X-ray imaging device and method using at least phase-contrast imaging

Abstract

The invention relates to an X-ray imaging device (100), the device (100) comprising: an X-ray source (10) arranged to emit an X-ray beam (11) towards a sample (1); an X-ray image detector (30) spaced apart from the X-ray source (10) by a distance greater than or equal to 80 cm and less than or equal to 1.6 m and arranged to capture the X-ray beam (11) having passed through the sample (1); a processing unit (40) configured to determine an image of the phase shift, and to reconstruct, from this image of the phase shift, a phase-contrast image of the sample, the device (100) having an optical magnification greater than or equal to 8 and less than 20.

Description

X-RAY IMAGING DEVICE AND METHOD USING AT LEAST PHASE CONTRAST IMAGING TECHNICAL FIELD OF THE INVENTION

[0001] The present invention relates generally to an X-ray imaging device and method using at least phase contrast imaging.

[0002] It relates more particularly to an X-ray imaging device and method using at least phase contrast imaging to image samples of biological tissue, for example tissue of human or animal origin, in particular breast macrobiopsy samples likely to contain microcalcifications. STATE OF THE ART

[0003] Breast cancer is now the leading cancer incident among women and also the leading cause of cancer death among women (685,000 deaths worldwide in 2020), ahead of lung and colorectal cancers. It accounts for one in four cancer incidents among women. In 2020, 2.3 million new cases were reported worldwide.

[0004] Breast microcalcifications are calcium deposits in breast tissue and appear as small, bright spots on conventional mammography images. Microcalcifications play a crucial role in breast cancer screening, particularly for non-palpable breast cancers, and are present in approximately one-third of all malignant lesions detected during screening mammography. Microcalcifications are more common in ductal carcinoma in situ than in invasive breast cancers.

[0005] Analysis of microcalcifications to distinguish their types is very useful in discerning the characteristics of breast lesions and thus improving the early diagnosis of breast cancer.

[0006] Microcalcification analysis is currently performed primarily in pathology departments on tissue samples taken during breast core biopsies. Pathologists then perform pathological studies using optical microscopy on these samples. These optical microscopy analyses require sample preparation, which is time-consuming, costly, and delays the delivery of results.

[0007] Following the collection of a macrobiopsy, the practitioner uses a specimen X-ray machine to X-ray this sample. However, to date, commercially available specimen X-ray systems are based on the Absorption X-ray imaging technique and provide images with low spatial resolution. Absorption X-ray imaging consists of measuring the differences in opacity of an object to X-rays, induced by its inhomogeneity in terms of materials or density. These devices are functional because they allow absorption images of the sample to be obtained. The absorption X-ray imaging technique is appropriate when the objects studied are made of materials with sufficient absorption differences.

[0008] However, existing specimen X-ray devices only allow validation that the samples contain the detected microcalcifications before sending the samples to the pathology department. These devices do not currently allow analysis of the detected microcalcifications or sorting them into benign or malignant categories.

[0009] Furthermore, the use of such images can lead to errors due to the low spatial resolution of these images.

[0010] On the one hand, it is desirable to provide an imaging device that can obtain images of samples, particularly breast macrobiopsy, with better spatial resolution. On the other hand, it is desirable to allow analysis of the images thus obtained of samples, for example of microcalcifications detected in breast macrobiopsy images, independently of an anatomopathology analysis by optical microscopy. PRESENTATION OF THE INVENTION

[0011] In order to overcome the aforementioned drawbacks of the state of the art, the present invention proposes an X-ray imaging device using at least phase contrast imaging, said device comprising: - an X-ray source arranged to emit a flux of X-rays from an emission spot having a diameter of between 1 pm and 20 pm, the flux of X-rays being emitted towards a sample placed on a sample holder, said flux of X-rays propagating in a free field towards said sample; - an X-ray image detector, said sample being positioned between the X-ray source and the X-ray image detector, the X-ray image detector being a two-dimensional image detector, the X-ray image detector being spaced from said X-ray source by a distance greater than or equal to 80 cm and less than or equal to 1.6 m (preferably between 80 cm and 1.5 m) and arranged to capture the X-ray flux having passed through said sample and to form an intensity image of the X-ray flux,; - a processing unit configured to determine, from the detected X-ray flux intensity image, a phase contrast image of the sample, said device having an optical magnification greater than or equal to 8 and less than 20.

[0012] In particular here, the arrangement of the source, the sample holder and the detector makes it possible to obtain a high optical magnification, which makes it possible to capture a particular phase shift on the imaging detector and to analyze this phase shift in order to be able to use phase contrast imaging.

[0013] The use of phase contrast imaging allows the reconstruction of an image of the sample with high contrast and high spatial resolution in 2D.

[0014] Other advantageous and non-limiting characteristics of the device according to the invention, taken individually or in all technically possible combinations, are as follows.

[0015] In one embodiment, the optical magnification is greater than 10 and less than 20, thereby improving the quality of the reconstructed phase contrast image. In one embodiment, the magnification is between 8 and 16 (advantageously between 8 and 15), and preferably ranging from 10 to 15, thereby achieving better results in terms of contrast and resolution. Very good results in terms of contrast and resolution are achieved with an optical magnification of between 14 and 16.

[0016] In one embodiment, the X-ray flux propagating between the sample holder and the X-ray detector is in free propagation. Thus, the device according to the present disclosure is based on an imaging technique which does not require an additional optical element to acquire the phase contrast image. This makes it possible, on the one hand, to limit the loss of X-ray flux, which improves the quantity of flux captured by the image detector. The phase contrast image obtained is therefore more contrasted. On the other hand, the device according to the present disclosure is also simpler to implement and less expensive.

[0017] In one embodiment, the X-ray source has an axis of propagation of the X-ray flux, the axis of propagation being oriented vertically relative to the ground.

