A Phase-Contrast breast CT facility based on a high-resolution CdTe photon-counting detector is under development at Elettra, the Italian Synchrotron Radiation (SR) facility in Trieste. The CT system exploits propagation-based phasecontrast imaging and phase-retrieval algorithm. The voxel size is 57×57×50 μm3 and the delivered MGDs, about 5 mGy, are comparable with clinical breast CT systems. In the present contribution, the comparisons between histological breast cancers and full breast CT images are presented from samples of breast mastectomy. The high resolution of the breast CT images and low noise due to the phase contrast allow a very fine matching between x-ray CT and histology at acceptable delivered doses.
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-μm 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 cm3) is reported. This investigation into surgical specimens indicates that SR BCT in terms of CNR, spatial resolution, scan duration, and scan volume is feasible.
A program devoted to perform the first in-vivo monochromatic breast computed tomography (BCT) is ongoing at the Elettra Synchrotron Facility. Since the synchrotron radiation provides high energy resolution and spatial coherence, 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 a wider framework, devoted to the optimization of acquisition and reconstruction parameters towards the clinical exam. Images are acquired with a state-of-the-art dead-time-free single-photon-counting CdTe detector with a 60 µm pixel size. The samples are imaged at 32 and 38 keV in continuous rotating mode, delivering 5-20 mGy of mean glandular dose (MGD). Contrast-to-noise ratio (CNR) and spatial resolution performances are evaluated for both absorption and phase-retrieved images considering tumor/adipose tissue interfaces. We discuss two different phase-retrieval approaches, showing that a remarkable CNR increase (from 0.5 to 3.6) can be obtained without a significant loss in spatial resolution. It is shown that, even if the non-phase-retrieved image has a poorer CNR, it is useful for evaluating the spiculation of a microcalcification: in this context, absorption and phase-retrieved images have to be regarded as complementary information. Furthermore, the first full volume acquisition of a mastectomy, with a 9 cm diameter and 3 cm height, is reported. This investigation on surgical specimens indicates that monochromatic BCT with synchrotron radiation in terms of CNR, spatial resolution, scan duration and scan volume is feasible.
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 (p<0.001). 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.
This article discusses two experimental setups of edge illumination (EI) x-ray phase contrast imaging (XPCi) as well as
the theory that is required to reconstruct quantitative tomographic maps using established methods, e.g. filtered back
projection (FBP). Tomographic EI XPCi provides the option to reconstruct volumetric maps of different physical
quantities, amongst which are the refractive index decrement from unity and the absorption coefficient, which can be
used for dual-mode imaging. EI XPCi scans of a custom-built wire phantom using synchrotron and x-ray tube generated
radiation were carried out, and tomographic maps of both parameters were reconstructed. This article further discusses
the theoretical basis for the tomographic reconstruction of images showing combined phase and attenuation contrast.
Corresponding experimental results are presented.
In 1948 Kirkpatrick and Baez showed that two crossed mirrors in a tandem configuration with concave surfaces can
focus hard x-rays by reflection. Right afterwards in 1949 Kirkpatrick showed theoretically that x-rays can also be
focused by refraction, when they are transmitted through a similar system, i.e. in conditions, when the reflectivity at the
concave interface is negligible. He performed an experiment, in which he refracted an x-ray beam at grazing incidence at
such a curved interface in one direction. Consequently this was the first reported practical use of a refractive x-ray lens.
The experiment was forgotten. Here we compare more systematically the focusing in such devise with the expectations.
We propose the use in a flat field spectrometer, which could provide better spectral resolution for fluorescence analysis
than the commonly used Si drift diodes, however, on the expense of a rather low efficiency. The application of the
system may thus be limited to the spectral characterisation of x-ray sources.
