System and method for interactively adjusting intensity window settings in nuclear medicine images

Abstract

Presented herein are systems and methods for providing improved computer-assisted display and analysis of nuclear medicine images. In particular, the systems and methods described herein provide for interactive adjustment of improved intensity window settings for displaying nuclear medicine images. The interactive intensity window selection tool described herein utilizes a nonlinear scaling function that maps user adjustments to the position of a display indicator widget on a scale to an intensity window threshold. The scaling function of the described form gradually amplifies user adjustments at the upper end of the scale, but remains linear at the lower end. The intensity window setting tool presented herein allows the user to adjust the intensity threshold over the full range of intensities encountered in an image, up to a maximum value, while still maintaining fidelity within an important range that includes lower intensities.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to and the benefit of U.S. Provisional Application No. 62 / 837,925, filed April 24, 2019, the contents of which are hereby incorporated by reference in their entirety. Technical Field

[0003] The present invention generally relates to systems and methods for creating, analyzing and / or presenting medical image data. More particularly, in certain embodiments, the present invention relates to systems and methods for improved computer-assisted display and analysis of nuclear medicine images. Background Art

[0004] Nuclear medicine imaging involves the use of radiolabeled compounds, also known as radiopharmaceuticals. Radiopharmaceuticals are administered to patients and accumulate in various areas of the body in a manner that depends on and therefore indicates the biophysical and / or biochemical properties of the tissues therein, such as those affected by the presence and / or status of diseases such as cancer. For example, after administration to a patient, certain radiopharmaceuticals accumulate in areas of abnormal bone formation associated with malignant bone lesions, which indicates metastasis. Other radiopharmaceuticals may bind to specific receptors, enzymes, and proteins in the body that change during the course of the disease. After administration to a patient, these molecules circulate in the blood until they find their intended target. The bound radiopharmaceuticals remain at the site of the disease, while the remaining reagents are cleared from the body.

[0005] Nuclear medicine imaging techniques capture images by detecting the radiation emitted from the radioactive portion of the radiopharmaceutical. The accumulated radiopharmaceutical acts as a beacon, allowing images depicting the location and concentration of the disease to be obtained using conventional nuclear medicine methods. Examples of nuclear medicine imaging methods include bone scan imaging (also known as scintigraphy), single photon emission computed tomography (SPECT), and positron emission tomography (PET). Bone scan, SPECT, and PET imaging systems can be found in most hospitals around the world. The choice of a specific imaging method depends on and / or dictates the specific radiopharmaceutical used. For example, technetium 99m ( 99m Tc)-labeled compounds are compatible with bone scan imaging and SPECT imaging, while PET imaging typically uses fluorinated compounds labeled with 18F. 99m Tc methylene diphosphonate ( 99m Tc MDP) is a popular radiopharmaceutical used in bone scan imaging to detect metastatic cancer. Radiolabeled prostate-specific membrane antigen (PSMA) targeting compounds, such as 99m Tc-labeled 1404 and PyL TM(also known as [18F]DCFPyL), can be used with SPECT and PET imaging, respectively, and offer the potential for highly specific prostate cancer detection.

[0006] Therefore, nuclear medicine imaging is a valuable technology that provides doctors with information that can be used to determine the presence and extent of disease in a patient. Doctors can use this information to provide patients with a recommended course of treatment and to track the progression of the disease.

[0007] For example, an oncologist may use nuclear medicine images from a patient study as input to their assessment of whether the patient has a particular disease (e.g., prostate cancer), the apparent stage of the disease, the recommended course of treatment (if any), the need for surgical intervention, and the likely prognosis. The oncologist may use a radiologist's report in this assessment. A radiologist's report is a technical evaluation of the nuclear medicine images that the radiologist prepares for the physician who requested the imaging study and contains, for example, the type of study performed, the clinical history, comparisons between the images, the techniques used to perform the study, the radiologist's observations and findings, and the radiologist's overall impression and recommendations based on the results of the imaging study. The signed radiologist's report is sent to the physician who requested the study for review, and the physician then discusses the results and treatment recommendations with the patient.

[0008] Thus, the process involves having a radiologist perform an imaging study on the patient, analyzing the images obtained, creating a radiologist's report, forwarding the report to the requesting physician, having the physician formulate an evaluation and treatment recommendation, and having the physician communicate the results, recommendations, and risks to the patient. The process may also involve repeating the imaging study due to inconclusive results or requesting further testing based on the initial results. If the imaging studies indicate that the patient has a specific disease or condition (e.g., cancer), the physician will discuss various treatment options, including surgery, as well as the risks of doing nothing or taking a watchful waiting or active surveillance approach without surgery.

