Multiscale X-ray phase-contrast tomography: From breast CT to micro-CT for virtual histology.

Phase-contrast imaging techniques address the issue of poor soft-tissue contrast encountered in traditional X-ray imaging. This can be accomplished with the propagation-based phase-contrast technique by employing a coherent photon beam, which is available at synchrotron facilities, as well as long sample-to-detector distances. This study demonstrates the optimization of propagation-based phase-contrast computed tomography (CT) techniques for multiscale X-ray imaging of the breast at the Elettra synchrotron facility (Trieste, Italy). Two whole breast mastectomy samples were acquired with propagation-based breast-CT using a monochromatic synchrotron beam at a pixel size of 60 µm. Paraffin-embedded blocks sampled from the same tissues were scanned with propagation-based micro-CT imaging using a polychromatic synchrotron beam at a pixel size of 4 µm. Images of both methodologies and of the same sample were spatially registered. The resulting images showed the transition from whole breast imaging with propagation-based breast-CT methodology to virtual histology with propagation-based micro-CT imaging of the same sample. Additionally, conventional histological images were matched to virtual histology images. Phase-contrast images offer a high resolution with low noise, which allows for a highly precise match between virtual and conventional histology. Furthermore, those techniques allow a clear discernment of breast structures, lesions, and microcalcifications, being a promising clinically-compatible tool for breast imaging in a multiscale approach, to either assist in the detection of cancer in full volume breast samples or to complement structure identification in paraffin-embedded breast tissue samples.

Optimization of a customized simultaneous algebraic reconstruction technique algorithm for phase-contrast breast computed tomography.

Objective.To introduce the optimization of a customized GPU-based simultaneous algebraic reconstruction technique (cSART) in the field of phase-contrast breast computed tomography (bCT). The presented algorithm features a 3D bilateral regularization filter that can be tuned to yield optimal performance for clinical image visualization and tissues segmentation.Approach.Acquisitions of a dedicated test object and a breast specimen were performed at Elettra, the Italian synchrotron radiation (SR) facility (Trieste, Italy) using a large area CdTe single-photon counting detector. Tomographic images were obtained at 5 mGy of mean glandular dose, with a 32 keV monochromatic x-ray beam in the free-space propagation mode. Three independent algorithms parameters were optimized by using contrast-to-noise ratio (CNR), spatial resolution, and noise texture metrics. The results obtained with the cSART algorithm were compared with conventional SART and filtered back projection (FBP) reconstructions. Image segmentation was performed both with gray scale-based and supervised machine-learning approaches.Main results.Compared to conventional FBP reconstructions, results indicate that the proposed algorithm can yield images with a higher CNR (by 35% or more), retaining a high spatial resolution while preserving their textural properties. Alternatively, at the cost of an increased image 'patchiness', the cSART can be tuned to achieve a high-quality tissue segmentation, suggesting the possibility of performing an accurate glandularity estimation potentially of use in the realization of realistic 3D breast models starting from low radiation dose images.Significance.The study indicates that dedicated iterative reconstruction techniques could provide significant advantages in phase-contrast bCT imaging. The proposed algorithm offers great flexibility in terms of image reconstruction optimization, either toward diagnostic evaluation or image segmentation.

Tomographic phase and attenuation extraction for a sample composed of unknown materials using x-ray propagation-based phase-contrast imaging.

Propagation-based phase-contrast x-ray imaging (PB-PCXI) generates image contrast by utilizing sample-imposed phase-shifts. This has proven useful when imaging weakly attenuating samples, as conventional attenuation-based imaging does not always provide adequate contrast. We present a PB-PCXI algorithm capable of extracting the x-ray attenuation  ß and refraction  δ, components of the complex refractive index of distinct materials within an unknown sample. The method involves curve fitting an error-function-based model to a phase-retrieved interface in a PB-PCXI tomographic reconstruction, which is obtained when Paganin-type phase retrieval is applied with incorrect values of δ and ß. The fit parameters can then be used to calculate true δ and ß values for composite materials. This approach requires no a priori sample information, making it broadly applicable. Our PB-PCXI reconstruction is single-distance, requiring only one exposure per tomographic angle, which is important for radiosensitive samples. We apply this approach to a breast-tissue sample, recovering the refraction component  Î´, with 0.6-2.4% accuracy compared with theoretical values.

