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A system using energy-dispersive X-ray diffraction (EDXRD) has been developed and tested using multivariate calibration for the quantitative analysis of tablet-form mixtures of common pharmaceutical ingredients. A principal advantage of EDXRD over the more traditional and common angular dispersive X-ray diffraction technique (ADXRD) is the potential of EDXRD to analyse tablets within their packaging, due to the higher energy X-rays used. In the experiment, a series of caffeine, paracetamol and microcrystalline cellulose mixtures were prepared and pressed into tablets. EDXRD profiles were recorded on each sample and a principal component analysis (PCA) was carried out in both unpackaged and packaged scenarios. In both cases the first two principal components explained >98% of the between-sample variance. The PCA projected the sample profiles into two dimensional principal component space in close accordance to their ternary mixture design, demonstrating the discriminating potential of the EDXRD system. A partial least squares regression (PLSR) model was built with the samples and was validated using leave-one-out cross-validation. Low prediction errors of between 2% and 4% for both unpackaged and packaged tablets were obtained for all three chemical compounds. The prediction capability through packaging demonstrates a truly non-destructive method for quantifying tablet composition and demonstrates good potential for EDXRD to be applied in the field of counterfeit medicine screening and pharmaceutical quality control., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

This pilot study examines the correlation of X-ray diffraction (XRD) measurements with the histopathological analysis of breast tissue. Eight breast cancer samples were investigated. Each sample contained a mixture of normal and cancerous tissues. In total, 522 separate XRD measurements were made at different locations across the samples (8 in total). The resulting XRD spectra were subjected to principal component analysis (PCA) in order to determine if there were any distinguishing features that could be used to identify different tissue components. 99.0% of the variation between the spectra were described by the first two principal components (PC). Comparing the location of points in PC space with the classification determined by histopathology indicated correlation between the shape/magnitude of the XRD spectra and the tissue type. These results are encouraging and suggest that XRD could be used for the intraoperative or postoperative classification of bulk tissue samples.

High-resolution, low-noise x-ray detectors based on the complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology have been developed and proposed for digital breast tomosynthesis (DBT). In this study, we evaluated the three-dimensional (3D) imaging performance of a 50 µm pixel pitch CMOS APS x-ray detector named DynAMITe (Dynamic Range Adjustable for Medical Imaging Technology). The two-dimensional (2D) angle-dependent modulation transfer function (MTF), normalized noise power spectrum (NNPS), and detective quantum efficiency (DQE) were experimentally characterized and modeled using the cascaded system analysis at oblique incident angles up to 30°. The cascaded system model was extended to the 3D spatial frequency space in combination with the filtered back-projection (FBP) reconstruction method to calculate the 3D and in-plane MTF, NNPS and DQE parameters. The results demonstrate that the beam obliquity blurs the 2D MTF and DQE in the high spatial frequency range. However, this effect can be eliminated after FBP image reconstruction. In addition, impacts of the image acquisition geometry and detector parameters were evaluated using the 3D cascaded system analysis for DBT. The result shows that a wider projection angle range (e.g.  ±30°) improves the low spatial frequency (below 5 mm -1 ) performance of the CMOS APS detector. In addition, to maintain a high spatial resolution for DBT, a focal spot size of smaller than 0.3 mm should be used. Theoretical analysis suggests that a pixelated scintillator in combination with the 50 µm pixel pitch CMOS APS detector could further improve the 3D image resolution. Finally, the 3D imaging performance of the CMOS APS and an indirect amorphous silicon (a-Si:H) thin-film transistor (TFT) passive pixel sensor (PPS) detector was simulated and compared.

Purpose: The Calcium/Phosphorus (Ca/P) ratio was shown to vary between healthy bones and bones with osteoporotic symptoms. The relation of the Ca/P ratio to bone quality remains under investigation. To study this relation and determine if the ratio can be used to predict bone fractures, a non-invasive 3D imaging technique is required. The first aim of this study was to test the effectiveness of a computed-tomography dual-energy analysis (CT-DEA) technique developed to assess the Ca/P ratio in bone apatite (collagen-free bone) in identifying differences between healthy and inflammation-mediated osteoporotic (IMO) bones. The second aim was to extend the above technique for its application to a more complex structure, intact bone, that could potentially lead to clinical use., Methods: For the first aim, healthy and IMO rabbit cortical bone apatite samples were assessed. For the second aim, some changes were made to the technique, which was applied to healthy and IMO intact bone samples., Results: Statistically significant differences between healthy and IMO bone apatite were found for the bulk Ca/P ratio, low Ca/P ratio proportion and interconnected low Ca/P ratio proportion. For the intact bone samples, the bulk Ca/P ratio was found to be significantly different between healthy and IMO., Conclusions: Results show that the CT-DEA technique can be used to identify differences in the Ca/P ratio between healthy and osteoporotic, in both bone apatite and intact bone. With quantitative imaging becoming an increasingly important advancement in medical imaging, CT-DEA for bone decomposition could potentially have several applications., (Copyright © 2015. Published by Elsevier Ltd.)

Wafer-scale CMOS active pixel sensors (APSs) have been developed recently for x-ray imaging applications. The small pixel pitch and low noise are very promising properties for medical imaging applications such as digital breast tomosynthesis (DBT). In this work, we evaluated experimentally and through modeling the imaging properties of a 50 μm pixel pitch CMOS APS x-ray detector named DynAMITe (Dynamic Range Adjustable for Medical Imaging Technology). A modified cascaded system model was developed for CMOS APS x-ray detectors by taking into account the device nonlinear signal and noise properties. The imaging properties such as modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) were extracted from both measurements and the nonlinear cascaded system analysis. The results show that the DynAMITe x-ray detector achieves a high spatial resolution of 10 mm(-1) and a DQE of around 0.5 at spatial frequencies  <1 mm(-1). In addition, the modeling results were used to calculate the image signal-to-noise ratio (SNRi) of microcalcifications at various mean glandular dose (MGD). For an average breast (5 cm thickness, 50% glandular fraction), 165 μm microcalcifications can be distinguished at a MGD of 27% lower than the clinical value (~1.3 mGy). To detect 100 μm microcalcifications, further optimizations of the CMOS APS x-ray detector, image aquisition geometry and image reconstruction techniques should be considered.

