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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).

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).

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.

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.

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.

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: 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.

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.

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.

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.

A system for in vivo breast imaging with monochromatic x-rays has been designed and built at the synchrotron radiation facility Elettra in Trieste (Italy) and will be operational in 2004. The system design involves the possibility of performing both planar mammography and breast tomography. In the present work, the first results obtained with a test set-up for breast tomography are shown and discussed. Tomographic images of in vitro breasts were acquired using monochromatic x-ray beams in the energy range 20-28 keV and a linear array silicon pixel detector. Tomograms were reconstructed using standard filtered backprojection algorithms; the effect of different filters was evaluated. The attenuation coefficients of fibroglandular and adipose tissue were measured, and a quantitative comparison of images acquired at different energies was performed by calculating the differential signal-to-noise ratio of fibroglandular details in adipose tissue. All images required a dose comparable to the dose delivered in clinical, conventional mammography and showed a high resolution of the breast structures without the overlapping effects that limit the visibility of the structures in 2D mammography. A quantitative evaluation of the images proves that the image quality at a given dose increases in the considered energy range and for the considered breast sizes.

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

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.

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 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.

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.

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.

Small prisms arranged such that the number of prisms to traverse by an x‐ray beam is linearly increasing with distance from the symmetry axis of the device will direct an incident wave to a common cross over point. This structure can be understood as a special form of the Fresnel version of a concave refractive x‐ray lens. Indeed it is obtained by removing blocks of optically passive material of equal height from the concave lens shape. It will be shown that the structure has a high refraction efficiency and that the losses are produced by problems in the fabrication of sufficiently sharp tips for the prisms.

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.

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.

The main purpose of the SYRMEP (SYnchrotron Radiation for MEdical Physics) research team is the investigation and development of innovative techniques for medical imaging. A dedicated beamline has been built at ELETTRA to evaluate the effectiveness of synchrotron-based techniques in medical radiology with particular interest to mammography, and more in general, to the imaging of biological and biomedical samples, either in planar or tomographic set-ups. Taking advantage of the high intensity and high spatial coherence of Synchrotron Radiation (SR), phase sensitive techniques such as Phase Contrast (PhC) and Diffraction Enhanced Imaging (DEI) can be applied. After successful studies carried out on test objects and in vitro samples, the research in mammography is aiming at in vivo clinical trials. For this purpose, the layout of the SYRMEP beamline has been substantially modified and the safety system has been completely redesigned to guarantee the compliance with current radiation protection guidelines. In the present paper, the main characteristics of the beamline and an overview of the results obtained in different contexts of biomedical imaging are presented. Moreover, the status of the project for clinical mammography is outlined.

Diffraction Enhanced Imaging (DEI) is an X-ray imaging method to provide additional contrast and diminish untoward image signals by reducing scattering. Previous reports demonstrated its applicability in soft and hard tissue imaging. Here we provide further evidence for the improved overall image quality and for the option to discriminate various tissue-specific properties, such as collagen fiber elements or mineralization. Comparative ex vivo data to medical MRI and to medical ultrasound are shown, utilizing human ankle and hip specimens.

Effect of spatial coherence on the application of in-line phase contrast imaging (IL-PCI) to synchrotron radiation (SR) mammography is investigated experimentally at SYRMEP/ELETTRA. Factors that are related to spatial coherence and IL-PCI image quality, which include vertical and horizontal beam, photon energy, slit width, sample–detector distance and detector resolution, are analyzed. The experimental results demonstrate that better IL-PCI image quality could be achieved in the vertical beam. As for the slit width, the spatial coherence for horizontal beam remains almost the same until the slit width is gradually closed to 5 mm. For mammography applications of IL-PCI, slit width of 100 mm could be employed and high-enough image quality can still be obtained. Lower photon energy results in better coherence and correspondingly better IL-PCI image quality. By compromising the dose and image quality, photon energy of ∼19 keV is recommended for SR mammography. To preserve the edge enhancement resulting from good coherence of SR, an appropriate sample–detector distance and a practical detector should be selected. The optimum sample–detector distance highly depends on detector resolution. For high-resolution film, the best IL-PCI imaging quality is obtained at a closer sample–detector distance. For an X-ray CCD with pixel size of 14 μm, about 1.5 m is needed to achieve optimum image quality. The large pixel size of the detector will deteriorate the edge-enhancing efficiency and results in lower IL-PCI imaging quality. In practice, the spatial resolution and sensitivity of the detectors should be compromised.

