Edge-illumination spectral phase-contrast tomography.

Following the rapid, but independent, diffusion of x-ray spectral and phase-contrast systems, this work demonstrates the first combination of spectral and phase-contrast computed tomography (CT) obtained by using the edge-illumination technique and a CdTe small-pixel (62µm) spectral detector. A theoretical model is introduced, starting from a standard attenuation-based spectral decomposition and leading to spectral phase-contrast material decomposition. Each step of the model is followed by quantification of accuracy and sensitivity on experimental data of a test phantom containing different solutions with known concentrations. An example of a micro CT application (20µm voxel size) on an iodine-perfusedex vivomurine model is reported. The work demonstrates that spectral-phase contrast combines the advantages of spectral imaging, i.e. high-Zmaterial discrimination capability, and phase-contrast imaging, i.e. soft tissue sensitivity, yielding simultaneously mass density maps of water, calcium, and iodine with an accuracy of 1.1%, 3.5%, and 1.9% (root mean square errors), respectively. Results also show a 9-fold increase in the signal-to-noise ratio of the water channel when compared to standard spectral decomposition. The application to the murine model revealed the potential of the technique in the simultaneous 3D visualization of soft tissue, bone, and vasculature. While being implemented by using a broad spectrum (pink beam) at a synchrotron radiation facility (Elettra, Trieste, Italy), the proposed experimental setup can be readily translated to compact laboratory systems including conventional x-ray tubes.

PEPI Lab: a flexible compact multi-modal setup for X-ray phase-contrast and spectral imaging.

This paper presents a new flexible compact multi-modal imaging setup referred to as PEPI (Photon-counting Edge-illumination Phase-contrast imaging) Lab, which is based on the edge-illumination (EI) technique and a chromatic detector. The system enables both X-ray phase-contrast (XPCI) and spectral (XSI) imaging of samples on the centimeter scale. This work conceptually follows all the stages in its realization, from the design to the first imaging results. The setup can be operated in four different modes, i.e. photon-counting/conventional, spectral, double-mask EI, and single-mask EI, whereby the switch to any modality is fast, software controlled, and does not require any hardware modification or lengthy re-alignment procedures. The system specifications, ranging from the X-ray tube features to the mask material and aspect ratio, have been quantitatively studied and optimized through a dedicated Geant4 simulation platform, guiding the choice of the instrumentation. The realization of the imaging setup, both in terms of hardware and control software, is detailed and discussed with a focus on practical/experimental aspects. Flexibility and compactness (66 cm source-to-detector distance in EI) are ensured by dedicated motion stages, whereas spectral capabilities are enabled by the Pixirad-1/Pixie-III detector in combination with a tungsten anode X-ray source operating in the range 40-100 kVp. The stability of the system, when operated in EI, has been verified, and drifts leading to mask misalignment of less than 1 [Formula: see text]m have been measured over a period of 54 h. The first imaging results, one for each modality, demonstrate that the system fulfills its design requirements. Specifically, XSI tomographic images of an iodine-based phantom demonstrate the system's quantitativeness and sensibility to concentrations in the order of a few mg/ml. Planar XPCI images of a carpenter bee specimen, both in single and double-mask modes, demonstrate that refraction sensitivity (below 0.6 [Formula: see text]rad in double-mask mode) is comparable with other XPCI systems based on microfocus sources. Phase CT capabilities have also been tested on a dedicated plastic phantom, where the phase channel yielded a 15-fold higher signal-to-noise ratio with respect to attenuation.

Motion artifacts assessment and correction using optical tracking in synchrotron radiation breast CT.

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.

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

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

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

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

Flattening filter for Gaussian-shaped monochromatic X-ray beams: an application to breast computed tomography.

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).

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

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

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

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

Quantitative characterization of breast tissues with dedicated CT imaging.

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

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

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

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

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

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

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

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

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

A proposal for a quality control protocol in breast CT with synchrotron radiation.

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

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

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

Dose and diagnostic performance comparison between phase-contrast mammography with synchrotron radiation and digital mammography: a clinical study report.

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

A Gaussian extension for Diffraction Enhanced Imaging.

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

High contrast microstructural visualization of natural acellular matrices by means of phase-based x-ray tomography.

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

A simplified edge illumination set-up for quantitative phase contrast mammography with synchrotron radiation at clinical doses.

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

Synchrotron based planar imaging and digital tomosynthesis of breast and biopsy phantoms using a CMOS active pixel sensor.

The SYRMEP (SYnchrotron Radiation for MEdical Physics) beamline at Elettra is performing the first mammography study on human patients using free-space propagation phase contrast imaging. The stricter spatial resolution requirements of this method currently force the use of conventional films or specialized computed radiography (CR) systems. This also prevents the implementation of three-dimensional (3D) approaches. This paper explores the use of an X-ray detector based on complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology as a possible alternative, for acquisitions both in planar and tomosynthesis geometry. Results indicate higher quality of the images acquired with the synchrotron set-up in both geometries. This improvement can be partly ascribed to the use of parallel, collimated and monochromatic synchrotron radiation (resulting in scatter rejection, no penumbra-induced blurring and optimized X-ray energy), and partly to phase contrast effects. Even though the pixel size of the used detector is still too large - and thus suboptimal - for free-space propagation phase contrast imaging, a degree of phase-induced edge enhancement can clearly be observed in the images.