Recently CMOS active pixels sensors (APSs) have become a valuable alternative to amorphous silicon and selenium flat panel imagers (FPIs) in bio-medical imaging applications. CMOS APSs can now be scaled up to the standard 20 cm diameter wafer size by means of a reticle stitching block process. However, despite wafer scale CMOS APS being monolithic, sources of non-uniformity of response and regional variations can persist representing a significant challenge for wafer scale sensor response. Non-uniformity of stitched sensors can arise from a number of factors related to the manufacturing process, including variation of amplification, variation between readout components, wafer defects and process variations across the wafer due to manufacturing processes. This paper reports on an investigation into the spatial non-uniformity and regional variations of a wafer scale stitched CMOS APS. For the first time a per-pixel analysis of the electro-optical performance of a wafer CMOS APS is presented, to address inhomogeneity issues arising from the stitching techniques used to manufacture wafer scale sensors. A complete model of the signal generation in the pixel array has been provided and proved capable of accounting for noise and gain variations across the pixel array. This novel analysis leads to readout noise and conversion gain being evaluated at pixel level, stitching block level and in regions of interest, resulting in a coefficient of variation ⩽1.9%. The uniformity of the image quality performance has been further investigated in a typical x-ray application, i.e. mammography, showing a uniformity in terms of CNR among the highest when compared with mammography detectors commonly used in clinical practice. Finally, in order to compare the detection capability of this novel APS with the technology currently used (i.e. FPIs), theoretical evaluation of the detection quantum efficiency (DQE) at zero-frequency has been performed, resulting in a higher DQE for this detector compared to FPIs. Optical characterization, x-ray contrast measurements and theoretical DQE evaluation suggest that a trade off can be found between the need of a large imaging area and the requirement of a uniform imaging performance, making the DynAMITe large area CMOS APS suitable for a range of bio-medical applications.

We report on the design and realization of an x-ray imaging system for quantitative phase-contrast microscopy at high x-ray energy with laboratory-scale instrumentation. Phase and amplitude were separated quantitatively at x-ray energies up to 80 keV with micrometric spatial resolution. The accuracy of the results was tested against numerical simulations, and the spatial resolution was experimentally quantified by measuring a Siemens star phase object. This simple setup should find broad application in those areas of x-ray imaging where high energy and spatial resolution are simultaneously required and in those difficult cases where the sample contains materials with similar x-ray absorption.

In this note we present the first proof-of-concept results on the potential effectiveness of the edge-illumination x-ray phase contrast method (in its 'coded-aperture' based lab implementation) combined with tomosynthesis. We believe that, albeit admittedly preliminary (e.g. we only present phantom work), these results deserve early publication in a note primarily for four reasons. First, we fully modelled the imaging acquisition method, and validated the simulation directly with experimental results. This shows that the implementation of the method in the new geometry is understood, and thus that it will be possible to use the model to simulate more complex scenarios in the future. Secondly, we show that a strong phase contrast signal is preserved in the reconstructed tomosynthesis slices: this was a concern, as the high spatial frequency nature of the signal makes it sensitive to any filtration-related procedure. Third, we show that, despite the non-optimized nature of the imaging prototype used, we can perform a full angular scan at acceptable dose levels and with exposure times not excessively distant from what is required by clinical practice. Finally, we discuss how the proposed phase contrast method, unlike other approaches apart from free-space propagation (which however requires a smaller focal spot, thus reducing the flux and increasing exposure times), can be easily implemented in a tomosynthesis geometry suitable for clinical use. In summary, we find that these technical results indicate a high potential for the combination of the two methods. Combining slice separation with detail enhancement provided by phase effects would substantially increase the detectability of small lesions and/or calcifications, which we aim to demonstrate in the next steps of this study.

The principal limitation to the widespread deployment of X-ray phase imaging in a variety of applications is probably versatility. A versatile X-ray phase imaging system must be able to work with polychromatic and non-microfocus sources (for example, those currently used in medical and industrial applications), have physical dimensions sufficiently large to accommodate samples of interest, be insensitive to environmental disturbances (such as vibrations and temperature variations), require only simple system set-up and maintenance, and be able to perform quantitative imaging. The coded-aperture technique, based upon the edge illumination principle, satisfies each of these criteria. To date, we have applied the technique to mammography, materials science, small-animal imaging, non-destructive testing and security. In this paper, we outline the theory of coded-aperture phase imaging and show an example of how the technique may be applied to imaging samples with a practically important scale.

Purpose: To provide an x-ray phase contrast imaging (XPCI) method working with conventional sources that could be readily translated into clinical practice. XPCI shows potential in synchrotron studies but attempts at translating it for use with conventional sources are subject to limitations in terms of field of view, stability, exposure time, and possibly most importantly, delivered dose., Methods: Following the adaptation of our "edge-illumination" XPCI technique for use with conventional x-ray sources through the use of x-ray masks, the authors have further modified the design of such masks to allow further reducing the dose delivered to the sample without affecting the phase sensitivity of the method., Results: The authors have built a prototype based on the new mask design and used it to image ex vivo breast tissue samples containing malignant lesions. The authors compared images acquired with this prototype to those obtained with a conventional system. The authors demonstrate and quantify image improvements, especially in terms of microcalcification detection. On calcifications detected also by the conventional system, the authors measure contrast increases from five to nine fold; calcifications and other features were also detected which are completely invisible in the conventional image. Dose measurements confirmed that the above enhancements were achieved while delivering doses compatible with clinical practice., Conclusions: The authors obtained phase-related image enhancements in mammography by means of a system built with components available off-the-shelf that operates under exposure time and dose conditions compatible with clinical practice. This opens the way to a straightforward translation of phase enhanced imaging methods into clinical practice.

