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Purpose: This study provides the first experimental application of multiscale 3-dimensional (3D) x-ray phase contrast imaging computed tomography (XPCI-CT) virtual histology for the inspection and quantitative assessment of the late-stage effects of radio-induced lesions on lungs in a small animal model.Methods and Materials: Healthy male Fischer rats were irradiated with x-ray standard broad beams and microbeam radiation therapy, a high-dose rate (14 kGy/s), FLASH spatially fractionated x-ray therapy to avoid beamlet smearing owing to cardiosynchronous movements of the organs during the irradiation. After organ dissection, ex vivo XPCI-CT was applied to all the samples and the results were quantitatively analyzed and correlated to histologic data.Results: XPCI-CT enables the 3D visualization of lung tissues with unprecedented contrast and sensitivity, allowing alveoli, vessel, and bronchi hierarchical visualization. XPCI-CT discriminates in 3D radio-induced lesions such as fibrotic scars and Ca/Fe deposits and allows full-organ accurate quantification of the fibrotic tissue within the irradiated organs. The radiation-induced fibrotic tissue content is less than 10% of the analyzed volume for all microbeam radiation therapy-treated organs and reaches 34% in the case of irradiations with 50 Gy using a broad beam.Conclusions: XPCI-CT is an effective imaging technique able to provide detailed 3D information for the assessment of lung pathology and treatment efficacy in a small animal model. [ABSTRACT FROM AUTHOR]

Purpose : Modern neuroimaging lacks the tools necessary for whole-brain, anatomically dense neuronal damage screening. An ideal approach would include unbiased histopathologic identification of aging and neurodegenerative disease. Methods: We report the postmortem application of multiscale X-ray phase-contrast computed tomography (X-PCI-CT) for the label-free and dissection-free organ-level to intracellular-level 3D visualization of distinct single neurons and glia. In deep neuronal populations in the brain of aged wild-type and of 3xTgAD mice (a triply-transgenic model of Alzheimer's disease), we quantified intracellular hyperdensity, a manifestation of aging or neurodegeneration. Results: In 3xTgAD mice, the observed hyperdensity was identified as amyloid-β and hyper-phosphorylated tau protein deposits with calcium and iron involvement, by correlating the X-PCI-CT data to immunohistochemistry, X-ray fluorescence microscopy, high-field MRI, and TEM. As a proof-of-concept, X-PCI-CT was used to analyze hippocampal and cortical brain regions of 3xTgAD mice treated with LY379268, selective agonist of group II metabotropic glutamate receptors (mGlu2/3 receptors). Chronic pharmacologic activation of mGlu2/3 receptors significantly reduced the hyperdensity particle load in the ventral cortical regions of 3xTgAD mice, suggesting a neuroprotective effect with locoregional efficacy. Conclusions: This multiscale micro-to-nano 3D imaging method based on X-PCI-CT enabled identification and quantification of cellular and sub-cellular aging and neurodegeneration in deep neuronal and glial cell populations in a transgenic model of Alzheimer's disease. This approach quantified the localized and intracellular neuroprotective effects of pharmacological activation of mGlu2/3 receptors. [ABSTRACT FROM AUTHOR]

Purpose: Experimental neuroimaging provides a wide range of methods for the visualization of brain anatomic morphology down to subcellular detail. Still, each technique-specific detection mechanism presents compromises among the achievable field-of-view size, spatial resolution, and nervous tissue sensitivity, leading to partial sample coverage, unresolved morphologic structures, or sparse labeling of neuronal populations and often also to obligatory sample dissection or other sample invasive manipulations. X-ray phase-contrast imaging computed tomography (PCI-CT) is an experimental imaging method that simultaneously provides micrometric spatial resolution, high soft-tissue sensitivity, and ex vivo full organ rodent brain coverage without any need for sample dissection, staining or labeling, or contrast agent injection. In the present study, we explored the benefits and limitations of PCI-CT use for in vitro imaging of normal and cancerous brain neuromorphology after in vivo treatment with synchrotron-generated x-ray microbeam radiation therapy (MRT), a spatially fractionated experimental high-dose radiosurgery. The goals were visualization of the MRT effects on nervous tissue and a qualitative comparison of the results to the histologic and high-field magnetic resonance imaging findings.Methods and Materials: MRT was administered in vivo to the brain of both healthy and cancer-bearing rats. At 45 days after treatment, the brain was dissected out and imaged ex vivo using propagation-based PCI-CT.Results: PCI-CT visualizes the brain anatomy and microvasculature in 3 dimensions and distinguishes cancerous tissue morphology, necrosis, and intratumor accumulation of iron and calcium deposits. Moreover, PCI-CT detects the effects of MRT throughout the treatment target areas (eg, the formation of micrometer-thick radiation-induced tissue ablation). The observed neurostructures were confirmed by histologic and immunohistochemistry examination and related to the micro-magnetic resonance imaging data.Conclusions: PCI-CT enabled a unique 3D neuroimaging approach for ex vivo studies on small animal models in that it concurrently delivers high-resolution insight of local brain tissue morphology in both normal and cancerous micro-milieu, localizes radiosurgical damage, and highlights the deep microvasculature. This method could assist experimental small animal neurology studies in the postmortem evaluation of neuropathology or treatment effects. [ABSTRACT FROM AUTHOR]

Phase-contrast x-ray imaging (PCI) is an innovative method that is sensitive to the refraction of the x-rays in matter. PCI is particularly adapted to visualize weakly absorbing details like those often encountered in biology and medicine. In past years, PCI has become one of the most used imaging methods in laboratory and preclinical studies: its unique characteristics allow high contrast 3D visualization of thick and complex samples even at high spatial resolution. Applications have covered a wide range of pathologies and organs, and are more and more often performed in vivo. Several techniques are now available to exploit and visualize the phase-contrast: propagation- and analyzer-based, crystal and grating interferometry and non-interferometric methods like the coded aperture. In this review, covering the last five years, we will give an overview of the main theoretical and experimental developments and of the important steps performed towards the clinical implementation of PCI. [ABSTRACT FROM AUTHOR]