Synchrotron microtomography applied to the volumetric analysis of internal structures of Thoropa miliaris tadpoles.

Amphibians are models for studying applied ecological issues such as habitat loss, pollution, disease, and global climate change due to their sensitivity and vulnerability to changes in the environment. Developmental series of amphibians are informative about their biology, and X-ray based 3D reconstruction holds promise for quantifying morphological changes during growth-some with a direct impact on the possibility of an experimental investigation on several of the ecological topics listed above. However, 3D resolution and discrimination of their soft tissues have been difficult with traditional X-ray computed tomography, without time-consuming contrast staining. Tomographic data were initially performed (pre-processing and reconstruction) using the open-source software tool SYRMEP Tomo Project. Data processing and analysis of the reconstructed tomography volumes were conducted using the segmentation semi-automatic settings of the software Avizo Fire 8, which provide information about each investigated tissues, organs or bone elements. Hence, volumetric analyses were carried out to quantify the development of structures in different tadpole developmental stages. Our work shows that synchrotron X-ray microtomography using phase-contrast mode resolves the edges of the internal tissues (as well as overall tadpole morphology), facilitating the segmentation of the investigated tissues. Reconstruction algorithms and segmentation software played an important role in the qualitative and quantitative analysis of each target structure of the Thoropa miliaris tadpole at different stages of development, providing information on volume, shape and length. The use of the synchrotron X-ray microtomography setup of the SYRMEP beamline of Elettra Synchrotron, in phase-contrast mode, allows access to volumetric data for bone formation, eye development, nervous system and notochordal changes during the development (ontogeny) of tadpoles of a cycloramphid frog Thoropa miliaris. As key elements in the normal development of these and any other frog tadpole, the application of such a comparative ontogenetic study, may hold interest to researchers in experimental and environmental disciplines.

Propagation-based x-ray phase-contrast tomography of mastectomy samples using synchrotron radiation.

PURPOSE: Propagation-based phase-contrast computed tomography (PB-CT) is a method for three-dimensional x-ray imaging that utilizes refraction, as well as absorption, of x rays in the tissues to increase the signal-to-noise ratio (SNR) in the resultant images, in comparison with equivalent conventional absorption-only x-ray tomography (CT). Importantly, the higher SNR is achieved without sacrificing spatial resolution or increasing the radiation dose delivered to the imaged tissues. The present work has been carried out in the context of the current development of a breast CT imaging facility at the Australian Synchrotron. METHODS: Seven unfixed complete mastectomy samples with and without breast cancer lesions have been imaged using absorption-only CT and PB-CT techniques under controlled experimental conditions. The radiation doses delivered to the mastectomy samples during the scans were comparable to those approved for mammographic screening. Physical characteristics of the reconstructed images, such as spatial resolution and SNR, have been measured and compared with the results of the radiological quality assessment of the complete absorption CT and PB-CT image stacks. RESULTS: Despite the presence of some image artefacts, the PB-CT images have outperformed comparable absorption CT images collected at the same radiation dose, in terms of both the measured objective image characteristics and the radiological image scores. The outcomes of these experiments are shown to be consistent with predictions of the theory of PB-CT imaging and previous reported experimental studies of this imaging modality. CONCLUSIONS: The results presented in this paper demonstrate that PB-CT holds a high potential for improving on the quality and diagnostic value of images obtained using existing medical x-ray technologies, such as mammography and digital breast tomosynthesis (DBT). If implemented at suitable synchrotron imaging facilities, PB-CT can be used to complement existing imaging modalities, leading to more accurate breast cancer diagnosis.

Free propagation phase-contrast breast CT provides higher image quality than cone-beam breast-CT at low radiation doses: a feasibility study on human mastectomies.

In this study we demonstrate the first direct comparison between synchrotron x-ray propagation-based CT (PB-CT) and cone-beam breast-CT (CB-CT) on human mastectomy specimens (N = 12) including different benign and malignant lesions. The image quality and diagnostic power of the obtained data sets were compared and judged by two independent expert radiologists. Two cases are presented in detail in this paper including a comparison with the corresponding histological evaluation. Results indicate that with PB-CT it is possible to increase the level of contrast-to-noise ratio (CNR) keeping the same level of dose used for the CB-CT or achieve the same level of CNR reached by CB-CT at a lower level of dose. In other words, PB-CT can achieve a higher diagnostic potential compared to the commercial breast-CT system while also delivering a considerably lower mean glandular dose. Therefore, we believe that PB-CT technique, if translated to a clinical setting, could have a significant impact in improving breast cancer diagnosis.

