the limited availability of MR-guided interventions, MRI-detected lesions usually undergo a second-look ultrasound (SLUS). We investigated the safety of a negative SLUS and a benign SLUS correlate in excluding malignant and high-risk lesions (B3) and evaluated criteria for the rate of detection on SLUS.METHODS:In the retrospective analysis, all breast MRIs performed between 2011 and 2013 were screened for newly detected lesions. We analyzed the SLUS detection rate dependent on breast density, mass character, lesion size, and histology. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a negative and benign SLUS for malignant lesions (B5) and lesions requiring surgical excision (including high-risk and B5 lesions).RESULTS:We successfully correlated 110 of 397 lesions. The detection rate was significantly higher for mass than for non-mass lesions and correlated with lesion size for mass lesions only. Lesions without/with a benign SLUS correlate were more frequently benign (including B3) or required no further procedure (B2). The sensitivity of SLUS in the detection of B3 and B5 lesions was 58%, and 73% in the detection of B5 lesions. The NPV of a negative or benign SLUS for B3 and B5 lesions was 89%, and 96% for B5 lesions.DISCUSSION:SLUS is a safe diagnostic tool for the management of MRI-detected lesions and can spare patients from undergoing invasive procedures.

Background The extent of intraductal carcinoma in situ (DCIS) is commonly underestimated due to the discontinuous growth and lack of microcalcifications. Specimen radiography has been established to reduce the rate of re-excision. However, the predictive value for margin assessment with conventional specimen radiography for DCIS is low. In this study we assessed the potential of grating-based phase-contrast computed tomography (GBPC-CT) at conventional X-ray sources for specimen tomography of DCIS containing samples. Materials and methods GBPC-CT was performed on four ex-vivo breast specimens containing DCIS and invasive carcinoma of non-specific type. Phase-contrast and absorption-based datasets were manually matched with corresponding histological slices as the standard of reference. Results Matching of CT images and histology was successful. GBPC-CT showed an improved soft tissue contrast compared to absorption-based images revealing more histological details in the same sections. Non-calcifying DCIS exceeding the invasive tumor could be correlated to areas of dilated bright ducts around the tumor. Conclusions GBPC-CT imaging at conventional X-ray sources offers improved depiction quality for the imaging of breast tissue samples compared to absorption-based imaging, allows the identification of diagnostically relevant tissue details, and provides full three-dimensional assessment of sample margins.

With the introduction of screening mammography, the mortality rate of breast cancer has been reduced throughout the last decades. However, many women undergo unnecessary subsequent examinations due to inconclusive diagnoses from mammography. Two pathways appear especially promising to reduce the number of false-positive diagnoses. In a clinical study, mammography using synchrotron radiation was able to clarify the diagnosis in the majority of inconclusive cases. The second highly valued approach focuses on the application of phase-sensitive techniques such as grating-based phase-contrast and dark-field imaging. Feasibility studies have demonstrated a promising enhancement of diagnostic content, but suffer from dose concerns. Here we present dose-compatible grating-based phase-contrast and dark-field images as well as conventional absorption images acquired with monochromatic x-rays from a compact synchrotron source based on inverse Compton scattering. Images of freshly dissected mastectomy specimens show improved diagnostic content over ex-vivo clinical mammography images at lower or equal dose. We demonstrate increased contrast-to-noise ratio for monochromatic over clinical images for a well-defined phantom. Compact synchrotron sources could potentially serve as a clinical second level examination.

The distant goal of this investigation is to reduce the number of invasive procedures associated with breast micro calcification biopsies, by improving and refining conventional BIRADS micro calcification assessments with x-ray dark-field mammography. The study was institutional review board (IRB) approved. A dedicated grating-based radiography setup (Mo-target, 40 keV, 70 mA) was used to investigate one breast mastectomy and 31 biopsies with dark-field mammography. Comparing the absorption and scattering properties of micro calcifications clusters enables accessing information on the interior morphology on the micron-scale retrieved in a non-invasive manner. Insights underlying the micro morphological nature of breast calcifications were verified by comprehensive high-resolution micro-CT measurements. It was found that Dark-field mammography allows a micro-structural classification of breast micro calcification as ultra-fine, fine, pleomorphic and coarse textured using conventional detectors. Dark-field mammography is thereby highly sensitive to minor structural deviations. Finally, the determined micro-texture of the investigated micro calcifications was correlated with findings obtained from histopathological work up. The presented results demonstrate that dark-field mammography yields the potential to enhance diagnostic validity of current micro calcification analysis - which is yet limited to the exterior appearance of micro calcification clusters - and thereby reduce the number of invasive procedures.

