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

A novel scheme for simultaneous X-ray ptychographic and fluorescence imaging is presented. The method is based on a dual energy X-ray beam, chromatic focusing optics and an energy discriminating photon counting detector., X-ray ptychography and X-ray fluorescence are complementary nanoscale imaging techniques, providing structural and elemental information, respectively. Both methods acquire data by scanning a localized beam across the sample. X-ray ptychography processes the transmission signal of a coherent illumination interacting with the sample, to produce images with a resolution finer than the illumination spot and step size. By enlarging both the spot and the step size, the technique can cover extended regions efficiently. X-ray fluorescence records the emitted spectra as the sample is scanned through the localized beam and its spatial resolution is limited by the spot and step size. The requisites for fast ptychography and high-resolution fluorescence appear incompatible. Here, a novel scheme that mitigates the difference in requirements is proposed. The method makes use of two probes of different sizes at the sample, generated by using two different energies for the probes and chromatic focusing optics. The different probe sizes allow to reduce the number of acquisition steps for the joint fluorescence–ptychography scan compared with a standard single beam scan, while imaging the same field of view. The new method is demonstrated experimentally using two undulator harmonics, a Fresnel zone plate and an energy discriminating photon counting detector.

Purpose Image processing plays a fundamental role in the study of central nervous system, for example in the analysis of the vascular network in neurodegenerative diseases. Synchrotron X-ray Phase-contrast micro-Tomography (SXPCT) is a very attractive method to study weakly absorbing samples and features, such as the vascular network in the spinal cord (SC). However, the identification and segmentation of vascular structures in SXPCT images is seriously hampered by the presence of image noise and strong contrast inhomogeneities, due to the sensitivity of the technique to small electronic density variations. In order to help with these tasks, we implemented a user-friendly ImageJ plugin based on a 3D Gaussian steerable filter, tuned up for the enhancement of tubular structures in SXPCT images. Methods The developed 3D Gaussian steerable filter plugin for ImageJ is based on the steerability properties of Gaussian derivatives. We applied it to SXPCT images of ex-vivo mouse SCs acquired at different experimental conditions. Results The filter response shows a strong amplification of the source image contrast-to-background ratio (CBR), independently of structures orientation. We found that after the filter application, the CBR ratio increases by a factor ranging from ~6 to ~60. In addition, we also observed an increase of 35% of the contrast to noise ratio in the case of injured mouse SC. Conclusion The developed tool can generally facilitate the detection/segmentation of capillaries, veins and arteries that were not clearly observable in non-filtered SXPCT images. Its systematic application could allow obtaining quantitative information from pre-clinical and clinical images.

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.

Due to several issues still affecting pixelated photon-counting detector technology, such as e.g. inhomogeneities in the energy threshold calibration, polarization effects of high-Z semiconductor sensors and limitations of the hardware solutions aimed at compensating for the charge sharing issue, several artifacts corrupt the reconstructed images when adopting these detectors for computed tomography (CT). This article presents and discusses the most recurrent artifacts occurring in the raw images acquired with the innovative CdTe Pixirad-1/Pixie-III detector. By considering an experimental CT dataset of a suitable test object, digital image processing solutions for spectral CT imaging are here suggested and optimized. The proposed solutions consist of a pre-reconstruction despeckle filtering of each acquired projection and a post-reconstruction ring artifacts removal. The effects of these filters are quantitatively analyzed in terms of spatial resolution and signal-to-noise ratio. Finally, the suitability of the optimized image processing procedure is validated with two practical CT applications in which a plastinated small animal specimen is considered.

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).

We present here a new method of performing X-ray edge-subtraction ptychographic imaging by combining multiple harmonics from an undulator synchtrotron source and an energy discriminating photon counting detector. Conventionally, monochromatic far-field X-ray ptychography is used to perform edge subtraction through the use of multiple monochromatic energy scans to obtain spectral information for a variety of applications. Here, we use directly the undulator spectrum from a synchrotron source, selecting two separate harmonics post sample using the Pixirad-1/Pixie-III detector. The result is two monochromatic images, above and below an absorption edge of interest. The proposed method is applied to obtain Au L-edge subtraction imaging of a Au-Ni grid test sample. The Au L-edge subtraction is particularly relevant for the identification of gold nanoparticles for biomedical applications. Switching the energy scan mechanism from a mechanical monochromator to an electronic detector threshold allows for faster spectral data collection with improved stability.

