BriXS, a new X-ray inverse Compton source for medical applications.

MariX is a research infrastructure conceived for multi-disciplinary studies, based on a cutting-edge system of combined electron accelerators at the forefront of the world-wide scenario of X-ray sources. The generation of X-rays over a large photon energy range will be enabled by two unique X-ray sources: a Free Electron Laser and an inverse Compton source, called BriXS (Bright compact X-ray Source). The X-ray beam provided by BriXS is expected to have an average energy tunable in the range 20-180 keV and intensities between 1011 and 1013 photon/s within a relative bandwidth ΔE/E=1-10%. These characteristics, together with a very small source size (~20 µm) and a good transverse coherence, will enable a wide range of applications in the bio-medical field. An additional unique feature of BriXS will be the possibility to make a quick switch of the X-ray energy between two values for dual-energy and K-edge subtraction imaging. In this paper, the expected characteristics of BriXS will be presented, with a particular focus on the features of interest to its possible medical applications.

Comprehensive data set to include interference effects in Monte Carlo models of x-ray coherent scattering inside biological tissues.

Interference effects are included in the x-ray coherent scattering models used in Monte Carlo codes by modifying each material form factor through a proper interference function, which is obtained directly from the measured scattering pattern. This approach is effective for non-biological materials, but it is impractical for biological tissues, due the wide composition variability they can feature. Instead, a given biological sample can be considered as a proper mixture of four basis materials: fat, water, collagen and calcium hydroxyapatite. The sample form factor can then be obtained through a weighted mean of the form factors of the basis materials, which include interference effects. Here, we fully demonstrate the validity of the proposed segmentation method by applying it to 31 biological tissue samples whose form factors are available in the literature. The segmentation, namely the determination of the optimal weight of the basis components, was carried out through a multiple linear regression or, in some cases, by using a controlled trial and error sequence. The form factors of the basis materials were extracted from previous works and elaborated to include more scattering features. In particular, they were interpolated at a denser grid. Furthermore, the data measured separately in wide angle and small angle regimes, for fat and collagen, were merged. In general, a very good agreement was obtained between the original sample and the calculated mixture, being the mean relative difference of their scattering profiles and their attenuation coefficients ∼10%. The segmentation method is fully supported by our extension to the Geant4 model of x-ray coherent scattering, which was used to compare simulated scatter distributions with known experimental data. The developed Geant4 code and a series of molecular form factors, including those of the basis materials, are freely downloadable from a dedicated web repository.

Inverse Compton radiation: a novel x-ray source for K-edge subtraction angiography?

Coronary angiography is clinically used worldwide to diagnose diseases of coronary arteries. Despite its effectiveness, this technique is quite invasive and it is associated with significant risks due to the arterial catheterisation needed to inject the contrast agent. A valid alternative is using the K-edge subtraction (KES) method, which is based on the subtraction of two images acquired at energies bracketing the K-edge of the contrast element. The enhanced sensitivity of KES allows the intravenous injection of the contrast agent, thus reducing the risks of catheterisation. This technique can be effectively implemented by using intense and quasi-monochromatic x-ray beams. Synchrotron radiation has been proven to work well for this purpose, but its cost and size prevent a widespread clinical application. Inverse Compton sources are among the most promising innovative sources of intense and quasi-monochromatic x-rays. These sources are intrinsically more compact than those based on synchrotron radiation. In this work, the potential application of inverse Compton radiation to KES angiography is investigated. To this purpose, after a short review of the physics behind the inverse Compton process, an analytical framework is described. The proposed model is based on the application of the KES algorithm to calculate the SNR of details inside a suitable mathematical phantom. That allowed us to identify the characteristics of an inverse Compton source required for KES imaging. In particular, it was estimated that a photon fluence of 108 ph mm-2 is necessary to detect signals of clinical interest. Novel sources based on inverse Compton promise to achieve this requirement with an acquisition time of few hundreds of ms. This feature, together with compactness, broad two-dimensional radiation field, absence of harmonic contamination and the ability to deliver high photon fluxes also at high energies, makes this kind of sources promising for KES angiography and other diagnostic applications.

Geant4 implementation of inter-atomic interference effect in small-angle coherent X-ray scattering for materials of medical interest.