[0018] In one embodiment, the emitted X-ray flux has a power greater than or equal to 3 W (or 5 W) and less than or equal to 100 W at the output of said X-ray source. Preferably, the emitted X-ray flux has a power greater than or equal to 5 W and less than or equal to 20 W (advantageously between 5 W and 10 W) at the output of said X-ray source. Such power makes it possible to improve the imaging quality of the device according to the present disclosure.

[0019] In one embodiment, the X-ray flux is emitted at an energy between 10 keV (0.12 nm) and 80 keV (0.015 nm).

[0020] In one embodiment, the X-ray source is configured to irradiate the sample for a time period between 5 seconds and 35 seconds.

[0021] In one embodiment, the X-ray source is configured to irradiate said sample at an X-ray dose of between 400 pSv and 650 pSv.

[0022] In one embodiment, the X-ray image detector comprises an array of pixels having a first spatial dimension and a second spatial dimension, the first spatial dimension being greater than 10 cm and the second spatial dimension being greater than 10 cm.

[0023] Advantageously, the first spatial dimension and the second spatial dimension of the X-ray image detector are each between 19 cm and 30 cm.

[0024] Advantageously, the pixel array of the X-ray image detector comprises square pixels with a side length less than or equal to 100 pm, and preferably greater than or equal to 5 pm. In one embodiment, the square pixels are less than 100 pm to improve the resolution of the reconstructed phase contrast image.

[0025] The combination of detector size and pixel size results in a high-resolution reconstructed phase contrast image.

[0026] Preferably, the square pixels have a side length ranging from 30 pm to 60 pm. This, combined with the dimensions of the image detector, improves the imaging quality.

[0027] In one embodiment, the processing unit is configured to determine, by using an edge detection algorithm on said phase contrast image, the presence of an object in said sample, and a morphology of each detected object.

[0028] In one embodiment, the processing unit is also arranged to reconstruct, from the phase shift image, an absorption image of said sample.

[0029] In one embodiment, the processing unit is also configured to sort each detected object into different classes.

[0030] In one embodiment, the device comprises a control circuit arranged to activate and deactivate the X-ray source and the X-ray image detector, said activation of the X-ray source and the X-ray image detector being performed synchronously.

[0031] In one embodiment, the device comprises a device for adjusting the orientation and / or position of said sample holder to adjust an orientation of said sample holder relative to the X-ray source according to at least one rotation angle and / or to adjust a position of said sample holder relative to the X-ray source along at least one spatial direction, said at least one spatial direction corresponding to a translation of said sample holder relative to the X-ray source.

[0032] In this embodiment, the device is configured to reconstruct a three-dimensional phase contrast image of said sample from at least three phase contrast images of said sample using a tomosynthesis reconstruction method.

[0033] In a particular and advantageous embodiment, the device comprises a plurality of sample holders arranged between the source and the image detector, each sample holder of the plurality of sample holders being located at a distinct distance from the X-ray source.

[0034] In one embodiment, the device comprises at least one of the following: - a support on which are mounted at least the X-ray source, the sample holder and the X-ray image detector, and optionally the processing unit, - a portable housing associated with the support and accommodating at least the X-ray source, the sample, the X-ray image detector, - a device for holding the support on the ground.

[0035] In one embodiment, the device for holding the support on the ground comprises casters or feet.

[0036] The invention also relates to a use of the device described above, for determining the presence of microcalcifications in the sample, said sample being a breast macrobiopsy type sample for producing 2D or 3D radiographic images.

[0037] In one embodiment, the use of the device is for determining the morphology of microcalcifications in the sample.

[0038] The invention also relates to a use of the device described above for determining the presence of microcalcifications in the sample, said sample being a macrobiopsy type sample for producing 2D radiographic images.

[0039] The invention also provides an X-ray imaging method using at least phase contrast imaging, said method comprising the following steps: - emission of a flux of X-rays by an X-ray source from an emission spot having a diameter of between 1 pm and 20 pm, the flux of X-rays being emitted towards a sample placed on a sample holder, said flux of X-rays propagating in a free field towards said sample; - detection, by means of an X-ray image detector spaced from said X-ray source by a distance greater than or equal to 80 cm and less than or equal to 1.6 m, of the X-ray flux having passed through said sample to form an intensity image of the X-ray flux, said sample being positioned between the X-ray source and the X-ray image detector so that the acquired intensity image of the X-ray flux has an optical magnification greater than or equal to 8 and less than 20; - processing of the X-ray flux intensity image acquired by the image detector to determine, from this X-ray image, a phase contrast image of said sample.

[0040] Such a method makes it possible to obtain a highly resolved two-dimensional phase contrast image with very good contrast.

[0041] In one embodiment, the optical magnification is greater than 10 and less than 20 to improve the quality of the phase contrast image obtained. In one embodiment, the optical magnification is between 8 and 16 (advantageously between 8 and 15), which allows better results to be obtained in terms of contrast and resolution.

[0042] Of course, the various features, variants and embodiments of the invention may be combined with each other in various combinations to the extent that they are not incompatible or mutually exclusive. DETAILED DESCRIPTION OF THE INVENTION

[0043] The description which follows with reference to the appended drawings, given as non-limiting examples, will make it clear what the invention consists of and how it can be implemented.