Since its advent during the mid-twentieth century, radiosurgery has undergone a steady evolution. Gamma Knife and linear accelerator based systems using rigid frames preceded the development of frameless devices. The present report describes the development of microbeam radiosurgery, a technique which uses submillimetric beams of radiation to treat disease. Typically, the technique is employed using parallel arrays of beams delivered via a high-fluence synchrotron source. Beam widths between 20 and 950 μm have been used with the majority of studies utilizing beam widths less than 100 μm. In addition to its high precision, the technique allows users to take advantage of two unique properties of microbeams. The first is a remarkable tolerance of healthy tissue to microbeams delivered at doses up to several hundred grays, while at the same time, tumors are highly susceptible to the lethal effects of microbeams. Together, these findings allow for a 'preferential tumoricidal effect' beyond the typical dose-volume relationship. Although only used in animal experiments so far, we explore the hypothetical clinical role of microbeam radiosurgery which may be feasible in the near future. In addition to the treatment of traditional radiosurgery targets such as malignancies and vascular malformations, microbeams may allow the non-invasive treatment of functional disease such as movement disorders, epilepsy, and mental illness. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aims at using a multi-technique approach to detect and analyze the effects of high dose rate spatially fractionated radiation therapies and to compare them to seamless broad beam irradiation targeting healthy and glioblastoma-bearing rat brains and delivering three different doses per each irradiation geometry. Brains were analyzed post mortem by multi-scale X-ray phase contrast imaging–computed tomography, histology, immunohistochemistry, X-ray fluorescence, and small- and wide-angle X-ray scattering to achieve detailed visualization, characterization and classification in 3D of the radio-induced effects on brain tissues. The original results bring new insights to the understanding of the response of cerebral tissue and tumors treated with high dose rate spatially fractioned radiotherapies and put the basis for channeling studies of in-vivo applications for monitoring RT effects. The purpose of this study is to use a multi-technique approach to detect the effects of spatially fractionated X-ray Microbeam (MRT) and Minibeam Radiation Therapy (MB) and to compare them to seamless Broad Beam (BB) irradiation. Healthy- and Glioblastoma (GBM)-bearing male Fischer rats were irradiated in-vivo on the right brain hemisphere with MRT, MB and BB delivering three different doses for each irradiation geometry. Brains were analyzed post mortem by multi-scale X-ray Phase Contrast Imaging–Computed Tomography (XPCI-CT), histology, immunohistochemistry, X-ray Fluorescence (XRF), Small- and Wide-Angle X-ray Scattering (SAXS/WAXS). XPCI-CT discriminates with high sensitivity the effects of MRT, MB and BB irradiations on both healthy and GBM-bearing brains producing a first-time 3D visualization and morphological analysis of the radio-induced lesions, MRT and MB induced tissue ablations, the presence of hyperdense deposits within specific areas of the brain and tumor evolution or regression with respect to the evaluation made few days post-irradiation with an in-vivo magnetic resonance imaging session. Histology, immunohistochemistry, SAXS/WAXS and XRF allowed identification and classification of these deposits as hydroxyapatite crystals with the coexistence of Ca, P and Fe mineralization, and the multi-technique approach enabled the realization, for the first time, of the map of the differential radiosensitivity of the different brain areas treated with MRT and MB. 3D XPCI-CT datasets enabled also the quantification of tumor volumes and Ca/Fe deposits and their full-organ visualization. The multi-scale and multi-technique approach enabled a detailed visualization and classification in 3D of the radio-induced effects on brain tissues bringing new essential information towards the clinical implementation of the MRT and MB radiation therapy techniques. [ABSTRACT FROM AUTHOR]

A crystal-less method for analyzing the phase shifts of an x-ray beam passed through a sample is here presented. An array-structured detector is used both to record and analyze the refracted and scattered radiation. Experimental studies of simple phase objects confirmed that images show features similar or equivalent to the ones produced using an analyzer crystal with comparable signal-to-noise ratio values. Using a detector for analyzing the refraction presents evident advantages in terms of optical stability. In addition, with a single acquisition, several refraction angles can be simultaneously analyzed permitting a better exploitation of the dose delivered to the sample. [ABSTRACT FROM AUTHOR]

• X-ray phase-contrast CT (X-PCI-CT) enables label-free 3D nervous-tissue microscopy. • Multiscale X-PCI-CT captures full-organ to intra-cellular spinal cord neuroanatomy. • Combination of aldehyde fixatives optimizes visualizations of deep micro-vasculature. • Osmium impregnation highlights white-matter and individual motor neuron perikarya. • Post-mortem X-PCI-CT resolving power can exceed that of post-mortem high-field MRI. Dense and unbiased cellular-resolution representations of extended volumetric central nervous system soft-tissue anatomy are difficult to obtain, even in experimental post-mortem settings. Interestingly, X-ray phase-contrast computed tomography (X-PCI-CT), an emerging soft-tissue-sensitive volumetric imaging technique, can provide multiscale organ- to cellular-level morphological visualizations of neuroanatomical structure. Here, we tested different nervous-tissue fixation procedures, conventionally used for transmission electron microscopy, to better establish X-PCI-CT-specific sample-preparation protocols. Extracted rat spinal medullas were alternatively fixed with a standard paraformaldehyde-only aldehyde-based protocol, or in combination with glutaraldehyde. Some specimens were additionally post-fixed with osmium tetroxide. Multiscale X-PCI-CT datasets were collected at several synchrotron radiation facilities, using state-of-the-art setups with effective image voxel sizes of 3.03 to 0.33 μm3, and compared to high-field magnetic resonance imaging, histology and vascular fluorescence microscopy data. Multiscale X-PCI-CT of aldehyde-fixed spinal cord specimens resulted in dense histology-like volumetric representations and quantifications of extended deep spinal micro-vascular networks and of intra-medullary cell populations. Osmium post-fixation increased intra-medullary contrast between white and gray-matter tissues, and enhanced delineation of intra-medullary cellular structure, e.g. axon fibers and motor neuron perikarya. Volumetric X-PCI-CT provides complementary contrast and higher spatial resolution compared to 9.4 T MRI. X-PCI-CT's advantage over planar histology is the volumetric nature of the cellular-level data obtained, using samples much larger than those fit for volumetric vascular fluorescence microscopy. Deliberately choosing (post-)fixation protocols tailored for optimal nervous-tissue structural preservation is of paramount importance in achieving effective and targeted neuroimaging via the X-PCI-CT technique. [ABSTRACT FROM AUTHOR]

X-ray dark-field or ultra-small angle scatter imaging has become increasingly important since the introduction of phase-based x-ray imaging and is having transformative impact in fields such as in vivo lung imaging and explosives detection. Here, we show that dark-field images acquired with the edge-illumination method (either in its traditional double mask or simplified single mask implementation) provide a direct measurement of the scattering function, which is unaffected by system-specific parameters such as the autocorrelation length. We show that this is a consequence both of the specific measurement setup and of the mathematical approach followed to retrieve the dark-field images. We show agreement with theoretical models for datasets acquired both with synchrotron and laboratory x-ray sources. We also introduce a new contrast mechanism, the variance of refraction, which is extracted from the same dataset and provides a direct link with the size of the scattering centers. We show that this can also be described by the same theoretical models. We study the behavior of both signals vs key parameters such as x-ray energy and scatterer radius. We find this allows quantitative and direct scattering measurements during imaging, with implications in all fields where dark-field imaging is used. [ABSTRACT FROM AUTHOR]