An extension to Geant4 Monte Carlo code was developed to take into account inter-atomic (molecular) interference effects in X-ray coherent scattering. Based on our previous works, the developed code introduces a set of form factors including interference effects for a selected variety of amorphous materials useful for medical applications, namely various tissues and plastics used to build phantoms. The code is easily upgradable in order to include new materials and offers the possibility to model a generic tissue as a combination of a set of four basic components. A dedicated Geant4 application for the simulation of X-ray diffraction experiments was created to validate the proposed upgrade of Rayleigh scattering model. A preliminary validation of the code obtained through a comparison with EGS4 and an experiment is presented, showing a satisfactory agreement.

Investigation of cerebral venous outflow in microgravity.

OBJECTIVE: The gravitational gradient is the major component to face when considering the physiology of venous return, and there is a growing interest in understanding the mechanisms ensuring the heart filling, in the absence of gravity, for astronauts who perform long-term space missions. APPROACH: The purpose of the Drain Brain project was to monitor the cerebral venous outflow of a crew member during an experiment on the International Space Station (ISS), so as to study the compensatory mechanisms that facilitate this essential physiological action in subjects living in a microgravity environment. Such venous function has been characterized by means of a novel application of strain-gauge plethysmography which uses a capacitive sensor. MAIN RESULTS: In this contribution, preliminary results of our investigation have been presented. In particular, comparison of plethysmography data confirmed that long duration spaceflights lead to a redistribution of venous blood volume, and showed interesting differences in the amplitude of cardiac oscillations measured at the level of the neck veins. SIGNIFICANCE: The success of the experiment has also demonstrated that thanks to its easy portability, non-invasiveness, and non-operator dependence, the proposed device can be considered as a novel tool for use aboard the ISS. Further trials are now under way to complete the investigation on the drainage function of the neck veins in microgravity.

Validation of a Hemodynamic Model for the Study of the Cerebral Venous Outflow System Using MR Imaging and Echo-Color Doppler Data.

BACKGROUND AND PURPOSE: A comprehensive parameter model was developed to investigate correlations between cerebral hemodynamics and alterations in the extracranial venous circulation due to posture changes and/or extracranial venous obstruction (stenosis). The purpose of this work was to validate the simulation results by using MR imaging and echo-color Doppler experimental blood flow data in humans. MATERIALS AND METHODS: To validate the model outcomes, we used supine average arterial and venous extracerebral blood flow, obtained by using phase-contrast MR imaging from 49 individuals with stenosis in the acquisition plane at the level of the disc between the second and third vertebrae of the left internal jugular vein, 20 with stenosis in the acquisition plane at the level of the disc between the fifth and sixth vertebrae of the right internal jugular vein, and 38 healthy controls without stenosis. Average data from a second group of 10 healthy volunteers screened with an echo-color Doppler technique were used to evaluate flow variations due to posture change. RESULTS: There was excellent agreement between experimental and simulated supine flows. Every simulated CBF fell inside the standard error from the corresponding average experimental value, as well as most of the simulated extracerebral arterial flow (extracranial blood flow from the head and face, measured at the level of the disc between second and third vertebrae) and venous flows. Simulations of average jugular and vertebral blood flow variations due to a change of posture from supine to upright also matched the experimental data. CONCLUSIONS: The good agreement between simulated and experimental results means that the model can correctly reproduce the main factors affecting the extracranial circulation and could be used to study other types of stenotic conditions not represented by the experimental data.

A new hemodynamic model for the study of cerebral venous outflow.

We developed a mathematical model of the cerebral venous outflow for the simulation of the average blood flows and pressures in the main drainage vessels of the brain. The main features of the model are that it includes a validated model for the simulation of the intracranial circulation and it accounts for the dependence of the hydraulic properties of the jugular veins with respect to the gravity field, which makes it an useful tool for the study of the correlations between extracranial blood redistributions and changes in the intracranial environment. The model is able to simulate the average pressures and flows in different points of the jugular ducts, taking into account the amount of blood coming from the anastomotic connections; simulate how the blood redistribution due to change of posture affects flows and pressures in specific points of the system; and simulate redistributions due to stenotic patterns. Sensitivity analysis to check the robustness of the model was performed. The model reproduces average physiologic behavior of the jugular, vertebral, and cerebral ducts in terms of pressures and flows. In fact, jugular flow drops from ∼11.7 to ∼1.4 ml/s in the passage from supine to standing. At the same time, vertebral flow increases from 0.8 to 3.4 ml/s, while cerebral blood flow, venous sinuses pressure, and intracranial pressure are constant around the average value of 12.5 ml/s, 6 mmHg, and 10 mmHg, respectively. All these values are in agreement with literature data.

