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

Abstract

The invention relates to an X-ray imaging device (100), said device (100) comprising: - an X-ray source (10) arranged to emit a flux (11) of X-rays towards a sample (1); - an X-ray image detector (30) spaced from said X-ray source (10) at 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); - a processing unit (40) configured to determine a phase-shift image, and to reconstruct, from this phase-shift image, a phase-contrast image of said sample, said device (100) having an optical magnification greater than or equal to 8 and less than 20. Figure for the abstract: Fig. 1

Description

Title of the invention: X-ray imaging device and method using at least phase-contrast imaging. Technical field of the invention

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

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

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

[0004] Breast microcalcifications are calcium deposits in breast tissue and appear as small, bright spots on conventional mammogram 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] The analysis of microcalcifications to distinguish their types is very useful for discerning the characteristics of breast lesions and thus improving the early diagnosis of breast cancer.

[0006] Today, microcalcification analysis is primarily performed in pathology departments on tissue samples obtained during breast biopsies. Pathologists then conduct pathological studies on these samples using optical microscopy. These optical microscopy analyses require sample preparation that is time-consuming, costly, and delays the availability of results.

[0007] Following the taking of a macrobiopsy, the practitioner uses a specimen radiography device to radiograph this sample. However, to date, commercially available specimen radiography systems are based on X-ray absorption imaging techniques provide images with low spatial resolution. X-ray absorption imaging measures the differences in an object's opacity to X-rays, caused by inhomogeneity in terms of material or density. These devices are functional because they allow for the acquisition of absorption images of the sample. X-ray absorption imaging is appropriate when the objects being studied are made of materials with significant absorption differences.

[0008] However, existing specimen radiography devices only allow for verification that the samples contain the detected microcalcifications before they are sent to the pathology department. These devices do not currently allow for the analysis of the detected microcalcifications or for classifying them as benign or malignant.

[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 capable of obtaining images of samples, particularly breast macrobiopsies, with improved spatial resolution. On the other hand, it is desirable to enable the analysis of these sample images, for example, of microcalcifications detected in breast macrobiopsy images, independently of histopathological analysis by optical microscopy. Presentation of the invention

[0011] In order to overcome the aforementioned drawbacks of the prior 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 an X-ray flux from an emission spot having a diameter between 1 pm and 20 pm, the X-ray flux being emitted towards a sample placed on a sample holder, said X-ray flux 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 makes it possible to reconstruct an image of the sample with high contrast and high spatial resolution in 2D.

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

[0015] In one embodiment, the magnification is between 8 and 15, and preferably from 10 to 14, which allows for better results in terms of contrast and resolution.

[0016] In one embodiment, the X-ray flux propagating between the sample holder and the X-ray detector is in free propagation.

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

[0018] In one embodiment, the emitted X-ray flux has a power greater than or equal to 5 W at the output of said X-ray source.

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

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

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

[0022] In one embodiment, the X-ray image detector comprises a pixel matrix 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 matrix 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.

[0025] The combination of detector size and pixel size makes it possible to obtain a phase-contrast image reconstructed at high resolution.

[0026] Preferably, the square pixels have a side length ranging from 30 pm to 60 pm.

[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 objects 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 includes 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 carried out synchronously.

[0031] In one embodiment, the device includes an adjustment device for 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 angle of rotation 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 elements: - 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 unit associated with the support and housing at least the X-ray source, the sample, and the X-ray image detector, -- a device for securing the support to the ground.

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

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

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

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

[0039] The invention also proposes an X-ray imaging method using at least phase-contrast imaging, said method comprising the following steps: - emission of an X-ray flux by an X-ray source from an emission spot having a diameter between 1 pm and 20 pm, the X-ray flux being emitted towards a sample placed on a sample holder, said X-ray flux propagating in a free field towards said sample; - detection, by means of an X-ray image detector spaced from said X-ray source at 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 intensity image of the X-ray flux acquired has an optical magnification greater than or equal to 8 and less than 30; - processing 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 said sample.

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

[0041] Preferably, the optical magnification is between 8 and 15, which allows for better results in terms of contrast and resolution.

[0042] Of course, the various features, variants, and embodiments of the invention can be combined in various ways, provided they are not incompatible or mutually exclusive. Detailed description of the invention

[0043] The following description, with reference to the attached drawings, given by way of non-limiting examples, will make it clear what the invention consists of and how it can be implemented.