Here we present a general alignment algorithm for an edge illumination x-ray phase contrast imaging system, which is used with the laboratory systems developed at UCL. It has the flexibility to be used with all current mask designs, and could also be applied to future synchrotron based systems. The algorithm has proved to be robust experimentally, and can be used for the automatization of future commercial systems through automatic alignment and alignment correction.

We present a quantitative, non-interferometric, X-ray differential phase contrast imaging technique based on the edge illumination principle. We derive a novel phase retrieval algorithm which requires only two images to be acquired and verify the technique experimentally using synchrotron radiation. The technique is useful for planar imaging but is expected to be important for quantitative phase tomography also. The properties and limitations of the technique are studied in detail.

Purpose: This study investigates the image quality of tomosynthesis slices obtained from several acquisition sets with synchrotron radiation using a breast phantom incorporating details that mimic various breast lesions, in a heterogeneous background., Methods: A complex Breast phantom (MAMMAX) with a heterogeneous background and thickness that corresponds to 4.5 cm compressed breast with an average composition of 50% adipose and 50% glandular tissue was assembled using two commercial phantoms. Projection images using acquisition arcs of 24°, 32°, 40°, 48°, and 56° at incident energy of 17 keV were obtained from the phantom with the synchrotron radiation for medical physics beamline at ELETTRA Synchrotron Light Laboratory. The total mean glandular dose was set equal to 2.5 mGy. Tomograms were reconstructed with simple multiple projection algorithm (MPA) and filtered MPA. In the latter case, a median filter, a sinc filter, and a combination of those two filters were applied on the experimental data prior to MPA reconstruction. Visual inspection, contrast to noise ratio, contrast, and artifact spread function were the figures of merit used in the evaluation of the visualisation and detection of low- and high-contrast breast features, as a function of the reconstruction algorithm and acquisition arc. To study the benefits of using monochromatic beams, single projection images at incident energies ranging from 14 to 27 keV were acquired with the same phantom and weighted to synthesize polychromatic images at a typical incident x-ray spectrum with W target., Results: Filters were optimised to reconstruct features with different attenuation characteristics and dimensions. In the case of 6 mm low-contrast details, improved visual appearance as well as higher contrast to noise ratio and contrast values were observed for the two filtered MPA algorithms that exploit the sinc filter. These features are better visualized at extended arc length, as the acquisition arc of 56° with 15 projection images demonstrates the highest image reconstruction quality. For microcalcifications, filtered MPA implemented with a combination of median and sinc filters indicates better feature appearance due to efficient suppression of background tissue. The image quality of these features is less sensitive to the acquisition arc. Calcifications with size ranging from 170 to 500 μm, like the ones presently studied, are well identified and visualized for all arcs used. The comparison of single projection images obtained under different beam conditions showed that the use of monochromatic beam can produce an image with higher contrast and contrast to noise ratio compared to an image corresponding to a polychromatic beam even when the latter is acquired with double incident exposure., Conclusions: Filter optimization in respect to the type of feature characteristics is important before the reconstruction. The MPA combined with median and sinc filters results in improved reconstruction of microcalcifications and low-contrast features. The latter are better visualized at extended arc length, while microcalcifications are less sensitive to this acquisition parameter. Use of monochromatic beams may result in tomographic images with higher contrast acquired at lower incident exposures.

X-ray phase contrast imaging has overcome the limitations of X-ray absorption imaging in many fields. Particular effort has been directed towards developing phase retrieval methods: These reveal quantitative information about a sample, which is a requirement for performing X-ray phase tomography, allows material identification and better distinction between tissue types, etc. Phase retrieval seems impossible with conventional X-ray sources due to their low spatial coherence. In the only previous example where conventional sources have been used, collimators were employed to produce spatially coherent secondary sources. We present a truly incoherent phase retrieval method, which removes the spatial coherence constraints and employs a conventional source without aperturing, collimation, or filtering. This is possible because our technique, based on the pixel edge illumination principle, is neither interferometric nor crystal based. Beams created by an X-ray mask to image the sample are smeared due to the incoherence of the source, yet we show that their displacements can still be measured accurately, obtaining strong phase contrast. Quantitative information is extracted from only two images rather than a sequence as required by several coherent methods. Our technique makes quantitative phase imaging and phase tomography possible in applications where exposure time and radiation dose are critical. The technique employs masks which are currently commercially available with linear dimensions in the tens of centimeters thus allowing for a large field of view. The technique works at high photon energy and thus promises to deliver much safer quantitative phase imaging and phase tomography in the future.

We have developed a pixellated high energy X-ray detector instrument to be used in a variety of imaging applications. The instrument consists of either a Cadmium Zinc Telluride or Cadmium Telluride (Cd(Zn)Te) detector bump-bonded to a large area ASIC and packaged with a high performance data acquisition system. The 80 by 80 pixels each of 250 μm by 250 μm give better than 1 keV FWHM energy resolution at 59.5 keV and 1.5 keV FWHM at 141 keV, at the same time providing a high speed imaging performance. This system uses a relatively simple wire-bonded interconnection scheme but this is being upgraded to allow multiple modules to be used with very small dead space. The readout system and the novel interconnect technology is described and how the system is performing in several target applications.

