WO2025004047A1

WO2025004047A1 - A device for optical mammography using red and/or near-infrared in diffuse reflectance geometry with patient's adjustable positioning

Info

Publication number: WO2025004047A1
Application number: PCT/IL2024/050634
Authority: WO
Inventors: Pamela Alejandra Pardini; Nicolás Abel CARBONE; Daniela Ines IRIARTE; María Victoria Waks Serra; Juan Antonio Pomarico; Héctor Alfredo García; Demián Augusto VERA
Original assignee: DR EYAL BRESSLER Ltd; Bionirs; Uncpba Universidad Nacional Del Centro de la Provincia De Buenos Aires
Current assignee: DR EYAL BRESSLER Ltd; Bionirs; Uncpba Universidad Nacional Del Centro de la Provincia De Buenos Aires
Priority date: 2023-06-27
Filing date: 2024-06-27
Publication date: 2025-01-02
Anticipated expiration: 2025-12-27

Abstract

The present invention is directed to mammographic imaging device configured to analyze and detect inhomogeneities in breast tissue in a patient. The mammographic imaging device uses laser light in the red and/or near-infrared (NIR) in diffuse reflectance geometry.

Description

A Device for Optical Mammography Using red and/or Near-Infrared in Diffuse Reflectance Geometry with Patient's Adjustable Positioning

FIELD OF THE INVENTION

The present invention relates to the field of medical imaging and more specifically, to a mammographic imaging device with patient's adjustable positioning, for analysis, detection and classification of possible inhomogeneities in breast tissue that may be caused by different neoplastic pathologies, using near-infrared laser in diffuse reflectance geometry.

BACKGROUND OF THE INVENTION

It is well known that mammography may save lives if breast cancer is detected early on. For this purpose, there exist several devices for analyzing breast tissue and detecting inhomogeneities, should there be any.

The main drawback of known devices used for mammography is that they present a relatively low specificity and low sensitivity. Normal breast tissue may hide a tumor, which may not be perceived by such devices, which provides a diagnosis described as a false negative (low sensitivity). Furthermore, these devices may identify some abnormality that may seem to be a tumor but that may end up not being one, which is described as a false positive (low specificity).

Devices most widely used nowadays for detecting inhomogeneities in breast tissue or mammography use X-ray ionizing radiation, which prevents the continued use of the devices for monitoring evolution of disease due to radiation exposition. Furthermore, the devices usually imply patient's breasts being compressed, which is quite atraumatic experience for patients in general.

Due to the above, alternative devices to those traditionally used have been developed, such as those that use radiation with infrared wavelengths.

This kind of device allows for better disease monitoring, as well as regular checkups as frequently as the medical practitioner considers it necessary, since infrared radiation is non-ionizing and, thus, poses no risks for patients. The devices that employ infrared light may further be used in situations where X-rays are not recommended, for example for continuous monitoring, examination of pregnant

There exist several devices in the current state of the art that employ infrared light or radiation, among those, the device described in U.S. patent application 2002/045833 Al, directed to a diagnostic medical imaging device and, in particular, to a mammograph using a near-infrared laser as radiation source. The apparatus consists of a CCD sensors array disposed in the form of a ring wherein one line of measurements is taken at a time for each position of the ring; this means that it does not involve fullfield imaging but a series of data that must be appropriately processed in order to rebuild an image.

Additionally, patent application WO 2018/132908 Al is directed to a handheld device for scanning human tissue through diffusion optical spectroscopy that comprises means for emitting electromagnetic radiation at one or more wavelengths corresponding to absorption associated with one or more human-tissue constituents, means for detecting electromagnetic radiation and processing means for producing, in response to the received electromagnetic radiation, one or more images of the human tissue. However, linear CCD arrangements that measure luminous intensity line to line are used, besides being a slow process (limited by the speed at which the measuring head may be manually moved), subject to operation errors. Furthermore, this device does not produce a full 2D-image of the area to be explored in just one use.

Finally, U.S. patent application 2016/0139039 Al is directed to an imaging system that includes an infrared camera that is sensitive to light of wavelengths in the near-infrared region, a lighting unit that emits light beams having multiple wavelengths in an infrared region that includes the wavelengths to which the infrared camera is sensitive, and a control unit that controls capture of an image by the infrared camera and emission of a light beam by the lighting unit. However, large UED sources are used in this device, which prevents the obtention of in-depth information and only registers a map of the surface. Moreover, in the case of breasts, compression between plates is required.

Alongside the need for a device with a specific and sensitive imaging method that avoids compression of the breast to be analyzed, there is a need to substantially improve patient comfort during imaging procedure.

Therefore, there is long felt unmet need for a breast imaging device that would: (i) provide a specific and sensitive imaging method and that would allow for the production of full-field images of the area to be analyzed, at a high speed

(ii) avoid compression of the breast to be analyzed

(iii) allow comfortable patient positioning with adjustable mechanisms for patient positioning

(iv) allow suitable technician access for proper breast positioning as needed;

BRIEF DESCRIPTION OF THE INVENTION

Based on the foregoing, the present invention provides a mammographic imaging device [100] for analysis and detection of possible inhomogeneities in breast tissue [300] of a patient [200] using laser light in the red and/or near-infrared (NIR) in diffuse reflectance geometry.

