A multi-method assessment of 3D printed micromorphological osteological features.

The evaluation of 3D printed osteological materials has highlighted the difficulties associated with accurately representing fine surface details on printed bones. Moreover, there is an increasing need for reconstructions to be demonstrably accurate and reliable for use in the criminal justice system. The aim of this study was to assess the surface quality of 3D prints (n = 9) that presented with micromorphological alterations from trauma, taphonomy and pathology processes. The archaeological bones were imaged using micro-CT scanning and 3D printed with selective laser sintering (SLS) printing. A multi-method experimental approach subsequently identified: (1) the 3D printed bones to be metrically accurate to within 1.0 mm; (2) good representation of micromorphological surface features overall, albeit with some loss of intricate details, depths, and fine textures that can be important for visual processing; (3) five of the nine 3D printed bones were quantitatively scored as accurate using the visual comparison method; and, (4) low mesh comparison distances (± 0.2 mm) between the original models and the digitised 3D print models. The findings offer empirical data that can be used to underpin 3D printed reconstructions of exhibits for use in courts of law. In addition, an adaptable pathway was presented that can be used to assess 3D print accuracy in future reconstructions.

Spatial resolution of drug crystallisation in the skin by X-ray micro-computed tomography.

Drug crystallisation in the skin is recognised as a significant problem in topical and transdermal drug delivery. Our recent investigations provided new evidence of drug crystallisation in the skin, however, confirming the precise location of crystals remains challenging. Of note, most approaches used have required disruption of the membrane by tape stripping, with crystal detection limited to the superficial skin layers. Hence, a non-destructive method for complete spatial resolution of crystallised drug in skin is still lacking. In this communication, we report the application of X-ray micro-computed tomography (microCT) to examine drug crystallisation in mammalian skin ex vivo. Permeation studies of a saturated solution of diclofenac sodium were conducted in porcine skin; subsequently, tissue samples were scanned using microCT to generate 2D and 3D maps. A layer of drug crystals was observed on the skin surface; microCT maps also confirmed the distribution of drug crystals up to a skin depth of 0.2 - 0.3 mm. MicroCT also allowed the identification of drug crystallisation as a distinct and confirmed event in the skin and as an extension from drug crystals formed on the skin. These preliminary results confirm the potential of microCT to study this important phenomenon in topical and transdermal drug delivery.

Improved X-ray computed tomography reconstruction of the largest fragment of the Antikythera Mechanism, an ancient Greek astronomical calculator.

The Antikythera Mechanism is an extraordinarily complex ancient Greek astronomical calculating device whose mode of operation is now relatively well understood particularly since imaging studies in 2005 revealed gears and inscriptions which were previously illegible. Unfortunately, the highest resolution X-ray computed tomography image of the largest fragment had some errors which meant that the reconstructed images were not as clear as had been expected. Here, the original X-ray data have been reanalysed and reconstructed. The new X-ray computed tomography images have improved contrast and resolution, leading to better clarity and legibility. The improvement in image quality is characterised and some examples of writing on the Mechanism which can now be read with increased confidence are given.

A novel method to remove the background from x-ray diffraction signal.

The first step that is required to extract the correct information from a two-dimensional (2D) diffraction signature is to remove the background accurately. However, direct background subtraction inevitably overcorrects the signal as it does not take into account the attenuation by the sample. Other traditional background removal methods, such as the rolling ball technique, can separate sharp diffraction peaks of crystalline materials from their background. These methods are unsuitable for biological tissue, which is amorphous and does not have sharp diffraction peaks. This technical note proposes a novel method that combines peak fitting and experimental results to estimate the background for 2D XRD signals.

Multivariate calibration of energy-dispersive X-ray diffraction data for predicting the composition of pharmaceutical tablets in packaging.

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.

Correlation of X-ray diffraction signatures of breast tissue and their histopathological classification.

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.

Phase-contrast microscopy at high x-ray energy with a laboratory setup.

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.

Imaging Cerenkov emission as a quality assurance tool in electron radiotherapy.

A new potential quality assurance (QA) method is explored (including assessment of depth dose, dose linearity, dose rate linearity and beam profile) for clinical electron beams based on imaging Cerenkov light. The potential of using a standard commercial camera to image Cerenkov light generated from electrons in water for fast QA measurement of a clinical electron beam was explored and compared to ionization chamber measurements. The new method was found to be linear with dose and independent of dose rate (to within 3%). The uncorrected practical range measured in Cerenkov images was found to overestimate the actual value by 3 mm in the worst case. The field size measurements underestimated the dose at the edges by 5% without applying any correction factor. Still, the measured field size could be used to monitor relative changes in the beam profile. Finally, the beam-direction profile measurements were independent of the field size within 2%. A simulation was also performed of the deposited energy and of Cerenkov production in water using GEANT4. Monte Carlo simulation was used to predict the measured light distribution around the water phantom, to reproduce Cerenkov images and to find the relation between deposited energy and Cerenkov production. The camera was modelled as a pinhole camera in GEANT4, to attempt to reproduce Cerenkov images. Simulations of the deposited energy and the Cerenkov light production agreed with each other for a pencil beam of electrons, while for a realistic field size, Cerenkov production in the build-up region overestimated the dose by +8%.