[0044] On the attached drawings:

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

[0046] [Fig.2] is a schematic cross-sectional representation of an image of a phase shift determined by a processing unit of the device according to the first embodiment;

[0047] [Fig.3] illustrates an example of a reconstructed phase contrast image and an absorption image by the device according to the first embodiment;

[0048] [Fig.4] illustrates a series of absorption images (4A, 4B, 4C) of different spots visible on the absorption images obtained with the device 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] [Fig.5] illustrates another example of a three-dimensional phase-contrast image reconstructed by the device according to the first embodiment;

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

[0051] [Fig.7] is a schematic representation of an X-ray imaging method according to the present disclosure.

[0052] Device

[0053] A first embodiment of an X-ray imaging device using at least phase contrast imaging will now be described using [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 an X-ray flux 11 from an emission spot (or luminous spot) having a diameter D between 1 pm and 20 pm at the output of the X-ray source 10. The diameter D of the emission spot (focal spot) is the minimum diameter of the X-ray flux 11. 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 that achieves a certain spatial coherence, which allows, as will be described below, the determination of 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 about a propagation axis A, having as its generatrix the exit diameter and having a vertex angle or opening angle at the exit 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 towards a sample 1. In other words, the X-ray flux 11 at the exit 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 allows the total surface of an X-ray image detector of the device 100, which will be described below, to be illuminated.

[0057] As illustrated in [Fig. 1], the X-ray flux 11 emitted by said X-ray source 10 has a propagation axis A oriented vertically with respect to the ground. In other words, the propagation axis A is parallel to the z-axis of the orthonormal coordinate system shown in [Fig. 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 X-ray flux 11 at a power ranging from a few watts to about ten watts, for example, 5 W. This X-ray flux is emitted here at energies between 10 keV (corresponding to a wavelength of 0.12 nm) and 80 kV (corresponding to a wavelength of 0.015 nm), preferably between 20 keV and 80 keV for a cathode current greater than 100 pA. In general, the anode of the X-ray source comprises at least one heavy material, for example, at least one of the 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 of between 40 kV and 80 kV, with a cathode current intensity greater than 100 pA for a power greater than 5W.

[0059] The X-ray flux 11 propagates in free space from the X-ray source 10 to a sample holder 20 within the device 100. Here, "free space" means 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] It is noted that the X-ray flux has an initial wavefront representing its propagation at the source output.

[0061] The sample holder 20 is used to hold a sample 1. In this case, in particular, the sample holder 20 is adapted to collect a breast macrobiopsy sample for obtaining 2D radiographic images. The sample is obtained, for example, by taking a sample of human biological tissue, for example a biopsy of flesh from a part of a patient's breast. For this purpose, device 100 can be used to detect microcalcifications present in sample 1.

[0062] As illustrated in [Fig. 1], the sample 1 is positioned within the emission cone of the X-ray source 10. In other words, the sample 1 is completely 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 of 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 sample 1 with a dose between 400 pSv and 650 pSv. This range avoids damaging sample 1 while generating enough signal for rapid X-ray image acquisition.

[0065] According to this disclosure, the sample holder 20 is separated from the X-ray source 10 by a distance dl 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 dl is determined between an emission plane PI 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 PI of the X-ray source 10 and perpendicular to the propagation axis A of the X-ray source 10.

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

[0067] The device 100 also includes the X-ray image detector 30 positioned opposite 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. Therefore, the X-ray flux 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 dl 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 dl and the distance d2 allow us to define an optical magnification of the device 100 as the ratio between the distance dl and the distance d2.

[0069] In particular, here the optical magnification of 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 between 8 and 15, or even between 8 and 14, in order to obtain a 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, in this case specifically to the emission cone of the X-ray source 10 used. 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 an array of cesium iodide (Csl) crystals coupled to an array of CMOS detectors. The X-ray image detector 30 thus comprises a pixel array, each pixel having a side length less than or equal to 100 pm.

[0073] Advantageously, the X-ray image detector 30 is a flat panel detector with a detection area of ​​at least 10 cm x 10 cm. The X-ray image detector 30 has an active face 31, oriented towards the X-ray source 10 and comprising a pixel matrix 32 in which each pixel is configured to capture a portion of the X-ray flux 11 passing through the sample 1. The image detector 30 thus records an intensity image of the X-ray flux that has 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 y-axis. Advantageously, the pixels of the pixel matrix 32 are arranged in rows and columns.

[0075] Without limitation, the first and second spatial dimensions are each greater than 10 cm; in particular, here the first spatial dimension is 22.8 cm and the second spatial dimension is 29.2 cm. Advantageously, the first and second spatial dimensions are each less than 40 cm, in order to limit the overall size of the device 100.

