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Purpose: The SYRMA-3D collaboration is setting up a breast computed tomography (bCT) clinical program at the Elettra synchrotron radiation facility in Trieste, Italy. Unlike the few dedicated scanners available at hospitals, synchrotron radiation bCT requires the patient's rotation, which in turn implies a long scan duration (from tens of seconds to few minutes). At the same time, it allows the achievement of high spatial resolution. These features make synchrotron radiation bCT prone to motion artifacts. This article aims at assessing and compensating for motion artifacts through an optical tracking approach. Methods: In this study, patients’ movements due to breathing have been first assessed on seven volunteers and then simulated during the CT scans of a breast phantom and a surgical specimen, by adding a periodic oscillatory motion (constant speed, 1 mm amplitude, 12 cycles/minute). CT scans were carried out at 28 keV with a mean glandular dose of 5 mGy. Motion artifacts were evaluated and a correction algorithm based on the optical tracking of fiducial marks was introduced. A quantitative analysis based on the structural similarity (SSIM) index and the normalized mean square error (nMSE) was performed on the reconstructed CT images. Results: CT images reconstructed through the optical tracking procedure were found to be as good as the motionless reference image. Moreover, the analysis of SSIM and nMSE demonstrated that an uncorrected motion of the order of the system's point spread function (around 0.1 mm in the present case) can be tolerated. Conclusions: Results suggest that a motion correction procedure based on an optical tracking system would be beneficial in synchrotron radiation bCT.

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.

Item does not contain fulltext 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.

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.

X-ray Photon Counting Detectors (XPCDs) with thick semiconductor sensors and small pixel sizes suffer from a charge-sharing effect which can induce multiple counts from a single interacting photon. This issue degrades not only the energy resolution, but it also worsens the spatial resolution. Multiple counts can be removed by acting on the discriminator threshold or they can be corrected by means of specific acquisition modalities implemented in the readout electronics. In this paper we present the results of the characterization of the Pixirad-1/Pixie-III device, a XPCD carrying a 650 μ m thick CdTe sensor with a small pixel ( 62 × 62 μ m 2 ). The Pixie-III readout system includes programmable energy thresholds and it implements three acquisition modes: a pure photon counting mode and two modes specially designed to correct charge-sharing effects. The measured energy resolution of the three acquisition modes for different energies are here reported. Moreover, we characterize the imaging performance for different combinations of acquisition modes and thresholds by measuring the presampling Modulation Transfer Function (MTF), the Normalized Noise Power Spectrum (NNPS) and by assessing the Noise Equivalent number of Quanta (NEQ).

A Phase-Contrast breast CT facility based on a high-resolution CdTe photon-counting detector is under development at Elettra, the Italian Synchrotron Radiation (SR) facility in Trieste. The CT system exploits propagation-based phasecontrast imaging and phase-retrieval algorithm. The voxel size is 57×57×50 μm3 and the delivered MGDs, about 5 mGy, are comparable with clinical breast CT systems. In the present contribution, the comparisons between histological breast cancers and full breast CT images are presented from samples of breast mastectomy. The high resolution of the breast CT images and low noise due to the phase contrast allow a very fine matching between X-ray CT and histology at acceptable delivered doses.

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.

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.

The vertical intensity distribution of synchrotron-based X-ray beams usually has a Gaussian profile encompassing large intensity variations. For biomedical imaging applications this may entail sub-optimal dose distributions and large fluctuations in terms of image noise. Commonly, planar metallic filters coupled with absorbing slits systems are applied to adjust the delivered flux and to limit intensity variations, respectively. The latter results in a reduction of the effective beam size. A flattening filter that counterbalances the transverse inhomogeneity, while retaining a sufficient flux, has been developed in the context of a monochromatic phase-contrast breast computed tomography application, ongoing at the Elettra synchrotron facility. The implementation of the new filtration system results in homogeneous intensity (hence dose) distribution and signal-to-noise ratio across the imaged volume. Finally, and most importantly, it allows a wider portion of the beam to be used, directly translating into a major (∼40%) reduction of the overall scan time for samples requiring a field of view larger than the beam size (i.e. multiple translation steps).

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.

X-ray spectral computed microtomography (µ-CT) has gained considerable interest in recent years thanks to the development of Photon Counting X-ray Detectors (PCXDs). Through the energy-based discrimination of the photons, obtained by setting up the discriminator threshold at different levels, PCXDs allow measuring photon energies with an accuracy appropriate for several practical applications. The major potentials of this approach are multiple contrast images (sometimes referred to as “color” or “spectral” images), obtained by using a single polychromatic source. In contrast to multiple acquisitions with different tube spectra, photon-counting spectral CT eliminates the risk of misregistration due to motion between consecutive scans and it allows for the elimination of dark noise in the image by rejecting all the events below the signal threshold. Of particular importance is the application of spectral CT in preclinical models where small animals are scanned and an effective discrimination among e.g. soft-tissue, bone and K-edge contrast agents can be in principle performed in a single shot. While spectral CT is considered very promising, its practical application has been hampered by the charge sharing issue that negatively affects the energy resolution of PCXDs. However, latest generations of PCXDs implement solutions to cope with the charge sharing effects, thus allowing sharp color sensitivity. This work presents a comparison of K-edge spectral CT images acquired with the Pixirad-I/Pixie-III detector with and without the application of a charge sharing recovery solution. When a solution for the charge sharing issue is considered both the spatial accuracy and energy resolution are preserved, thus allowing accurate K-edge subtraction imaging.