Following spinal cord injury (SCI) the degree of functional (motor, autonomous, or sensory) loss correlates with the severity of nervous tissue damage. An imaging technique able to capture non-invasively and simultaneously the complex mechanisms of neuronal loss, vascular damage, and peri-lesional tissue reorganization is currently lacking in experimental SCI studies. Synchrotron X-ray phase-contrast tomography (SXPCT) has emerged as a non-destructive three-dimensional (3D) neuroimaging technique with high contrast and spatial resolution. In this framework, we developed a multi-modal approach combining SXPCT, histology and correlative methods to study neurovascular architecture in normal and spinal level C4-contused mouse spinal cords (C57BL/6J mice, age 2–3 months). The evolution of SCI lesion was imaged at the cell resolution level during the acute (30 min) and subacute (7 day) phases. Spared motor neurons (MNs) were segmented and quantified in different volumes localized at and away from the epicenter. SXPCT was able to capture neuronal loss and blood–brain barrier breakdown following SCI. Three-dimensional quantification based on SXPCT acquisitions showed no additional MN loss between 30 min and 7 days post-SCI. In addition, the analysis of hemorrhagic (at 30 min) and lesion (at 7 days) volumes revealed a high similarity in size, suggesting no extension of tissue degeneration between early and later time-points. Moreover, glial scar borders were unevenly distributed, with rostral edges being the most extended. In conclusion, SXPCT capability to image at high resolution cellular changes in 3D enables the understanding of the relationship between hemorrhagic events and nervous structure damage in SCI. [ABSTRACT FROM AUTHOR]

The magnitude and distribution of strain imposed on the peripheral airspaces by mechanical ventilation at the microscopic level and the consequent deformations are unknown despite their importance for understanding the mechanisms occurring at the onset of ventilator-induced lung injury. Here a 4-Dimensional (3D + time) image acquisition and processing technique is developed to assess pulmonary acinar biomechanics at microscopic resolution. Synchrotron radiation phase contrast CT with an isotropic voxel size of 6 µm3 is applied in live anesthetized rats under controlled mechanical ventilation. Video animations of regional acinar and vascular strain are acquired in vivo. Maps of strain distribution due to positive-pressure breaths and cardiovascular activity in lung acini and blood vessels are derived based on CT images. Regional strain within the lung peripheral airspaces takes average values of 0.09 ± 0.02. Fitting the expression S = kVn, to the changes in peripheral airspace area (S) and volume (V) during a positive pressure breath yields an exponent n = 0.82 ± 0.03, suggesting predominant alveolar expansion rather than ductal expansion or alveolar recruitment. We conclude that this methodology can be used to assess acinar conformational changes during positive pressure breaths in intact peripheral lung airspaces. [ABSTRACT FROM AUTHOR]

Medical imaging and radiation therapy are widely used synchrotron-based techniques which have one thing in common: a significant dose delivery to typically biological samples. Among the ways to provide the experimenters with image guidance techniques indicating optimization strategies, Monte Carlo simulation has become the gold standard for accurately predicting radiation dose levels under specific irradiation conditions. A highly important hampering factor of this method is, however, its slow statistical convergence. A track length estimator (TLE) module has been coded and implemented for the first time in the open-source Monte Carlo code GATE/Geant4. Results obtained with the module and the procedures used to validate them are presented. A database of energy-absorption coefficients was also generated, which is used by the TLE calculations and is now also included in GATE/Geant4. The validation was carried out by comparing the TLE-simulated doses with experimental data in a synchrotron radiation computed tomography experiment. The TLE technique shows good agreement versus both experimental measurements and the results of a classical Monte Carlo simulation. Compared with the latter, it is possible to reach a pre-defined statistical uncertainty in about two to three orders of magnitude less time for complex geometries without loss of accuracy. [ABSTRACT FROM AUTHOR]

The article presents a study on the comparison of in vitro breast cancer visibility using analyzer-based X-ray imaging (ABI), histopathology mammography and magnetic resonance imaging (MRI). It mentions that analyzer-based imaging provides better visibility compared to standard radiology imaging. It also notes that analyzer-based X-ray imaging computed tomography holds a valuable role in breast diagnostics.

Several synchrotrons around the world are currently developing innovative radiotherapy techniques with the aim of palliating and possibly curing human brain tumors. Amongst them, microbeam radiation therapy (MRT) and, more recently, minibeam radiation therapy (MBRT) have shown promising results. In MBRT the beam thickness ranges from 500 to 700 urn with a separation between two adjacent minibeams of the same value, whilst in MRT the thickness is of the order of 25-50 urn with a distance between adjacent microbeams of the order of 200 tim. An original method has been developed and tested at the ESRF 1D17 biomedical beamline to produce the minibeam patterns. It utilizes a specially developed high-energy white-beam chopper whose action is synchronized with the vertical motion of the target moving at constant speed. Each opening of the chopper generates a horizontal beam print. The method described here has the advantage of being simple and reliable, and it allows for an easy control of the patient safety in future clinical trials. To study the feasibility of the method, dosimetric measurements have been performed using Gafchromic HD-810 films and compared with Monte Carlo simulations. The results of this comparison are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Modern synchrotron radiation (SR) sources have dramatically fostered the use of SR-based X-ray imaging. The relevant information such as density, chemical composition, chemical states, structure, and crystallographic perfection is mapped in two, or, increasingly, in three dimensions. The development of nano-science requires pushing spatial resolution down towards the nanoscale. The present article describes a selection of hard X-ray imaging and microanalysis techniques that emerged over the last few years, by taking advantage of the flux and coherence of the SR beams, as well as exploiting the advances in X-ray optics and detectors, and the increased possibilities of computers (memory, speed). Examples are given to illustrate the opportunities associated with the use of these techniques, and a number of recent references are provided. To cite this article: J. Baruchel et al., C. R. Physique 9 (2008). [Copyright &y& Elsevier]

A new algorithm is introduced for separation of the scattered and non-scattered parts of a monochromatic and well collimated synchrotron radiation beam transmitted through a sample and analyzed by reflection from a perfect crystal in the non-dispersive setting. The observed rocking curve is described by the Voigt function, which is a convolution of Lorentzian and Gaussian functions. For the actual fitting, pseudo-Voigtians are used. The fit yields the scaled integrated intensity (the effect of absorption), the center of the rocking curve (the effect of refraction), and the intensity of the transmitted beam is divided into the scattered and non-scattered parts. The algorithm is tested using samples that exhibit various degrees of refraction and scattering. Very close fits are achieved in an angular range that is 15 times the full width at half-maximum of the intrinsic rocking curve of the analyzer. The scattering part has long tails of Lorentzian shape owing to the `long-slit geometry' of the set-up. Quantitative images of absorption, refraction and scattering are constructed and compared with results of earlier treatments. The portion of scattering and the second moment of the observed rocking curve both increase linearly with the sample thickness and yield identical maps of the effects of scattering. The effects of refraction are calculated using the geometrical optics approximation, and a good agreement with experiment is found. The fits with reduced number of data points (minimum number is five) yield closely the same results as fits to the full data set. [ABSTRACT FROM AUTHOR]

Medical application of synchrotron radiation (SR) is a fast-growing field of research. Since the advent of the angiography studies at SSRL first and then at NSLS in the U.S. in the 1990s, preclinical and clinical research protocols have been developed at Hasylab (Germany), Photon Factory (Japan), ELETTRA (Italia) and at the ESRF (France). Despite the fact that there are only a few dedicated beamlines in the world (two new ones are under construction at the Australian and Canadian synchrotrons), medical research is carried out in almost all synchrotron facilities. [ABSTRACT FROM AUTHOR]