For the purposes of this invention, expressions “laser light”, “light beams”, “laser light beams”, “NIR light”, “NIR light beams” and variations thereof will be used interchangeably, meaning in all cases coherent light beams emitted with red and/or near-infrared wavelength.

The object of the present invention is to disclose a mammographic imaging device [100] for analysis and detection of possible inhomogeneities in breast tissue [300] of a patient [200] using laser light in the red and/or near-infrared (NIR) in diffuse reflectance geometry, wherein the device comprises an inclined patient vertical support [102] with at least one transparent window [104] for exposing the breast under examination [300] to a laser light source.

It is another object of the present invention to disclose the device as defined in any of the above, wherein measuring means [106] are placed below the at least one transparent window [104] and carried by the support [102], the measuring means [106] comprise:

(i) laser-light emitting means [108] for emitting laser light beams in the red and/or near-infrared;

(ii) light-directing means [110] for directing said laser light beams towards the at least one transparent window [104];

(iii) at least one wavelength filter [ 112] ; (iv) light-sensing and imaging means [114] for sensing light and producing images; and

(v) an image controlling, processing and normalizing unit [116] for controlling, processing and normalizing images;

(iii) at least one wavelength filter [ 112] ;

(iv) light-sensing and imaging means [114] for sensing light and producing images; and

(v) an Al-based image processing and normalizing unit [116] for processing and normalizing images.

(iii) at least one wavelength filter [ 112] ;

(vi) an image controlling, processing and normalizing unit [116] for controlling, processing and normalizing images; an Al-based image processing unit [116] for processing and normalizing images, or any combination thereof. It is another object of the present invention to disclose the device as defined in any of the above, wherein the device [100] is configured to enable breast imaging procedure while the patient [200] is sitting and/or leaning down facing towards the measurement front panel [1021] of the support [102],

It is another object of the present invention to disclose the device as defined in any of the above, wherein said device [100] is configured to enable breast imaging procedure, while both breasts [300] are resting against the measurement front panel [1021], with the breast being measured centered in the optically transparent window [104],

It is another object of the present invention to disclose the device as defined in any of the above, wherein the patient's inclined vertical support [102] comprises means for height and incline angle control [1022],

It is another object of the present invention to disclose the device as defined in any of the above, wherein the measurement front panel [1021] is modular, providing several options, available to the physician, to ensure optimal accommodation of different breast sizes.

It is another object of the present invention to disclose the device as defined in any of the above, wherein the measurement front panel [1021] is made of a shape memory material to ensure patient's optimal comfort.

It is another object of the present invention to disclose the device as defined in any of the above, wherein the device [100] is configured to allow space [1023] for patient's wheel chair or any other positioning adaptation during breast imaging procedure.

It is another object of the present invention to disclose the device as defined in any of the above, wherein the device [100] is configured to enable breast imaging procedure in patients with large physical size, reduced mobility and/or with back or postural problems.

It is another object of the present invention to disclose the device as defined in any of the above, wherein the device [100] is configured to enable the positioning of the patient [200] to explore breast [300] lateral size, rotating the chest, and supporting the chest from one side to explore the external area of the breast. It is another object of the present invention to disclose the device as defined in any of the above, wherein the shape memory material of said measurement front panel [1021] is selected from the group consisting of foams, hydrogels, or any other shape memory material. In some embodiments, the shape memory material is a soft memory material.

It is another object of the present invention to disclose the device as defined in any of the above, wherein the at least one window [104] is made from a transparent material.

It is another object of the present invention to disclose the device as defined in any of the above, wherein the transparent material of the measurement front panel [1021] is selected from the group comprising: glass, transparent polymer, or any other transparent material.

It is another object of the present invention to disclose the device as defined in any of the above, wherein the at least one window [104] presents flat and parallel upper and bottom surfaces.

It is another object of the present invention to disclose the device as defined in any of the above, wherein the light-regulating means [118] are placed below the at least one window [104] and mounted to the support; further wherein the light-regulating means [118] control the amount of light entering the transparent window [104]; further wherein the light-regulating means [118] comprise a diaphragm ; further wherein the diaphragm adjusts the quantity of light that enters the transparent window; further wherein the light-regulating means [118] control the illumination and optimization of the image quality captured by a CCD camera.

It is another object of the present invention to disclose the device as defined in any of the above, wherein a cover [140] for isolating ambient light is disposed between the at least one transparent window [104] and the light-sensing means [114],

It is another object of the present invention to disclose the device as defined in any of the above, wherein the laser-light emitting means [108] in the red and/or near-infrared comprise at least two laser light emitters of different wavelengths.

It is another object of the present invention to disclose the device as defined in any of the above, wherein the at least two laser light emitters [108] are placed so that the emitted beams inci de collinearly on the light-directing means [110], It is another object of the present invention to disclose the device as defined in any of the above, wherein the light-intensity regulating means [130] for regulating the intensity of laser light beams are placed in front of each of the laser-light emitting means [108],

It is another object of the present invention to disclose the device as defined in any of the above, wherein the light-intensity regulating means [130] comprise a variable attenuator.

