X-ray irradiation apparatus including an optically shaping X-ray optical device and a spectral filter aperture device, an X-ray fluorescence imaging apparatus, and its application, particularly in X-ray fluorescence imaging

Abstract

The X-ray irradiation apparatus (100) includes an X-ray source device (110) for generating X-rays (2) having a polychromatic spectrum, and an X-ray optical device (120) having a longitudinal beam axis (3), the X-ray optical device (120) including a polycrystalline reflector device (121) having a reflector geometry, a reflector mosaicity, and a reflector thickness, the reflector device (121) being configured to receive a portion of the X-rays (2) within an acceptance angle of the reflector device (121) and to direct the X-rays (2) along the beam axis (3) to a focal position thereof. The X-ray irradiation device (100) is arranged to generate a beam (4) by Bragg reflection, the beam having a spectral distribution determined by the polychromatic spectrum of the X-rays (2), the reflector geometry, the reflector mosaicity and the reflector thickness, the X-ray irradiation device (100) comprising a reflector device (121) arranged downstream from the reflector device (121) for forming a filter gap (123) which transmits a first spectral portion (4A) of the spectral distribution of the X-ray beam (4) and blocks a second spectral portion (4B) and a third spectral portion (4C) of said spectral distribution. The reflector device (121) further comprises a spectral filter aperture device (122), the first spectral portion (4A) having a higher energy than the second spectral portion (4B) and a lower energy than the third spectral portion (4C), the reflector device (121) having an acceptance solid angle of at least 100 microsteradians, and the reflector geometry, reflector mosaicity, reflector thickness, and acceptance angle of the reflector device (121) are such that the radiation flux of the first spectral portion (4A) is reflected by a reflector having a peak reflectance of at least 1%. The first spectral portion (4A) has a spectral bandwidth of at most 15%, the second and third spectral portions (4B, 4C) have a flux that is reduced by at least three orders of magnitude compared to the flux of the first spectral portion (4A), and the X-ray beam (4) has a focal spot size of less than 1.5 mm in the transverse dimension relative to the longitudinal beam axis. Further, methods of using the X-ray fluorescence imaging apparatus (200) and the X-ray irradiation apparatus (100) are described.

Description

[Technical field]

[0001] The present invention relates to an X-ray irradiation apparatus for irradiating a sample under investigation with X-rays, in particular an X-ray irradiation apparatus comprising an X-ray source device for generating X-rays with a polychromatic spectrum and an X-ray optical device for selecting a spectral portion of the X-rays and directing the spectral portion of the X-rays towards the sample. The present invention also relates to an X-ray fluorescence imaging apparatus comprising an X-ray irradiation apparatus. Furthermore, the present invention relates to a method of using an X-ray irradiation apparatus for an X-ray imaging modality, in particular for X-ray fluorescence imaging of a sample. Applications of the present invention can be used in the fields of using X-rays for measurement, imaging, material processing and / or testing purposes. [Background technology]

[0002] The following prior art is referenced herein to provide the technical background of the present invention: [1]Baldelli et al., “Quasi-monochromatic x-rays for diagnostic radiology”Phys.Med.Biol.48(2003)3653-3665 [2] Baldelli et al., “A prototype of a quasi-monochromatic system for mammography applications,” Phys.Med.Biol.50(2005)2225-2240. [3] International Publication No. German Translation No. 112019004433 [4] International Publication No. 2011 / 073148 [5] Rosentreter et al.2017 “Experimental investigation of a HOPG crystal fan for x-ray fluorescence molecular imaging” in “Medical Imaging 2017:Physics of Medical Imaging”, Proc. of SPIE Vol.10132, 2017. [6]Lawaczeck et al., “Monochromatic X-rays in Digital Mammography” in “Investigative Radiology” vol.40, 2005, p.33. [7] German Patent No. 102007018102 [8] International Publication No. 2008 / 052002 [9] International Publication No. 02 / 065481

[10] M. Gerlach et al. “Characterization of HAPG mosaic crystals using synchrotron radiation” in “J. Appl. Cryst.” (2015), 48, 1381-1390.

[11] T. Rosentreter, “X-ray fluorescence imaging: experimental and numerical analysis of a crystal based concept”, Dissertation, Otto-von-Guericke-Universitaet Magdeburg; 2021.

[12] EP 3610249 A1

[13] International Publication No. 2021 / 078950

[14] MSDel Rio et al. in “Journal of synchrotron radiation” 18(Pt 5), p.708-716, 2011.

[15] M. Shmi´d et al., in “Computer Physics Communications” 262, p. 107881, 2020.

[16] C. Schlesiger et al. in “J. Appl. Cryst.” 50, p. 1490-1497, 2017.

[17] D. Girou et al. “Development of a second generation SiLC-based Laue lens” in “Proc.SPIE 10399-Optics for EUV,X-Ray, and Gamma-Ray Astronomy” VIII, 103991Y (4 October 2017), doi:10.1117 / 12.2273830.

[18] U.S. Patent Application Publication No. 2021 / 356412

[19] U.S. Patent No. 5,127,028

[0003] It is generally known that X-rays have been used in medical imaging for over 100 years. In addition to absorption imaging (e.g., computed tomography, CT, or projection X-ray imaging), further X-ray-based imaging modalities have been developed, such as phase contrast imaging or X-ray fluorescence imaging (XRF imaging). XRF imaging allows new preclinical and clinical applications, for example, in improved pharmacokinetics with high spatial resolution and sensitivity, immune cell tracking, and in vivo determination of the population dynamics of different immune cell types in infectious or inflammatory diseases, as well as accelerated drug development through diagnosis, for example, in tumors and metastases.

[0004] XRF imaging is based on labeling the substances to be imaged in vivo, for example immune cells or drug molecules. Label atoms are bound to the substances, which, after being excited by X-rays, emit fluorescent photons whose energies are also in the X-ray range, so that a signal can leave the sample, for example the human body or a small animal, and be measured by a detector. Advantageously, in contrast to other imaging methods (such as PET or MRI), XRF imaging allows for an arbitrarily long diagnostic time window, since no radioactive decay labels are used. Furthermore, XRF imaging allows for a very wide range of the periodic table to be used as labels (approximately all elements from zirconium onwards).

[0005] XRF imaging requires finely focused X-rays with a well-defined energy bandwidth and sufficient energy to excite the fluorescence of label atoms with sufficient spatial resolution and detection sensitivity. These requirements cannot be effectively met by conventional X-ray sources. For example, in an X-ray tube, electrons are accelerated by high voltage towards the anode and emit X-ray quanta on collision, but without a preferred direction. The radiation is therefore isotropic and polychromatic. Only the so-called characteristic lines, generated by the X-ray fluorescence of the anode material, have a narrow bandwidth, but they are only present on top of a very wide continuous Bremsstrahlung-induced background. Furthermore, the maximum power of an X-ray tube is limited by the thermal input of the electrons into the anode material.

[0006] The best conventional X-ray source for XRF imaging is the synchrotron, which can generate very narrow band X-rays with very high flux in a very finely focused beam. Thus, for example, preclinical X-ray fluorescence-based studies are performed as fundamental research only in large synchrotron facilities. However, these large and costly facilities are not suitable for more widespread use and clinical applications, nor for laboratory applications, for example in the research-based pharmaceutical industry. Measurement stations for XRF imaging with synchrotrons are connected to large research facilities, i.e., the investigated objects have to be transported there. Thus, testing close to the laboratory or clinic is not possible. From many locations, long distance, cross-border transport is required. Also, certain sample environments are very costly or not feasible at all. Furthermore, the investment and ownership costs required for synchrotron facilities are very high, so the possibilities offered by XRF imaging are not widely exploited.