[0044] On the attached drawings:

[0045] Figure 1 is a schematic representation of a first embodiment of a device according to the present invention;

[0046] Figure 2 is a schematic representation in sectional view of an image of a phase shift determined by a processing unit of the device according to the first embodiment;

[0047] Figure 3 illustrates an example of a reconstructed phase contrast image (right image) and absorption image (left image) by the device according to the first embodiment;

[0048] Figure 4 illustrates a series of absorption images (4A, 4B, 4C) of different spots visible on the absorption images obtained with the apparatus according to the first embodiment in the first imaging configuration and a series of phase contrast images (4D, 4E, 4F) of the same spots reconstructed from the second imaging configuration;

[0049] Figure 5 illustrates another example of a three-dimensional phase contrast image reconstructed by the device according to the first embodiment;

[0050] Figure 6 is a schematic representation of a second embodiment of a device according to the present invention;

[0051] Figure 7 is a schematic representation of a ray imaging method X according to this disclosure.

[0052] Device

[0053] A first embodiment of an X-ray imaging device 100 using at least phase contrast imaging will now be described with the aid of FIG. 1, FIG. 2, FIG. 3 and FIG. 4.

[0054] The device 100 comprises an X-ray source 10. The X-ray source 10 is arranged to emit a flux 11 of X-rays from an emission spot (or light spot) having a diameter D of between 1 pm and 20 pm at the output of the X-ray source 10. The diameter D of the emission spot (focal spot in English) is the minimum diameter of the flux 11 of X-rays. Such an X-ray source is also called a microfocus source. In particular, the use of an X-ray flux having such a diameter D at the source output makes it possible to obtain an X-ray flux which achieves a certain spatial coherence, which makes it possible, as will be described below, to determine the image by phase contrast.

[0055] Typically here, the X-ray source 10 has an emission cone, specific to the source, through which the X-ray flux 11 propagates. Here, by emission cone, we mean a cone of revolution around a propagation axis A, having as generator the output diameter and having an apex angle or opening angle at the output of the X-ray source 10. The emission cone represents the volume in which the X-ray flux propagates from the X-ray source 10 to a sample 1. In other words, the X-ray flux 11 at the output of the X-ray source 10 is divergent, and propagates along the emission cone of the X-ray source 10.

[0056] Preferably, the total opening angle of the emission cone of the X-ray source 10 is greater than 5 degrees, for example 45 degrees, and makes it possible to illuminate the total surface of an X-ray image detector of the device 100 which will be described below.

[0057] As illustrated in Figure 1, the flux 11 of X-rays emitted by said X-ray source 10 has a propagation axis A oriented vertically relative to the ground. In other words, the propagation axis A is parallel to the z axis of the orthonormal reference frame shown in Figure 1 and defined by the x, y, and z axes.

[0058] In this example, the X-ray source 10 is a microfocus source based on an X-ray tube comprising an anode and a cathode. The X-ray source is configured to emit, at its output, the flux 11 of X-rays at a power ranging from a few watts to around ten watts, for example 5 W. This flux of X-rays is here emitted at energies between 10keV (corresponding to a wavelength of 0.12nm) and 80kV (corresponding to a wavelength of 0.015nm), preferably between 20keV and 80keV for a cathode current greater than 100pA. In general, the anode of the X-ray source comprises at least one heavy material, for example at least one of following materials: copper, molybdenum, tungsten, gallium. In our example, the anode material is molybdenum. In this case, the X-ray source 10 generates a continuous X-ray emission spectrum with an emission peak around 17 keV corresponding here to the emission lines of molybdenum, by applying a high voltage between cathode and anode between 40 kV and 80 kV, with a cathode current intensity greater than 100 pA for a power greater than 5 W. In a preferred embodiment, the flux emitted at the output of the X-ray source is between 3 W and 100 W (preferably between 5 W and 100 W) to improve the quality of the images, preferably between 5 W and 20 W, preferably between 5 W and 10 W (advantageously between 5 W and 7 W) to further improve the quality of the images acquired by the device according to the present disclosure.Here, the X-ray flux is selected to improve the quantity of X-rays captured by the image detector 30 without damaging the sample 1. In one embodiment, the power emitted by the X-ray source 10 is adapted to or is a function of the diameter D of the emission spot. Typically, this power can be 5 W for a diameter D of 5 μm, which makes it possible to have a good signal-to-noise ratio on the signal obtained from the flux captured by the image detector 30. In one embodiment, the power emitted by the X-ray source 10 can be 3 W for a diameter D of 3 μm.

[0059] The X-ray flux 11 propagates in a free field at the output of the X-ray source 10 towards a sample holder 20 included in the device 100. Here, by free field, we mean propagation in free space. In other words, the X-ray flux 11 does not encounter any other element of the device 100 before reaching the sample 1 on the sample holder 20.

[0060] Note that the X-ray flux has an initial wavefront representing its propagation at the source exit.

[0061] The sample holder 20 is used to hold a sample 1. Here, in particular, the sample holder 20 is adapted to collect a sample of the breast macrobiopsy type to produce 2D radiographic images. The sample is for example obtained by taking a sample of human biological tissue, for example a sample of flesh from a part of the breast of a patient. For this purpose, the device 100 can be used to detect microcalcifications present in the sample 1. This sample can have a thickness of between 1 cm and 6 cm.

[0062] As illustrated in Figure 1, the sample 1 is positioned in the emission cone of the X-ray source 10. In other words, the sample 1 is entirely irradiated by the X-ray flux 11. It is thus understood that the size of the sample is adapted to the emission cone of the X-ray source 10.

[0063] Here in this example the X-ray source is configured to irradiate sample 1 for a time period between 15 seconds and 35 seconds in order to generate enough signal to reconstruct the phase contrast image which will be described below.

[0064] The X-ray source 10 is configured to irradiate the sample 1 at a dose between 400 pSv and 650 pSv. Such a range avoids damaging the sample 1 while generating enough signal to make a rapid acquisition of the X-ray image.

