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In CdTe X-ray photon counting detectors (PCD) featuring small pixel sizes (< 100 μm), charge-sharing and fluorescences emitted by Cd and Te are responsible for multiple counts from a single interacting photon. These effects can impair the imaging and spectroscopic performance of PCDs. Multiple counts can be partially or totally discriminated by properly setting the energy threshold implemented by the PCD system. Using monochromatic radiation and the Pixirad-1/Pixie-II CdTe PCD, this work characterizes and quantifies clusters of multiple counts as a function of energy and threshold.

By means of a combined microscopy-, spectroscopy-, and tomography-based approach, we investigated surface and interface defects in metal-polymer heterostacks. The aim was to characterize both morphological and compositional alterations of the surfaces, originating in the physical vapor deposition (PVD) growth methods adopted in the fabrication process. Synchrotron radiation X-ray computed tomography (CT) and scanning electron microscopy (SEM) coupled with energy dispersive X-ray Spectroscopy (EDS) indicate that both chemical contaminations, introduced in the fabrication process, and growth conditions strongly affect the presence of defects. On the basis of our results, we classified the defects into four main families. Interestingly, the faults are mainly located at the metal-polymer interface. Thanks to this study, we have been able to gain a deeper insight into the defects' origins and nature, allowing the identification of the precise production steps involved in the generation of the selected defects.

The development of accurate simulation tools including x-ray phase-contrast effects is of great use in the design and optimization of x-ray phase-contrast imaging (XPCI) experimental setups. When the lateral coherence of the imaging system is limited, as in most compact laboratory-based XPCI applications, phase-contrast can be effectively described through refraction effects that can be simulated with a ray-tracing approach. This work presents a practical implementation of the x-ray phase-contrast in Geant4 and validates the simulation results against theoretical predictions for the propagation-based (PB) and edge-illumination (EI) imaging configurations. The simulation includes a realistic polychromatic tungsten anode spectrum and an extended x-ray source, a virtual phantom made of plastic wires with a diameter of 1 mm, as well as an accurate description of the absorbing masks and related movement during data acquisition. Results show a good agreement between theory and simulations, with maximum discrepancies below 2% in the intensity of PB images, below 0.3 μrad for EI refraction, and below 0.03 mm for EI projected thickness. Additionally, an often disregarded effect such as the refraction sensitivity inhomogeneity across the field of view (around 20%) was reproduced by the simulation and quantitatively explained through a theoretical model. The presented simulation platform will be extensively used for the design of a novel EI facility that is under construction at the INFN laboratories in Trieste (Italy) in the framework of the Photon-counting Edge-illumination Phase-contrast Imaging (PEPI) project.

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.

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.

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.

Iterative CT reconstruction algorithms coupled with edge-preserving filters are attracting a growing interest in the field of biomedical X-ray imaging. In many cases the application of such algorithms results in an improved reconstruction quality when compared with filtered back-projection (FBP). Iterative algorithms commonly entail a decrease of image noise or, equivalently, an increase of contrast-to-noise ratio, while preserving image detail. Conversely, they modify the shape of noise power spectrum, producing a shift towards lower spatial frequencies with respect to FBP. This results in a "patchy" or "waxy" appearance of the reconstructed images. Changes in image texture affect radiologists’ perception of image quality, possibly influencing their willingness to use an iterative algorithm in clinical practice. In this work we present a GPU implementation of a simultaneous algebraic reconstruction technique algorithm, combined with a bilateral regularization filter, and we discuss the optimization of the algorithm’s parameters in terms of noise texture, selecting those parameters which preserve its "natural" appearance. We evaluated the performances of the algorithm, compared to FBP, both on a test phantom and on a surgical mastectomy sample by using contrast-to-noise ratio and spatial resolution metrics. Samples were imaged at the SYRMEP beamline of the Elettra synchrotron facility with a monochromatic beam (32 keV) in propagation-based phase-contrast configuration, delivering a clinically-compatible radiation dose of 5 mGy and using a large-area CdTe photon-counting detector. Results show, in the specific application on breast specimens, that the implemented algorithm can be tuned to preserve the noise texture and spatial resolution observed in FBP reconstructions, while improving contrast-to-noise ratio up to 30%.

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.