Item does not contain fulltext Two dosimetric quantities [mean glandular dose (MGD) and entrance surface air kerma (ESAK)] and the diagnostic performance of phase-contrast mammography with synchrotron radiation (MSR) are compared to conventional digital mammography (DM). Seventy-one patients (age range, 41 to 82 years) underwent MSR after a DM examination if questionable or suspicious breast abnormalities were not clarified by ultrasonography. The MGD and the ESAK delivered in both examinations were evaluated and compared. Two on-site radiologists rated the images in consensus according to the Breast Imaging Reporting and Data System assessment categories, which were then correlated with the final diagnoses by means of statistical generalized linear models (GLMs). Receiver operating characteristic curves were also used to assess the diagnostic performance by comparing the area under the curve (AUC). An important MGD and ESAK reduction was observed in MSR due to the monoenergetic beam. In particular, an average 43% reduction was observed for the MGD and a reduction of more than 50% for the ESAK. GLM showed higher diagnostic accuracy, especially in terms of specificity, for MSR, confirmed by AUC analysis ([Formula: see text]). The study design implied that the population was characterized by a high prevalence of disease and that the radiologists, who read the DM images before referring the patient to MSR, could have been influenced in their assessments. Within these limitations, the use of synchrotron radiation with the phase-contrast technique applied to mammography showed an important dose reduction and a higher diagnostic accuracy compared with DM. These results could further encourage research on the translation of x-ray phase-contrast imaging into the clinics.

Background The SYRMA-3D collaboration is setting up the first clinical trial of phase-contrast breast CT with synchrotron radiation at the Elettra synchrotron facility in Trieste, Italy. In this communication, a quality control protocol for breast CT is proposed, and a first test of image quality measurements is performed by means of a custom-made radiographic phantom. Materials and methods A set of projections is acquired and used to perform a CT reconstruction of two selected portions of the phantom. Such portions contain a uniform layer of water and a set of radiographic inserts, respectively. Together, they allow to perform several image quality measurements, namely CT number linearity, reconstruction accuracy, uniformity, noise, and low contrast resolution. All measurements are repeated at different beam energies in the range of interest, and at two different dose values. Results Measurements show a good linearity in the soft tissue range, paired to a high accuracy of the CT number reconstruction. Uniformity and noise measurements show that reconstruction inhomogeneities are bound to a few percent of the average pixel values. However, low contrast detectability is limited to the higher portion of the explored energy range. Conclusions The results of the measurements are satisfactory in terms of their quality, feasibility and reproducibility. With minimal modifications, the phantom is promising to allow a set of image quality measurements to be used in the upcoming clinical trial.

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.

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.

Unlike conventional x-ray attenuation one of the advantages of phase contrast x-ray imaging is its capability of extracting useful physical properties of the sample. In particular the possibility to obtain information from small angle scattering about unresolvable structures with sub-pixel resolution sensitivity has drawn attention for both medical and material science applications. We report on a novel algorithm for the analyzer based x-ray phase contrast imaging modality, which allows the robust separation of absorption, refraction and scattering effects from three measured x-ray images. This analytical approach is based on a simple Gaussian description of the analyzer transmission function and this method is capable of retrieving refraction and small angle scattering angles in the full angular range typical of biological samples. After a validation of the algorithm with a simulation code, which demonstrated the potential of this highly sensitive method, we have applied this theoretical framework to experimental data on a phantom and biological tissues obtained with synchrotron radiation. Owing to its extended angular acceptance range the algorithm allows precise assessment of local scattering distributions at biocompatible radiation doses, which in turn might yield a quantitative characterization tool with sufficient structural sensitivity on a submicron length scale.

Purpose We propose a technique for the characterization of tissues, based on a hybrid phase contrast-attenuation imaging. The technique, first introduced in [1] , makes use of a method for material basis decomposition proposed by Alvarez and Macovski [2] . We present a semi-analytical simulation of the imaging process, as well as a preliminary implementation on a set of radiographic images of a dedicated phantom. Methods The phantom consists in a thin plastic plate composed of two “soft” materials, arranged in such a way to create a faint pattern of decreasing radiographic contrasts. The imaging was performed using synchrotron radiation (i.e. a quasi-parallel, monochromatic and coherent X-ray beam) and placing the phantom at different distances from the detector, so as to enhance the contribution of phase contrast. The images were acquired at the SYRMEP beamline of the Elettra synchrotron facility (Trieste, Italy). Results The reconstructed composition of the phantom was compared to the results of the semi-analytical simulation, showing a good agreement with the theoretical expectations. In particular, the technique proved able to enhance the visibility of faint contrasts with respect to the standard attenuation-based imaging. Moreover, it provided a precise quantitative estimate of the local composition of the imaged phantom. Conclusions The application of the basis decomposition method to the context of phase contrast imaging allows an effective rendering of a broad spectrum of radiographic patterns, from low frequency textures (which are captured by the attenuation effects) to high frequency details (highlighted by the phase shift effects). In addition, thanks to the simultaneous enforcement of two separate imaging channels, it also allows a two-component reconstruction of the imaged object.