It is another object of the present invention to disclose the device as defined in any of the above, wherein the light-directing means [110] comprise a galvanometric scanner.

It is another object of the present invention to disclose the device as defined in any of the above, wherein the at least one wavelength filter [112] is an interferometric filter.

It is another object of the present invention to disclose the device [100] allows taking full-field images of the area to be analyzed and does not involve breast compression, and thus overcoming the problems mentioned above.

It is another object of the present invention to disclose the device as defined in any of the above, wherein the light-sensing and imaging means [114] comprise a high- sensitivity CCD camera.

It is another object of the present invention to disclose the device as defined in any of the above, wherein the high-sensitivity CCD camera is a 2D CCD camera.

It is another object of the present invention to disclose the device as defined in any of the above, wherein said image controlling, processing and normalizing unit [116]:

(i) eliminates noise from images produced by the light-sensing and imaging means [114];

(ii) determines the position of the light beam as it hits the studied surface and is captured by the CCD and clips an area of interest around the same;

(iii) creates a reference image with clippings;

(iv) normalizes clippings using the reference image; and

(v) rebuilds images repositioning the normalized clippings. It is another object of the present invention to disclose the device as defined in any of the above, wherein the device comprises a lid [1024] for maintenance and access to said measuring means [106],

It is another object of the present invention to disclose the device as defined in any ofthe above, wherein the Al-based image processing and normalizing unit provides breast tissue absorption map by Al image-to-image algorithms.

BRIEF DESCRIPTION OF THE DRAWINGS

Figures 1A-1B discloses the design of a breast imaging device provided by the present invention, in a front (Fig.lA) and back (Fig.lB) view of the device.

Figure 2 is a detailed schematic view of the device of the present invention, disclosing the components of the measuring means in said device, comprising three laser emitters [108],

Figures 3A-3B show imaging results of ink absorption in phantom experiments.

Figures 4A-4B show the results of the imaging device for the evaluation of HbR (Fig.4A), HbO (Fig.4B) and total HB (Fig.4C) in clinical case 1.

Figure 5A-5B show the results of the imaging device for the evaluation of HbR (Fig.5A), HbO (Fig.5B) and total HB (Fig.5C) in clinical case 2.

DETAILED DESCRIPTION OF THE INVENTION

The following description is provided, alongside all chapters of the present invention, so as to enable any person skilled in the art to make use of the invention and sets forth the best modes contemplated by the inventor of carrying out this invention. Various modifications, however, are adapted to remain apparent to those skilled in the art, since the generic principles of the present invention have been defined specifically to provide a red and/or NIR-based imaging device that aims to use red and/or NIR light to detect, characterize and follow the evolution of neoplastic lesions of the breast, with an adjustable positioning of the patient during imaging procedure.

NIR light is known to provide valuable data on cell function and biological processes such as blood flow, hemoglobin concentration, and oxygen saturation. NIR imaging has been used to determine the concentration of oxygen saturation of hemoglobin in healthy and cancerous tissue. Cancer tissue differs from normal tissue in its metabolic activity, and density: malignant lesions tend to be surrounded by neovascularization and oxygen-rich blood that feeds its growth. In addition, when tumors grow rapidly or reach a certain size, the central areas of the tumors may not receive sufficient oxygen to support further growth. This can lead to the formation of necrotic lesions that are rich in deoxygenated blood, even when neovascularization is present in the peripheral region. Prior studies show unique scattering and/or absorption signatures associated with dysplastic, malignant and benign tissue transformations.

The present invention provides a continuous wave, wide-field reflectance device [100] that aims to use red and/or NIR light to detect, characterize and follow the evolution of neoplastic lesions of the breast [300], with an adjustable positioning of the patient [200] during imaging procedure.

The measuring means [106] in the imaging device of the present invention consists of at least two continuous wave (CW) lasers of different wavelengths within the red and/or NIR region, a high sensitivity CCD camera, and a galvanometric scanner that allows directing the laser beam to scan a specific area of study. For each position of the laser, an image of the entire field is taken. The images are then treated with a self-developed algorithm that cleans, processes and reconstructs a final image for clinical evaluation. Due to the fact that the extinction coefficients of tissue’s compounds, such as oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (HbR), strongly depend on light’s wavelength, it is possible to obtain maps of oxy- and deoxygenated blood using at least two wavelengths; these maps are directly relatable to metabolic function and, as mentioned before, with the existence of different types of inhomogeneities.

EXAMPLE 1

Hardware Design

The imaging device of the present invention relies on acquiring, by a CCD camera, diffusely reflected light images of the breast under study, which may contain lesions (benign or malignant) with optical properties, i.e. scattering and absorption coefficients, that differ from those of the healthy background tissue. Images are normalized to the background intensity to emphasize the difference between background homogeneous tissue and any inhomogeneity that may be present. This was tested through numerical methods (MC) simulations and phantoms that simulate biological tissues.