The authors previously provided evidence of synchrotron radiation computed tomography (SRCT) efficacy for quantitative in vivo brain perfusion measurements using monochromatic X-ray beams. However, this technique was limited for small-animal studies by partial volume effects. In this paper, high-resolution absolute cerebral blood volume and blood–brain barrier permeability coefficient measurements were obtained on a rat glioma model using SRCT and a CCD camera (47 × 47 μm2 pixel size). This is the first report of in vivo high-resolution brain vasculature parameter assessment. The work gives interesting perspectives to quantify brain hemodynamic changes accurately in healthy and pathological small animals.Journal of Cerebral Blood Flow & Metabolism (2005) 25, 145–153. doi:10.1038/sj.jcbfm.9600017 [ABSTRACT FROM AUTHOR]

Background: The evolution of cartilage degeneration is still not fully understood, partly due to its thinness, low radio-opacity and therefore lack of adequately resolving imaging techniques. X-ray phase-contrast imaging (X-PCI) offers increased sensitivity with respect to standard radiography and CT allowing an enhanced visibility of adjoining, low density structures with an almost histological image resolution. This study examined the feasibility of X-PCI for high-resolution (sub-) micrometer analysis of different stages in tissue degeneration of human cartilage samples and compare it to histology and transmission electron microscopy. Methods: Ten 10%-formalin preserved healthy and moderately degenerated osteochondral samples, post-mortem extracted from human knee joints, were examined using four different X-PCI tomographic set-ups using synchrotron radiation the European Synchrotron Radiation Facility (France) and the Swiss Light Source (Switzerland). Volumetric datasets were acquired with voxel sizes between 0.7 × 0.7 × 0.7 and 0.1 × 0.1 × 0.1 µm3. Data were reconstructed by a filtered back-projection algorithm, post-processed by ImageJ, the WEKA machine learning pixel classification tool and VGStudio max. For correlation, osteochondral samples were processed for histology and transmission electron microscopy. Results: X-PCI provides a three-dimensional visualization of healthy and moderately degenerated cartilage samples down to a (sub-)cellular level with good correlation to histologic and transmission electron microscopy images. X-PCI is able to resolve the three layers and the architectural organization of cartilage including changes in chondrocyte cell morphology, chondrocyte subgroup distribution and (re-)organization as well as its subtle matrix structures. Conclusions: X-PCI captures comprehensive cartilage tissue transformation in its environment and might serve as a tissue-preserving, staining-free and volumetric virtual histology tool for examining and chronicling cartilage behavior in basic research/laboratory experiments of cartilage disease evolution. [ABSTRACT FROM AUTHOR]

Mechanical ventilation can damage the lungs, a condition called Ventilator-Induced Lung Injury (VILI). However, the mechanisms leading to VILI at the microscopic scale remain poorly understood. Here we investigated the within-tidal dynamics of cyclic recruitment/derecruitment (R/D) using synchrotron radiation phase-contrast imaging (PCI), and the relation between R/D and cell infiltration, in a model of Acute Respiratory Distress Syndrome in 6 anaesthetized and mechanically ventilated New-Zealand White rabbits. Dynamic PCI was performed at 22.6 µm voxel size, under protective mechanical ventilation [tidal volume: 6 ml/kg; positive end-expiratory pressure (PEEP): 5 cmH2O]. Videos and quantitative maps of within-tidal R/D showed that injury propagated outwards from non-aerated regions towards adjacent regions where cyclic R/D was present. R/D of peripheral airspaces was both pressure and time-dependent, occurring throughout the respiratory cycle with significant scatter of opening/closing pressures. There was a significant association between R/D and regional lung cellular infiltration (p = 0.04) suggesting that tidal R/D of the lung parenchyma may contribute to regional lung inflammation or capillary-alveolar barrier dysfunction and to the progression of lung injury. PEEP may not fully mitigate this phenomenon even at high levels. Ventilation strategies utilizing the time-dependence of R/D may be helpful in reducing R/D and associated injury. [ABSTRACT FROM AUTHOR]

Recent trends in hard X‐ray micro‐computed tomography (microCT) aim at increasing both spatial and temporal resolutions. These challenges require intense photon beams. Filtered synchrotron radiation beams, also referred to as 'pink beams', which are emitted by wigglers or bending magnets, meet this need, owing to their broad energy range. In this work, the new microCT station installed at the biomedical beamline ID17 of the European Synchrotron is described and an overview of the preliminary results obtained for different biomedical‐imaging applications is given. This new instrument expands the capabilities of the beamline towards sub‐micrometre voxel size scale and simultaneous multi‐resolution imaging. The current setup allows the acquisition of tomographic datasets more than one order of magnitude faster than with a monochromatic beam configuration. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons. Pre‐clinical studies drive the development of animal models that well mimic ALS disorder and enable both the dissection of disease processes and an early assessment of therapy efficacy. A comprehensive knowledge of neuronal and vascular lesions in the brain and spinal cord is an essential factor to understand the development of the disease. Spatial resolution and bidimensional imaging are important drawbacks limiting current neuroimaging tools, while neuropathology relies on protocols that may alter tissue chemistry and structure. In contrast, recent ex vivo studies in mice demonstrated that X‐ray phase‐contrast tomography enables study of the 3D distribution of both vasculature and neuronal networks, without sample sectioning or use of staining. Here we present our findings on ex vivo SOD1G93A ALS mice spinal cord at a micrometric scale. An unprecedented direct quantification of neuro‐vascular alterations at different stages of the disease is shown. [ABSTRACT FROM AUTHOR]

Despite the diversity in fish auditory structures, it remains elusive how otolith morphology and swim bladder-inner ear (= otophysic) connections affect otolith motion and inner ear stimulation. A recent study visualized sound-induced otolith motion; but tank acoustics revealed a complex mixture of sound pressure and particle motion. To separate sound pressure and sound-induced particle motion, we constructed a transparent standing wave tube-like tank equipped with an inertial shaker at each end while using X-ray phase contrast imaging. Driving the shakers in phase resulted in maximised sound pressure at the tank centre, whereas particle motion was maximised when shakers were driven out of phase (180°). We studied the effects of two types of otophysic connections—i.e. the Weberian apparatus (Carassius auratus) and anterior swim bladder extensions contacting the inner ears (Etroplus canarensis)—on otolith motion when fish were subjected to a 200 Hz stimulus. Saccular otolith motion was more pronounced when the swim bladder walls oscillated under the maximised sound pressure condition. The otolith motion patterns mainly matched the orientation patterns of ciliary bundles on the sensory epithelia. Our setup enabled the characterization of the interplay between the auditory structures and provided first experimental evidence of how different types of otophysic connections affect otolith motion. [ABSTRACT FROM AUTHOR]