[0009] Therefore, the process of reviewing and analyzing multiple patient images over time plays a crucial role in the diagnosis and treatment of cancer. Therefore, there is a significant need for improved tools that facilitate and improve the accuracy of image review and analysis for cancer diagnosis and treatment. Improving the toolkit used by physicians, radiologists, and other healthcare professionals in this way could significantly improve the standard of care and the patient experience. Summary of the Invention

[0010] Presented herein are systems and methods for providing improved computer-assisted display and analysis of nuclear medicine images. In particular, the systems and methods described herein provide for interactive adjustment of improved intensity window settings for displaying nuclear medicine images. The interactive intensity window selection tool described herein utilizes a nonlinear scaling function that maps user adjustments to the position of a display indicator widget on a scale to an intensity window threshold. The scaling function of the described form gradually amplifies user adjustments at the upper end of the scale, but remains linear at the lower end. The intensity window setting tool presented herein allows the user to adjust the intensity threshold over the full range of intensities encountered in the image, up to a maximum value, while still maintaining fidelity within an important range that includes lower intensities. This approach allows the user to analyze in detail high-intensity areas that typically represent metastases.

[0011] Intensity windowing is used to render images for display and is part of the process of converting the underlying stored pixel values ​​of an image (which may be in a variety of units and vary over a wide range of values) into the brightness levels and / or different colors that are visually displayed on a screen such as a computer monitor. In particular, the intensity of a pixel in a medical image typically represents and / or is determined based on a physical quantity, such as an electrical signal (e.g., current or voltage) produced by a detector, the power of light or another form of electromagnetic radiation, photon counts, etc. In a bone scan image, pixel intensity represents (e.g., in) photon counts, which are the number of photons registered from the radioactive decay of a radiopharmaceutical injected into the patient and accumulated in the patient's body prior to recording the image.

[0012] When rendering an image for display, the pixel intensities are converted to grayscale or different colors so that changes in the intensity representing the physical signal can be visually inspected. For example, the intensity of a pixel in a bone scan image may range from a minimum of 0 counts to a maximum of approximately 10,000 counts. In order to display the bone scan image as an 8-bit (e.g., 256-level) grayscale image, the different pixel intensities are assigned (e.g., mapped to) integer grayscale levels from 0 (e.g., black) to 255 (e.g., white). An intensity window of 0 to 10,000 may initially be used, so that, for example, intensities from 0 to 10,000 are converted to grayscale values ​​from 0 to 255 using a linear function. Intensities of 0 or less will be assigned a grayscale value of 0, and intensities of 10,000 or greater will be mapped to a grayscale value of 255.

[0013] However, using a limited number of gray levels to represent such a wide range of intensity values ​​means that small fluctuations in intensity are masked, making such subtle color changes indistinguishable to the human eye even if more bits are used. Therefore, the intensity window can be adjusted to emphasize significant fluctuations and make them appear within a small subrange of intensity values. For example, rendering and displaying an image using an intensity window from 500 to 2,500 allocates all 256 gray levels to represent the subrange of 500 to 2,500 counts. In this way, small intensity fluctuations within this subrange are emphasized and easily observed, but at the expense of making variations outside the intensity window unobservable.

[0014] Intensity windows can also be used to facilitate visual comparison between two or more images by rendering them in a way that compensates for overall variations in their underlying intensities, such as a constant baseline and / or multiplicative scaling, which arise from external influences and correspond to noise. By choosing different intensity windows for different images, these effects are minimized or removed from the images when rendered and displayed, and only meaningful, desired intensity fluctuations are apparent.

[0015] Addressing such uncontrolled variations via intensity window settings is particularly important for bone scan imaging, as well as other nuclear medicine imaging modalities (e.g., SPECT imaging). In particular, as described herein, bone scan images are obtained by injecting a patient with a radioactive drug that accumulates in various regions of the patient's body and emits radiation that is detected to form an image. High accumulation results in high levels of radioactivity, which in turn results in high count values. High intensities or count values ​​in an image region indicate a large amount of accumulation, while zero count values ​​mean zero or very low radioactivity, and therefore, a lower accumulation. Therefore, fluctuations in intensity-count values ​​in a bone scan image can be used to infer the accumulation level of the radioactive drug in different regions, and therefore to infer the presence and / or status of a disease (e.g., metastasis).

