Experimental optimization of the energy for breast-CT with synchrotron radiation.

Breast Computed Tomography (bCT) is a three-dimensional imaging technique that is raising interest among radiologists as a viable alternative to mammographic planar imaging. In X-rays imaging it would be desirable to maximize the capability of discriminating different tissues, described by the Contrast to Noise Ratio (CNR), while minimizing the dose (i.e. the radiological risk). Both dose and CNR are functions of the X-ray energy. This work aims at experimentally investigating the optimal energy that, at fixed dose, maximizes the CNR between glandular and adipose tissues. Acquisitions of both tissue-equivalent phantoms and actual breast specimens have been performed with the bCT system implemented within the Syrma-3D collaboration at the Syrmep beamline of the Elettra synchrotron (Trieste). The experimental data have been also compared with analytical simulations and the results are in agreement. The CNR is maximized at energies around 26-28 keV. These results are in line with the outcomes of a previously presented simulation study which determined an optimal energy of 28 keV for a large set of breast phantoms with different diameters and glandular fractions. Finally, a study on photon starvation has been carried out to investigate how far the dose can be reduced still having suitable images for diagnostics.

Radiochromic film dosimetry in synchrotron radiation breast computed tomography: a phantom study.

This study relates to the INFN project SYRMA-3D for in vivo phase-contrast breast computed tomography using the SYRMEP synchrotron radiation beamline at the ELETTRA facility in Trieste, Italy. This peculiar imaging technique uses a novel dosimetric approach with respect to the standard clinical procedure. In this study, optimization of the acquisition procedure was evaluated in terms of dose delivered to the breast. An offline dose monitoring method was also investigated using radiochromic film dosimetry. Various irradiation geometries have been investigated for scanning the prone patient's pendant breast, simulated by a 14 cm-diameter polymethylmethacrylate cylindrical phantom containing pieces of calibrated radiochromic film type XR-QA2. Films were inserted mid-plane in the phantom, as well as wrapped around its external surface, and irradiated at 38 keV, with an air kerma value that would produce an estimated mean glandular dose of 5 mGy for a 14 cm-diameter 50% glandular breast. Axial scans were performed over a full rotation or over 180°. The results point out that a scheme adopting a stepped rotation irradiation represents the best geometry to optimize the dose distribution to the breast. The feasibility of using a piece of calibrated radiochromic film wrapped around a suitable holder around the breast to monitor the scan dose offline is demonstrated.

Single-shot K-edge subtraction x-ray discrete computed tomography with a polychromatic source and the Pixie-III detector.

K-edge subtraction (KES) imaging is a technique able to map a specific element such as e.g. a contrast agent within the tissues, by exploiting the sharp rise of its absorption coefficient at the K-edge energy. Whereas mainly explored at synchrotron radiation sources, the energy discrimination properties of modern x-ray photon counting detectors (XPCDs) pave the way for an implementation of single-shot KES imaging with conventional polychromatic sources. In this work we present an x-ray CT imaging system based on the innovative Pixie-III detector and discrete reconstruction. The results reported here show that a reliable automatic localization of Barium (above a certain concentration) is possible with a few dozens of tomographic projections for a volume having an axial slice of 512 [Formula: see text] 512 pixels. The final application is a routine high-fidelity 3D mapping of a specific element ready for further morphological quantification by means of x-ray CT with potential promising applications in vivo.

Image quality comparison between a phase-contrast synchrotron radiation breast CT and a clinical breast CT: a phantom based study.