Purpose There is a worldwide shortage of clinical medical physics professionals and medical physics academics. Adequate academic education and structured clinical training of medical physicists play a vital role in ensuring the safe and effective use of advanced technologies in both diagnosis and treatment. In order to address the problem of supporting high-level skills in countries without post-graduate education in Medical Physics an international Master of Advanced Studies in Medical Physics has been jointly organized by our institutions. Methods The Master offers a study program in line with the best international practices that provides both knowledge and practical skills to graduate students. It is a two-years program: one academic year of theoretical classes followed by one year of supervised clinical training in radiotherapy or medical imaging. The clinical training is organized according to the IAEA, AFRA and IOMP guidelines. It is jointly organized by the Physics Department of the local university, and by an international scientific institution located in the same area. The university hospital actively supports the program. Most fellowships are provided by an international agency, and are supplemented by others from local or international institutions. Results The 5th cycle of the Master was opened in 2018. Up to now 86 students have been enrolled in the Master from all the continents: 39 from Africa, 21 from Asia, 19 from Latin America, 1 from Oceania and 6 from Europe (25 women and 61 men). The cooperation between university and the international scientific institution is a recognized example of effective synergy: the university has experience in high-level education and organization of courses while the international institution has an efficient network for the international enrolment of students and a large experience in international mobility. The generous collaboration of a large number of hospitals with medical physics departments guarantees a one-year-long supervised clinical training per each student. Conclusions The Master programme requires an extensive effort from both students and the organizing institutions, but the results are very satisfactory as the graduates are highly appreciated in the hospitals in their home countries.

Computed x-ray phase contrast micro-tomography is the most valuable tool for a three dimensional (3D) and non destructive analysis of the tissue engineered bone morphology. We used a Talbot interferometer installed at SYRMEP beamline of the ELETTRA synchrotron (Trieste, Italy) for a precise 3D reconstruction of both bone and soft connective tissue, regenerated in vivo within a porous scaffold. For the first time the x-ray tomographic reconstructions have been combined with x-ray scanning micro-diffraction measurement on the same sample, in order to give an exhaustive identification of the different tissues participating to the biomineralization process. As a result, we were able to investigate in detail the different densities in the tissues, distinguishing the 3D organization of the amorphous calcium phosphate from the collagen matrix. Our experimental approach allows for a deeper understanding of the role of collagen matrix in the organic-mineral transition, which is a crucial issue for the development of new bio-inspired composites.

We present the implementation of the CT iterative reconstruction strategy developed within the SYRMA-CT project for in vivo phase contrast CT of the uncompressed breast, ongoing at the ELETTRA synchrotron radiation facility (Trieste, Italy). Propagation-based phase-contrast imaging exploited the high spatial coherence of the monoenergetic laminar X-ray beam (3-mm high along the chest-wall-to-nipple direction), as well as the large object-to-detector distance (∼2 m) and the use of a prototype of Pixirad-8 high-resolution photon counting CdTe detector (60-μm pitch, eight detector units arranged in a row). The signal in projection views depends on the X-ray absorption as well as on the phase shift introduced by the breast tissue in the beam path. A phase retrieval algorithm allows recovering the projected 2D phase map of the irradiated tissue layer, which were input to the CT reconstruction; then, the 3D image of the breast was reconstructed via a simultaneous algebraic reconstruction technique (SART) algorithm. The developed iterative reconstruction — coupled with a filtering process for reducing the noise level and ring artifacts by preserving edges sharpness — showed better image quality than conventional filtered backprojection (FBP) reconstruction. A phantom study showed that the iterative reconstruction produced images with a contrast-to-noise-ratio up to 65% and a spatial resolution up to 12% higher than those obtained with FBP. Finally, the developed algorithm removed ring-like artifacts caused by the detector dead space (0.16 mm) across adjacent detector units and by no perfect equalization after flat-field correction, without worsening the image quality.

The SYRMA-CT project aims to set-up the first clinical trial of phase-contrast breast Computed Tomography with synchrotron radiation at the SYRMEP beamline of Elettra, the Italian synchrotron light source. The challenge in a dedicated breast CT is to match a high spatial resolution with a low dose level. In order to fulfil these requirements, the SYRMA-CT project uses a large area CdTe single photon counting detector (Pixirad-8), simultaneous algebraic reconstruction technique (SART) and phase retrieval pre-processing. This work investigates the imaging performances of the system in a continuous acquisition mode and with a low dose level towards the clinical application. A custom test object and a large surgical sample have been studied.

The aim of the SYRMA-CT collaboration is to set-up the first clinical trial of phase-contrast breast CT with synchrotron radiation (SR). In order to combine high image quality and low delivered dose a number of innovative elements are merged: a CdTe single photon counting detector, state-of-theart CT reconstruction and phase retrieval algorithms. To facilitate an accurate exam optimization, a Monte Carlo model was developed for dose calculation using GEANT4. In this study, high isotropic spatial resolution (120 mu m)(3) CT scans of objects with dimensions and attenuation similar to a human breast were acquired, delivering mean glandular doses in the range of those delivered in clinical breast CT (5-25 mGy). Due to the spatial coherence of the SR beam and the long distance between sample and detector, the images contain, not only absorption, but also phase information from the samples. The application of a phase-retrieval procedure increases the contrast-to-noise ratio of the tomographic images, while the contrast remains almost constant. After applying the simultaneous algebraic reconstruction technique to low-dose phase-retrieved data sets (about 5 mGy) with a reduced number of projections, the spatial resolution was found to be equal to filtered back projection utilizing a four fold higher dose, while the contrast-to-noise ratio was reduced by 30%. These first results indicate the feasibility of clinical breast CT with SR.