[0016] Although comparison of multiple images is often important for assessing disease state and / or progression (e.g., tracking disease progression in a single patient over time or comparing multiple patients in a study to evaluate the efficacy of a drug, etc.), non-zero intensity values ​​are generally not comparable between different bone scan images. This is because the exact intensity values ​​(photon counts) recorded also depend on a complex combination of factors such as dose, scan time, patient characteristics, and camera hardware. Therefore, healthcare professionals reading bone scan images will use intensity windowing to adjust how the brightness and / or color levels of displayed image pixels are determined based on their underlying intensity values ​​in the image so that similar areas have similar brightness and / or color levels when displayed. Thus, intensity windowing allows images from different studies, such as images recorded from a patient at different time points, to be displayed in a manner that allows them to be visually compared to each other and analyzed in a meaningful way.

[0017] It is worth noting that adjusting the intensity window in this manner is not a trivial task. In particular, the very wide range of intensity values ​​that bone scan image pixels can assume makes it challenging to finely and accurately adjust the intensity window threshold within this wide range. This is particularly problematic in images of patients with metastatic cancer, as radiopharmaceuticals accumulate in large quantities in metastases, resulting in extremely high intensities in the corresponding image pixels. The interactive intensity window adjustment tool described herein addresses this challenge through a unique graphical control that allows the user to adjust the position of the display indicator widget along a scale. The graphical control utilizes a nonlinear scaling function to map increments along the scale to intensity values, allowing the intensity window threshold to be calculated based on adjustments to the display indicator widget position. A special form of the scaling function is chosen to amplify user adjustments to the intensity threshold at the upper end of the scale, where intensity changes rapidly and reaches extremes, while maintaining linearity and allowing for finer adjustments at the lower end of the scale, where high fidelity is required.

[0018] In this way, the methods described herein allow users to easily analyze in detail high-intensity areas that often represent metastases. Previously, setting intensity windows to allow investigation of such high-intensity areas was extremely challenging, time-consuming, tedious, or simply impossible. The user-friendly graphical controls and adjustment procedures of the present disclosure allow users to make adjustments in a convenient manner without having to consider the challenges addressed by the underlying scaling procedures. To the user, the software tools provided herein appear to "just work," allowing them to focus their attention on important tasks such as image review and decision making.

[0019] In one aspect, the present invention relates to a method for interactively adjusting an intensity window threshold to display a nuclear medicine image (e.g., a bone scan image; e.g., a PET image; e.g., a SPECT image), the method comprising: (a) accessing (e.g., receiving) the nuclear medicine image by a processor of a computing device, the image comprising a plurality of pixels [e.g., pixels representing a 2D area; e.g., pixels representing a 3D volume (e.g., voxels)], each pixel having an intensity representing a level of a detection signal (e.g., photon counts; e.g., detector voltage; e.g., detection power); and (b) rendering the nuclear medicine image by the processor according to an initial intensity window for imaging. a graphical display, the rendering comprising visually representing the pixel intensities using a set of available color map values ​​[e.g., a set of grayscale and / or RGB values ​​provided by a particular bit depth for the graphics display (e.g., 8-bit, 16-bit, 32-bit, etc.)] such that the full range of available color map values ​​is assigned to a subset of the pixel intensities within a range from a minimum threshold of the initial intensity window to a maximum threshold of the initial intensity window [e.g., a single minimum color map value of the set is used to represent pixel intensity values ​​less than or equal to the minimum intensity threshold, and a single maximum color map value of the set is used to represent pixel intensity values ​​greater than or equal to the maximum intensity threshold]; (c) by the processing The processor causes display of a graphical control element to enable user selection of a subsequent intensity window different from the initial intensity window via user adjustment of one or more display indicator widgets according to which one or more thresholds for the subsequent intensity window are determined, wherein the display indicator widgets are adjustable along a scale having increments mapped to intensity values ​​via a scaling function, wherein the scaling function is non-linear for at least a portion of the increments; (d) receiving, by the processor, the user selection of the subsequent intensity window corresponding to the adjusted position of the one or more display indicator widgets of the graphical control element; and (e) receiving, in response to the user selection of the subsequent intensity window, (f) causing, by the processor, display of the updated rendering from step (e), thereby dynamically updating (e.g., in real time) the display of the nuclear medicine image as the user adjusts selection of the one or more display indicator widgets to select the subsequent intensity window.

