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 flow (11) of X-rays towards a sample (1); - 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 and arranged to capture the flow (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 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 in women and also the leading cause of cancer death in women (685,000 deaths in 2020 worldwide), ahead of lung and colorectal cancers. It represents one in four cancer incidents in 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 mammographic 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] The analysis of microcalcifications is currently mainly carried out in pathology departments on tissue samples taken during macrobiopsies of the patient's breast. Pathologists therefore carry out pathological studies by optical microscopy on these samples. These analyses by optical microscopy require sample preparation which is time-consuming, expensive and delays obtaining results.

[0007] Following the collection 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 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 of the fact 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 may lead to errors due to the low spatial resolution of these images.

[0010] On the one hand, it is desirable to provide an imaging apparatus making it possible to obtain images of samples, in particular breast macrobiopsy, with better spatial resolution. On the other hand, it is desirable to allow an analysis of the images thus obtained of samples, for example of microcalcifications detected in the images of breast macrobiopsies, 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 makes it possible to reconstruct an image of the sample having 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 magnification is between 8 and 15, and preferably ranging from 10 to 14, which makes it possible to obtain 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 relative 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 (0.12 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 of 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 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 allows for a high-resolution reconstructed phase contrast image.

[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 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 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 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 30; - 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] Preferably, the optical magnification is between 8 and 15, which makes it possible to obtain better results 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 to be carried out.

[0044] In 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 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] [Fig.3] illustrates an example of a reconstructed phase contrast image and 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 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] [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 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 μm and 20 μm 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 the output diameter as its generator 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 flux of X-rays propagate 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 [Fig. 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 [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 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 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 between 40 kV and 80 kV, with a cathode current intensity greater than 100pA for a power greater than 5W.

[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] It is noted 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.

[0062] As illustrated in [Fig.l], 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 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 the sample 1 at a dose between 400 pSv and 650 pSv. Such a range makes it possible to avoid 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 dl comprised 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 flux 11 of X-rays propagates in free field from the source 10 of X-rays towards the sample 1 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 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 make it possible to define an optical magnification of the device 100 as being the ratio between the distance dl 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 between 8 and 15, or even between 8 and 14, 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. In other words, the X-ray image detector 30 is arranged to capture the total flux 11 of X-rays 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.

[0073] Advantageously, the X-ray image detector 30 is a flat screen detector (fiat panel, in English) with a detection surface of at least 10cm x 10cm. 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 y spatial 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 matrix 32 are all identical and each have 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 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 matrix 32 is made of square-shaped pixels with a side length of 49.5 pm. The pixel matrix 32 of the X-ray image detector 30 comprises 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 captured flux of X-rays, an X-ray image, hereinafter called an intensity image.

[0081] As illustrated in [Fig. 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, the small changes in the direction of propagation cause variations in intensity resulting in an enhancement of the internal and external contours or edges of sample 1, where the lateral gradients of the X-ray phase are the most significant.

[0084] For example, [Fig.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, [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 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 [Fig.2] has a main curved part 5, representing the intensity of the X beam passing through the sample framed by two edges 6 in which the intensity signal here 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 [Fig.2], enhanced edge effects are visible in the image in intensity. 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 variations in intensity which are used to obtain 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 the 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 ( xy, z ) = 1 + A ( xy, 0 ) where 1 is the intensity of the detected radiation, / . the wavelength of the X-rays and <e>(x,y) the background phase studied on which the two-dimensional Laplace operator A acts in the xy plane.

[0088] The measured intensity is not here a direct measurement 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 the 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 different 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 [Fig.l] is at least connected to the X-ray image detector 30 described above. By connected, it is meant that the unit of 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 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 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, 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 phase of the signal. Here this phase contrast image is a free-propagation 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 30, and preferably 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] [Fig. 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 11 of 10 pm for the left image and respectively 30 pm for the right image. Here, by increasing the size of the emission spot, the spatial coherence condition is degraded, as a result, the intensity image associated with the left image has only a curved part and does not does not present edge enhancement unlike [Fig.2]. Therefore, 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 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 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 manner similar 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] [Fig.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 [Fig.4] corresponds to the same microcalcification of the same portion of breast of the same patient. The three columns of images in [Fig.4] here correspond 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 size 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 [Fig.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 [Fig. 4] shows for each case that the phase contrast image has better contrast and better resolution compared to the absorption image obtained. For example, in the pair of images (4A, 4D), an object 91 opaque to X-rays is detected in the absorption image 4A and it is observed on the phase contrast image 4D that the contours of this object 91 are irregular. In the example of the pair of images (4B, 4E), two objects 92, 93 opaque to X-rays are detected in the absorption image and it is observed on 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 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 presenting asperities or hollows. The radiology practitioner or doctor can then associate such an object shape with a low risk of pathology or with a risk of specific pathology.

[0108] It is understood that the resolution and contrast of the phase contrast image being better than those of the absorption image, the detection and / or sorting from the phase contrast image is more precise and therefore makes it possible to obtain better results.

[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 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. 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, [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, 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 plane P2) 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 turn 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 again rotated, 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] Nevertheless, 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 holder sample 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 [Fig. 1], the support 70 also comprises a holding element 72 (for example a holding plate) oriented perpendicular to the rail 71 and making it possible to stabilize the device 100.

[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] [Fig.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 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 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 fixed 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 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 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 may be a computer positioned outside the housing 90 and having a screen 53 serving as a man-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 guaranteeing better safety for an operator using the device 200.

[0135] Method

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

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

[0138] The method 300 comprises a step E1 of emission of 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 flux 11 of X-rays propagates in free field towards the 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 flux 11 of X-rays 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] The method 300 also comprises a step E3 of processing 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 shown, but those skilled in the art will be able to provide any variant in accordance with the invention.< / e>

Claims

Claims

1. An 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 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.;

2. A device according to claim 1, wherein the optical magnification is between 8 and 15.

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, 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.

6. Device according to any one of claims 1 to 5 comprising a device for adjusting the orientation and / or position of the sample holder (20) for adjusting an orientation of the sample holder (20) by relative to the X-ray source according to at least one rotation angle and / or to adjust a position of the sample holder (20) relative to the X-ray source according to 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.

7. The device of claim 6, 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.

8. A device according to any one of claims 1 to 5 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).

9. Device according to any one of claims 1 to 8 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.

10. X-ray imaging method using at least phase contrast imaging, said method comprising the following steps: emission (El) 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 X-ray flux intensity image, 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 X-ray flux intensity image acquired by the image detector to determine, from this ray image; X, a phase contrast image of the sample.

Images