[0007] Therefore, compact X-ray sources are needed, especially for clinical research and clinical diagnostic applications. Laser-based X-ray sources (so-called Thomson sources) offer a compact alternative to synchrotron facilities, but are still relatively expensive and maintenance-intensive. Furthermore, Thomson sources have the disadvantage that the repetition rates are still very low for the high-power lasers required for this purpose, and that their intensity is limited due to insufficient long-term stability. As a further alternative, conventional X-ray sources (X-ray tubes), which in principle deliver divergent polychromatic radiation, are combined with X-ray optics.

[0008] X-ray optics for photon energies above 50 keV can be, for example, reflective optics made of polycrystalline materials such as highly oriented pyrolytic graphite (HOPG) or highly annealed pyrolytic graphite (HAPG). The deflection of X-rays by X-ray optics is based on Bragg diffraction, which can be described in terms of grazing incidence reflection (Bragg lenses, see e.g. [1] or [6]) or bulk reflection or transmission (Laue lenses, see

[17] ) and depends on the wavelength of the X-rays, so that any X-ray deflection by Bragg-based X-ray optics is inherently combined with a wavelength (energy) selection effect. HOPG-based X-ray optics are widely used with flat reflectors (see e.g. [1]-[5]) or curved reflectors (see e.g. [6]-[9]). HAPG-based X-ray optics are described, for example, in

[10] and

[11] . The main functions of conventional X-ray optics are to deflect the X-ray beam with a planar reflector, to spectrally filter the X-ray beam, and / or to focus the X-ray beam.

[0009] For the following reasons, conventional approaches combining X-ray tubes with polycrystalline X-ray optics, as described for example in [7] and [8], are only suitable for XRF imaging in a limited way. First, the efficiency of the wavelength selection effect is limited, resulting in deflection of X-rays that also have relatively low energy, a relatively wide range of X-ray wavelengths, and a large spectral background noise (especially in [7]). XRF imaging only allows a certain bandwidth in the spectrum of the exciting X-ray beam, which is limited to a maximum of 15% FWHM. A larger bandwidth leads to a significant decrease in detection sensitivity due to an increase in the multiple scattering background in the measured spectral region of the XRF signal. Maximum sensitivity requires a high degree of spectral purity of the scanning X-ray beam, i.e. photons in the incident beam outside the desired narrow bandwidth leave the scanned object with the same energy as the XRF photons and can therefore be Compton scattered inside this object and thus add to the spectral background in the XRF signal range, ultimately reducing the detection sensitivity. Conventional combinations of X-ray sources with X-ray optics do not meet the bandwidth conditions required for XRF imaging. Moreover, the radiation flux obtained with conventional X-ray optics is not sufficient for XRF imaging applications, which is important for in vivo imaging, where exposure times need to be minimized.A further disadvantage is that when X-ray optics are adapted to focus the X-rays (e.g., [8]), a conical beam is formed that illuminates a large part of the investigated object and thus reduces the spatial resolution, which is a disadvantage in terms of imaging resolution.

[0010] According to [7], a therapeutic irradiation application of X-rays is described, where the energy of X-rays for treating a sample is selected by a polycrystalline X-ray optics. A collimator ring and a central beam stop are arranged downstream and adjacent to the polycrystalline X-ray optics. By using the collimator ring, the shape of the X-ray radiation transmitted to the sample can be selected as required for the therapeutic irradiation application, e.g. to adapt the radiation to the complex shape of a tumor. In particular, the broadband radiation obtained with the technique of [7] makes it unsuitable for XRF imaging applications of X-rays.

[0011] Thus, no compact X-ray source exists so far that approaches the requirements for XRF imaging, especially if one wants to operate XRF at its sensitivity limit, where as few label atoms as possible need to be detected within the X-ray beam volume with the minimum radiation dose. [Prior art documents] [Patent documents]

[0012] [Patent Document 1] International Publication No. German Translation No. 112019004433 [Patent Document 2] International Publication No. 2011 / 073148 [Patent Document 3] German Patent Invention No. 102007018102 [Patent Document 4] International Publication No. 2008 / 052002 [Patent Document 5] WO 02 / 065481 [Patent Document 6] European Patent Application Publication No. 3610249 [Patent Document 7] International Publication No. 2021 / 078950 [Patent Document 8] US Patent Application Publication No. 2021 / 356412 [Patent Document 9] U.S. Patent No. 5,127,028 [Non-patent literature]

[0013] [Non-Patent Document 1] Baldelli, P. et al. Quasi-monochromatic x-rays for diagnostic radiology.Phys.Med.Biol.2003,vol.48,p.3653-3665. [Non-Patent Document 2] Baldelli, P. et al.A prototype of a quasi-monochromatic system for mammography applications.Phys.Med.Biol.2005,vol.50,p.2225-2240. [Non-Patent Document 3] Rosentreter, T. et al.Experimental investigation of a HOPG crystal fan for x-ray fluorescence molecular imaging.Medical Imaging 2017:Physics of Medical Imaging.Proc.of SPIE.2017,vol.10132. [Non-Patent Document 4] Lawaczeck, R. et al.Monochromatic X-rays in Digital Mammography.Investigative Radiology.2005,vol.40,p.33-39. [Non-Patent Document 5] Gerlach, M. et al.Characterization of HAPG mosaic crystals using synchrotron radiation.J.Appl.Cryst.2015,vol.48,p.1381-1390. [Non-Patent Document 6] Rosentreter,TX-ray fluorescence imaging: experimental and numerical analysis of a crystal based concept.Otto von Guericke University Magdeburg,2021,Dissertation. [Non-Patent Document 7] Sanchez Del Rio, M. et al.SHADOW3:a new version of the synchrotron X-ray optics modeling package.Journal of synchrotron radiation.2011,vol.18,p.708-716. [Non-Patent Document 8] Shmi´d,M. et al. X-ray spectrometer simulation code with a detailed support of mozaic crystals.Computer Physics Communications.2021,vol.262,p.107811. [Non-Patent Document 9] Schlesiger, C. et al.A new model for the description of X-ray diffraction from mosaic crystals for ray-tracing calculations.J.Appl.Cryst.”50,p.1490-1497,2017. [Non-Patent Document 10] Girou, D. et al.Development of a second generation SiLC-based Laue lens.Optics for EUV,X-Ray,and Gamma-Ray Astronomy VIII,Proc. of SPIE.2017,vol.10399,103991Y. Summary of the Invention [Problem to be solved by the invention]

[0014] It is an object of the present invention to provide an improved X-ray irradiator, for example for XRF imaging applications or other X-ray imaging modalities or other X-ray applications, which is in particular able to avoid the above-mentioned limitations of the prior art. In particular, the X-ray irradiator should be capable of generating narrowband X-rays with higher photon energy, reduced spectral background and / or increased radiation flux. The X-ray irradiator should be capable of generating X-rays with parameters comparable to those generated in synchrotron facilities, while being of compact configuration. According to a particular embodiment, the X-ray irradiator should be capable of irradiating with high sensitivity to the sample under investigation for XRF imaging. Furthermore, it is an object of the present invention to provide an improved X-ray fluorescence imaging device and / or an improved method for generating X-rays for X-ray imaging, in particular for X-ray fluorescence imaging of the sample under investigation. [Means for solving the problem]

[0015] These objects are correspondingly solved by an X-ray irradiation device, an X-ray fluorescence imaging device and a method of using an X-ray irradiation device for X-ray imaging of a sample under investigation, each comprising the features of the independent claims. Preferred embodiments and applications of the invention result from the dependent claims.

[0016] According to a first general aspect of the invention, the above object is solved by an X-ray irradiation device configured to irradiate a sample to be investigated. The sample comprises, for example, biological material, in particular a human for clinical or a small animal for preclinical imaging, or a part thereof, or a phantom. The X-ray irradiation device comprises an X-ray source device arranged to generate X-rays with a polychromatic spectrum. Preferably, the X-ray source device comprises an X-ray source, such as an X-ray tube, in particular a clinical X-ray tube, configured to generate X-rays by accelerating electrons from a cathode to an anode. Alternatively, X-ray sources based on irradiation of a target by accelerated electrons, including for example a linear accelerator, such as a linac-based source or a betatron X-ray source, or X-ray sources based on laser illumination of a target, such as a Thomson source or an inverse Compton scattering X-ray source, or X-ray sources including a radioactive source may be used, but clinical X-ray tubes are the cheapest and most widely used solution.