[0020] In some embodiments, the method repeats steps (d)-(f) to update and display the nuclear medicine image in real time as the user adjusts the subsequent intensity window.

[0021] In some embodiments, the graphical control element includes a visual representation of the scale as a path (e.g., a slider), wherein the display indicator widget has an adjustable (e.g., via user interaction with the graphical control element, such as clicking, dragging, and dropping, etc.) position along the path.

[0022] In some embodiments, the scale includes reference increments mapped to reference intensity values, and the graphical control element includes a visual indication of the reference increments along the path.

[0023] In some embodiments, a minimum increment of the scale maps to an intensity value of 0, and a maximum increment of the scale maps to a maximum intensity value in the nuclear medicine image.

[0024] In some embodiments, the scale includes reference increments mapped to reference intensity values, wherein the scaling function has a greater slope for intensity values ​​above the reference intensity value than for intensity values ​​below the reference increments.

[0025] In some embodiments, the scaling function is non-linear above the reference intensity value and linear below the reference intensity value.

[0026] In some embodiments, the method includes: before step (b), the processor normalizing the nuclear medicine image using a normalization factor (e.g., a preset normalization factor; e.g., an automatically determined normalization factor; e.g., a user-selected normalization factor) to produce a normalized version of the nuclear medicine image for rendering and display; and calculating, by the processor, the reference intensity value as a function of the normalization factor [e.g., wherein the reference increment is proportional to the normalization factor (e.g., calculated as a predetermined constant multiplied by the normalization factor)].

[0027] In some embodiments, the reference increment is located more than halfway along the scale from the smallest end to the largest end of the scale (eg, two-thirds along the scale).

[0028] In some embodiments, the method includes: before step (b), the processor normalizing the nuclear medicine image using a normalization factor (e.g., a preset normalization factor; e.g., an automatically determined normalization factor; e.g., a user-selected normalization factor) to generate a normalized version of the nuclear medicine image for rendering and display.

[0029] In some embodiments, the normalization factor is determined by the processor (e.g., iteratively) identifying healthy tissue regions in the nuclear medicine image that are determined to not contain any hot spots (e.g., local areas of relatively high intensity) and calculating the normalization factor by the processor such that the product of the normalization factor and the average intensity of the identified healthy tissue regions is a predefined intensity level.

[0030] In certain embodiments, the nuclear medicine image is a bone scan image (eg, a whole body bone scan image).

[0031] In another aspect, the present invention relates to a system for interactively adjusting an intensity window threshold for displaying a nuclear medicine image (e.g., a scintigraphy image; e.g., a PET image; e.g., a SPECT image), the system comprising: a processor of a computing device; and a memory having instructions stored thereon, wherein the instructions, when executed by the processor, cause the processor to: (a) access (e.g., receive) the nuclear medicine image, the image comprising a plurality of pixels [e.g., pixels representing a 2D area; e.g., pixels representing a 3D volume (e.g., voxels)], each pixel having a value representing a detection signal (e.g., photon count; e.g., detector voltage; e.g., photon count); e.g., photon voltage; ... (e.g., intensity of a level of detection power); (b) rendering the nuclear medicine image for graphic display according to an initial intensity window using a set of available color map values ​​[e.g., a set of grayscale and / or RGB values ​​provided by a particular bit depth for graphic display (e.g., 8-bit, 16-bit, 32-bit, etc.)] to visually represent the pixel intensities such that the full range of available color map values ​​is assigned to a subset of the pixel intensities within a range from a minimum threshold value of the initial intensity window to a maximum threshold value of the initial intensity window [e.g., pixel intensity values ​​less than or equal to the minimum intensity threshold value are represented using a single minimum color map value of the set, and pixel intensity values ​​less than or equal to the minimum intensity threshold value are represented using a single maximum color map value of the set] (c) causing display of a graphical control element to enable user selection of a subsequent intensity window different from the initial intensity window via user adjustment of one or more display indicator widgets according to which one or more thresholds for the subsequent intensity window are determined, wherein the display indicator widgets are adjustable along a scale having increments mapped to intensity values ​​via a scaling function, wherein the scaling function is non-linear for at least a portion of the increments; and (d) receiving the user selection of the subsequent intensity window corresponding to the adjusted position of the one or more display indicator widgets of the graphical control element. (e) in response to receiving the subsequent intensity window, rendering the nuclear medicine image for a graphical display according to the subsequent intensity window using the set of available color map values ​​to visually represent the pixel intensities such that the full range of available color map values ​​is assigned to a subset of the pixel intensities within a range from a minimum threshold value of the subsequent intensity window to a maximum threshold value of the subsequent intensity window, thereby creating an updated rendering; and (f) causing display of the updated rendering from step (e) to dynamically update (e.g., in real time) the display of the nuclear medicine image as the user adjusts selection of the one or more display indicator widgets to make selection of the subsequent intensity window.