Conventional X-ray medical imaging makes use of the transmission properties of the sample. On the other hand, recently introduced phase-sensitive techniques take advantage of the phase shifts that occur when an electromagnetic wave encounters different refraction indices. Diffraction-Enhanced Imaging (DEI) is a phase-sensitive X-ray imaging technique based on the use of an analyzer placed between the sample and the detector. DEI performed at several synchrotron radiation facilities worldwide has proven outstanding image quality both in material science and medical imaging. At the medical imaging beamline SYRMEP under operation at the synchrotron radiation facility ELETTRA (Trieste, Italy), an analyzer system has been implemented to perform DEI. Experiments to evaluate the associated improvements in image quality were carried out on phantoms and biological samples and to prove that DEI is an appropriate tool for studying refraction and scattering properties. The results observed on the examples reported in this work suggest that the edge-enhancement effects and the superior sensitivity to soft tissue make DEI a valuable tool for early diagnosis of subtle diseases in many different fields.

This report discusses the optimization strategy, the theoretical background and first experimental data of a new refractive lens for focusing X-rays. In order to reduce the absorption of X-rays in this transmission lens, optically passive material was removed from the necessarily concave lens shape in a highly regular pattern. The feature dimensions require lens production and replication by deep X-ray lithography, which allows shaping in only one dimension. Consequently such a lens can focus in one direction only, so a crossed lens pair is needed for two-dimensional focusing. The single lens is composed of two large prisms of millimetre size, which touch each other at one of the tips, like an old sand clock. Each large prism contains a highly regular structure of essentially identical prism-like smaller segments. The first lens prototypes focused an X-ray beam with a vertical size of 500 microm and a photon energy of 8 keV to a line with a width of only 2.8 microm. This is only slightly worse than the line width of 1.73 microm expected for its focal length of f = 2.18 m. The photon density enhancement in the focus was 25, but could have been larger as the lens can intercept a beam height of 2.6 mm.

Objective: To determine the feasibility of detecting the structural orientation in cartilage with Diffraction Enhanced X-Ray Imaging. Design: Human tali and femoral head specimens were Diffraction Enhanced X-Ray Imaged (DEI) at the SYRMEP beamline at Elettra at various energy levels to detect the architectural arrangement of collagen within cartilage. DEI utilizes a monochromatic and highly collimated beam, with an analyzer crystal that selectively weights out photons according to the angle they have been deviated with respect to the original direction. This provides images of very high contrast, and with the rejection of X-ray scatter. Results: DEI allowed the visualization of articular cartilage and a structural orientation, resembling arcades, within. Conclusion: Our diffraction enhanced images represent the first radiographic detection of the structural orientation in cartilage. Our data are in line with previous studies on the structural organization of joint cartilage. They confirm the model of a vaulting system of collagen fiber bundles interrupted by proteoglycan aggregates.

This work presents the first study of x-ray phase contrast imaging based on a simple implementation of the edge illumination method (EIXPCi) in the field of mammography with synchrotron radiation. A simplified EIXPCi set-up was utilized to study a possible application in mammography at clinical doses. Moreover, through a novel algorithm capable of separating and quantifying absorption and phase perturbations of images acquired in EIXPCi modality, it is possible to extract quantitative information on breast images, allowing an accurate tissue identification. The study was carried out at the SYRMEP beamline of Elettra synchrotron radiation facility (Trieste, Italy), where a mastectomy specimen was investigated with the EIXPCi technique. The sample was exposed at three different energies suitable for mammography with synchrotron radiation in order to test the validity of the novel algorithm in extracting values of linear attenuation coefficients integrated over the sample thickness. It is demonstrated that the quantitative data are in good agreement with the theoretical values of linear attenuation coefficients calculated on the hypothesis of the breast with a given composition. The results are promising and encourage the current efforts to apply the method in mammography with synchrotron radiation.

Phase-contrast mammography with synchro-tron radiation is an innovative x-ray imaging technique that improves the identification of breast lesions. Previous studies have proven the superiority of the mammography images taken in the phase contrast modality using synchrotron radia-tion beams as compared with images taken in conventional mammography by subjective analyses. However, to our knowledge, no previous study has compared different acquisi-tion systems in order to quantify this improvement by means of objective robust indicators. In this research, we intend to quantify the superiority of phase contrast imaging by means of objective metrics of image quality. The initial analyses were made using phantom images from two digital equipment for mammography and phase contrast images using synchrotron radiation. The acquisition conditions were varied and three indexes of image quality estimated in order to compare the image quality. The results showed an improvement of the contrast in phase contrast images. This contrast improvements is important in the detection of small lesions and details.

