Systems and methods for in vivo tissue imaging using coded aperture x-ray scattering tomography - Patents.com

Abstract

A system and method for in vivo tomographic tissue imaging using coded aperture x-ray scattering tomography is disclosed. The imaging system includes a coded aperture for spatially encoding x-ray scattering originating from within a patient's body. An x-ray detector array is used to record modulated scatter signals that are analyzed to generate a spatially resolved x-ray scattering spectral reconstruction of the tissue and a spatially resolved scattering tissue image of the irradiated tissue.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 331,764, filed April 15, 2022, entitled "Systems and Methods for In Vivo Tissue Imaging Using Coded Aperture X-Ray Scattering Tomography," the entire contents of which are incorporated by reference herein.

[0002] The present invention relates to medical imaging and x-ray scattering tomography, and more particularly to a system and method for in vivo tissue imaging using coded aperture x-ray scattering tomography. [Background technology]

[0003] In vivo non-invasive volumetric imaging techniques allow clinicians to create 3D images of the inside of a patient. Four techniques in particular are commonly used by clinicians to perform various medical evaluations: X-ray transmission computed tomography (transmission CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and ultrasound (US). All of these conventional techniques suffer from insufficient tissue contrast in various applications, especially those that require differentiation between regions of soft tissue with different characteristics. Cancer detection applications are one such application that requires the ability to differentiate between cancerous and benign soft tissue regions. Existing in vivo volumetric tissue imaging techniques require extensive training and experience by clinicians to assess the malignancy of imaged tissue regions, but even for the most skilled clinicians using any of these conventional techniques, the misclassification rate for cancer detection still leaves room for significant improvement. Misclassification in cancer detection applications also results in significant costs to the healthcare system, poorer patient health, and unnecessary stress for patients. Therefore, there is a need for in vivo non-invasive volumetric imaging techniques that can more accurately distinguish tissue types, especially in soft tissue regions and in cancer detection applications. Summary of the Invention

[0004] According to one embodiment of the present invention, a spatially resolved volumetric tissue imaging system for in vivo imaging of a patient's body is disclosed. The imaging system includes a housing including a bore and a gantry disposed around the bore, the bore configured to accommodate at least a portion of a human body. The imaging system further includes an X-ray source for irradiating at least a portion of in vivo tissue of the body with a primary X-ray beam. The X-ray source is mounted on the gantry, the X-ray source being configurable to change the direction and exposure time of the primary X-ray beam about the bore axis. The imaging system further includes a collimator disposed between the X-ray source and the tissue for shaping the primary X-ray beam. The imaging system further includes an X-ray detector array including an arrangement of at least two-dimensional X-ray detector elements. The plurality of X-ray detector elements are disposed distal to the X-ray source outside of a path of the primary X-ray beam passing through the irradiated portion of the body and for measuring scattered X-ray radiation from the primary X-ray beam passing through the tissue. The imaging system further includes a coded aperture disposed between the tissue and the X-ray detector array. The coded aperture is configured to modulate scattered X-ray radiation from the tissue detected by the X-ray detector array. The imaging system further includes a control system including a memory and a processor. The processor is configured to configure the imaging system to perform X-ray scatter measurements based on configuration data including an orientation of the primary beam relative to the bore axis and an exposure time of the X-ray source. The processor is further configured to perform X-ray scatter measurements using the configured imaging system. The processor is further configured to receive data representative of the scattered X-ray radiation detected by the X-ray detector array. The processor is further configured to estimate a spatially resolved X-ray scatter spectrum reconstruction of the tissue based on the received X-ray scatter data and the configuration data. The processor is further configured to determine spatially resolved tissue properties based on the received X-ray scatter data. The processor is further configured to generate a spatially resolved scattered tissue image based on the received X-ray scatter data.

[0005] According to another embodiment, an imaging system for performing in vivo imaging of a human body is disclosed. The imaging system includes an x-ray source mounted on a configurable arm for irradiating an in vivo tissue of at least a portion of the body with a primary x-ray beam. The position and orientation of the x-ray source are adjustable by a user. The imaging system further includes a collimator disposed between the x-ray source and the tissue for shaping the primary x-ray beam. The imaging system further includes an x-ray detector array including a plurality of x-ray detection elements arranged in at least two dimensions. At least one of the x-ray detection elements is disposed distal to the x-ray source outside a path of the primary x-ray beam passing through the irradiated portion of the body and measures scattered x-ray radiation from the primary x-ray beam passing through the tissue. The imaging system further includes a coded aperture disposed between the tissue and the x-ray detector array. The coded aperture is configured to modulate scattered x-ray radiation from the tissue detected by the x-ray detector array. The imaging system further includes a control system including a memory and a processor. The processor is configured to determine configuration data for the imaging system. The configuration data includes a position and an orientation of the X-ray source. The processor is further configured to perform X-ray scattering measurements using the configured imaging system. The processor is further configured to receive data representative of scattered X-ray radiation detected by the X-ray detector array. The processor is further configured to estimate a spatially resolved X-ray scattering spectral reconstruction of the tissue based on the received X-ray scattering data and the configuration data. The processor is further configured to determine spatially resolved tissue properties based on the received X-ray scattering data. The processor is further configured to generate a spatially resolved scattered tissue image based on the received X-ray scattering data.

[0006] According to another embodiment, a method of performing in vivo tissue imaging within a patient's body is disclosed. The method includes disposing at least a portion of the body in an imaging system. The method further includes configuring the imaging system for X-ray scatter measurements based on configuration data including an orientation of the primary beam relative to a bore axis and an exposure time of the X-ray source. The method further includes performing X-ray scatter measurements using the configured imaging system. The X-ray scatter measurements include irradiating at least a portion of in vivo tissue of the body with a primary X-ray beam from an X-ray source through a collimator disposed between the X-ray source and the tissue, and shaping the primary X-ray beam. The X-ray scatter measurements further include modulating scattered X-ray radiation from the tissue using a coded aperture disposed between the tissue and an X-ray detector array including an arrangement of at least two-dimensional X-ray detection elements. The X-ray scatter measurements further include detecting modulated scattered X-ray radiation signals from the tissue with a plurality of X-ray detection elements disposed distal to the X-ray source outside the path of the primary X-ray beam passing through the irradiated portion of the body, and measuring scattered X-ray radiation from the primary X-ray beam passing through the tissue. The X-ray scatter measurement further includes receiving data representative of the detected scattered X-ray radiation from the X-ray detector array. The X-ray scatter measurement further includes estimating a spatially resolved X-ray scatter spectrum reconstruction of the tissue based on the received X-ray scatter data and the composition data. The X-ray scatter measurement further includes determining spatially resolved tissue properties based on the received X-ray scatter data. The X-ray scatter measurement further includes generating a spatially resolved scattered tissue image based on the received X-ray scatter data.

[0007] It should be understood that the above brief description is provided to introduce in a simplified form a selection of concepts that are further described in the detailed description. It is not intended to identify key or essential features of the claimed subject matter, the scope of which is uniquely defined by the claims that follow the detailed description. Moreover, the claimed subject matter is not limited to implementations that solve the disadvantages noted above or in any part of this disclosure, but may be applied more generally.

[0008] The disclosed invention will be better understood upon reading the following non-limiting description of embodiments, which refers to the attached drawings, in which: [Brief description of the drawings]

[0009] [Figure 1] 1 shows a schematic diagram of a CT system with a coded aperture for scatter measurements, where according to an embodiment of the subject matter described herein, the coded aperture and detector may be located within the gantry housing or within the CT scanner bore. [Diagram 2] 1 shows a flow chart for performing CT transmission and scatter acquisition by a system according to an embodiment of the subject matter described herein. [Diagram 3] 1 shows a schematic diagram of a coded aperture and how it is flat or curved with respect to incident scattered x-rays, according to an embodiment of the subject matter described herein. [Figure 4] According to an embodiment of the subject matter described herein, a schematic diagram of a CT system with a motorized mechanism for moving a coded aperture in and out of the beam path for transmission versus scatter measurement modes is shown. [Diagram 5] FIG. 1 shows a schematic diagram of a CT system illustrating how the primary pencil / fan beam enters the patient from any angle while the coded aperture moves with the detector to perform measurements, according to an embodiment of the subject matter described herein. [Figure 6] FIG. 1 shows a schematic diagram of a CT system illustrating angled source-side collimation for converting a fan beam into a pencil beam to measure scattering through a target area of ​​a patient, according to an embodiment of the subject matter described herein. [Figure 7] 1 shows a schematic diagram of a CT with a coded aperture and an additional detector integrated in the gantry outside the primary x-ray beam path, according to an embodiment of the subject matter described herein. [Figure 8]1 shows a schematic diagram of a CT system with separate X-ray sources and detectors at different tunnel depth locations for transmission and scattering measurements according to an embodiment of the subject matter described herein. [Figure 9] 1 shows a schematic diagram of a CT scanner with two light sources and detectors for performing transmission and scattering measurements in the same plane, according to an embodiment of the subject matter described herein. [Figure 10] FIG. 1 shows a schematic diagram illustrating accounting for patient motion during scattering measurements, according to an embodiment of the subject matter described herein. [Figure 11] FIG. 1 shows a schematic diagram of a CT system that uses a highly focused coded aperture near the detector for single-point scatter measurements along a pencil beam path, according to an embodiment of the subject matter described herein. [Figure 12] FIG. 12 shows a schematic diagram of a pencil beam and highly focused coded aperture raster scan shown in FIG. 11 for measuring multiple voxels according to an embodiment of the subject matter described herein. [Figure 13] 1 shows a schematic diagram of a C-arm X-ray transmission system combined with a coded aperture for scatter measurements, where the coded aperture can be mounted on the system and moved to an optimal measurement position according to an embodiment of the subject matter described herein. [Figure 14] 1 shows a schematic diagram of a ceiling-mounted X-ray transmission system combined with a coded aperture for scatter measurements, according to an embodiment of the subject matter described herein, the coded aperture may be placed in the air or in the patient table to encode the scatter data. [Figure 15] 1 shows a schematic diagram of a portable X-ray transmission system in combination with a coded aperture for scatter measurements; in accordance with an embodiment of the subject matter described herein, the coded aperture and detector may be positioned in combination with the portable X-ray system for measurements. [Figure 16] According to an embodiment of the subject matter described herein, a schematic diagram of a typical CT system is shown with an arrow passing through the bore of the gantry to indicate an axis called the bore axis or patient motion axis. [Figure 17] According to an embodiment of the subject matter described herein, a schematic diagram of a CT bore and gantry system with a coded aperture integrated into the table for receiving and scatter imaging of a patient's breast during breast CT imaging is shown. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The subject matter described herein includes systems, methods and control systems for tomographic x-ray scattering imaging of in vivo tissue. The present disclosure can be used to obtain spatially resolved volumetric tissue property estimates of in vivo tissue.

[0011] As used herein, the phrase "reconstructing an image" is not intended to exclude embodiments of the invention in which data representative of an image is generated, but a displayable image is not generated. Thus, as used herein, the term "image" refers broadly to both a displayable image and data representing a displayable image. However, many embodiments generate (or are configured to generate) at least one displayable image.

[0012] In the present description, including but not limited to the measured scattering signal and the reconstructed spatially resolved scattering spectrum, the description will be referred to as relating to "X-ray scattering", although the X-ray scattering field is generally comprised of both Rayleigh and Compton scattering, also known as coherent and incoherent scattering. Although the terms "scattering" or "diffraction" are used generally in these descriptions, this is not intended to limit the invention to scattering resulting from any physical process.

[0013] X-ray transmission computed tomography (transmission CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) are existing in-vivo volumetric imaging techniques commonly used by clinicians to perform a variety of medical evaluations. These techniques detect electromagnetic radiation as it passes through or is emitted from the body.

[0014] The details of the acquired data vary by technique, but in general, detectors are used to quantify the intensity and frequency of the signal as a function of the time and location at which the signal was measured. Modulation of the intensity or frequency in space or time of the measured signal may result from the physical mechanisms underlying each technique (e.g., x-ray attenuation in transmission CT) and the measurement type protocol (e.g., the use of shorter repetition times and time to echo in T1-weighted MRI scans). In any of these techniques, the raw measurement data is complex and multidimensional and therefore of no immediate diagnostic value to the clinician. Specialized data processing and algorithmic techniques are chosen to reconstruct from the modulation of the raw data the spatially resolved tissue data that are valuable to the clinician.

[0015] Two factors are used by clinicians to judge the diagnostic value of images produced by in vivo imaging diagnostic techniques: spatial resolution and image contrast. Increasing spatial resolution allows clinicians to discern smaller features and more accurately analyze the shape of tissue features. Image contrast in this context refers to the change in intensity of the spatially resolved reconstructed data and is determined by the specific protocol of a particular measurement type, the choice of data processing procedures and reconstruction algorithms used to generate the image, and the physics underlying the technique, this last physics setting a fundamental limit to what can be quantified from the raw data. The value of image contrast to the clinician varies with application. Measurement techniques, data processing and reconstruction algorithms are preferably selected to maximize the contrast between tissue types and features that are most useful to the clinician in making a particular assessment. Because the contrast of the reconstructed image is related to the physical mechanisms underlying each technique, transmission CT, MRI and PET imaging have associated advantages and disadvantages depending on the types of tissues the clinician wishes to distinguish in a particular application.

[0016] One example of image contrast enhancement is the development of a variety of new contrast-enhancing dyes for both MRI and transmission CT that can preferentially enhance the contrast of certain tissue types. An example of a technique designed to enhance tissue contrast is dynamic contrast-enhanced MRI, which can detect microvascular differences through spatially resolved changes in reconstructed intensity over time in a series of consecutive measurements.

[0017] Although application-specific image contrast is important to produce useful images for clinicians, the raw measurement data of each of these techniques contains more information than is typically quantified in the reconstructed tissue images used by clinicians. In general, these techniques may produce spatially resolved spectral tissue maps, i.e., the reconstructed spatial map is not a scalar value but can have an additional spectral dimension at each voxel, allowing for different, potentially application-specific contrast at each spectral bin. Methods for obtaining spectral tissue maps include combining techniques such as PET / CT or PET / MRI imaging, performing multiple measurements using different parameters such as T1-weighted and T2-weighted MRI scans or transmission CT scans with different x-ray source filtering, or performing multiple measurements using different levels or types of contrast-enhancing dyes using MRI or transmission CT. Some specialized variations of these techniques can also produce spatially resolved spectral tissue maps with a single measurement, such as hyperspectral transmission CT, which uses energy-discriminating x-ray detectors to quantify the radiodensity of tissue voxels at multiple energy ranges, and magnetic resonance spectroscopic imaging, which quantifies the magnetic resonance spectrum of each tissue voxel.

[0018] In vivo imaging techniques are used by clinicians in cancer detection applications such as cancer screening, diagnosis, and staging, as well as in prescribing and monitoring treatments such as radiation therapy, to assess regions of tissue maps as cancerous or benign based on shape and contrast. Most cancer detection applications require tissue discrimination in soft tissue regions, but despite significant advances in transmission CT, MRI, and PET techniques, soft tissue contrast is generally weak, especially between cancerous and benign tissues. When using any of these techniques, extensive training and experience by the clinician is required for accurate classification. Enhanced contrast between soft tissue types could significantly improve cancer classification performance in all cancer detection applications. Advances that enhance contrast, especially between cancerous and benign soft tissues, or provide clinicians with spatially resolved spectral information to aid in the evaluation of in vivo images, could fill an unmet need and significantly improve expected patient outcomes and reduce costs.

[0019] X-ray scattering tomography is another non-invasive imaging technique that can be used to generate spatially resolved volumetric spectral maps of materials that have not been implemented in in vivo tissue imaging to date. More specifically, tomographic X-ray scattering imaging modalities can generate spatially resolved volumetric maps of X-ray scattering spectra. In particular, for tomographic X-ray diffraction imaging modalities, spatially resolved volumetric maps of momentum transfer spectra of materials can be reconstructed. Momentum transfer spectral data are not accessible with existing in vivo imaging techniques such as transmission CT, MRI, and PET. Momentum transfer spectra reflect local molecular order and can have a number of different features for each material, making them particularly suitable for distinguishing materials. In vivo implementations of X-ray scattering tomography for medical imaging applications can provide clinicians with volumetric tissue images generated from the reconstructed spectral maps in an application-specific manner, with contrast selected based on specific known features that distinguish the most relevant tissue types, such as cancerous and benign tissues. Such images with tissue type contrast generated from the momentum transfer spectral signatures of specific tissue types are never accessible with existing imaging techniques.

[0020] Components of the in vivo imaging systems and methods described herein may vary from embodiment to embodiment. A non-exhaustive description of such variations is provided below. Variations in the X-ray source include, but are not limited to, the type of source (e.g., X-ray generator vs. radioisotope), generator anode material, generator focal spot size, etc. Variations in the collimator include changes in the size and shape of the collimator opening to control the spatial extent and cross-sectional shape of the initial X-ray beam, respectively. These aspects of the collimator opening are controllable by a control system in some embodiments of the system. Variations in the coded aperture design include, but are not limited to, the type of pattern (e.g., periodic, Fresnel zone plate, random or optimized random, uniform redundant array), material, aperture ratio, thickness. The system may include multiple coded apertures that can be selected by the user or automatically selected based on the measurement conditions, e.g., the optimal coded aperture may be selected algorithmically based on the geometric constraints and estimated radiation dose for the X-ray scatter measurement in a user-specified sub-region of tissue. Variations in X-ray detector arrays include, but are not limited to, the number of X-ray detectors that make up the array, the number of detector elements or pixels per detector, the size and pitch of the pixels, the dimensionality of the detector and detector array (e.g., 2D or 3D), the detection mechanism (e.g., scintillator or direct conversion), the thickness of the absorbing layer, and the energy or photon discrimination capability (e.g., energy integration, stacked multi-energy channels, energy discrimination or photon counting). Although energy-integrating X-ray detector types, common in most X-ray transmission imaging systems, can also be used, the use of energy-discriminating or photon-counting detectors improves the signal-to-noise ratio, reduces the radiation dose to the patient, and improves overall system performance. Larger or higher dimensional X-ray detector arrays can capture more of the scattered X-ray signal, which can also improve the signal-to-noise ratio, reduce the radiation dose to the patient, and improve overall system performance.

[0021] An embodiment of the in-vivo system and method described herein includes reconstructing spatially resolved volumetric X-ray spectral data from an irradiated volume of tissue using a coded aperture to modulate scattering, an X-ray detector array including an at least two-dimensional arrangement of X-ray detection elements to measure the modulated scattering signal, a forward matrix model of the physical properties and geometry of the measurement configuration, and a processor to iteratively estimate the spatially resolved volumetric X-ray spectral data from the forward matrix model. Another embodiment further includes estimating the momentum transfer spectrum on a pixel or voxel basis. Another embodiment further includes using the spatially resolved momentum transfer spectrum map in combination with a reference library of existing tissue momentum transfer spectra of known tissue types to calculate a spatially resolved estimate of the tissue type of the irradiated tissue volume. The reference momentum transfer spectra specifically include spectra of cancerous or benign tissue types to calculate a spatially resolved estimate of the likelihood of cancer.

