High resolution hard X-ray 3D mapping of a Macaca fascicularis eye: A feasibility study without contrast agents.

Several complementary methods able to visualize the internal structures of eyes are used in the clinical practice in the diagnosis of pathologies affecting a specific zone of the eye. Despite the significant technological progress, the visualization of the entire eyeball at micrometric resolution is yet an unsolved task both in clinical diagnostics and in laboratory research. With this respect, high resolution 3D images of the eyeball would be extremely useful, in the study of various pathologies of the retina, the lens, and of the optic nerve. In this work we combined the state-of-the-art of micro computed tomography technology with phase-contrast imaging, a recent highly sensitive technique well adapted to investigate soft tissues without the use of contrast agents; we applied the technique in the post-mortem analysis of monkey eyes, which share several similitudes with the human organ. We reported here vascular, nervous and anatomical details of monkey eyes imaged with a 3.1 × 3.1 × 3.1 µm3 voxel size as well as the first 3D visualisation of the entire globe of Macaca's fascicularis eye. Results have also been compared with, and validated by, histological analysis.

Characterizing pearls structures using X-ray phase-contrast and neutron imaging: a pilot study.

Some cultured and natural pearls can be reliably distinguished by visual inspection and by the use of lens and microscope. However, assessing the origin of the pearls could be not straightforward since many different production techniques can now be found in the pearl market, for example in salt or freshwater environments, with or without a rigid nucleus. This wide range of products requires the use of new effective scientific techniques. Indeed, X-ray radiography has been used by gemologists since last century as the only safe and non-destructive way to visually inspect the interior of a pearl, and recently, also X-ray computed micro-tomography was used to better visualize the inner parts of the gems. In this study we analyzed samples of natural and cultured pearls by means of two non-destructive techniques: the X-ray Phase-Contrast Imaging (PCI) and the Neutron Imaging (NI). PCI and NI results will be combined for the first time, to better visualize the pearls internal morphology, thus giving relevant indications on the pearl formation process.

Refraction and ultra-small-angle scattering of X-rays in a single-crystal diamond compound refractive lens.

In this work a double-crystal setup is employed to study compound refractive lenses made of single-crystal diamond. The point spread function of the lens is calculated taking into account the lens transmission, the wavefront aberrations, and the ultra-small-angle broadening of the X-ray beam. It is shown that, similarly to the wavefront aberrations, the ultra-small-angle scattering effects can significantly reduce the intensity gain and increase the focal spot size. The suggested approach can be particularly useful for the characterization of refractive X-ray lenses composed of many tens of unit lenses.

X-Ray Phase Contrast Tomography Reveals Early Vascular Alterations and Neuronal Loss in a Multiple Sclerosis Model.

The degenerative effects of multiple sclerosis at the level of the vascular and neuronal networks in the central nervous system are currently the object of intensive investigation. Preclinical studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapy in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis, but the neuropathology of specific lesions in EAE and the effects of MSC treatment are under debate. Because conventional imaging techniques entail protocols that alter the tissues, limiting the reliability of the results, we have used non-invasive X-ray phase-contrast tomography to obtain an unprecedented direct 3D characterization of EAE lesions at micro-to-nano scales, with simultaneous imaging of the vascular and neuronal networks. We reveal EAE-mediated alterations down to the capillary network. Our findings shed light on how the disease and MSC treatment affect the tissues, and promote X-ray phase-contrast tomography as a powerful tool for studying neurovascular diseases and monitoring advanced therapies.

Hard X-ray index of refraction tomography of a whole rabbit knee joint: A feasibility study.

We report results of the computed tomography reconstruction of the index of refraction in a whole rabbit knee joint examined at the photon energy of 51keV. Refraction based images make it possible to delineate the bone, cartilage, and soft tissues without adjusting the contrast window width and level. Density variations, which are related to tissue composition and are not visible in absorption X-ray images, are detected in the obtained refraction based images. We discuss why refraction-based images provide better detectability of low contrast features than absorption images.

Virtual unrolling and deciphering of Herculaneum papyri by X-ray phase-contrast tomography.

A collection of more than 1800 carbonized papyri, discovered in the Roman 'Villa dei Papiri' at Herculaneum is the unique classical library survived from antiquity. These papyri were charred during 79 A.D. Vesuvius eruption, a circumstance which providentially preserved them until now. This magnificent collection contains an impressive amount of treatises by Greek philosophers and, especially, Philodemus of Gadara, an Epicurean thinker of 1st century BC. We read many portions of text hidden inside carbonized Herculaneum papyri using enhanced X-ray phase-contrast tomography non-destructive technique and a new set of numerical algorithms for 'virtual-unrolling'. Our success lies in revealing the largest portion of Greek text ever detected so far inside unopened scrolls, with unprecedented spatial resolution and contrast, all without damaging these precious historical manuscripts. Parts of text have been decoded and the 'voice' of the Epicurean philosopher Philodemus is brought back again after 2000 years from Herculaneum papyri.