Purpose: The x-ray performance evaluation of digital x-ray detectors is based on the calculation of the modulation transfer function (MTF), the noise power spectrum (NPS), and the resultant detective quantum efficiency (DQE). The flat images used for the extraction of the NPS should not contain any fixed pattern noise (FPN) to avoid contamination from nonstochastic processes. The "gold standard" method used for the reduction of the FPN (i.e., the different gain between pixels) in linear x-ray detectors is based on normalization with an average reference flat-field. However, the noise in the corrected image depends on the number of flat frames used for the average flat image. The aim of this study is to modify the standard gain correction algorithm to make it independent on the used reference flat frames., Methods: Many publications suggest the use of 10-16 reference flat frames, while other studies use higher numbers (e.g., 48 frames) to reduce the propagated noise from the average flat image. This study quantifies experimentally the effect of the number of used reference flat frames on the NPS and DQE values and appropriately modifies the gain correction algorithm to compensate for this effect., Results: It is shown that using the suggested gain correction algorithm a minimum number of reference flat frames (i.e., down to one frame) can be used to eliminate the FPN from the raw flat image. This saves computer memory and time during the x-ray performance evaluation., Conclusions: The authors show that the method presented in the study (a) leads to the maximum DQE value that one would have by using the conventional method and very large number of frames and (b) has been compared to an independent gain correction method based on the subtraction of flat-field images, leading to identical DQE values. They believe this provides robust validation of the proposed method.

Purpose: This paper proposes the further development of a resolution modification routine which is used to simulate the presampling modulation transfer function (pMTF) of digital x-ray detectors., Methods: It suggests a method to reconstruct anisotropic two dimensional (2D) pMTF matrices from the experimentally measured horizontal and vertical 1D pMTFs. In this study, the horizontal dimension of the detector is 17.3 cm, while the vertical one is 24 cm. This matrix is multiplied with the 2D Fourier transform of the super-sampled ideal input image to simulate blurring. Then, the restored image is sampled to form the pixels of the digital image. The authors suggest convolution with the comb function instead of the rectangular function to avoid the correction with the sinc function required by the latter. It is demonstrated that this correction is avoided when the comb function is used. Moreover, this study suggests a way to effectively sample the images in the case when the ratio between the "analog" pitch of the super-sampled input image and the pixel pitch of the digital x-ray detector is a semi-integer., Results: The validation of the simulation algorithm demonstrated that when the comb function was used the average absolute difference between the pMTF measured from the output images and the input ones was less than 1%, while this was of 13% when the rectangular function was used. When a sinc correction was applied in the latter case the difference decreased again to less than 1%., Conclusions: The developed modification routine provides the means to simulate the spatial resolution of digital x-ray detectors under a wider range of conditions.

X-ray baggage scanners play a basic role in the protection of airports, customs, and other strategically important buildings and infrastructures. The current technology of baggage scanners is based on x-ray attenuation, meaning that the detection of threat objects relies on how various objects differently attenuate the x-ray beams going through them. This capability is enhanced by the use of dual-energy x-ray scanners, which make the determination of the x-ray attenuation characteristics of a material more precise by taking images with different x-ray spectra, and combining the information appropriately. However, this still has limitations whenever objects with similar attenuation characteristics have to be distinguished. We describe an alternative approach based on a different x-ray interaction phenomenon, x-ray refraction. Refraction is a familiar phenomenon in visible light (e.g., what makes a straw half immersed in a glass of water appear bent), which also takes place in the x-ray regime, only causing deviations at much smaller angles. Typically, these deviations occur at the boundaries of all objects. We have developed a system that, like other "phase contrast" based instruments, is capable of detecting such deviations, and therefore of creating precise images of the contours of all objects. This complements the material-related information provided by x-ray attenuation, and helps contextualizing the nature of the individual objects, therefore resulting in an increase of both sensitivity (increased detection rate) and specificity (reduced rate of false positives) of baggage scanners.

We discuss the problem of signal diffusion among neighbouring pixels in x-ray phase contrast imaging (XPCi) specifically for coded-aperture (CA) XPCi, but many of the discussed observations are directly transferable to other XPCi modalities. CA XPCi exploits the principle of pixel edge illumination by means of two CA masks. The first mask, placed in contact with the detector, creates insensitive regions between adjacent pixels; the second one, placed immediately before the sample, creates individual beams impinging on the boundaries between sensitive and insensitive regions on the detector, as created by the detector mask. In this way, edge illumination is achieved for all pixels of an area detector illuminated by a divergent and polychromatic beam generated by a conventional source. As the detector mask redefines the resolution properties of the detector, sample dithering can be used to effectively increase the system spatial resolution, without having to apply any post-processing procedure (e.g., deconvolution). This however creates artifacts in the form of secondary fringes (which have nothing to do with phase-related secondary fringes) if there is signal diffusion between adjacent pixels. In non-dithered images, signal diffusion between adjacent pixels causes a reduction in image contrast. This effect is investigated both theoretically and experimentally, and its direct implications on image quality are discussed. The interplay with the sample positioning with respect to the detector pixel matrix, which also has an effect on the obtained image contrast, is also discussed.

An ongoing project is being carried out to develop a high purity germanium (HPGe) Compton camera for medical applications. The Compton camera offers many potential advantages over the conventional gamma camera. The camera reported in this paper comprises two pixellated germanium detector planes housed 9.6 cm apart in the same vacuum housing. The camera has 177 pixels, 152 in the scatter detector and 25 in the absorption detector. The pixels are 4 × 4 mm(2) with a thickness of 4 mm in the scatter detector and 10 mm in the absorption detector. Images have been taken for a variety of test objects including point sources, a ring source and a Perspex phantom. The measured angular resolution is 9.4° ± 0.4° for a 662 keV gamma-ray source at 3 cm. Due to the limited number of readout modules a multiple-view technique was used to image the source distributions from different angles and simulate the pixel arrangement in the full camera.