[0022] An embodiment of the method described herein further includes optimizing the X-ray scatter measurement configuration by calculating a radiation dose to the patient and an estimated X-ray scatter data quality of the measurement. The method includes calculating an estimate of a radiation dose to the patient for the X-ray scatter measurement from the configuration data, calculating an estimate of an X-ray scatter data quality metric obtained from the configuration data, and optimizing the configuration data using the estimated radiation dose and the estimated X-ray scatter data quality metric. The optimized configuration data used by the processor to perform an X-ray scatter measurement optimized for the estimated radiation dose and the estimated X-ray scatter data quality metric. Such an embodiment includes controlling various components of the system. An example includes an embodiment in which the X-ray source is an X-ray generator and the X-ray source current or the X-ray source voltage is optimized. Another example includes an embodiment in which the size or shape of the collimator opening can be optimized. Another example includes an embodiment in which a moveable filter can be placed in the initial X-ray beam to optimize the energy spectrum and irradiance of the beam. Another example includes an embodiment in which the relative position or orientation of at least one of the X-ray source, collimator, coded aperture, or multiple X-ray detector elements can be optimized. Another example includes an embodiment in which the relative position of the tissue can be optimized. An important metric for the quality of X-ray scattering data is the signal-to-noise ratio. The measured X-ray scattering signal will be significantly less intense than the transmitted X-ray signal for the same initial X-ray beam and irradiated volume, and the relatively weak X-ray scattering signal will be attenuated by the tissue, affecting the signal-to-noise ratio of the measured signal. An embodiment of the method described herein includes configuring components to reduce the effect of tissue attenuation on the measured X-ray scattering signal, specifically the signal-to-noise ratio. This is achieved by defining the initial X-ray beam path and selecting a tissue viewpoint to minimize attenuation of the initial X-ray beam along the initial X-ray beam path to the point in the tissue, or to minimize attenuation of the scattered X-ray signal from the point in the tissue to the X-ray detector element. This includes minimizing the path length or avoiding paths with high attenuation, such as paths through bone.

[0023] The methods and imaging systems of the present invention provide in vivo tissue imaging using a single, a few, or many views of the patient based on the configuration of the X-ray source, collimator, coded aperture, and X-ray detector elements relative to the patient in a given embodiment. In embodiments that allow multiple views of the patient, 3D or hyperspectral tissue maps can be generated tomographically from data acquired at each view. In some embodiments, incorporating multiple X-ray sources at different locations within the imaging system also allows multiple views of the patient. Additionally, in some embodiments, movable or rotatable X-ray sources and X-ray detector elements can be used to allow different views of the patient. In some embodiments, these movable or rotatable components can be controlled by a control system. For example, a gantry on which the X-ray sources and X-ray detector elements positioned around the patient may be mounted can be rotated around the patient and translated along the bore axis (i.e., longitudinal axis) in which the patient (or a portion of the patient) is located, allowing any number of views of the patient to be viewed from any angle. In embodiments in which the x-ray detector elements and x-ray source are movable, measurements can be taken from a single viewpoint with the major components fixed, from multiple viewpoints repeated at multiple fixed positions, or the major components moved so that the viewpoints change over time. In embodiments in which the collimator is movable in a manner controllable by the processor, the collimator can be held in a constant relative position and orientation between the x-ray source and the tissue, or moved independently of said x-ray source to control the direction of the beam relative to the x-ray source, tissue, and x-ray detector elements to further increase the diversity of imaging viewpoints. Detailed specifications of the method and imaging system of the present invention that facilitate integration with transmission CT imaging components and methods are described below in conjunction with the accompanying drawings.

[0024] Considering the quality metrics that can be calculated by the disclosed invention and optimize the configuration for X-ray scatter measurements, there are various characteristics that can be considered when optimizing the quality of the measurement. These factors can include, but are not limited to, X-ray attenuation of the primary beam or scattered X-rays, with the goal of minimizing the dose to the patient or maximizing the signal-to-noise ratio (SNR) of the measured data. For quality metrics that consider the noise of the measurement, the optimization can focus on the total noise in the acquired data, the ratio of noise to signal in the total or area of ​​the detected data, or the type of noise present in the measurement (e.g., Poissonian, Gaussian). This quality metric can also direct the measurement to limit the primary X-ray beam path or scattered X-rays emitted through organs where dose reduction is desired. Additionally, the quality metric can consider the location of the patient's bones that absorbed more primary or scattered X-rays, avoiding the reduction in signal or the increase in scan time or dose required to overcome this additional absorption. Additionally, where an embodiment of the invention is one in which only sub-regions of a patient are scatter scanned to lower dose, the quality metric of the measurement may take into account measuring multiple suspected masses or regions of interest within a single pencil or fan beam measurement, with the illumination geometry optimized to measure all required regions using the minimum number of exposures required to accomplish the task. Additionally, a quality metric for scatter imaging may take into account the spatial location of the region of interest (e.g., suspected mass) and control the position of the coded aperture or x-ray source to bring the region closer to the coded aperture or x-ray source to achieve a desired level of geometric magnification of the scatter x-ray or coded aperture features at the detector. While these provided examples suggest various factors that may be included in the quality metric used to optimize an imaging procedure, the list is not exhaustive and other factors used and known in the art may be applied to the quality metric and measurement optimization process.

[0025] The components mounted on the gantry may be configured to move along any curve, rather than along a circular path. It should be noted that in some CT systems, the x-ray source and detector may be fixed while the object or patient rotates, and the description herein may also be applicable to such imaging methods.

[0026] In addition to allowing multiple imaging viewpoints and tomographic image reconstruction, there are further advantages to embodiments of the method that allow control of the positions and orientations of key components. Embodiments with filters that can be moved in or out of the initial beam allow control of irradiance and energy spectrum. Similarly, collimators of various shapes (e.g., pencil, fan, cone, or annular) can be moved in or out of the beam to control the cross-sectional shape of the initial beam, and moving the collimators closer or further from the source focal spot allows control of the beam divergence, which in turn controls the irradiated tissue volume and radiation dose to the patient. Controlling the position and orientation of the coding aperture allows for variation in the relative distances of points on the coding aperture to the irradiated tissue volume and the x-ray detector elements, optimizing the code magnification. Controlling the position and orientation of the x-ray detector elements allows for optimization of the range of momentum transfer space data collected based on the relative positions of the x-ray detector elements and the irradiated tissue volume and the energy spectrum of the initial beam, and also allows optimization of the momentum transfer space resolution based on the size and relative positions of the detector elements or pixels. In embodiments where the X-ray source, collimator, coded aperture, or X-ray detector elements are movable, the configuration data further includes the relative positions or relative orientations of the movable components. The calculation of the illuminated tissue representation is based on these configuration data. The accuracy of the system geometry used in the calculation to generate the illuminated representation, and in particular the accuracy of the coded aperture geometry, can limit the accuracy of the reconstructed spectral tissue map.

[0027] In another embodiment of the invention, rather than other embodiments using a small detector with an x-ray source rotating on a gantry, typical of third generation transmission CT scanner designs, a full circle or semicircular ring of x-ray detectors surrounds the bore and is used to measure x-rays scattered from the primary beam or to measure the primary beam transmitted through tissue, typical of fourth and fifth generation transmission CT scanners. In another embodiment of the invention, the x-ray source rotates on the gantry, and the ring of detectors is fixed around the patient. Yet another embodiment uses a full ring or sections of detectors placed around the bore or patient, and multiple x-ray sources are placed in multiple different orientations around the bore axis, allowing multiple views of the patient without moveable components. In this embodiment, the x-ray source can be multiple radioactive sources with separate shutters that can be timed simultaneously for CT data collection, or x-ray generators, including currently available models or models using new technologies such as carbon nanotubes that can be placed around the patient. These multiple x-ray sources and detectors can be used to collect multi-view data simultaneously or sequentially.

[0028] Further advantages of the imaging system described herein may be associated with various embodiments that include multiple specific components. For example, embodiments that use multiple x-ray generators with different anode materials allow for initial x-ray beams with different peak energies. In embodiments with multiple filters, the filters can be switched or combined to control the irradiance and energy spectrum of the initial x-ray beam. Embodiments with multiple collimators, particularly those that can be moved independently, allow for varying the spatial extent of the beam, the irradiated tissue volume, and the radiation dose to the patient. Embodiments with multiple coded apertures, particularly those that can be moved independently, allow for switching one coded aperture to another with a different code pattern, thereby better coding the measured scatter for a particular measurement configuration (e.g., location and / or orientation) and the type of tissue that the user is trying to classify and differentiate. Since the scattered x-ray signal is weaker than the transmitted x-ray signal, one advantage of embodiments with an x-ray detector array made up of multiple x-ray detectors, or a large x-ray detector array in general, is that it allows for as much x-ray scatter signal as possible to be recorded. An embodiment of a 3D X-ray detector array including multiple separate 2D X-ray detectors may also allow each detector element or pixel to be more precisely oriented toward the irradiated tissue volume than an X-ray detector array including a single 2D X-ray detector with the same total detector area. An X-ray detector array made of curved X-ray detectors is another example of a 3D X-ray detector array that may allow each detector element or pixel to be more precisely oriented toward the irradiated tissue volume.

[0029] The method of the present invention can be combined with a variety of other imaging techniques to exploit the complementary strengths of the two techniques. One such embodiment of the method of the present invention combines tomographic X-ray scattering images with transmission X-ray images, incorporating the advantage of also being able to use X-ray hardware. Some embodiments of the method exploit this by sharing the same X-ray source, filters, collimators or X-ray detector elements for both X-ray scattering and X-ray transmission measurements.

[0030] Some embodiments of the invention use an x-ray generator as the x-ray source, while other embodiments utilize a radioactive material as the x-ray source, and some embodiments include both types of sources. In embodiments using a radioactive source, the radioactive material, when placed in an enclosure that absorbs x-rays and is shielded with a window and shutter, can be used to control the x-rays that exit the window and generate a primary beam for irradiating tissue and performing scatter measurements. In such embodiments, the exposure time is controlled by opening and closing the shutter, rather than turning on and off the voltage and current to the anode as in the case of x-ray generators. Such embodiments may be advantageous for scatter imaging by having a narrower or nearly monoenergetic energy spectrum of the primary beam compared to the broader energy spectrum typically representative of bremsstrahlung radiation generated in the anode of an x-ray generator. As some illustrative examples, but not intended to be limiting, Cobalt-57 (emitting 136.6 keV X-rays with a half-life of 270 days) or Americium-241 (emitting 59.5 keV X-rays with a half-life of 432 years) are radioisotopes that produce X-rays with energies that are useful and acceptable for clinical applications of the disclosed embodiments of the invention. A narrower or nearly monoenergetic spectrum can reduce the complexity of the system model used to estimate the spatially resolved scatter reconstruction, thereby reducing computational cost and improving accuracy. This allows for a similarly accurate reconstruction while reducing the radiation dose to the patient by reducing the number of photons delivered to the patient within a particular energy range. In such embodiments, the radioactive source may need to be replaced over time as activity decreases. In another embodiment, an X-ray generator is used for 2D or 3D X-ray transmission imaging, and a radioactive source is utilized for scatter imaging.

[0031] Certain embodiments of the method of the present invention, including both tomographic X-ray scatter imaging and X-ray transmission imaging, may further include performing X-ray transmission measurements on the tissue volume followed by X-ray scattering measurements on designated sub-regions of the tissue volume, i.e., spot checking regions from the initial X-ray transmission measurement with X-ray scattering measurements. Such method embodiments have the advantage of reduced radiation dose compared to X-ray scattering measurements performed on the entire volume of tissue. Such embodiments allow for estimation of spatially resolved tissue properties of sub-regions of tissue of concern to the operator, such as tissue suspected of cancer, while minimizing the radiation dose to the patient required for the measurements. X-ray scatter measurements in sub-regions of tissue may be performed in a variety of ways depending on the particular embodiment. Some examples of the step of defining a sub-region for X-ray scatter measurements include, but are not limited to, using an additional collimator to change the spatial extent of the beam, moving the collimator to change the direction or divergence of the initial X-ray beam, changing the size of the collimator opening to change the spatial extent of the beam, moving the X-ray source or X-ray detector to change the view of the tissue, and moving the tissue to change the view of the tissue. In some embodiments of the method, the processor receives user input to select a sub-region of tissue for X-ray scattering measurements. The processor calculates configuration data for the user input for at least one of the X-ray source, the collimator, the coded aperture, or the plurality of X-ray detection elements, and applies the calculated configuration data to the components to perform the X-ray scattering measurements in the sub-region of tissue. In another embodiment, the method further includes transmitting a radiodensity tissue image calculated from the X-ray transmission measurements to a display, and the user input further includes an indication of a sub-region in the displayed radiodensity tissue image. In another embodiment, the method further includes calculating a spatially resolved estimate of cancer likelihood from the radiodensity tissue image, calculating a region of interest in the radiodensity tissue image using the spatially resolved estimate of cancer likelihood, and transmitting the region of interest data to the display. In another embodiment, the method further includes calculating a region of interest in the radiodensity tissue image using a machine learning algorithm.Such an embodiment with a region of interest indicator helps to point out possible cancerous regions to the operator, who can select the regions as sub-regions in which to perform X-ray scatter measurements. A particular embodiment of an imaging system and method for X-ray scatter measurement spot checks in a CT scanner system is described in further detail below and illustrated in FIG.

[0032] The embodiment of the present method including X-ray transmission imaging is advantageous because the X-ray transmission data can be used in the reconstruction algorithm to generate a joint reconstruction estimate of the radiodensity and X-ray scattering spectrum of the tissue voxels. In such an embodiment, the physical properties of the interaction of the irradiated tissue volume with X-rays can already be contained in the forward matrix model of the system, along with the geometry and related properties of any hardware shared between the imaging modalities. In other embodiments of the method, the X-ray transmission data can be incorporated into the calculation of the estimated tissue type, thereby improving the classification performance. Due to the advantages of the embodiment of the present method including transmission X-ray imaging, there are several specific embodiments described in more detail below that show how the imaging system described in the current method can be integrated into the general configuration of an in-vivo transmission CT scanner using similar components.

[0033] There are numerous x-ray scattering properties that are a subset of the properties of tissues that can be measured, calculated, or displayed to a user by the invention disclosed herein. For example, and not by way of limitation, a reconstruction algorithm can utilize the measured scattered x-rays to calculate a momentum transfer spectrum, which is a type of x-ray diffraction spectrum that takes into account the energy of the x-rays that affect the scattering angle, but the system can also calculate an intensity versus scattering angle (or 2θ) profile that does not take into account the energy of the x-rays generated by the x-ray source. From these various types of scattering spectra, additional properties can be calculated including total scattering intensity (sum of intensity versus angle or momentum transfer), intensity-weighted average scattering angle or intensity-weighted average momentum transfer value, scattering intensity q values ​​for sub-ranges of scattering angles or momentum transfer, and ratios of scattering intensities for different spectral peaks or sub-ranges of scattering angles or momentum transfer. These additional metrics can be utilized in classification algorithms or prognostic applications to identify / distinguish different tissue types. Additionally, the various scattering-based metrics can be utilized to generate images for viewing by a user, which may be comprised solely of data from scattering measurements or a combination of imaging data types. Combined images may include, but are not limited to, CT / 2D radiographs / MRI data color coded by scattering properties, or the ability for a user to select pixels / voxels / toxels of interest in a medical image and report information about their scattering properties. This report may be automatically flagged or visually displayed, particularly for areas with scattering properties corresponding to cancer or a condition of interest, allowing the user to easily identify areas that may require further investigation.

[0034] While the topic of conditions and tissue characteristics of interest has been specifically emphasized on cancer, there is a range of other tissue characteristics associated with other diseases or biological conditions that the disclosed invention may be utilized to identify or provide prognostic information. In addition to identifying whether a suspicious mass in the body is malignant, other diseases such as ductal carcinoma in situ (DCIS) in the breast are often referred to as latent cancer, although there are many patients whose DCIS does not progress to invasive cancer. The measured scattering characteristics can help identify which patients have DCIS that will progress to cancer and which patients can be observed for longer or are deemed to be no threat to the patient. Inflammatory conditions in organs, including the lungs, during disease or infection may also lead to changes in scattering characteristics that may be measured by the disclosed invention and utilized for various clinical purposes. Additionally, changes in the liver during cirrhosis may lead to changes in X-ray scattering characteristics, representing another change in tissue characteristics that may be identified utilizing the present invention. Additionally, changes that occur in the brain during the onset and progression of dementia, particularly Alzheimer's disease, may lead to changes in cellular composition or structure that may be measured by scattered x-ray properties. These examples of additional tissue properties and associated conditions / diseases are not intended to be limiting, but rather to illustrate the variety of useful properties that may be measured and reported by the disclosed invention.

[0035] Transmission CT scanners typically use a circular gantry within a housing that allows the x-ray source and x-ray detector to be rapidly positioned at various positions relative to the object being imaged, both radially around the longitudinal axis and translationally in the direction of the longitudinal axis. The components rotate on the gantry to capture data from multiple views from which 2D slices can be reconstructed. The bore of a CT scanner is a central opening with a bore axis, or longitudinal axis, through which the patient can be positioned on a table that moves the patient within the bore relative to the x-ray imaging system, allowing for multiple slice measurements or continuously acquired helical scan data, in either case from which a full 3D image can be reconstructed.

[0036] FIG. 1 shows a schematic diagram of a CT system with a coded aperture for scatter measurements, and according to an embodiment of the subject matter described herein, the coded aperture and the X-ray detector may be located in a gantry housing or in a CT scanner bore. FIG. 1 shows one view along the bore or longitudinal axis of a configuration in which the imaging architecture described above can be modified for coded aperture scatter imaging and in which the components of the imaging system can be located. With reference to FIG. 1, the imaging system 100 includes a gantry housing 101, an X-ray source 102, an X-ray primary beam 103, a CT scanner bore 104, a patient table 105, a patient 106, an X-ray scatter 107, a coded aperture 108, an X-ray detector 109, gantries 110 and 111 for rotating the X-ray components, and a non-CT gantry translation and rotation of the X-ray detector and the coded aperture in the CT bore 112. The left panel of FIG. 1 shows how the coding aperture 108 is incorporated into the gantry 110, moving with the X-ray detector 109 for scatter imaging from any viewpoint of the patient. The center panel of FIG. 1 is another configuration where the coding aperture 108 is located within the confines of the CT bore 104 (either in open air or as part of an enclosure in a typical bore location). The right panel of FIG. 1 shows the X-ray detector 109 and coding aperture 108 located within the CT bore 104. Each of the three options for the location of the coding aperture 108 and the X-ray scatter detector 109 has advantages. Because both components are mounted on the gantry 110 outside the bore (as shown in the left panel of FIG. 1), they do not take up space within the bore, keeping the patient size limitations the same as existing CT scanners, and they can rotate together on the gantry to maintain the same relative positions. When the coding aperture 108 is located inside the bore (as shown in the center panel of FIG. 1), it is closer to the irradiated tissue, allowing the coded scatter features to be further magnified on the X-ray detector 109 outside the bore. Using an X-ray scatter detector 109 inside the bore (as shown in the right panel of FIG. 1) results in a higher signal level because the bore wall material does not attenuate the scattered X-rays. This improves the quality of the reconstruction in a shorter time and therefore reduces the radiation dose required for the patient.