A crucial issue in the development of therapies to treat pathologies of the central nervous system is represented by the availability of non-invasive methods to study the threedimensional morphology of spinal cord, with a resolution able to characterize its complex vascular and neuronal organization. X-ray phase contrast micro-tomography enables a highquality, 3D visualization of both the vascular and neuronal network simultaneously without the need of contrast agents, destructive sample preparations or sectioning. Until now, high resolution investigations of the post-mortem spinal cord in murine models have mostly been performed in spinal cords removed from the spinal canal. We present here post-mortem phase contrast micro-tomography images reconstructed using advanced computational tools to obtain high-resolution and high-contrast 3D images of the fixed spinal cord without removing the bones and preserving the richness of micro-details available when measuring exposed spinal cords. We believe that it represents a significant step toward the in-vivo application. (C) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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.

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

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.

Thanks to their high detection efficiency and low intrinsic noise, direct conversion X-ray Photon Counting Detectors (XPCDs) are particularly suitable for low dose imaging applications such as mammography. The photon counting technology can implement also two or more acquisition thresholds to perform single-shot spectral imaging with one polychromatic source. However, XPCDs with thick high Z crystal sensor and small pixel size are affected by the charge sharing effect. This issue can induce multiple counts from a single interaction reducing both spectral and spatial resolutions. In a pure counting mode, multiple counts from charge sharing can be partially or totally removed by increasing the acquisition threshold at the cost of a loss of efficiency. Thus, the performances of XPCDs can be threshold-dependent. New generation XPCDs implement solutions to cope with charge sharing issue. If the charge sharing is properly corrected, no multiple counts are recorded and the performances (detection efficiency, spectral and spatial resolutions) of the acquisition system are expected to be independent from the acquisition threshold. This work presents a study of a Pixirad-1 detection system based on a CdTe Schottky sensor and PIXIE-III readout system. This chip can be configured in three different operation modes, two of which implement solutions to remove multiple counts. Using monochromatic radiation, the performances of these different operation modes have been compared trough a measure of the integral spectra and the Signal to Noise Ratio (SNR) as function of the acquisition threshold.

Computational imaging techniques such as X-ray computed tomography (CT) rely on a significant amount of computing. The acquired tomographic projections are digitally processed to reconstruct the final images of interest. This process is generically called reconstruction, and it includes additional steps prior to or at the end of the execution of an actual reconstruction algorithm. Most of these steps aim at improving image quality, mainly in terms of artifacts compensation and noise reduction. The reconstructed images are then digitally analyzed to derive quantitative data and to support the qualitative visual interpretation. This part involves computational approaches that fall within the generic term image segmentation. Pre- and post- segmentation image processing is often required to improve the final quantification and extract reliable data from a CT dataset. This chapter presents an overview of the reconstruction and segmentation fundamentals for the 3D analysis of high-resolution X-ray CT data. Better knowledge about artifacts and reconstruction issues avoid misinterpretation of the images. Similarly, more insights about the limitations of image segmentation and quantification help commenting the reliability of the derived numerical values. A deeper understanding of these elements is therefore beneficial to optimize the whole workflow that starts from sample preparation and leads to CT-based scientific results.

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.

Rationale and Objectives This study employs clinical/radiological evaluation in establishing the optimum imaging conditions for breast cancer imaging using the X-ray propagation-based phase-contrast tomography. Materials and Methods Two series of experiments were conducted and in total 161 synchrotron-based computed tomography (CT) reconstructions of one breast mastectomy specimen were produced at different imaging conditions. Imaging factors include sample-to-detector distance, X-ray energy, CT reconstruction method, phase retrieval algorithm applied to the CT projection images and maximum intensity projection. Observers including breast radiologists and medical imaging experts compared the quality of the reconstructed images with reference images approximating the conventional (absorption) CT. Various radiological image quality attributes in a visual grading analysis design were used for the radiological assessments. Results The results show that the application of the longest achievable sample-to-detector distance (9.31 m), the lowest employed X-ray energy (32 keV), the full phase retrieval, and the maximum intensity projection can significantly improve the radiological quality of the image. Several combinations of imaging variables resulted in images with very high-quality scores. Conclusion The results of the present study will support future experimental and clinical attempts to further optimize this innovative approach to breast cancer imaging.