[0065] According to the present disclosure, the sample holder 20 is spaced from the X-ray source 10 by a distance d1 between 0 cm and 20 cm, preferably between 10 cm and 20 cm in order to adjust a magnification value of the device 100 which will be explained below. This distance d1 is determined between an emission plane P1 of the X-ray source 10, here oriented perpendicular to the propagation axis A of the X-ray source (or perpendicular to the z axis) and a plane P2 of the sample 1 oriented parallel to the emission plane P1 of the X-ray source 10 and perpendicular to the propagation axis A of the X-ray source 10.

[0066] Thus, the flux 11 of X-rays propagates in free field from the source 10 of X-rays towards the sample 1 and then passes through the sample 1.

[0067] The device 100 also comprises the X-ray image detector 30 positioned facing the X-ray source 10. It is thus understood that the sample 1 is positioned between the X-ray source 10 and the X-ray image detector 30. Thus, the flux of X-rays passing through the sample 1 reaches the X-ray image detector 30. In the device 100, the X-ray image detector 30 is positioned at a distance d2 from the X-ray source 10. The distance d2 is between 80 cm and 1.70 m, preferably between 80 cm and 1.50 m.

[0068] The distance d1 separates the X-ray source 10 from the sample holder 20. The distance d2 separates the X-ray source 10 from the X-ray image detector 30. The distance d1 and the distance d2 make it possible to define an optical magnification of the device 100 as being the ratio between the distance d1 and the distance d2.

[0069] Here in particular, the optical magnification of the device 100 is greater than or equal to 8 and less than or equal to 20.

[0070] Preferably, the optical magnification of the device 100 is greater than 10 and less than 20 to improve the quality of the reconstructed phase contrast image. Advantageously, the optical magnification of the device 100 is between 8 and 16 (here between 8 and 15), or even between 14 and 16, in order to obtain better resolution on the phase contrast image reconstructed by the device 100.

[0071] Typically, in the device 100, the X-ray image detector 30 has a size adapted to the X-ray source 10 used, here in particular to the emission cone of the X-ray source 10 used (function of the diameter D). In other words, the X-ray image detector 30 is arranged to capture the total X-ray flux 11 passing through the sample.

[0072] The X-ray image detector 30 operates, for example, by indirect detection, using a matrix of cesium iodide (Csl) crystals coupled to a matrix of CMOS detectors. The X-ray image detector 30 thus comprises a matrix of pixels, each pixel having a side length less than or equal to 100 pm (preferably less than 100 pm).

[0073] Advantageously, the X-ray image detector 30 is a flat screen detector (fiat panel, in English) with a detection surface of at least 10cmx10cm. The X-ray image detector 30 has an active face 31, oriented opposite the X-ray source 10 and comprising a pixel matrix 32 in which each pixel is configured to capture a portion of the flux 11 of X-rays passing through the sample 1. The image detector 30 thus records an intensity image of the flux of X-rays having passed through the sample 1.

[0074] This pixel matrix 32 has a first spatial dimension oriented parallel to a spatial axis, for example the x axis, and a second spatial dimension perpendicular to the first spatial dimension and oriented parallel to the spatial y axis. Advantageously, the pixels of the pixel matrix 32 are arranged in rows and columns.

[0075] In a non-limiting manner, the first spatial dimension and the second spatial dimension are each greater than 10 cm, here in particular the first spatial dimension is 22.8 cm and the second spatial dimension is 29.2 cm. Advantageously, the first spatial dimension and the second spatial dimension are each less than 40 cm, in order to limit the size of the device 100.

[0076] Thus, in this example, the pixel matrix 32 of the X-ray image detector 30 is rectangular in shape. Of course, the image detector 30 may, in a variant, have other shapes, for example a square shape when the first spatial dimension and the second spatial dimension are of the same size.

[0077] The pixels of the pixel array 32 are all identical and each have a first dimension, oriented parallel to the first spatial dimension of the pixel array 32 and a second dimension, perpendicular to the first dimension and oriented parallel to the second spatial dimension of the pixel array. The first dimension and second dimension are each less than or equal to 100 pm and preferably between 40 pm and 60 pm. Here, typically, the pixel array 32 is made of square-shaped pixels with a side length of 49.5 pm. The pixel array 32 of the X-ray image detector 30 has a number of pixels ranging from 4000 to 6000 pixels in each direction, for example 4600 pixels in one direction and 5800 pixels in the other direction.

[0078] The present dimensions of the image detector 30 (size range and pixel size range) and the high number of pixels make it possible to obtain a high-resolution phase contrast image.

[0079] The X-ray image detector 30 is arranged to capture the flux 11 of X-rays passing through the sample 1. It is understood that the flux 11 of X-rays captured by the X-ray image detector 30 has a wavefront.

[0080] This flux 11 of X-rays captured by the X-ray image detector 30 is in the form of a two-dimensional intensity signal representing an intensity image of the wavefront of the flux of X-rays having passed through the sample 1. As a result, the X-ray image detector 30 is configured to detect, from the flux of X-rays captured, an X-ray image, hereinafter called an intensity image.

[0081] As illustrated in Figure 1, no optical element is positioned on the optical path of the flux 11 of X-rays passing through the sample 1. Thus, the flux 11 of X-rays passing through the sample propagating between the sample and the X-ray image detector 30 is in free propagation (i.e. it propagates in free space).

[0082] Furthermore, the free propagation phase contrast imaging method thus makes it possible to measure a phase contrast by observing the deviation of the X-ray flux 11 from the intensity signal measured with the high-resolution X-ray image detector 30, positioned here at the distance d2.

[0083] Indeed, when a distorted wavefront propagates far enough, small changes in the propagation direction cause intensity variations resulting in an enhancement of the internal and external contours or edges of the sample 1 , where the lateral gradients of the X-ray phase are the most important.