[0032] In some embodiments, the instructions cause the processor to repeat steps (d)-(f) to update and display the nuclear medicine image in real time as the user adjusts the subsequent intensity window.

[0033] In some embodiments, the graphical control element includes a visual representation of the scale as a path (e.g., a slider), wherein the display indicator widget has an adjustable (e.g., via user interaction with the graphical control element, such as clicking, dragging, and dropping, etc.) position along the path.

[0034] In some embodiments, the scale includes reference increments mapped to reference intensity values, and the graphical control element includes a visual indication of the reference increments along the path.

[0035] In some embodiments, a minimum increment of the scale maps to an intensity value of 0, and a maximum increment of the scale maps to a maximum intensity value in the nuclear medicine image.

[0036] In some embodiments, the scale includes reference increments mapped to reference intensity values, wherein the scaling function has a greater slope for intensity values ​​above the reference intensity value than for intensity values ​​below the reference increments.

[0037] In some embodiments, the scaling function is non-linear above the reference intensity value and linear below the reference intensity value.

[0038] In some embodiments, the instructions cause the processor to: prior to step (b), normalize the nuclear medicine image using a normalization factor (e.g., a preset normalization factor; e.g., an automatically determined normalization factor; e.g., a user-selected normalization factor) to produce a normalized version of the nuclear medicine image for rendering and display; and calculate the reference intensity value as a function of the normalization factor [e.g., wherein the reference increment is proportional to the normalization factor (e.g., calculated as a predetermined constant multiplied by the normalization factor)].

[0039] In some embodiments, the reference increment is located more than halfway along the scale from the smallest end to the largest end of the scale (eg, two-thirds along the scale).

[0040] In some embodiments, the instructions cause the processor, prior to step (b), to: normalize the nuclear medicine image using a normalization factor (e.g., a preset normalization factor; e.g., an automatically determined normalization factor; e.g., a user-selected normalization factor) to generate a normalized version of the nuclear medicine image for rendering and display.

[0041] In some embodiments, the instructions cause the processor to determine the normalization factor by (e.g., iteratively) identifying healthy tissue regions in the nuclear medicine image that are determined to not contain any hot spots (e.g., local areas of relatively high intensity) and calculating the normalization factor such that the product of the normalization factor and the average intensity of the identified healthy tissue regions is a predefined intensity level.

[0042] In certain embodiments, the nuclear medicine image is a bone scan image (eg, a whole body bone scan image).

[0043] Embodiments described with respect to one aspect of the invention may be applicable to another aspect of the invention (e.g., it is contemplated that features of embodiments described with respect to one independent claim, such as a method claim, are applicable to other embodiments of other independent claims, such as a system claim, and vice versa). BRIEF DESCRIPTION OF THE DRAWINGS

[0044] The foregoing and other objects, aspects, features and advantages of the present disclosure will become more apparent and better understood by referring to the following description taken in conjunction with the accompanying drawings, in which:

[0045] Figure 1 is a set of bone scan images from three studies of the same patient, displayed without normalization and without intensity window adjustment, according to an illustrative embodiment.

[0046] Figure 2 According to an illustrative embodiment Figure 1 The same set of bone scan images shown in , after normalization and displayed using the initial intensity window.

[0047] Figure 3 is a diagram illustrating the use of intensity windows for image display in accordance with one illustrative embodiment.

[0048] Figure 4 is a screenshot of a graphical user interface for viewing a bone scan image, wherein the GUI includes graphical controls for adjusting an intensity window used to display the bone scan image, according to an illustrative embodiment.

[0049] Figure 5 is a block flow diagram illustrating a process for interactively adjusting an intensity window according to the methods described herein, according to one illustrative embodiment.

[0050] Figure 6 is a diagram illustrating different slider scaling methods according to an illustrative embodiment.