Objectives: Airway closure is involved in adverse effects of mechanical ventilation under both general anesthesia and in acute respiratory distress syndrome patients. However, direct evidence and characterization of individual airway closure is lacking. Here, we studied the same individual peripheral airways in intact lungs of anesthetized and mechanically ventilated rabbits, at baseline and following lung injury, using high-resolution synchrotron phase-contrast CT.Design: Laboratory animal investigation.Setting: European synchrotron radiation facility.Subjects: Six New-Zealand White rabbits.Interventions: The animals were anesthetized, paralyzed, and mechanically ventilated in pressure-controlled mode (tidal volume, 6 mL/kg; respiratory rate, 40; FIO2, 0.6; inspiratory:expiratory, 1:2; and positive end-expiratory pressure, 3 cm H2O) at baseline. Imaging was performed with a 47.5 × 47.5 × 47.5 μm voxel size, at positive end-expiratory pressure 12, 9, 6, 3, and 0 cm H2O. The imaging sequence was repeated after lung injury induced by whole-lung lavage and injurious ventilation in four rabbits. Cross-sections of the same individual airways were measured.Measurements and Main Results: The airways were measured at baseline (n = 48; radius, 1.7 to 0.21 mm) and after injury (n = 32). Closure was observed at 0 cm H2O in three of 48 airways (6.3%; radius, 0.35 ± 0.08 mm at positive end-expiratory pressure 12) at baseline and five of 32 (15.6%; radius, 0.28 ± 0.09 mm) airways after injury. Cross-section was significantly reduced at 3 and 0 cm H2O, after injury, with a significant relation between the relative change in cross-section and airway radius at 12 cm H2O in injured, but not in normal lung (R = 0.60; p < 0.001).Conclusions: Airway collapsibility increases in the injured lung with a significant dependence on airway caliber. We identify "compliant collapse" as the main mechanism of airway closure in initially patent airways, which can occur at more than one site in individual airways. [ABSTRACT FROM AUTHOR]

The detection system is a key part of any imaging station. Here the performance of the novel sCMOS-based detection system installed at the ID17 biomedical beamline of the European Synchrotron Radiation Facility and dedicated to high-resolution computed-tomography imaging is analysed. The system consists of an X-ray-visible-light converter, a visible-light optics and a PCO.Edge5.5 sCMOS detector. Measurements of the optical characteristics, the linearity of the system, the detection lag, the modulation transfer function, the normalized power spectrum, the detective quantum efficiency and the photon transfer curve are presented and discussed. The study was carried out at two different X-ray energies (35 and 50 keV) using both 2× and 1× optical magnification systems. The final pixel size resulted in 3.1 and 6.2 µm, respectively. The measured characteristic parameters of the PCO.Edge5.5 are in good agreement with the manufacturer specifications. Fast imaging can be achieved using this detection system, but at the price of unavoidable losses in terms of image quality. The way in which the X-ray beam inhomogeneity limited some of the performances of the system is also discussed. [ABSTRACT FROM AUTHOR]

Objectives: Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathologic process remains elusive. The goal of this study was to describe recruitment/derecruitment at acinar length scales over short-time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of recruitment/derecruitment, using a computational model.Design: Experimental animal study.Setting: International synchrotron radiation laboratory.Subjects: Four anesthetized rabbits, ventilated in pressure controlled mode.Interventions: The lung was consecutively imaged at ~ 1.5-minute intervals using phase-contrast synchrotron imaging, at positive end-expiratory pressures of 12, 9, 6, 3, and 0 cm H2O before and after lavage and mechanical ventilation induced injury. The extent and spatial distribution of recruitment/derecruitment was analyzed by subtracting subsequent images. In a realistic lung structure, we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and recruited lung fractions (Fderecruited, Frecruited) were computed based on the comparison of the aerated volumes at successive time points.Measurements and Main Results: Alternative recruitment/derecruitment occurred in neighboring alveoli over short-time scales in all tested positive end-expiratory pressure levels and despite stable pressure controlled mode. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of Fderecruited and Frecruited when mechanical interdependence was included, while its exclusion gave Frecruited values of zero at positive end-expiratory pressure greater than or equal to 3 cm H2O.Conclusions: These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent recruitment/derecruitment and subsequent lung damage. [ABSTRACT FROM AUTHOR]

The article presents a study on new pathogenetic mechanisms beyond the neurocentrical view for chemotherapy-induced peripheral painful neuropathy. Topics include information on micro vascular network in the central and peripheral nervous system of rats; information on chemotherapy-induced painful peripheral neuropathy (CIPPN); and information on permanent neurological damages of chemotherapy.

Objectives: Neoadjuvant chemotherapy is the state-of-the-art treatment in advanced breast cancer. A correct visualization of the post-therapeutic tumor size is of high prognostic relevance. X-ray phase-contrast computed tomography (PC-CT) has been shown to provide improved soft-tissue contrast at a resolution formerly restricted to histopathology, at low doses. This study aimed at assessing ex-vivo the potential use of PC-CT for visualizing the effects of neoadjuvant chemotherapy on breast carcinoma. Materials and Methods: The analysis was performed on two ex-vivo formalin-fixed mastectomy samples containing an invasive carcinoma removed from two patients treated with neoadjuvant chemotherapy. Images were matched with corresponding histological slices. The visibility of typical post-therapeutic tissue changes was assessed and compared to results obtained with conventional clinical imaging modalities. Results: PC-CT depicted the different tissue types with an excellent correlation to histopathology. Post-therapeutic tissue changes were correctly visualized and the residual tumor mass could be detected. PC-CT outperformed clinical imaging modalities in the detection of chemotherapy-induced tissue alterations including post-therapeutic tumor size. Conclusions: PC-CT might become a unique diagnostic tool in the prediction of tumor response to neoadjuvant chemotherapy. PC-CT might be used to assist during histopathological diagnosis, offering a high-resolution and high-contrast virtual histological tool for the accurate delineation of tumor boundaries. [ABSTRACT FROM AUTHOR]

Objective: To demonstrate the feasibility of using X-ray phase-contrast tomography to assess internal organs in a post-mortem piglet model, as a possible non-invasive imaging autopsy technique. Methods: Tomographic images of a new-born piglet were obtained using a free-space propagation X-ray phase-contrast imaging setup at a synchrotron (European Synchrotron Radiation Facility, Grenoble, France). A monochromatic X-ray beam (52 keV) was used in combination with a detector pixel size of 46 × 46 µm². A phase-retrieval algorithm was applied to all projections, which were then reconstructed into tomograms using the filtered-back projection algorithm. Images were assessed for diagnostic quality. Results: Images obtained with the free-space propagation setup presented high soft-tissue contrast and sufficient resolution for resolving organ structure. All of the main body organs (heart, lungs, kidneys, liver and intestines) were easily identified and adequately visualized. In addition, grey/white matter differentiation in the cerebellum while still contained within the skull was shown. Conclusion: The feasibility of using X-ray phase-contrast tomography as a post-mortem imaging technique in an animal model has been demonstrated. Future studies will focus on translating this experiment to a laboratory-based setup. Advances in knowledge: Appropriate image processing and analysis enable the simultaneous visualization of both soft- and hard-tissue structures in X-ray phase-contrast images of a complex, thick sample. [ABSTRACT FROM AUTHOR]