This report describes the optimization, first experimental data and the performance outlook for a special refractive lens for the focusing of x-rays. The lens was obtained by applying the strategy of Fresnel to lighten a lens by removing efficiently optically passive material. This strategy was applied to objects, which were produced by deep x-ray lithography and which can thus be shaped in only one dimension. Consequently this class of lenses can focus in only one dimension. While in the normal Fresnel lenses as much material as possible is removed, in the present lens the remaining segments were kept as large as possible, in order to finally obtain a rigid and deep structure. The resultant structure is composed of small prisms of almost identical shape, which are combined such that the final lens looks like an hour glass, i.e. two large prisms touch each other at one of their tips. Such a lens has better transmission than a normal refractive lens of equal focal length. And even though it has worse transmission than the normal Fresnel lenses, it could be produced with an unprecedented geometrical aperture of 2.6 mm for 8 keV photon energy. The uniformly etched structure depth was found to be at least 0.4 mm, over which the lens can focus free of aberrations. A lens with focal length 2.183 m was found to provide after very rapid alignment a focus size of 2.8 μm, while slightly better 1.73 μm were ideally expected.

Diffraction Enhanced Imaging is a phase sensitive imaging modality, which recently has been demonstrated to be a powerful tool for improving the visibility of tiny low absorbing structures. Especially in medical imaging the capability to detect small details, not visible in a conventional radiograph is of relevant importance. An analyzer crystal is used as angular filter to select or reject X-rays that are deviated when traversing a sample if a gradient of the real part of the refractive index is encountered. At the medical imaging beamline of the synchrotron radiation facility Elettra (Trieste) experiments were carried out to assess the applicability of this technique to materials where a combined refraction from a large amount of small structures, not detectable separately, gives rise to an overall effect of multiple scattering. Tuning the analyzer crystal in different angular positions the variation of the contrast was studied. Strong contrast enhancement was measured in comparison to the conventional absorption image.

A synchrotron radiation-based X-ray source offers a powerful tool for mammography due to the energy spectrum properties and the peculiar laminar beam geometry. Significant improvements in image quality have been achieved by the SYRMEP (SYnchrotron Radiation for MEdical Physics) collaboration, which has designed and built a beamline devoted to medical physics at the SR facility Elettra in Trieste (Italy). The detection system developed for digital mammography consists of a silicon pixel detector with 200 300 mm2 pixel size and high conversion efficiency. The detector is equipped with a low noise read-out electronics working in single photon counting mode. Mammographic phantoms and in vitro full breast samples have been investigated: the digital images show higher contrast resolution and lower absorbed dose than the images of the same samples obtained at the clinical mammographic unit.The SYRMEP collaboration is carrying out a breast tomography feasibility study to evaluate the image quality and the delivered dose. The SYRMEP beam is an ideal tool for tomography due to the laminar and monochromatic beam with negligible divergence. The experimental set-up and the acquisition protocol have been studied and the tomographic images of full breast samples acquired in the energy range 20–28 keV indicate that good quality images can be obtained with delivered doses comparable to conventional mammography.