We report on what are believed to be the first full-scale images obtained with the coded aperture concept, which uses conventional x-ray sources without the need to collimate/aperture their output. We discuss the differences in the underpinning physical principles with respect to other methods, and explain why these might lead to a more efficient use of the source. In particular, we discuss how the evaluation of the first imaging system provided promising indications on the method's potential to detect details invisible to conventional absorption methods, use an increased average x-ray energy, and reduce exposure times-all important aspects with regards to real-world implementations., (© 2011 Optical Society of America)

A method for sample characterization using energy-dispersive X-ray diffraction computed tomography (EDXRDCT) is presented. The procedures for extracting diffraction patterns from the data and the corrections applied are discussed. The procedures were applied to the characterization of breast tissue samples, 6mm in diameter. Comparison with histological sections of the samples confirmed the possibility of grouping the patterns into five families, corresponding to adipose tissue, fibrosis, poorly differentiated cancer, well differentiated cancer and benign tumour., (Copyright 2010 Elsevier Ltd. All rights reserved.)

There is currently much interest in developing X-ray Phase Contrast Imaging (XPCI) systems which employ laboratory sources in order to deploy the technique in real world applications. The challenge faced by nearly all XPCI techniques is that of efficiently utilising the x-ray flux emitted by an x-ray tube which is polychromatic and possesses only partial spatial coherence. Techniques have, however, been developed which overcome these limitations. Such a technique, known as coded aperture XPCI, has been under development in our laboratories in recent years for application principally in medical imaging and security screening. In this paper we derive limitations imposed upon source polychromaticity and spatial extent by the coded aperture system. We also show that although other grating XPCI techniques employ a different physical principle, they satisfy design constraints similar to those of the coded aperture XPCI.

It is hoped that x-ray phase contrast imaging (XPCi) will provide a generational improvement in the effectiveness of mammography. XPCi is sensitive to the refraction which x-rays undergo as a result of the variation in x-ray propagation speeds within an object. XPCi is, however, seldom used in clinical applications owing mainly to a lack of suitable systems. The radiation physics group at UCL has previously designed and built an XPCi system sensitive to phase gradients in one dimension for application in security inspection. We present here the design methodology and final design of a prototype XPCi system sensitive to phase gradients in two directions for use in mammography. The technique makes efficient use of the flux available from a laboratory x-ray source, thus making it suitable for clinical use.

X-ray phase contrast imaging is a very promising technique that may lead to significant advancements in a variety of fields, perhaps most notably, medical imaging. The radiation physics group at University College London is currently developing an x-ray phase contrast imaging technique that works with laboratory x-ray sources. This system essentially measures the degree to which photons are refracted by regions of an imaged object. The amount of refraction that may be expected to be encountered in practice impacts strongly upon the design of the imaging system. In this paper, we derive an approximate expression between the properties of archetypal imaged objects encountered in practice and the resulting distribution of refracted photons. This is used to derive constraints governing the design of the system.

Purpose: In this article, the image quality of reconstructed volumes by four algorithms for digital tomosynthesis, applied in the case of breast, is investigated using synchrotron radiation., Methods: An angular data set of 21 images of a complex phantom with heterogeneous tissue-mimicking background was obtained using the SYRMEP beamline at ELETTRA Synchrotron Light Laboratory, Trieste, Italy. The irradiated part was reconstructed using the multiple projection algorithm (MPA) and the filtered backprojection with ramp followed by hamming windows (FBR-RH) and filtered backprojection with ramp (FBP-R). Additionally, an algorithm for reducing the noise in reconstructed planes based on noise mask subtraction from the planes of the originally reconstructed volume using MPA (MPA-NM) has been further developed. The reconstruction techniques were evaluated in terms of calculations and comparison of the contrast-to-noise ratio (CNR) and artifact spread function., Results: It was found that the MPA-NM resulted in higher CNR, comparable with the CNR of FBP-RH for high contrast details. Low contrast objects are well visualized and characterized by high CNR using the simple MPA and the MPA-NM. In addition, the image quality of the reconstructed features in terms of CNR and visual appearance as a function of the initial number of projection images and the reconstruction arc was carried out. Slices reconstructed with more input projection images result in less reconstruction artifacts and higher detail CNR, while those reconstructed from projection images acquired in reduced angular range causes pronounced streak artifacts., Conclusions: Of the reconstruction algorithms implemented, the MPA-NM and MPA are a good choice for detecting low contrast objects, while the FBP-RH, FBP-R, and MPA-NM provide high CNR and well outlined edges in case of microcalcifications.

X-ray phase contrast imaging is a very promising technique which may lead to significant advancements in medical imaging. One of the impediments to the clinical implementation of the technique is the general requirement to have an x-ray source of high coherence. The radiation physics group at UCL is currently developing an x-ray phase contrast imaging technique which works with laboratory x-ray sources. Validation of the system requires extensive modelling of relatively large samples of tissue. To aid this, we have undertaken a study of when geometrical optics may be employed to model the system in order to avoid the need to perform a computationally expensive wave optics calculation. In this paper, we derive the relationship between the geometrical and wave optics model for our system imaging an infinite cylinder. From this model we are able to draw conclusions regarding the general applicability of the geometrical optics approximation.