A method is proposed which enables the retrieval of the thickness or of the projected electron density of a sample from a single input image acquired with an edge illumination phase-contrast imaging setup. The method assumes the case of a quasi-homogeneous sample, i.e. a sample with a constant ratio between the real and imaginary parts of its complex refractive index. Compared with current methods based on combining two edge illumination images acquired in different configurations of the setup, this new approach presents advantages in terms of simplicity of acquisition procedure and shorter data collection time, which are very important especially for applications such as computed tomography and dynamical imaging. Furthermore, the fact that phase information is directly extracted, instead of its derivative, can enable a simpler image interpretation and be beneficial for subsequent processing such as segmentation. The method is first theoretically derived and its conditions of applicability defined. Quantitative accuracy in the case of homogeneous objects as well as enhanced image quality for the imaging of complex biological samples are demonstrated through experiments at two synchrotron radiation facilities. The large range of applicability, the robustness against noise and the need for only one input image suggest a high potential for investigations in various research subjects. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To quantify the late dose-related responses of the rat cervical spinal cord to X-ray irradiations by an array of microbeams or by a single millimeter beam. Materials and methods: Necks of anesthetized rats were irradiated transversely by an 11mm wide array of 52 parallel, 35μm wide, vertical X-ray microbeams, separated by 210μm intervals between centers. Comparison was made with rats irradiated with a 1.35mm wide single beam of similar X-rays. Rats were killed when paresis developed, or up to 383days post irradiation (dpi). Results: Microbeam peak/valley doses of ≈357/12.7Gy to 715/25.4Gy to an 11mm long segment of the spinal cord, or single beam doses of ≈146–454Gy to a 1.35mm long segment caused foreleg paresis and histopathologically verified spinal cord damage; rats exposed to peak/valley doses up to 253/9Gy were paresis-free at 383dpi. Conclusions: Whereas microbeam radiation therapy [MRT] for malignant gliomas implanted in rat brains can be safe, palliative or curative, the high tolerance of normal rat spinal cords to similar microbeam exposures justifies testing MRT for autochthonous malignancies in the central nervous system of larger animals with a view to subsequent clinical applications. [Copyright &y& Elsevier]

Synchrotron-generated X-ray microplanar beams (microbeams) are characterized by the ability to deliver extremely high doses of radiation to spatially restricted volumes of tissue. Minimal dose spreading outside the beam path provides an exceptional degree of protection from radio-induced damage to the neurons and glia adjacent to the microscopic slices of tissue irradiated. The preservation of cortical architecture following high-dose microbeam irradiation and the ability to induce non-invasively the equivalent of a surgical cut over the cortex is of great interest for the development of novel experimental models in neurobiology and new treatment avenues for a variety of brain disorders. Microbeams (size 100 µm/600 µm, center-to-center distance of 400 µm/1200 µm, peak entrance doses of 360-240 Gy/150-100 Gy) delivered to the sensorimotor cortex of six 2-month-old naïve rats generated histologically evident cortical transections, without modifying motor behavior and weight gain up to 7 months. Microbeam transections of the sensorimotor cortex dramatically reduced convulsive seizure duration in a further group of 12 rats receiving local infusion of kainic acid. No subsequent neurological deficit was associated with the treatment. These data provide a novel tool to study the functions of the cortex and pave the way for the development of new therapeutic strategies for epilepsy and other neurological diseases. [ABSTRACT FROM AUTHOR]

Mammography is the primary imaging tool for screening and diagnosis of human breast cancers, but ∼10-20% of palpable tumors are not detectable on mammograms and only about 40% of biopsied lesions are malignant. Here we report a high-resolution, low-dose phase contrast X-ray tomographic method for 3D diagnosis of human breast cancers. By combining phase contrast X-ray imaging with an image reconstruction method known as equally sloped tomography, we imaged a human breast in three dimensions and identified a malignant cancer with a pixel size of 92 μm and a radiation dose less than that of dual-view mammography. According to a blind evaluation by five independent radiologists, our method can reduce the radiation dose and acquisition time by ∼74% relative to conventional phase contrast X-ray tomography, while maintaining high image resolution and image contrast. These results demonstrate that high-resolution 3D diagnostic imaging of human breast cancers can, in principle, be performed at clinical compatible doses. [ABSTRACT FROM AUTHOR]

Abstract: Computer tomography (CT) technology has greatly contributed to the feasibility and convenience of detecting and visualizing the internal material constitution and geometrical fabrication of museum artifacts. This paper presents a case study of 3D virtual reconstruction for the CT-acquisition-based study of a cultural heritage artifact. It documents the complete procedure, including the preprocessing, segmentation and visualization of the data by providing coarse interactive exploration and integrated high-quality renderings. A parallel aim achieved was to use open source tools and free software for segmentation and visualization, thus providing full transparency of the adopted methodology and 3D visualization methods, and a cost effective solution for ordinary CPU-based PC users. Furthermore, the challenges of the large data volumes involved have been addressed using preprocessing, a segmentation scheme and linked front-to-back management to keep interaction and high-quality rendering available, thus achieving corresponding demands. [Copyright &y& Elsevier]

Purpose: To explore the effects of microbeam radiation (MR) on vascular biology, we used the chick chorioallantoic membrane (CAM) model of an almost pure vascular system with immature vessels (lacking periendothelial coverage) at Day 8 and mature vessels (with coverage) at Day 12 of development. Methods and Materials: CAMs were irradiated with microplanar beams (width, ∼25 μm; interbeam spacing, ∼200 μm) at entrance doses of 200 or 300 Gy and, for comparison, with a broad beam (seamless radiation [SLR]), with entrance doses of 5 to 40 Gy. Results: In vivo monitoring of Day-8 CAM vasculature 6 h after 200 Gy MR revealed a near total destruction of the immature capillary plexus. Conversely, 200 Gy MR barely affected Day-12 CAM mature microvasculature. Morphological evaluation of Day-12 CAMs after the dose was increased to 300 Gy revealed opened interendothelial junctions, which could explain the transient mesenchymal edema immediately after irradiation. Electron micrographs revealed cytoplasmic vacuolization of endothelial cells in the beam path, with disrupted luminal surfaces; often the lumen was engorged with erythrocytes and leukocytes. After 30 min, the capillary plexus adopted a striated metronomic pattern, with alternating destroyed and intact zones, corresponding to the beam and the interbeam paths within the array. SLR at a dose of 10 Gy caused growth retardation, resulting in a remarkable reduction in the vascular endpoint density 24 h postirradiation. A dose of 40 Gy damaged the entire CAM vasculature. Conclusions: The effects of MR are mediated by capillary damage, with tissue injury caused by insufficient blood supply. Vascular toxicity and physiological effects of MR depend on the stage of capillary maturation and appear in the first 15 to 60 min after irradiation. Conversely, the effects of SLR, due to the arrest of cell proliferation, persist for a longer time. [ABSTRACT FROM AUTHOR]

Purpose: Synchrotron microbeam radiation therapy (MRT) relies on spatial fractionation of the incident photon beam into parallel micron-wide beams. Our aim was to analyze the effects of MRT on normal brain and 9L gliosarcoma tissues, particularly on blood vessels. Methods and Materials: Responses to MRT (two arrays, one lateral, one anteroposterior (2 × 400 Gy), intersecting orthogonally in the tumor region) were studied during 6 weeks using MRI, immunohistochemistry, and vascular endothelial growth factor Western blot. Results: MRT increased the median survival time of irradiated rats (×3.25), significantly increased blood vessel permeability, and inhibited tumor growth; a cytotoxic effect on 9L cells was detected 5 days after irradiation. Significant decreases in tumoral blood volume fraction and vessel diameter were measured from 8 days after irradiation, due to loss of endothelial cells in tumors as detected by immunochemistry. Edema was observed in the normal brain exposed to both crossfired arrays about 6 weeks after irradiation. This edema was associated with changes in blood vessel morphology and an overexpression of vascular endothelial growth factor. Conversely, vascular parameters and vessel morphology in brain regions exposed to one of the two arrays were not damaged, and there was no loss of vascular endothelia. Conclusions: We show for the first time that preferential damage of MRT to tumor vessels versus preservation of radioresistant normal brain vessels contributes to the efficient palliation of 9L gliosarcomas in rats. Molecular pathways of repair mechanisms in normal and tumoral vascular networks after MRT may be essential for the improvement of such differential effects on the vasculature. [ABSTRACT FROM AUTHOR]