X-ray-Based 3D Virtual Histology-Adding the Next Dimension to Histological Analysis.

Histology and immunohistochemistry of thin tissue sections have been the standard diagnostic procedure in many diseases for decades. This method is highly specific for particular tissue regions or cells, but mechanical sectioning of the specimens is required, which destroys the sample in the process and can lead to non-uniform tissue deformations. In addition, regions of interest cannot be located beforehand and the analysis is intrinsically two-dimensional. Micro X-ray computed tomography (µCT) on the other hand can provide 3D images at high resolution and allows for quantification of tissue structures, as well as the localization of small regions of interest. These advantages advocate the use of µCT for virtual histology tool with or without subsequent classical histology. This review summarizes the most recent examples of virtual histology and provides currently known possibilities of improving contrast and resolution of µCT. Following a background in µCT imaging, ex vivo staining procedures for contrast enhancement are presented as well as label-free virtual histology approaches and the technologies, which could rapidly advance it, such as phase-contrast CT. Novel approaches such as zoom tomography and nanoparticulate contrast agents will also be considered. The current evidence suggests that virtual histology may present a valuable addition to the workflow of histological analysis, potentially reducing the workload in pathology, refining tissue classification, and supporting the detection of small malignancies.

Multimodal-3D imaging based on µMRI and µCT techniques bridges the gap with histology in visualization of the bone regeneration process.

Bone repair/regeneration is usually investigated through X-ray computed microtomography (µCT) supported by histology of extracted samples, to analyse biomaterial structure and new bone formation processes. Magnetic resonance imaging (µMRI) shows a richer tissue contrast than µCT, despite at lower resolution, and could be combined with µCT in the perspective of conducting non-destructive 3D investigations of bone. A pipeline designed to combine µMRI and µCT images of bone samples is here described and applied on samples of extracted human jawbone core following bone graft. We optimized the coregistration procedure between µCT and µMRI images to avoid bias due to the different resolutions and contrasts. Furthermore, we used an Adaptive Multivariate Clustering, grouping homologous voxels in the coregistered images, to visualize different tissue types within a fused 3D metastructure. The tissue grouping matched the 2D histology applied only on 1 slice, thus extending the histology labelling in 3D. Specifically, in all samples, we could separate and map 2 types of regenerated bone, calcified tissue, soft tissues, and/or fat and marrow space. Remarkably, µMRI and µCT alone were not able to separate the 2 types of regenerated bone. Finally, we computed volumes of each tissue in the 3D metastructures, which might be exploited by quantitative simulation. The 3D metastructure obtained through our pipeline represents a first step to bridge the gap between the quality of information obtained from 2D optical microscopy and the 3D mapping of the bone tissue heterogeneity and could allow researchers and clinicians to non-destructively characterize and follow-up bone regeneration.

Size and specimen-dependent strategy for x-ray micro-ct and tem correlative analysis of nervous system samples.

Correlative approaches are a powerful tool in the investigation of biological samples, but require specific preparation procedures to maintain the strength of the employed methods. Here we report the optimization of the embedding protocol of nervous system samples for a correlative synchrotron X-ray computed microtomography (micro-CT) and transmission electron microscopy (TEM) approach. We demonstrate that it is possible to locate, with the micrometric resolution of micro-CT, specific volumes of interest for a further ultrastructural characterization to be performed with TEM. This approach can be applied to samples of different size and morphology up to several cm. Our optimized method represents an invaluable tool for investigating those pathologies in which microscopic alterations are localized in few confined regions, rather than diffused in entire tissues, organs or systems. We present a proof of concept of our method in a mouse model of Globoid Cells Leukodistrophy.

Optimization of propagation-based x-ray phase-contrast tomography for breast cancer imaging.