[0084] For example, Figure 2 illustrates an example in sectional view of an intensity image of a sample detected from the flow 11 of X-rays captured by the X-ray image detector 30. More precisely, Figure 2 represents an intensity profile of the X-rays captured on the image detector 30 by pixels extending for example along the x axis or the y axis. The object or sample 1 analyzed is in this example an object that absorbs little X-rays in the energy range defined previously, for example it corresponds to a breast macrobiopsy sample.

[0085] Here, for example, the intensity image of Figure 2 has a main curved part 5, representing the intensity of the X-ray beam passing through the sample, framed by two edges 6 in which the intensity signal has a hollow shape followed by a peak which correspond to the internal and external edges of the sample. These edges 6 are, in the following, called the enhanced edge effect.

[0086] As illustrated in Figure 2, enhanced edge effects are visible in the intensity image. The refraction of the X-ray beam at the edges of the sample, where the lateral gradients of the X-ray phase are greatest, causes intensity variations that are used to achieve an enhancement of the internal and external contours (or edges) of the sample.

[0087] The observed edge enhancement can be interpreted more rigorously using the wave nature of X-rays and Fresnel diffraction theory. From this point of view, the intensity distribution on the image detector 30 is the result of the interference of waves obtaining a variable phase shift by passing through the sample under study. At distance d2, the intensity distribution after the sample is described by a formula which, for a weakly absorbing object such as biological samples, can be written as follows: where I is the intensity of the detected radiation, A is the wavelength of the X-rays and < (x,y) is the phase of the wave under study on which the two-dimensional Laplace operator A acts in the xy plane.

[0088] The measured intensity here is not a direct measure of the phase, but rather the Laplacian of the phase of the wavefront, noted in the sequence transmitted wavefront, which represents a spatial distribution of the flux 11 of X-rays passing through sample 1.

[0089] In practice, in the device 100, the two edges depend on the optical magnification of the device 100 described above. Thus, it is understood that the optical magnification of the device 100 is adapted in the device 100 to visualize the edges of the image in intensity. Indeed, the two edges 6 are visible only when the propagation distance is sufficient and the diffraction operates in the Fresnel regime.

[0090] The device 100 also comprises a processing unit 40.

[0091] By processing unit is meant any calculation unit or processor or computer or any other electronic element making it possible to implement a succession of commands and / or calculations. This processing unit 40 typically comprises a processor, a memory and various input and output interfaces.

[0092] By means of its input and output interfaces, the processing unit 40 is programmed to receive any image acquired by the X-ray image detector 30.

[0093] Thanks to its memory, the processing unit 40 stores a computer application, consisting of computer programs comprising instructions whose execution by the processor makes it possible to reconstruct a phase contrast image from the intensity image acquired by the image detector 30.

[0094] The processing unit 40 illustrated in Figure 1 is at least connected to the detector of X-ray image 30 described above. By connected, it is meant that the processing unit 40 is arranged to communicate with another element, for example, by being configured to transmit and / or receive data from this element (here for example by wire). Here, in this case, the processing unit 40 is configured to determine an image of the phase shift from the intensity image captured by the X-ray detector 30, this intensity image being representative of the wavefront of the flux 11 of X-rays transmitted. The processing unit 40 is configured to reconstruct, from this intensity image with enhanced edges, a phase contrast image of the sample 1.

[0095] In practice, the processing unit 40 is configured to extract the Laplacian of the phase of the signal according to phase extraction techniques known to those skilled in the art, for example as described in the document Burvall, A., Lundstrôm, II., Takman, PA, Larsson, DH, & Hertz, HM (2011), “Phase retrieval in X-ray phase-contrast imaging suitable for tomography”.

[0096] The processing unit is also configured to reconstruct a phase contrast image from the Laplacian of the signal phase. Here this phase contrast image is a free-propagating phase contrast image.

[0097] Of course, it should be noted that the curved part 5 of the recorded signal can be analyzed and processed by the processing unit 40 to reconstruct an absorption image of the sample.

[0098] It is thus understood that the particular arrangement of the device 100, here in particular its magnification, makes it possible to precisely visualize the enhanced edges of the object in the intensity image. On the contrary, for a lower magnification, in particular less than 8, these edges are barely or weakly visible in the intensity X-ray image. As a result, the intensity X-ray image obtained with a magnification greater than or equal to 8 and less than 20 (advantageously greater than 10 and less than 20), and preferably between 8 and 16 (advantageously between 8 and 15), is much more precise and makes it possible to extract therefrom a high-contrast and highly spatially resolved phase contrast image.

[0099] The implementation of the free-propagation phase contrast imaging technique makes it possible to reduce the costs of the device 100 because fewer components are required in the device 100.

[0100] Figure 3 illustrates, on the right, a phase contrast image 7 of a sample reconstructed by the processing unit 40 and, on the left, an absorption image 8, or intensity image, of the same sample. In this example, these images were obtained with an optical magnification of 15 (distance d1 of 200 mm and distance d2 of 3000 mm), for an X-ray flux emission spot diameter 11 of 10 pm for the left image and respectively 30 pm for the right image. Here, by increasing the spot size emission, the spatial coherence condition is degraded, therefore, the intensity image associated with the left image only has a curved part and does not have edge enhancement unlike figure 2. Consequently, for this left image, the phase regime is not obtained at the distance d2 of 300 cm (source-detector).

[0101] As can be seen, the phase contrast image 7 on the right of Figure 3 has better contrast and resolution compared to the absorption image 8 obtained in the left image of Figure 3.

[0102] The processing unit 40 is optionally configured to determine, by using a contour detection algorithm on said phase contrast image, the presence of object 9 in said sample, and a morphology of each detected object.

[0103] Of course, if the processing unit 40 also reconstructs an absorption image of the sample, it can also determine the presence of an object in this latter image in a similar manner to the method used for the phase contrast image of the sample.