In addition, detectability limits and the potential to obtain 3D information of the position and characteristics of the inclusion were studied. Results indicated that (i) detection of absorption variations is achieved if images are normalized to background intensity and (ii) inclusions are detected in realistic conditions of depth and absorption contrast for breast lesions. Moreover, a method was developed to normalize reflectance images using only experimental data; results indicated that it is useful to increase the contrast in the absorption channel.

The general design of the imaging device of the present invention is shown in Figure 1. It consists of a patient inclined vertical support [102] with a transparent window [ 104] under which the measurement means [ 106] are placed. The patient [200] is sitting and/or leaning down facing towards the measurement front panel [ 1021] of said support [102] with the breasts [300] resting on the transparent window [104]; no mechanical compression of the breast is needed, as is usual in any X-ray mammography. This arrangement flattens the patient’s breasts in a relatively comfortable way, allowing its measurement to be modeled as a reflectance geometry and also allowing light to explore deeper zones.

In Figures 1A-1B and Figure 2, the transparent window [104] is shown, on which the breasts [300] are resting during the imaging procedure. The use of the transparent window [104] avoids compression of the breast between two plates, which is typical of traditional mammographic devices, and patient comfort is substantially improved. The transparent window [104] has two flat surfaces, an upper surface and a bottom surface, parallel and opposite to one another.

Additionally, measuring means [106] below the transparent window [104] that comprise laser-light emitting means [108] and light-sensing and imaging means [114] are shown, the laser-light emitting means [108] and light-sensing and imaging means [114] comprise, respectively, laser light emitters, which emit in the red and/or near-infrared, and a 2D or bi-dimensional CCD camera which enables taking full-field images, that is, it makes it possible to produce an image of the whole surface to be analyzed in just one take. The means are positioned in diffuse reflectance geometry, thus, the phenomenon by which the device of the present invention operates is light reflectance, that is, light enters through the same face through which it exits. These laser-light emitting means [108] and light-sensing and imaging means [114] will be described in greater detail below, along with Figure 2.

Figure 2 shows a detailed schematic view of the device of the present invention which comprises laser-light emitting means [108] , light-sensing and imaging means [114] , a transparent window [104], light-directing means [110] for directing said light beams, light-regulating means [118], a wavelength fdter [112], a cover [140], three variable attenuators as light-intensity regulating means [130] for regulating the intensity of light beams, a light-beam divider [120] to redirect part of the beam (10%) to a power meter [119] to have real-time feedback of the power of the lasers, and an image controlling, processing and normalizing unit [116] for controlling, processing and normalizing images.

The laser-light emitting means [108] comprise three laser light emitters that emit coherent light beams (shown in continuous lines in Figure 2) in different wavelengths within the wavelength interval corresponding to red and/or near-infrared (NIR). Said laser light emitters [108] are positioned so that laser light beams are combined into one beam using two dichroic fdters [410], It should be mentioned that three laser light emitters are used, with different red and/or near-infrared wavelengths so as to distinguish, in the obtained images, the differential absorption between oxyhemoglobin and deoxyhemoglobin, which have absorption peaks at said different wavelengths. This generates an oxygen saturation map through a technique known as differential optical absorption spectroscopy (DOAS). This is particularly important from a diagnosis point of view, since oxygen saturation distribution is a differentiating factor between malignant and benign tumors. Generally, benign tumors have homogeneous oxygen saturation on their surface, while malignant tumors have a hypoxic zone in their oxygen-less center.

The light-sensing and imaging means [114] comprise a high-sensitivity CCD camera, preferably a 2D CCD camera. Said CCD camera incorporates an optic (i.e. a lens and/or any other optical component) which allows measuring lightning intensity of the full 2D surface of the breast, when the patient is sitting and/or leaning down facing towards the measurement front panel [1021] of said patient's support [102], as a single photograph of the red and/or NIR light reflected by each position of each laser light beam. It should be mentioned that it is not possible to perform this with a lineal arrangement of CCD cameras or sensors, as it is necessary to scan the complete area, capturing line by line. That is, the main advantage of using a 2D CCD with image production optics is that the complete area of interest is measured in only one take per laser position. It is even possible to take multiple images of each position in quick succession so as to improve the dynamic range with a high dynamic range (HDR) algorithm and improve the signal - noise ratio. Said camera may also compensate for the position and the size of the breast resting on the transparent window [104],

An interchangeable attenuator in the light-intensity regulating means [130] is positioned in front of each of the laser-light emitting means [108], reducing the intensity of said light beams as necessary in order to regulate the intensity of the laser light that incides on the breast of the patient and make up for the different relative absorptions, so as not to saturate the camera detectors. As mentioned above, said laserlight emitters [108] are positioned so that the light beams, with red and/or nearinfrared wavelength, are combined into a single beam by the use of calibration mirrors [400] and dichroic/ interferometric fdters [410], Light-directing means [110] comprise a galvanometric scanner that directs the red and/or NIR light beams, independently, towards the same area on the transparent window [104] and scans the area to be analyzed. Said galvanometric scanner comprises a positioning system that allows the area of incidence of the produced light beams to be changed, which is also the only movable part of the measuring means [106] in the device of the present invention. Two images are taken with the 2D CCD camera per each position of the scanner, one for each laser light of different wavelength, to then change to a new position, take the corresponding images and so on until the complete area to be analyzed is covered.