Photon counting semiconductor detectors in radiation imaging present attractive properties, such as high efficiency, low noise, and energy sensitivity. The very complex electronics limits the sensitive area of current devices to a few square cm. This disadvantage is often compensated by tiling a larger matrix with an adequate number of detector units but this usually results in non-negligible insensitive gaps between two adjacent modules. When considering the case of Computed Tomography (CT), these gaps lead to degraded reconstructed images with severe streak and ring artifacts. This work presents two digital image processing solutions to fill in these gaps when considering the specific case of synchrotron radiation x-ray parallel beam phase contrast CT. While not discussed with experimental data, other CT modalities, such as spectral, cone beam and other geometries might benefit from the presented approaches.

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.

CONTENTS 50.1 Introduction 50.2 General Considerations 50.3 Analyzer-Based Imaging 50.3.1 The Rocking Curve 50.3.2 A Simple Model of AB Image Formation 50.3.2.1 The Sample Introduces Refraction, But No USAXS 50.3.2.2 The Sample Introduces USAXS, But No Refraction 50.3.2.3 The Sample Introduces Both Refraction and USAXS 50.3.3 Phase Retrieval 50.3.3.1 The Sample Introduces Refraction, But No USAXS 50.3.3.2 The Sample Introduces USAXS, But No Refraction 50.3.3.3 The Sample Introduces Both Refraction and USAXS 50.3.3.4 Other Approaches to Phase Retrieval 50.3.4 Requirements 50.4 Edge Illumination 50.4.1 The Illumination Curve 50.4.2 Phase Retrieval and Sensitivity 50.4.3 Coherence Requirements 50.5 Computed Tomography 50.6 Applications to Biomedical Imaging 50.6.1 Breast 50.6.2 Musculoskeletal Phase-Contrast Imaging 50.6.3 Lung 50.6.4 Neuroimaging 50.6.5 Vasculature, Circulation, and Other Tissues 50.7 Conclusion References

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.

X-ray phase contrast imaging arises from changes of the propagation direction of the radiant wave field when traversing the object and it can yield higher contrast for soft tissues than conventional x-ray radiology based on attenuation. Commonly intermediate steps are required to transform wave front modulations into intensity modulations measurable by the detection system. One of these phase contrast techniques is analyzer-based imaging (ABI), which utilizes an analyzer crystal as angular filter with a bandwidth in the micro-radian regime placed between the sample and the detector. Furthermore employing appropriate algorithms, attenuation, refraction and scattering/dark field images can be extracted providing complementary information. The implementation of ABI requires X-ray optics with very high stability and micro-radian resolution. In return, this method possesses an extremely high sensitivity among the phase contrast techniques. At the medical beamline of the Italian synchrotron ELETTRA, a patient room has been imple-mented in order to perform clinical mammography with free-space propagation phase contrast. In this work we have tested the feasibility of ABI in a preclinical set-up implementing the system in the patient room. High quality images of breast tissues samples are presented and compared to images acquired at a conventional mammography unit. The system has shown excellent stability and imaging performances.

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.

SYRMA-3D (SYnchrotron Radiation MAmmography 3D) aims to develop a breast CT system based on monochromatic synchrotron radiation and a single photon counting detector (PIXIRAD-8) with CdTe sensor. Due to the demanding requests on high contrast resolution and low dose, images in breast CT are particularly sensitive to small imperfections of the flat field correction applied before the CT reconstruction. Detectors based on high Z crystal sensors show inhomogeneous pixels gain, which depends on the time from the switching-on of the high voltage polarization. This effect has been studied in our CdTe detector with the purpose of develop an effective flat field correction procedure. In the PIXIRAD-8 detector, the time-dependent inhomogeneities of the flat field signal appear to be local, small and systematically reproducible, with the exception of the pixels on the sensors edges.

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.

Purpose PCDs with energy discrimination led to new possibilities of improving the quality of X-ray medical images. PCDs are direct detection devices in which the charge delivered by a single interacting photon is directly collected and discriminated at single pixels level. The limit of high densely pixelated PCDs is the charge sharing which can lead to multiple counts from a single interaction degrading the spatial resolution of the system. Increasing the discrimination threshold, multiple counts can be partially or totally removed from images improving the spatial resolution at the cost of a reduction of the detection area of single pixels with a consequent loss of statistics. This work aims to show a simple method to find the optimal threshold which gives the best trade-off between spatial resolution and statistics. Methods The acquisitions have been performed at the SYRMEP beamline (Elettra Trieste) using the tomographic experimental set-up of INFN project SYnchrotron Radiation MAmmography (SYRMA-3D). SYRMA-3D uses ‘Pixirad-8’, a PCD with CdTe sensor and a pixel size of 60 μm. For this study, we used a monochromatic beam of 38 keV acquiring a set of images of an edge and a set of images of the beam with different detection thresholds. The two sets of images have been used respectively for the measurement of the Modulation transfer function (MTF) and the noise power spectrum (NPS). Combining both NPS and MTF the Number of Equivalent Quanta (NEQ) can be determined. The NEQ summarizes both informations about spatial resolution and noise and is an useful metrics for the global image quality assessment. Results The comparison between NEQ curves shows that lower thresholds give better NEQ response. Conclusions The increase of the discrimination threshold improves the spatial resolution but worsens the noise. The global image quality, measured using NEQ, is higher for lower thresholds.