[0037] FIG. 2 illustrates a flow chart of exemplary steps for performing CT transmission and scatter acquisition by a system according to an embodiment of the subject matter described herein. With reference to FIG. 2, the measurement begins in step 201 with a transmission CT scan of the patient, which is used to calculate a radiodensity image of the tissue in step 202. In step 203, a machine learning algorithm operates on the radiodensity image to generate a probability of cancer that can be used to calculate a potential region of interest in step 204, which can be utilized by the user to select sub-region(s) of interest for further scatter measurement in step 205, and can be used by the operator to highlight the region of interest for scatter measurement in step 202. After this selection is made, in step 206, the system configures a scatter measurement mode in which the processor converts the user-entered region of interest into system configuration data for X-ray scatter measurement of the region of interest. The system configuration data can be further optimized by the processor to minimize radiation dose and / or maximize quality metrics of the estimated X-ray scatter data. The processor then implements the system configuration, which can include movement of major components. For example, if the same X-ray detector is used for the transmission and scatter measurements, the coded aperture may be moved to the area between the irradiated tissue and the X-ray detector. The collimator may be moved relative to the focal point of the source to change the initial beam direction or the total volume of irradiated tissue. Separate X-ray components, such as the X-ray source and X-ray detector, may also be used for the scatter measurements. Alternatively, the same components may be used with different operating parameters. Other components used for the scatter measurements but not for standard CT transmission measurements may also be moved to a different position, such as placing a beam block that blocks the initial beam transmitted for the scatter measurements. Next, the scatter measurements are performed in step 207, followed by post-processing of the scatter data in step 208. The post-processing generates tissue information that may be displayed to the operator. For example, the tissue information that may be displayed to the operator may include the likelihood that the tissue voxel is cancerous. While this is one possible implementation, the embodiments of the invention described below also allow for simultaneous acquisition of transmission and scatter data.Additionally, the operational steps of the system may vary to perform scatter measurements in a region of interest (e.g., from measured transmission data or an alternative 3D imaging modality), or scatter measurements in a larger region or over the patient's entire body that does not require a prior 3D image to guide the scatter measurement location, without departing from the scope of the subject matter described herein.

[0038] FIG. 3 shows a schematic diagram of a coded aperture and how it is flat or curved with respect to the incident scattered x-rays according to an embodiment of the subject matter described herein. To optimize performance, one or more coded aperture settings or configurations can be used. In FIG. 3, a coded aperture 301 is shown, where the black areas represent materials that absorb the scattered x-rays and the white areas allow the x-rays to pass. This coded aperture shown in FIG. 3 represents one potential pattern (e.g., 2D random), but other potential patterns (e.g., periodic, Fresnel zone plate, random or optimized random, uniform redundant array) can also be used. Other configurable settings or configurations of the coded aperture include, for example, but are not limited to, (1) feature size, which may affect the reconstructed spatial and spectral resolution, and (2) open fraction, which controls the overall measured scattered signal intensity. The central opening 302 of the coded aperture 301 allows the primary x-ray beam to pass for transmission measurements without being absorbed or causing undesired background scattering. In one embodiment, the coded aperture 301 can be a flat panel 303 relative to the x-ray source, as shown in FIG. 3. Alternatively, the coded aperture 301 can have a curvature 304 that is beneficial for larger fan beams and / or curved x-ray detector arrays used in CT systems. Using a curved coded aperture allows the relative angular collimation of features to be maintained for different positions along the fan range or angles of incidence of the pencil beam. While the coded aperture can include an opening through which the primary beam can pass, imaging systems may also use coded apertures that incorporate beam blocks or that translate or rotate in position depending on whether transmission or scatter data is being measured.

[0039] 4 shows a side view of a CT system with a motorized mechanism for moving the coded aperture in and out of a position that optimally modulates the detected scattered X-ray signal for either the scatter or transmission measurement modes, respectively, according to an embodiment of the subject matter described herein. With reference to FIG. 4, the CT system 400 has a gantry housing 401, an X-ray source 402, an X-ray primary beam 403, a patient table 404, a patient 405, a CT scanner bore 406, X-ray scatter 407, a coded aperture 408, an X-ray detector 409, and a mechanism 410 for moving the coded aperture 408. While moving the coded aperture out of the beam path is useful for CT transmission measurements, being able to move the coded aperture into a desired position for scatter measurements is useful for optimizing the size of the patient or the relative location of the region of interest within the bore (i.e., the proximity of the coded aperture to the patient versus the proximity of the coded aperture to the X-ray detector).

[0040] FIG. 5 shows a schematic diagram of a CT system showing how the primary pencil or fan beam can be incident on the patient from any angle while the coded aperture moves with the X-ray detector to perform measurements according to an embodiment of the subject matter described herein. Regardless of whether the coded aperture is located in the gantry housing or in the CT bore area (movable or fixed position), the gantry rotation and coding aperture positioning capabilities allow for performing scattered measurements at different angles, thereby optimizing the measurement process. With reference to FIG. 5, the imaging system 500 includes a CT gantry housing 501, an X-ray source 502, a primary pencil or fan beam 503, a CT scanner bore 504, a patient table 505, a patient 506, scattered X-rays 507, a coded aperture 508, a connector between the coded aperture and the X-ray detector 509, an X-ray detector 510, and a gantry 511 for rotating the X-ray components. The left panel of FIG. 5 shows a scatter measurement performed using an X-ray source 502 at the bottom of the gantry 511, while the right panel shows that the scatter measurement can occur at any angle relative to the patient 506. This change in measurement angle can be used to optimize for lower patient radiation dose (due to a narrower path through the body) or higher measurement quality (due to less absorption of scattered X-rays by moving the tissue of interest closer to the exit location of the primary beam from the patient). This approach can be used regardless of whether the coded aperture is located within the gantry housing or within the bore region.

[0041] FIG. 6 shows a schematic diagram of a CT system showing angled source-side collimation for converting a fan beam into a pencil beam to measure scattering through a target area of ​​a patient, according to an embodiment of the subject matter described herein. One possible implementation for implementing scatter measurements in a manner that reduces radiation dose, uses fewer components, and allows exploration of the area of ​​interest is shown in FIG. 6. The imaging system 600 includes an X-ray source 601, a primary source pencil beam collimator outside the beam path 602, a primary X-ray fan beam 603, a patient 604, a first area of ​​interest 605 (e.g., a suspicious mass), a second area of ​​interest 606, a coded aperture 607, and an X-ray detector 608. In another configuration, as described in more detail below, the imaging system 600 further includes a collimator 609 that generates a pencil beam 610 for measuring the first area of ​​interest, the pencil beam 610 being targeted to the first area of ​​interest and scattering X-rays 611 from the pencil beam 610. In another configuration, as described in more detail below, the imaging system 600 further includes a new angle collimator 612 for generating a pencil beam 613 for measuring a second region of interest, the pencil beam 613 targeted at the second region of interest and scattering X-rays 614 from the pencil beam 613.

[0042] The left panel of Figure 6 shows how the collimation can be out of the primary beam path (or with jaws open around the primary beam), allowing a standard X-ray fan beam to be used for transmission measurements. The coded aperture can be placed out of the path of the primary X-ray fan beam 603 (or have a slit as shown in Figure 3) to avoid interaction with the primary beam 603.

[0043] The center panel of Figure 6 shows how collimation is used to generate a pencil beam that targets a first region of interest while generating only scatter signals along the pencil beam's path. Coded apertures and post-processing algorithms allow localization of the scatter source and angle along the pencil beam's path, generating a momentum transfer spectrum of the region of interest that can be used for tissue evaluation.

[0044] The right panel of Figure 6 shows how collimation can be altered to target a second region of interest. For example, the pencil beam angle and the relative angular placement of the x-ray components with respect to the patient can be optimized for multiple parameters, including acquiring scatter data over a wider portion of the width of the x-ray detector while having the pencil beam pass to the left or right of the x-ray detector, as shown in Figure 5.

[0045] FIG. 7 shows a schematic diagram of a CT scanner with a coded aperture and an additional X-ray detector integrated in the gantry outside the primary X-ray beam path, according to an embodiment of the subject matter described herein. In the system embodiment of the imaging system shown in FIG. 7, the additional X-ray detector(s) offset from the initial beam path along the bore axis direction allows for simultaneous acquisition of transmission and scattered data, or scatter measurements with minimal component movement. The imaging system 700 includes a gantry housing 701, an X-ray source 702, a CT scanner bore 703, a patient table 704, a patient 705, scattered X-rays 706, a coded aperture 707, an X-ray transmission detector 708, and an X-ray scatter detector(s) 709. In FIG. 7, the X-ray detector for measuring the scatter data is positioned outside the primary beam path along the bore axis direction. Another advantage of this embodiment is to avoid adverse effects on the scatter data from the primary beam hitting the X-ray scatter detector. Placing the X-ray scatter detector 709 and coded aperture 707 in a different plane relative to the transmission measurement plane (or adjacent but outside the primary beam path) allows both data types to be measured simultaneously. These X-ray scatter measurement components may be fixed within the machine or may be mounted on a rotating gantry to allow measurements of the patient at different angles of incidence.

[0046] FIG. 8 shows a schematic diagram of a CT system with separate x-ray sources and x-ray detectors at different positions along the bore axis for transmission and scatter measurements, according to an embodiment of the subject matter described herein. Separating the transmission and scatter measurement components into different planes relative to patient motion can also be achieved by providing a larger separation in the gantry housing, as shown in FIG. 8. The imaging system 800 includes a gantry housing 801, an x-ray source 802 for transmission, a CT scanner bore 803, a patient table 804, a patient 805, an x-ray transmission detector 806, patient motion 807 for scatter measurements, an x-ray source 808 for scatter, a coded aperture 809, a mechanism 810 for moving the coded aperture 809, and an x-ray scatter detector 811. In FIG. 8, the components for each measurement type are in different planes of the system along the bore axis, which is also the direction of patient motion into the bore. If a different X-ray source and X-ray detector are required for X-ray scatter measurements, it may be desirable to have some separation of all components within the same system compared to the strategy shown in the previous figures, which uses the same X-ray source for both transmission and scatter measurements. It may be appreciated that if a fixed position for the coded aperture 809 works for all patient sizes / dimensions, then the mechanism 810 for moving the coded aperture 809 may not be required. However, incorporating the mechanism 810 allows for further optimization of the measurement geometry.

[0047] FIG. 9 shows a schematic diagram of a CT scanner with two light sources and an X-ray detector for transmission and scattering measurements in the same plane, according to an embodiment of the subject matter described herein. Instead of having separate X-ray components for transmission and scattering measurements at different bore tunnel depths, the components may be in the same plane but at different angles, as shown in FIG. 9. The imaging system 900 includes a gantry housing 901, an X-ray source 902 for transmission, a CT scanner bore 903, an X-ray fan beam 904 for transmission measurements, a patient table 905, a patient 906, an area of ​​interest 907 (e.g., a suspected mass), an X-ray transmission detector 908, an X-ray source 909 for scattering, an X-ray pencil beam 910 for scattering measurements, scattered X-rays 911 from the pencil beam, a coded aperture 912 with a central beam block for the pencil beam, an X-ray scatter detector, and a gantry 914 for rotating the X-ray components. This approach is compatible with CT scanners with a vertical dual source. While the system of FIG. 9 shows the second source and X-ray detector dedicated to scatter measurements, both source and X-ray detector pairs can be used for transmission and scatter measurements, thereby increasing the measurement speed for both data types without departing from the scope of the subject matter described herein. The X-ray detector array shown in FIG. 9 allows both sets of X-ray sources and X-ray detectors to acquire transmission and scatter data simultaneously. Alternatively, the method of changing between transmission and scatter measurement modes described above can be used for one or both of the X-ray source and X-ray detector pairs to first acquire a transmission measurement and then switch to scatter measurement mode for one or both sources.

[0048] The described imaging system may be used to analyze tissue at various locations within a patient's body. For tissue in areas such as the brain or suspicious masses, minimal motion is expected during measurements. In contrast, when measuring scattering properties of lung tissue, the patient's breathing can result in tissue motion during measurements. During standard CT imaging, the patient is asked to hold their breath to reduce the effects of this type of motion. For scattering measurements, the system may be able to acquire all the data required during a single breath hold, although certain embodiments, such as methods involving whole-body or whole-slice scattering measurements, may take time. With this in mind, the method shown in FIG. 10 may be implemented.

[0049] 10 shows a schematic diagram illustrating consideration of patient motion during scattering measurements according to an embodiment of the subject matter described herein. The imaging system 1000 includes a gantry housing 1001, an X-ray source for transmission 1002, a CT scanner bore 1003, an X-ray fan beam 1004, a patient table 1005, a patient 1006, a region of interest 1007 (e.g., a suspected mass), an X-ray transmission detector 1008, an X-ray source for scattering 1009, an X-ray pencil beam 1010, scattered X-rays 1011 from the pencil beam 1010, a coded aperture plus beam block 1012, an X-ray scattering detector 1013, and a gantry 1014 for rotating the X-ray components. In another embodiment, as described in more detail below, the imaging system 1000 may further include body expansion / motion due to breathing of the patient 1015, and a region of interest 1016 that has moved to a new position due to patient movement. According to another embodiment, a plot of patient motion is displayed where the patient's motion is measured by transmission or other motion tracking techniques. For example, fiducial markers on the patient and camera can show a target mass moving up and down over time with respiration 1017. A time window of displacement 1018 is displayed when the patient exhales and the region of interest is in the desired position for the scatter measurement. If this is necessary because the scan time is longer than the patient's appropriate breath hold time in areas where patient motion cannot be prevented, the frequency 1017 of the target mass moving up and down over time can be used to obtain scatter data from a consistent patient position by turning the x-ray beam being used for the scatter measurement on and off (or opening and closing the x-ray source window).

[0050] The left panel of FIG. 10 shows how to acquire transmission and scatter measurements of a patient. The center panel of FIG. 10 shows how scatter measurements are gated by patient motion. The right panel of FIG. 10 shows how to track patient motion. Using this type of gating or motion management may produce more accurate reconstructions of scatter measurements of moving targets because little or no data collection occurs if the region of interest is not within the primary beam path or changes position within this path.

[0051] 11 and 12 relate to an embodiment of the invention for measuring specific tissue regions in the body. The measured tissue region can be defined by the user. Although the coded aperture has already been shown at a distance between the X-ray detector and the irradiated tissue (shown in a 2D random pattern in FIG. 3), the coded aperture can also be placed right next to the patient or the X-ray detector. If the coded aperture is a thick, periodic pattern (e.g., sinusoidal) on the X-ray detector with angled openings that target specific points in the body, the primary pencil beam can be used to make scatter measurements of individual voxels in the patient. This coded aperture embodiment can be a single attenuating component with an opening, or a set of attenuating components arranged in a pattern, which together constitute an effective coded aperture for modulating the measured scatter. In either arrangement, the thick opening can be controlled to focus the aperture to focus the scatter from specific points in the imaging system, and in particular from specific points in the patient's body.

[0052] 11 shows a schematic diagram of a CT system using a highly focused coded aperture near an X-ray detector for scatter measurements of a single point along a pencil beam path, according to an embodiment of the subject matter described herein. Referring to FIG. 11, an imaging system 1100 includes a gantry housing 1101, an X-ray source 1102, an X-ray pencil beam 1103, a CT scanner bore 1104, a patient table 1105, a patient 1106, a first scatter measurement spot 1107, scattered X-rays 1108 from the first measurement spot, a highly focused coded aperture collimator 1109 that receives scattered X-rays from the first spot 1107, an X-ray detector 1110, a gantry 1111 for rotating the X-ray components, a beam block 1112 for the primary X-ray beam to reduce background scatter, a second scatter measurement spot 1114, a CT scanner bore 1104, a patient table 1105, a patient 1106, a first scatter measurement spot 1107, scattered X-rays 1108 from the first measurement spot, a highly focused coded aperture collimator 1109 that receives scattered X-rays from the first spot 1107, an X-ray detector 1110, a gantry 1111 for rotating the X-ray components, a beam block 1112 for the primary X-ray beam to reduce background scatter, a second scatter measurement spot 1116, and a CT scanner bore 1104. 11 includes a fixed spot 1113, scattered X-rays 1114 from a second measurement spot 1113, a moving focal coded aperture 1115 for measuring scattered X-rays from the second measurement spot, an X-ray detector 1116 that can also be moved independently of the X-ray source if required for the desired range of scatter angle measurements, and an enlarged window 1117 showing how the highly focused coded aperture collimation can be tilted by rotation of the entire component or by motorized movement of the individual parts that make up the coded aperture to change the position of the focal point along the X-ray pencil beam. In contrast to the above embodiments that use a coded aperture and X-ray detector system for simultaneous scatter measurements of multiple tissue regions illuminated by a pencil or fan beam, the embodiment shown in FIG. 11 may be used when reducing this multiplexed measurement to a single point measurement approach is optimal for a given task.

[0053] 12 shows a schematic diagram of raster scanning of the pencil beam and highly focused coded aperture shown in FIG 11 to measure multiple voxels according to an embodiment of the subject matter described herein. This implementation can be used for planar or volumetric imaging by measuring the scatter data of individual points and raster scanning the focal point of the pencil beam and highly focused coded aperture at different locations within the patient as shown in FIG 12. Imaging system 1200 includes a gantry housing 1201, an X-ray source 1202, a movable X-ray pencil beam collimation 1203, an X-ray pencil beam 1204, a CT scanner bore 1205, a patient table 1206, a patient 1207, a first row of scatter measurement spots 1208, a highly focused coded aperture 1209 that can be tilted to change the focal position, an X-ray detector that potentially moves independently relative to the X-ray source 1210, a gantry for rotating the X-ray component 1211, a beam block for primary X-rays 1212, an X-ray pencil beam collimator shifted to measure a new row of spots 1213, a shifted X-ray pencil beam 1214, and a second row of scatter measurement spots 1215. If the scatter measurements are made rapidly, the measurements described in Figures 11 and 12 allow for rapid measurement of an area through fast raster scanning.