[0104] Typically, the contour detection algorithm may be based on at least one of the following algorithms: - segmentation using a histogram; - a Laplace algorithm; - a gradient algorithm, etc.

[0105] Figure 4 shows, at the top, three X-ray images (4A, 4B, 4C) of a microcalcification in a portion of breast of different patients obtained by absorption (denoted Abs.), and, at the bottom, three X-ray images (4D, 4E, 4F) of the same microcalcifications of the same portions of breast obtained by phase contrast (denoted C. Ph.). Each column of images in Figure 4 corresponds to the same microcalcification of the same portion of breast of the same patient. The three columns of images in Figure 4 correspond here to different patients. The three absorption images 4A, 4B, 4C are obtained with the device 100 in the first configuration, for example with a magnification of 15. The phase contrast images 4D, 4E, 4F are obtained with the same device 100 in the second configuration with the same detector 30, for example with a magnification of 15.In this example, the same magnification is used in both imaging configurations but not the same source spot size: in the first configuration, for absorption images, the spot of the X-ray source 11a is 100p and in the second configuration for phase contrast images, the diameter of the source 11b is 10p. Each image makes it possible to visualize one or more elements 91, 92, 92, 94, 95 opaque to X-rays, for example breast microcalcifications. As illustrated in Figure 4, different objects are extracted from the phase contrast image and the absorption image.

[0106] However, the comparison of the absorption and phase contrast images of Figure 4 shows for each case that the phase contrast image has better contrast and resolution compared to the obtained absorption image. For example, in the image pair (4A, 4D), an object 91 opaque to X-rays is detected in the absorption image 4A and it is observed in the phase contrast image 4D that the contours of this object 91 are irregular. In the example of the image pair (4B, 4E), two objects 92, 93 opaque to X-rays are detected in the absorption image and it is observed in the phase contrast image that the contours of these two objects 92, 93 are regular in the shape of a lozenge or diamond.In the example of the pair of images (4C, 4F), two spots 94, 95 partially opaque to X-rays are detected in the absorption image and it is observed on the phase contrast image that these two spots 94, 95 are diffuse and have irregular contours, for example filamentary in shape for spot 95. In all cases, the phase contrast image is much sharper than the absorption image.

[0107] Typically, these microcalcifications can then be classified into different classes, for example, based on the morphology of the objects detected in the images described above. In particular, the detected objects are classified according to their shape, which can be regular, for example, round or diamond-shaped, or irregular, possibly with roughness or hollows. The radiologist or doctor can then associate such an object shape with a low risk of pathology or a specific risk of pathology.

[0108] It is understood that since the resolution and contrast of the phase contrast image are better than those of the absorption image, detection and / or sorting from the phase contrast image is more precise and therefore allows better results to be obtained.

[0109] Optionally, the device 100 comprises a control circuit 50 arranged to activate and deactivate the X-ray source 10 and the X-ray image detector 30. In practice, the control circuit 50 comprises a control unit 51 arranged to control the different elements of the device 100, here at least the X-ray source 10, the X-ray image detector 30 and the processing unit 40.

[0110] Here, in particular, the control circuit 50 is configured to control an activation of the X-ray source 10 and the X-ray image detector 30 independently, synchronously or asynchronously.

[0111] By control unit 51 is meant any calculation unit or processor or computer or any other electronic element making it possible to implement a succession of commands and / or calculations. This control unit 51 typically comprises a processor, a memory and different input and output interfaces. Typically, the control unit 51 may comprise a microcontroller.

[0112] Thanks to its input and output interfaces, the control unit 51 is programmed to receive any image acquired by the image detector 30 of the device 100 and / or any image extracted by the processing unit 40. In a non-limiting manner, the device 100 comprises a screen 53 connected to the control unit 51. The control unit 51 is also programmed to control the screen 53 and more generally any Human-Machine interface making it possible to communicate information to a user using the device 100. This screen 53 may or may not be touch-sensitive.

[0113] In practice, the processing unit 40 and the control unit 51 may be two separate calculation modules or a single calculation module, or be the same element performing the functions of the processing unit 40 and the control unit 51.

[0114] Optionally, the device 100 comprises a device for adjusting the orientation and / or position of said sample holder 20 to adjust an orientation of said sample holder 20 relative to the X-ray source 10 according to at least one rotation angle and / or to adjust a position of said sample holder 20 relative to the X-ray source 10 along at least one spatial direction. Here, the at least one spatial direction corresponds to a translation of said sample holder 20 relative to the X-ray source 10, i.e. a translation along the z axis. Optionally, the device for adjusting the orientation and / or position of the sample holder 20 makes it possible to move the sample in the xy plane, along the x axis and / or the y axis.

[0115] Typically, the position and / or orientation adjustment device comprises a mobile support 60 arranged to move the sample 1 along the translation axis (z axis) via the sample holder 10 and modify its position by translation along the axes transverse to the z axes, here the x, y axes and / or its orientation by rotation around the x, y and / or z axes.

[0116] Of course, this mobile support 60 can be moved / oriented manually or automatically by using at least one motor configured to move the mobile support and / or modify the orientation of the mobile support.

[0117] Typically, this movable support 60 is controlled by the control circuit 50 in order to obtain the desired position and orientation.

[0118] It is understood that to obtain the desired magnification, it is sufficient to position the sample holder 20 relative to the X-ray source 10 and the X-ray image detector 30. To do this, it is sufficient to manually or automatically adjust one of the distances d1, d2. Preferably, one of these distances can be adjusted using the human-machine interface. In this case, the user enters, for example, the distance d1 (corresponding here to an input data item) into the human-machine interface and the control circuit automatically moves the sample holder 20 via the mobile support 60.

[0119] In the case where the mobile support 60 can also apply a rotation to the sample, the processing unit 40 can be configured to synthesize or reconstruct a three-dimensional phase contrast image of said sample.