The aim of this study was to optimise the experimental protocol and data analysis for in-vivo breast cancer x-ray imaging. Results are presented of the experiment at the SYRMEP beamline of Elettra Synchrotron using the propagation-based phase-contrast mammographic tomography method, which incorporates not only absorption, but also x-ray phase information. In this study the images of breast tissue samples, of a size corresponding to a full human breast, with radiologically acceptable x-ray doses were obtained, and the degree of improvement of the image quality (from the diagnostic point of view) achievable using propagation-based phase-contrast image acquisition protocols with proper incorporation of x-ray phase retrieval into the reconstruction pipeline was investigated. Parameters such as the x-ray energy, sample-to-detector distance and data processing methods were tested, evaluated and optimized with respect to the estimated diagnostic value using a mastectomy sample with a malignant lesion. The results of quantitative evaluation of images were obtained by means of radiological assessment carried out by 13 experienced specialists. A comparative analysis was performed between the x-ray and the histological images of the specimen. The results of the analysis indicate that, within the investigated range of parameters, both the objective image quality characteristics and the subjective radiological scores of propagation-based phase-contrast images of breast tissues monotonically increase with the strength of phase contrast which in turn is directly proportional to the product of the radiation wavelength and the sample-to-detector distance. The outcomes of this study serve to define the practical imaging conditions and the CT reconstruction procedures appropriate for low-dose phase-contrast mammographic imaging of live patients at specially designed synchrotron beamlines.

X-Ray based Lung Function measurement-a sensitive technique to quantify lung function in allergic airway inflammation mouse models.

In mice, along with the assessment of eosinophils, lung function measurements, most commonly carried out by plethysmography, are essential to monitor the course of allergic airway inflammation, to examine therapy efficacy and to correlate animal with patient data. To date, plethysmography techniques either use intubation and/or restraining of the mice and are thus invasive, or are limited in their sensitivity. We present a novel unrestrained lung function method based on low-dose planar cinematic x-ray imaging (X-Ray Lung Function, XLF) and demonstrate its performance in monitoring OVA induced experimental allergic airway inflammation in mice and an improved assessment of the efficacy of the common treatment dexamethasone. We further show that XLF is more sensitive than unrestrained whole body plethysmography (UWBP) and that conventional broncho-alveolar lavage and histology provide only limited information of the efficacy of a treatment when compared to XLF. Our results highlight the fact that a multi-parametric imaging approach as delivered by XLF is needed to address the combined cellular, anatomical and functional effects that occur during the course of asthma and in response to therapy.

Towards breast tomography with synchrotron radiation at Elettra: first images.

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-the-art 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 µm)(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.

Energy dependent calibration of XR-QA2 radiochromic film with monochromatic and polychromatic x-ray beams.

PURPOSE: This work investigates the energy response and dose-response curve determinations for XR-QA2 radiochromic film dosimetry system used for synchrotron radiation work and for quality assurance in diagnostic radiology, in the range of effective energies 18-46.5 keV. METHODS: Pieces of XR-QA2 films were irradiated, in a plane transverse to the beam axis, with a monochromatic beam of energy in the range 18-40 keV at the ELETTRA synchrotron radiation facility (Trieste, Italy) and with a polychromatic beam from a laboratory x-ray tube operated at 80, 100, and 120 kV. The film calibration curve was expressed as air kerma (measured free-in-air with an ionization chamber) versus the net optical reflectance change (netΔR) derived from the red channel of the RGB scanned film image. Four functional relationships (rational, linear exponential, power, and logarithm) were tested to evaluate the best curve for fitting the calibration data. The adequacy of the various fitting functions was tested by using the uncertainty analysis and by assessing the average of the absolute air kerma error calculated as the difference between calculated and delivered air kerma. The sensitivity of the film was evaluated as the ratio of the change in net reflectance to the corresponding air kerma. RESULTS: The sensitivity of XR-QA2 films increased in the energy range 18-39 keV, with a maximum variation of about 170%, and decreased in the energy range 38-46.5 keV. The present results confirmed and extended previous findings by this and other groups, as regards the dose response of the radiochromic film XR-QA2 to monochromatic and polychromatic x-ray beams, respectively. CONCLUSIONS: The XR-QA2 radiochromic film response showed a strong dependence on beam energy for both monochromatic and polychromatic beams in the range of half value layer values from 0.55 to 6.1 mm Al and corresponding effective energies from 18 to 46.5 keV. In this range, the film response varied by 170%, from a minimum sensitivity of 0.0127 to a maximum sensitivity of 0.0219 at 10 mGy air kerma in air. The more suitable function for air kerma calibration of the XR-QA2 radiochromic film was the power function. A significant batch-to-batch variation, up to 55%, in film response at 120 kV (46.5 keV effective energy) was observed in comparison with published data.