A simulation model to study the role of the extracranial venous drainage pathways in intracranial hemodynamics.

Alterations in the extracranial venous circulation due to posture changes, and/or extracranial venous obstructions in patients with vascular diseases, can have important implications on cerebral hemodynamics. A hemodynamic model for the study of cerebral venous outflow was developed to investigate the correlations between extracranial blood redistributions and changes in the intracranial environment. Flow data obtained with both magnetic resonance (MR) and Echo-Color Doppler (ECD) technique are used to validate the model. The very good agreement between simulated supine and upright flows and experimental results means that the model can correctly reproduce the main factors affecting the extracranial venous circulation.

Experimental and Monte Carlo simulated spectra of a liquid-metal-jet x-ray source.

A prototype x-ray system based on a liquid-metal-jet anode was evaluated within the framework of the LABSYNC project. The generated spectrum was measured using a CZT-based spectrometer and was compared with spectra simulated by three Monte Carlo codes: MCNPX, PENELOPE and EGS5. Notable differences in the simulated spectra were found. These are mainly attributable to differences in the models adopted for the electron-impact ionization cross section. The simulation that more closely reproduces the experimentally measured spectrum was provided by PENELOPE.

Gauge approach to the 'pseudogap' phenomenology of the spectral weight in high Tc cuprates.

We assume the t-t'-J model to describe the CuO(2) planes of hole-doped cuprates and we adapt the spin-charge gauge approach, previously developed for the t-J model, to describe the holes in terms of a spinless fermion carrying the charge (holon) and a neutral boson carrying spin 1/2 (spinon), coupled by a slave-particle gauge field. In this framework we consider the effects of a finite density of incoherent holon pairs in the normal state. Below a crossover temperature, identified as the experimental 'upper pseudogap', the scattering of the 'quanta' of the phase of the holon-pair field against holons reproduces the phenomenology of nodal Fermi arcs coexisting with a gap in the antinodal region. We thus obtain a microscopic derivation of the main features of the hole spectra due to the pseudogap. This result is obtained through a holon Green function which follows naturally from the formalism and analytically interpolates between a Fermi liquid-like and a d-wave superconductor behaviour as the coherence length of the holon-pair order parameter increases. By inserting the gauge coupling with the spinon we construct explicitly the hole Green function and calculate its spectral weight and the corresponding density of states. So we prove that the formation of holon pairs induces a depletion of states on the hole Fermi surface. We compare our results with ARPES and tunnelling experimental data. In our approach the hole preserves a finite Fermi surface until the superconducting transition, where it reduces to four nodes. Therefore we propose that the gap seen in the normal phase of cuprates is due to the thermal broadening of the SC-like peaks masking the Fermi-liquid peak in the spectral weight. The Fermi arcs then correspond to the region of the Fermi surface where the Fermi-liquid peak is unmasked.

Optimization of radiography applications using x-ray beams emitted by compact accelerators. Part I. Monte Carlo study of the hard x-ray spectrum.