[0017] Furthermore, the X-ray irradiation apparatus includes an X-ray optical device having a longitudinal beam axis, the X-ray optical device including a polycrystalline reflector device having reflector geometry (particularly the shape, e.g. radius or radius of curvature and size, of the reflector layer and / or its layer parts), reflector mosaicity and reflector thickness (thickness of the reflector layer and / or its layer parts). An X-ray source device, for example an X-ray tube, in particular its anode, or a Linac or Thomson source, in particular its output end, is arranged on the beam axis. The X-ray optical device is a reflective optical system arranged to receive a portion of X-rays from the X-ray source device within a solid angle of acceptance of the X-ray optical device of at least 100 microsteradians and generate an X-ray beam by Bragg reflection (in particular Bragg diffraction, such as a Bragg lens or a Laue lens), the X-ray beam being directed along the beam axis to its focal position and having a spectral distribution determined by the polychromatic spectrum, the reflector geometry, the reflector mosaicity and the reflector thickness. Bragg reflections occur only at the crystal planes of polycrystalline bodies, i.e. there is no Bragg reflection in multi-layer structures. Preferably, the reflector geometry is selected such that the reflector surface faces the beam axis with axisymmetrical relation to the beam axis. In particular, the reflector surface preferably completely surrounds the beam axis along the axial length of the reflector device. Alternatively, the reflector surface can partially surround the beam axis along the axial length of the reflector device.

[0018] The focal position of the X-ray optical device on the sample to be irradiated is determined by Bragg reflection, therefore the X-ray optical device is typically placed at half the distance between the X-ray source device and the sample.

[0019] According to the invention, the X-ray irradiation device comprises a spectral filter aperture device arranged at a distance downstream of the X-ray optical device, in particular downstream of the reflector device, to form a filter gap transmitting a first spectral portion of the spectral distribution of the reflected X-ray beam and blocking a second and a third spectral portion of the spectral distribution of the reflected X-ray beam, the first spectral portion having a higher energy than the second spectral portion and a lower energy than the third spectral portion. Advantageously, this blocking results in a maximum of the spectral purity of the scanning X-ray beam, thus meeting the above-mentioned requirements for high sensitivity XRF imaging in the form of a synchrotron beam-like spectrum with a narrow bandwidth and an order of magnitude reduction in the photon flux outside this bandwidth. Blocking the second and third spectral portions of the spectral distribution of the reflected X-ray beam preferably comprises absorbing the second and third spectral portions of the spectral distribution, resulting in at least three orders of magnitude reduction in the number of photons per energy interval, for example per 100 eV, in the second and third spectral ranges, thus providing a very high spectral purity. The spectral filter aperture device preferably comprises a ring-shaped X-ray transparent diaphragm (ring-shaped X-ray transparent aperture) providing the filter gap. The ring-shaped x-ray transparent aperture may be provided by a ring-shaped x-ray transparent portion, e.g., a slit, disposed in a single sheet of x-ray blocking material. Alternatively, the ring-shaped x-ray transparent aperture may be provided between separate components of x-ray blocking material. The ring-shaped x-ray transparent portion preferably has a circular shape with the beam axis intersecting the center of the x-ray transparent portion.

[0020] Advantageously, the ring-shaped filter aperture mainly blocks photons outside the narrow bandwidth and allows photons within the bandwidth to pass through the filter. For example, for a cylindrical HOPG reflector with a thickness of 200 μm with a W anode, a further reduction in the number of photons per spectral energy bin (e.g. 100 eV) in the second and third spectral parts is on the order of three orders of magnitude to meet the requirements of XRF imaging. This spatial filter concept is based on the inventor's discovery that there is a very close correlation between the Bragg reflected photon energy and the position of the reflected photon on a virtual transverse plane where the filter aperture appears as a ring, where the majority of photons within the narrow bandwidth are located and most other photons are outside this ring.

[0021] Preferably, the spectral filter aperture device provides a single filter gap. Alternatively, multiple filter gaps can be arranged between the reflector device and the sample. In the case of rotationally symmetric optics, a single annular orifice or a combination of pinholes and circular apertures can be used, depending on the required free distance to the focal point in the sample.

[0022] The position of the spectral filter aperture device between the X-ray optical device and its focal point in the sample may be selected based on ray tracing simulations and / or optimization. A shorter distance from the X-ray optical device reduces the size of the filter gap and increases the requirements for positioning accuracy. Preferably, the spectral filter aperture device is located at half the distance between the center of the X-ray optical device and its focal point position in the sample.

[0023] Further, according to the present invention, the reflector geometry, reflector mosaicity, reflector thickness and acceptance angle of the polycrystalline reflector device are selected such that (a) the radiation flux of the first spectral portion is at least 1% of the incident flux of the same spectral portion of X-rays received by the X-ray optical device with a peak reflectivity of at least 1%, preferably at least 5%, (b) the first spectral portion has a spectral bandwidth of up to 15%, (c) the second and third spectral portions have a flux that is reduced by at least three orders of magnitude compared to the flux of the first spectral portion, and (d) the X-ray beam has a focal spot size of less than 1.5 mm.

[0024] The first spectral portion is defined by a maximum 15% spectral bandwidth BW. The spectral bandwidth BW is the energy range E2-E1 that includes 68.3% of the reflected X-ray photons and the energy E peak Ratio of BW=(E2-E1) / E peak More specifically, the energy range containing 68.3% of the reflected X-ray photons is defined by low and high energy integral boundaries containing the intensity maximum of the X-ray beam. The low energy integral boundary E1 is defined, for example, such that 16.35% of the total intensity is included in the second spectral portion (energy 0 keV to E1), and the high energy integral boundary E2 is defined, for example, such that 16.35% of the total intensity is included in the third spectral portion (E2 to maximum energy).

[0025] The spot size is the characteristic diameter of the X-ray beam, within which the X-ray intensity exceeds a certain percentage, for example 68.3%, of the total X-ray intensity at the center of the considered beam spot, e.g., the focal spot. Preferably, the X-ray beam is shaped to have a spot size of less than 1.5 mm along the irradiation volume in the sample including the focal spot, particularly in the left-right transverse dimension relative to the longitudinal beam axis. The beam path length along the irradiation volume inside the sample is preferably less than 10 cm, particularly preferably less than 5 cm, for example 3 cm or less. Due to the resulting small divergence, the X-ray beam is also called a "pencil beam".

[0026] To achieve features (a)-(d) for a given X-ray source device, e.g. a clinical X-ray tube, numerical ray tracing calculations can be applied, e.g. using commercially or publicly available software (see e.g. SHADOW

[14] or

[15] ) or self-described software (

[16] ), simulating the X-ray path, reflector geometry and crystal response. The ray tracing calculations use the reflector geometry, reflector mosaicity and reflector thickness of the polycrystalline reflector device as variable input quantities in order to obtain features (a)-(d) by optimizing the input quantities. The reflector geometry is determined by the shape and dimensions of the reflector carrier substrate. In a preferred example, a rotationally symmetric elliptical, cylindrical or spherical shape of the reflector carrier substrate or a superposition of at least two of these shapes can be used. Designing the reflector device of the X-ray irradiation device of the invention by applying ray tracing calculations provides a further independent subject of the invention.

[0027] A polycrystalline reflector layer of a certain thickness is applied onto the reflector carrier substrate as a closed layer or as an arrangement of several layer parts. A single polycrystalline reflector layer is provided (preferably made of a single polycrystalline material), i.e. there is no multilayer reflector made of different materials. The thickness is also one of the parameters optimized by ray tracing simulation. Finally, the shape, position and size of the filter gap are defined by ray tracing simulation to filter the required part of the reflection spectrum. A preferred carrier material is, for example, glass.