The suppression of ring artifacts in x-ray computed tomography (CT) is a required step in practical applications; it can be addressed by introducing refined digital low pass filters within the reconstruction process. However, these filters may introduce additional ringing artifacts when simultaneously imaging pure phase objects and elements having a non-negligible absorption coefficient. Ringing originates at sharp interfaces, due to the truncation of spatial high frequencies, and severely affects qualitative and quantitative analysis of the reconstructed slices. In this work, we discuss the causes of ringing artifacts, and present a general compensation procedure to account for it. The proposed procedure has been tested with CT datasets of the mouse central nervous system acquired at different synchrotron radiation facilities. The results demonstrate that the proposed method compensates for ringing artifacts induced by low pass ring removal filters. The effectiveness of the ring suppression filters is not altered; the proposed method can thus be considered as a framework to improve the ring removal step, regardless of the specific filter adopted or the imaged sample.

The use of platelet rich plasma (PRP) in bone repair remains highly controversial. In this work, we evaluated the effect of lyophilized PRP on bone regeneration when associated with a silicon stabilized hydroxyapatite tricalcium phosphate scaffold in a rabbit calvarial defect (Skelite™). Critical defects were created in the calvaria of twenty-four rabbits. The periosteum was removed and the defects were either left empty or filled with allogeneic PRP gel; Skelite particles; Skelite and PRP gel. Four animals were killed after 4 weeks, 10 animals after 8 and 10 after 16 weeks. Specimens were processed for X-ray microtomography (μCT) and for resin embedded histology. μCT analysis revealed significant osteoid-like matrix and new bone deposition in PRP + Skelite group at both 8 and 16 weeks in respect to Skelite alone. Histologically, PRP + Skelite defects were highly cellular with more abundant osteoid deposition and more regular collagen fibres. Moreover, in vitro migration assays confirmed the chemotactic effect of PRP to endothelial and osteoprogenitor cells. We conclude that the addition of PRP influenced the local tissue microenvironment by providing key cryptic factors for regeneration, thereby enhancing progenitor cell recruitment, collagen and bone matrix deposition, and by creating a bridging interface between the scaffold and bone.

The degenerative effects of multiple sclerosis at the level of the vascular and neuronal networks in the central nervous system are currently the object of intensive investigation. Preclinical studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapy in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis, but the neuropathology of specific lesions in EAE and the effects of MSC treatment are under debate. Because conventional imaging techniques entail protocols that alter the tissues, limiting the reliability of the results, we have used non-invasive X-ray phase-contrast tomography to obtain an unprecedented direct 3D characterization of EAE lesions at micro-to-nano scales, with simultaneous imaging of the vascular and neuronal networks. We reveal EAE-mediated alterations down to the capillary network. Our findings shed light on how the disease and MSC treatment affect the tissues, and promote X-ray phase-contrast tomography as a powerful tool for studying neurovascular diseases and monitoring advanced therapies.

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

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

When considering the acquisition of experimental synchrotron radiation (SR) X-ray CT data, the reconstruction workflow cannot be limited to the essential computational steps of flat fielding and filtered back projection (FBP). More refined image processing is often required, usually to compensate artifacts and enhance the quality of the reconstructed images. In principle, it would be desirable to optimize the reconstruction workflow at the facility during the experiment (beamtime). However, several practical factors affect the image reconstruction part of the experiment and users are likely to conclude the beamtime with sub-optimal reconstructed images. Through an example of application, this article presents SYRMEP Tomo Project (STP), an open-source software tool conceived to let users design custom CT reconstruction workflows. STP has been designed for post-beamtime (off-line use) and for a new reconstruction of past archived data at user’s home institution where simple computing resources are available. Releases of the software can be downloaded at the Elettra Scientific Computing group GitHub repository https://github.com/ElettraSciComp/STP-Gui.

In recent years great interest has been posed in imaging techniques like X-ray computed microtomography which in a nondestructive way produce three-dimensional (3D) images of the internal structure of, e.g. porous media. A major challenge lies in the quantitative analysis of the resulting images that allows a more comprehensive and objective characterization of the sample under investigation. A software able to handle and process large 3D image datasets with common hardware is therefore necessary in order to extract morphological and textural information directly from the images. In the present paper the Pore3D software library developed by the SYRMEP research group of the Elettra Synchrotron Light Laboratory in Trieste (Italy) is presented. The library consists of several state-of-the-art functions and procedures for performing filtering, segmentation and quantitative analysis of 3D images. The current status of the project and some applications are here reported.