X-Ray Phase-Contrast (XPC) imaging is a novel technology with a great potential for applications in clinical practice, with breast imaging being of special interest. This work introduces an intuitive methodology to combine and visualize relevant diagnostic features, present in the X-ray attenuation, phase shift and scattering information retrieved in XPC imaging, using a Fourier domain fusion algorithm. The method allows to present complementary information from the three acquired signals in one single image, minimizing the noise component and maintaining visual similarity to a conventional X-ray image, but with noticeable enhancement in diagnostic features, details and resolution. Radiologists experienced in mammography applied the image fusion method to XPC measurements of mastectomy samples and evaluated the feature content of each input and the fused image. This assessment validated that the combination of all the relevant diagnostic features, contained in the XPC images, was present in the fused image as well.

Introduction: Organic food has become increasingly popular with consumers. People seem to recognize it as a valuable alternative to popular brands from conventional food producers. Still, the basis of such consumer behavior remains unclear, with the literature supporting motivations ranging from health-related to more hedonic. Methods: To investigate the underlying brain processes, we looked for neural correlates of the perceptions of two types of psychological added value that brands could provide (popular/organic). Eighteen subjects were exposed to logos of brands of either category for the very same types of food that was typed below the logo (i.e. French fries) and blood-oxygen-level dependent brain activation was recorded using functional magnetic resonance imaging (fMRI). Results: The results show higher activations in medial prefrontal cortex for popular brands, as expected with respect to the existing literature on decision-making and self-control. For organic brands, we found relatively higher activations in dorsolateral parts of the prefrontal cortex. Conclusions: Our study contributes data from the food field to the converging evidence in the literature that the lateral and medial parts of the prefrontal cortex have discrete and independent influences on decision-making: Brand information (as a secondary inducer) substantially affects the processing of food stimuli (as a primary inducer).

Since the breast is one of the most radiosensitive organs, mammography is arguably the area where lowering radiation dose is of the uttermost importance. Phase-based x-ray imaging methods can provide opportunities in this sense, since they do not require x-rays to be stopped in tissue for image contrast to be generated. Therefore, x-ray energy can be considerably increased compared to those usually exploited by conventional mammography. In this article we show how a novel, optimized approach can lead to considerable dose reductions. This was achieved by matching the edge-illumination phase method, which reaches very high angular sensitivity also at high x-ray energies, to an appropriate image processing algorithm and to a virtually noise-free detection technology capable of reaching almost 100% efficiency at the same energies. Importantly, while proof-of-concept was obtained at a synchrotron, the method has potential for a translation to conventional sources.

Breast microcalcifications play an essential role in the detection and evaluation of early breast cancer in clinical diagnostics. However, in digital mammography, microcalcifications are merely graded with respect to their global appearance within the mammogram, while their interior microstructure remains spatially unresolved and therefore not considered in cancer risk stratification. In this article, we exploit the sub-pixel resolution sensitivity of X-ray dark-field contrast for clinical microcalcification assessment. We demonstrate that the micromorphology, rather than chemical composition of microcalcification clusters (as hypothesised by recent literature), determines their absorption and small-angle scattering characteristics. We show that a quantitative classification of the inherent microstructure as ultra-fine, fine, pleomorphic and coarse textured is possible. Insights underlying the micromorphological nature of breast calcifications are verified by comprehensive high-resolution micro-CT measurements. We test the determined microtexture of microcalcifications as an indicator for malignancy and demonstrate its potential to improve breast cancer diagnosis, by providing a non-invasive tool for sub-resolution microcalcification assessment. Our results indicate that dark-field imaging of microcalcifications may enhance the diagnostic validity of current microcalcification analysis and reduce the number of invasive procedures.

Objectives Neoadjuvant chemotherapy is the state-of-the-art treatment in advanced breast cancer. A correct visualization of the post-therapeutic tumor size is of high prognostic relevance. X-ray phase-contrast computed tomography (PC-CT) has been shown to provide improved soft-tissue contrast at a resolution formerly restricted to histopathology, at low doses. This study aimed at assessing ex-vivo the potential use of PC-CT for visualizing the effects of neoadjuvant chemotherapy on breast carcinoma. Materials and Methods The analysis was performed on two ex-vivo formalin-fixed mastectomy samples containing an invasive carcinoma removed from two patients treated with neoadjuvant chemotherapy. Images were matched with corresponding histological slices. The visibility of typical post-therapeutic tissue changes was assessed and compared to results obtained with conventional clinical imaging modalities. Results PC-CT depicted the different tissue types with an excellent correlation to histopathology. Post-therapeutic tissue changes were correctly visualized and the residual tumor mass could be detected. PC-CT outperformed clinical imaging modalities in the detection of chemotherapy-induced tissue alterations including post-therapeutic tumor size. Conclusions PC-CT might become a unique diagnostic tool in the prediction of tumor response to neoadjuvant chemotherapy. PC-CT might be used to assist during histopathological diagnosis, offering a high-resolution and high-contrast virtual histological tool for the accurate delineation of tumor boundaries.