Small triangular prisms are arranged very regularly in Clessidra type x-ray lenses: they are interconnected at their tips and form a
larger prism of equal shape very similarly to a stylised Christmas tree. Two opposing prisms of this type then form the Clessidra
prism array. The name arrives from the similarity with an old hourglass, Clessidra in Italian. The construction principle makes the
lens highly periodic in the vertical direction perpendicular to the incident beam. Thus with sufficiently spatially coherent x-ray
illumination, the structure can be looked at as a linear transmission grating, i.e. a diffracting object. It is a special feature of the
Clessidra lenses, that they have inherent focusing capabilities in the near field, or Fresnel regime of diffraction. In this regime the
structure periodicity of the diffracting object is reproduced with different linear magnifications at the Talbot distances. The refraction in the prism structure then directs all incident intensities to a common crossover point at one of the Talbot distances. This situation was studied rigorously from the theoretical point of view. This report then presents simple models, which are in agreement with the rigorous calculations, and which can consistently explain our experimental data. For a given lens we varied the photon energy of the incident radiation and the distance between the lens and a CCD detector. In addition we moved a small slit of varying opening through the lens aperture. The experimental data will be interpreted also depending on the spatially coherently illuminated area at the lens.
Description of purpose: Treatment of osteoarthritis in stages of reversible disease requires high resolution visualization of early cartilage damage and of subchondral bone. Here, DEI (Diffraction Enhanced Imaging) is compared to MRI, computed X-ray tomography (CT) and ultrasound (UI) in its ability to detect early degeneration of articular cartilage. In contrast to conventional absorptive X-ray examination where cartilage is poorly visible DEI captures cartilage by detection of selected refraction. Methods: Human femoral heads were investigated by macroscopic inspection, conventional X-ray examination, DEI, MRI, CT, UI and histology. DEI is an imaging technique applying a monochromatic parallel synchrotron X-ray beam. Image features were verified by histology. Results: DEI, MRI and ultrasound lead to interpretable images of cartilage. Of all techniques, DEI provided highest image resolution revealing the structural tissue architecture. MRI needs a very long exposure time (more than 5 hours) to achieve comparable quality. Application of ultrasound is limited because of joint geometry and, at high sound frequency, the necessity of close contact between cartilage and transducer. DEI is an experimental technique which needs synchrotron radiation. Conclusion: DEI is a very promising imaging technique for visualization of cartilage and bone. It may serve as an excellent analytical tool for experimental studies. Our pictures show a part of future of optimised techniques for imaging. Synchrotron based DEI may lead the way towards optimisation of improved techniques for imaging. Upon development of adequate small scale X-ray sources, DEI will also be an important supplementation for medical imaging.
Werner Jark, Frederic Perennes, Marco Matteucci, Lucia Mancini, Francesco Montanari, Luigi Rigon, Giuliana Tromba, Andrea Somogyi, Remi Tucoulou, Sylvain Bohic
This report describes the optimization, first experimental data and the performance outlook for a special refractive lens for the focusing of x-rays. The lens was obtained by applying the strategy of Fresnel to lighten a lens by removing efficiently optically passive material. This strategy was applied to objects, which were produced by deep x-ray lithography and which can thus be shaped in only one dimension. Consequently this class of lenses can focus in only one dimension. While in the normal Fresnel lenses as much material as possible is removed, in the present lens the remaining segments were kept as large as possible, in order to finally obtain a rigid and deep structure. The resultant structure is composed of small prisms of almost identical shape, which are combined such that the final lens looks like an hour glass, i.e. two large prisms touch each other at one of their tips. Such a lens has better transmission than a normal refractive lens of equal focal length. And even though it has worse transmission than the normal Fresnel lenses, it could be produced with an unprecedented geometrical aperture of 2.6 mm for 8 keV photon energy. The uniformly etched structure depth was found to be at least 0.4 mm, over which the lens can focus free of aberrations. A lens with focal length 2.183 m was found to provide after very rapid alignment a focus size of 2.8 μm, while slightly better 1.73 μm were ideally expected.