Background Structural MRI measures for monitoring Alzheimer's Disease (AD) progression are becoming instrumental in the clinical practice, and more so in the context of longitudinal studies. This investigation addresses the impact of four image analysis approaches on the longitudinal performance of the hippocampal volume. Methods We present a hippocampal segmentation algorithm and validate it on a gold-standard manual tracing database. We segmented 460 subjects from ADNI, each subject having been scanned twice at baseline, 12-month and 24 month follow-up scan (1.5 T, T1 MRI). We used the bilateral hippocampal volume v and its variation, measured as the annualized volume change Λ = δv / year ( mm 3 / y ). Four processing approaches with different complexity are compared to maximize the longitudinal information, and they are tested for cohort discrimination ability. Reference cohorts are Controls vs. Alzheimer's Disease (CTRL/AD) and CTRL vs. Mild Cognitive Impairment who subsequently progressed to AD dementia (CTRL/MCI -co ). We discuss the conditions on v and the added value of Λ in discriminating subjects. Results The age-corrected bilateral annualized atrophy rate (%/year) were: − 1.6 (0.6) for CTRL, − 2.2 (1.0) for MCI- nc , − 3.2 (1.2) for MCI- co and − 4.0 (1.5) for AD. Combined ( v , Λ) discrimination ability gave an Area under the ROC curve ( auc ) = 0.93 for CTRL vs AD and auc = 0.88 for CTRL vs MCI- co . Conclusions Longitudinal volume measurements can provide meaningful clinical insight and added value with respect to the baseline provided the analysis procedure embeds the longitudinal information.

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.

We present the outcomes of combined feasibility studies carried out at Elettra and Australian Synchrotron to evaluate novel protocols for threedimensional (3D) mammographic phase contrast imaging. A custom designed plastic phantom and some tissue samples have been studied at diverse resolution scales and experimental conditions. Several computed tomography (CT) reconstruction algorithms with different pre-processing and post-processing steps have been considered. Special attention was paid to the effect of phase retrieval on the diagnostic value of the reconstructed images. The images were quantitatively evaluated using objective quality indices in comparison with subjective assessments performed by three experienced radiologists and one pathologist. We show that the propagation-based phase-contrast imaging (PBI) leads to substantial improvement to the contrast-to-noise and to the intrinsic quality of the reconstructed CT images compared with conventional techniques as well as to an important reduction of the delivered doses, thus opening the way to clinical implementations.

Results are presented of a recent experiment at the Imaging and Medical beamline of the Australian Synchrotron intended to contribute to the implementation of low-dose high-sensitivity three-dimensional mammographic phase-contrast imaging, initially at synchrotrons and subsequently in hospitals and medical imaging clinics. The effect of such imaging parameters as X-ray energy, source size, detector resolution, sample-to-detector distance, scanning and data processing strategies in the case of propagation-based phase-contrast computed tomography (CT) have been tested, quantified, evaluated and optimized using a plastic phantom simulating relevant breast-tissue characteristics. Analysis of the data collected using a Hamamatsu CMOS Flat Panel Sensor, with a pixel size of 100 µm, revealed the presence of propagation-based phase contrast and demonstrated significant improvement of the quality of phase-contrast CT imaging compared with conventional (absorption-based) CT, at medically acceptable radiation doses.

Defaults in vascular (VN) and neuronal networks of spinal cord are responsible for serious neurodegenerative pathologies. Because of inadequate investigation tools, the lacking knowledge of the complete fine structure of VN and neuronal systems is a crucial problem. Conventional 2D imaging yields incomplete spatial coverage leading to possible data misinterpretation, whereas standard 3D computed tomography imaging achieves insufficient resolution and contrast. We show that X-ray high-resolution phase-contrast tomography allows the simultaneous visualization of three-dimensional VN and neuronal systems of mouse spinal cord at scales spanning from millimeters to hundreds of nanometers, with neither contrast agent nor a destructive sample-preparation. We image both the 3D distribution of micro-capillary network and the micrometric nerve fibers, axon-bundles and neuron soma. Our approach is a crucial tool for pre-clinical investigation of neurodegenerative pathologies and spinal-cord-injuries. In particular, it should be an optimal tool to resolve the entangled relationship between VN and neuronal system., Comment: 15 pages, 6 figures