Objective: There is ongoing debate whether cancer qualifies as traumatic stressor. We investigated prevalence and course of posttraumatic stress in patients with early breast cancer (BC) during their first year after diagnosis and determined effects of mastectomy and chemotherapy.Methods: Patients with stage 0-III BC aged <= 65 years were evaluated with the Structured Clinical Interview for DSM-IV modules for acute and posttraumatic stress disorder (ASD and PTSD, respectively) before treatment, after chemotherapy, and 1 year after diagnosis. Matched controls were assessed at matched intervals. Effects of time, mastectomy, and chemotherapy on BC-related PTSD symptom severity were tested with linear mixed model analysis.Results: Stress disorder (ASD or PTSD) related to BC was diagnosed in 6 (3.6%) of 166 patients before treatment and in 3 patients (2.0%) 1 year later. The rate of patients who experienced PTSD symptoms related to BC decreased from 82.5 to 57.3% (p<0.001), and the mean of BC-related PTSD symptoms diminished from 3.1 to 1.7 (p<0.001). Only university education significantly predicted the course of BC-related PTSD symptom severity (p=0.009). In 60 controls, no diagnosis of stress disorder, a rate of 18% women experiencing PTSD symptoms, and a mean of 0.4 PTSD symptoms (p vs. patients <0.001) were found.Conclusions: Most newly diagnosed patients with BC experience PTSD symptoms, whereas full diagnoses of DSM-IV stress disorder are rare. Symptoms diminish somewhat within 1 year furthered by university education but independently from mastectomy and chemotherapy. Throughout the year after diagnosis, having BC entails markedly increased PTSD symptom burden. Copyright (C) 2016 John Wiley & Sons, Ltd.

OBJECTIVES:Conventional X-ray attenuation-based contrast is inherently low for the soft-tissue components of the female breast. To overcome this limitation, we investigate the diagnostic merits arising from dark-field mammography by means of certain tumour structures enclosed within freshly dissected mastectomy samples.METHODS:We performed grating-based absorption, absolute phase and dark-field mammography of three freshly dissected mastectomy samples containing bi- and multifocal carcinoma using a compact, laboratory Talbot-Lau interferometer. Preoperative in vivo imaging (digital mammography, ultrasound, MRI), postoperative histopathological analysis and ex vivo digital mammograms of all samples were acquired for the diagnostic verification of our results.RESULTS:In the diagnosis of multifocal tumour growth, dark-field mammography seems superior to standard breast imaging modalities, providing a better resolution of small, calcified tumour nodules, demarcation of tumour boundaries with desmoplastic stromal response and spiculated soft-tissue strands extending from an invasive ductal breast cancer.CONCLUSIONS:On the basis of selected cases, we demonstrate that dark-field mammography is capable of outperforming conventional mammographic imaging of tumour features in both calcified and non-calcified tumours. Presuming dose optimization, our results encourage further studies on larger patient cohorts to identify those patients that will benefit the most from this promising additional imaging modality.KEY POINTS:• X-ray dark-field mammography provides significantly improved visualization of tumour features • X-ray dark-field mammography is capable of outperforming conventional mammographic imaging • X-ray dark-field mammography provides imaging sensitivity towards highly dispersed calcium grains.

Phase-contrast mammography using laboratory X-ray sources is a promising approach to overcome the relatively low sensitivity and specificity of clinical, absorption-based screening. Current research is mostly centered on identifying potential diagnostic benefits arising from phase-contrast and dark-field mammography and benchmarking the latter with conventional state-of-the-art imaging methods. So far, little effort has been made to adjust this novel imaging technique to clinical needs. In this article, we address the key points for a successful implementation to a clinical routine in the near future and present the very first dose-compatible and rapid scan-time phase-contrast mammograms of both a freshly dissected, cancer-bearing mastectomy specimen and a mammographic accreditation phantom.