A single-image method for x-ray refractive index CT.

X-ray refraction-based computer tomography imaging is a well-established method for nondestructive investigations of various objects. In order to perform the 3D reconstruction of the index of refraction, two or more raw computed tomography phase-contrast images are usually acquired and combined to retrieve the refraction map (i.e. differential phase) signal within the sample. We suggest an approximate method to extract the refraction signal, which uses a single raw phase-contrast image. This method, here applied to analyzer-based phase-contrast imaging, is employed to retrieve the index of refraction map of a biological sample. The achieved accuracy in distinguishing the different tissues is comparable with the non-approximated approach. The suggested procedure can be used for precise refraction computer tomography with the advantage of a reduction of at least a factor of two of both the acquisition time and the dose delivered to the sample with respect to any of the other algorithms in the literature.

A track length estimator method for dose calculations in low-energy X-ray irradiations: implementation, properties and performance.

The track length estimator (TLE) method, an "on-the-fly" fluence tally in Monte Carlo (MC) simulations, recently implemented in GATE 6.2, is known as a powerful tool to accelerate dose calculations in the domain of low-energy X-ray irradiations using the kerma approximation. Overall efficiency gains of the TLE with respect to analogous MC were reported in the literature for regions of interest in various applications (photon beam radiation therapy, X-ray imaging). The behaviour of the TLE method in terms of statistical properties, dose deposition patterns, and computational efficiency compared to analogous MC simulations was investigated. The statistical properties of the dose deposition were first assessed. Derivations of the variance reduction factor of TLE versus analogous MC were carried out, starting from the expression of the dose estimate variance in the TLE and analogous MC schemes. Two test cases were chosen to benchmark the TLE performance in comparison with analogous MC: (i) a small animal irradiation under stereotactic synchrotron radiation therapy conditions and (ii) the irradiation of a human pelvis during a cone beam computed tomography acquisition. Dose distribution patterns and efficiency gain maps were analysed. The efficiency gain exhibits strong variations within a given irradiation case, depending on the geometrical (voxel size, ballistics) and physical (material and beam properties) parameters on the voxel scale. Typical values lie between 10 and 10(3), with lower levels in dense regions (bone) outside the irradiated channels (scattered dose only), and higher levels in soft tissues directly exposed to the beams.

Breast tumor segmentation in high resolution x-ray phase contrast analyzer based computed tomography.

PURPOSE: Phase contrast computed tomography has emerged as an imaging method, which is able to outperform present day clinical mammography in breast tumor visualization while maintaining an equivalent average dose. To this day, no segmentation technique takes into account the specificity of the phase contrast signal. In this study, the authors propose a new mathematical framework for human-guided breast tumor segmentation. This method has been applied to high-resolution images of excised human organs, each of several gigabytes. METHODS: The authors present a segmentation procedure based on the viscous watershed transform and demonstrate the efficacy of this method on analyzer based phase contrast images. The segmentation of tumors inside two full human breasts is then shown as an example of this procedure's possible applications. RESULTS: A correct and precise identification of the tumor boundaries was obtained and confirmed by manual contouring performed independently by four experienced radiologists. CONCLUSIONS: The authors demonstrate that applying the watershed viscous transform allows them to perform the segmentation of tumors in high-resolution x-ray analyzer based phase contrast breast computed tomography images. Combining the additional information provided by the segmentation procedure with the already high definition of morphological details and tissue boundaries offered by phase contrast imaging techniques, will represent a valuable multistep procedure to be used in future medical diagnostic applications.

Radiation dose in breast CT imaging with monochromatic x-rays: simulation study of the influence of energy, composition and thickness.

Recent developments have shown that high resolution phase contrast x-ray computed tomography (CT) of the breast can be performed at clinically compatible doses. Results have yet been obtained in vitro on full breasts, and the clinical translation of the technique seems more and more possible. This work presents a method to quickly estimate the average dose in the organ using the software GATE. The influence of different parameters on the dose distribution, like breast composition and thickness, and for preclinical test, the presence of a skin/PMMA external layer, has been investigated. Several correction factors, to be applied to the given dose database, are also introduced to allow the use of these results in geometries different from those studied here. An energy optimization study is presented that considers also the influence on the energy choice of x-ray detector. A simple analytical method to estimate the best energy that minimizes the dose-transmittance ratio in CT imaging is presented and compared with the results of simulations.