Among the medical physics community, there is nowadays a great interest in the possible implementation of scatter imaging techniques, especially in the field of breast imaging. It is well known that malignant lesions and normal tissue differ in their scattering signatures, and thus scattered radiation can provide a powerful tool to distinguish between the two cases. Up to now, most of the proposed techniques rely on the detection of radiation scattered at angles of the order of a few degrees, which in most cases results in very high contrast values. On the other hand, at those relatively large angles the scattered flux is relatively low with respect to the primary, which often implies the necessity of increasing the dose delivered to the sample in order to achieve sufficient statistics. Furthermore, most of these techniques are based on pencil beam set-ups, which results in an increase of the overall duration of the examination. We propose here an alternative approach based on the detection of radiation scattered at extremely small angles, of the order of approximately 100-200 microrad. This results in a relatively high scattered flux (5-10% of the primary) and in the possibility of utilizing a fan beam geometry, which reduces the acquisition times with respect to pencil beam set-ups. Images of several samples have been acquired, demonstrating that the proposed technique results in an increased contrast with respect to absorption imaging. Possible in vivo implementations of the technique at no dose expense are finally discussed.

X-ray phase contrast imaging (XPCi) methods are sensitive to phase in addition to attenuation effects and, therefore, can achieve improved image contrast for weakly attenuating materials, such as often encountered in biomedical applications. Several XPCi methods exist, most of which have already been implemented in computed tomographic (CT) modality, thus allowing volumetric imaging. The Edge Illumination (EI) XPCi method had, until now, not been implemented as a CT modality. This article provides indications that quantitative 3D maps of an object's phase and attenuation can be reconstructed from EI XPCi measurements. Moreover, a theory for the reconstruction of combined phase and attenuation maps is presented. Both reconstruction strategies find applications in tissue characterisation and the identification of faint, weakly attenuating details. Experimental results for wires of known materials and for a biological object validate the theory and confirm the superiority of the phase over conventional, attenuation-based image contrast.

A linear array silicon pixel detector has been developed to perform digital radiology with synchrotron radiation: in this communication we present the first results obtained using a three layer prototype at the Elettra Synchrotron Radiation Facility (Trieste, Italy). High efficiency (about 85% at 20 keV) is achieved by means of an Si strip detector irradiated in an 'edge-on' geometry: the pixel dimensions are 200 X 300 micrometer2. To obtain a sensitive area of about 50 X 1 mm2 stack of three layers has been assembled. Images are obtained by means of scanning techniques and their spatial resolution is determined by the scanning step. Detectors are read-out by dedicated, low noise VLSI CMOS chips in single photon counting mode. The distance between each detector layer has been measured to be 115 plus or minus 10 micrometer and the layers are parallel within a maximum tilt angle of 0.08 degrees. Cross-talk effects were found to be always smaller than 2% of the counts of the neighboring layers. The MTF in the scan direction has been evaluated. The acquisition time needed to acquire an image of a mammographic test object is about 6 minutes. The mean glandular dose is about 30% of the dose delivered at the conventional mammographic unit for the same test object while the detail visibility is comparable. These preliminary results indicate that a large area linear array silicon pixel detector can be developed: using this detector and a monochromatic synchrotron radiation beam the delivered mean glandular dose is significantly reduced when compared to conventional mammographic examinations.© (1999) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The refraction angle of x rays as they pass through a refractive prism is proportional to the square of the x-ray wavelength. This was used to discriminate between different harmonic orders, which have different energies, created by a two-crystal 111 monochromator [Z. Zhong, J. Appl. Crystallogr 33, 1082 (2000)]. Refractive prisms inserted between the two monochromator crystals allowed selection, among the 111, 333, 444, and 555 diffractions, in our diffraction enhanced imaging program at National Synchrotron Light Source’s X15A beamline, and facilitated convenient change of sensitivity in our efforts to optimize DEI system for mammography and other radiographic applications. The selection of 111 and 333 refractions were straightforward since the necessary angle of refraction is small. The challenge of selecting 444 and 555 reflections was met by designing an acrylic prism that offered an angle of refraction much larger than 10 μrad and was compact enough to be manipulated in the small space between the crystals. Examples are given on use of the prism for studying the effects of diffraction orders on DEI’s refraction and extinction contrasts. Its modes of operation and limitations are discussed. The principle of harmonics selection through prism and the specific design of the device could be relevant for other synchrotron monochromators that have a harmonics concern or can benefit from change of energy, through selection of harmonic orders, without changing crystals.