Background Fibroadenoma is the most common benign solid breast lesion type and a very common cause for histologic assessment. To justify a conservative therapy, a highly specific discrimination between fibroadenomas and other breast lesions is crucial. Phase-contrast imaging offers improved soft-tissue contrast and differentiability of fine structures combined with the potential of 3-dimensional imaging. In this study we assessed the potential of grating-based phase-contrast CT imaging for visualizing diagnostically relevant features of fibroadenomas. Materials and Methods Grating-based phase-contrast CT was performed on six ex-vivo formalin-fixed breast specimens containing a fibroadenoma and three samples containing benign changes that resemble fibroadenomas using Talbot Lau interferometry and a polychromatic X-ray source. Phase-contrast and simultaneously acquired absorption-based 3D-datasets were manually matched with corresponding histological slices. The visibility of diagnostically valuable features was assessed in comparison with histology as the gold-standard. Results In all cases, matching of grating-based phase-contrast CT images and histology was successfully completed. Grating-based phase-contrast CT showed greatly improved differentiation of fine structures and provided accurate depiction of strands of fibrous tissue within the fibroadenomas as well as of the diagnostically valuable dilated, branched ductuli of the fibroadenomas. A clear demarcation of tumor boundaries in all cases was provided by phase- but not absorption-contrast CT. Conclusions Pending successful translation of the technology to a clinical setting and considerable reduction of the required dose, the data presented here suggest that grating-based phase-contrast CT may be used as a supplementary non-invasive diagnostic tool in breast diagnostics. Phase-contrast CT may thus contribute to the reduction of false positive findings and reduce the recall and core biopsy rate in population-based screening. Phase-contrast CT may further be used to assist during histopathological workup, offering a 3D view of the tumor and helping to identify diagnostically valuable tissue sections within large tumors.

Phase-contrast x-ray imaging is a promising improvement of conventional absorption-based mammography for early tumor detection. This potential has been demonstrated recently, utilizing structured gratings to obtain differential phase and dark-field scattering images. However, the inherently anisotropic imaging sensitivity of the proposed mono-directional approach yields only insufficient diagnostic information, and has low diagnostic sensitivity to highly oriented structures. To overcome these limitations, we present a two-directional x-ray phase-contrast mammography approach and demonstrate its advantages by applying it to a freshly dissected, cancerous mastectomy breast specimen. We illustrate that the two-directional scanning procedure overcomes the insufficient diagnostic value of a single scan, and reliably detects tumor structures, independently from their orientation within the breast. Our results indicate the indispensable diagnostic necessity and benefit of a multi-directional approach for x-ray phase-contrast mammography.

PURPOSE:Phase contrast computed tomography has emerged as an imaging method, which is able to outperform present day clinical mammography in breast tumor visualization while maintaining an equivalent average dose. To this day, no segmentation technique takes into account the specificity of the phase contrast signal. In this study, the authors propose a new mathematical framework for human-guided breast tumor segmentation. This method has been applied to high-resolution images of excised human organs, each of several gigabytes.METHODS:The authors present a segmentation procedure based on the viscous watershed transform and demonstrate the efficacy of this method on analyzer based phase contrast images. The segmentation of tumors inside two full human breasts is then shown as an example of this procedure's possible applications.RESULTS:A correct and precise identification of the tumor boundaries was obtained and confirmed by manual contouring performed independently by four experienced radiologists.CONCLUSIONS:The authors demonstrate that applying the watershed viscous transform allows them to perform the segmentation of tumors in high-resolution x-ray analyzer based phase contrast breast computed tomography images. Combining the additional information provided by the segmentation procedure with the already high definition of morphological details and tissue boundaries offered by phase contrast imaging techniques, will represent a valuable multistep procedure to be used in future medical diagnostic applications.

Brustkrebs ist weltweit die häufigste Tumorerkrankung und die häufigste Krebstodesursache der Frau.

Early detection of breast cancer largely contributes to an improved prognosis and results in reduced disease mortality. The breast cancer screening technique used today in clinics is known as dual-view digital mammography. Its limitation is that it only provides two images of the breast, which can explain why up to 20% of breast tumors are not detectable on mammograms. Mammograms can also appear abnormal although no breast cancers are actually present. Computed tomography (CT) allows a precise 3D visualization of the human body, but it cannot be routinely used for breast cancer diagnosis because of the breast’s high radiosensitivity. This vulnerability significantly reduces the benefit-risk ratio owing to the potential for tumor development resulting from the exam itself. Recognizing these limitations, we developed a way to produce 3D x-ray images of the breast at a radiation dose that is lower than 2D radiographies.1 We performed phase-contrast x-ray tomography at 60keV of a whole human breast at the biomedical beamline of the European Synchrotron Radiation Facility (ESRF) in France. We reconstructed images by applying the novel mathematical equally sloped tomography (EST) algorithm using 512 projections to produce 3D images of the tissue at a resolution higher than that used in clinical CT (pixel size of 92 m versus more than 200 m for clinical CT scanners) and at a dose lower than that of dual view mammography (which is typically about 3mGy). The new method allowed a clear and precise identification of a malignant cancer. According to a blind evaluation by five experienced radiologists, this method can reduce the radiation dose and acquisition time by 74% relative to conventional phase-contrast x-ray tomography while maintaining high resolution and contrast. Despite the significant reduction in the number of projections used (corresponding to important savings in dose and Figure 1. Comparison between a conventional computed tomography (CT) scan of the breast based on the filtered back projection algorithm and one based on the equally sloped tomography algorithm with phasecontrast imaging. In the second image, the tumor is highlighted in red. The radiation dose needed for the scans is shown at the bottom of each image.