[0028] As mentioned above, the inventors have found that reflector dispersion, i.e. the trajectories of photons with different energies along spatially separated paths, can be used in the X-ray beam design, and that low energy X-ray photons generate background noise that should be suppressed in XRF imaging. Advantageously, the spectral filter aperture device is arranged to transmit only the first spectral range of interest and to block low energy photons (second spectral part), which arrangement also helps to reduce the radiation dose and to increase the detection sensitivity, since the spectral background in the signal region is significantly reduced. The low energy photons can no longer reach the sample due to this blocking effect of the spectral filter aperture device. Furthermore, the spectral filter aperture device is arranged to block X-ray photons with higher energy than the first spectral range (third spectral part). The higher energy photons do not contribute significantly to the XRF signal intensity, but increase the spectral background noise and radiation dose. Blocking the third spectral part is therefore particularly advantageous in terms of reducing the radiation dose.

[0029] The spectral filter aperture device is thus a spatial filter for filtering out a first spectral range from the spectrum emitted by the X-ray source device and reflected from the X-ray optical device. By adjusting the position of the spectral filter aperture device, in particular its distance from the output end of the reflector along the beam axis, and the radial width of the filter gap, the energy of the first spectral range can be set precisely. This can be done by calibration measurements and / or numerical simulations.

[0030] The inventors have investigated the effect of the spectral filter aperture device by ray tracing simulations and test measurements. It has been found that the low and high energy parts of the spectrum of the X-ray source device are dramatically reduced, resulting in a reduction in the radiation exposure of the sample and an increase in the signal-to-background ratio for XRF imaging detection. Without this reduction of the low energy part of the incident X-ray spectrum, the closer the incident photon energy is to the XRF imaging signal photon energy, the more likely it is that the Compton scattering (single or multiple) of such low energy photons will cover the fluorescence energy range, thus increasing the spectral background of the XRF signal range and thus reducing the signal-to-noise ratio. This reduces the local amount of XRF imaging label "invisible" in the detected spectrum in cases where the background noise is stronger than the number of signal photons. The present invention provides sufficient background suppression that was previously only available with nearly perfect monochromatic synchrotron sources. Since access to these large synchrotron facilities is effectively limited (they are usually oversubscribed and therefore applications for beam time cannot be fulfilled), this invention will pave the way for much wider deployment of the currently widespread XRF imaging technology that is now feasible with clinical X-ray tubes.

[0031] Furthermore, the inventors have found that by setting the above characteristics (a) to (d), X-rays suitable for high-sensitivity XRF imaging applications can be obtained. In particular, the inventors have found that the above characteristics (a) to (d) can be obtained by setting the reflector geometric condition, reflector mosaicity, and reflector thickness of the X-ray optical device. The specific characteristics of the reflector geometric condition, reflector mosaicity, reflector thickness, and acceptance angle of the X-ray optical device can be selected based on test experiments and / or numerical ray tracing simulations. In a preferred example, particularly for a first spectral portion having an energy of 25 keV to 100 keV and a reflector having a shape of a hollow cylinder, the reflector mosaicity is selected to be less than 1.0°, typically in the range of 0.05° to 0.4°, the reflector thickness is selected in the range of 50 μm to 500 μm, while the acceptance solid angle of the X-ray optical device is selected in the range of 100 to 1000 microsteradians.

[0032] According to a second general aspect of the present invention, the above object is solved by an X-ray fluorescence imaging apparatus configured for X-ray fluorescence imaging of a sample under investigation, comprising an X-ray irradiation device according to the first general aspect of the present invention or an embodiment thereof, arranged to irradiate the sample with an X-ray beam having a first spectral part of a spectral distribution, a sample stage arranged to accommodate the sample, and an energy dispersive detector device arranged to detect sample fluorescence excited by the X-ray beam. Furthermore, the X-ray fluorescence imaging apparatus comprises a control device, e.g. a computer unit, arranged for controlling the X-ray irradiation device and for processing output data of the detector device.

[0033] According to a third general aspect of the present invention, the above object is solved by a method of using an X-ray irradiation device according to the first general aspect of the present invention or an embodiment thereof for X-ray fluorescence imaging of a sample under investigation. XRF imaging is intended for imaging applications resulting in tomographic X-ray images of the sample under investigation and / or X-ray measurements of image features of the sample.

[0034] According to a fourth general aspect of the present invention, the above object is solved by a method of using an X-ray irradiation device according to the first general aspect of the present invention or an embodiment thereof for other imaging modalities using a pencil-shaped X-ray beam of narrow bandwidth, such as for example X-ray phase contrast imaging or X-ray scattering experiments. Thus, as an alternative to XRF imaging, the present invention is also suitable for imaging methods that require a pencil-shaped beam as well, but may have different target parameters in energy, flux, bandwidth and aperture angle.

[0035] An important advantage of the present invention comes from the fact that the properties of the reflector device material, e.g. HOPG or HAPG material, including in particular its integral reflectivity and malleability, can be combined with the selected reflector device geometry, so that the beam parameters of a conventional divergent X-ray source can be optimized, e.g. for X-ray imaging applications, at low cost and with maximum imaging sensitivity. Advantageously, the X-ray source device can include a conventional X-ray source, e.g. an available clinical X-ray source, so that in combination with the X-ray optics of the present invention, XRF imaging is possible, similar to a synchrotron. Furthermore, the combination of the X-ray source and the X-ray optics provides a compact X-ray irradiator that can be operated at a relatively low cost and without the need for specific operator skills. In particular, the X-ray irradiator can accurately generate pencil beams with sufficiently high photon energy, intensity, and low bandwidth that preclinical and clinical XRF imaging is immediately applicable. Compared to all conventional alternatives, the present invention is not only directly realizable in current practice, but also the most cost-effective and accurate, since X-ray sources are already available, already approved, and personnel are already trained. Therefore, no other special (and more expensive) X-ray source is required, and personnel do not need to be specially trained. The addition of the X-ray optical device of the present invention to a clinical X-ray tube may be performed according to a standardized protocol, and the XRF imaging mode can then be performed. This is a decisive step to enable the transition of XRF imaging applications from basic research to very widespread applications, for example in research-based pharmaceutical companies, or in future clinical diagnostics.

[0036] The advantages of the present invention stem in particular from the high photon energy, narrow bandwidth, and high achievable flux and small spot size of X-rays irradiating the sample. This is in contrast to prior art, such as for example conventional approaches in diagnostic mammography or radiotherapy ([7]). In particular, in the technique of [7], the achievable beam spot is about three times the spot size achieved in the present invention. The achievable flux of the prior art is more than two orders of magnitude smaller than the flux achieved in the present invention using one and the same X-ray source. Also, in particular, the spectral width is too wide to perform sensitive XFI measurements.

[0037] According to a preferred embodiment of the invention, the reflector geometry, reflector mosaicity and reflector thickness of the X-ray optical device are selected and the spectral filter aperture device is configured in such a way that the first spectral part of the spectral distribution is included in the energy range between 25 keV and 100 keV, in particular in the energy range above 60 keV, for example up to 85 keV or even higher up to 100 keV, which is particularly advantageous for high sensitivity XRF imaging with available label atoms.

[0038] Preferably, the spectral filter aperture device comprises at least one X-ray blocking material, which forms the filter gap, has X-ray absorption and can reduce the intensity by at least two orders of magnitude for all parts of the spectrum. Preferably, the X-ray blocking material comprises molybdenum (Mo) or tungsten (W). Advantageously, these materials have a high blocking effect, so that the spectral filter aperture device can be provided with low complexity and low thickness along the beam axis. The spectral filter aperture device is easy to adjust. The X-ray blocking material may consist of Mo and / or W or may comprise an alloy containing Mo and / or W. Another example of an X-ray blocking material is copper (Cu).