Light-regulating means [118] are placed below the transparent window [104] and comprise a diaphragm capable of regulating the amount of light that enters into the window [104], Said light-regulating means [118] control the illumination and optimization of the image quality captured by a CCD camera.

The red and/or NIR light directed by the galvanometric scanner impinges on the area of interest of the breast, one part of it being reflected and the other part being propagated into the breast. Propagation of red and/or NIR light upon finding any possible inhomogeneity within the breast, whether a tumor or a cyst, will be affected when exiting the breast due to transport within said inhomogeneity. If the inhomogeneity is more absorbent, as may be a tumor, a lower-intensity light will exit said breast due to additional absorption by said inhomogeneity. If the inhomogeneity is less absorbent, as may be a cyst, light will exit said breast with a higher intensity. This behavior of intensity of the reflected light beams is expected as tumors are more absorbent since, due to neovascularization, they have a higher blood supply, which makes them darker. On the contrary, cysts are almost translucent, and infrared light can easily go through them. Accordingly, the breast imaging device of the present invention allows to differentiate between malignant tumors and benign tumors such as Fibroadenoma.

Prior to being received by 2D CCD camera, reflected light goes through a wavelength filter [112], which is an interferometric filter that enables selection of determined wavelengths, useful in the optic characterization of the analyzed breast tissue to reduce light contamination from outside sources and improve the resolution of the images produced by the CCD camera. It should be highlighted that a cover [140] for isolating ambient light is placed between the transparent window [104] and said CCD camera, so that ambient light does not affect image capturing and does not hinder the detection of inhomogeneities in breast tissue.

The image controlling, processing and normalizing unit [116] for controlling, processing and normalizing the images is connected (dashed line in Figure 2), whether through a wire or wirelessly, to the three laser light emitters [108], the galvanometric scanner and the 2D CCD camera, so as to control each of them. In order to process, normalize and rebuild images obtained by the 2D CCD camera, said unit [116] carries out a method comprising different steps. In a first step, noise is eliminated from the obtained images using a background image that accounts for ambient noise and noise from CCD electronics. In a second stage, the position of the red and/or NIR light beam is determined for each image, and an area is clipped around the same, so that the incident source or red and/or NIR light beam is always placed at the center of the area being photographed. Each individual image obtained in the corresponding clipping is smaller than the analyzed area, and a step size is determined so that translation is less than the image of the individual images, in order to obtain some overlap that aids in the final rebuilding and the noise reduction. In a third stage, since the source is always located at the center of each image, and it is expected that hypothetical inhomogeneities may be in different positions in each image, an average image is generated with each of the clippings obtained in the previous stage, wherein the presence of possible inhomogeneities is blurred. Said average image serves as reference for normalization. In a fourth stage, each of the clippings is normalized using the average image from the previous stage. This normalization is needed to homogenize exposure of the complete explored area and highlight the presence of possible inhomogeneities. In a fifth and last stage, the normalized, clipped images are repositioned to their original position, rebuilding a normalized full-field image where the presence of inhomogeneities may be assessed and tumor and cyst areas may be distinguished from the rest of the healthy tissue of the tissue being analyzed.

The Al-based image processing and normalizing unit is configured to provide an absorption map of a breast tissue. The Al-based image processing and normalizing unit comprises an image-to-image algorithm. In some embodiments, the image-to- image algorithm comprises or is Patch-Based Graph Networks (GNNs), U-Net Algorithm, Generative adversarial networks, dense models, or any combination thereof. In some embodiments, the Al-based image processing and normalizing unit comprises or is (a) U-Net Algorithm, (b) GNN, or any combination thereof.

In some embodiments, the U-Net configured to obtain an absorption Map, comprising a fully conventional network (FCN). In some embodiments, the FCN input comprises or is a stack of images and the FCN output comprises or is the absorption map of the breast. In some embodiments, the stack of images is padded with black images to enable a constant depth. In some embodiments, padding refers to the addition of extra images, herein black images, to ensure uniformity or consistency in the number of images which may defer from patient to patient. In some embodiments, the U-Net further employs skip connection to preserve high-resolution features. As used herein, the term "stack" refers to a number of images obtained by imaging means As used herein the terms "image" and "photograph" are used interchangeably. As used herein, the term "absorption map" refers to a representation of how laser light is absorbed within a breast tissue.

In some embodiments, the FCN comprises an encoder-decoder architecture. In some embodiments, the encoder comprises a N 2D convolutional layers followed by 1:M pooling operations. In some embodiments, N=3 and M=2 resolution is halved after each pooling operation. As used herein, the term "N 2D" refers to a collection or a sequence of 2-dimentional images, organized in a specific order. In some embodiments, the decoder comprises a stack ofN 2D transposed convolutions, after which the resolution is multiplied by M. In some embodiments, transported convolution increases the spatial resolution of feature maps. The feature maps produced by each of the transposed convolutions are concatenated with the corresponding features of the decoder, through skip connections, to enrich the hidden representations with higher-resolution features that may have been lost in the depth of the network. As used herein the term, "skip connection" refer to a direct connection between non-sequential layers in a neural network.