[0051] Figure 7is a graph illustrating a scaling function that maps user-adjustable scale increments (slider positions) to intensity window thresholds in accordance with one illustrative embodiment.

[0052] Figure 8A is a block flow diagram illustrating a quality control and reporting workflow for generating a BSI report according to one illustrative embodiment.

[0053] Figure 8B is a screenshot of a graphical user interface (GUI) for selecting patient data for review according to an illustrative embodiment. Figure 8A The software-based implementation of the quality control and reporting workflow is shown.

[0054] Figure 8C is a screen shot of a graphical user interface (GUI) for reviewing patient information according to an illustrative embodiment. Figure 8A The software-based implementation of the quality control and reporting workflow is shown.

[0055] Figure 8D is a screenshot of a graphical user interface (GUI) for reviewing a patient's image data and editing hotspot selections according to an illustrative embodiment. Figure 8A The software-based implementation of the quality control and reporting workflow is shown.

[0056] Figure 8E is a screenshot of a graphical user interface (GUI) according to an illustrative embodiment of an automatically generated report that a user follows Figure 8A The software-based implementation of the quality control and reporting workflow shown in FIG was generated.

[0057] Figure 9A is a screenshot of a GUI window displaying a bone scan image, which uses an intensity window that covers only a limited range of intensity values.

[0058] Figure 9B is a screenshot of a GUI window displaying a bone scan image using the intensity window up to a maximum intensity value in accordance with an illustrative embodiment.

[0059] Figure 9C yes Figure 9A A screenshot of a portion of the GUI in Figure 1 shows the graphical controls for adjusting the intensity window threshold.

[0060] Figure 9D yes Figure 9BA screenshot of a portion of the GUI in , showing another graphical control for adjusting the intensity window threshold.

[0061] Figure 9E is a screenshot of a GUI displaying the anterior and posterior images of a bone scan image set, with each image displayed using a separate intensity window.

[0062] Figure 9F is a screenshot of the GUI showing the anterior and posterior images of a bone scan image set, where the same intensity window is used for both images.

[0063] Figure 10 is a block diagram of an exemplary cloud computing environment used in certain embodiments.

[0064] Figure 11 is a block diagram of an exemplary computing device and an exemplary mobile computing device used in certain embodiments

[0065] The features and advantages of the present disclosure will become more apparent from the following detailed description taken in conjunction with the accompanying drawings, in which like reference numerals identify corresponding elements throughout the text. In the drawings, like reference numerals generally indicate identical, functionally similar, and / or structurally similar elements. DETAILED DESCRIPTION

[0066] It is contemplated that the systems, apparatuses, methods, and processes claimed herein cover variations and adaptations developed using information from the embodiments described herein. Adaptations and / or modifications of the systems, apparatuses, methods, and processes described herein may be made by one of ordinary skill in the relevant art.

[0067] Throughout this specification, if articles, apparatuses, and systems are described as having, containing, or comprising particular components, or processes and methods are described as having, containing, or comprising particular steps, it is contemplated that there are additionally articles, apparatuses, and systems of the invention that consist of, or consist essentially of, those components, and that there are processes and methods of the invention that consist of, or consist essentially of, those process steps.

[0068] Should be understood that, as long as the present invention remains operable, the order of steps or the order in which certain actions are performed is irrelevant.In addition, two or more steps or actions can be performed simultaneously.

[0069] Reference herein to any publication, such as in the Background section, is not an admission that the publication is prior art with respect to any claim presented herein. The Background section is presented for clarity purposes and is not intended as a description of prior art with respect to any claim.

[0070] Headings are provided for the convenience of the reader - the presence and / or arrangement of headings is not intended to limit the scope of the subject matter described herein.

[0071] In this application, unless otherwise stated, the use of "or" means "and / or". As used in this application, the term "comprise" and variations of the term, such as "comprising / comprises", are not intended to exclude other additives, components, integers or steps. As used in this application, the terms "about" and "approximately" are used as equivalents. Any number used in this application with or without about / approximately is intended to cover any normal fluctuations understood by one of ordinary skill in the relevant art. In certain embodiments, the term "about" or "approximately" refers to a range of values ​​that falls within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1% or less in either direction (greater than or less than) of the reference value, unless otherwise stated or obvious from the context (unless such number would exceed 100% of the possible value).