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

[0077] The pixels of the pixel matrix 32 are all identical and each has a first dimension, oriented parallel to the first spatial dimension of the pixel matrix 32, and a second dimension, perpendicular to the first dimension and oriented parallel to the second spatial dimension of the pixel matrix. The first and second dimensions are each less than or equal to 100 pm and preferably between 40 pm and 60 pm. Here, typically, the pixel matrix 32 is made of square pixels with sides of 49.5 pm. The pixel matrix 32 of the X-ray image detector 30 has a number of pixels ranging from 4000 to 6000 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 X-ray flux 11 passing through the sample 1. It is understood that the X-ray flux 11 captured by the X-ray image detector 30 has a wavefront.

[0080] This X-ray flux 11 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 X-ray flux having passed through the sample 1. As a result, the X-ray image detector 30 is configured to detect, from the captured X-ray flux, an X-ray image, referred to hereafter as an intensity image.

[0081] As illustrated in [Fig. 1], no optical element is positioned on the optical path of the X-ray flux 11 passing through the sample 1. Thus, the X-ray flux 11 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 a distance d2.

[0083] Indeed, when a distorted wavefront propagates sufficiently far, small changes in the direction of propagation cause variations in intensity leading to an improvement 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, [Fig. 2] illustrates a cross-sectional example of an intensity image of a sample detected from the X-ray flux 11 captured by the X-ray image detector 30. More precisely, [Fig. 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 in this example is a weakly absorbing object in the energy range defined above; for example, it corresponds to a breast macrobiopsy sample.

[0085] Here, for example, the intensity image of [Fig. 2] has a main convex 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 of a peak which correspond to the inner and outer edges of the sample. These edges 6 are, in the following, called edge enhancement effect.

[0086] As illustrated in [Fig. 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 exploited to enhance 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's diffraction theory. From this perspective, the intensity distribution on the image detector 30 is the result of the interference of waves with a variable phase shift as they pass through the sample under study. At a 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: I(x, y, z) = 1 + where 1 is the intensity of the detected radiation, X the wavelength of the X-rays and <b(x,y) la phase de fonde étudiée sur laquelle l'opérateur de Laplace A bidimensionnel agit dans le plan x-y.

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

[0089] In practice, in device 100, the two edges depend on the optical magnification of device 100 described above. Thus, it is understood that the optical magnification of device 100 is adapted 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 includes a processing unit 40.

[0091] A processing unit is defined as any computing unit, processor, computer, or other electronic element that enables the execution of a series of commands and / or calculations. This processing unit 40 typically comprises a processor, memory, and various input and output interfaces.

[0092] Thanks to 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 allows to reconstruct an image by phase contrast from the intensity image acquired by the image detector 30.

[0094] The processing unit 40 illustrated in [Fig. 1] is at least connected to the X-ray image detector 30 described above. By connected, we mean that the processing unit 40 is arranged to communicate with another element, for example, by being configured to transmit and / or receive data from that element (here, for example, via a wired connection). In this case, the processing unit 40 is configured to determine a phase-shift image from the intensity image captured by the X-ray detector 30, this intensity image being representative of the wavefront of the transmitted X-ray flux 11. The processing unit 40 is configured to reconstruct, from this enhanced-edge intensity image, 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 using phase extraction techniques known to those skilled in the art, for example as described in the document Burvall, A., Lundstrôm, U., 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 convex 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 especially its magnification, allows for the precise visualization of the object's raised edges in the intensity image. Conversely, at lower magnifications, particularly below 8, these edges are barely or not at all visible in the intensity X-ray image. Consequently, the intensity X-ray image obtained with a magnification greater than or equal to 8 and less than 30, and preferably between 8 and 15, is much more precise and allows for the extraction of a high-contrast, 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 needed 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 dl of 200 mm and distance d2 of 3000 mm), for an X-ray flux emission spot diameter of 10 pm for the left image and 30 pm for the right image. Here, by increasing the emission spot size, the spatial coherence condition is degraded; consequently, the intensity image associated with the left image shows only a convex portion and does not exhibit edge enhancement, unlike [Fig. 2]. Therefore, for this left image, the phase regime is not obtained at the source-detector distance d2 of 300 cm.