An exemplary U-Net Algorithm Pseudocode:

The architectural hyperparameters are representative, and are optimized in practice for performance

Input (denoted by x): stack of photographs, interpolated to 256x256, padded to 100 in depth (with black photographs), resulting in a 256x256x100 array (a rank-3 tensor). Note: the size of the interpolated input can vary.

Output (denoted by y): absorption map (either 3D or a 2D average along z), also interpolated to 256x256.

NC = [100, 64, 128, 256, 512] # number of channels

NL = 3 = number of layers in encoder/decoder h = hidden feature maps for 1 in 1:NL: h[l] = Conv2D[l](x, in_channels=NC[l-l], out_channels=NC[l]) h[l] = ReLU(h[l]) h[l] = MaxPooling(h[l])

#bottleneck h[NL+l] = Conv2D[NL](h[NL], in_channels=NC[-l], out_channels=NC[-2]) NC[O] = 50 or 1 (depth of the absorption map) for 1 in 1:NL: h[NL+l+l] = ConvTranspose2D[l](h[NL+l], in_channels=NC[-l-l], out_channels=NC[-l-2]) h[NL+l+l] = Concat(h[NL+l+l], h[NL-l]) # skip connection h[NL+l+l] = Conv2D[NL+l](h[NL+l+l], in_channels=NC[-l-l], out_channels=NC[- 1-2]) y = h[2NL+l] # output

In some embodiments, GNN algorithm is configured to obtain an absorption map, comprising (a) extracting features from patches into one dimensional vector, and (b) processing the localized patches using a graph-based network, to generate an absorption map. In some embodiments, GNN algorithm further comprising, cropping of the images obtained by the imaging means into localized patches. In some embodiments, cropping is performed before the extracting of features. In some embodiments, input to the graphbased network is a graph constructed from nodes representing extracted features and edges representing the relationship between these features, the network's task is to reconstruct the absorption map, which has been map onto a grid through interpolation.

An exemplary GNN Algorithm Pseudocode:

Input (denoted by x): 64x64 patches centered at each source, i.e. an array of N_PATCHESx64x64. Note: the size of the input is dependent on the source grid and can vary. Output (denoted by y): absorption map (either 3D or a 2D average along z), interpolated to the nodes of each grid, i.e. an array of N PATCHESxN PATCHESxDEPTH.

1. Build graph G from a grid of N PATCHES sources. Each node of the graph is associated with a patch p, and the graph connectivity is given by the proximity of the sources on the grid.

2. h = node (patch) features for p in EN PATCHES:

# h[0][p] is of dimension 32x1 or 64x1. h[0][p] ⁼ Feature Extractor(x[p]) # an autoencoder’s encoder for 1 in 1:NL: for p in EN PATCHES: h[l] [p] = GraphAttentionLayer(h[l]

EXAMPLE 2

Phantom experiments

Phantoms are artificial means that emulate the optic properties of biological tissues, for example breast tissue. In order to validate the hardware of the imaging device of the present invention, phantoms are designed to emulate the absorption and scattering coefficients of both, healthy and diseased breast tissue.

The homogeneous tissue was represented by a liquid phantom composed of a mixture of whole milk (Ilolay, 3% fat) and distilled water. The inclusions, which are solid, were created using a similar mixture of whole milk and distilled water, with the addition of agarose as a gelling agent. These inclusions were suspended at desired positions within the liquid medium using a stretched thread. To simulate the additional absorption of the inclusions, two types of inks were introduced. One inclusion was infused with ADS830WS dye obtained from American Dye Source, while the other inclusion was supplemented with inkjet printer ink from Epson (model 673).

The phantom was then measured in the imaging device as if it were a real breast. Figures 3A-3B show the result using the reconstruction applying the algorithms described in the previous Sections. It can be seen that the difference in absorption of both inclusions (ADS830WS dye, Figure 3A and Epson ink, Figure 3B) is clearly visible, and they are represented as differences in ink concentrations relative to the medium.

EXAMPLE 3

Clinical Research

As part of the on-going development of the imaging device of the present invention, clinical research was conducted with several objectives: (i) Evaluate the feasibility of clinical use of the imaging device of the present invention in patients with BIRADS III - V breast nodules

(ii) Describe the findings of the images from the imaging device of the present invention in patients with BIRADS III - V.

(iii) Characterize the clinical, imaging (X-Ray mammography, breast ultrasound, and/or breast MRI), and histopathological profile of patients with BIRADS III - V.

(iv) Identify patterns of red and/or NIR images obtained through the breast imaging device of the present invention with their clinical-radiological and pathological counterparts.