[0054] Although some embodiments of the in vivo scattering imaging system have been described as being able to be combined with a standard transmission type CT scanner, there are other X-ray imaging architectures that can be combined with the present invention. FIG. 13 shows an embodiment combining in vivo coded aperture scattering imaging with a C-arm transmission type X-ray system. Since a C-arm system may be used during surgery, combining the present invention within a C-arm architecture is valuable for imaging applications that do not use a CT scanner type device. In FIG. 13, an imaging system 1300 is shown that includes an X-ray source 1301, a primary X-ray beam 1302, a patient table 1303, a patient 1304, an X-ray scattering 1305, a coded aperture 1306, an X-ray detector 1307, a C-arm 1308, and a C-arm body 1309. As described in the previous figures, the coded aperture can be connected to the C-arm and placed in an ideal position depending on the size of the patient and the application.

[0055] FIG. 14 shows an additional embodiment of the invention with an alternative X-ray transmission imaging system, where in vivo coded aperture scatter imaging technology is combined with a ceiling mounted X-ray transmission system. Ceiling mounted X-ray transmission systems are often used for 2D X-ray imaging applications and are useful for collecting scatter data during these examinations to obtain additional tissue contrast. In FIG. 14, imaging system 1400 is comprised of a movable ceiling mount 1401, an X-ray source 1402, a primary X-ray beam 1403, a patient 1404, X-ray scatter 1405, a patient table 1406, a coded aperture 1407, and an X-ray detector 1408. Another embodiment of the invention combines in vivo coded aperture X-ray scatter imaging in a portable X-ray imaging system, as shown in FIG. 15, similar to the ceiling mounted X-ray system of FIG. 14. A portable X-ray imaging system is used in clinical settings where it is advantageous to bring the imaging device to the patient without the need to transport the imaging device to a separate imaging room. In these applications, an X-ray detector may be placed behind the patient or in the bed for data acquisition. Similarly, a coded aperture may be placed behind the patient and in front of the X-ray detector to spatially encode the X-ray scatter signal. In FIG. 15, imaging system 1500 includes an X-ray source 1501, a primary X-ray beam 1502, a patient 1503, X-ray scatter 1504, a patient table 1505, a coded aperture 1506, and an X-ray detector 1507. The in vivo coded aperture X-ray scatter imaging embodiments of FIGS. 13-15 are provided as additional examples of accompanying techniques that may be combined with the present invention, although this list is not intended to be exhaustive.

[0056] 16 shows a schematic diagram of a typical CT system with an arrow passing through the bore of the gantry to indicate an axis referred to as the bore axis or patient motion axis, according to embodiments of the subject matter described herein. For visualization purposes, FIG. 16 shows a typical CT scanner with an imaging system 1600 including a primary CT scanner frame / gantry 1601, a CT bore 1602, a patient table 1603, and a bore axis arrow 1604. This schematic diagram may facilitate understanding of what is referred to herein as the bore axis or patient motion axis to which certain embodiments of the subject matter refer.

[0057] FIG. 17 shows a schematic diagram of a CT bore and gantry system with a coded aperture integrated into the table for the purpose of receiving and scatter imaging a patient's breast during breast CT imaging, according to an embodiment of the subject matter described herein. In embodiments of the invention designed for specific clinical tasks, such as imaging specific regions of the human body (e.g., head, breast), a coded aperture is placed in the bore and gantry system to enable scatter imaging. As a demonstration of one such implementation, FIG. 17 shows a breast CT system with a coded aperture for scatter imaging. In FIG. 17, a schematic diagram of a breast CT imaging system 1700 is shown, in which a patient 1701 lies prone on a table 1702, which has a vertical bore 1703 surrounded by a vertical gantry 1704 that can rotate around the patient's breast placed in the bore. Additionally, the gantry component that rotates around the breast includes an x-ray source 1705 that may include collimation to shape or aim the primary beam, a coded aperture 1706 to modulate the scattered x-rays, and an x-ray detector 1707 to receive the transmission and scatter signals. In this format, a mammography screening or diagnostic exam can be performed without compressing the breast using an x-ray cone or fan beam geometry. If a suspicious mass is identified, scatter imaging with any x-ray beam geometry using fixed or rotating components can be performed to obtain further diagnostic information. Additionally, the system can be designed with a fan beam geometry and a coded aperture with a slit through which the primary beam passes, or the coded aperture can be placed outside of the primary beam path to provide simultaneous 3D transmission and scatter imaging to generate a 4D image that can be utilized for breast screening or diagnostic applications. This breast imaging CT example illustrates one embodiment of the present invention, other embodiments include head CT imaging systems or other specialized CT systems that image specific body regions.

[0058] The following paragraphs highlight additional embodiments of collimators referred to herein, providing examples, but not limitation, of what may be understood as collimators. X-ray collimators can be multi-stage, with elements present to shape or collimate the X-ray beam at different distances from the X-ray source. Many collimators in modern imaging systems have two-stage collimation, with two pairs of jaws closest to the X-ray source creating a square or rectangular illumination, and another two pairs of jaws further away from the X-ray source to further control the divergence and absorb some of the scattered X-rays generated by the first pair of jaws. Additionally, the number of collimation stages can be arbitrary, for example, in one embodiment of the disclosed invention, a third stage can be provided within the primary collimator or near the patient, which does not interact with or absorb the primary X-ray beam, but can function as a guard collimator whose sole purpose is to absorb scattered X-rays generated by the primary beam interacting with the previous collimator stage. Multi-leaf collimators, commonly used in radiation therapy, allow for more complex primary X-ray beam shapes beyond rectangular, and can be utilized within the disclosed embodiments of the invention. In a more simplified case than jaw and multi-leaf collimators, the collimator can have a pinhole collimator that can be moved into the beam path to change the shape of the X-ray primary beam from a cone or fan to a pencil beam X-ray shape. The collimator can further be constructed as one solid manufactured part (either cut from a bulk material or created by additive methods) rather than as separate stages, and its position and orientation can be controlled to image desired areas within the patient's body. Any of the collimator versions described can be used individually or in combination with each other, and since there are many known collimation techniques that can be implemented, they are not intended to be limiting and are provided as examples.

[0059] Beyond the variety of collimator options, there are a variety of methods that may be utilized to create a coded aperture or encoder to aid in localizing the source of scattered X-rays. By way of non-limiting example, the coded aperture may be CNC cut from a metal plate, water jet or laser cut, additive manufacturing methods including 3D printing, or photochemically etched into a metal plate. While these different methods have different limitations and advantages, the resulting manufactured part will be a coded aperture as described in the disclosed embodiments of the invention, useful for a variety of imaging applications including telescope and camera systems, but as applied herein to X-ray scattering imaging.

[0060] On the topic of optional modifications in the design elements of the disclosed invention within the scope of the disclosed invention, embodiments of the disclosed invention may utilize alternatives to physics forward modeling for tissue property estimation while utilizing coded apertures within the imaging system. Both rule-based and machine learning classification algorithms may be operated on the raw encoded scatter data detected without explicitly reconstructing the scattered x-ray spectrum within the pixel / voxel / toxel of the image. Additionally, other reconstruction methods may utilize modeling that is not typically defined as forward modeling to obtain the desired tissue property data from the encoded scattered x-ray measurements, such as inverse modeling or machine learning modeling. The description of the disclosed invention uses the general term forward model to describe what is utilized in describing the physics of this computational system, but this is not intended to be limiting in embodiments that utilize alternative forms of modeling or no modeling at all to estimate tissue properties from the measured encoded x-ray scatter data.

[0061] Regarding the reconstruction algorithms that can be used in the disclosed embodiments of the invention to utilize the measured encoded scattering data to reconstruct data useful for tissue property measurement, there are multiple reconstruction algorithms that can be used without departing from the spirit of the disclosed invention. The reconstruction algorithms can be analytical (e.g., backprojection algorithms used in CT imaging), iterative (e.g., maximum likelihood estimation), machine learning, or any combination of these reconstruction types, examples are provided that are not intended to be limiting. The use of general reconstruction algorithms for coded aperture scattering imaging reconstruction, advanced combinations of reconstruction techniques, or new reconstruction algorithms yet to be invented are within the scope of the disclosed invention.

[0062] In one embodiment, an in vivo tissue imaging system is disclosed. The imaging system includes an X-ray source for irradiating the in vivo tissue with an initial X-ray beam. The imaging system further includes a collimator disposed between the X-ray source and the tissue to direct the initial X-ray beam. The imaging system further includes an X-ray detector array including an at least two-dimensional arrangement of X-ray detection elements, the plurality of X-ray detection elements arranged to detect scattered X-ray radiation from the initial X-ray beam passing through the tissue. The imaging system further includes a coded aperture disposed between the tissue and the X-ray detector array to modulate scattered X-ray radiation from the tissue detected by the X-ray detector array. The imaging system further includes a control system including a processor and a memory. The processor is configured to configure the imaging system for X-ray scatter measurements based on configuration data, the configuration data including at least one of timing data, position data, and orientation data for the X-ray source and the plurality of X-ray detection elements. The processor is further configured to perform X-ray scatter measurements using the configured imaging system. The processor is further configured to receive data representative of the detected scattered X-ray radiation from the X-ray detector array. The processor is further configured to analyze the received data to generate a representation of the irradiated tissue. The representation is generated from the received X-ray scattering data based on the composition data. The representation includes spatially resolved properties of the irradiated tissue.

[0063] In embodiments of the imaging system described above, the representation of the irradiated tissue includes an indication of potentially cancerous regions within the irradiated tissue.

[0064] In an embodiment of the imaging system described above, the processor is further configured to reconstruct an estimate of a spatially resolved X-ray scatter spectrum of the irradiated tissue using the received X-ray scattering data and a forward model of the imaging system. In this embodiment, the estimate of the spatially resolved X-ray scatter spectrum of the irradiated tissue is used to generate a representation of the irradiated tissue.

[0065] In embodiments of the imaging system described above, the processor is further configured to use the configuration data to select an existing forward model of the imaging system or to generate a new forward model of the imaging system using the configuration data.

[0066] In an embodiment of the imaging system described above, a spatially resolved estimate of a momentum transfer spectrum of the irradiated tissue is calculated from the x-ray scattering data, in which the processor is further configured to calculate a spatially resolved estimate of a tissue property of the irradiated tissue using the spatially resolved estimate of the momentum transfer spectrum of the irradiated tissue.

[0067] In embodiments of the imaging system described above, the processor is further configured to calculate a spatially resolved estimate of tissue properties of the irradiated tissue using a reference library of momentum transfer spectra of existing tissues in combination with the spatially resolved estimate of the momentum transfer spectrum of the irradiated tissue.

[0068] In embodiments of the imaging system described above, the processor is further configured to calculate spatially resolved estimates of tissue properties of the irradiated tissue using a classification algorithm.

[0069] In embodiments of the imaging system described above, the processor is further configured to use a machine learning algorithm for classification in computing the spatially resolved estimate of the tissue property.

[0070] In embodiments of the imaging system described above, the processor is further configured to use a rule-based algorithm for classification in computing the spatially resolved estimate of the tissue property.

[0071] In the imaging system embodiment described above, at least one of the coded aperture, the x-ray source, the collimator, or the plurality of x-ray detection elements may be movable. In this embodiment, the processor is further configured to receive configuration data including at least one of position data or orientation data for the coded aperture, the x-ray source, the collimator, or the plurality of x-ray detection elements.

[0072] In an embodiment of the imaging system described above, the X-ray source is an X-ray generator controllable by the processor. In this embodiment, the configuration data further includes at least one of an X-ray source current or an X-ray source voltage.

[0073] In an embodiment of the imaging system described above, the collimator includes an aperture controllable by the processor. In this embodiment, the configuration data further includes at least one of timing data for the controllable aperture, a size of the collimator aperture for configuring the spatial extent of the initial x-ray beam, or a shape of the collimator aperture for configuring the cross-sectional shape of the initial x-ray beam.

[0074] The imaging system embodiment described above further includes a moveable filter controllable by the processor for placement between the x-ray source and the tissue when the x-ray source is irradiating the tissue and for modifying the energy spectrum and irradiance of the initial x-ray beam. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the filter.

[0075] In an embodiment of the imaging system described above, the irradiated tissue is movable and controllable by the processor. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the tissue.

[0076] In an embodiment of the imaging system described above, at least one of the coded aperture, the x-ray source, the collimator, or the plurality of x-ray detector elements is movable and controllable by the processor. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the at least one movable x-ray source, the collimator, the coded aperture, or the plurality of x-ray detector elements.

[0077] In an embodiment of the imaging system described above, at least one of the X-ray source or the plurality of X-ray detector elements is movable and controllable by the processor. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the at least one movable X-ray source or the plurality of X-ray detector elements. In this embodiment, the at least one movable X-ray source or the plurality of X-ray detector elements is operable during movement.

[0078] In an embodiment of the imaging system described above, the at least one movable X-ray source, collimator, coded aperture, or multiple X-ray detection elements are configurable to enable multiple different views of the tissue for X-ray scattering measurements. In this embodiment, the processor is further configured to analyze the X-ray scattering data received from the multiple different views of the tissue to generate a representation of the irradiated tissue.

[0079] In the above-described imaging system embodiments, at least one of the movable X-ray source, collimator, coded aperture, or multiple X-ray detector elements is rotatable about the tissue.

[0080] In an embodiment of the imaging system described above, the processor is further configured to calculate an estimate of a data quality metric for the X-ray scatter data obtained from the configuration data. In this embodiment, the processor is further configured to calculate optimized configuration data using the estimated X-ray scatter data quality metric. In this embodiment, the optimized configuration data is calculated to define a viewpoint for the X-ray scatter measurement of a point in the tissue to satisfy at least one of minimizing attenuation of the initial X-ray beam along an initial X-ray beam path to the point in the tissue or minimizing attenuation of the scattered X-ray signal from the point in the tissue to the X-ray detecting element.

[0081] In an embodiment of the imaging system described above, the processor is further configured to calculate an estimate of a radiation dose to the patient for the X-ray scatter measurement from the configuration data. In this embodiment, the processor is further configured to calculate an estimate of a data quality metric for the obtained X-ray scatter data from the configuration data. In this embodiment, the processor is further configured to calculate optimized configuration data using the estimated radiation dose and the estimated X-ray scatter data quality metric. In this embodiment, the processor is further configured to configure the imaging system for the X-ray scatter measurement based on the calculated configuration data.

[0082] The imaging system embodiment described above further includes a camera for recording the patient. In this embodiment, the processor is further configured to receive recorded data from the camera. In this embodiment, the processor is further configured to analyze the recorded data from the camera to calculate an estimate of patient motion. In this embodiment, the processor is further configured to use the calculated estimate of patient motion in combination with the received x-ray scattering data to generate a representation of the irradiated tissue that accounts for the effects of patient motion.

[0083] In the imaging system embodiment described above, at least one of the X-ray source, the collimator, the coded aperture, or the plurality of X-ray detector elements may be further configurable by the processor. In this embodiment, the processor is further configured to analyze the patient motion estimate to calculate configuration data for at least one further configurable X-ray source, the collimator, the coded aperture, or the plurality of X-ray detector elements. In this embodiment, the configuration data is calculated to minimize the effect of patient motion on the X-ray scatter data. In this embodiment, the processor is further configured to configure the imaging system for X-ray scatter measurements based on the calculated configuration data.

[0084] In the imaging system embodiments described above, a beam block is placed in the path of the initial X-ray beam between the tissue and the X-ray detector array to block the initial X-ray beam during X-ray scatter measurements.

[0085] In an embodiment of the imaging system described above, the coded aperture includes a periodic pattern in at least one dimension having a single attenuating component with an opening focused to a millimeter-scale focal point 100-2000 millimeters away from the coded aperture. In this embodiment, the coded aperture is moveable and controllable by the processor. In this embodiment, the tissue to be irradiated is moveable and controllable by the processor. In this embodiment, the configuration data further includes at least one of timing data for the tissue, position data for the tissue, orientation data for the tissue, timing data for the coded aperture, position data for the coded aperture, or orientation data for the coded aperture to direct the focus of the coded aperture to a point in the tissue.

[0086] In an embodiment of the imaging system described above, the coded aperture includes a set of movable and controllable attenuation components arranged in a pattern that is periodic in at least one dimension. In this embodiment, the tissue to be irradiated is movable and controllable by the processor. In this embodiment, the configuration data further includes at least one of timing data for the tissue, position data for the tissue, orientation data for the tissue, timing data for the attenuation components, position data for the attenuation components, or orientation data for the attenuation components to focus the coded aperture to a millimeter-scale focal spot 100-2000 millimeters away from the coded aperture and to direct the focal spot to a point within the tissue.

[0087] In embodiments of the imaging system described above, the processor is further configured to transmit a representation of the illuminated tissue to a display.

[0088] The imaging system embodiments described above further include at least one of a secondary collimator positioned between the tissue and the X-ray detector array to collimate the scattered X-ray radiation, or a filter positioned between the tissue and the X-ray detector array to modify the energy spectrum and irradiance of the scattered X-ray radiation.

[0089] The imaging system embodiments described above further include a secondary coding aperture disposed between the x-ray source and the tissue and configured to modulate the initial x-ray beam.

[0090] In an embodiment of the imaging system described above, the plurality of x-ray detector elements are positioned to detect x-rays directly transmitted through tissue from the initial x-ray beam, such that the in-vivo imaging system operates as an x-ray transmission imaging system. In this embodiment, the processor is further configured to configure the imaging system for x-ray transmission measurements based on the configuration data. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the x-ray source and the plurality of x-ray detector elements. In this embodiment, the processor is further configured to perform x-ray transmission measurements using the configured imaging system. In this embodiment, the processor is further configured to receive data representative of the detected transmitted x-ray radiation from the x-ray detector array. In this embodiment, the processor is further configured to calculate an x-ray radiodensity tissue image from the received x-ray transmission data.

[0091] In the imaging system embodiments described above, the constructed data for the X-ray transmission measurements is different from the constructed data for the X-ray scattering measurements.

[0092] In an embodiment of the imaging system described above, the coded aperture is movable and controllable by the processor. In this embodiment, the coded aperture is movable to a position where the coded aperture is disposed between the tissue and the X-ray detector array and modulates the scattered X-ray signal during the X-ray scattering measurement. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the coded aperture.

[0093] In an embodiment of the imaging system described above, at least one of the X-ray source, the collimator, or the plurality of X-ray detector elements is movable and controllable by the processor. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the at least one movable X-ray source, the collimator, or the plurality of X-ray detector elements, such that the plurality of X-ray detector elements are offset from an initial X-ray beam path for the X-ray scatter measurement to increase the relative solid angle coverage of the X-ray detector array for a range of X-ray scatter angles from a point in the tissue.

[0094] In an embodiment of the imaging system described above, at least one of the x-ray source, the collimator, the coded aperture, or the plurality of x-ray detecting elements is further configurable by the processor, in this embodiment, the configuration data specifies a configuration of an x-ray scattering measurement subsequent to an x-ray transmission measurement such that the tissue volume imaged during the subsequent x-ray scattering measurement is a sub-region of the tissue volume imaged during the x-ray transmission measurement.