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

[0102] The processing unit 40 is optionally configured to determine, by using a phase-contrast edge detection algorithm on said 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 edge detection algorithm can be based on at least the following algorithms: - a 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 the breast of different patients obtained by absorption radiography (noted Abs.), and, at the bottom, three X-ray images (4D, 4E, 4F) of the same microcalcifications in the same portions of the breast obtained by phase contrast radiography (noted C. Ph.). Each column of images in Figure 4 corresponds to the same microcalcification in the same portion of the breast of the same patient. The three columns of images in Figure 4 correspond to different patients. The three absorption images 4A, 4B, 4C are obtained with 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 X-ray source spot is lOOp and in the second configuration for phase contrast images, the diameter of the . Source 11b is 10p. Each image allows visualization of one or more X-ray opaque elements 91, 92, 92, 94, 95, for example, breast microcalcifications. As illustrated in [Fig. 4], different objects are extracted from the phase-contrast image and the absorption image.

[0106] However, a comparison of the absorption and phase-contrast images in [Fig. 4] shows that, in each case, the phase-contrast image exhibits better contrast and resolution compared to the absorption image. For example, in the image pair (4A, 4D), an object 91 opaque to X-rays is detected in the absorption image 4A, while the phase-contrast image 4D shows 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, while the phase-contrast image shows that the contours of these two objects 92, 93 are regular, in the shape of a rhombus or diamond.In the example of the image pair (4C, 4F), two spots 94, 95 partially opaque to X-rays are detected in the absorption image, and these two spots 94, 95 are observed to be diffuse and have irregular contours, for example, a filamentary 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, according to 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 asperities or depressions. The radiologist or physician can then associate a particular object shape with a low risk of pathology or with 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 for better results.

[0109] Optionally, the device 100 includes 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 includes a control unit 51 arranged to control the various 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, we mean any computing unit, processor, computer, or other electronic element capable of implementing a sequence of commands and / or calculations. This control unit 51 typically includes a processor, memory, and various input and output interfaces. Typically, the control unit 51 may include 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. By way of exception, the device 100 includes 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 enabling the communication of information to a user operating 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 can be two separate calculation modules or a single calculation module, or be a single element performing the functions of the processing unit 40 and the control unit 51.

[0114] Optionally, the device 100 includes an orientation and / or position adjustment device for said sample holder 20 to adjust the orientation of said sample holder 20 relative to the X-ray source 10 by at least one angle of rotation and / or to adjust the 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 orientation and / or position adjustment device for the sample holder 20 allows the sample to be moved in the xy-plane, along the x-axis and / or the y-axis.

[0115] Typically, the position and / or orientation adjustment device includes a movable support 60 arranged to move the sample 1 along the translation axis (z-axis) via the sample holder 10 and to modify its position by translation along the axes transverse to the z-axis, 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 change the orientation of the mobile support.

[0117] Typically, this mobile 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. This can be done manually or automatically. One of the distances dl, d2. Preferably, one of these distances can be set using the human-machine interface. In this case, the user enters, for example, the distance dl (corresponding here to an input value) into the human-machine interface and the control circuit automatically moves the sample holder 20 via the movable 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, [Fig.5] illustrates an example of a three-dimensional phase-contrast image reconstructed by the device according to the first embodiment.

[0121] Typically for this purpose, 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 suffices to irradiate an initial profile of the sample (for example, the face oriented in plane P2) and reconstruct a first phase-contrast image from the flux transmitted by the sample in this configuration. Then, for the second image, it suffices to rotate the sample holder via the movable support 60 by at least an angle greater than zero degrees, preferably less than 1 degree, for example, 0.9 degrees, and repeat the irradiation and reconstruction of the second phase-contrast image. The selected angle can be entered by an operator as input data into 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 sample position used for the second image, and the irradiation and reconstruction of the third phase-contrast image are repeated.Typically, between 300 and 400 images are taken by rotating around 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 include a position and / or orientation adjustment device 61, respectively 62 of the X-ray source and / or image detector operating in a similar manner to the orientation and / or position adjustment device of the sample holder 20. Thus in this case, it is understood that the X-ray source 10 and / or image detector 30 are mounted on a movable support 61, respectively 62 as described above.

[0124] However, preferably, the X-ray source 10 is fixed (i.e., non-moving). Thus, to obtain the desired magnification, only the sample holder 20 and optionally the X-ray image detector 30 may be movable along the z-axis by means of a movable support 60, 61 as described above.

[0125] Optionally, the device 100 includes 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, this support 70 includes a rail 71 oriented parallel to the propagation axis A of the X-ray source, i.e., vertically with respect to the ground. On this rail 71 are mounted the source 10, the movable support 60 of the sample holder 20 (if present) or the sample holder 20 itself, and the image detector 30 or the movable support 61 of the image detector 30 (if present).