Acellular scaffolds obtained via decellularization are a key instrument in regenerative medicine both per se and to drive the development of future-generation synthetic scaffolds that could become available off-the-shelf. In this framework, imaging is key to the understanding of the scaffolds’ internal structure as well as their interaction with cells and other organs, including ideally post-implantation. Scaffolds of a wide range of intricate organs (esophagus, lung, liver and small intestine) were imaged with x-ray phase contrast computed tomography (PC-CT). Image quality was sufficiently high to visualize scaffold microarchitecture and to detect major anatomical features, such as the esophageal mucosal-submucosal separation, pulmonary alveoli and intestinal villi. These results are a long-sought step for the field of regenerative medicine; until now, histology and scanning electron microscopy have been the gold standard to study the scaffold structure. However, they are both destructive: hence, they are not suitable for imaging scaffolds prior to transplantation and have no prospect for post-transplantation use. PC-CT, on the other hand, is non-destructive, 3D and fully quantitative. Importantly, not only do we demonstrate achievement of high image quality at two different synchrotron facilities, but also with commercial x-ray equipment, which makes the method available to any research laboratory.

This article discusses two experimental setups of edge illumi nation (EI) x-ray phase contrast imaging (XPCi) as well as the theory that is required to reconstruct quantitative tomographic maps using established methods, e.g. filtered back projection (FBP). Tomographic EI XPCi provides the option to reconstruct volumetric maps of different physical quantities, amongst which are the refractive index decrement from unity and the absorption coefficient, which can be used for dual-mode imaging. EI XPCi scans of a custom-built wire phantom using synchrotron and x-ray tube generated radiation were carried out, and tomographic maps of both para meters were reconstructed. This article further discusses the theoretical basis for the tomographic reconstruction of images showing combined phase and attenuation contrast. Corresponding experimental results are presented. Keywords: X-ray Phase Contrast Imaging, Tomography, Edge Illumination Phase Contrast, Quantitative Imaging, Laboratory-based Phase Imaging

Recently, new imaging modalities based on the detection of weak phase perturbations effects, among which are phase contrast and diffraction imaging, have been developed by several researchers. Due to their high sensitivity to weakly absorbing details, these techniques seem to be very promising for applications in the medical field. On the other hand, digital radiology is undergoing a wide diffusion, and its benefits are presently very well understood. Up to now, however, the strong pixel size constraints associated with phase contrast pattern detection limited the possibility of exploiting the advantages of phase contrast in digital radiology applications. In this paper, an innovative setup capable of removing the pixel size constraints, and thus opening the way to low dose digital phase contrast imaging, is described. Furthermore, we introduce an imaging technique based on the detection of radiation scattered at small angles: the information extracted from the sample is increased at no dose expense. We believe that several radiological fields, mammography being the first important example, may benefit from the herein described innovative imaging techniques.

FRONTier RADiography is an R&D project to assess the feasibility of digital mammography with Synchrotron Radiation at the ELETTRA Light Source in Trieste. In order to reach an acceptable time duration of the exam, a fast- and low-noise photon counting ASIC has been developed in collaboration with Aurelia Microelettronica, called Frontrad ReadOut SysTem. It is a multichannel counting system, each channel being made of a low-noise charge-sensitive preamplifier optimized for X-ray energy range (10–100 keV), a CR-RC 2 shaper, a discriminator and a 16-bit counter. In order to set the discriminator threshold, a set of a global 6-bit DAC and a local (per channel) 3-bit DAC has been implemented within the ASIC. We report on the measurements done with the 8-channel prototype chip and the comparison with the simulation results.

X-Ray Phase Contrast Imaging (XPCI) has been arguably the hottest topic in X-ray imaging research over the last two decades, due to the significant advantages it can bring to medicine, biology, material science and many other areas of application. Considerable progress has recently been achieved, in terms of the first in vivo implementations at synchrotrons (notably at Elettra in Trieste), and of new XPCI methods working with conventional sources. Among the latter, edge-illumination (EI) is possibly one of the most promising in terms of mainstream translation, due to set-up simplicity, scalability and flux efficiency compared to other approaches. EI is indeed the only method working with a completely incoherent source: however, it was recently demonstrated that neither the ability to perform quantitative phase retrieval, nor the method's phase sensitivity are affected by the source's incoherence. Here its implementation with different detector technologies is discussed.

Charge sharing plays an important role in the performance of single-photon counting microstrip detectors, since the comparator threshold defines the effective pixel width. In this contribution, the PICASSO (Phase Imaging for Clinical Application with Silicon detector and Synchrotron radiatiOn) single-photon counting microstrip detector oriented in edge-on configuration has been used to study its spatial resolution as a function of the comparator threshold. The experiment was carried out with monochromatic x-rays at the SYRMEP beamline of the Elettra synchrotron radiation facility in Trieste (Italy). The Edge Spread Function (i.e. the integral of the Line spread Function, LSF) was measured by horizontally translating vertical slits from a bar-pattern test-object in front of the detector, at four different photon energies (19, 20, 22, and 25 keV) and for several different values of the comparator threshold. The effect of charge sharing between strips on the spatial resolution has been quantified by calculating the horizontal Modulation Transfer Function (MTF). Moreover, the composite LSF from neighboring pixels was obtained: this allowed estimating the optimal threshold for each photon energy by selecting the threshold at which the composite LSF would approach unity along the entire width of the pixel. The results show that at thresholds lower than half of the photon energy, charge sharing increases the effective pixel width, causing a drop of the MTF, and it is responsible for the appearance of peaks in the composite LSF. Conversely, at thresholds higher than half of the photon energy, the effective pixel width is reduced and the spatial resolution is increased, but the collection efficiency is compromised, as demonstrated by the presence of valleys in the composite LSF.