[0095] In an embodiment of the imaging system described above, the processor is further configured to receive a user input to select a sub-region of tissue for X-ray scattering measurements. In this embodiment, the processor is further configured to use the user input to calculate configuration data for at least one further configurable X-ray source, collimator, coded aperture, or a plurality of X-ray detection elements. In this embodiment, the processor is further configured to configure the imaging system for X-ray scattering measurements based on the calculated configuration data.

[0096] In an embodiment of the imaging system described above, the processor is further configured to transmit the x-ray radiodensity tissue image to a display. In this embodiment, the user input includes an indication of a sub-region of the displayed x-ray radiodensity tissue image.

[0097] In an embodiment of the imaging system described above, the processor is further configured to calculate a spatially resolved estimate of the likelihood of cancer from the x-ray radiodensity tissue image. In this embodiment, the processor is further configured to calculate a region of interest in the x-ray radiodensity tissue image using the spatially resolved estimate of the likelihood of cancer. In this embodiment, the processor is further configured to transmit the region of interest data to a display.

[0098] In embodiments of the imaging system described above, the processor is further configured to calculate a region of interest in the x-ray radio density tissue image using a machine learning algorithm.

[0099] The imaging system embodiment described above further includes a beam block that blocks the initial x-ray beam during the x-ray scattering measurement. In this embodiment, the beam block is movable and controllable by the processor. In this embodiment, the beam block is movable to a position that places the beam block in a path of the initial x-ray beam between the tissue and the x-ray detector array to block the initial x-ray beam during the x-ray scattering measurement. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the beam block.

[0100] In embodiments of the imaging system described above, the processor is further configured to configure the imaging system such that the X-ray scattering measurements and the X-ray transmission measurements are performed synchronously.

[0101] In an embodiment of the imaging system described above, the processor is further configured to overlay a representation of the tissue generated from the x-ray scattering data onto an x-ray radiodensity tissue image calculated from the x-ray transmission data, in this embodiment, the processor is further configured to transmit the overlaid representation and image to a display.

[0102] In embodiments of the imaging system described above, the processor is further configured to analyze the received X-ray transmission data in combination with the received X-ray scattering data to generate a representation of the irradiated tissue.

[0103] In an embodiment of the imaging system described above, the X-ray source includes multiple X-ray sources, where at least one X-ray source is configured for X-ray transmission measurements and at least one X-ray source is configured for X-ray scattering measurements.

[0104] In embodiments of the imaging system described above, at least one of the X-ray detection elements is configured to detect transmitted X-ray radiation during X-ray transmission measurements and to detect scattered X-ray radiation during X-ray scattering measurements.

[0105] In an embodiment of the imaging system described above, the processor is further configured to analyze the received X-ray transmission data to calculate an estimate of patient motion. In this embodiment, the processor is further configured to use the estimate of patient motion in combination with the received X-ray scatter data to generate a representation of the irradiated tissue that takes into account the effects of patient motion.

[0106] In the embodiment of the imaging system described above, at least one of the x-ray source, the collimator, the coded aperture, or the plurality of x-ray detection elements is further configurable by the processor. In this embodiment, the processor is further configured to analyze the received x-ray transmission data to calculate configuration data for at least one further configurable x-ray source, the collimator, the coded aperture, or the plurality of x-ray detection elements. In this embodiment, the configuration data is calculated to minimize the effect of patient motion on the x-ray scatter data. In this embodiment, the processor is further configured to configure the imaging system for x-ray scatter measurements based on the calculated configuration data.

[0107] In the embodiment of the imaging system described above, at least one of the X-ray source, the collimator, or the plurality of X-ray detection elements is movable and controllable by the processor. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the at least one movable X-ray source, the collimator, or the plurality of X-ray detection elements, enabling a plurality of different views of the tissue for X-ray transmission measurement. In this embodiment, the processor is further configured to calculate an X-ray transmission computed tomography (CT) reconstruction from the X-ray transmission data received from the plurality of views of the tissue, such that the imaging system operates as an X-ray transmission computed tomography (CT) imaging system.

[0108] In an embodiment of the imaging system described above, at least one of the x-ray source or the plurality of x-ray detector elements is rotatable about the tissue and controllable by the processor. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the at least one rotatable x-ray source or the plurality of x-ray detector elements to enable multiple different views of the tissue for x-ray transmission measurements.

[0109] The imaging system embodiment described above further includes a bore in which the tissue is placed, a rotatable gantry around the bore, and a housing around the gantry. In this embodiment, the X-ray source and the multiple X-ray detector elements are rotatable about the tissue and controllable by the processor. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the rotatable X-ray source and the multiple X-ray detector elements, enabling multiple different views of the tissue for X-ray transmission measurements. In this embodiment, the rotatable X-ray source and the multiple X-ray detector elements are mounted on the gantry and rotate with the gantry.

[0110] In the imaging system embodiment described above, the coded aperture is within a gantry housing of an X-ray transmission computed tomography (CT) imaging system.

[0111] In an embodiment of the imaging system described above, the coded aperture is within the bore of an X-ray transmission computed tomography (CT) imaging system.

[0112] In the imaging system embodiments described above, the coded aperture and the multiple X-ray detection elements positioned to detect scattered X-ray signals are maintained in a position along the bore axis direction in an X-ray transmission computed tomography (CT) imaging system, such that the initial X-ray beam does not impinge on the coded aperture or the multiple X-ray detection elements positioned to detect scattered X-ray signals.

[0113] In an embodiment of the imaging system described above, the x-ray source includes multiple x-ray sources disposed within the imaging system at different locations along the bore or longitudinal axis, where at least one x-ray source is configured for x-ray transmission measurements and at least one x-ray source is configured for x-ray scattering measurements.

[0114] In an embodiment of the imaging system described above, the x-ray source includes multiple x-ray sources, the x-ray sources being positioned within the imaging system at the same location along the bore or longitudinal axis, in which at least one x-ray source is configured for x-ray transmission measurements and at least one x-ray source is configured for x-ray scattering measurements.

[0115] In the embodiment of the imaging system described above, the gantry is movable along the bore axis direction. In this embodiment, the rotatable X-ray source and the multiple X-ray detector elements mounted on the gantry are movable and controllable by the processor. In this embodiment, the movable and rotatable X-ray source and the multiple X-ray detector elements mounted on the gantry are operable during the movement. In this embodiment, the processor is further configured to configure the rotatable and movable X-ray source and the multiple X-ray detector elements to move during the X-ray transmission measurement while the gantry rotates about the bore axis direction and simultaneously moves along the bore axis direction.

[0116] The embodiments of the in-vivo tissue imaging system described above may be integrated into a C-arm X-ray imaging system, a ceiling mounted X-ray imaging system, or a portable / mobile X-ray imaging system.

[0117] In an embodiment of the imaging system as described above, the plurality of x-ray detector elements are arranged to detect x-rays directly transmitted through tissue from the primary x-ray beam, such that the imaging system operates as an x-ray transmission imaging system, and the processor is further configurable to configure the imaging system to perform x-ray transmission measurements based on the configuration data. The configuration data further includes an orientation of the primary beam relative to the bore axis and an exposure time for the x-ray transmission measurements. The processor is further configured to perform the x-ray transmission measurements using the configured imaging system. The processor is further configured to receive data representative of transmitted x-ray radiation detected by the x-ray detector array. The processor is further configured to calculate an x-ray radiodensity tissue image from the received x-ray transmission data.

[0118] In embodiments of the imaging system described above, the processor is further configured to configure the imaging system such that the X-ray scattering measurements and the X-ray transmission measurements are performed synchronously.

[0119] In embodiments of the imaging system described above, the processor is further configured to generate a spatially resolved scattered tissue image based on the received X-ray transmission data and the received X-ray scattering data.

[0120] In embodiments of the imaging system described above, the processor is further configured to estimate a spatially resolved X-ray scattering spectral reconstruction based on the received X-ray scattering data, the received X-ray transmission data and the configuration data.

[0121] In embodiments of the imaging system described above, the X-ray source includes multiple X-ray sources, at least one X-ray source configurable for X-ray transmission measurements and at least one X-ray source configurable for X-ray scattering measurements.

[0122] In embodiments of the imaging system described above, at least one of the X-ray detection elements is positioned to detect transmitted X-ray radiation during an X-ray transmission measurement and to detect scattered X-ray radiation during an X-ray scattering measurement.

[0123] In embodiments of the imaging system described above, the processor is further configured to calculate an estimate of patient motion based on the received X-ray transmission data, and to estimate a spatially resolved X-ray scatter spectral reconstruction based on the received X-ray scatter data and the estimate of patient motion.

[0124] In an embodiment of the imaging system described above, the processor is further configured to calculate configuration data for the X-ray scatter measurement based on the received X-ray transmission data and the effect of patient movement on the X-ray scatter data, and to configure the imaging system for the X-ray scatter measurement based on the calculated configuration data.

[0125] In an embodiment of the imaging system described above, the configuration data for the x-ray transmission measurement further includes multiple orientations of the primary beam about the bore axis, and the x-ray transmission measurement includes measuring x-rays directly transmitted through the tissue from the primary x-ray beam from multiple orientations about the bore axis, and the processor is further configured to calculate an x-ray transmission computed tomography (CT) reconstruction from the x-ray transmission data received from the multiple views of the tissue, such that the imaging system operates as a x-ray transmission computed tomography (CT) imaging system.

[0126] In the above-described imaging system embodiments, the X-ray source includes multiple X-ray sources at different orientations about the bore axis, allowing for generation of primary X-ray beams from multiple directions about the bore axis.

[0127] In the imaging system embodiments described above, the x-ray source is rotatable about the bore axis, allowing the generation of primary x-ray beams from multiple directions about the bore axis.

[0128] In the imaging system embodiment described above, the coded aperture is disposed within the housing.

[0129] In the imaging system embodiment described above, the coded aperture is disposed within the bore.

[0130] In the imaging system embodiments described above, the coded aperture and the multiple X-ray detection elements positioned for detecting scattered X-ray signals are maintained at positions along the bore axis direction within the imaging system, such that the primary X-ray beam does not impinge on the coded aperture or the multiple X-ray detection elements positioned for detecting scattered X-ray signals during scatter measurements.

[0131] In embodiments of the imaging system described above, the X-ray source includes multiple X-ray sources positioned within the imaging system at different positions along the bore axis, at least one X-ray source being configurable for X-ray transmission measurements and at least one X-ray source being configurable for X-ray scattering measurements.

[0132] In embodiments of the imaging system described above, the X-ray source includes multiple X-ray sources disposed within the imaging system at the same position along the bore axis, at least one X-ray source being configurable for X-ray transmission measurements and at least one X-ray source being configurable for X-ray scattering measurements.

[0133] In embodiments of the imaging system described above, the X-ray source and the plurality of X-ray detection elements are translatable along the bore axis direction and operable while being moved, and the processor is further configured to configure the X-ray source and the plurality of X-ray detection elements to translate along the bore axis direction during X-ray transmission measurements.

[0134] In an embodiment of the imaging system described above, the coded aperture is movable to a position between the tissue and the X-ray detector array to modulate the scattered X-ray signal during X-ray scattering measurements, the movement of the coded aperture is controllable by a processor, and the configuration data further includes at least one of timing data, position data, or orientation data for the coded aperture.

[0135] In an embodiment of the imaging system described above, at least one of the X-ray source, collimator, or multiple X-ray detection elements is movable and controllable by the processor, and the configuration data further includes at least one of timing data, position data, or orientation data for the at least one movable X-ray source, collimator, or multiple X-ray detection elements, such that the multiple X-ray detection elements are offset at an angle from the primary X-ray beam path for the X-ray scatter measurement to increase the relative solid angle coverage of the X-ray detector array for a range of X-ray scatter angles from a point in the tissue.

[0136] In embodiments of the imaging system described above, the processor is further configured to identify a patient region of interest based on the X-ray radiodensity tissue image, calculate configuration data for the X-ray scatter measurement based on the identified patient region of interest, and configure the imaging system for the X-ray scatter measurement based on the calculated configuration data.

[0137] In embodiments of the imaging system described above, the processor is further configured to receive user input selecting a region of interest for X-ray scattering measurements.

[0138] In an embodiment of the imaging system described above, the processor is further configured to transmit the X-ray radiodensity tissue image to a display, and the user input includes an indication of a sub-region of the X-ray radiodensity tissue image to be displayed on the display.

[0139] In embodiments of the imaging system described above, the processor is further configured to calculate spatially resolved estimates of tissue properties from the X-ray radio density tissue image and to calculate a region of interest within the X-ray radio density tissue image using the spatially resolved estimates of tissue properties.

[0140] In embodiments of the imaging system described above, the processor is further configured to calculate a region of interest in the x-ray radio density tissue image using a machine learning algorithm.

[0141] In an embodiment of the imaging system described above, the system further includes a movable beam block configurable to move to a position in the path of the primary x-ray beam between the tissue and the x-ray detector array to block the primary x-ray beam during x-ray scattering measurements. The beam block is controllable by the processor, and the configuration data further includes at least one of timing data, position data, or orientation data for the beam block.

[0142] In embodiments of the imaging system described above, the spatially resolved tissue characteristics include a tissue type indicative of cancerous or benign tissue.

[0143] In embodiments of the imaging system described above, the processor is further configured to reconstruct an estimate of a spatially resolved X-ray scattering spectrum of the irradiated tissue using the received X-ray scattering data and a forward model of the imaging system, and the estimate of the spatially resolved X-ray scattering spectrum of the irradiated tissue is used to generate a spatially resolved scattering tissue image.

[0144] In embodiments of the imaging system described above, the processor is further configured to use the configuration data to select an existing forward model of the imaging system or to generate a new forward model of the imaging system using the configuration data.

[0145] In embodiments of the imaging system described above, the processor is further configured to calculate a spatially resolved estimate of the momentum transfer spectrum of the irradiated tissue from the X-ray scattering data, and to generate a spatially resolved scattering tissue image using the spatially resolved estimate of the momentum transfer spectrum of the irradiated tissue.

[0146] In embodiments of the imaging system described above, the processor is further configured to calculate a spatially resolved estimate of tissue properties of the irradiated tissue using a reference library of momentum transfer spectra of existing tissues in combination with the spatially resolved estimate of the momentum transfer spectrum of the irradiated tissue.

[0147] In embodiments of the imaging system described above, the processor is further configured to calculate spatially resolved estimates of tissue properties of the irradiated tissue using a classification algorithm.

[0148] In embodiments of the imaging system described above, the processor is further configured to use a machine learning algorithm for classification in computing the spatially resolved estimate of the tissue property.

[0149] In embodiments of the imaging system described above, the processor is further configured to use a rule-based algorithm for classification in computing the spatially resolved estimate of the tissue property.

[0150] In an embodiment of the imaging system described above, the X-ray source is an X-ray generator controllable by the processor, and the configuration data further includes at least one of an X-ray source current or an X-ray source voltage.

[0151] In an embodiment of the imaging system described above, the collimator includes an aperture configurable in at least one dimension to shape the primary x-ray beam, at least one dimension of the collimator aperture being controllable by the processor, and the configuration data further includes a dimension of the collimator opening.

[0152] In an embodiment of the imaging system described above, the system further includes a moveable filter controllable by the processor for placement between the x-ray source and the tissue when the x-ray source is irradiating the tissue and for modifying the energy spectrum and irradiance of the initial x-ray beam, and the configuration data further includes at least one of timing data, position data, or orientation data for the filter.

[0153] In an embodiment of the imaging system described above, the irradiated tissue is movable and controllable by the processor, and the configuration data further includes at least one of timing data, position data, or orientation data for the tissue.

[0154] In embodiments of the imaging system described above, at least one of the coded aperture, the X-ray source, the collimator or the plurality of X-ray detection elements is movable and controllable by the processor, and the preconfiguration data further includes at least one of timing data, position data or orientation data for the at least one movable X-ray source, the collimator, the coded aperture or the plurality of X-ray detection elements.

[0155] In embodiments of the imaging system described above, at least one or more X-ray detection elements of the X-ray source are movable and controllable by the processor, and the configuration data further includes at least one of timing data, position data or orientation data for the at least one movable X-ray source or the plurality of X-ray detection elements, and the at least one movable X-ray source or the plurality of X-ray detection elements are operable while being moved.

[0156] In an embodiment of the imaging system described above, the configuration data for the X-ray scattering measurement further includes multiple orientations of the primary beam about the bore axis, the X-ray scattering measurement includes measuring scattered X-ray radiation from the primary X-ray beam passing through the tissue from multiple orientations about the bore axis, and the processor is further configured to estimate a spatially resolved X-ray scattering spectral reconstruction of the tissue based on the X-ray scattering data received from the multiple views of the tissue.

[0157] In an embodiment of the imaging system described above, the processor is further configured to calculate an estimate of a data quality metric for the X-ray scattering data obtained from the configuration data, and to calculate optimized configuration data using the estimated X-ray scattering data quality metric.

[0158] In embodiments of the imaging system described above, the processor is further configured to calculate an estimate of the radiation dose to the patient for the X-ray scatter measurement from the configuration data, calculate an estimate of a data quality metric for the X-ray scatter data obtained from the configuration data, and calculate optimized configuration data using the estimated radiation dose and the estimated X-ray scatter data quality metric.

[0159] In an embodiment of the imaging system described above, the system further includes a camera for recording the patient, the processor being further configured to receive recorded data from the camera, calculate an estimate of patient motion based on the received recorded data, and estimate a spatially resolved x-ray scatter spectrum reconstruction based on the received x-ray scatter data and the estimate of patient motion.

[0160] In an embodiment of the imaging system described above, the processor is further configured to calculate calibration data for the X-ray scatter measurements based on the received recorded data, the calibration data being calculated based on an effect of patient motion on the X-ray scatter data.

[0161] In an embodiment of the imaging system described above, the coded aperture includes a periodic pattern in at least one dimension having a single attenuating component with an opening focused to a millimeter-scale focal point between the coded aperture and the X-ray source, the coded aperture is moveable and controllable by the processor, and the tissue to be irradiated is moveable and controllable by the processor, and the configuration data further includes at least one of timing data for the tissue, position data for the tissue, orientation data for the tissue, timing data for the coded aperture, position data for the coded aperture, or orientation data for the coded aperture to direct the focal point of the coded aperture to a point within the tissue.

[0162] In an embodiment of the imaging system described above, the coded aperture includes a set of movable and controllable attenuation components arranged in a periodic pattern in at least one dimension, the tissue to be irradiated is movable and controllable by the processor, and the configuration data further includes at least one of timing data for the tissue, position data for the tissue, orientation data for the tissue, timing data for the attenuation components, position data for the attenuation components, or orientation data for the attenuation components to focus the coded aperture to a millimeter-scale focal spot between the coded aperture and the X-ray source and to direct the focal spot to a point within the tissue.