[0126] As illustrated in [Fig. 1], the support 70 also includes a retaining element 72 (for example a retaining plate) oriented perpendicularly to the rail 71 and enabling the device 100 to be stabilized.

[0127] Optionally, the device 100 also includes a retaining device 80 for the support on the floor. In practice, this retaining device 80 is attached to the support 70 (here by means of the retaining element 72 of the support 70). In a preferred embodiment, the retaining device 80 includes casters 81 in contact with the floor, here distributed along the surface of the retaining element 72, so as to allow the device 100 to be moved easily. In a variant, the retaining device 80 may include feet in contact with the floor.

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

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

[0131] Here, the retaining device 80 is fixed directly to the support 70.

[0132] The housing 90 may include closable opening elements to access the various components within the housing 90. Typically, the closable opening elements may be plates fixed to the housing 90 by means of screws, or doors that can be closed and / or held closed by means of screws, or even drawers. Such openings also allow the sample 1 to be placed in the sample holder system 20. In this embodiment, the sample holder system 20 comprises several sample holders, for example, 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 include for example a radio-transparent support plate, for example made of PEEK, PMMA. Each sample holder 21, 22, 23, 24, 25 is located at a different distance dl from the X-ray source 10. For example, the sample holder 21 is located at a distance dl of 7.5 cm corresponding to a magnification of the X-ray image of 20, the sample holder 22 is located at a distance dl of 10 cm corresponding to a magnification of the X-ray image of 15, the sample holder 23 is located at a distance dl of 15 cm corresponding to a magnification of the X-ray image of 10, the sample holder 24 is located at a distance dl 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 dl 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 at a 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 external elements 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 attached 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 limits the propagation of X-rays outside the enclosure 90, thus ensuring greater 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 with the aid of [Fig.7] will be written.

[0137] The method illustrated in [Fig.7] is implemented on device 100 or device 200 described above.

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

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

[0140] Method 300 also includes a detection step E2 of 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 X-ray flux 11 having passed through said sample 1. This flux 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 acquired image has an optical magnification greater than or equal to 8 and less than 30, preferably between 8 and 15 to obtain better performance in terms of contrast and spatial resolution.

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

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

Claims

1.

2.

3. Demands 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 an X-ray flux (11) from an emission spot having a diameter between 1 pm and 20 pm, the X-ray flux (11) being emitted towards a sample (1) disposed on a sample holder (20, 21, 22, 23, 24, 25), said X-ray flux (11) 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 X-ray flux (11) having passed through said sample (1) and to form an intensity image of said X-ray flux;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, in which the X-ray flux propagating between the sample holder (20, 21, 22, 23, 24, 25) and the X-ray detector is in free propagation, the emitted X-ray flux has a power between 5 W and 10 W at the output of said X-ray source and said image detector (30) comprising a pixel matrix 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 and the pixel matrix of the X-ray image detector (30) comprising square pixels of side length less than or equal to 100 pm. Device according to claim 1, wherein the optical magnification is between 8 and 15. Device according to any one of claims 1 to 2, wherein said X-ray source has a propagation axis of X-ray flux, the propagation axis being oriented vertically with respect to the ground.

4. Device according to any one of claims 1 to 3, wherein the processing unit (40) 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.

5. Device according to any one of claims 1 to 4 comprising an orientation and / or position adjustment device for the sample holder (20) to adjust an orientation of the sample holder (20) relative to the X-ray source by 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.

6. Device according to claim 5, 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.

7. Device according to any one of claims 1 to 4 comprising a plurality of sample holders (21, 22, 23, 24, 25) disposed 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).

8. Device according to any one of claims 1 to 7 comprising 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, a portable housing associated with the support and housing at least the X-ray source, the sample, the X-ray image detector, a device for securing the support to the ground.

9. An X-ray imaging method using at least phase-contrast imaging, said method comprising the following steps: emission (E1) of an X-ray flux (E1) from an X-ray source (E1) from an emission spot having a diameter between 1 pm and 20 pm, the X-ray flux (E1) being emitted in the direction of a sample (1) placed on a sample holder (20, 21, 22, 23, 24, 25), the emitted X-ray flux having a power between 5 W and 10 W at the output of said X-ray source, said X-ray flux (11) 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) at 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 intensity image of the acquired X-ray flux has an optical magnification greater than or equal to 8 and less than 20, the X-ray flux propagating between the sample holder (20, 21, 22, 23, 24, 25) and the X-ray detector is in free propagation,said image detector (30) comprising a pixel matrix 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, and the pixel matrix of the X-ray image detector (30) comprising square pixels with a side length less than or equal to 100 pm; 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