The use of alginate based microcapsules to deliver drugs and cells with a minimal host interaction is increasingly being proposed. A proficient method to track the position of the microcapsules during such therapies, particularly if they are amenable to commonly used instrumentation, would greatly help the development of such treatments. Here we propose to label the microcapsules with gold nanoparticles to provide a bright contrast on small animal x-ray micro-CT systems enabling single microcapsule detection. The microcapsules preparation is based on a simple protocol using inexpensive compounds. This, combined with the widespread availability of micro-CT apparatus, renders our method more accessible compared with other methods. Our labeled microcapsules showed good mechanical stability and low cytotoxicity in-vitro . Our post-mortem rodent model data strongly suggest that the high signal intensity generated by the labeled microcapsules permits the use of a reduced radiation dose yielding a method fully compatible with longitudinal in-vivo studies. From the Clinical Editor The authors of this study report the development of a micro-CT based tracking method of alginate-based microcapsules by incorporating gold nanoparticles in the microcapsules. They demonstrate the feasibility of this system in rodent models, where due to the high signal intensity, even reduced radiation dose is sufficient to track these particles, providing a simple and effective method to track these commonly used microcapsules and allowing longitudinal studies.

The SYRMEP beam line is currently in the upgrading phase for mammographic examinations on patients at Elettra in Trieste. At the same time, a digital detection system, suitable for in -vivo breast imaging, is under development; it consists of a silicon laminar detector array operating in single photon counting mode. The duration of a clinical examination should not exceed a few seconds. Fast read out electronics is therefore necessary with the aim of avoiding losses in image contrast in presence of high counting rates. A custom ASIC working with 100% efficiency for rates up to 100 kHz per pixel has been designed and tested, and other solutions based on commercially available ASICs are currently under test. Several detector prototypes have been assembled, and images of mammographic test objects have been acquired. Image quality, efficiency and contrast losses have been evaluated in all cases as a function of the counting rate.

Digital detectors based on complementary metal-oxide-semiconductors (CMOS) active pixel sensor (APS) technology have been introduced recently in many scientific applications. This work is focused on the X-ray performance evaluation of a novel CMOS APS detector in low energy medical imaging applications using monochromatic synchrotron radiation (i.e., 17-35 keV), which also allows studying how the performance varies with energy. The CMOS sensor was coupled to a Thallium-activated structured cesium iodide (CsI:Tl) scintillator and the detector's X-ray performance evaluation was carried out in terms of sensitivity, presampling modulation transfer function (pMTF), normalized noise power spectrum (NNPS) and the resulting detective quantum efficiency (DQE). A Monte Carlo simulation was used to validate the experimentally measured low frequency DQE. Finally, the effect of iodine's secondary generated K-fluorescence X-rays on pMTF and DQE results was evaluated. Good agreement (within 5%) was observed between the Monte Carlo and experimentally measured low frequency DQE results. A CMOS APS detector was characterized for the first time over a wide range of low energies covering the mammographic spectra. The detector's performance is limited mainly by the detectability of the scintillator. Finally, we show that the current data could be used to calculate the detector's pMTF, NNPS and DQE for any mammographic spectral shape within the investigated energies.

Over the last decade different phase contrast approaches have been exploited at the medical beamline SYRMEP of the synchrotron radiation facility Elettra in Trieste, Italy. In particular special focus has been drawn to analyzer based imaging and the associated imaging theory and processing. Analyzer based Imaging (ABI) and Diffraction Enhanced Imaging (DEI) techniques have been successfully applied in several biomedical applications. Recently it has been suggested to translate the acquired knowledge in this field towards a Thomson Backscattering Source (TBS), which is presently under development at the Frascati National Laboratories of INFN (Istituto Nazionale di Fisica Nucleare) in Rome, Italy. Such source is capable of producing intense and quasi-monochromatic hard X-ray beams. For the technical implementation of biomedical phase imaging at the TBS a grating interferometer for differential phase contrast imaging has been designed and successfully tested at SYRMEP beamline.

A three-image method to extract absorption, refraction and scattering information for hard x-ray grating interferometry is presented. The method comprises a post-processing approach alternative to the conventional phase stepping procedure and is inspired by a similar three-image technique developed for analyzer-based x-ray imaging. Results obtained with this algorithm are quantitatively comparable with phase-stepping. This method can be further extended to samples with negligible scattering, where only two images are needed to separate absorption and refraction signal. Thanks to the limited number of images required, this technique is a viable route to bio-compatible imaging with x-ray grating interferometer. In addition our method elucidates and strengthens the formal and practical analogies between grating interferometry and the (non-interferometric) diffraction enhanced imaging technique.

We present a quantitative, non-interferometric, X-ray differential phase contrast imaging technique based on the edge illumination principle. We derive a novel phase retrieval algorithm which requires only two images to be acquired and verify the technique experimentally using synchrotron radiation. The technique is useful for planar imaging but is expected to be important for quantitative phase tomography also. The properties and limitations of the technique are studied in detail.