When free-space propagation x-ray phase contrast imaging is implemented outside synchrotron radiation facilities, the combined effect of detector resolution and source size swamps the fine phase contrast fringes, often making them almost undetectable. In an attempt to mitigate this effect, a simple deconvolution procedure based on division in the Fourier space plus multiplication by an appropriate filter was applied to experimental x-ray phase contrast images of a simple geometric phantom. The filter parameter was varied in order to assess its impact on the level of retrieved phase signal. The deconvolved images were compared to simulated ones obtained under different resolution conditions, showing that this simple procedure provided signals equivalent to those that would be obtained with a detector with three times better resolution. By accepting an increase in the overall image noise, the method also appears to bring up secondary phase contrast fringes, which are not visible in the unprocessed signal.

This paper describes the potential application of an active pixel sensor-based x-ray diffraction (APXRD) system in the field of breast cancer diagnosis. The design and initial testing of the system was reported previously (Bohndiek et al 2008b Phys. Med. Biol. 53 655-72). The system has potential both as a 'diffraction enhanced breast imager' (DEBI) and as a probe for quantitative analysis of breast biopsy samples. The resolution of the system in a DEBI arrangement is 1 mm and the contrast available using a material-specific x-ray diffraction image was found to be up to seven times greater than that of a transmission image. Scatter signatures from a series of biopsy-equivalent samples, ranging in composition from 100% fat to 100% fibrous tissue, were acquired with the APXRD system. Multivariate data analysis was used to produce a partial least squares (PLS) model sensitive to sample fat content. The final model is able to accurately predict the fat content of a series of unknown samples and is robust to significant added noise. This suggests that the APXRD system could provide a simple, semi-automated, quantitative measurement system for analysis of breast biopsy samples. Training on a range of scatter signatures from real breast biopsy samples covering various stages of disease is now needed to test this hypothesis.

Even though the potential of phase contrast (PC) imaging has been demonstrated in a number of biological tissue samples, the availability of free-space propagation phase contrast images of real breast tumours is still limited. The aim of this study was to obtain phase contrast images of two different pathological breast specimens containing tumours of differing morphological type at two synchrotron radiation (SR) facilities, and to assess any qualitative improvements in the evaluation and characterisation of the masses through the use of phase contrast imaging. A second aim was to assess the effects of parameters such as detector resolution, beam energy and sample-to-detector distance on image quality using the same breast specimens, as to date these effects have been modelled and discussed only for geometric phantoms. At each synchrotron radiation facility a range of images was acquired with different detectors and by varying the above parameters. Images of the same samples were also acquired with the absorption-based approach to allow a direct comparison and estimation of the advantages specifically ascribable to the PC technique.

Complementary metal-oxide-semiconductors (CMOS) active pixel sensors can be optically coupled to CsI:Tl phosphors forming a indirect active pixel flat panel imager (APFPI) for high performance medical imaging. The aim of this work is to determine the x-ray imaging capabilities of CMOS-based APFPI and study the signal and noise transfer properties of CsI:Tl phosphors. Three different CsI:Tl phosphors from two different vendors have been used to produce three system configurations. The performance of each system configuration has been studied in terms of the modulation transfer function (MTF), noise power spectra, and detective quantum efficiency (DQE) in the mammographic energy range. A simple method to determine quantum limited systems in this energy range is also presented. In addition, with aid of monochromatic synchrotron radiation, the effect of iodine characteristic x-rays of the CsI:Tl on the MTF has been determined. A Monte Carlo simulation of the signal transfer properties of the imager is also presented in order to study the stages that degrade the spatial resolution of our current system. The effect of using substrate patterning during the growth of CsI:Tl columnar structure was also studied, along with the effect of CsI:Tl fixed pattern noise due to local variations in the scintillation light. CsI:Tl fixed pattern noise appears to limit the performance of our current system configurations. All the system configurations are quantum limited at 0.23 microC/kg with two of them having DQE (0) equal to 0.57. Active pixel flat panel imagers are shown to be digital x-ray imagers with almost constant DQE throughout a significant part of their dynamic range and in particular at very low exposures.

A novel prototype step and shoot x-ray system, the intelligent imaging system (I-Imas), has been developed in the UCL Radiation Physics laboratories. The system uses collimators to split the beam into two: the first, "scout" beam, strongly attenuated, identifies regions of interest in the image. This information is then fed back to the system so that the intensity of the second beam is modulated to optimize the dose distribution--i.e., "interesting" regions of the sample receive a higher dose, whereas other regions receive a lower one. Such systems may be capable of improved diagnostic capability at the same overall patient dose levels as typical when using large area digital plates. This acquisition mode means that large overall images are obtained by aligning many smaller images. This paper investigates the effects that this acquisition modality has on the overall spatial resolution of the system. We review different modulation transfer function (MTF) evaluation techniques and those shown to be optimal are used in the investigation of two considerations key to such a system: (i) whether there is a minimum size sensor whose MTF can accurately be determined using these techniques and (ii) whether the MTF of the large overall image differs significantly from those of the many constituent images. As the use of step and shoot systems is becoming more and more widespread, both are important considerations. We found that, for a fixed pixel pitch, the MTF is determined marginally less accurately the smaller the sensor area, with the perceived resolution varying by up to 0.1 lp/mm. It was also found that use of such a step and shoot technique does cause a very small overall degradation in resolution. The resolution of overall images was calculated to be 0.1 lp/mm lower than that of the individual images acquired.

