In situ visualization of aortic dissection propagation in notched rabbit aorta using synchrotron X-ray tomography.

Aortic dissection is a complex, intramural, and dynamic condition involving multiple mechanisms, hence, difficult to observe. In the present study, a controlled in vitro aortic dissection was performed using tension-inflation tests on notched rabbit aortic segments. The mechanical test was combined with conventional (cCT) and synchrotron (sCT) computed tomography for in situ imaging of the macro- and micro-structural morphological changes of the aortic wall during dissection. We demonstrate that the morphology of the notch and the aorta can be quantified in situ at different steps of the aortic dissection, and that the notch geometry correlates with the critical pressure. The phenomena prior to propagation of the notch are also described, for instance the presence of a bulge at the tip of the notch is identified, deforming the remaining wall. Finally, our method allows us to visualize for the first time the propagation of an aortic dissection in real-time with a resolution that has never previously been reached. STATEMENT OF SIGNIFICANCE: With the present study, we investigated the factors leading to the propagation of aortic dissection by reproducing this mechanical process in notched rabbit aortas. Synchrotron CT provided the first visualisation in real-time of an aortic dissection propagation with a resolution that has never previously been reached. The morphology of the intimal tear and aorta was quantified at different steps of the aortic dissection, demonstrating that the early notch geometry correlates with the critical pressure. This quantification is crucial for the development of better criteria identifying patients at risk. Phenomena prior to tear propagation were also described, such as the presence of a bulge at the tip of the notch, deforming the remaining wall.

Investigation of the refractive index decrement of 3D printing materials for manufacturing breast phantoms for phase contrast imaging.

3D breast modelling for 2D and 3D breast x-ray imaging would benefit from the availability of digital and physical phantoms that reproduce accurately the complexity of the breast anatomy. While a number of groups have produced digital phantoms with increasing level of complexity, physical phantoms reproducing that software approach have been scarcely developed. One possibility is offered by 3D printing technology. This implies the assessment of the energy dependent absorption index ß of 3D printing materials for absorption based imaging, as well as the assessment of the refractive index decrement, δ, of the printing material, for phase contrast imaging studies, at the energies of interest for breast imaging. In this work we set-up a procedure and performed a series of measurements (at 30, 45 and 60 keV, at the European Synchrotron Radiation Facility) for assessing the relative value of δ with respect to that of breast tissues, for twelve 3D printing materials. The method included propagation based phase contrast 2D imaging and retrieval of the estimated phase shift map, using the Paganin's algorithm. Breast glandular, adipose and skin tissues were used as reference materials of known ratio δ/ß. A percentage difference Δδ was introduced to assess the suitability of the printing materials as tissue substitutes. The accuracy of the method (about 4%) was assessed based on the properties of PMMA and Nylon, acting as gold standard. Results show that, for the above photon energies, ABS is a good substitute for adipose tissue, Hybrid as a substitute of the glandular tissue and PET-G for simulating the skin. We plan to realize a breast phantom manufactured by fused deposition modelling (FDM) technology using ABS, Hybrid and PET-G as substitutes of the glandular and skin tissue and a second phantom by stereolithography (SLA) technology with the resins Flex, Tough and Black.

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.

Evaluation of the Profile and Mechanism of Neurotoxicity of Water-Soluble [Cu(P)4]PF6 and [Au(P)4]PF6 (P = thp or PTA) Anticancer Complexes.

[Cu(thp)4]PF6, [Cu(PTA)4]PF6, [Au(thp)4]PF6 and [Au(PTA)4]PF6 are phosphane (thp = tris(hydroxymethyl)phosphane; PTA = 1,3,5-triaza-7-phosphaadamantane) copper(I) and gold(I) water-soluble complexes characterized by high anticancer activity in a wide range of solid tumors, often able to overcome drug resistance of platinum-based compounds. For these reasons, they have been proposed as a valid alternative to platinum-based chemotherapeutic drugs (e.g., cisplatin and oxaliplatin). In vitro experiments performed on organotypic cultures of dorsal root ganglia (DRG) from 15-day-old rat embryos revealed that copper-based compounds were not neurotoxic even at concentrations higher than the IC50 obtained in human cancer cells while [Au(PTA)4]PF6 was neurotoxic at lower concentration than IC50 in cancer cell lines. The ability of these compounds to hinder the proteasome machinery in DRG neurons was tested by fluorimetric assay showing that the non-neurotoxic copper-based complexes do not inhibit proteasome activity in DRG primary neuron cultures. On the contrary, the neurotoxic complex [Au(PTA)4]PF6, induced a significant inhibition of proteasome activity even at concentrations lower than the IC50 in cancer cells. The proteasome inhibition induced by [Au(PTA)4]PF6 was associated with a significant increase in α-tubulin polymerization that was not observed following the treatment with copper-based compounds. Uptake experiments performed by atomic absorption spectrometry showed that both copper-based complexes and [Au(PTA)4]PF6 are internalized in neuron cultures. In vitro and in vivo preliminary data confirmed copper-based complexes as the most promising compounds, not only for their anticancer activity but also concerning the peripheral neurotoxicity profile.