[0163] In embodiments of the imaging system described above, the system further includes a secondary collimator positioned between the tissue and the X-ray detector array to collimate the scattered X-ray radiation, or a filter positioned between the tissue and the X-ray detector array to modify the energy spectrum and irradiance of the scattered X-ray radiation.

[0164] In an embodiment of the imaging system described above, the system further includes a secondary coding aperture disposed between the x-ray source and the tissue and configured to modulate the initial x-ray beam.

[0165] In another aspect, an imaging system for performing in vivo imaging of a human body is disclosed. The imaging system includes an x-ray source attached to a configurable arm for irradiating an in vivo tissue of at least a portion of the body with a primary x-ray beam. The position and orientation of the x-ray source are adjustable by a user. The imaging system further includes a collimator disposed between the x-ray source and the tissue for shaping the primary x-ray beam. The imaging system further includes an x-ray detector array including a plurality of x-ray detection elements arranged in at least two dimensions. At least one of the x-ray detection elements is disposed distal to the x-ray source outside a path of the primary x-ray beam passing through the irradiated portion of the body and measures scattered x-ray radiation from the primary x-ray beam passing through the tissue. The imaging system further includes a coded aperture disposed between the tissue and the x-ray detector array. The coded aperture is configured to modulate scattered x-ray radiation from the tissue detected by the x-ray detector array. The imaging system further includes a control system including a memory and a processor. The processor is configured to determine configuration data for the imaging system. The configuration data includes a position and an orientation of the X-ray source. The processor is further configured to perform X-ray scattering measurements using the configured imaging system. The processor is further configured to receive data representative of scattered X-ray radiation detected by the X-ray detector array. The processor is further configured to estimate a spatially resolved X-ray scattering spectral reconstruction of the tissue based on the received X-ray scattering data and the configuration data. The processor is further configured to determine spatially resolved tissue properties based on the received X-ray scattering data. The processor is further configured to generate a spatially resolved scattered tissue image based on the received X-ray scattering data.

[0166] In an embodiment of the imaging system described above, the configurable arm is a C-arm, an X-ray source is mounted near a first end of the C-arm, and at least one of the X-ray detector elements is mounted near a second end of the C-arm, and the C-arm is adjustable by a user such that at least a portion of the body is positioned between the X-ray source and the at least one detector element for X-ray scatter measurements.

[0167] In the imaging system embodiments described above, the configurable arm may be mounted to a ceiling, floor, wall, or other fixed surface, or may be mounted to a movable carriage, which may be positioned by a user.

[0168] In the aforementioned imaging system embodiments, at least one x-ray detector element is positioned to detect x-rays directly transmitted through tissue from the initial primary x-ray beam, such that the imaging system operates as an x-ray transmission imaging system. The processor is further configured to perform x-ray transmission measurements using the configured imaging system, receive data representative of transmitted x-ray radiation detected by the x-ray detector array, and calculate an x-ray radio density tissue image from the received x-ray transmission data.

[0169] In embodiments of the imaging system described above, the processor is further configured to determine a position and orientation of the X-ray source based on the received X-ray transmission data.

[0170] According to another aspect, a method of performing in vivo tissue imaging of a human body is disclosed. According to one embodiment, the method includes placing at least a portion of the body in an imaging system. The method further includes configuring the imaging system for X-ray scatter measurements based on configuration data including at least one of timing data, position data, and orientation data for an X-ray source and a plurality of X-ray detector elements configured to rotate about a bore axis of the body. The method further includes performing X-ray scatter measurements using the configured imaging system. The X-ray scatter measurements include irradiating the in vivo tissue with an initial X-ray beam from the X-ray source through a collimator configured to rotate about a bore axis between the X-ray source and the tissue to direct the initial X-ray beam. The X-ray scatter measurements further include modulating scattered X-ray radiation from the tissue using a coded aperture configured to rotate about a bore axis between the tissue and an X-ray detector array including an array of X-ray detector elements in at least two dimensions. The X-ray scatter measurements further include detecting modulated scattered X-ray radiation signals from the tissue using a plurality of X-ray detector elements configured to rotate about the bore axis and positioned to detect scattered X-ray radiation. The X-ray scatter measurement further includes receiving data representative of the detected scattered X-ray radiation from the X-ray detector array. The method further includes analyzing the received data to generate a representation of the irradiated tissue from the received data based on the constituent data. The representation includes spatially resolved properties of the irradiated tissue.

[0171] According to another aspect, a method of in vivo tissue imaging is disclosed. According to one embodiment, the method further includes configuring an imaging system for X-ray scatter measurements based on configuration data including at least one of timing data, position data, and orientation data for an X-ray source and a plurality of X-ray detector elements. The method further includes performing X-ray scatter measurements using the configured imaging system. The X-ray scatter measurements include irradiating the in vivo tissue with an initial X-ray beam from the X-ray source through a collimator disposed between the X-ray source and the tissue to direct the initial X-ray beam. The X-ray scatter measurements further include modulating the scattered X-ray radiation from the tissue using a coded aperture disposed between the tissue and an X-ray detector array including an arrangement of at least two-dimensional X-ray detector elements. The X-ray scatter measurements further include detecting a modulated scattered X-ray radiation signal from the tissue using a plurality of X-ray detector elements arranged to detect the scattered X-ray radiation. The X-ray scatter measurements further include receiving data representative of the detected scattered X-ray radiation from the X-ray detector array. The method further includes analyzing the received data to generate a representation of the irradiated tissue. A representation is generated from the received data, the representation being based on the constituent data, the representation including spatially resolved properties of the irradiated tissue.

[0172] In an embodiment of the aforementioned method, the representation of the irradiated tissue includes an indication of potentially cancerous regions within the irradiated tissue.

[0173] In an embodiment of the method described above, the received X-ray scattering data and a forward model of the in vivo tissue imaging system are used to reconstruct an estimate of the spatially resolved X-ray scattering spectrum of the irradiated tissue. In an embodiment of the method, the estimate of the spatially resolved X-ray scattering spectrum of the irradiated tissue is used to generate a representation of the irradiated tissue.

[0174] Embodiments of the aforementioned method further include using the configuration data to select an existing forward model of the in-vivo tissue imaging system or using the configuration data to generate a new forward model of the in-vivo tissue imaging system.

[0175] An embodiment of the aforementioned method further includes calculating a spatially resolved estimate of a momentum transfer spectrum of the irradiated tissue from the x-ray scattering data. An embodiment further includes calculating a spatially resolved estimate of a tissue property of the irradiated tissue using the spatially resolved estimate of the momentum transfer spectrum of the irradiated tissue.

[0176] In embodiments of the above-described method, a reference library of existing tissue momentum transfer spectra is used in combination with a spatially resolved estimate of the momentum transfer spectrum of the irradiated tissue to calculate a spatially resolved estimate of the tissue properties of the irradiated tissue.

[0177] In embodiments of the aforementioned methods, a classification algorithm is used to calculate spatially resolved estimates of tissue properties of the irradiated tissue.

[0178] In embodiments of the aforementioned methods, machine learning algorithms are used for classification in computing spatially resolved estimates of tissue properties.

[0179] In embodiments of the aforementioned methods, rule-based algorithms are used for classification in computing spatially resolved estimates of tissue properties.

[0180] In an embodiment of the aforementioned method, at least one of the coded aperture, the X-ray source, the collimator, or the plurality of X-ray detecting elements is movable. This embodiment further includes moving the at least one movable coded aperture, the X-ray source, the collimator, or the plurality of X-ray detecting elements prior to the X-ray scattering measurement. This embodiment further includes receiving configuration data including at least one of position data or orientation data for the at least one movable coded aperture, the X-ray source, the collimator, or the plurality of X-ray detecting elements.

[0181] In an embodiment of the aforementioned method, the X-ray source is an X-ray generator controllable by the processor. In this embodiment, the configuration data further includes at least one of an X-ray source current or an X-ray source voltage. This embodiment further includes configuring the X-ray source current or the X-ray source voltage for the X-ray scattering measurement.

[0182] In an embodiment of the aforementioned method, the collimator includes a controllable aperture. In this embodiment, the configuration data further includes at least one of timing data for the controllable aperture, a size of the collimator aperture, or a shape of the collimator aperture. This embodiment further includes at least one of controlling the spatial extent of the initial X-ray beam by configuring a size of the collimator aperture for the X-ray scatter measurement, or controlling a cross-sectional shape of the initial X-ray beam by configuring a shape of the collimator aperture for the X-ray scatter measurement.

[0183] In an embodiment of the aforementioned method, the configuration data further includes at least one of timing data, position data, or orientation data for a movable and controllable filter. This embodiment further includes configuring a position or orientation of the movable filter to modify the energy spectrum and irradiance of the initial x-ray beam by positioning the filter between the x-ray source and tissue for x-ray scattering measurements.

[0184] In an embodiment of the method described above, the irradiated tissue is movable and controllable. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the tissue. This embodiment further includes configuring at least one of the position or orientation of the tissue for the x-ray scattering measurement.

[0185] In an embodiment of the aforementioned method, at least one of the coded aperture, the X-ray source, the collimator, or the plurality of X-ray detecting elements is movable and controllable. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the at least one movable coded aperture, the X-ray source, the collimator, or the plurality of X-ray detecting elements. This embodiment further includes configuring at least one of the position or orientation for the at least one movable coded aperture, the X-ray source, the collimator, or the plurality of X-ray detecting elements for X-ray scattering measurements.

[0186] In an embodiment of the aforementioned method, at least one of the X-ray source or the plurality of X-ray detecting elements is movable and controllable. In this embodiment, the configuration data includes at least one of timing data, position data, or orientation data for the at least one movable X-ray source or the plurality of X-ray detecting elements. In this embodiment, the at least one movable X-ray source or the plurality of X-ray detecting elements is operable while moving. This embodiment further includes configuring the at least one movable X-ray source or the plurality of X-ray detecting elements to move during the X-ray scattering measurement.

[0187] The aforementioned method embodiment further includes controlling a viewpoint of the tissue for the X-ray scattering measurements by configuring at least one of a position or orientation for at least one movable X-ray source, a collimator, a coded aperture, or a plurality of X-ray detecting elements. This embodiment further includes performing a plurality of X-ray scattering measurements from different viewpoints of the tissue. This embodiment further includes analyzing data received from the plurality of different viewpoints to generate a representation of the irradiated tissue.

[0188] In an embodiment of the method described above, the at least one movable x-ray source, collimator, coded aperture, or multiple x-ray detecting elements is rotatable about the tissue. In this embodiment, configuring at least one of the position or orientation for the at least one rotatable x-ray source, collimator, coded aperture, or multiple x-ray detecting elements further includes rotating the at least one movable x-ray source, collimator, coded aperture, or multiple x-ray detecting elements about the tissue.

[0189] An embodiment of the method as described above further includes calculating an estimate of a data quality metric for the X-ray scatter data obtained from the configuration data, and calculating optimized configuration data using the estimated X-ray scatter data quality metric. In this embodiment, the optimized configuration data is calculated to define a viewpoint for the X-ray scatter measurement of a point in the tissue to satisfy at least one of minimizing attenuation of the initial X-ray beam along an initial X-ray beam path to the point in the tissue, or minimizing attenuation of the scattered X-ray signal from the point in the tissue to the X-ray detecting element.

[0190] An embodiment of the method as described above further includes calculating an estimate of a radiation dose to the patient for the X-ray scatter measurement from the configuration data. This embodiment further includes calculating an estimate of a data quality metric for the obtained X-ray scatter data from the configuration data. This embodiment further includes calculating optimized configuration data using the estimated radiation dose and the estimated X-ray scatter data quality metric. This embodiment further includes configuring the imaging system for the X-ray scatter measurement based on the calculated configuration data.

[0191] An embodiment of the method as described above further includes recording the patient with a camera. This embodiment further includes receiving camera recorded data. This embodiment further includes analyzing the recorded data to calculate an estimate of patient motion. This embodiment further includes using the calculated estimate of patient motion in combination with the received x-ray scatter data to generate a representation of the irradiated tissue that accounts for the effects of patient motion.

[0192] In an embodiment of the aforementioned method, at least one of the X-ray source, the collimator, the coded aperture, or the plurality of X-ray detector elements is further configurable. This embodiment further includes analyzing the estimate of the patient motion to calculate configuration data for at least one further configurable X-ray source, the collimator, the coded aperture, or the plurality of X-ray detector elements. In this embodiment, the configuration data is calculated to minimize an effect of the patient motion on the X-ray scatter data. This embodiment further includes configuring the imaging system for X-ray scatter measurements based on the calculated configuration data.

[0193] An embodiment of the above method further includes blocking the initial x-ray beam with a beam block positioned in a path of the initial x-ray beam between the tissue and the x-ray detector array.

[0194] In an embodiment of the aforementioned method, the coded aperture includes a periodic pattern in at least one dimension having a single attenuating component with an opening focused to a millimeter-scale focal point 100-2000 millimeters away from the coded aperture. In this embodiment, the coded aperture is movable and controllable. In this embodiment, the tissue to be irradiated is movable and controllable. In this embodiment, the configuration data further includes at least one of timing data for the tissue, position data for the tissue, orientation data for the tissue, timing data for the coded aperture, position data for the coded aperture, or orientation data for the coded aperture. This embodiment further includes directing the focus of the coded aperture to a point in the tissue for X-ray scattering measurements by configuring at least one of the coded aperture position, coded aperture orientation, tissue position, or tissue orientation.

[0195] In an embodiment of the aforementioned method, the coded aperture includes a set of movable and controllable attenuation components arranged in a periodic pattern in at least one dimension. In this embodiment, the irradiated tissue is movable and controllable by the processor. In this embodiment, the configuration data further includes at least one of timing data for the tissue, position data for the tissue, orientation data for the tissue, timing data for the attenuation component, position data for the attenuation component, or orientation data for the attenuation component. This embodiment further includes focusing the coded aperture to a millimeter-scale focal spot 100-2000 millimeters away from the coded aperture and directing the focal spot to a point in the tissue for X-ray scattering measurements by configuring at least one of the position of the attenuation component, the orientation of the attenuation component, the position for the tissue, or the orientation for the tissue.

[0196] An embodiment of the method as described above further includes transmitting a representation of the illuminated tissue to a display.

[0197] Embodiments of the aforementioned methods further include at least one of collimating the scattered X-ray radiation with a secondary collimator positioned between the tissue and the X-ray detector array, or modifying the energy spectrum and irradiance of the scattered X-ray radiation with a filter positioned between the tissue and the X-ray detector array.

[0198] An embodiment of the aforementioned method further includes modulating the initial x-ray beam with a secondary coded aperture disposed between the x-ray source and the tissue.

[0199] An embodiment of the aforementioned method further includes configuring the imaging system for an x-ray transmission measurement based on the configuration data. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the x-ray source and the plurality of x-ray detection elements. This embodiment further includes performing an x-ray transmission measurement using the configured imaging system. The x-ray transmission measurement includes irradiating the in vivo tissue with an initial x-ray beam from the x-ray source through a collimator. The x-ray transmission measurement further includes detecting x-ray radiation directly transmitted through the tissue by a plurality of x-ray detection elements positioned to detect x-rays directly transmitted through the tissue from the initial x-ray beam such that the imaging system operates as an x-ray transmission imaging system. The x-ray transmission measurement further includes receiving data representative of the detected transmitted x-ray radiation from the x-ray detector array. In this embodiment, the imaging system further includes calculating an x-ray radiodensity tissue image from the received x-ray transmission data.

[0200] In the above method embodiments, the constructed data for the X-ray transmission measurements is different from the constructed data for the X-ray scattering measurements.

[0201] In an embodiment of the aforementioned method, the coded aperture is movable and controllable by the processor. In this embodiment, the coded aperture is movable to a position between the tissue and the X-ray detector array and modulates the scattered X-ray signal during the X-ray scattering measurement. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the coded aperture. This embodiment further includes modulating the scattered X-ray signal by configuring at least one of a position or orientation of the coded aperture such that the coded aperture is disposed between the tissue and the X-ray detector array.

[0202] In an embodiment of the aforementioned method, at least one of the X-ray source, the collimator, or the plurality of X-ray detector elements is movable and controllable. In this embodiment, the configuration data further includes timing data, position data, or orientation data for the at least one movable X-ray source, the collimator, or the plurality of X-ray detector elements. This embodiment further includes configuring at least one of the orientation or position of the at least one movable X-ray source, the collimator, or the plurality of X-ray detector elements to offset the plurality of X-ray detector elements at an angle from an initial X-ray beam path during the X-ray scattering measurement to increase the relative solid angle coverage of the X-ray detector array for a range of X-ray scattering angles from a point in the tissue.

[0203] In an embodiment of the method described above, at least one of the x-ray source, the collimator, the coded aperture, or the plurality of x-ray detecting elements is further configurable, in which the configuration data specifies a configuration of an x-ray scattering measurement subsequent to an x-ray transmission measurement such that the tissue volume imaged during the subsequent x-ray scattering measurement is a sub-region of the tissue volume imaged during the x-ray transmission measurement.

[0204] An embodiment of the method as described above further includes receiving a user input to select a sub-region of tissue for X-ray scatter measurements. This embodiment further includes using the user input to calculate configuration data for at least one further configurable X-ray source, collimator, coded aperture, or a plurality of X-ray detecting elements. This embodiment further includes configuring the imaging system for X-ray scatter measurements at the selected sub-region of tissue based on the calculated configuration data.

[0205] An embodiment of the method as described above further includes transmitting the x-ray radiodensity tissue image to a display, in which the user input includes an indication of a sub-region of the displayed tissue image.

[0206] An embodiment of the method as described above further includes calculating a spatially resolved estimate of cancer likelihood from the x-ray radiodensity tissue image. This embodiment further includes calculating a region of interest in the displayed x-ray radiodensity tissue image using the spatially resolved estimate of cancer likelihood. This embodiment further includes transmitting the region of interest data to a display.

[0207] An embodiment of the aforementioned method further includes using a machine learning algorithm to calculate a region of interest within the displayed x-ray radio density tissue image.

[0208] In an embodiment of the aforementioned method, the configuration data further includes at least one of timing data, position data, or orientation data for the movable and controllable beam block. In this embodiment, the beam block is movable to a position where the beam block is disposed in a path of the initial X-ray beam between the tissue and the X-ray detector array for blocking the initial X-ray beam during the X-ray scattering measurement. This embodiment further includes configuring at least one of a position or orientation of the beam block to place the beam block in the path of the initial X-ray beam between the tissue and the X-ray detector array for the X-ray scattering measurement, thereby blocking the initial X-ray beam.

[0209] An embodiment of the method described above further includes configuring the imaging system such that the X-ray scattering measurements and the X-ray transmission measurements are performed synchronously.