Purpose To measure the dose distribution in a phantom during a synchrotron radiation (SR) computed tomography (CT) scan using radiochromic films, for procedure assessment and for offline dose monitoring in SR breast CT. Methods We used XR-QA2 radiochromic films (calibrated in terms of free air kerma) and a 14-cm PMMA cylindrical phantom. Measurements were performed at the SYRMEP beamline of ELETTRA facility, within the SYRMA-3D project for phase-contrast breast CT [1] . The phantom was positioned at isocenter, pending from the patient bed. Measurements were performed at 38 keV, beam size of 3 mm × 150 mm (H × W), at an air kerma corresponding to a mean glandular dose of 5 mGy in a 14-cm diameter 50% glandular breast. The phantom was irradiated over 360° first with a film at the mid-plane, and then with film strips wrapped on its surface. Additional tests were made over 180° with an axial scan pitch of 1, 0.8 or 0.5. Results Results show a dose map at mid-plane the phantom, indicating the cup-shaped horizontal profile due to primary and scatter dose. Analogous maps were recorded with the films at the periphery of the phantom, representing the surface dose maps. Conclusions We performed measurements of the dose distribution in a phantom during a SR CT scan with different irradiation geometries. This technique produces evidence for selecting the suitable scan procedure. Moreover, as an offline monitor system, a piece of calibrated radiochromic film wrapped on a suitable holder around the breast could record the history of the organ irradiation.

Purpose Breast Computed Tomography (CT) is a dedicated 3D imaging modality that provides a complete volumetric reconstruction of the uncompressed organ, thus matching a high image quality with an acceptable delivered dose. The SYRMA-3D collaboration is developing the first clinical trial of phase-contrast breast CT with synchrotron radiation at the Elettra synchrotron facility in Trieste. We present a proposal for a Quality Control (QC) protocol, including a custom made QC phantom that was designed and built by the laboratories of the University of Ferrara. Methods The synchrotron beam is monochromatic in the energy range 8.5–40 keV. The images were acquired with a photon counting detector placed at about 2 m from the organ, so as to generate a phase contrast signal. The QC phantom consists of a water filled PMMA cylinder, hung from the patient support through the breast aperture. It contains several inserts that allow measurements of geometric alignment, reconstruction uniformity and linearity, low and high contrast resolution. Results CT images of the phantom were acquired at several beam energies within the range of interest, to explore the energy dependence of the results. Uniformity and linearity appeared to be preserved by the reconstruction for all energies. Conversely, low contrast details exhibited a more pronounced dependence on the energy choice. Finally, the visibility of high contrast details was always found above acceptance levels. Conclusions The main goal of the study was to verify the compatibility of the QC phantom with the experimental environment of the SYRMA-3D project, and to test the validity and feasibility of the proposed QC protocol. With minimal modifications, they proved viable instruments to perform the necessary quality assessments for the innovative diagnostic device developed by the SYRMA-3D collaboration.

Purpose: In the past decade, phase-contrast imaging (PCI) has been applied to study different kinds of tissues and human body parts, with an increased improvement of the image quality with respect to simple absorption radiography. A technique closely related to PCI is phase-retrieval imaging (PRI). Indeed, PCI is an imaging modality thought to enhance the total contrast of the images through the phase shift introduced by the object (human body part); PRI is a mathematical technique to extract the quantitative phase-shift map from PCI. A new phase-retrieval algorithm for the in-line phase-contrast x-ray imaging is here proposed. Methods: The proposed algorithm is based on a mixed transfer-function and transport-of-intensity approach (MA) and it requires, at most, an initial approximate estimate of the average phase shift introduced by the object as prior knowledge. The accuracy in the initial estimate determines the convergence speed of the algorithm. The proposed algorithm retrieves both the object phase and its complex conjugate in a combined MA (CMA). Results: Although slightly less computationally effective with respect to other mixed-approach algorithms, as two phases have to be retrieved, the results obtained by the CMA on simulated data have shown that the obtained reconstructed phase maps are characterized by particularly low normalized mean square errors. The authors have also tested the CMA on noisy experimental phase-contrast data obtained by a suitable weakly absorbing sample consisting of a grid of submillimetric nylon fibers as well as on a strongly absorbing object made of a 0.03 mm thick lead x-ray resolution star pattern. The CMA has shown a good efficiency in recovering phase information, also in presence of noisy data, characterized by peak-to-peak signal-to-noise ratios down to a few dBs, showing the possibility to enhance with phase radiography the signal-to-noise ratio for features in the submillimetric scale with respect to the attenuation-based imaging. Conclusions: It has been shown that phase-retrieved radiographies can be used both to have quantitative phase information about soft tissues, complementary to the attenuation information, and to enhance the visibility of details inside soft tissues, with higher efficiency with respect to phase radiography.