Microbeam Radiation Therapy (MRT) is a preclinical form of radiosurgery dedicated to brain tumor treatment. It uses micrometer-wide synchrotron-generated X-ray beams on the basis of spatial beam fractionation. Due to the radioresistance of normal brain vasculature to MRT, a continuous blood supply can be maintained which would in part explain the surprising tolerance of normal tissues to very high radiation doses (hundreds of Gy). Based on this well described normal tissue sparing effect of microplanar beams, we developed a new irradiation geometry which allows the delivery of a high uniform dose deposition at a given brain target whereas surrounding normal tissues are irradiated by well tolerated parallel microbeams only. Normal rat brains were exposed to 4 focally interlaced arrays of 10 microplanar beams (52 mm wide, spaced 200 mm on-center, 50 to 350 keV in energy range), targeted from 4 different ports, with a peak entrance dose of 200Gy each, to deliver an homogenous dose to a target volume of 7 mm³ in the caudate nucleus. Magnetic resonance imaging follow-up of rats showed a highly localized increase in blood vessel permeability, starting 1 week after irradiation. Contrast agent diffusion was confined to the target volume and was still observed 1 month after irradiation, along with histopathological changes, including damaged blood vessels. No changes in vessel permeability were detected in the normal brain tissue surrounding the target. The interlacing radiation-induced reduction of spontaneous seizures of epileptic rats illustrated the potential pre-clinical applications of this new irradiation geometry. Finally, Monte Carlo simulations performed on a human-sized head phantom suggested that synchrotron photons can be used for human radiosurgical applications. Our data show that interlaced microbeam irradiation allows a high homogeneous dose deposition in a brain target and leads to a confined tissue necrosis while sparing surrounding tissues. The use of synchrotron-generated X-rays enables delivery of high doses for destruction of small focal regions in human brains, with sharper dose fall-offs than those described in any other conventional radiation therapy. [ABSTRACT FROM AUTHOR]

The technical feasibility of temporal and spatial fractionations of the radiation dose has been evaluated using synchrotron microbeam radiation therapy for brain tumors in rats. A significant increase in lifespan (216%, p < 0.0001) resulted when three fractions of microbeam irradiation were applied to the tumor through three different ports, orthogonal to each other, at 24 h intervals. However, there were no long-term survivors, and immunohistological studies revealed that 9 L tumors were not entirely ablated. [ABSTRACT FROM AUTHOR]

One of the most fascinating objects in the Rijksmuseum (Amsterdam, The Netherlands) is an early 16th century prayer nut. This spherical wooden object measures 4 cm in diameter and consists of two hemispheres connected with a small hinge so that it can be opened. The interior of the nut holds wood carvings with scenes from the life of Christ. These miniature reliefs show an incredible degree of finish with carving details well beyond the millimetre scale. In the present paper it is shown how synchrotron-based computer X-ray tomography revealed the structure and fabrication method of the bead. The central part of the relief was cut from a single piece of wood, rather than assembled from multiple components, underlining the extraordinary manual dexterity of its maker. In addition, a piece of fibrous material contained in the inner structure of the bead is revealed. This may have served as a carrier for an odorous compound, which would be in line with the religious function of the prayer nut. [ABSTRACT FROM AUTHOR]

Abstract: Microbeam radiation therapy (MRT) is a form of radiosurgery first dedicated to the treatment of brain tumors. It uses arrays of synchrotron generated X-rays microbeams of very high doses (typically 625Gy). Microbeams are typically few micrometers large (25μm) and few hundred micrometers spaced (200μm). Previous experiments have shown that despite a good tumor eradication rate (5/11), a 100-μm spacing unidirectional irradiation (skin dose 625Gy, width 25μm) was too invasive for normal tissue. On the contrary, a 200-μm spacing unidirectional irradiation preserved healthy tissue with a low tumor eradication rate (2/32). The purpose of this study was to enhance the potential of the 200μm spacing irradiation protocol. After diagnosis of the tumor by MRI, 9L tumor-bearing rats were laterally irradiated with 51 microbeams (625Gy, 25μm, 200μm) 14 days after implantation. Three drugs (Gd-DTPA, CisPt, temozolomide) were tested, after intratumoral injection at the theoretical center of the tumor. Control rats displayed a median survival time of 19 days. There was no significant difference between drug-treated rats and control group. Irradiated animals showed an increase in life span (ILS) of 60.5%. Interestingly, the ILS increased to 131.6% and 1/6 rat survived more than 1 year in case of MRT combined with gadolinium injection. These results showed that the synergy between gadolinium injection (acting as a dose enhancer) and MRT improved significantly the life span of tumor bearing rats (more than a factor 2). [Copyright &y& Elsevier]

Abstract: Background: Disturbances of memory function are frequently observed in patients with malignant brain tumours and as adverse effects after radiotherapy to the brain. Experiments in small animal models of malignant brain tumour using synchrotron-based microbeam radiation therapy (MRT) have shown a promising prolongation of survival times. Materials and methods: Two animal models of malignant brain tumour were used to study survival and memory development after MRT. Thirteen days after implantation of tumour cells, animals were submitted to MRT either with or without adjuvant therapy (buthionine-SR-sulfoximine=BSO or glutamine). We used two orthogonal 1-cm wide arrays of 50microplanar quasiparallel microbeams of 25μm width and a center-to-center distance of about 200μm, created by a multislit collimator, with a skin entrance dose of 350Gy for each direction. Object recognition tests were performed at day 13 after tumour cell implantation and in monthly intervals up to 1 year after tumour cell implantation. Results: In both animal models, MRT with and without adjuvant therapy significantly increased survival times. BSO had detrimental effects on memory function early after therapy, while administration of glutamine resulted in improved memory. [Copyright &y& Elsevier]

Abstract: Monitoring the progression of osteoarthritis (OA) and the effects of therapy during clinical trials is still a challenge for present clinical imaging techniques since they present intrinsic limitations and can be sensitive only in case of advanced OA stages. In very severe cases, partial or complete joint replacement surgery is the only solution for reducing pain and restoring the joint functions. Poor imaging quality in practically all medical imaging technologies with respect to joint surfaces and to metal implant imaging calls for the development of new techniques that are sensitive to stages preceding the point of irreversible damage of the cartilage tissue. In this scenario, X-ray phase contrast modalities could play an important role since they can provide improved contrast compared to conventional absorption radiography, with a similar or even reduced tissue radiation dose. In this study, the analyzer-based imaging (ABI), a technique sensitive to the X-ray refraction and permitting a high scatter rejection, has been successfully applied in vitro on excised human synovial joints and sheep implants. Pathological and healthy joints as well as metal implants have been imaged in projection and computed tomography ABI mode at high resolution and clinically compatible doses (<10mGy). Volume rendering and segmentation permitted visualization of the cartilage from volumetric CT-scans. The results demonstrate that ABI can provide an unequivocal non-invasive diagnosis of the state of disease of the joint and be considered a new tool in orthopaedic research. [Copyright &y& Elsevier]