[0039] According to a further preferred embodiment of the present invention, at least one of the reflector device and the spectral filter aperture device is adapted to move along the beam axis, in particular to adjust the distance between the reflector device, e.g. its output end, and the spectral filter aperture device, e.g. the position of the filter gap on the beam axis, and to set the energy of the first spectral portion transmitted by the spectral filter aperture device. As an example, the spectral filter aperture device may be adapted to move the filter gap along the beam axis. Additionally or alternatively, the spectral filter aperture device may be adapted to adjust the filter gap width. In a further option, the reflector device may be moved along the beam axis. Advantageously, by these features of adjusting the distance between the reflector device and the spectral filter aperture device and / or the radial width of the filter gap, the first spectral range can be effectively set. The X-ray beam generated with the technique of the present invention is energy adjustable. This is a great advantage since XRF imaging can be optimized by optimizing the energy for each sample to be irradiated and the XRF label atoms used, which are facilitated by the adjustable X-ray source. The energy adjustment can be brought about within a short operating time of a few minutes. Conversely, changing energy at a synchrotron can take several hours.

[0040] Preferably, for the energy adjustment function, at least one of the reflector device and the spectral filter aperture device is coupled to a carrier device arranged such that the coupled device moves parallel to the beam axis, and / or the spectral filter aperture device is coupled to a filter gap setting device arranged such that a component of the spectral filter aperture device moves radially to set the radial width of the filter gap.

[0041] In order to maintain a high photon flux when adjusting the above distance, in further embodiments the X-ray optical device may be adapted, for example exchanged for another optical system having different geometric conditions, in particular with an adjusted inner diameter, such that the Bragg condition is met for the new desired energy of the resulting pencil beam.

[0042] According to a particularly preferred embodiment of the invention, the X-ray optical device is configured such that the X-ray beam has a beam focus with a focus size in the range of 0.5 mm to 1.5 mm in the left-right transverse dimension and an increase in the beam spot size at the incidence plane of the sample of less than 50% compared to the focus beam size. As an example, the incidence plane of the sample is preferably at a distance of 50 mm or less, particularly preferably 25 mm or less, for example 15 mm or less, from the focal position, for example in the case of small animal imaging. In another example, the incidence plane of the sample is preferably at a distance of 20 cm or less, particularly preferably 15 cm or less, for example 10 cm or less, from the focal position, for example in the case of large animal or human imaging. These ranges provide advantages for imaging modalities with high spatial resolution in the millimeter or sub-millimeter range.

[0043] The polycrystalline reflector device may comprise a monolithic component (a monolithic hollow reflector extending along the beam axis) or an arrangement of several components (several reflector elements are arranged along the beam axis with the reflector element surfaces facing the beam axis). The reflector surface or all parts thereof are concave. The reflector device is configured such that the imaging coefficient of the radiation source of the X-ray source device, for example the anode or output of a linac source, is 1:1. Preferably, one monolithic reflector device is provided, i.e. there is only one monolithic reflecting component or only one group of several reflecting components that can only reflect the X-ray beam in common. A monolithic reflector device has the advantage of saving space between the X-ray source device and the spectral filter aperture device. Alternatively, several reflector devices may be provided. Advantageously, this allows the beam path to be adapted to, for example, the geometric conditions of the application site of the X-ray imaging apparatus. In case of several reflector devices, preferably the first reflector device downstream of the X-ray source device provides the beam parameters set according to the invention.

[0044] Preferably, the polycrystalline reflector device has a hollow cylindrical or hollow elliptical shape. Thus, advantages are obtained in terms of compact reflector geometry. The term "cylinder" encompasses not only geometrically ideal cylinders, but also cylinders that deviate from the ideal geometry, in particular cylinders whose inner reflector surface is curved towards the beam axis so that the divergence of the X-ray beam is easier to set. Alternatively, the polycrystalline reflector device has a spherical reflector shape with a stepped surface of Johansson or Johann type geometry (see, for example,

[18] or

[19] ), which shape includes a spherical stepped portion with a stepped edge between them. Advantageously, the stepped geometry allows a more accurate match of the desired Bragg angle and the actual reflection position along a longer reflector length, so that the focal spot size can be minimized while still increasing the reflected flux in the first spectral portion.

[0045] Elliptical reflector shapes, and even spherical reflector shapes with stepped reflector surfaces, have the advantage, compared to cylindrical shapes, that the length of the reflector device along the beam path can be increased. Thus, the resulting flux of the reflected X-ray beam can be increased as the solid angle of capture increases, while the Bragg condition is still satisfied for each position of the X-ray optics, within the limits of crystal mosaicity. Compared to other shapes, spherical reflector shapes with stepped reflector surfaces have the additional advantage that the spectral bandwidth of the reflector device is narrower.

[0046] In the case of Johansson type geometrical condition, the step edge is placed on a manifold of Rowland circles possible by equal radii, where the X-ray source device and the sample are placed. The Johansson type geometrical condition comprises a singly or doubly curved polycrystalline material, where one radius of curvature of the crystal plane is twice the radius of the Rowland circle, and the radius of curvature of the surface may be the distance between the optical surface and the optical axis (the line between the light source and the focal position) at each point. In a single ideal crystal, only the first radius of curvature is realized. The Johann type geometrical condition also comprises a singly or doubly curved polycrystalline material (e.g., torus shape), where one radius of curvature may be twice the radius of the Rowland circle. The curved ideal crystal can be obtained from a perfect crystal by grinding the crystal and placing it on a curved carrier surface. In the case of a thin mosaic crystal, a carrier substrate with a stepped carrier surface is provided. Furthermore, mosaic-based crystals can be curved in a second direction (due to the substrate shape) that is technically impossible for perfect crystals with available techniques, allowing for a better approximation of the preferred Johansson-type geometric conditions.

[0047] According to a further particularly preferred embodiment of the invention, the polycrystalline reflector device is made of pyrolytic graphite. The use of pyrolytic graphite has the advantage that it provides a mosaic crystal on a curved and optionally stepped carrier substrate. In pyrolytic graphite crystals, the mosaicity can be optimized, thereby maximizing the reflectivity and the X-ray flux while reducing the bandwidth. Furthermore, the divergent radiation from the X-ray source can be captured from a larger solid angle and directed to the sample by the low divergence of the invention.

[0048] Preferably, the pyrolytic graphite comprises highly oriented pyrolytic graphite (HOPG) or highly annealed pyrolytic graphite (HAPG) deposited on a reflector carrier substrate. HOPG may have advantages in terms of the thickness of the reflector layer (e.g., up to 2 mm), but the mosaicity drops to 0.2°. Using HAPG crystals as reflector material may have advantages in terms of reducing the X-ray focal spot size and the spectral bandwidth for irradiating the sample, and the mosaicity drops to less than 0.1°. Thus, HAPG crystals, in combination with the spectral filter gap, achieve an optimized mosaicity that maximizes the signal-to-noise ratio. The mosaicity, which represents a deviation from the ideal crystal, results in a high integrated reflectivity over a wider bandwidth range, around the energy suitable for the Bragg angle. Also, HAPG-based materials are extremely flexible and can be applied to highly curved surfaces. Thus, HAPG crystals have a special advantage in terms of flexibility in choosing the reflector geometric conditions, especially with regard to the radius of curvature of the reflector surface.

[0049] According to an alternative preferred embodiment of the invention, the polycrystalline reflector device is made of a metal crystal, for example Al or Cu, or made of diamond or other solid solutions, such as crystalline alloys, for example diatomic crystals, such as GaAs. The use of a metal crystal, diamond or other solid solutions can provide advantages in terms of increasing the X-ray reflectivity, and / or beam size, and / or spectral bandwidth.