In this study we compared the image quality of a synchrotron radiation (SR) breast computed tomography (BCT) system with a clinical BCT in terms of contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), noise power spectrum (NPS), spatial resolution and detail visibility. A breast phantom consisting of several slabs of breast-adipose equivalent material with different embedded targets (i.e., masses, fibers and calcifications) was used. Phantom images were acquired using a dedicated BCT system installed at the Radboud University Medical Center (Nijmegen, The Netherlands) and the SR BCT system at the SYRMEP beamline of Elettra SR facility (Trieste, Italy) based on a photon-counting detector. Images with the SR setup were acquired mimicking the clinical BCT conditions (i.e., energy of 30 keV and radiation dose of 6.5 mGy). Images were reconstructed with an isotropic cubic voxel of 273 µm for the clinical BCT, while for the SR setup two phase-retrieval (PhR) kernels (referred to as "smooth" and "sharp") were alternatively applied to each projection before tomographic reconstruction, with voxel size of 57 × 57 × 50 µm3. The CNR for the clinical BCT system can be up to 2-times higher than SR system, while the SNR can be 3-times lower than SR system, when the smooth PhR is used. The peak frequency of the NPS for the SR BCT is 2 to 4-times higher (0.9 mm-1 and 1.4 mm-1 with smooth and sharp PhR, respectively) than the clinical BCT (0.4 mm-1). The spatial resolution (MTF10%) was estimated to be 1.3 lp/mm for the clinical BCT, and 5.0 lp/mm and 6.7 lp/mm for the SR BCT with the smooth and sharp PhR, respectively. The smallest fiber visible in the SR BCT has a diameter of 0.15 mm, while for the clinical BCT is 0.41 mm. Calcification clusters with diameter of 0.13 mm are visible in the SR BCT, while the smallest diameter for the clinical BCT is 0.29 mm. As expected, the image quality of the SR BCT outperforms the clinical BCT system, providing images with higher spatial resolution and SNR, and with finer granularity. Nevertheless, this study assesses the image quality gap quantitatively, giving indications on the benefits associated with SR BCT and providing a benchmarking basis for its clinical implementation. In addition, SR-based studies can provide a gold-standard in terms of achievable image quality, constituting an upper-limit to the potential clinical development of a given technique.

Optimization of the energy for Breast monochromatic absorption X-ray Computed Tomography.

The limits of mammography have led to an increasing interest on possible alternatives such as the breast Computed Tomography (bCT). The common goal of all X-ray imaging techniques is to achieve the optimal contrast resolution, measured through the Contrast to Noise Ratio (CNR), while minimizing the radiological risks, quantified by the dose. Both dose and CNR depend on the energy and the intensity of the X-rays employed for the specific imaging technique. Some attempts to determine an optimal energy for bCT have suggested the range 22 keV-34 keV, some others instead suggested the range 50 keV-60 keV depending on the parameters considered in the study. Recent experimental works, based on the use of monochromatic radiation and breast specimens, show that energies around 32 keV give better image quality respect to setups based on higher energies. In this paper we report a systematic study aiming at defining the range of energies that maximizes the CNR at fixed dose in bCT. The study evaluates several compositions and diameters of the breast and includes various reconstruction algorithms as well as different dose levels. The results show that a good compromise between CNR and dose is obtained using energies around 28 keV.

Advancements towards the implementation of clinical phase-contrast breast computed tomography at Elettra.

Breast computed tomography (BCT) is an emerging application of X-ray tomography in radiological practice. A few clinical prototypes are under evaluation in hospitals and new systems are under development aiming at improving spatial and contrast resolution and reducing delivered dose. At the same time, synchrotron-radiation phase-contrast mammography has been demonstrated to offer substantial advantages when compared with conventional mammography. At Elettra, the Italian synchrotron radiation facility, a clinical program of phase-contrast BCT based on the free-space propagation approach is under development. In this paper, full-volume breast samples imaged with a beam energy of 32 keV delivering a mean glandular dose of 5 mGy are presented. The whole acquisition setup mimics a clinical study in order to evaluate its feasibility in terms of acquisition time and image quality. Acquisitions are performed using a high-resolution CdTe photon-counting detector and the projection data are processed via a phase-retrieval algorithm. Tomographic reconstructions are compared with conventional mammographic images acquired prior to surgery and with histologic examinations. Results indicate that BCT with monochromatic beam and free-space propagation phase-contrast imaging provide relevant three-dimensional insights of breast morphology at clinically acceptable doses and scan times.