It is widely demonstrated that phase contrast imaging yields better contrast resolution on soft-tissue with respect to conventional absorption radiography. In this feasibility study an application of synchrotron radiation imaging for arthritic bone erosion is presented. In particular two phase-contrast imaging techniques are investigated and analyzed in order to differentiate different aspects of bone microarchitecture and cartilages, with the ultimate aim to demonstrate the translation of the technique in in-vivo studies.

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.

Introduction The first clinical trial of phase-contrast mammography with monochromatic beam was performed at Elettra, the Italian Synchrotron Radiation facility. A lower Mean Glandular Dose (MGD) and a higher specificity were achieved compared to the digital mammography for the patient cohort (more than 70). Purpose The SYRMA-CT project (SYnchrotron Radiation for MAmmography – Computed Tomography) aims to perform the first clinical trial of phase-sensitive breast CT with monochromatic beam. High image quality and low dose are expected according to the results of the first mammography trial. Materials and methods A large area CdTe single photon counting detector (PIXIRAD-8) is used. Phase-retrieval algorithm are applied, thus exploiting propagation based phase-contrast imaging (PPCI). The dose system of the beamline has been calibrated to match the energy requirement up to 40 keV. Due to the peculiar irradiation modality, ad hoc Monte Carlo simulations and experimental measurements were performed for dose evaluation. Results Images of surgical samples included in large test objects (up to 12 cm diameter) were acquired at 38 keV in clinical compatible dose conditions (MGD ∼5 mGy). Phase-retrieval pre-processing was applied improving the CNR of the high-resolution images with (120 μm) 3 voxel size. Conclusion The upgrade of the mammographic facility of the Elettra laboratory towards a new clinical trial is going on. Image quality and dose assessment indicate its feasibility with monochromatic beam. This clinical trial will allow the evaluation of PPCI breast CT in optimal conditions and will give indication for the translation to the hospital of phase-sensitive techniques. Disclosure Nothing to declare.

An analyzer-based X-ray phase contrast imaging setup (ABI) based on four bounce Si(444) monochromators at 18 keV mounted at the SYRMEP beamline at Elettra is presented. The system was stable for the employed exposure times. Contrasts, visibility of the object edges and signal to noise ratio of the acquired images were studied. Simulation procedures of the images were also exploited. The results show that such setup can be used for high sensitivity (high contrast) experiments at Elettra. Also, due to intrinsic properties, this setup can be useful for future ultra-small angle X-ray scattering experiments.

In this work, we intend to relate the mineral to non-mineral bone scattering intensity ratio with the bone-mineral density (BMD) reduction. In this way, EDXRD can be a novel technique to measure BMD loss in function of the mineral and non-mineral scattering intensity. The scattering profiles were obtained at Laboratorio Nacional de Luz Sincrotron (LNLS) at the X-ray diffraction beamline XD2. A double-crystal Si(1 1 1) pre-monochromator, upstream of the beamline, was used to select a small energy bandwidth (Δ λ / λ ≈10 −4 ) at 11 keV. The sample holder has a circle depression in the center to contain a range of bone and fat mixture ratios. The mixture consists of powdered cortical bone and fat, which together simulate in vivo bone. The diffraction patterns were carried out with 0.5 mm slits after and behind of the sample holder. The data were collected in 0.05° increments every 0.5 s. EDXRD results show an indication of different bone densities may be distinguished which suggested that X-ray coherent scattering technique may have a role in monitoring changes in BMD via changes in the related scattering intensity of mineral and non-mineral bone. The main aim of the Synchrotron Radiation for MEdical Physics (SYRMEP) project at the ELETTRA is the investigation and the development of innovative techniques for medical imaging. The beamline provides, at a distance of about 23 m from the source, a monochromatic, laminar section X-ray beam with a maximum area of about 160×5 mm 2 at 20 keV. The monochromator, that covers the entire angular acceptance of the beamline, is based on a double-Si (1 1 1) crystal system working in Bragg configuration. A micrometric vertical and horizontal translation stage allows the positioning and scanning of the sample with respect to the stationary beam. In this case, the detector is kept stationary in front of the beam, while the object is rotated in discrete steps in front of it. At each rotation, a projection is acquired. A goniometric double-cradle system is used to adjust the rotation axis, which must be orthogonal with respect to the detector plane in transmission computed tomography (CT). The samples consisted of a 8 mm cube of bovine bone surrounded of a cartilage interface. High-resolution images of the trabecular structure were obtained by means a 16-bit CCD camera, 2048×2048 pixels, 14 μm pixel size (maximum spatial resolution: 25 μm).