These clinical trials were done in conjunction with clinical researchers of the Hospital Privado de la Comunidad (HPC) at their facilities. For the present contribution, below are described two selected cases of the on-going feasibility study. They were chosen as representative cases and consist in one patient (clinical case 1) with (post-study) diagnosis of invasive ductal carcinoma; and one patient (clinical case 2) in which no malignant lesions were diagnosed.

Patient admission criteria: All patients who require biopsy or follow-up due to their mammography or ultrasound findings according to the treating physician’s recommendation will be prospectively included.

Inclusion criteria:

• Age > 18 years.

• Agreement to the informed consent process.

• BI-RADS III, IV and V.

• Ability to undergo the study (i.e., the patient’s size can be accommodated on the table)

• Biopsy and/or further studies to be performed at the institution (HPC).

Exclusion criteria:

• Acute inflammatory lesion or any other condition that, in the medical investigator’s opinion, could alter the red and/or NIR signal. Refusal to undergo the informed consent process.

• Inability to perform the study due to mechanical or format issues with the table, such as the table not accommodating the patient’s size.

Clinical case 1: Malignant lesion

Description of Mammography Findings

The mammography examination reveals an ACRtype B pattern, indicating the presence of scattered and symmetrical fibro glandular tissue in the breast. In the upper outer quadrant of the left breast, specifically at hour 1, an oval-shaped lesion is observed. This lesion appears hyperdense with spiculated edges, and exhibits microcalcifications within it. The dimensions of the lesion are approximately 24 x 18 mm in diameter. Moreover, the lesion is causing retraction of the adjacent superficial planes. No significant abnormalities are detected in the right breast, and the axillary regions appear normal without any notable findings.

Description of Ultrasound findings

The ultrasound examination reveals bilateral breast parenchyma characterized by a uniform and homogeneous fibro glandular echo structure. In the left breast, precisely at the 3 o’clock position, consistent with the clinical and mammographic findings, a nodular and bilobed image is observed. This image exhibits a partial echogenic halo and appears hypoechoic. Furthermore, the nodular lesion displays punctiform calcifications and shows the presence of vessels within it. The dimensions of the lesion are measured to be 18.6 x 9.7 mm. No abnormalities are detected in the axillary regions.

Considering both the mammography and ultrasound findings, the patient is categorized as BIRADS IV, indicating a suspicious lesion that requires further evaluation.

Pathological Anatomy Results

The macroscopic examination reveals the presence of six yellowish-white cylinders, with the largest measuring 1.5 cm in length. The diagnosis of the core biopsy taken from the left breast, specifically at the 3 o’clock position, indicates the presence of nonspecial type invasive carcinoma, specifically invasive ductal carcinoma. The histological assessment classifies the carcinoma as grade 2, with a nuclear grade of 3 and mitotic grade of 2, resulting in an overall Nottingham II grade. The histological examination further identifies areas of necrosis, prominent fibrosis, and minimal peritumoral inflammatory reaction (TILs). Notably, there is no evidence of vascular invasion observed in the examined tissue.

Description of findings from the imaging device of the present invention

Figure 4 shows the results of the breast imaging device of the present invention for the clinical case 1. The evaluation of the HbR (Figure 4A), HbO (Figure 4B) and total HB (Figure 4C) in the left breast reveals that the periphery of the upper and lower outer quadrants cannot be adequately assessed due to artifacts resulting from improper contact between the breast and the device window. However, in the central region, there is an area exhibiting enhanced metabolism, absorption, or uptake, which corresponds to the hyperpigmentation of the nipple. At the peri areolar level, a distinct region with increased metabolism, absorption, or uptake is observed (Figure 4A, black circle). This region displays irregular margins and measures approximately 32mm x 25mm ± 0.5mm. The characteristics of this area are indicative of a neo proliferative lesion, aligning with the findings obtained from both the mammography and ultrasound examinations.

Clinical Case 2: Benign Lesion

Description of ultrasound findings

The ultrasound examination reveals bilateral breast parenchyma characterized by a uniform and homogeneous fibre glandular echo structure. In the left breast, specifically at the 7 o’clock position, an ovoid hypoechoic image is observed. This image exhibits well-defined and circumscribed margins, without apparent vascularization. The dimensions of the hypoechoic lesion are measured to be 23.3 mm. No abnormalities are detected in the axillary regions. Considering these imaging findings, the patient is classified as BIRADS III, indicating a lesion with intermediate suspicion that requires short-term follow-up and further evaluation.

Description of findings from the imaging device of the present invention Figures 5A-C show the results from the breast imaging device of the present invention for the clinical case 2. The evaluation of the HbR (Figure 5A), HbO (Figure 5B) and total HB (Figure 5C) are shown. Similar to the previous case, the region of increased metabolism or absorption in the breast corresponds to the hyperpigmentation of the nipple. No focal areas with increased metabolism or absorption are identified in the current study (Figure 5A), indicating the absence of metabolically active lesions. It is important to note that fibroadenomas, which are known to have limited vascularity and metabolic activity, are consistent with these findings.