[0120] For example, Figure 5 illustrates an example of a three-dimensional phase contrast image reconstructed by the device according to the first embodiment.

[0121] Typically for this, this phase contrast image can be determined by reconstructing at least three phase contrast images of said sample obtained under three different angular orientations and using a tomography or tomosynthesis method.

[0122] In practice, it is sufficient to irradiate an initial profile of the sample (for example the face oriented in the P2 plane) and to reconstruct a first image by phase contrast from the flux transmitted by the sample in this configuration. Then, for the second image, it is sufficient to rotate the sample holder via the mobile support 60 by at least one angle greater than zero degrees, preferably less than 1 degree, for example equal to 0.9 degrees and to repeat the irradiation and the reconstruction of the second image by phase contrast. The selected angle can be entered by an operator as input data in the human-machine interface described above. Similarly, for the third image, the sample is rotated again, for example by 0.9 degrees relative to the position of the sample used for the second image and to repeat the irradiation and the reconstruction of the third image by phase contrast.Typically, 300 to 400 images are taken while circling the object. The tomography algorithm then compiles these images and processes them to reconstruct a three-dimensional phase contrast image.

[0123] Optionally, the device 100 may also comprise a device for adjusting the position and / or orientation 61, respectively 62 of the X-ray source and / or the image detector operating in a similar manner to the device for adjusting the orientation and / or position of the sample holder 20. Thus, in this case, it is understood that the X-ray source 10 and / or the image detector 30 are mounted on a mobile support 61, respectively 62 as described above.

[0124] However, preferably, the X-ray source 10 is fixed (i.e. not mobile). Thus, to obtain the desired magnification, only the sample holder 20 and optionally the X-ray image detector 30 can be mobile along the z axis by means of a mobile support 60, 61 as described above.

[0125] Optionally, the device 100 comprises a support 70 on which are mounted at least the X-ray source 10, the sample holder 20 and the X-ray image detector 30. Typically here, this support 70 comprises a rail 71 oriented parallel to the propagation axis A of the X-ray source, that is to say vertically relative to the ground. On this rail 71 are mounted the source 10, the mobile support 60 of the sample holder 20 (if present) or directly the sample holder 20, and the image detector 30 or the mobile support 61 of the image detector 30 (if present).

[0126] As illustrated in Figure 1, the support 70 also includes a holding element 72 (e.g., a holding plate) oriented perpendicular to the rail. 71 and allowing the device 100 to be stabilized.

[0127] Optionally, the device 100 also comprises a device 80 for holding the support on the ground. In practice, this holding device 80 is fixed to the support 70 (here by means 72 for holding the support 70). In a preferred embodiment, the holding device 80 comprises casters 81 in contact with the ground, here distributed along the surface of the holding element 72, in order to be able to easily move the device 100. In a variant, the holding device 80 may comprise feet in contact with the ground.

[0128] Figure 6 illustrates a second embodiment of a device 200 according to the present invention. The device 200 comprises all the elements of the device 100 described above.

[0129] Unlike the device 100, the device 200 comprises a portable housing 90 associated with the support 70 and accommodating at least the X-ray source 10, the sample holder system 20, the X-ray image detector 30.

[0130] As illustrated, the bracket 70 is attached to the lower sides of the housing 90, for example by means of screws. It is understood that in this case, the holding means 72 of the support 70 may correspond to an inner face of the housing 90 or be fixed to this same inner face of the housing 90.

[0131] Here, the holding device 80 is attached directly to the support 70.

[0132] The housing 90 may comprise closable opening elements in order to access the various elements included in the housing 90. Typically, the closable opening elements may be plates fixed by screws to the housing 90 or closable doors and / or held by screws or drawers. Such openings also make it possible to place the sample 1 in the sample holder system 20. In this embodiment, the sample holder system 20 comprises several sample holders, for example here five sample holders 21, 22, 23, 24, 25 arranged one above the other along the z axis. In this example, the X-ray source 10 and the image detector 30 are fixed, for example located at a distance d2 of 150 cm from each other. Each sample holder 21, 22, 23, 24, 25 comprises, for example, a support plate transparent to X-rays, for example made of PEEK, PMMA.Each sample holder 21, 22, 23, 24, 25 is located at a different distance d1 from the X-ray source 10. For example, the sample holder 21 is located at a distance d1 of 7.5 cm corresponding to a magnification of the X-ray image of 20, the sample holder 22 is located at a distance d1 of 10 cm corresponding to a magnification of the image of. X-rays of 15, the sample holder 23 is located at a distance d1 of 15 cm corresponding to a magnification of the X-ray image of 10, the sample holder 24 is located at a distance d1 of 20 cm corresponding to a magnification of the X-ray image of 7.5 and the sample holder 25 is located at a distance d1 of 25 cm corresponding to a magnification of the X-ray image of 6. In this way, each sample holder 21, 22, 23, 24, 25 makes it possible to obtain an X-ray image of different magnification, without requiring a system for moving the source 10, the detector 30 or the sample holder 20.

[0133] In this embodiment, it can be seen that the screen 53 and the keyboard of the control circuit 50 are elements external to the housing 90. Similarly, it is understood that the control unit 50 can be a computer positioned outside the housing 90 and having a screen 53 serving as a human-machine interface.

[0134] The device 200 comprises shielded walls 91 or shielded plates fixed to the walls of the device 200. Typically these shielded walls or shielded plates are made of metal, for example lead or tungsten. Such an arrangement makes it possible to limit the propagation of X-rays outside the housing 90, thus ensuring better safety for an operator using the device 200.

[0135] Process

[0136] A first example of a 300 X-ray imaging method using at least phase contrast imaging will be written using Figure 7.

[0137] The method illustrated in Figure 7 is implemented by the device 100 or the device 200 described above.