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.

Quantitative 3D investigation of Neuronal network in mouse spinal cord model.

The investigation of the neuronal network in mouse spinal cord models represents the basis for the research on neurodegenerative diseases. In this framework, the quantitative analysis of the single elements in different districts is a crucial task. However, conventional 3D imaging techniques do not have enough spatial resolution and contrast to allow for a quantitative investigation of the neuronal network. Exploiting the high coherence and the high flux of synchrotron sources, X-ray Phase-Contrast multiscale-Tomography allows for the 3D investigation of the neuronal microanatomy without any aggressive sample preparation or sectioning. We investigated healthy-mouse neuronal architecture by imaging the 3D distribution of the neuronal-network with a spatial resolution of 640 nm. The high quality of the obtained images enables a quantitative study of the neuronal structure on a subject-by-subject basis. We developed and applied a spatial statistical analysis on the motor neurons to obtain quantitative information on their 3D arrangement in the healthy-mice spinal cord. Then, we compared the obtained results with a mouse model of multiple sclerosis. Our approach paves the way to the creation of a "database" for the characterization of the neuronal network main features for a comparative investigation of neurodegenerative diseases and therapies.

Multi-strip silicon sensors for beam array monitoring in micro-beam radiation therapy.

We present here the latest results from tests performed at the ESRF ID17 and ID21 beamlines for the characterization of novel beam monitors for Microbeam Radiation Therapy (MRT), which is currently being implemented at ID17. MRT aims at treating solid tumors by exploiting an array of evenly spaced microbeams, having an energy spectrum distributed between 27 and 600keV and peaking at 100keV. Given the high instantaneous dose delivered (up to 20kGy/s), the position and the intensity of the microbeams has to be precisely and instantly monitored. For this purpose, we developed dedicated silicon microstrip beam monitors. We have successfully characterized them, both with a microbeam array at ID17, and a submicron scanning beam at ID21. We present here the latest results obtained in recent tests along with an outlook on future developments.

Good Outcomes in Kidney Transplantation With Deceased Donor With Acute Kidney Injury: Donor's Age and Not Acute Kidney Injury Predicts Graft Function.

BACKGROUND: With the increased demand for kidney transplants and the short supply of organs, it is necessary to have a better strategy to evaluate the available organs, especially from donors with acute kidney injury (AKI), because these organs are often rejected for transplantation. METHODS: We evaluated patients undergoing transplantation with kidneys from deceased donors with AKI. The cases were divided into AKI stages according to the Acute Kidney Injury Network (AKIN) criteria. The outcomes examined were delayed graft function (DGF), creatinine (Cr), and creatinine clearance (CrCl) at 6 months after transplantation. RESULTS: We evaluated 101 patients and included 53 in the final model. There was no statistical difference in the demographic characteristics, comorbidities, and immunosuppression according to each AKIN stage, showing a population of homogeneous transplant recipients. Recipients in AKIN stages I, II, and III, respectively had DGF in 72.7%, 61.9%, and 71.4% of cases; Cr of 1.6 ± 0.5, 1.7 ± 0.7, and 1.6 ± 0.2 mg/dL at 6 months; and CrCl of 60.6 ± 22.4, 52.4 ± 27.4, and 52.03 ± 12.1 mL/min at 6 months. Each additional year in donor age increased the relative risk of DGF by 1.08 (1.0-1.13) (P = .01), and organs from older donors were associated with worse renal function at 6 months. CONCLUSION: Kidney transplantation of organs from deceased donors with AKI showed greater DGF but good outcomes. Donor age was the only characteristic that correlated with outcome.

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.

In-line phase-contrast breast tomosynthesis: a phantom feasibility study at a synchrotron radiation facility.