[0072] The articles "a" and "an" are used herein to refer to one or more than one (i.e., to at least one) of the grammatical object of the article. For example, "an element" refers to one element or more than one element. Thus, in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to a pharmaceutical composition comprising "an agent" includes reference to two or more agents.

[0073] The systems and methods described herein relate to a unique and user-friendly method for selecting an intensity window for displaying nuclear medicine images. The method is described herein with particular reference to bone scan (also known as scintigraphy) images, but is also applicable to other nuclear medicine imaging modalities where intensity window adjustment is required or can be used for comparison between images. Such adjustment is particularly important for imaging modalities where measured intensity values ​​are not standardized to common units or reference values ​​and may vary due to a constant baseline and / or multiplication factors. This presents significant challenges to meaningful review and comparison of images, and is present in scintigraphy images as well as, for example, single photon emission tomography (SPECT) images.

[0074] A. Nuclear medicine images

[0075] Nuclear medicine images are obtained using nuclear imaging modalities such as bone scan imaging, positron emission tomography (PET) imaging, and single photon emission tomography (SPECT) imaging.

[0076] As used herein, an "image"—e.g., a 3-D image of a mammal—includes any visual representation, such as a photograph, a video frame, a streaming video, and any electronic, digital, or mathematical simulation of a photograph, video frame, or streaming video. In certain embodiments, any apparatus described herein includes a display for displaying an image or any other result generated by a processor. In certain embodiments, any method described herein includes a step of displaying an image or any other result generated by the method.

[0077] As used herein, "3-D" or "three-dimensional" with respect to an "image" is intended to convey information about three dimensions. A 3-D image may be rendered as a three-dimensional data set and / or may be displayed as a set of two-dimensional representations or as a three-dimensional representation.

[0078] In certain embodiments, nuclear medicine images use imaging agents that include radiopharmaceuticals. Nuclear medicine images are obtained after administering a radiopharmaceutical to a patient (e.g., a human subject) and provide information about the distribution of the radiopharmaceutical within the patient's body. A radiopharmaceutical is a compound that includes a radionuclide.

[0079] As used herein, "administering" an agent refers to introducing a substance (e.g., an imaging agent) into a subject. Generally, any route of administration can be utilized, including, for example, parenteral (e.g., intravenous), oral, topical, subcutaneous, peritoneal, intraarterial, inhalation, vaginal, rectal, nasal, introduction into the cerebrospinal fluid, or instillation into a body compartment.

[0080] As used herein, "radionuclide" refers to a moiety that includes a radioactive isotope of at least one element. Exemplary suitable radionuclides include, but are not limited to, those described herein. In some embodiments, the radionuclide is a radionuclide used in positron emission tomography (PET). In some embodiments, the radionuclide is a radionuclide used in single photon emission computed tomography (SPECT). In some embodiments, a non-limiting list of radionuclides includes 99m Tc, 111 In, 64 Cu, 67 Ga, 68 Ga, 186 Re、 188 Re、 153 Sm, 177 Lu, 67 Cu, 123 I. 124 I. 125 I. 126 I. 131 I. 11 C. 13 N.15 O. 18 F. 153 Sm, 166 Ho, 177 Lu, 149 Pm, 90 Y. 213 Bi, 103 Pd, 109 Pd, 159 Gd, 140 La, 198 Au, 199 Au, 169 Yb, 175 Yb, 165 Dy, 166 Dy, 105 Rh, 111 Ag, 89 Zr, 225 Ac, 82 Rb, 75 Br, 76 Br, 77 Br, 80 Br, 80m Br, 82 Br, 83 Br, 211 At and 192 Ir.

[0081] As used herein, the term "radiopharmaceutical" refers to a compound that includes a radionuclide. In certain embodiments, radiopharmaceuticals are used for diagnostic and / or therapeutic purposes. In certain embodiments, radiopharmaceuticals include small molecules labeled with one or more radionuclides, antibodies labeled with one or more radionuclides, and antigen-binding portions of antibodies labeled with one or more radionuclides.