I-ImaS (Intelligent Imaging Sensors) is a European project aiming to produce real-time adaptive X-ray imaging systems using Monolithic Active Pixel Sensors (MAPS) to create images with maximum diagnostic information within given dose constraints. Initial systems concentrate on mammography and cephalography. In our system, the exposure in each image region is optimised and the beam intensity is a function of tissue thickness and attenuation, and also of local physical and statistical parameters in the image. Using a linear array of detectors, the system will perform on-line analysis of the image during the scan, followed by optimisation of the X-ray intensity to obtain the maximum diagnostic information from the region of interest while minimising exposure of diagnostically less important regions. This paper presents preliminary images obtained with a small area CMOS detector developed for this application. Wedge systems were used to modulate the beam intensity during breast and dental imaging using suitable X-ray spectra. The sensitive imaging area of the sensor is 512 x 32 pixels 32 x 32 microm(2) in size. The sensors' X-ray sensitivity was increased by coupling to a structured CsI(Tl) scintillator. In order to develop the I-ImaS prototype, the on-line data analysis and data acquisition control are based on custom-developed electronics using multiple FPGAs. Images of both breast tissues and jaw samples were acquired and different exposure optimisation algorithms applied. Results are very promising since the average dose has been reduced to around 60% of the dose delivered by conventional imaging systems without decrease in the visibility of details.

X-ray diffraction studies give material-specific information about biological tissue. Ideally, a large area, low noise, wide dynamic range digital x-ray detector is required for laboratory-based x-ray diffraction studies. The goal of this work is to introduce a novel imaging technology, the CMOS active pixel sensor (APS) that has the potential to fulfil all these requirements, and demonstrate its feasibility for coherent scatter imaging. A prototype CMOS APS has been included in an x-ray diffraction demonstration system. An industrial x-ray source with appropriate beam filtration is used to perform angle dispersive x-ray diffraction (ADXRD). Optimization of the experimental set-up is detailed including collimator options and detector operating parameters. Scatter signatures are measured for 11 different materials, covering three medical applications: breast cancer diagnosis, kidney stone identification and bone mineral density calculations. Scatter signatures are also recorded for three mixed samples of known composition. Results are verified using two independent models for predicting the APS scatter signature: (1) a linear systems model of the APS and (2) a linear superposition integral combining known monochromatic scatter signatures with the input polychromatic spectrum used in this case. Cross validation of experimental, modelled and literature results proves that APS are able to record biologically relevant scatter signatures. Coherent scatter signatures are sensitive to multiple materials present in a sample and provide a means to quantify composition. In the future, production of a bespoke APS imager for x-ray diffraction studies could enable simultaneous collection of the transmitted beam and scattered radiation in a laboratory-based coherent scatter system, making clinical transfer of the technique attainable.

Identification of specific tissue types in conventional mammographic examinations is extremely limited. However, the use of x-ray diffraction effects during imaging has the potential to characterize the tissue types present due to the fact that each tissue type produces its own unique diffraction signature. Nevertheless, the analysis and categorization of these diffraction signatures by tissue type can be hampered by the inhomogeneous nature of breast tissue, leading to categorization errors where several types are present. This work aims to reduce sample categorization errors by combining spectral diffraction signature collection with sample imaging, giving more detailed data on the composition of each sample. Diffraction microCT was carried out on 19 unfixed breast tissue samples using an energy resolving translate-rotate CT system. High-resolution transmission microCT images were also recorded for comparison and sample composition analysis. Following imaging, the samples were subjected to histopathological analysis. Reconstructing on various momentum transfer regions allows different tissue types to be identified in the diffraction images. Results show a correlation between measured x-ray diffraction images and stained histopathological tissue sections. X-ray diffraction signatures generated from the measured data were categorized and analysed, with a t-test indicating that they have the potential for use in tissue type identification.

A novel method for producing customized x-ray test objects and clinically realistic phantoms has been developed. Test objects can be created with a drawing software package and the digital images can be printed on a standard inkjet printer but using potassium iodide solution in place of the cartridge's ink. The reproducibility and the consistency, the limiting spatial resolution, the uniformity as well as the potassium iodide thickness per print have been evaluated. The relationship between the number of prints, grey levels and the radiation contrast was investigated and quantified. A copy of the Leeds TO10 contrast detail test object was printed and the x-ray images of the Leeds TO10 and of the printed Leeds TO10 were compared. In addition, the potential use of this method was demonstrated by reproducing a percutaneous transluminal coronary angioplasty clinical digital image. The reproducibility and consistency of this method was found to be better than 0.1%. The limiting spatial resolution of the printer using ink was found to be 3.55 1p mm(-1) but it deteriorated when the ink was replaced with potassium iodide and as the print density increases. The uniformity across the printed area was found to be satisfactory although an artefact due to the printer was present in the x-ray images. The comparison between the Leeds TO10 and the printed Leeds TO10 gave differences less than 10%. A good agreement between the clinical image and the printed clinical image was found. In conclusion, the method is a reliable, cost-effective, flexible and alternative way for producing x-ray test objects and clinically related phantoms.

Measurements of breast tissue scattering properties have been made in an energy dispersive x-ray diffraction system over the momentum transfer range of 0.70 to 3.50 nm(-1). One hundred samples of excised tissue have been used. Results from the diffraction system have been compared with the histological analysis for each individual sample. It has been found that tissue types can be characterized on the basis of the shape of the scatter spectrum and on its relative intensity. The shapes are significantly different between tissue types in the range 1.0 to 1.8 nm(-1) and suggest that if particular values of momentum transfer are monitored, a discriminating signal could be obtained. Analysis of the maximum intensity in the signature also reveals a change of up to a factor of 2 between adipose and fat-free tissues.