Quantitative characterization of breast tissues with dedicated CT imaging.

A quantitative characterization of the soft tissues composing the human breast is achieved by means of a monochromatic CT phase-contrast imaging system, through accurate measurements of their attenuation coefficients within the energy range of interest for breast CT clinical examinations. Quantitative measurements of linear attenuation coefficients are performed on tomographic reconstructions of surgical samples, using monochromatic x-ray beams from a synchrotron source and a free space propagation setup. An online calibration is performed on the obtained reconstructions, in order to reassess the validity of the standard calibration procedure of the CT scanner. Three types of healthy tissues (adipose, glandular, and skin) and malignant tumors, when present, are considered from each sample. The measured attenuation coefficients are in very good agreement with the outcomes of similar studies available in the literature, although they span an energy range that was mostly neglected in the previous studies. No globally significant differences are observed between healthy and malignant dense tissues, although the number of considered samples does not appear sufficient to address the issue of a quantitative differentiation of tumors. The study assesses the viability of the proposed methodology for the measurement of linear attenuation coefficients, and provides a denser sampling of attenuation data in the energy range useful to breast CT.

Fully Automated Support System for Diagnosis of Breast Cancer in Contrast-Enhanced Spectral Mammography Images.

Contrast-Enhanced Spectral Mammography (CESM) is a novelty instrumentation for diagnosing of breast cancer, but it can still be considered operator dependent. In this paper, we proposed a fully automatic system as a diagnostic support tool for the clinicians. For each Region Of Interest (ROI), a features set was extracted from low-energy and recombined images by using different techniques. A Random Forest classifier was trained on a selected subset of significant features by a sequential feature selection algorithm. The proposed Computer-Automated Diagnosis system is tested on 48 ROIs extracted from 53 patients referred to Istituto Tumori "Giovanni Paolo II" of Bari (Italy) from the breast cancer screening phase between March 2017 and June 2018. The present method resulted highly performing in the prediction of benign/malignant ROIs with median values of sensitivity and specificity of 87 . 5 % and 91 . 7 % , respectively. The performance was high compared to the state-of-the-art, even with a moderate/marked level of parenchymal background. Our classification model outperformed the human reader, by increasing the specificity over 8 % . Therefore, our system could represent a valid support tool for radiologists for interpreting CESM images, both reducing the false positive rate and limiting biopsies and surgeries.

Post-reconstruction 3D single-distance phase retrieval for multi-stage phase-contrast tomography with photon-counting detectors.

In the case of single-distance propagation-based phase-contrast X-ray computed tomography with synchrotron radiation, the conventional reconstruction pipeline includes an independent 2D phase retrieval filtering of each acquired projection prior to the actual reconstruction. In order to compensate for the limited height of the X-ray beam or the small sensitive area of most modern X-ray photon-counting detectors, it is quite common to image large objects with a multi-stage approach, i.e. several acquisitions at different vertical positions of the sample. In this context, the conventional reconstruction pipeline may introduce artifacts at the margins of each vertical stage. This article presents a modified computational protocol where a post-reconstruction 3D volume phase retrieval is applied. By comparing the conventional 2D and the proposed 3D reconstructions of a large mastectomy specimen (9 cm in diameter and 3 cm in height), it is here shown that the 3D approach compensates for the multi-stage artifacts, it avoids refined projection stitching, and the image quality in terms of spatial resolution, contrast and contrast-to-noise ratio is preserved.

Monochromatic breast computed tomography with synchrotron radiation: phase-contrast and phase-retrieved image comparison and full-volume reconstruction.