[0138] The method 300 comprises a step E1 of emitting the flux 11 of X-rays from an emission spot of the X-ray source 10. As specified above, the X-ray emission spot has a diameter D of between 1 pm and 20 pm and is emitted in the direction of the sample 1 placed on the sample holder 20.

[0139] Here, the X-ray flux 11 propagates in free field towards sample 1 and presenting an initial wavefront.

[0140] The method 300 also comprises a step E2 of detecting the X-ray image via the X-ray image detector. The latter is spaced from the X-ray source 10 by a distance d2 greater than or equal to 80 cm and less than or equal to 1.6 m (preferably between 80 cm and 1.5 m).

[0141] The X-ray image detector is in this step arranged to capture the flow 11 of X-rays having passed through said sample 1. This flow has a wavefront transmitted by the sample 1.

[0142] As described above, in this step, the sample is positioned between the X-ray source 10 and the X-ray image detector 30 so that the image acquired has an optical magnification greater than or equal to 8 and less than 20, preferably between 8 and 16 (advantageously between 8 and 15) to obtain better performance in terms of contrast and spatial resolution.

[0143] The method 300 also comprises a step E3 of processing the image acquired by the image detector to determine an image of the phase shift and reconstruct, from this image of the phase shift, a phase contrast image of said sample.

[0144] The present invention is in no way limited to the embodiments described and shown, but those skilled in the art will be able to provide any variation in accordance with the invention.

Claims

CLAIMS 1. X-ray imaging device (100, 200) using at least phase contrast imaging, said device (100, 200) comprising: an X-ray source (10) arranged to emit a flux (11) of X-rays from an emission spot having a diameter of between 1 pm and 20 pm, the flux (11) of X-rays being emitted towards a sample (1) arranged on a sample holder (20, 21, 22, 23, 24, 25), said flux (11) of X-rays propagating in a free field towards said sample (1);an X-ray image detector (30), said sample (1) being positioned between the X-ray source (10) and the X-ray image detector (30), the X-ray image detector (30) being a two-dimensional image detector, the X-ray image detector (30) being spaced from said X-ray source (10) by a distance greater than or equal to 80 cm and less than or equal to 1.6 m and arranged to capture the flux (11) of X-rays having passed through said sample (1) and to form an intensity image of said flux of X-rays; a processing unit (40) configured to determine, from the detected intensity image, a phase contrast image of the sample (1), said device (100, 200) having an optical magnification greater than or equal to 8 and less than 20.; 2. Device according to claim 1, in which the optical magnification is between 8 and 16.

3. Device according to any one of claims 1 to 2, in which the flux of X-rays propagating between the sample holder (20, 21, 22, 23, 24, 25) and the X-ray detector is in free propagation.

4. Device according to any one of claims 1 to 3, wherein said X-ray source has an axis of propagation of the X-ray flux, the propagation axis being oriented vertically relative to the ground.

5. Device according to any one of claims 1 to 4, in which the flux of X-rays emitted has a power greater than or equal to 5 W and less than or equal to 100 W at the output of said X-ray source.

6. Device according to any one of claims 1 to 5, wherein the X-ray image detector (30) comprises an array of pixels having a first spatial dimension and a second spatial dimension, the first spatial dimension being greater than 10 cm and the second spatial dimension being greater than 10 cm.

7. Device according to any one of claims 1 to 6, in which the pixel matrix of the X-ray image detector comprises square pixels with a side length less than or equal to 100 pm.

8. Device according to any one of claims 1 to 7, wherein the processing unit (40) is configured to determine, by using a contour detection algorithm on said phase contrast image, the presence of an object in said sample, and a morphology of each detected object.

9. Device according to any one of claims 1 to 8 comprising a device for adjusting the orientation and / or position of the sample holder (20) to adjust an orientation of the sample holder (20) relative to the X-ray source according to at least one angle of rotation and / or to adjust a position of the sample holder (20) relative to the X-ray source along at least one spatial direction, said at least one spatial direction corresponding to a translation of said sample holder relative to the X-ray source.

10. The device of claim 9, wherein said device is configured to reconstruct a three-dimensional phase contrast image of said sample from at least three phase contrast images of said sample using a tomosynthesis reconstruction method.

11. Device according to any one of claims 1 to 10 comprising a plurality of sample holders (21, 22, 23, 24, 25) arranged between the source (10) and the image detector (30), each sample holder of the plurality of sample holders (21, 22, 23, 24, 25) being located at a distinct distance from the X-ray source (10).

12. Device according to any one of claims 1 to 11 comprising at least one of the following elements: a support on which are mounted at least the X-ray source, the sample holder and the X-ray image detector, a portable housing associated with the support and accommodating at least the X-ray source, the sample, the X-ray image detector, a device for holding the support on the ground.

13. X-ray imaging method using at least phase contrast imaging, said method comprising the following steps: emission (E1) of a flux (11) of X-rays by an X-ray source (10) from an emission spot having a diameter of between 1 pm and 20 pm, the flux (11) of X-rays being emitted towards a sample (1) arranged on a sample holder (20, 21, 22, 23, 24, 25), said flux (11) of X-rays propagating in a free field towards said sample (1); detection (E2) by means of an X-ray image detector (30) spaced from said X-ray source (10) by a distance greater than or equal to 80 cm and less than or equal to 1.6 m, of the X-ray flux (11) having passed through said sample (1) to form an intensity image of the X-ray flux, said sample (1) being positioned between the X-ray source (10) and the X-ray image detector (30) so that the acquired X-ray flux intensity image has an optical magnification greater than or equal to 8 and less than 20; processing (E3) of the intensity image of the X-ray flux acquired by the image detector to determine, from this X-ray image, a phase contrast image of the sample.

Images