Phantoms have been constructed to simulate trabecular bone mineral loss and cortical bone thinning which consist of a mixture of hydroxylapatite powder and animal fat in various quantities, surrounded by a varying thickness of dural sleeve. Energy dispersive X-ray diffraction (EDXRD) spectra have been recorded, and multivariate calibration has been performed on the spectra from the bone phantoms. The multivariate technique of partial least squares (PLS) was used to predict the hydroxylapatite content of the phantoms and the dural thickness for measurement times of 250, 50 and 5 s. The calibration phantoms consisted of 10 hydroxylapatite densities ranging from 0.5852 g cm-3 to 0.3703 g cm-3 representing a loss of hydroxylapatite of approx. 40% in 4% intervals. Each phantom had four dural sleeves of thickness 0.5, 1.0, 1.5 and 2.0 mm. Nine test phantoms were constructed with a range of densities that were inside the calibration range. For a measurement time of 250 s the average accuracy of prediction for hydroxylapatite content was approx. +/- 3% while for a measurement time of 5 s this fell to approx. +/- 8%. The dural thickness was predicted to within approx. +/- 0.25 mm for a measurement time of 250 s. The results show that multivariate calibration is a useful technique for obtaining quantitative data of a desired variable from EDXRD measurements which may otherwise be masked or corrupted by other variables.

A system for monitoring multiple scatter during a clinical Compton scatter densitometry measurement of bone density is described. Multiple scatter from the measurement site was measured using a supplementary collimated detector positioned so that only multiply scattered photons could enter the detector. The data from the detector were used to form a multiple-scatter correction factor (mcf) to correct for the bias attributed to multiple scatter. The results of experimental and computer simulations are presented which demonstrate the relationship between the multiple-scatter reading and calculated mcf values. The influence of bone size on the values of mcf in large measurement sites, such as the femoral neck, was shown to be negligible. A simulation was used to produce a visualization of the multiple scatter in order to ascertain the optimum position of the supplementary detector. This technique was shown to be a rapid and accurate method of measuring the multiple-scatter bias and suitable for use during clinical CSD measurements.

This is the first reported use of low-angle X-ray scattering for the investigation of urinary calculi. Low-angle X-ray scattering (LAXS) measures the diffraction of a broad spectrum of X-rays at a single angle and uses a conventional diagnostic X-ray beam, and could thus be developed for use in vivo. A total of 45 calculi were investigated using this technique. Calcium oxalate stones showed a bimodal signature with peaks of almost even photon energies. Signatures for the other stone types were less well-defined. The results are discussed in more detail below. Our preliminary results show that the technique is capable of distinguishing between calcium oxalate stones and other stone types in vitro. Further work is in progress to correlate the results of this technique with objective parameters of stone hardness.

Dual-energy techniques can be used to provide additional information during x-ray examinations. A recent development has been in the application of dual-energy analysis to fluoroscopic procedures. In this paper the effects of scattered radiation upon the results obtained with a small area, dual-energy probe used during fluoroscopy has been evaluated. The method employed has been the development and application of a Monte Carlo photon transport computer program. Experimental confirmation of the model has been performed and the model extended to study the effects of scattered radiation upon the chemical sensitivity of the dual-energy probe. These effects have been studied using a simplified phantom geometry to represent a homogeneous patient. The results indicate that for tissue analysis where the effective atomic number (Z) is less than 13 the effects of scattered radiation lead to errors in estimates of Z of +/- 0.25 when the acceptance angle of the detected radiation is below +/- 20 degrees.

The aim of this paper is to apply the technique of quantitative x-ray diffraction analysis (QXDA) to trabecular bone tissue to demonstrate that quantitative data of the ratio of bone and marrow volumes within the trabecular region can be obtained. Apparatus has been constructed for measuring energy dispersive x-ray diffraction spectra of human femoral head samples in the diagnostic x-ray energy range. Individual diffraction peaks due to bone and marrow tissue were identified in the measured spectra. The relative intensities of the two peaks within the spectra quantify the relative proportions of the two components, and so the bone to marrow peak ratio is proposed as a parameter which is capable of providing information on the osteoporotic state of trabecular tissue. Preliminary results indicate a significant correlation between this method and the bone density measurement techniques of quantitative computed tomography and Compton scatter densitometry. Results have shown that the use of a synthetically prepared calibration curve can enable absolute measurement of bone or marrow volumes.

Rapid, quantative assessment of x-radiation source intensity distributions would be useful in several areas of radiation physics. A simple x-ray sensitive CCD based camera for the measurement of focal spot and radiation beam intensity profiles has been constructed. Focal spot images recorded with the CCD camera and radiographic emulsion are compared and the advantage of the CCD camera in rapidly recording true radiation intensity distributions is demonstrated.

The helical scanning mode in computed tomography (CT) entails continuous table movement during image acquisition. The projections acquired in this mode will not be consistent with those in the axial scanning mode. A comparison of the helical and axial modes of scanning on the IGE HiSpeed Advantage CT system (software version ZA) has been made using a contrast-detail phantom. Differences seen between the two modes include shadow and streaking artefacts and an increase in the partial volume effect in the helical scan mode.

In the past dual-energy techniques have been applied with a variety of detector systems. However, making clinical decisions during a diagnostic x-ray procedure by using dual-energy information has not been possible. This paper looks at the development of a dual-energy probe that permits real time analysis. The technique is based on the local analysis procedure introduced by Speller and co-workers and uses spectral filtering for energy separation. The split-detector probe is optimized using computer models, and the effects of beam hardening and scattered radiation are considered. It is shown that a 0.25 mm CsI/25 mm NaI combination of detector elements with a 0.3 mm Cu filter offers the best performance. Preliminary results using the probe for in vivo analysis of gall stone composition compare well with the more accepted methods of x-ray diffraction and atomic absorption spectroscopy. The two groups of stones evaluated were found to have mean effective atomic numbers of 5.6 +/- 1.7 and 9.6 +/- 0.5. It is suggested that such a procedure could prove useful in patient management in the use of lithotripsy.