X-ray computed tomography (CT) experiments performed at synchrotron radiation fa- cilities require adequate computing and storage resources due to the large amount of acquired and reconstructed data produced. To satisfy the heterogeneous needs of beamline users, flexible solu- tions are also required. Moreover, the growing demand of quantitative image analysis impose an easy integration between the CT reconstruction process and the subsequent feature extraction step. This paper presents some of the software solutions adopted by the SYRMEP beamline of the Italian synchrotron radiation facility Elettra. By using the enhanced version of the reconstruction software here presented as well as data reduction and data analysis tools, beamline users can easily imple- ment an integrated and comprehensive approach to the digital image processing and image analysis required by a tomography-oriented scientific workflow.

Microtomographic (micro-CT) experiments can be performed in the so-called Propagation Based Imaging (PBI) modality by using a sufficiently coherent X-ray beam, such as the one obtained at e.g. third generation synchrotron laboratories or at enhanced liquid-metal-jet-anode micro focus facilities. Then, a quantitative relationship exists between the phase shift induced by the object and the recorded intensity. The inversion of this relationship is called phase retrieval and in PBI this can be performed via digital image processing. Several phase retrieval algorithms have been developed through years and freely available software has also recently appeared. In this paper, preliminary results of a qualitative comparison of the phase retrieval image processing offered by two free software tools are shown by considering two experimental micro-CT PBI datasets acquired at the SYRMEP beamline of the Italian synchrotron radiation facility (Elettra - Sincrotrone Trieste S.C.p.A.). An algorithm based on the solution of the Transport of Intensity Equation (TIE) implemented into the open source software ANKAPhase is compared against the solution based on the first Born approximation offered by the PITRE free software tool. A deep understanding of how these phase retrieval algorithms affect the resulting images is crucial in order to accurately interpret the reconstructed micro-CT PBI datasets.

The presence of ring artifacts in X-ray computed microtomography affects the qualitative and quantitative analyses of the reconstructed images. Although digital image processing approaches to ring artifacts removal via direct filtering of the reconstructed images exist, in synchrotron radiation microtomography this issue is usually faced during the actual reconstruction process by de-striping the sinogram image. In this work different de-striping algorithms are discussed and preliminary compared using a suitably created test image as well as actual imaged data. Because of the increasing need for fast reconstruction workflows, details of the implementation and the related computational aspects are also considered. Moreover, the hardware and software solution developed and deployed for the SYRMEP (SYnchrotron Radiation for MEdical Physics) microtomographic beamline of the Italian synchrotron radiation facility (Elettra - Sincrotrone Trieste S.C.p.A) is presented. This solution is based on a highperformance computing (HPC) cluster with the Oracle Grid Engine distributed resource management (DRM) system and Python code that takes advantage of the NumPy and SciPy libraries. This work makes available high resolution test images as well as source code at: ulisse.elettra.trieste.it/uos/pore3d/ringrem.

Introduction Iterative tomographic reconstruction techniques are particularly interesting when the number of acquired projections is not enough to match the Nyquist criteria. These techniques differ in computational time and image quality. Purpose SIRT, SART and CGLS algorithms have been studied in order to evaluate the application of iterative reconstruction methods to low-dose phase-contrast breast tomography, in the framework of the SYRMA-CT project. The number of iterations has been optimized while reducing the number of projections used during the reconstruction. Materials and methods The tomographic data set of two large breast tissue samples (9 cm) has been acquired using a monochromatic X-ray beam at 38 keV. Images were acquired in propagation-based phase-contrast mode and a single-material single-distance phase-retrieval algorithm was applied to the projections before reconstruction. The codes applied are part of the ASTRA Tomography Toolbox. The quality of the images was evaluated using the CNR and few full-reference quality indexes. The reconstruction performed with the filter back-projection including all the acquired projections was considered as gold standard. Results According to full-reference indexes the best quality is achieved when the CNR is similar to the one of the gold standard. The number of iterations can be used to optimize the noise preserving the visibility of the details. Conclusion Full reference indexes require a gold standard acquired at higher statistics, due to their strong dependence on the noise. The evaluation of a team of radiologists is required to compare full-references quality indexes and diagnostic quality of the reconstructed images. Disclosure Nothing to declare.