Proof-of-concept demonstration of edge-illumination x-ray phase contrast imaging combined with tomosynthesis.

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.

Direct action of radiation on mummified cells: modeling of computed tomography by Monte Carlo algorithms.

X-ray imaging is a nondestructive and preferred method in paleopathology to reconstruct the history of ancient diseases. Sophisticated imaging technologies such as computed tomography (CT) have become common for the investigation of skeletal disorders in human remains. Researchers have investigated the impact of ionizing radiation on living cells, but never on ancient cells in dry tissue. The effects of CT exposure on ancient cells have not been examined in the past and may be important for subsequent genetic analysis. To remedy this shortcoming, we developed different Monte Carlo models to simulate X-ray irradiation on ancient cells. Effects of mummification were considered by using two sizes of cells and three different phantom tissues, which enclosed the investigated cell cluster. This cluster was positioned at the isocenter of a CT scanner model, where the cell hit probabilities P(0,1,…, n) were calculated according to the Poisson distribution. To study the impact of the dominant physics process, CT scans for X-ray spectra of 80 and 120 kVp were simulated. Comparison between normal and dry tissue phantoms revealed that the probability of unaffected cells increased by 21 % following cell shrinkage for 80 kVp, while for 120 kVp, a further increase of unaffected cells of 23 % was observed. Consequently, cell shrinkage caused by dehydration decreased the impact of X-ray radiation on mummified cells significantly. Moreover, backscattered electrons in cortical bone protected deeper-lying ancient cells from radiation damage at 80 kVp X-rays.

A quantitative, non-interferometric X-ray phase contrast imaging technique.

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.

Feasibility testing of a pre-clinical coded aperture phase contrast imaging configuration using a simple fast Monte Carlo simulator.

A simple method of simulating possible coded aperture phase contrast X-ray imaging apparatus is presented. The method is based on ray tracing, with the rays treated ballistically within a voxelized sample and with the phase-shift-induced angular deviations and absorptions applied at a plane in the middle of the sample. For the particular case of a coded aperture phase contrast configuration suitable for small animal pre-clinical imaging we present results obtained using a high resolution voxel array representation of a mathematically-defined 'digital' mouse. At the end of the article a link to the software is supplied.

Phase and absorption retrieval using incoherent X-ray sources.

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.

Technical Note: modification of the standard gain correction algorithm to compensate for the number of used reference flat frames in detector performance studies.

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.

Technical note: further development of a resolution modification routine for the simulation of the modulation transfer function of digital x-ray detectors.

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.

Noninterferometric phase-contrast images obtained with incoherent x-ray sources.

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.

Texture-based quantification of lumbar intervertebral disc degeneration from conventional T2-weighted MRI.

BACKGROUND: Disc degeneration quantification is important for monitoring the effects of new therapeutic methods, such as cell and growth factor therapy. Magnetic resonance (MR) image texture reflects biochemical and structural tissue properties and has been used for differentiating between normal and pathological status in a variety of medical applications. PURPOSE: To investigate the suitability of textural descriptors for the quantification of intervertebral disc degeneration using conventional T2-weighted magnetic resonance images of the lumbar spine. MATERIAL AND METHODS: A 3 Tesla scanner was used, and conventional T2- weighted MR images were obtained, and a total of 255 lumbar discs were analyzed. An atlas-based method was used for segmenting the disc regions from the images. A set of first and second order statistics describing texture of each region were calculated. The validity and reliability of these descriptors for disc degeneration severity quantification was tested through their correlation with patient age and qualitative clinical grading of degeneration severity. Texture quantification results were compared to a widely accepted method for disc degeneration quantification based on the measurement of disc's mean signal intensity. RESULTS: Out of the set of texture descriptors tested, two descriptors quantifying image intensity inhomogeneity, i.e. the grey level standard deviation and co-occurrence derived sum of squares displayed the strongest association to patient age and clinical grading of disc degeneration severity (P<0.001). This is attributed to these inhomogeneity descriptors' capability to capture the progressive loss of nucleus-annulus distinction in the degenerative progress. Statistical analysis indicates that these descriptors can effectively separate between early stages of degeneration. Quantitative measurements are highly repeatable (intraclass correlation >0.98). CONCLUSION: Inhomogeneity descriptors could be a valuable tool for tracking the evolution of disc degeneration and monitoring the response to treatment in a simple, precise and repeatable manner.

A New Generation of X-ray Baggage Scanners Based on a Different Physical Principle.

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.

Source size and temporal coherence requirements of coded aperture type x-ray phase contrast imaging systems.

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.

Limitations imposed by specimen phase gradients on the design of grating based x-ray phase contrast imaging systems.

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.