A theoretical analysis of the x-ray phase contrast imaging and its validation via synchrotron radiation imaging is here presented. Two different mathematical models have been followed: the simpler ray-optical approach and the more rigorous Fresnel-Kirchoff diffraction theory. Subsequently, the conditions upon which the x-ray optical approximation can be used to describe the image formation mechanism have been analyzed, taking into account also the effects due to the finite source size and detector resolution. It is possible to demonstrate that the ray-optics results can also be obtained by opportunely developing the diffraction formalism only with some restrictions on the spatial frequencies present in the final image, without any limitation on the maximum phase shift. The conditions allowing the use of the simplified ray-optical approach to describe the phase contrast images have been here defined and their validation has been proved by means of computer simulations and phantom experiments.

The goal of this project is to determine the feasibility of utilizing colloidal gold as a marker for C6 glioblastoma cells implanted into rat brain as an appropriate model for volumetric measurements of tumors using absorption edge subtraction (AES). Phase sensitive X-ray imaging is combined with KES to give good soft tissue contrast. Current methods for volumetric measurements of implanted C6 glioblastoma tumors in rat brains using MRI technology are inadequate due to the small size of the tumor (2.5–4 mm in diameter) and the thickness of the MRI slice (1–1.5 mm). Previously, our group has shown that AES detection of colloidal gold labeled C6 glioblastoma cells implanted into a rat brains may be feasible. The long-term goal for this project is to establish a method, which would allow the researcher to monitor the development of a tumor over time. Most importantly, this technique should allow researchers to accurately determine the potency of a treatment on the size and growth rate for a C6 implanted tumors. In addition, we plan to challenge the hypothesis that tumors of the glioma type do not metastasize outside of the brain. A sensitive technique for the detection of C6 cells, such as that using colloidal gold and AES/DEI, should enable researchers to detect C6 cells, which have metastasized and migrated to different areas of the body. The ability to detect implanted C6 cells followed by the development of the tumor, the possible migration of the cells and the ability to accurately measure the effects of treatments on the volume of the tumor would be of the utmost importance to brain tumor research.

Enhanced contrast X-ray imaging is achieved by exploiting the real part ofthe refraction index, which is responsible for the phase shifts, in addition to the imaginary part, which is responsible for the absorption. Such techniques are called X-ray phase contrast imaging. An analyzer-based X-ray phase contrast imaging set-up with Diffraction Enhanced Imaging processing (DEI) were used for preliminary studies in anatomy and embryology of insects. Parasitized stinkbug and moth eggs used as control agents ofpests in vegetables and adult stinkbugs and mosquitoes (Aedes aegypti) were used as samples. The experimental setup was mounted in the SYRMEP beamline at ELETTRA. Images were obtained using a high spatial resolution CCD detector (pixel size 14 � 14mm 2 ) coupled with magnifying optics. Analyzer-based X-ray phase contrast images (PCI) and edge detection images show contrast and details not observed with conventional synchrotron radiography and open the possibility for future study in the embryonic development ofinsects. r 2005 Elsevier B.V. All rights reserved.

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.

Glioblastoma multiforme (GBM) is the commonest and most aggressive primary brain tumor in humans. The high rate of tumor recurrence results in a poor prognosis despite multimodality treatment. One reason for high rate of recurrence is the invasive nature of the tumor into the surrounding normal brain tissue or multifocal occurrence at sites remote from that of the primary tumor establishment. Existing imaging demonstrates the primary tumor but fail to show the residual tumor microaggregates left behind following initial treatment. In this study, we employed diffraction-enhanced imaging (DEI) in an attempt to find an imaging modality that will provide visualization of residual disease that is not be apparent on MRI or CT scans.