An attempt has been made, for the first time, to extend the capabilities of diffraction enhanced imaging (DEI) using low
concentrations of a contrast agent. A phantom has been constructed to accommodate a systematic series of diluted bromine deoxyuridase (BrDU) samples in liquid form. This was imaged using a conventional DEI arrangement and at a range of energies traversing the Br K-edge. The images were analyzed to provide a quantitative measure of contrast as a function of X-ray energy and (BrDU) concentration. The results indicate that the particular experimental arrangement was not optimized to exploit the potential of this contrast enhancement and several suggestions are discussed to improve this further.
Preliminary experiments have been carried out in order to evaluate the potential of the Diffraction Enhanced Imaging (DEI) technique in combination with contrast agents not based on X-ray absorption properties, but that provide strong scattering signals. The contrast agents tested in this study are microbubble echo-enhancing agents, usually used in ultrasound examinations, which are completely invisible with conventional X-ray absorption techniques.
A DEI set-up has been implemented at the Medical Beamline at the synchrotron radiation facility ELETTRA (Trieste, Italy). The analyzer crystal is a single flat silicon crystal utilized in the [111] reflection. By shifting the analyzer crystal to different positions of the rocking curve it is possible to detect the scattered photons; in particular, if the sample consists of a large number of particles with size smaller than the pixel size of the detector, an overall effect can be visualized. Phantoms containing ultrasound contrast agents have been built and imaged at different angular positions of the analyzer crystal at 17 keV and 25 keV. For all the phantoms a much stronger contrast has been measured in comparison to the contrast evaluated from the images produced with normal absorption methods.
Diffraction Enhanced Imaging (DEI) is a powerful X-ray imaging technique that allows the visualization of structures having different refraction and/or absorption properties with respect to the background. In DEI, the sample is irradiated with a monochromatic and highly collimated X-ray beam, and the outgoing beam is analyzed by means of a perfect crystal. A comparison was drawn among DEI images of a standard (ACR) and a custom phantom using different harmonic diffraction orders. Images were obtained at two different synchrotron beamlines, the SYRMEP beamline at Elettra and the X15A beamline at the NSLS (Brookhaven, NY), utilizing a double-crystal Si monochromator and a single-crystal Si analyzer, operated in the symmetric, non-dispersive Bragg configuration. The harmonic order was separated by placing a refractive prism between the two crystals of the monochromator. The use of the and the reflections resulted in a 5-fold improvement in the analyzer angular sensitivity, consequently enhancing the extinction and refraction contrasts with respect to the reflection. The detail visibility was improved by 1-2 orders of magnitude. By means of the refractive prism technique, even higher harmonics might be used, thus promising even better image quality.
Conventional x-ray imaging relies almost entirely on differences in the absorption of x-rays between tissues to produce contrast. While these differences are substantial between bone and soft tissue, they are very small between different soft tissue types resulting in poor visualization of soft tissues. Diffraction enhanced imaging (DEI) is currently in development by several groups as a new imaging modality that exploits information contained within the x- ray scattering distribution at low angles. We have used the SYRMEP beam line at the Elettra Synchrotron facility in Trieste, Italy to image a variety of tissue specimens, together with several phantoms. Mono-energetic photons in the range 17 keV to 25 keV were used with an analyzer crystal which diffracted the x-rays onto a detector. We have obtained some spectacular images which display remarkable contrast and resolution. The images can be processed to separate the pure absorption and pure refraction effects in a quantitative manner. These images demonstrate that DEI provides tissue morphology information not accessible with conventional radiographic imaging. The contrast caused primarily by refraction as the x-ray passes from one tissue type to another in the specimen is evident. Since x-ray refraction is much less energy dependent than absorption there is considerable potential for extremely low dose imaging. We believe that the potential of this technique is considerable and we present dat to illustrate the quality of the images.