PURPOSE: A 3-year project called LABSYNC has been recently funded by the European Commission, with the aim of designing a radiation facility based on a compact light source, i.e., a laboratory-sized commercial synchrotron, capable of accelerating electrons up to 6 or 20 MeV. An accurate spectral description of hard x rays emitted from thin targets, irradiated by electron beams circulating in the storage ring, is of primary interest for the design and the characterization of a beamline. This article, Part I, aims at optimizing some of the parameters which are critical for the design of medical applications based on the above compact light source. The goal was to evaluate the dependence of photon fluence and beam monochromaticity on electron-beam energy, target material, and thickness. METHODS: The transport of 6 and 20 MeV electrons in a thin molybdenum, rhodium, and tungsten target is studied by means of Monte Carlo simulations using MCNPX. Configurations of the x-ray output port, different from the default forward-directed emission of the beam, are also investigated. A comparison with reference spectra for general diagnostic radiology and mammography is carried out. RESULTS: It is shown that the emitted x-ray beams can be far more intense than those generated by conventional x-ray tubes for radiography applications. The profiles of the calculated polychromatic spectra resemble those generated by conventional x-ray tubes, with x-ray energies up to the energy of the incident-electron beam. An appreciable improvement in the monochromaticity of the beams can be obtained by viewing the x-ray emission from an output port antiparallel to the direction of the incident-electron beam. CONCLUSIONS: The optimum target thickness for tungsten target spectra is practically constrained by a trade-off between bremsstrahlung efficiency and focal-spot size requirements. A larger margin for optimization of target thickness is probably available for mammographic spectra. The constraint of a backward-directed (or, to a lesser extent, orthogonal) output port is to be considered mandatory for minimizing the high-energy tail of the spectral distribution and keeping the radiation dose to a reasonable level. It is also fundamental to evaluate the impact of the high-energy tail of the emitted spectra in x-ray imaging applications, since the energy range involved is significantly beyond the diagnostic range. This topic will be dealt with in Part II of the article.

Structural characterization of the human cerebral myelin sheath by small angle x-ray scattering.

Myelin is a multi-lamellar membrane surrounding neuronal axons and increasing their conduction velocity. When investigated by small-angle x-ray scattering (SAXS), the lamellar quasi-periodical arrangement of the myelin sheath gives rise to distinct peaks, which allow the determination of its molecular organization and the dimensions of its substructures. In this study we report on the myelin sheath structural determination carried out on a set of human brain tissue samples coming from surgical biopsies of two patients: a man around 60 and a woman nearly 90 years old. The samples were extracted either from white or grey cerebral matter and did not undergo any manipulation or chemical-physical treatment, which could possibly have altered their structure, except dipping them into a formalin solution for their conservation. Analysis of the scattered intensity from white matter of intact human cerebral tissue allowed the evaluation not only of the myelin sheath periodicity but also of its electronic charge density profile. In particular, the thicknesses of the cytoplasm and extracellular regions were established, as well as those of the hydrophilic polar heads and hydrophobic tails of the lipid bilayer. SAXS patterns were measured at several locations on each sample in order to establish the statistical variations of the structural parameters within a single sample and among different samples. This work demonstrates that a detailed structural analysis of the myelin sheath can also be carried out in randomly oriented samples of intact human white matter, which is of importance for studying the aetiology and evolution of the central nervous system pathologies inducing myelin degeneration.

Effect of x-ray energy dispersion in digital subtraction imaging at the iodine K-edge--a Monte Carlo study.

The effect of the energy dispersion of a quasi-monochromatic x-ray beam on the performance of a dual-energy x-ray imaging system is studied by means of Monte Carlo simulations using MCNPX (Monte Carlo N-Particle eXtended) version 2.6.0. In particular, the case of subtraction imaging at the iodine K-edge, suitable for angiographic imaging application, is investigated. The average energies of the two beams bracketing the iodine K-edge are set to the values of 31.2 and 35.6 keV corresponding to the ones obtained with a compact source based on a conventional x-ray tube and a mosaic crystal monochromator. The energy dispersion of the two beams is varied between 0 and 10 keV of full width at half-maximum (FWHM). The signal and signal-to-noise ratio produced in the simulated images by iodine-filled cavities (simulating patient vessels) drilled in a PMMA phantom are studied as a function of the x-ray energy dispersion. The obtained results show that, for the considered energy separation of 4.4 keV, no dramatic deterioration of the image quality is observed with increasing x-ray energy dispersion up to a FWHM of about 2.35 keV. The case of different beam energies is also investigated by means of fast simulations of the phantom absorption.

Quantitative analysis of the effect of energy separation in k-edge digital subtraction imaging.