Synchrotron-radiation computed tomography has been applied in many research fields. Here, PITRE (Phase-sensitive X-ray Image processing and Tomography REconstruction) and PITRE_BM (PITRE Batch Manager) are presented. PITRE supports phase retrieval for propagation-based phase-contrast imaging/tomography (PPCI/PPCT), extracts apparent absorption, refractive and scattering information of diffraction enhanced imaging (DEI), and allows parallel-beam tomography reconstruction for conventional absorption CT data and for PPCT phase retrieved and DEI-CT extracted information. PITRE_BM is a batch processing manager for PITRE: it executes a series of tasks, created via PITRE, without manual intervention. Both PITRE and PITRE_BM are coded in Interactive Data Language (IDL), and have a user-friendly graphical user interface. They are freeware and can run on Microsoft Windows systems via IDL Virtual Machine, which can be downloaded for free and does not require a license. The data-processing principle and some examples of application will be presented.

To prospectively evaluate the diagnostic contribution of mammography with synchrotron radiation in patients with questionable or suspicious breast abnormalities identified at combined digital mammography (DM) and ultrasonography (US).The ethics committee approved this prospective study, and written informed consent was obtained from all patients. Mammography with synchrotron radiation was performed with a phase-detection technique at a synchrotron radiation laboratory. Forty-nine women who met at least one of the inclusion criteria (palpable mass, focal asymmetry, architectural distortion, or equivocal or suspicious mass at DM; none clarified at US) were enrolled. Forty-seven women (mean age, 57.8 years ± 8.8 [standard deviation]; age range, 43-78 years) completed the study protocol, which involved biopsy or follow-up for 1 year as the reference standard. Breast Imaging Reporting and Data System (BI-RADS) scores of 1-3 were considered to indicate a negative result, while scores 4-5 were considered to indicate a positive result. The visibility of breast abnormalities and the glandular parenchymal structure at DM and at mammography with synchrotron radiation was compared by using the Wilcoxon signed rank test.In 29 of the 31 patients with a final diagnosis of benign entity, mammography with synchrotron radiation yielded BI-RADS scores of 1-3. In 13 of the remaining 16 patients with a final diagnosis of malignancy, mammography with synchrotron radiation yielded BI-RADS scores of 4-5. Therefore, a sensitivity of 81% (13 of 16 patients) and a specificity of 94% (29 of 31 patients) were achieved with use of the described BI-RADS dichotomization system.These study results suggest that mammography with synchrotron radiation can be used to clarify cases of questionable or suspicious breast abnormalities identified at DM.http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11100745/-/DC1.

The SYRMEP (Synchrotron Radiation for Medical Physics) collaboration has performed, for the first time in the world, a clinical program of mammography with synchrotron radiation. This program provided excellent results, although utilizing a commercial screen-film system as a detector. The PICASSO (Phase Imaging for Clinical Application with Silicon detector and Synchrotron radiation) project has developed a detector prototype capable of fully exploiting the peculiar characteristics of the synchrotron source, utilizing silicon microstrip sensors illuminated in the edge-on geometry and operated in single-photon counting. In this paper the potential of the PICASSO detector in breast computed tomography was evaluated by means of custom phantoms. Very encouraging results have been obtained with severe dose constrains as far as both spatial and contrast resolution are concerned. Moreover, the capability of detecting phase contrast effects was demonstrated, albeit with a higher delivered dose. (C) 2010 Elsevier B.V. All rights reserved.

Prisms deflect and disperse X-rays due to refraction very similar to visible light. As X-rays are always attenuated while traversing material, the intensity distribution in the transmitted beam carries information about the prism transmission function. This study will show that sufficient information is contained in a single digitally registered radiograph from a rectangular prism, for deriving both the refractive index of the material and its attenuation length. The measured data can be prepared such that neither intensity fluctuations nor false light content in the incident beam will introduce systematic errors into the result. The strategy is thus very adapted, when single shot pictures are taken at X-ray sources with limited shot reproducibility. This technique is favourably be used at very grazing angles of incidence of the order of the critical angle for the prism material, when the beam deflection becomes significant. In such a geometry dimensional parameters, like sample thickness, do not affect the data analysis, which is particularly insensitive to even significant errors in the tip angle. (C) 2011 Elsevier B.V. All rights reserved.

In line X-ray phase contrast micro-computed tomography (IL-XPCT), which can be implemented at third generation synchrotron radiation sources or by using a micro-focus X-ray tube, is a powerful technique for non-destructive, high-resolution investigations of a broad variety of materials. At the Shanghai Synchrotron Radiation Facility (SSRF), the X-ray Imaging and Biomedical Applications Beamline was built and started regular user operation in May 2009. Both qualitative (without phase retrieval) and quantitative (with phase retrieval) three-dimensional IL-XPCT experimental techniques have been established at the beamline. IL-XPCT experiments of a test sample (plastic pipes) used to evaluate the technique, and of a biological sample (locust) at the beamline are reported. Two series of images, qualitative and quantitative, including tomographic slices and three-dimensional rendering images were obtained. In qualitative images, there is a strong edge-enhancement which leads to very clear sample contours, while in quantitative images, the edge-enhancement fades but quantitative measurement of sample's phase information could be achieved. The experiments demonstrate that the combination of qualitative and quantitative images is useful for biological sample studies.