Introduction MRI longitudinal studies have been proposed to detect abnormal brain changes in the early phase of the Alzheimer’s disease (AD) during its asymptomatic phase. Purpose In order to obtain a very high sensitivity in MRI longitudinal studies a number of technical issues have to be addressed. Materials and methods In the present study a high resolution MRI protocol focused on the medial temporal lobe mainly conceived for 1.5T MRI device is developed. A grey-level reference object was designed to be used during acquisition to help image post-processing when gray-level comparison is required. A prospective study on healthy volunteers is ongoing. An image analysis protocol for longitudinal studies has been developed, including pre-processing (gray level normalization, image registration) and voxel-based time-course analysis. The protocol has been tested on the MIRIAD dataset. Results The new acquisition and gray-level normalization technique was applied and comparison indexes (PSNR, SSI, NCC) have been calculated to demonstrate the increased reproducibility of the images. The image processing developed for this study demonstrates that the time-course of brain atrophy let us differentiate normal and AD subjects with repeated images acquired in less than 2 years. Conclusion Applying our imaging techniques, longitudinal studies will likely be more accurate than the study based on MIRIAD dataset. Therefore we expect that repeated images with our acquisition and normalization protocol will allow the discrimination between normal and AD subjects with a reduced number of images acquired in a period of about one year. Disclosure Nothing to declare.

Concentric rings are among the most recurrent artifacts in X-ray computed microtomography imaging. Their presence have a negative impact on the quantitative and qualitative analyses of the data. An interesting approach for ring artifacts removal is based on direct filtering of the reconstructed slices. Slice filtering does not require additional imaging data (i.e. flat fielding images), it does not exclude methods applied during the reconstruction process (i.e. sinogram processing) and it can be applied also to past archived tomographic data. In this work four different approaches for the removal of complete ring artifacts are presented and preliminary compared using a suitably created artificial image as well as an experimental image. After a critical analysis of the considered filters, the results support that an approach based on a modified Sijbers and Postnov [1] method effectively compensates ring artifacts in reconstructed slices, thus resulting in a powerful tool for established microtomography workflows.

Differences in the individual pixel response of detector elements introduce ring artifacts in tomographic images seriously degrading image quality. Removing or at least significantly reducing such artifacts is indispensable. In this paper an improved ring artifacts remover filter based on the approach of I. Sijbers and A. Postnov [1] is presented. The principal advantage and core characteristic of the proposed method is that it can be applied directly on images that have been already reconstructed, thus eliminating the need for additional imaging data like sinograms, flat fields and dark fields that are traditionally used for ring removal. The proposed method is computationally inexpensive and can be used even within established CT workflows or on past archived tomographic data.

Results are presented of a feasibility study of three-dimensional X-ray tomographic mammography utilising in-line phase contrast. Experiments were performed at SYRMEP beamline of Elettra synchrotron. A specially designed plastic phantom and a mastectomy sample containing a malignant lesion were used to study the reconstructed image quality as a function of different image processing operations. Detailed evaluation and optimization of image reconstruction workflows have been carried out using combinations of several advanced computed tomography algorithms with different pre-processing and post-processing steps. Special attention was paid to the effect of phase retrieval on the diagnostic value of the reconstructed images. A number of objective image quality indices have been applied for quantitative evaluation of the results, and these were compared with subjective assessments of the same images by three experienced radiologists and one pathologist. The outcomes of this study provide practical guidelines for the optimization of image processing workflows in synchrotron-based phase-contrast mammo-tomography.

The SYRMEP Beamline at the ELETTRA Synchrotron (Trieste, Italy) has already been performing clinical mammographic examinations using X-rays generated by one bending magnet. These examinations have been performed with traditional screen-film systems, but in order to exploit the characteristics of the beam (monochromatic in the energy range 8.5-35 keV, with a rate up to 7 × 107 photons/(mm2·s) at 17 keV), a double layer Silicon detector has been developed within the INFN PICASSO project. This detector is the evolution of the single layer already deployed by the INFN MATISSE project, in collaboration with the Paul Scherrer Institut. This single layer was based on a microstrip Silicon sensor (50 (μm pitch) coupled to the Mythen-II high-rate photon counting ASIC, used in the edge-on configuration to improve the detection efficiency. This contribution presents the development of a double layer with limited coverage (5.5 cm instead of 21 cm), used to verify all the steps in view of the construction of the full scale assembly. We present the results in terms of rate and of the imaging capability of standard phantoms, recorded in the phase contrast imaging modality.