The experimental results described above contribute to the growing body of literature on red and/or NIRS devices and their application in breast cancer diagnosis. The success of the imaging device of the present invention in detecting different types of breast lesions, along with its promising results in ongoing clinical trials, holds significant potential for improving breast cancer diagnosis and treatment. With further development and refinement, the imaging device of the present invention has the potential to make a substantial impact on breast cancer management, ultimately leading to improved patient outcomes.

Claims

1. A mammographic imaging device [100] for analysis and detection of possible inhomogeneities in breast tissue [300] of a patient [200] using laser light in the red and/or near-infrared (NIR) in diffuse reflectance geometry, wherein said device comprises an inclined patient vertical support [102] with a transparent window [104] for exposing the breast under examination [300] to a laser light source and emitters, measuring means [106] below said at least one transparent window [104] and carried by said support [102], said measuring means [106] comprise:

(vi) laser-light emitting means [108] for emitting laser light beams in the red and/or near-infrared wavelength;

(vii) light-directing means [110] for directing said laser light beams towards the at least one transparent window [104];

(viii) at least one wavelength filter [ 112] ;

(ix) light-sensing and imaging means [114] for sensing light and producing images; and

(x) an image controlling, processing and normalizing unit [116] for controlling, processing and normalizing images; an Al-based image processing and normalizing unit for processing and normalizing images; or any combination thereof; further wherein said device [100] is configured to enable breast imaging procedure while said patient [200] is sitting and/or leaning down facing towards a measurement front panel [1021] of said support [102]; further wherein said device [100] is configured to enable breast imaging procedure, while both breasts [300] are resting against said measurement front panel [1021], with said breast being measured centered in the optically transparent window [104]; further wherein said patient's inclined vertical support [102] comprises means for height and incline angle control [1022]; further wherein said measurement front panel [1021] comprising said transparent window [104], is modular, providing several options, available to a physician, to ensure optimal accommodation of different breast sizes; further wherein said measurement front panel [1021] is made of a shape memory material to ensure patient's optimal comfort; further wherein said device [100] is configured to allow space [1023] forpatienfs wheel chair or any other positioning adaptation during breast imaging procedure; further wherein said device [100] is configured to enable breast imaging procedure in patients with large physical size, reduced mobility and/or with back or postural problems; further wherein said device [100] is configured to enable the positioning of the patient [200] to explore breast [300] lateral size, rotating the chest, and supporting the chest from one side to explore the external area of the breast.

2. The device [100] according to claim 1, wherein said shape memory material is selected from a group consisting of foams, hydrogels, or any other shape memory material.

3. The device [100] according to claim 1, wherein said at least one window [104] is made from a transparent material.

4. The device [100] according to claim 3, wherein said transparent material is selected from a group consisting of glass, transparent polymer, or any other transparent material .

5. The device [100] according to claim 1, wherein said at least one window [104] presents flat and parallel upper and bottom surfaces.

6. The device [100] according to claim 1, wherein light-regulating means [118] are placed below said at least one window [104] and mounted to said support.

7. The device [100] according to claim 1, wherein a cover [140] for isolating ambient light is disposed between said at least one transparent window [104] and the lightsensing means [114],

8. The device [100] according to claim 7, wherein said light-regulating means [118] comprise a diaphragm capable of regulating the amount of light that enters into the window [104],

9. The device [100] according to claim 1, wherein said laser-light emitting means [108] comprise at least two laser light emitters of different wavelengths.

10. The device [100] according to claim 9, wherein said at two laser light emitters [108] are placed in a position allowing the emitted beams to incide collinearly on said lightdirecting means [110],

11. The device [100] according to claim 1, wherein light-intensity regulating means [130] for regulating the intensity of laser light beams are placed in front of each of the laser-light emitting means [108],

12. The device [100] according to claim 11, wherein said light-intensity regulating means [130] comprise a variable attenuator.

13. The device [100] according to claim 1, wherein said measuring means [106] comprise a light-beam divider [120] and a power meter [119], said light-beam divider [120] redirecting part of a laser beam (10%) to said power meter [119], providing real-time feedback of the power of said laser-light emitting means [108],

14. The device [100] according to claim 1, wherein said light-directing means [110] comprise a galvanometric scanner.

15. The device [100] according to claim 1, wherein said at least one wavelength filter [112] is an interferometric filter.

16. The device [100] according to claim 1, wherein said light-sensing and imaging means [114] comprise a high-sensitivity CCD camera.

17. The device [100] according to claim 16, wherein said high-sensitivity CCD camera is a 2D CCD camera.

18. The device [100] according to claim 1, wherein said image controlling, processing and normalizing unit [116]:

(i) eliminates noise from images produced by said light-sensing and imaging means [114];

(ii) determines the position of said light beams and clips an area of interest around the same;

(iii) creates a reference image with clippings;

(iv) normalizes clippings using said reference image; and

(v) rebuilds images repositioning said normalized clippings.

19. The device [100] according to claim 1, wherein said Al-based image processing and normalizing unit provides breast tissue absorption map by Al image-to-image algorithms.

20. The device [100] according to claim 1, wherein said device comprises a lid [1024] for maintenance and access to said measuring means [106],