Objective measurements of image quality in synchrotron radiation phase-contrast imaging versus digital mammography.

PURPOSE: Phase-contrast mammography with synchrotron radiation is an innovative X-ray imaging practice that improves the identification of breast lesions. Previous studies have proven the superiority of the mammography images taken in the phase-contrast modality using synchrotron radiation beams as compared with images taken in conventional mammography by subjective analyses. However, to our knowledge, no previous study has compared different acquisition systems in order to quantify this improvement by means of objective robust indicators. In this research, we intend to quantify the superiority of phase-contrast imaging by means of objective metrics of image quality. METHODS: Images from the American College of Radiology Mammographic Accreditation Phantom were obtained at hospitals, in two digital mammography equipment and at the Elettra synchrotron radiation facility (Trieste, Italy), using free space propagation phase-contrast modality. Regions of interest were selected to analyze image quality at the fibers (phase object) and masses (area object) simulated on the phantom by means of the signal-to-noise ratio, the figure of merit, the contrast and the edge visibility. RESULTS: The image contrast and edge visibility were significantly higher at the phase-contrast modality as compared with digital mammography equipment. The figure of merit using phase-contrast modality was higher for the fibers and comparable for the masses. CONCLUSION: The results showed an improvement of the contrast and edge visibility in phase-contrast images. These improvements may be important in the detection of small lesions and details.

Osteogenic potential of dualblocks cultured with human periodontal ligament stem cells: in vitro and synchrotron microtomography study.

BACKGROUND AND OBJECTIVE: In the present study, the early stages of in vitro bone formation in collagenated porcine scaffolds cultured with human periodontal ligament cells were investigated. The comparison between the osteogenic potential of this structure in basal and differentiating culture media was explored to predict the mechanism of its biological behavior as graft in human defect. Results were validated by synchrotron radiation X-Ray phase contrast computed microtomography (micro-CT). As the periodontal disease plays a key role in systemic and oral diseases, it is crucial to find advanced therapeutic clinical interventions to repair periodontal defects. This has been recently explored using cells and tissues developed in vitro that should ideally be immunologically, functionally, structurally and mechanically identical to the native tissue. MATERIAL AND METHODS: In vitro cultures of human periodontal ligament cells, easily obtained by scraping of alveolar crestal and horizontal fibers of the periodontal ligament, were seeded on to collagenated porcine blocks constituted by natural cancellous and cortical bone. 3D images were obtained by synchrotron radiation micro-CT and processed with a phase-retrieval algorithm based on the transport of intensity equation. RESULTS: Starting from the second week of culture, newly formed mineralized bone was detected in all the scaffolds, both in basal and differentiating media. Bone mineralization was proved to occur preferentially in the trabecular portion and in differentiating media. CONCLUSION: The chosen method, supported by phase contrast micro-CT analysis, successfully and quantitatively monitored the early stages of bone formation and the rate of the bioscaffold resorption in basal and differentiating culture media.

Energy response of GR-200A thermoluminescence dosemeters to 60Co and to monoenergetic synchrotron radiation in the energy range 28-40 keV.

The response of LiF:Mg,Cu,P thermoluminescence dosemeters (type GR-200A) to monoenergetic radiation of energy 28, 35, 38 and 40 keV was evaluated with respect to irradiation with a calibrated (60)Co gamma-ray source. High-precision measurements of the relative air kerma response performed at the SYRMEP beamline of the ELETTRA synchrotron radiation facility (Trieste, Italy) showed a significant deviation of the average response to low-energy X-rays from that to (60)Co, with an over-response from 6 % (at 28 keV) to 22 % (at 40 keV). These data are not consistent with literature data for these dosemeters, where model predictions gave deviation from unity of the relative air kerma response of about 10 %. The authors conclude for the need of additional determinations of the low-energy relative response of GR-200A dosemeters, covering a wider range of monoenergetic energies sampled at a fine energy step, as planned in future experiments by their group at the ELETTRA facility.