[0050] According to another preferred embodiment of the invention, if at least one additional scattering absorber, e.g. a conical tube aperture (or tube opening), is arranged downstream of the X-ray optical device, in particular between the X-ray optical device and the spectral filter aperture device, or preferably downstream of the spectral filter aperture device, i.e. between the spectral filter aperture device and the sample, advantages are obtained in terms of further suppression of background noise, e.g. from Rayleigh scattered photons and / or Compton scattered photons from the X-ray optics.

[0051] Preferably, the beam stop component is arranged on the beam axis in the X-ray optical device or between the X-ray source device and the X-ray optical device to block radiation traveling along the beam axis. Particularly preferably, the beam stop component is made of an X-ray blocking material such as Mo or W. Advantageously, direct, i.e. non-reflected and non-scattered radiation emitted by the X-ray source device is blocked by the beam stop component.

[0052] Further details and advantages of the invention are described below with reference to the accompanying drawings. [Brief description of the drawings]

[0053] [Figure 1] 1 is a schematic diagram of an X-ray fluorescence imaging device including an X-ray irradiation device according to an advantageous embodiment of the present invention; [Diagram 2] FIG. 2 is a graphical illustration of advantageous beam characteristics obtained with the present invention. [Diagram 3] 4 is a graph showing the effect of a spectral filter aperture device included in an X-ray irradiation apparatus according to the present invention. [Figure 4] 4 is a graph showing the effect of a spectral filter aperture device included in an X-ray irradiation apparatus according to the present invention. [Diagram 5] FIG. 4 is an illustration of a schematic reflector geometry according to a further advantageous embodiment of the present invention; [Figure 6]FIG. 2 is a graphical representation of the shape of an X-ray beam at the focal point of a sample such as a small animal (eg, a mouse). [Figure 7] Measured cross-sectional image of an X-ray beam exiting an X-ray optical device (measured in front of the focal plane). [Figure 8] FIG. 13 illustrates the placement of a scattering absorber downstream of an X-ray optical device. [Figure 9] FIG. 13 illustrates the placement of a scattering absorber downstream of an X-ray optical device. [Figure 10] FIG. 13 illustrates the placement of a scattering absorber downstream of an X-ray optical device. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0054] Features of preferred embodiments of the invention are described below with exemplarily reference to the XRF imaging application of the X-ray irradiation device of the invention. It should be noted that the invention is not limited to this application of the X-ray irradiation device, and alternative applications of other imaging modalities are possible, such as, for example, phase contrast imaging, material processing of samples, and / or testing of samples. Details of XRF imaging are not described, but may be implemented (for example, as described in

[12] and

[13] ). The invention is not limited to the details presented in an exemplary manner. For example, HOPG or HAPG may be replaced by other polycrystalline materials, such as metal crystals or diamond crystals, provided that they have similarly low mosaicity as HOPG / HAPG.

[0055] 1 shows a schematic representation of an embodiment of an X-ray irradiation device 100 of the invention included in an X-ray fluorescence imaging device 200 for imaging a sample 1 under investigation. The X-ray irradiation device 100 is arranged for irradiating an X-ray beam 4 onto a sample 1 on a sample stage 210 along a beam axis 3. The sample stage 210 is adapted to scan the sample 1 in space along at least one of two orthogonal directions perpendicular to the direction of the beam axis 3. Furthermore, the X-ray fluorescence imaging device 200 comprises an energy dispersive detector 220 for detecting sample fluorescence excited in the sample 1 by the X-ray beam 4 and / or for recording an X-ray fluorescence spectrum with spatial resolution.

[0056] The X-ray irradiation apparatus 100 includes an X-ray source device 110 for generating X-rays 2. The X-ray source device 110 is, for example, a clinical X-ray tube manufactured by Siemens Healthineers or Barex Imaging. The X-rays 2 have a polychromatic spectrum (see curve A in FIG. 2). Preferably, the X-ray tube is configured to operate at an acceleration voltage of more than 120 kV and a tube current of about 30 mA.

[0057] Furthermore, the X-ray irradiation apparatus 100 comprises an X-ray optical device 120 arranged with a longitudinal beam axis 3 extending from the X-ray source device 110 to the sample 1. The X-ray optical device 120 comprises a polycrystalline reflector device 121 comprising a mosaic crystal-based reflector layer on a carrier substrate. The reflector device 121 preferably has a perfectly rotationally symmetric elliptical or cylindrical shape. Other shapes are also possible (see for example FIG. 5). The reflector layer is made of HOPG, for example with a thickness of 0.2 mm, a reflector mosaicity of 0.4° and an acceptance angle of 600 μsr, or HAPG, for example with a thickness of 0.1 mm, a reflector mosaicity of 0.1° and an acceptance angle of 600 μsr. The reflector device 121 has an axial length of for example 3.2 cm and an inner diameter of the reflector layer, for example 2 cm. The distance from the X-ray source device 110 to the input end of the reflector device 121 is, for example, 30.5 cm, and the distance from the output end of the reflector device 121 to the sample 1 is, for example, 30.5 cm.

[0058] Downstream of the reflector device 121, the X-ray irradiator 100 includes a spectral filter aperture device 122 made of an X-ray blocking material 124 such as W, with a ring-shaped slit providing an axially centered filter gap 123. The distance from the output end of the reflector device 121 to the spectral filter aperture device 122 is for example 12.5 cm and the radial width of the filter gap 123 is for example 2 mm centered on a radius of 5.5 mm. The spectral filter aperture device 122 can have a more complex structure made of components with one or two apertures aligned to provide the filter gap 123.

[0059] The spectral filter aperture device 122 has the following advantageous effects (see Figs. 3 and 4): the mosaicity of the applied optical material (e.g. HOPG or HAPG) leads to a dispersion and therefore an angular, i.e. spatial, separation of the X-ray energy, as shown in Fig. 7, which allows a further spatial filtering of the spectrum emitted by the X-ray source by the spectral filter aperture device 122. The X-ray beam 4 emerging from the reflector device 121 has a spectral distribution with different spectral parts, referred to here as a first spectral part 4A, a second spectral part 4B and a third spectral part 4C (schematically shown in Fig. 1). The first spectral part 4A, which has a higher energy than the second spectral part 4B and a lower energy than the third spectral part 4C, is spatially separated from the other spectral parts 4B, 4C by the spectral filter aperture device 122. Via the filter gap 123 the first spectral portion 4A is transmitted to the sample 1 and the second and third spectral portions 4B, 4C are blocked by the X-ray blocking material of the spectral filter aperture device 122. The X-ray beam 4 irradiating the sample, in particular the first spectral portion 4A of the X-ray beam 4, has a focal spot size of e.g. 1 mm.

[0060] In particular, the spectral filter aperture device 122 can simultaneously (i) select the focused energy (first spectral portion 4A), i.e., maximizing the transmittance of the entire optical system for the selected energy, (ii) remove the high and low energy portions of the excitation spectrum (second and third spectral portions 4B, 4C), thus reducing the radiation exposure and background of the sample 1 within the fluorescence signal energy range, thus increasing the signal-to-noise ratio and allowing for further reduction in radiation exposure and measurement time, and (iii) reduce the focal width, thus helping to improve spatial resolution.

[0061] The spectral filter aperture device 122 also has an advantage in terms of spatial resolution when illuminating the sample. In the above example, the beam profile leaving the reflector device 121 without the spectral filter aperture device 122 would have a width (diameter containing 68.3% of the reflected photons) at the focal plane (focal spot size) of, for example, 1.3 mm. With the spectral filter aperture device 122, the focal spot size is, for example, 0.8 mm.

[0062] The X-ray optical device 120 optionally includes a beam stop component 125 arranged on the beam axis 3, for example at the input end of the reflector device 121, for blocking X-rays 2 emitted directly on the beam axis 3. The beam stop component 125 is made of, for example, Mo and has a diameter of, for example, 16 mm and a thickness of, for example, 2 mm.