[0210] An embodiment of the method further includes overlaying a representation of the tissue generated from the x-ray scattering data onto an x-ray radiodensity tissue image calculated from the x-ray transmission data, and transmitting the overlaid representation and image to a display.

[0211] An embodiment of the aforementioned method further includes analyzing the received X-ray transmission data in combination with the received X-ray scattering data to generate a representation of the irradiated tissue.

[0212] In an embodiment of the method described above, the X-ray source includes a plurality of X-ray sources. In this embodiment, at least one X-ray source is configured for X-ray transmission measurements and at least one X-ray source is configured for X-ray scattering measurements. This embodiment further includes performing the X-ray transmission measurements using the X-ray source configured for the X-ray transmission measurements and performing the X-ray scattering measurements using the X-ray source configured for the X-ray transmission measurements.

[0213] Embodiments of the aforementioned methods further include configuring at least one of the X-ray detection elements to detect transmitted X-ray radiation during the X-ray transmission measurement and to detect scattered X-ray radiation during the X-ray scattering measurement.

[0214] An embodiment of the method as described above further includes analyzing the received x-ray transmission data to calculate an estimate of patient motion. This embodiment further includes using the estimate of patient motion in combination with the received x-ray scatter data to generate a representation of the irradiated tissue that accounts for the effects of patient motion.

[0215] In an embodiment of the aforementioned method, at least one of the x-ray source, the collimator, the coded aperture, or the plurality of x-ray detector elements is further configurable. This embodiment further includes analyzing the x-ray transmission data to calculate configuration data for at least one further configurable x-ray source, the collimator, the coded aperture, or the plurality of x-ray detector elements. In this embodiment, the configuration data is calculated to minimize the effect of patient motion on the x-ray scatter data. This embodiment further includes configuring the imaging system for x-ray scatter measurements based on the calculated configuration data.

[0216] In an embodiment of the aforementioned method, at least one of the x-ray source, the collimator, or the plurality of x-ray detection elements is movable and controllable. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the at least one movable x-ray source, the collimator, or the plurality of x-ray detection elements. This embodiment further includes controlling a viewpoint of the tissue for the x-ray transmission measurement by configuring at least one of a position or orientation for the at least one movable x-ray source, the collimator, or the plurality of x-ray detection elements. This embodiment further includes performing a plurality of x-ray transmission measurements from different viewpoints of the tissue. This embodiment further includes calculating a x-ray transmission computed tomography (CT) reconstruction from the x-ray transmission data received from the plurality of viewpoints of the tissue such that the imaging system operates as a x-ray transmission computed tomography (CT) imaging system.

[0217] In an embodiment of the method described above, at least one of the x-ray source or x-ray detector is rotatable and controllable about the tissue. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the at least one rotatable x-ray source or the plurality of x-ray detector elements. This embodiment further includes controlling a viewpoint of the tissue for multiple x-ray transmission measurements from different viewpoints by configuring an orientation of the at least one rotatable x-ray source or the plurality of x-ray detector elements about the tissue.

[0218] In an embodiment of the aforementioned method, the x-ray source and the multiple x-ray detector elements are rotatable and controllable about the tissue. In this embodiment, the configuration data further includes at least one of timing data, position data, or orientation data for the rotatable x-ray source and the multiple x-ray detector elements. In this embodiment, the rotatable x-ray source and the multiple x-ray detector elements are mounted on a rotatable gantry in a gantry housing about a bore in which the tissue is located and rotate with the rotatable gantry. This embodiment further includes controlling a viewpoint of the tissue for multiple x-ray transmission measurements from different viewpoints by configuring an orientation of the rotatable x-ray source and the multiple x-ray detector elements on the gantry about the tissue.

[0219] In an embodiment of the aforementioned method, the coded aperture is disposed within a gantry housing of an X-ray transmission computed tomography (CT) imaging system or within a bore of the X-ray transmission computed tomography (CT) imaging system.

[0220] In an embodiment of the above method, the coded aperture and the multiple X-ray detection elements positioned to detect scattered X-ray signals are maintained in a position along the bore axis direction in an X-ray transmission computed tomography (CT) imaging system, such that the initial X-ray beam does not impinge on the coded aperture or the multiple X-ray detection elements positioned to detect scattered X-ray signals.

[0221] In an embodiment of the aforementioned method, the X-ray source includes a plurality of X-ray sources, the X-ray sources being disposed within the X-ray transmission computed tomography (CT) imaging system at different positions along the bore axis. In this embodiment, at least one X-ray source is configured for X-ray transmission measurements and at least one X-ray source is configured for X-ray scattering measurements. This embodiment further includes performing the X-ray transmission measurements using the X-ray source configured for the X-ray transmission measurements and performing the X-ray scattering measurements using the X-ray source configured for the X-ray transmission measurements.

[0222] In an embodiment of the aforementioned method, the X-ray source includes multiple X-ray sources, the X-ray sources being disposed within the X-ray transmission computed tomography (CT) imaging system at the same location along the bore axis. In this embodiment, at least one X-ray source is configured for X-ray transmission measurements and at least one X-ray source is configured for X-ray scattering measurements. This embodiment further includes performing the X-ray transmission measurements using the X-ray source configured for the X-ray transmission measurements and performing the X-ray scattering measurements using the X-ray source configured for the X-ray transmission measurements.

[0223] In an embodiment of the aforementioned method, the gantry is translatable along the bore axis direction with the attached X-ray source and multiple X-ray detector elements. In this embodiment, the rotatable X-ray source and multiple X-ray detector elements are translatable and controllable along the bore axis direction. In this embodiment, the configuration data further includes at least one of position data for the rotatable and translatable X-ray source and multiple X-ray detector elements. In this embodiment, the X-ray source and multiple X-ray detector elements are operable during movement. This embodiment further includes configuring the rotatable and movable X-ray source and multiple X-ray detector elements to move while the gantry rotates about the bore axis direction and simultaneously moves along the bore axis direction during X-ray transmission measurements.

[0224] The above-described method embodiments are performed on a C-arm X-ray imaging system, a ceiling mounted X-ray imaging system, or a portable / mobile X-ray imaging system.

[0225] In one embodiment, a control system of an in vivo tissue imaging system for performing in vivo imaging of a human body is disclosed. The control system includes a memory and a processor. The processor is configured to configure the imaging system for X-ray scatter measurement based on configuration data including at least one of timing data, position data, and orientation data for an X-ray source and a plurality of X-ray detector elements for the X-ray scatter measurement. The processor is further configured to perform the X-ray scatter measurement using the configured imaging system. The X-ray scatter measurement includes irradiating the in vivo tissue with an initial X-ray beam from the X-ray source through a collimator disposed between the X-ray source and the tissue to direct the initial X-ray beam. The X-ray scatter measurement further includes modulating the scattered X-ray radiation from the tissue using a coded aperture disposed between the tissue and an X-ray detector array including an array of X-ray detector elements in at least two dimensions. The X-ray scatter measurement further includes detecting a modulated scattered X-ray radiation signal from the tissue using a plurality of X-ray detector elements arranged to detect the scattered X-ray radiation. The X-ray scatter measurement further includes receiving data at the processor representing the scattered X-ray radiation detected by the X-ray detector array. The processor is further configured to analyze the received data to generate a representation of the irradiated tissue from the received data based on the configuration data, the representation including spatially resolved properties of the irradiated tissue.

[0226] In an embodiment of the control system for an in vivo tissue imaging system disclosed above, the plurality of x-ray detection elements are arranged to detect x-rays directly transmitted through the tissue from the initial x-ray beam, such that the imaging system operates as an x-ray transmission imaging system. The processor is further configured to configure the imaging system for x-ray transmission measurements based on the configuration data. The configuration data further includes at least one of timing data, position data, and orientation data for the x-ray source and the plurality of x-ray detection elements for the x-ray transmission measurements. The processor is further configured to perform x-ray transmission measurements using the configured imaging system. The processor is further configured to receive data representative of transmitted x-ray radiation detected by the x-ray detector array. The processor is further configured to calculate an x-ray radiodensity tissue image from the received x-ray transmission data.

[0227] In the embodiments of the control system for an in-vivo tissue imaging system disclosed above, the configuration data for the X-ray transmission measurements is different from the configuration data for the X-ray scattering measurements.

[0228] In an embodiment of the control system for an in vivo tissue imaging system disclosed above, the coded aperture is movable and controllable by the processor. The coded aperture is movable to a position where the coded aperture is between the tissue and the X-ray detector array and modulates the scattered X-ray signal during an X-ray scattering measurement. The configuration data further includes at least one of timing data, position data, or orientation data for the coded aperture.

[0229] In an embodiment of the control system for the in vivo tissue imaging system disclosed above, at least one of the X-ray source, collimator or multiple X-ray detector elements is movable and controllable by the processor. The configuration data further includes at least one of timing data, position data or orientation data for the at least one movable X-ray source, collimator or multiple X-ray detector elements, such that the multiple X-ray detector elements are offset at an angle from an initial X-ray beam path for the X-ray scatter measurement to increase the relative solid angle coverage of the X-ray detector array for a range of X-ray scatter angles from a point in the tissue.

[0230] In an embodiment of a control system for an in vivo tissue imaging system disclosed above, the configuration data specifies the configuration of an X-ray scattering measurement following an X-ray transmission measurement such that the tissue volume imaged during the subsequent X-ray scattering measurement is a sub-region of the tissue volume imaged during the X-ray transmission measurement.

[0231] In an embodiment of the control system for an in vivo tissue imaging system disclosed above, the processor is further configured to receive user input for selecting a sub-region of tissue for X-ray scattering measurements. The processor is further configured to use the user input to calculate configuration data for the X-ray source, collimator, coded aperture, or multiple X-ray detecting elements. The processor is further configured to configure the imaging system for X-ray scattering measurements based on the calculated configuration data.

[0232] In an embodiment of a control system for an in vivo tissue imaging system disclosed above, the processor is further configured to transmit the X-ray radiodensity tissue image to a display, and the user input includes an indication of a sub-region of the displayed X-ray radiodensity tissue image.

[0233] In an embodiment of the control system for an in vivo tissue imaging system disclosed above, the processor is further configured to calculate a spatially resolved estimate of cancer likelihood from the x-ray radiodensity tissue image. The processor is further configured to calculate a region of interest within the x-ray radiodensity tissue image using the spatially resolved estimate of cancer likelihood. The processor is further configured to transmit the region of interest data to a display.

[0234] In an embodiment of the control system for an in-vivo tissue imaging system disclosed above, the processor is further configured to calculate a region of interest in the X-ray radio density tissue image using a machine learning algorithm.

[0235] In an embodiment of a control system for an in vivo tissue imaging system disclosed above, the configuration data further includes at least one of timing data, position data, or orientation data for a beam block configured to rotate about the bore axis to a position in the path of the initial X-ray beam between the tissue and the X-ray detector array to block the initial X-ray beam during X-ray scattering measurements.

[0236] In an embodiment of the control system for an in-vivo tissue imaging system disclosed above, the processor is further configured to configure the imaging system such that the X-ray scattering measurements and the X-ray transmission measurements are performed synchronously.

[0237] In an embodiment of a control system for an in vivo tissue imaging system disclosed above, the processor is further configured to overlay a representation of the tissue generated from the x-ray scattering data onto an x-ray radiodensity tissue image calculated from the x-ray transmission data, and transmit the overlaid representation and image to a display.

[0238] In an embodiment of a control system for an in vivo tissue imaging system disclosed above, the processor is further configured to analyze the received X-ray transmission data in combination with the received X-ray scattering data to generate a representation of the irradiated tissue.

[0239] In an embodiment of a control system for an in vivo tissue imaging system disclosed above, the processor is further configured to analyze the received x-ray transmission data to calculate an estimate of patient motion, and the processor is further configured to use the estimate of patient motion in combination with the received x-ray scattering data to generate a representation of the irradiated tissue that takes into account the effects of patient motion.

[0240] In an embodiment of the control system for an in-vivo tissue imaging system disclosed above, the processor is further configured to analyze the received X-ray transmission data to calculate configuration data for the X-ray source, collimator, coded aperture, or multiple X-ray detection elements, the configuration data being calculated to minimize an effect of patient motion on the X-ray scatter data, and the processor is further configured to configure the imaging system for X-ray scatter measurements based on the calculated configuration data.

[0241] In an embodiment of the control system for an in vivo tissue imaging system disclosed above, the configuration data further includes at least one of timing data, position data, or orientation data for at least one of the x-ray source, the collimator, or the plurality of x-ray detection elements to enable a plurality of different views of the tissue for x-ray transmission measurements. The processor is further configured to calculate a x-ray transmission computed tomography (CT) reconstruction from the x-ray transmission data received from the plurality of views of the tissue, such that the imaging system operates as a x-ray transmission computed tomography (CT) imaging system.

[0242] In an embodiment of a control system for an in vivo tissue imaging system disclosed above, the configuration data further includes at least one of timing data, position data, or orientation data for the x-ray source or multiple x-ray detection elements to enable multiple different views of the tissue for x-ray transmission measurements.

[0243] In an embodiment of the control system for the in vivo tissue imaging system disclosed above, at least one of the x-ray source and the plurality of x-ray detector elements is rotatable about the tissue and controllable by the processor. The configuration data further includes at least one of timing data, position data, or orientation data for the x-ray source and the plurality of x-ray detector elements to enable multiple different views of the tissue for x-ray transmission measurements. The x-ray source and the plurality of x-ray detector elements are mounted on a rotatable gantry within a gantry housing centered on a bore in which the tissue is located and rotate with the rotatable gantry.

[0244] In an embodiment of a control system for an in vivo tissue imaging system disclosed above, the gantry is movable along the bore axis direction, the X-ray source and the multiple X-ray detection elements mounted on the gantry are movable along the bore axis direction, the X-ray source and the multiple X-ray detection elements mounted on the gantry are operable during the movement, and the processor is further configured to configure the X-ray source and the multiple X-ray detection elements to move during the X-ray transmission measurement while the gantry rotates about the bore axis and simultaneously moves along the bore axis direction.

[0245] In an embodiment of a control system for an in-vivo tissue imaging system disclosed above, the representation of the irradiated tissue includes an indication of potentially cancerous regions within the irradiated tissue.

[0246] In an embodiment of a control system for an in vivo tissue imaging system disclosed above, the processor is further configured to reconstruct an estimate of a spatially resolved X-ray scattering spectrum of the irradiated tissue using the received X-ray scattering data and a forward model of the imaging system, and the estimate of the spatially resolved X-ray scattering spectrum of the irradiated tissue is used to generate a representation of the irradiated tissue.

[0247] In an embodiment of the control system for the in-vivo tissue imaging system disclosed above, the processor is further configured to use the configuration data to select an existing forward model of the imaging system or to generate a new forward model of the imaging system using the configuration data.

[0248] In an embodiment of the control system for an in vivo tissue imaging system disclosed above, the processor is further configured to calculate a spatially resolved estimate of a momentum transfer spectrum of the irradiated tissue from the x-ray scattering data. The processor is further configured to calculate a spatially resolved estimate of a tissue property of the irradiated tissue using the spatially resolved estimate of the momentum transfer spectrum of the irradiated tissue.

[0249] In an embodiment of the control system for the in vivo tissue imaging system disclosed above, the processor is further configured to calculate a spatially resolved estimate of tissue properties of the irradiated tissue using a reference library of momentum transfer spectra of existing tissues in combination with the spatially resolved estimate of the momentum transfer spectrum of the irradiated tissue.

[0250] In an embodiment of the control system for the in vivo tissue imaging system disclosed above, the processor is further configured to calculate spatially resolved estimates of tissue properties of the irradiated tissue using a classification algorithm.

[0251] In an embodiment of the control system for an in-vivo tissue imaging system disclosed above, the processor is further configured to use a machine learning algorithm for classification in computing the spatially resolved estimate of the tissue property.

[0252] In an embodiment of the control system for an in-vivo tissue imaging system disclosed above, the processor is further configured to use a rule-based algorithm for classification in computing the spatially resolved estimate of the tissue property.

[0253] In an embodiment of the control system for the in vivo tissue imaging system disclosed above, the processor is further configured to receive configuration data including at least one of position data or orientation data for at least one of the coded aperture, the x-ray source, the collimator, or the plurality of x-ray detection elements.

[0254] In an embodiment of the control system for the in vivo tissue imaging system disclosed above, the X-ray source is an X-ray generator controllable by the processor, and the configuration data further includes at least one of an X-ray source current or an X-ray source voltage.

[0255] In an embodiment of a control system for an in vivo tissue imaging system disclosed above, the collimator includes a controllable aperture (controllable by the processor), and the configuration data further includes at least one of timing data for the aperture, a size of the aperture for configuring the spatial extent of the initial x-ray beam, or a shape of the aperture for configuring the cross-sectional shape of the initial x-ray beam.

[0256] In an embodiment of the control system for the in vivo tissue imaging system disclosed above, the configuration data further includes at least one of timing data, position data, or orientation data, and the filter is movable in position between the X-ray source and the tissue while the X-ray source is irradiating the tissue to modify the energy spectrum and irradiance of the initial X-ray beam.

[0257] In an embodiment of the control system for the in vivo tissue imaging system disclosed above, the configuration data further includes at least one of timing data, position data, or orientation data for the tissue, wherein the tissue is movable relative to the imaging system.

[0258] In an embodiment of the control system for the in vivo tissue imaging system disclosed above, at least one of the coded aperture, the x-ray source, the collimator or the plurality of x-ray detection elements is movable and controllable by the processor, and the pre-configuration data further includes at least one of timing data, position data or orientation data for the at least one movable x-ray source, collimator, coded aperture or the plurality of x-ray detection elements.

[0259] In an embodiment of the control system for the in vivo tissue imaging system disclosed above, at least one or more X-ray detecting elements of the X-ray source are movable and controllable by the processor, and the configuration data further includes at least one of timing data, position data or orientation data for the at least one movable X-ray source or the plurality of X-ray detecting elements, and the at least one movable X-ray source or the plurality of X-ray detecting elements are operable while being moved.

[0260] In an embodiment of a control system for an in vivo tissue imaging system disclosed above, at least one of the X-ray source, the collimator, the coded aperture, or the plurality of X-ray detection elements is configurable to enable a plurality of different views of the tissue for X-ray scattering measurements, and the processor is further configured to analyze the X-ray scattering data received from the plurality of different views of the tissue to generate a representation of the irradiated tissue.

[0261] In an embodiment of a control system for an in-vivo tissue imaging system disclosed above, the processor is further configured to calculate an estimate of a data quality metric for the X-ray scatter data obtained from the configuration data. The processor is further configured to calculate optimized configuration data using the estimated X-ray scatter data quality metric, the optimized configuration data calculated to define a viewpoint for the X-ray scatter measurement of a point in the tissue to satisfy at least one of minimizing attenuation of the initial X-ray beam along an initial X-ray beam path to the point in the tissue, or minimizing attenuation of the scattered X-ray signal from the point in the tissue to the X-ray detecting element.