The aim of the work is to quantitatively compare the effect of the energy separation in the k-edge digital subtraction imaging technique. Images of a custom-made, iodine filled (k-edge = 33.17 keV) test object have been acquired with monochromatic x-ray beams (energy spread <0.1 keV) at the ID17 biomedical beamline of the ESRF. Image acquisition has been performed using two energy separations, namely 0.65 keV (32.85 keV and 33.5 keV, respectively) and 4.4 keV (31.2 keV and 35.6 keV, respectively), using beams of energies on either side of the iodine k-edge. Signal and signal-to-noise ratio (SNR) analysis has been performed as a function of DeltaE and the contrast medium concentrations. The results show that the SNR values measured for DeltaE < 1 keV are only slightly higher than those measured for DeltaE = 4.4 keV. This preliminary study shows that monochromaticity and the energy separation obtained with quasi monochromatic beams from conventional x-ray sources might be suitable for this imaging technique.

Guidelines on the standards for the training of specialised health professionals dealing with breast cancer.

According to EUSOMA position paper 'The requirements of a specialist breast unit', each breast unit should have a core team made up of health professionals who have undergone specialist training in breast cancer. In this paper, on behalf of EUSOMA, authors have identified the standards of training in breast cancer, to harmonise and foster breast care training in Europe. The aim of this paper is to contribute to the increase in the level of care in a breast unit, as the input of qualified health professionals increases the quality of breast cancer patient care.

Evaluation of the minimum iodine concentration for contrast-enhanced subtraction mammography.

Early manifestation of breast cancer is often very subtle and is displayed in a complex and variable pattern of normal anatomy that may obscure the disease. The use of dual-energy techniques, that can remove the structural noise, and contrast media, that enhance the region surrounding the tumour, could help us to improve the detectability of the lesions. The aim of this work is to investigate the use of an iodine-based contrast medium in mammography with two different double exposure techniques: K-edge subtraction mammography and temporal subtraction mammography. Both techniques have been investigated by using an ideal source, like monochromatic beams produced at a synchrotron radiation facility and a clinical digital mammography system. A dedicated three-component phantom containing cavities filled with different iodine concentrations has been developed and used for measurements. For each technique, information about the minimum iodine concentration, which provides a significant enhancement of the detectability of the pathology by minimizing the risk due to high dose and high concentration of contrast medium, has been obtained. In particular, for cavities of 5 and 8 mm in diameter filled with iodine solutions, the minimum concentration needed to obtain a contrast-to-noise ratio of 5 with a mean glandular dose of 2 mGy has been calculated. The minimum concentrations estimated with monochromatic beams and K-edge subtraction mammography are 0.9 mg ml(-1) and 1.34 mg ml(-1) for the biggest and smallest details, respectively, while for temporal subtraction mammography they are 0.84 mg ml(-1) and 1.31 mg ml(-1). With the conventional clinical system the minimum concentrations for the K-edge subtraction mammography are 4.13 mg ml(-1) (8 mm diameter) and 5.75 mg ml(-1) (5 mm diameter), while for the temporal subtraction mammography they are 1.01 mg ml(-1) (8 mm diameter) and 1.57 mg ml(-1) (5 mm diameter).

K-edge digital subtraction imaging with dichromatic x-ray sources: SNR and dose studies.

The aim of the present work is to analytically evaluate the signal to noise ratio (SNR) and the delivered dose in K-edge digital subtraction imaging (KES) using two types of x-ray sources: a monochromatic x-ray source (available at synchrotron radiation facilities and considered as gold standard) and a quasi-monochromatic compact source. The energy separation DeltaE between the two monochromatic beams is 1 keV and 4 keV for the two sources, respectively. The evaluation has been performed for both radiography and computed tomography. Different geometries have been studied to mimic clinical situations. In mammography, a pathology perfused by a contrast agent has been modelled; in angiography, a vessel superimposed to a ventricle or a stand-alone artery stenosis has been studied. The SNR and the skin dose have been calculated as a function of the detail diameter, the contrast agent (iodine and gadolinium), and its concentration in the tissues. Results show that for DeltaE = 4 keV a slightly higher delivered dose is required to obtain the same SNR with respect to DeltaE < 1 keV. A similar study has been performed for KES-CT. Computer simulations of CT images performed with Snark software are shown to validate the analytical calculations.