The major objective is to adopt, apply and test developed in-house algorithms for volumetric breast reconstructions from projection images, obtained in in-line phase-contrast mode. Four angular sets, each consisting of 17 projection images obtained from four physical phantoms, were acquired at beamline ID17, European Synchroton Radiation Facility, Grenoble, France. The tomosynthesis arc was ±32°. The physical phantoms differed in complexity of texture and introduced features of interest. Three of the used phantoms were in-house developed, and made of epoxy resin, polymethyl-methacrylate and paraffin wax, while the fourth phantom was the CIRS BR3D. The projection images had a pixel size of 47 µm × 47 µm. Tomosynthesis images were reconstructed with standard shift-and-add (SAA) and filtered backprojection (FBP) algorithms. It was found that the edge enhancement observed in planar x-ray images is preserved in tomosynthesis images from both phantoms with homogeneous and highly heterogeneous backgrounds. In case of BR3D, it was found that features not visible in the planar case were well outlined in the tomosynthesis slices. In addition, the edge enhancement index calculated for features of interest was found to be much higher in tomosynthesis images reconstructed with FBP than in planar images and tomosynthesis images reconstructed with SAA. The comparison between images reconstructed by the two reconstruction algorithms shows an advantage for the FBP method in terms of better edge enhancement. Phase-contrast breast tomosynthesis realized in in-line mode benefits the detection of suspicious areas in mammography images by adding the edge enhancement effect to the reconstructed slices.

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.

Improved normal tissue protection by proton and X-ray microchannels compared to homogeneous field irradiation.

The risk of developing normal tissue injuries often limits the radiation dose that can be applied to the tumour in radiation therapy. Microbeam Radiation Therapy (MRT), a spatially fractionated photon radiotherapy is currently tested at the European Synchrotron Radiation Facility (ESRF) to improve normal tissue protection. MRT utilizes an array of microscopically thin and nearly parallel X-ray beams that are generated by a synchrotron. At the ion microprobe SNAKE in Munich focused proton microbeams ("proton microchannels") are studied to improve normal tissue protection. Here, we comparatively investigate microbeam/microchannel irradiations with sub-millimetre X-ray versus proton beams to minimize the risk of normal tissue damage in a human skin model, in vitro. Skin tissues were irradiated with a mean dose of 2 Gy over the irradiated area either with parallel synchrotron-generated X-ray beams at the ESRF or with 20 MeV protons at SNAKE using four different irradiation modes: homogeneous field, parallel lines and microchannel applications using two different channel sizes. Normal tissue viability as determined in an MTT test was significantly higher after proton or X-ray microchannel irradiation compared to a homogeneous field irradiation. In line with these findings genetic damage, as determined by the measurement of micronuclei in keratinocytes, was significantly reduced after proton or X-ray microchannel compared to a homogeneous field irradiation. Our data show that skin irradiation using either X-ray or proton microchannels maintain a higher cell viability and DNA integrity compared to a homogeneous irradiation, and thus might improve normal tissue protection after radiation therapy.

A software platform for phase contrast x-ray breast imaging research.

PURPOSE: To present and validate a computer-based simulation platform dedicated for phase contrast x-ray breast imaging research. METHODS: The software platform, developed at the Technical University of Varna on the basis of a previously validated x-ray imaging software simulator, comprises modules for object creation and for x-ray image formation. These modules were updated to take into account the refractive index for phase contrast imaging as well as implementation of the Fresnel-Kirchhoff diffraction theory of the propagating x-ray waves. Projection images are generated in an in-line acquisition geometry. To test and validate the platform, several phantoms differing in their complexity were constructed and imaged at 25 keV and 60 keV at the beamline ID17 of the European Synchrotron Radiation Facility. The software platform was used to design computational phantoms that mimic those used in the experimental study and to generate x-ray images in absorption and phase contrast modes. RESULTS: The visual and quantitative results of the validation process showed an overall good correlation between simulated and experimental images and show the potential of this platform for research in phase contrast x-ray imaging of the breast. The application of the platform is demonstrated in a feasibility study for phase contrast images of complex inhomogeneous and anthropomorphic breast phantoms, compared to x-ray images generated in absorption mode. CONCLUSIONS: The improved visibility of mammographic structures suggests further investigation and optimisation of phase contrast x-ray breast imaging, especially when abnormalities are present. The software platform can be exploited also for educational purposes.

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.