[0063] Optionally, the X-ray irradiator 100 further comprises at least one additional scattering absorber 126, as shown diagrammatically in FIG. 1, downstream of the spectral filter aperture device 122. The scattering absorber 126, which will be described in more detail with reference to FIGS. 8-10 below, suppresses Rayleigh and / or Compton scattered photons exiting the X-ray optics. The scattering absorber 126 can extend along the entire length of the longitudinal axis 3 from the spectral filter aperture device 122 to the sample 1, or along a portion thereof. The downstream end of the scattering absorber 126 can be considered as the output of the X-ray irradiator 100. As an alternative to the illustration according to FIGS. 1 and 8-10, multiple scattering absorbers (absorber portions) may be arranged in series along the longitudinal axis 3, and each scattering absorber may be configured like the single scattering absorber shown.

[0064] The reflector device and / or the spectral filter aperture device are coupled to a carrier device (not shown) for moving the coupled reflector device and / or the spectral filter aperture device parallel to the beam axis. The carrier device comprises, for example, a carrier rod or a carrier platform movable on rails. Optionally, a filter gap setting device may be provided for radially moving a component of the spectral filter aperture device, so that the radial width of the filter gap is set.

[0065] During operation of the X-ray irradiation apparatus 100, a part of the divergent polychromatic radiation 2 of the X-ray source device 110 is collected by the X-ray optical device 120 and refocused in the plane of the sample 1. The direct beam is blocked by the beam stop component 125. If the reflector device 121 is used as a Bragg lens with grazing incidence, the radiation 2 strikes the inner crystal face of the reflector device 121. Alternatively, if the reflector device 121 is used as a Laue lens, the radiation 2 strikes the front side of the crystal of the reflector device. Due to the use of high X-ray photon energy, especially the Bragg angle of the pyrolytic mosaic crystal of the reflector device 121 is low, and the convergence of the X-ray beam 4 is small enough to perform X-ray fluorescence imaging (XRF) analysis. In a practical example, the radiation flux of the first spectral portion 4A is at least 4% of the incident flux of the same spectral portion of the X-rays 2 emitted by the X-ray source device 110 for photons above 50 keV, the first spectral portion 4A having, for example, a spectral bandwidth of 11% for WKa1 (59.3 keV), and the second and third spectral portions 4B, 4C having a flux reduced by at least three orders of magnitude compared to the flux in the first spectral portion 4A. The first spectral portion 4A irradiates the sample 1. Since XRF imaging is a scanning technique, the X-ray irradiating device 100 is moved relative to the fixed sample 1, which is more appropriate for clinical diagnosis of the sample 1 or of the patient.

[0066] Using computer simulations to model beam parameters depending on the spectrum of the initial X-ray beam 2, the reflector geometry of the polycrystalline reflector device 121, the reflector mosaicity, the reflector thickness, and the acceptance angle, the inventors have shown that the X-ray beam 4 delivered to the sample 1 satisfactorily meets the target requirements of XRF imaging, for example in medical diagnostics. Examples of simulation results are described below with reference to Figures 2 to 4.

[0067] FIG. 2 shows a comparison between X-ray beam parameters simulated by the inventors for the same X-ray tube of the X-ray source device 110. More specifically, FIG. 2 shows simulated spectra of an X-ray tube with a tungsten anode (typical anode current of 30 mA) after a pinhole with a diameter of 1 mm at a distance of 641 mm from the X-ray tube for different configurations. The spectra are scaled to produce an equal number of photons at the characteristic WKα1 (59.3 keV). Curve A shows the direct tube spectrum with high background (illustrated at 18 times the intensity), for curve B (scaled at 153 times the intensity) an absorbing filter with a thickness of 0.3 mm gold is simulated in the beam path to suppress the low energy background, and in curve C (not scaled) the spectrum after reflection from the reflector device 121, e.g. a HAPG coated optics. For example, the gain in efficiency of excitation of GdKα (43 keV) is here about 4 times compared to unfiltered X-ray tube excitation, but has a very high background that interferes with XRF imaging, and is 30 times compared to the X-ray tube spectrum after the absorption filter, where again the spectral background after reflection at the reflector device 121 is much better.

[0068] Figures 3 and 4 further illustrate the effect of the spectral filter aperture device 122 on the spectrum reflected by the cylindrical pyrolytic graphite-based reflector device 121. Figure 3 shows the spectrum in the sample plane without the energy filtering filter gap 123 for cylindrical HOPG (curve A) and HAPG (curve B) based reflector devices 121 with beam stop components 125. Figure 4 shows the corresponding spectrum in the sample plane with application of the spectral filter aperture device 122 with the energy filtering filter gap 123 in particular, such that the focal spot size is also reduced to a full width at half maximum of 1 mm. Comparing Figures 3 and 4 clearly shows that in sample 1, the low and high energy parts of the spectrum are effectively suppressed, while the characteristic lines of the tube excitation are efficiently fed into the focal spot. The spectrum with the HAPG optics (curve B, mosaicity = 0.1°, thickness = 100 μm) is generally about 50% more intense (note the logarithmic scale). As an important advantage of the present invention, the background suppression is not only in the range of 10% to 20%, but also exceeds 90%.

[0069] FIG. 5 shows a schematic representation of an alternative embodiment of the invention, where the polycrystalline reflector device 121 has a stepped spherical reflector shape. A cross-sectional view including a surface view is shown when using complete rotational symmetry. The reflector layer of the reflector device 121 has a stepped surface with curved, in particular spherical or cylindrical and conical stepped sections 121A, 121B, 121C, ... with step edges between them. The X-ray source device 110, in particular its anode, and the sample 1 are arranged on a circle (a so-called Rowland circle of radius R). The stepped sections 121A, 121B, 121C, ... are rotationally symmetric with respect to the optical axis connecting the X-ray source device 110 and the sample 1. The stepped sections 121A, 121B, 121C, ... are a local approximation to the ideal Johansson type geometric condition. The center of each step section is arranged on a manifold of possible Rowland circles of radius R, and the X-ray source device 110 and the sample 1 are arranged on the intersection of all these Rowland circles (rotational symmetry). The step sections 121A, 121B, 121C, ... have a characteristic dimension of, for example, 5 mm, and the Rowland circle has a radius of, for example, 515 cm. According to the illustrated example, the spherical step sections 121A, 121B, 121C, ... are arranged on the Rowland circle (Johansson type geometric condition). Alternatively, the doubly curved toroidal section may be arranged on a circle with a radius twice the radius of the Rowland circle (Johansson type geometric condition).

[0070] Figure 6 shows the radius (beam size) of the first spectral portion of the X-rays reflected by the X-ray optical device as an illuminating X-ray beam to the sample around the focal position for various configurations of the X-ray optical device with and without a spectral filter aperture device (aperture). This shows that the spectral filter aperture device not only removes low-energy and high-energy spectral portions, but also reduces the beam size and therefore improves the spatial resolution of the illumination. The straight line and the drawn angle θ show the divergence of the beam (far from the focal position). However, for the spatial resolution of XRF imaging, it is the average cross-section of the volume inside the object (e.g., a small animal) illuminated by the pencil beam that is relevant, and not the divergence of the beam, which is shown for completeness.

[0071] An example of a measured spatial distribution of X-ray photons reflected by a polycrystalline reflector device 121 such as a HAPG optical system (see FIG. 1), measured outside the focal point, is shown in FIG. 7. Advantageously, a pronounced ring-shaped distribution is obtained, which represents the first spectral portion 4A (see FIG. 1) of the photons reflected by the reflector device 121, while outside the ring-shaped distribution, fewer photons of the second and third spectral portions 4B and 4C are measured. The spatial distribution is measured, for example, at half the distance between the center of the reflector device 121 and its focal position in the sample.

[0072] In Figure 7, two spatially separated ring-like structures can be clearly seen, which show the spatial distribution of the two Kα emission lines of the W anode from the X-ray source used in this measurement. These two emission lines (59.3 keV and 58.0 keV) are spectrally separated by only 1.3 keV, which means that when a spatial filtering gap aperture is constructed and positioned to allow only one emission line to pass through the gap, the achieved spectral width is less than 1.0 keV, which is superior to other X-ray optics setups based on Bragg diffraction.