The first practical application of X-rays, more than 100 years ago, was for biomedical imaging. Although not central to the initial development of 3rd generation synchrotron light sources, imaging techniques have today established themselves as a core element of the research program at all major light sources, including the ESRF, where X-ray imaging has been identified as one of five main themes for its Upgrade Programme [1]. [ABSTRACT FROM AUTHOR]

A hybrid approach was developed to compute the dose deposited in cancerous and healthy tissues during stereotactic synchrotron radiation therapy treatment. The proposed approach divides the computation into two parts: (1) the dose deposited by primary radiation (coming directly from the incident X-ray beam) is calculated using a deterministic algorithm based on ray casting, optimized for transport in voxelized geometries; (2) the dose deposited by secondary radiation (Rayleigh and Compton scattering, fluorescence) is computed using a hybrid algorithm combining Monte Carlo and deterministic calculations. In the Monte Carlo part, a set of scattering and fluorescence events occurring in the patient is determined. These events are further processed in a deterministic way, which considerably improves the statistics of the final dose map. The results obtained in test cases are compared to those obtained with the Monte Carlo method alone (Geant4 and MCNPX codes) and found to be in excellent agreement. The proposed simulation scheme makes it possible to simulate dose maps with a single PC, featuring computation time and statistical fluctuations substantially reduced in comparison with full Monte Carlo simulations. [ABSTRACT FROM PUBLISHER]

The purpose of this work was to assess the imaging performance of an indirect conversion detector (taper optics CCD `FReLoN' camera) in terms of the modulation transfer function (MTF), normalized noise power spectrum (NNPS) and detective quantum efficiency (DQE). Measurements were made with a synchrotron radiation laminar beam at various monochromatic energies in the 20–51.5 keV range for a gadolinium-based fluorescent screen varying in thickness; data acquisition and analysis were made by adapting to this beam geometry protocols used for conventional cone beams. The presampled MTFs of the systems were measured using an edge method. The NNPS of the systems were determined for a range of exposure levels by two-dimensional Fourier analysis of uniformly exposed radiographs. The DQEs were assessed from the measured MTF, NNPS, exposure and incoming number of photons. The MTF, for a given screen, was found to be almost energy independent and, for a given energy, higher for the thinnest screen. At 33 keV and for the 40 (100) µm screen, at 10% the MTF is 9.2 (8.6) line-pairs mm−1. The NNPS was found to be different in the two analyzed directions in relation to frequency. Highest DQE values were found for the combination 100 µm and 25 keV (0.5); it was still equal to 0.4 at 51.5 keV (above the gadolinium K-edge). The DQE is limited by the phosphor screen conversion yield and by the CCD efficiency. At the end of the manuscript the results of the FReLoN characterization and those from a selected number of detectors presented in the literature are compared. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess the early effects of microbeam irradiation on the vascular permeability and volume in the parietal cortex of normal nude mice using two-photon microscopy and immunohistochemistry. Methods and Materials: The upper part of the left hemisphere of 55 mice was irradiated anteroposteriorly using 18 vertically oriented beams (width 25 μm, interdistance 211 μm; peak entrance doses: 312 or 1000 Gy). At different times after microbeam exposure, the microvasculature in the cortex was analyzed using intravital two-photon microscopy after intravascular injection of fluorescein isothiocyanate (FITC)-dextrans and sulforhodamine B (SRB). Changes of the vascular volume were observed at the FITC wavelength over a maximum depth of 650 μm from the dura. The vascular permeability was detected as extravasations of SRB. Results: For all times (12 h to 1 month) after microbeam irradiation and for both doses, the FITC-dextran remained in the vessels. No significant change in vascular volume was observed between 12 h and 3 months after irradiation. Diffusion of SRB was observed in microbeam irradiated regions from 12 h until 12 days only after a 1000 Gy exposure. Conclusion: No radiation damage to the microvasculature was detected in normal brain tissue after a 312 Gy microbeam irradiation. This dose would be more appropriate than 1000 Gy for the treatment of brain tumors using crossfired microbeams. [Copyright &y& Elsevier]

The dosimetry of X-ray microbeams using MOSFETs results in an asymmetrical beam profile due to a lack of lateral charged particle equilibrium. Monte Carlo simulations were carried out using PENELOPE and GEANT4 codes to study this effect and a MOSFET on a micropositioner was scanned in the microbeam. Based on the simulations a new method of microbeam dosimetry is proposed. The proposed edge-on face-to-face (EOFF) MOSFET detector, a die arrangement proposed here for the first time, should alleviate the asymmetry. Further improvement is pos- sible by thinning the silicon body of the MOSFET. [ABSTRACT FROM AUTHOR]

The combination of X-ray ‘propagation-based’ and ‘analyzer-based’ phase-contrast imaging with a perfect crystal-analyzer is investigated. The image pattern produced using this ‘hybrid’ imaging technique presents peculiar features that can be interpreted as a mixture of the two independent phase-contrast signals. A quantitative analysis has been performed in terms of signal-to-noise ratio for the three techniques considered in this paper. Results show that in the ‘hybrid imaging’ technique this parameter has a weaker dependence on the angular alignment of the crystal analyser with respect to the ‘analyser-based’ imaging. This pioneering experiment indicates that this hybrid imaging technique might permit simultaneous advantage of the specific features of the two imaging methods to be taken. [ABSTRACT FROM AUTHOR]

Six excised human breast tissue specimens carrying benign and malignant tumours were examined with the diffraction-enhanced imaging technique. Diffraction-enhanced images were compared with diagnostic screen-film mammograms and the correlation with histological information of the specimens was established. The enhanced visibility of calcifications, some of which were smaller than 0.15 mm in diameter, is reported in detail. Fine details of the structures such as strands of collagen and contours between glandular and adipose tissue, which are barely visible at the contrast detection limit in the conventional absorption-based mammograms, are clearly visible in the diffraction-enhanced images. Microscopic study of the stained histopathological sections unequivocally confirms the correlation of the radiographic findings with the morphologic changes in specimens. An increased soft tissue contrast and a combination of information obtained with disparate diffraction-enhanced images provide better visibility of mammographically indistinguishable features. This kind of additional structural information of the breast tissue is required to improve assessment accuracy and earlier detection of the breast lesions. These advances in image quality make the method a very promising candidate for mammography. [ABSTRACT FROM AUTHOR]

Examines an online micrometer-scanning computer-controlled metal-oxide-silicon field-effect transistor (MOSFET) dosimetry system with improved spatial resolution. Overview of online MOSFET dosimetry system; Experimental results and discussion; Conclusion.