A program devoted to performing the first in vivo synchrotron radiation (SR) breast computed tomography (BCT) is ongoing at the Elettra facility. Using the high spatial coherence of SR, phase-contrast (PhC) imaging techniques can be used. The latest high-resolution BCT acquisitions of breast specimens, obtained with the propagation-based PhC approach, are herein presented as part of the SYRMA-3D collaboration effort toward the clinical exam. Images are acquired with a 60 - µ m pixel dead-time-free single-photon-counting CdTe detector. The samples are imaged at 32 and 38 keV in a continuous rotating mode, delivering 5 to 20 mGy of mean glandular dose. Contrast-to-noise ratio (CNR) and spatial resolution performances are evaluated for both PhC and phase-retrieved images, showing that by applying the phase-retrieval algorithm a five-time CNR increase can be obtained with a minor loss in spatial resolution across soft tissue interfaces. It is shown that, despite having a poorer CNR, PhC images can provide a sharper visualization of microcalcifications, thus being complementary to phase-retrieved images. Furthermore, the first full-volume scan of a mastectomy sample ( 9 × 9 × 3 cm 3 ) is reported. This investigation into surgical specimens indicates that SR BCT in terms of CNR, spatial resolution, scan duration, and scan volume is feasible.

Phase-contrast breast CT: the effect of propagation distance.

X-ray phase imaging has the potential to dramatically improve soft tissue contrast sensitivity, which is a crucial requirement in many diagnostic applications such as breast imaging. In this context, a program devoted to perform in vivo phase-contrast synchrotron radiation breast computed tomography is ongoing at the Elettra facility (Trieste, Italy). The used phase-contrast technique is the propagation-based configuration, which requires a spatially coherent source and a sufficient object-to-detector distance. In this work the effect of this distance on image quality is quantitatively investigated scanning a large breast surgical specimen at three object-to-detector distances (1.6, 3, 9 m) and comparing the images both before and after applying the phase-retrieval procedure. The sample is imaged at 30 keV with a [Formula: see text] pixel pitch CdTe single-photon-counting detector, positioned at a fixed distance of 31.6 m from the source. The detector fluence is kept constant for all acquisitions. The study shows that, at the largest distance, a 20-fold SNR increase can be obtained by applying the phase-retrieval procedure. Moreover, it is shown that, for phase-retrieved images, changing the object-to-detector distance does not affect spatial resolution while boosting SNR (four-fold increase going from the shortest to the largest distance). The experimental results are supported by a theoretical model proposed by other authors, whose salient results are presented in this paper.

K-edge spectral computed tomography with a photon counting detector and discrete reconstruction.

X-ray K-Edge Subtraction Computed Tomography (KES-CT) is based on the acquisition of two images at different energies, one below and one above the Kedge of a contrast agent. KES-CT is mainly performed at synchrotron facilities where a tunable monochromatic X-ray beam is available. Thanks to innovative Photon Counting Xray Detectors (PCXDs), it would be desirable to collect the two images in a single shot with a conventional polychromatic Xray spectrum. This approach, sometimes called spectral-CT or color-CT eliminates the risk of misregistration due to motion between consecutive acquisitions and it should allow for scans with much lower doses of contrast medium. Spectral CT is considered very promising but its practical application is being hampered by several practical issues, one of these being the charge sharing affecting the energy resolution of PCXDs. However, latest generations of PCXDs implement hardware solutions to cope with the charge sharing effects, thus allowing sharper color sensitivity. This work presents a K-edge spectral CT imaging preliminary protocol based on the Pixirad-I/PixieIII detector where discrete tomography is used to present the reconstructed slices as color images. Results show that when a solution for the charge sharing issue is considered and refined reconstruction methods are applied, accurate K-edge subtraction imaging with conventional sources can be performed.

Large-area single-photon-counting CdTe detector for synchrotron radiation computed tomography: a dedicated pre-processing procedure.