Glandular dose in breast computed tomography with synchrotron radiation.

The purpose of this work is to provide an evaluation of the mean glandular dose (MGD) for breast computed tomography (CT) with synchrotron radiation in an axial scanning configuration with a partial or total organ volume irradiation, for the in vivo program of breast CT ongoing at the ELETTRA facility (Trieste, Italy). A Geant4 Monte Carlo code was implemented, simulating the photon irradiation from a synchrotron radiation source in the energetic range from 8 to 50 keV with 1 keV intervals, to evaluate the MGD. The code was validated with literature data, in terms of mammographic normalized glandular dose coefficients (DgN) and with ad hoc experimental data, in terms of computed tomography dose index (CTDI). Simulated cylindrical phantoms of different sizes (diameter at phantom base 8, 10, 12, 14 or 16 cm, axial length 1.5 times the radius) and glandular fraction by weight (0%, 14.3%, 25%, 50%, 75% and 100%) were implemented into the code. The validation of the code shows an excellent agreement both with previously published work and in terms of DgN and CDTI measurements. The implemented simulations show a dependence of the glandular dose estimate on the vertical dimension of the irradiated zone when a partial organ irradiation was implemented. Specific normalized coefficients for calculating the MGD to the whole breast or to the single irradiated slice were reported.

Clinical application of low-dose phase contrast breast CT: methods for the optimization of the reconstruction workflow.

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.

Imaging collagen packing dynamics during mineralization of engineered bone tissue.

The structure and organization of the Type I collagen microfibrils during mineral nanoparticle formation appear as the key factor for a deeper understanding of the biomineralization mechanism and for governing the bone tissue physical properties. In this work we investigated the dynamics of collagen packing during ex-vivo mineralization of ceramic porous hydroxyapatite implant scaffolds using synchrotron high resolution X-ray phase contrast micro-tomography (XPCµT) and synchrotron scanning micro X-ray diffraction (SµXRD). While XPCµT provides the direct 3D image of the collagen fibers network organization with micrometer spatial resolution, SµXRD allows to probe the structural statistical fluctuations of the collagen fibrils at nanoscale. In particular we imaged the lateral spacing and orientation of collagen fibrils during the anisotropic growth of mineral nanocrystals. Beyond throwing light on the bone regeneration multiscale process, this approach can provide important information in the characterization of tissue in health, aging and degeneration conditions. STATEMENT OF SIGNIFICANCE: BONE grafts are the most common transplants after the blood transfusions. This makes the bone-tissue regeneration research of pressing scientific and social impact. Bone is a complex hierarchical structure, where the interplay of organic and inorganic mineral phases at different length scale (from micron to atomic scale) affect its functionality and health. Thus, the understanding of bone tissue regeneration requires to image its spatial-temporal evolution (i) with high spatial resolution and (ii) at different length scale. We exploited high spatial resolution X-ray Phase Contrast micro Tomography and Scanning micro X-ray Diffraction in order to get new insight on the engineered tissue formation mechanisms. This approach could open novel routes for the early detection of different degenerative conditions of tissue.

First application of computed radiology to mammography with synchrotron radiation.

OBJECTIVE: The aim of this study was to evaluate the feasibility of phase-contrast mammography with synchrotron radiation using a high-resolution computed radiology (CR) system devoted to mammography. MATERIALS AND METHODS: The study was performed at the Synchrotron Radiation for Medical Physics (SYRMEP) beamline of the Elettra synchrotron radiation (SR) facility in Trieste (Italy); X-ray beams were in the range 16-22 keV with a high degree of monochromaticity and spatial coherence. The CR system evaluated is the FCR Profect CS by Fujifilm Global. The first images were obtained from test objects and surgical breast specimens. Images obtained using SR and both screen-film and the CR system were compared with images of the same samples acquired with digital mammography equipment. In view of the good quality of the results obtained, the CR system was used in two mammographic examinations with SR. RESULTS: Images acquired using SR and both screen-film and CR were obtained with the same level of delivered dose. Image quality obtained with CR was similar or superior to that of screen-film images. Moreover, the digital images obtained with SR were always better than those acquired using the digital mammography system. CONCLUSIONS: Phase-contrast mammography with SR using the studied CR system is a feasible option.