As different methods to improve diffraction enhanced imaging are proposed, the authors introduce a simple algorithm that follows the original idea of Chapman et al. (Phys. Med. Biol. 42, 2015, 1997), but extend it to a general object featuring absorption, refraction, and ultrasmall-angle scattering. The information relative to the three effects is decoupled, requiring only three images in input. Simulation and experiment give accurate results, provided the refraction and scattering angles are small compared to the rocking curve width. The proposed algorithm can be readily and fruitfully implemented in several applications, particularly when time and dose constraints are relevant.

This work investigates the use of XR-QA2 radiochromic films for quantitative imaging of a synchrotron radiation (SR) beam. Pieces (200 × 30 mm2) of XR-QA2 film were irradiated in a plane transverse to the beam axis, at the SYRMEP beamline at ELETTRA (Trieste), with a monochromatic beam of size 170 × 3.94 mm2 (H × V) and energy of 28, 35, 38 or 40 keV. The response was calibrated in terms of average air kerma (120 mGy), measured with a calibrated ionization chamber. Films were digitized in reflectance mode using a flatbed scanner. The 16-bit red channel was used. The netreflectance was then converted to photon fluence per unit air kerma (mm-2 mGy-1). The SR beam profile was acquired also with a scintillator (GOS) based, fiberoptic coupled CCD camera as well as with a scintillator based flat panel detector. Horizontal profiles obtained with the two modalities were compared, evaluated in a ROI of 17.71 × 0.59 mm2, across the beam centre. Once corrected for flat field, the CCD profile was scaled in order to have the same average value as the normalized profile acquired with the gafchromic film. The same procedure was followed for the beam images acquired with the flat panel detector. Horizontal and vertical line profiles acquired with the radiochromic film show an uneven 2D distribution of the beam intensity, with variations in the order of 1520% in the horizontal direction, while the statistical uncertainties evaluated for the radiochromic dose measurements were 6% at 28 keV. Larger variations up to 64% were observed in the vertical direction. The response of the radiochromic film is comparable to that of the other imaging detectors, within less than 5% variation.

In this work we present a novel 3D Monte Carlo photon transport program for simulation of multiple refractive scattering based on the refractive properties of X-rays in highly scattering media, like lung tissue. Multiple scattering reduces not only the quality of the image, but contains also information on the internal structure of the object. This information can be exploited utilizing image modalities such as Diffraction Enhanced Imaging (DEI). To study the effect of multiple scattering a Monte Carlo program was developed that simulates multiple refractive scattering of X-ray photons on monodisperse PMMA (poly-methyl-methacrylate) microspheres representing alveoli in lung tissue. Eventually, the results of the Monte Carlo program were compared to the measurements taken at the SYRMEP beamline at Elettra (Trieste, Italy) on special phantoms showing a good agreement between both data., 5 page, 7 figures

Description of purpose: Treatment of osteoarthritis in stages of reversible disease requires high resolution visualization of early cartilage damage and of subchondral bone. Here, DEI (Diffraction Enhanced Imaging) is compared to MRI, computed X-ray tomography (CT) and ultrasound (UI) in its ability to detect early degeneration of articular cartilage. In contrast to conventional absorptive X-ray examination where cartilage is poorly visible DEI captures cartilage by detection of selected refraction. Methods: Human femoral heads were investigated by macroscopic inspection, conventional X-ray examination, DEI, MRI, CT, UI and histology. DEI is an imaging technique applying a monochromatic parallel synchrotron X-ray beam. Image features were verified by histology. Results: DEI, MRI and ultrasound lead to interpretable images of cartilage. Of all techniques, DEI provided highest image resolution revealing the structural tissue architecture. MRI needs a very long exposure time (more than 5 hours) to achieve comparable quality. Application of ultrasound is limited because of joint geometry and, at high sound frequency, the necessity of close contact between cartilage and transducer. DEI is an experimental technique which needs synchrotron radiation. Conclusion: DEI is a very promising imaging technique for visualization of cartilage and bone. It may serve as an excellent analytical tool for experimental studies. Our pictures show a part of future of optimised techniques for imaging. Synchrotron based DEI may lead the way towards optimisation of improved techniques for imaging. Upon development of adequate small scale X-ray sources, DEI will also be an important supplementation for medical imaging.

Silicon microstrip detectors in the edge on geometry, i.e. oriented with the strips parallel to the incoming beam, allow a high absorption efficiency for X-rays in the 10–100 keV energy range. In medical imaging, this results in a significant reduction of the dose given to the patient with respect to conventional screen-film systems. This geometrical configuration was first proposed in the early 90s and since then it has been applied to several medical imaging projects. In this short review, an overview of some medical imaging applications using edge on detectors will be presented, focusing the attention on the main characteristics of the detection systems. The studies performed in Trieste in order to optimize such detectors for digital mammography with synchrotron radiation will be described in detail. In particular, novel imaging techniques (phase contrast, refraction and scatter imaging, computed tomography) implemented and tested at the Trieste synchrotron light source will be shortly discussed.