Gadovist, a 1.0-molar Gd contrast agent from Schering AG, Berlin, Germany, in use in clinical MRI in Europe, was evaluated as a radiography contrast agent. In a collaboration with Brookhaven National Laboratory (BNL), Schering AG is developing several such lanthanide-based contrast agents, while BNL evaluates them using different x-ray beam energy spectra. These energy spectra include a 'truly' monochromatic beam (0.2 keV energy bandwidth) from the National Synchrotron Light Source (NSLS), BNL, tuned above the Gd K-edge, and x-ray-tube beams from different kVp settings and beam filtrations. Radiographs of rabbits' kidneys were obtained with Gadovist at the NSLS. Furthermore, a clinical radiography system was used for imaging rabbits' kidneys comparing Gadovist and Conray, an iodinated contrast agent. The study, using 74 kVp and standard Al beam filter for Conray and 66 kVp and an additional 1.5 mm Cu beam filter for Gadovist, produced comparable images for Gadovist and Conray; the injection volumes were the same, while the radiation absorbed dose for Gadovist was slightly smaller. A bent-crystal silicon monochromator operating in the Laue diffraction mode was developed and tested with a conventional x-ray tube beam; it narrows the energy spectrum to about 4 keV around the anode tungsten's K' line. Preliminary beam-flux results indicate that the method could be implemented in clinical CT if x-ray tubes with approximately twice higher output become available.
One major goal of modern radiology is the improvement of image quality and subsequently the development of sophisticated radiographic methods which are capable of detecting low contrast and small size details in organic samples in particular in mammography where the requirements on contrast resolution and spatial resolution are extremely high. Significant improvements in image quality have been achieved by the SYRMEP (SYnchrotron Radiation for MEdical Physics) collaboration which has designed and built a beamline devoted to medical physics at the synchrotron radiation facility ELETTRA in Trieste (Italy). The detection system developed for digital mammography consists of a silicon pixel detector with a pixel size of 200 X 300 micrometers 2 used in the `edge on' configuration in order to achieve a high conversion efficiency. The detector is equipped with a low noise VLSI amplifier chain; at present. Recently, a multilayer detector prototype has been implemented, consisting of a stack of three single silicon strip layers. This set-up provides a larger sensitive area and subsequently a reduction of the exposure time. Digital images of mammographic phantoms and of in vitro full breast tissue samples show a higher contrast resolution and lower absorbed dose when compared to conventional mammographic images. Besides, further promising studies have been initiated developing novel imaging methods based on the phase effects evidenced by the high degree of coherence of the SR source. At the SYRMEP beamline several experiments have been carried out in order to exploit the potentials of two different techniques, Phase Contrast and Diffraction Enhanced Imaging, respectively. Images showing better detail visibility and enhanced contrast were produced with dose lower or comparable to the conventional one.
A linear array silicon pixel detector has been developed to perform digital radiology with synchrotron radiation: in this communication we present the first results obtained using a three layer prototype at the Elettra Synchrotron Radiation Facility (Trieste, Italy). High efficiency (about 85% at 20 keV) is achieved by means of an Si strip detector irradiated in an 'edge-on' geometry: the pixel dimensions are 200 X 300 micrometer2. To obtain a sensitive area of about 50 X 1 mm2 stack of three layers has been assembled. Images are obtained by means of scanning techniques and their spatial resolution is determined by the scanning step. Detectors are read-out by dedicated, low noise VLSI CMOS chips in single photon counting mode. The distance between each detector layer has been measured to be 115 plus or minus 10 micrometer and the layers are parallel within a maximum tilt angle of 0.08 degrees. Cross-talk effects were found to be always smaller than 2% of the counts of the neighboring layers. The MTF in the scan direction has been evaluated. The acquisition time needed to acquire an image of a mammographic test object is about 6 minutes. The mean glandular dose is about 30% of the dose delivered at the conventional mammographic unit for the same test object while the detail visibility is comparable. These preliminary results indicate that a large area linear array silicon pixel detector can be developed: using this detector and a monochromatic synchrotron radiation beam the delivered mean glandular dose is significantly reduced when compared to conventional mammographic examinations.
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