[0262] In an embodiment of the control system for the in vivo tissue imaging system disclosed above, the processor is further configured to calculate an estimate of a radiation dose to the patient for the X-ray scatter measurement from the configuration data, calculate an estimate of a data quality metric for the X-ray scatter data obtained from the configuration data, calculate optimized configuration data using the estimated radiation dose and the estimated X-ray scatter data quality metric, and configure the imaging system for the X-ray scatter measurement based on the calculated configuration data.

[0263] In an embodiment of a control system for an in vivo tissue imaging system disclosed above, the processor is further configured to receive recorded data from a camera recording the patient, analyze the recorded data from the camera to calculate an estimate of patient motion, and use the calculated estimate of patient motion in combination with the received X-ray scattering data to generate a representation of the irradiated tissue that takes into account the effects of patient motion.

[0264] In an embodiment of the control system for an in-vivo tissue imaging system disclosed above, the processor is further configured to analyze the estimate of patient motion to calculate configuration data for the x-ray source, collimator, coded aperture, or multiple x-ray detector elements. The configuration data is calculated to minimize the effect of patient motion on the x-ray scatter data. The processor is further configured to configure the imaging system for x-ray scatter measurements based on the calculated configuration data.

[0265] In an embodiment of a control system for an in vivo tissue imaging system disclosed above, the coded aperture includes a periodic pattern in at least one dimension having a single attenuating component with an opening focused to a millimeter-scale focal point 100-2000 millimeters away from the coded aperture, the coded aperture is moveable and controllable by the processor, and the tissue to be irradiated is moveable and controllable by the processor, and the configuration data further includes at least one of timing data for the tissue, position data for the tissue, orientation data for the tissue, timing data for the coded aperture, position data for the coded aperture, or orientation data for the coded aperture to direct the focus of the coded aperture to a point within the tissue.

[0266] In an embodiment of a control system for an in vivo tissue imaging system disclosed above, the coded aperture includes a set of movable and controllable attenuation components arranged in a periodic pattern in at least one dimension, the tissue to be irradiated is movable and controllable by the processor, and the configuration data further includes at least one of timing data for the tissue, position data for the tissue, orientation data for the tissue, timing data for the attenuation components, position data for the attenuation components or orientation data for the attenuation components to focus the coded aperture to a millimeter-scale focal spot 100-2000 millimeters away from the coded aperture and to direct the focal spot to a point within the tissue.

[0267] In an embodiment of a control system for an in-vivo tissue imaging system disclosed above, the processor is further configured to transmit a representation of the illuminated tissue to a display.

[0268] As will be appreciated by those skilled in the art, aspects of the present invention may be embodied as a system, method, or computer program product. Accordingly, aspects of the present invention may take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, microcode, etc.), or an embodiment combining software and hardware aspects, generally referred to herein as a "module" or "system." Additionally, aspects of the present invention may take the form of a computer program product embodied in one or more computer readable medium(s) having computer readable program code embodied therein.

[0269] Any combination of one or more computer readable medium(s) may be utilized. The computer readable medium may be a computer readable signal medium or a computer readable storage medium (including, but not limited to, a non-transitory computer readable storage medium). The computer readable storage medium may be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing. More specific examples (non-exhaustive list) of computer readable storage media include an electrical connection with one or more wires, a portable computer diskette, a hard disk, a random access memory (RAM), a read only memory (ROM), an erasable programmable read only memory (EPROM or flash memory), an optical fiber, a portable compact disk read only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the above. In the context of this specification, a computer readable storage medium may be any tangible medium of expression that can contain or store a program for use by or in connection with an instruction execution system, apparatus, or device.

[0270] A computer-readable signal medium may include a propagated data signal having computer-readable program code embodied therein, for example, in baseband or as part of a carrier wave. Such a propagated signal may take any of a variety of forms, including, but not limited to, electromagnetic, optical, or any suitable combination thereof. A computer-readable signal medium is not a computer-readable storage medium, but may be any computer-readable medium that can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, apparatus, or device.

[0271] The program code embodied by the computer readable medium may be transmitted using any suitable medium, including but not limited to wireless, wired, fiber optic cable, RF, etc., or any suitable combination of the above.

[0272] Computer program code for carrying out operations for embodiments of the present invention may be written in any combination of one or more programming languages, including object-oriented programming languages ​​such as Java, Smalltalk, C++, and conventional procedural programming languages ​​such as the "C" programming language or similar programming languages. The program code may run entirely on the user's computer, partially on the user's computer, as a standalone software package, partially on the user's computer and partially on a remote computer, or entirely on a remote computer or server. In the latter scenario, the remote computer may be connected to the user's computer via any type of network, including a local area network (LAN) or wide area network (WAN), or may be connected to an external computer (e.g., through the Internet using an Internet Service Provider).

[0273] Aspects of the present invention are described below with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of the invention. It will be understood that each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to generate a machine, such that the instructions, executed via a processor of the computer or other programmable data processing apparatus, create means for implementing the functions / acts specified in the flowchart and / or block diagram blocks.

[0274] These computer program instructions may be stored on a computer-readable medium that can direct a computer, other programmable data processing apparatus, or other device to function in a particular manner, such that the instructions stored on the computer-readable medium result in an article of manufacture that includes instructions that implement the functions / acts specified in the flowchart and / or block diagram blocks.

[0275] The computer program instructions may be loaded into a computer, other programmable data processing apparatus, or other device and a series of operational steps may be executed on the computer, other programmable apparatus, or other device to generate a computer-implemented process, such that the instructions executing on the computer or other programmable apparatus provide a process for implementing the function / act specified in the block (or blocks) of the flowcharts and / or block diagrams.

[0276] In certain embodiments, the present invention can connect to multiple displays, printers, workstations, and / or similar devices located locally or remotely, such as within a facility or hospital, or to multiple displays, printers, workstations, and / or similar devices located at entirely different locations, via one or more configurable wired and / or wireless networks, such as the Internet and / or a virtual private network, a wireless telephone network, a wireless local area network, a wired local area network, a wireless wide area network, a wired wide area network, etc. This embodiment can be connected to a picture archiving and communication system (PACS).

[0277] The flowcharts and block diagrams in the drawings illustrate the architecture, functionality and operation of possible implementations of systems, methods and computer program products according to various embodiments of the present invention. In this regard, each block in the flowcharts or block diagrams may represent a module, segment or portion of code, including one or more executable instructions for implementing the specified logical functions. It should be noted that in some alternative implementations, the functions described in the blocks may occur out of the order described in the drawings. For example, two blocks shown in succession may in fact be executed substantially simultaneously, or the blocks may sometimes be executed in the reverse order, depending on the functionality involved. It should also be noted that each block in the block diagrams and / or flowchart diagrams, as well as combinations of blocks in the block diagrams and / or flowchart diagrams, may be implemented by a dedicated hardware-based system that performs the specified functions or operations, or a combination of dedicated hardware and computer instructions.

[0278] The terms used herein are for the purpose of describing particular embodiments only and are not intended to limit the present invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and / or "comprising", as used herein, specify the presence of described features, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0279] In the following claims, the corresponding structure, material, acts, and equivalents of all means-plus-function or step-plus-function elements are intended to include any structure, material, or act for performing that function in combination with other specifically claimed elements. The description of the present invention has been presented for purposes of illustration and description, but is not intended to be exhaustive or limited to the invention in the form disclosed. Many modifications and variations will become apparent to those skilled in the art without departing from the scope and spirit of the invention. The present embodiment has been chosen and described in order to best explain the principles and practical application of the invention and to enable others skilled in the art to understand the invention in various embodiments with various modifications as suited to the particular use contemplated.

[0280] The description of various embodiments of the present invention is presented for illustrative purposes, but is not intended to be exhaustive and is not limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terms used in this specification are selected to best express the principles of the embodiments, practical applications or technical improvements to the technology found in the market, or to enable those skilled in the art to understand the embodiments disclosed herein.

Claims

1. A spatially decomposed volume tissue imaging system for performing in vivo imaging of a patient, wherein the imaging system is A housing comprising a bore and a gantry positioned around the bore, wherein the bore is configured to accommodate at least a portion of the patient along the bore axis, An X-ray source for irradiating at least a portion of the tissue volume of the patient with a primary X-ray beam, The X-ray source is attached to the gantry. The X-ray source is configured to change the direction and exposure time of the primary X-ray beam around the bore axis, To shape the primary X-ray beam, a collimator is positioned between the X-ray source and at least a portion of the patient along the bore axis, An X-ray detector array comprising at least two dimensions and a plurality of X-ray detection elements, At least one of the plurality of X-ray detection elements is positioned distal to the X-ray source outside the path of the primary X-ray beam passing through at least a portion of the irradiated patient, and measures scattered X-ray emission from the primary X-ray beam passing through the tissue volume, and is an X-ray detector array, An encoding aperture positioned between at least a portion of the patient and the X-ray detector array along the bore axis, The encoding aperture is configured to modulate the scattered X-ray emission from the tissue volume detected by the X-ray detector array, A control system including memory and a processor, wherein the processor is The imaging system is configured to perform X-ray scattering measurements based on configuration data including the direction of the primary beam with respect to the bore axis and the exposure time of the X-ray source. Using the imaging system configured above, the X-ray scattering measurement is performed. The X-ray detector array receives data representing scattered X-ray radiation detected by the aforementioned X-ray detector array. The system comprises a control system configured to estimate the spatially resolved X-ray scattering spectral reconstruction of the tissue volume based on the received X-ray scattering data and the configuration data, An imaging system in which spatially resolved tissue characteristics or images thereof are determined based on the estimated spatially resolved X-ray scattering spectral reconstruction of the tissue volume.

2. At least one of the plurality of X-ray detection elements is arranged to detect X-rays that have directly passed through the tissue volume from the primary X-ray beam, and as a result, the imaging system operates as an X-ray transmission imaging system. The aforementioned processor, The imaging system is configured to perform X-ray transmission measurements based on the aforementioned configuration data. The configuration data further includes the direction of the primary beam with respect to the bore axis and the exposure time for the X-ray transmission measurement. Using the imaging system configured above, the X-ray transmission measurement is performed. The X-ray detector array receives data representing transmitted X-ray emission, The imaging system according to claim 1, further configured to calculate X-ray radiation concentration tissue reconstruction from the received X-ray transmission data.

3. The imaging system according to claim 1, wherein the encoding aperture is attached to the gantry or positioned within the bore.

4. The imaging system according to claim 1, wherein at least one of the plurality of X-ray detection elements positioned distal to the X-ray source for detecting the scattered X-ray emission is maintained in a position along the bore axis within the imaging system, so that the primary X-ray beam does not collide with at least one of the plurality of X-ray detection elements positioned for detecting the scattered X-ray emission during the scattering measurement.

5. The encoding aperture is movable along the bore axis between at least a portion of the patient and the X-ray detector array, and modulates the scattered X-ray emission during the X-ray scattering measurement. The movement of the encoding aperture is controllable by the processor. The imaging system according to claim 2, wherein the configuration data further includes at least one of timing data, position data, or direction data for the encoding aperture.

6. The X-ray source, the collimator, or at least one of the plurality of X-ray detection elements is movable and controllable by the processor. The imaging system according to claim 2, wherein the configuration data further includes at least one of timing data, position data, or direction data for at least one of the at least one movable X-ray source, collimator, or plurality of X-ray detection elements, so that as a result, at least one of the plurality of X-ray detection elements is offset at an angle from the primary X-ray beam path for X-ray scattering measurement, thereby increasing the relative solid angle coverage of the X-ray detector array with respect to a range of X-ray scattering angles from a point in the tissue volume.

7. The aforementioned processor, Based on the aforementioned X-ray radiation concentration tissue reconstruction, the patient's region of interest is identified. Based on the identified region of interest of the patient, the configuration data for the X-ray scattering measurement is calculated. The imaging system according to claim 2, further configured to configure the imaging system for X-ray scattering measurement based on the calculated configuration data.

8. The aforementioned processor, From the aforementioned X-ray radiation concentration tissue reconstruction, spatially decomposed estimates of tissue characteristics are calculated. The imaging system according to claim 7, further configured to calculate a region of interest in the X-ray radiation concentration tissue reconstruction using the spatially resolved estimates of the tissue characteristics.

9. The imaging system according to claim 1, wherein the processor is further configured to reconstruct an estimate of the spatially resolved X-ray scattering spectrum of the irradiated tissue volume using the received X-ray scattering data and a forward model of the imaging system.

10. The aforementioned processor, The imaging system according to claim 1, further configured to calculate a spatially resolved estimate of the momentum transfer spectrum of the irradiated tissue volume from the X-ray scattering data.

11. The imaging system according to claim 1, wherein the collimator includes an aperture that can be configured in at least one dimension for shaping the primary X-ray beam, at least one dimension of the collimator aperture is controllable by the processor, and the configuration data further includes the dimension of the aperture of the collimator.

12. The imaging system according to claim 1, wherein at least one of the encoding aperture, the X-ray source, the collimator, or the plurality of X-ray detection elements is movable and controllable by the processor, and the configuration data further includes at least one of timing data, position data, or direction data for the at least one of the movable X-ray source, the collimator, the encoding aperture, or the plurality of X-ray detection elements.

13. The configuration data for the X-ray scattering measurement further includes a plurality of directions of the primary X-ray beam centered on the bore axis, The X-ray scattering measurement includes measuring the scattered X-ray emission from the primary X-ray beam passing through the tissue volume from multiple directions centered on the bore axis, The imaging system according to claim 1, wherein the processor is further configured to estimate the spatially resolved X-ray scattering spectral reconstruction of the tissue volume based on the X-ray scattering data received from a plurality of viewpoints of the tissue volume.

14. The aforementioned processor, From the above configuration data, an estimated value of the radiation dose to the patient for X-ray scattering measurement is calculated. An estimated value of the data quality metric for X-ray scattering data obtained from the above configuration data is calculated. The imaging system according to claim 1, further configured to calculate optimized configuration data using the estimated radiation dose and the estimated value of the X-ray scattering data quality metric.

15. The coding aperture comprises a single attenuation component having at least one-dimensional aperture patterns, the apertures focusing on a millimeter-scale focal point between the coding aperture and the X-ray source. The encoding aperture is movable and controllable by the processor, The imaging system according to claim 1, wherein the irradiated tissue volume is movable and controllable by the processor, and the configuration data further includes at least one of the following: timing data for the tissue volume, position data for the tissue volume, direction data for the tissue volume, timing data for the encoding aperture, position data for the encoding aperture, or direction data for the encoding aperture, in order to direct the focus of the encoding aperture to a point within the tissue volume.

16. The encoding aperture includes a set of movable and controllable attenuation components arranged in a pattern in at least one dimension, The irradiated tissue volume is movable and controllable by the processor. The imaging system according to claim 1, wherein the configuration data further includes at least one of the following: timing data for the tissue volume, position data for the tissue volume, direction data for the tissue volume, timing data for the attenuation component, position data for the attenuation component, or direction data for the attenuation component, in order to focus the encoded aperture to a millimeter-scale focal point between the encoded aperture and the X-ray source and to direct the focal point to a point within the tissue volume.

17. An imaging system for performing in vivo imaging of a patient, wherein the imaging system is: An X-ray source mounted on a configurable arm for irradiating at least a portion of the tissue volume of the patient with a primary X-ray beam, The position or direction of the X-ray source is adjustable by the user, and the X-ray source and To shape the primary X-ray beam, a collimator is placed between the X-ray source and at least a portion of the patient, An X-ray detector array comprising a plurality of X-ray detection elements arranged in at least two dimensions, At least one of the plurality of X-ray detection elements is positioned distal to the X-ray source outside the path of the primary X-ray beam passing through at least a portion of the irradiated patient, and measures scattered X-ray emission from the primary X-ray beam passing through the tissue volume, and is an X-ray detector array, An encoded aperture is positioned between at least a portion of the patient and the X-ray detector array, and is configured to modulate the scattered X-ray emission from the tissue volume detected by the X-ray detector array, A control system including memory and a processor, wherein the processor is The configuration data for the aforementioned imaging system is determined, The aforementioned configuration data includes the position or direction of the X-ray source, Using the imaging system configured above, the X-ray scattering measurement is performed. The X-ray detector array receives data representing scattered X-ray radiation detected by the aforementioned X-ray detector array. Based on the received X-ray scattering data and the configuration data, the system is configured to estimate the spatially resolved X-ray scattering spectral reconstruction of the tissue volume. An imaging system comprising a control system, wherein spatially resolved tissue characteristics or images thereof are determined based on the estimated spatially resolved X-ray scattering spectral reconstruction of the tissue volume.

18. The configurable arm is a C-arm, wherein the X-ray source is mounted near the first end of the C-arm, and at least one of the plurality of X-ray detection elements is mounted near the second end of the C-arm. The imaging system according to claim 17, wherein the C-arm is adjustable by the user so that at least a portion of the patient is positioned between the X-ray source and at least one of the plurality of X-ray detection elements for X-ray scattering measurement.

19. The imaging system according to claim 17, wherein the configurable arm is attached to a ceiling, floor, wall or other fixed surface.

20. The imaging system according to claim 17, wherein the configurable arm is mounted on a movable carriage, the carriage can be positioned by the user.

21. A method for performing in vivo tissue imaging of a patient, wherein the method is To place at least a portion of the aforementioned patients within the imaging system, The imaging system is configured for X-ray scattering measurement based on configuration data including the direction of the primary X-ray beam relative to the bore axis and the exposure time of the X-ray source. This includes performing the X-ray scattering measurement using the imaging system configured above, The aforementioned X-ray scattering measurement is, The primary X-ray beam from the X-ray source is irradiated onto the tissue volume of at least a portion of the patient via a collimator placed between the X-ray source and at least a portion of the patient, and the primary X-ray beam is shaped. Modulation of scattered X-ray emission from the tissue volume using an encoded aperture placed between at least a portion of the patient and an X-ray detector array including at least two-dimensional X-ray detection elements, The modulated scattered X-ray emission from the tissue volume is detected by at least one of the plurality of X-ray detection elements positioned distal to the X-ray source outside the path of the primary X-ray beam passing through at least a portion of the irradiated patient, and the scattered X-ray emission from the primary X-ray beam passing through the tissue volume is measured. Receiving data representing the detected scattered X-ray emission from the X-ray detector array, A method comprising estimating a spatially resolved X-ray scattering spectral reconstruction of the tissue volume based on the received X-ray scattering data and the constituent data, A method in which spatially resolved tissue properties or images thereof are determined based on the estimated spatially resolved X-ray scattering spectral reconstruction of the tissue volume.

22. The imaging system according to claim 1, wherein the processor of the control system is further configured to determine spatially resolved tissue characteristics based on the received X-ray scattering data.

23. The imaging system according to claim 1, wherein the processor of the control system is further configured to generate spatially resolved scattered tissue images based on the received X-ray scattering data.

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