[0073] Therefore, as a preferred feature of the invention, by positioning the spectral filter aperture device 122 at an axial position along the longitudinal beam axis 3 where the ring-shaped spatial distribution of X-ray photons reflected by the polycrystalline reflector device 121 is measurable, in particular at half the distance between the center of the reflector device 121 and its focal position in the sample, the spectral filter aperture device 122 precisely cuts out the first spectral portion 4A to be obtained (the ring visible in particular in FIG. 7 ) and at the same time limits the spectrum of photons behind the ring diaphragm. Thus, photons with lower and higher energies associated with a selected energy falling outside the ring-shaped spatial distribution of X-ray photons are blocked, so that, for example in the case of XRF imaging applications, the spectral background is clearly significantly reduced compared to using only optical systems.

[0074] 8 shows diagrammatically the provision of a scattering absorber 126 downstream of the spectral filter aperture device 122 and the polycrystalline reflector device 121. The scattering absorber 126 is made, for example, of an X-ray absorbing metal composition, for example a composition of W, Ni and Fe. In a preferred example, the scattering absorber 126 may be made of an alloy of W, Ni and Fe called "Densimet" (trade name).

[0075] Typically, the scattering absorber 126 has a tubular shape with an inner hollow channel 126A having a first diameter at the upstream end of the scattering absorber 126, i.e. the end facing the spectral filter aperture device 122, and a second diameter at the opposite downstream end of the scattering absorber 126, the second diameter being smaller than the first diameter. This tapering from the first diameter towards the second diameter can be obtained by a conical hollow channel 126A as shown in Figure 9, or by a cylindrical hollow channel 126A with an end diaphragm plate 126B as shown in Figure 10. A front diaphragm plate 126C can be optionally provided, which may have the advantage for further absorbing scattered radiation.

[0076] In a practical example, the longitudinal length of the tubular shape may range from 40mm to 60mm, while the first diameter may range from 7mm to 10mm and the second diameter may range from 2mm to 4mm. The radial thickness of the scattering absorber 126 along the tubular shape may range from 1mm to 5mm. The optional front diaphragm plate 126C may have a diameter in the range from 20mm to 40mm and a thickness in the range from 2mm to 5mm.

[0077] The features of the invention disclosed in the above description, drawings and claims may be important, both individually and in combination or subcombination, for the realization of the invention in its various embodiments. The invention is not limited to the preferred embodiments described above. Rather, multiple variations and derivations using the inventive concept are possible and therefore within the scope of protection. Moreover, the invention also claims protection for the subject matter and features of the dependent claims independently of the features and claims to which they refer.

Claims

1. An X-ray irradiation device (100) configured to irradiate a sample (1) under investigation, an X-ray source device (110) arranged to generate X-rays (2) having a polychromatic spectrum; an X-ray optical device (120) having a longitudinal beam axis (3); the X-ray optical device (120) comprises a polycrystalline reflector device (121) having a reflector geometry, a reflector mosaicity, and a reflector thickness, the X-ray optical device (120) is arranged to receive a portion of the X-rays (2) from the X-ray source device (110) within an acceptance angle of the X-ray optical device (120) and to generate an X-ray beam (4) by Bragg reflection, the X-ray beam (4) being directed to its focal position along the beam axis (3) and having a spectral distribution determined by the polychromatic spectrum, the reflector geometry, the reflector mosaicity, and the reflector thickness; a spectral filter aperture device (122) arranged at a distance downstream from the X-ray optical device (120) for forming a filter gap (123) for transmitting a first spectral portion (4A) of the spectral distribution of the reflected X-ray beam (4) and blocking second and third spectral portions (4B, 4C) of the spectral distribution of the reflected X-ray beam (4), said first spectral portion (4A) having a higher energy than said second spectral portion (4B) and a lower energy than said third spectral portion (4C); the x-ray optical device (120) has a solid angle of acceptance of at least 100 microsteradians; The reflector geometry, the reflector mosaicity, the reflector thickness and the acceptance angle of the polycrystalline reflector device (121) are selected such that: (a) the radiation flux in the first spectral portion (4A) is at least 1% of the incident flux of the same spectral portion of the X-rays (2) received by the X-ray optical device (120) with a peak reflectivity of at least 1%, (b) the first spectral portion (4A) has a spectral bandwidth of up to 15%, (c) the second and third spectral portions (4B, 4C) have a flux that is reduced by at least three orders of magnitude compared to the flux in the first spectral portion (4A), and (d) the X-ray beam (4) has a focal spot size of less than 1.5 mm in the left-right transverse dimension. X-ray irradiation equipment.

2. the reflector geometry, the reflector mosaicity, and the reflector thickness of the X-ray optical device (120) are selected and the spectral filter aperture device (122) is configured such that the first spectral portion (4A) of the spectral distribution is included in an energy range of 25 keV to 100 keV.

2. The X-ray irradiation device according to claim 1.

3. the spectral filter aperture device (122) includes at least one material (124) that forms the filter gap (123) and is capable of reducing X-ray intensity by at least two orders of magnitude for all parts of the spectrum; 3. The X-ray irradiation device according to claim 1 or 2.

4. At least one of the reflector device (121) and the spectral filter aperture device (122) is adapted to move along the beam axis (3). The X-ray irradiation device according to any one of claims 1 to 3.

5. the spectral filter aperture device (122) is adapted to adjust the width of the filter gap (123); The X-ray irradiation device according to any one of claims 1 to 4.

6. the x-ray optical device (120) is configured such that the x-ray beam (4) has a beam focus with the focus size in the range of 0.5 mm to 1.5 mm in the transverse dimension and an increase in beam spot size at the incidence plane of the sample of less than 50%. The X-ray irradiation device according to any one of claims 1 to 5.

7. The polycrystalline reflector device (121) has the shape of a hollow cylinder or a hollow ellipsoid. The X-ray irradiation device according to any one of claims 1 to 6.

8. The polycrystalline reflector device (121) has a spherical reflector shape with step faces having a Johann type geometric condition or a Johansson type geometric condition, and includes spherical step portions (121A, 121B, 121C) having step edges therebetween. The X-ray irradiation device according to any one of claims 1 to 6.

9. the polycrystalline reflector device (121) is made of pyrolytic graphite, in particular highly oriented pyrolytic graphite (HOPG) or highly annealed pyrolytic graphite (HAPG), and / or of metallic crystals and / or of crystalline alloys and / or of diamond, The X-ray irradiation device according to any one of claims 1 to 8.

10. and at least one additional scattering absorber (126) disposed downstream of said X-ray optical device (120). The X-ray irradiation device according to any one of claims 1 to 9.

11. a beam stop component (125) arranged on the beam axis (3) within the X-ray optical device (120) or between the X-ray source device (110) and the X-ray optical device (120) for blocking radiation traveling along the beam axis (3); The X-ray irradiation device according to any one of claims 1 to 10, further comprising:

12. An X-ray fluorescence imaging device (200) configured for X-ray fluorescence imaging of a sample (1) under investigation, comprising: An X-ray irradiation device (100) according to any one of claims 1 to 11, arranged to irradiate the sample (1) with the X-ray beam (4) having the first spectral portion (4A) of the spectral distribution; a sample stage (210) arranged to accommodate the sample (1); an energy dispersive detector device (220) arranged to detect fluorescence of the sample (1) excited by said X-ray beam (4); 1. An X-ray fluorescence imaging device comprising:

13. Use of an X-ray irradiation device (100) according to any one of claims 1 to 11 for X-ray fluorescence imaging of a sample (1) under investigation.

14. Use of an X-ray irradiation device (100) according to any one of claims 1 to 11 for an imaging modality using a pencil-shaped X-ray beam (4) with narrow bandwidth, e.g. for X-ray phase contrast imaging or X-ray scattering experiments.

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