Large-area CdTe single-photon-counting detectors are becoming more and more attractive in view of low-dose imaging applications due to their high efficiency, low intrinsic noise and absence of a scintillating screen which affects spatial resolution. At present, however, since the dimensions of a single sensor are small (typically a few cm2), multi-module architectures are needed to obtain a large field of view. This requires coping with inter-module gaps and with close-to-edge pixels, which generally show a non-optimal behavior. Moreover, high-Z detectors often show gain variations in time due to charge trapping: this effect is detrimental especially in computed tomography (CT) applications where a single tomographic image requires hundreds of projections continuously acquired in several seconds. This work has been carried out at the SYRMEP beamline of the Elettra synchrotron radiation facility (Trieste, Italy), in the framework of the SYRMA-3D project, which aims to perform the world's first breast-CT clinical study with synchrotron radiation. An ad hoc data pre-processing procedure has been developed for the PIXIRAD-8 CdTe single-photon-counting detector, comprising an array of eight 30.7 mm × 24.8 mm modules tiling a 246 mm × 25 mm sensitive area, which covers the full synchrotron radiation beam. The procedure consists of five building blocks, namely dynamic flat-fielding, gap seaming, dynamic ring removal, projection despeckling and around-gap equalization. Each block is discussed and compared, when existing, with conventional approaches. The effectiveness of the pre-processing is demonstrated for phase-contrast CT images of a human breast specimen. The dynamic nature of the proposed procedure, which provides corrections dependent upon the projection index, allows the effective removal of time-dependent artifacts, preserving the main image features including phase effects.

Achromatic approach to phase-based multi-modal imaging with conventional X-ray sources.

Compatibility with polychromatic radiation is an important requirement for an imaging system using conventional rotating anode X-ray sources. With a commercially available energy-resolving single-photon-counting detector we investigated how broadband radiation affects the performance of a multi-modal edge-illumination phase-contrast imaging system. The effect of X-ray energy on phase retrieval is presented, and the achromaticity of the method is experimentally demonstrated. Comparison with simulated measurements integrating over the energy spectrum shows that there is no significant loss of image quality due to the use of polychromatic radiation. This means that, to a good approximation, the imaging system exploits radiation in the same way at all energies typically used in hard-X-ray imaging.

Characterization of mammographic masses using a gradient-based segmentation algorithm and a neural classifier.

Computerized methods have recently shown a great potential in providing radiologists with a second opinion about the visual diagnosis of the malignancy of mammographic masses. The computer-aided diagnosis (CAD) system we developed for the mass characterization is mainly based on a segmentation algorithm and on the neural classification of several features computed on the segmented mass. Mass-segmentation plays a key role in most computerized systems. Our technique is a gradient-based one, showing the main characteristic that no free parameters have been evaluated on the data set used in this analysis, thus it can directly be applied to data sets acquired in different conditions without any ad hoc modification. A data set of 226 masses (109 malignant and 117 benign) has been used in this study. The segmentation algorithm works with a comparable efficiency both on malignant and benign masses. Sixteen features based on shape, size and intensity of the segmented masses are extracted and analyzed by a multi-layered perceptron neural network trained with the error back-propagation algorithm. The capability of the system in discriminating malignant from benign masses has been evaluated in terms of the receiver-operating characteristic (ROC) analysis. A feature selection procedure has been carried out on the basis of the feature discriminating power and of the linear correlations interplaying among them. The comparison of the areas under the ROC curves obtained by varying the number of features to be classified has shown that 12 selected features out of the 16 computed ones are powerful enough to achieve the best classifier performances. The radiologist assigned the segmented masses to three different categories: correctly-, acceptably- and non-acceptably-segmented masses. We initially estimated the area under ROC curve only on the first category of segmented masses (the 88.5% of the data set), then extending the classification to the second subclass (reaching the 97.8% of the data set) and finally to the whole data set, obtaining A(z)=0.805+/-0.030, 0.787+/-0.024 and 0.780+/-0.023, respectively.