[0082] Nuclear medicine images (e.g., PET scans; e.g., SPECT scans; e.g., whole-body bone scans; e.g., composite PET-CT images; e.g., composite SPECT-CT images) detect radiation emitted from the radionuclide of a radiopharmaceutical to form an image. The distribution of a particular radiopharmaceutical within a patient's body can be determined by biological mechanisms such as blood flow or perfusion, as well as specific enzymatic or receptor binding interactions. Different radiopharmaceuticals can be designed to exploit different biological mechanisms and / or specific specific enzymatic or receptor binding interactions, and thus selectively concentrate in specific types of tissues and / or regions within the patient's body when administered to the patient. Greater amounts of radiation will be emitted from regions of the patient's body that have higher concentrations of the radiopharmaceutical than other regions, causing these regions to appear brighter in the nuclear medicine image. Therefore, intensity variations within a nuclear medicine image can be used to map the distribution of the radiopharmaceutical within the patient's body. For example, such a mapped distribution of the radiopharmaceutical within the patient's body can be used to infer the presence of cancerous tissue within various regions of the patient's body.

[0083] For example, after administration to a patient, technetium-99m methylene diphosphonate ( 99m Tc MDP) selectively accumulates in bone regions of the patient, particularly at sites of abnormal bone formation associated with malignant bone lesions. The selective concentration of the radiopharmaceutical at these sites produces identifiable hot spots—localized areas of high intensity—in nuclear medicine images. Therefore, the presence of malignant bone lesions associated with metastatic prostate cancer can be inferred by identifying such hot spots in a patient's whole-body scan. As described below, the presence of malignant bone lesions associated with metastatic prostate cancer can be determined based on the presence of these hot spots. 99m Automated analysis of intensity changes in whole-body scans obtained after administration of Tc MDP to a patient is used to calculate a risk index associated with the patient's overall survival and other prognostic indicators of disease status, progression, treatment efficacy, etc. In certain embodiments, a method similar to 99m Tc MDP approaches use other radiopharmaceuticals.

[0084] In some embodiments, the specific radiopharmaceutical used depends on the specific nuclear medicine imaging modality used. For example, 18F sodium fluoride (NaF) can also accumulate in bone lesions, similar to 99m Tc MDP, but can be used with PET imaging. In certain embodiments, PET imaging can also utilize a radioactive form of the vitamin choline, which is readily taken up by prostate cancer cells.

[0085] In certain embodiments, radiopharmaceuticals that selectively bind to specific proteins or receptors of interest, particularly those whose expression is increased in cancer tissue, may be used. Such proteins or receptors of interest include, but are not limited to, tumor antigens such as CEA, which is expressed in colorectal cancer; Her2 / neu, which is expressed in various cancers; BRCA 1 and BRCA2, which are expressed in breast and ovarian cancers; and TRP-1 and -2, which are expressed in melanomas.

[0086] For example, human prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer (including metastatic disease). PSMA is expressed in almost all prostate cancers, and its expression is further increased in poorly differentiated, metastatic, and hormone-refractory cancers. Therefore, radiopharmaceuticals corresponding to PSMA binders (e.g., compounds with high affinity for PSMA) labeled with one or more radionuclides can be used to obtain nuclear medicine images of patients, based on which the presence and / or status of prostate cancer in multiple regions of the patient (e.g., including but not limited to bone regions) can be assessed. In certain embodiments, when the disease is localized, nuclear medicine images obtained using PSMA binders are used to identify the presence of cancerous tissue within the prostate. In certain embodiments, nuclear medicine images obtained using radiopharmaceuticals including PSMA binders are used to identify the presence of cancerous tissue in multiple regions, including not only the prostate, but also other organs and tissue regions, such as the lungs, lymph nodes, and bones, which is relevant when the disease is metastatic.

[0087] In particular, after administration to a patient, radionuclide-labeled PSMA-binding agents selectively accumulate in cancer tissue based on their affinity for PSMA. 99m In a manner similar to that described for Tc MDP, the selective concentration of a radionuclide-labeled PSMA binder at specific sites within a patient's body can produce detectable hotspots in nuclear medicine images. Because the PSMA binder concentrates in various cancerous tissues and regions of the body that express PSMA, localized cancer within a patient's prostate and / or metastatic cancer in various regions of the patient's body can be detected and evaluated. Risk indices associated with a patient's overall survival and other prognostic indicators of disease status, progression, treatment efficacy, etc. can be calculated based on automated analysis of intensity changes in nuclear medicine images obtained after administration of a PSMA-binding radiopharmaceutical to a patient.

[0088] Various radionuclide-labeled PSMA binding agents can be used as radiopharmaceutical imaging agents for nuclear medicine imaging to detect and evaluate prostate cancer. In certain embodiments, the specific radionuclide-labeled PSMA binding agent used depends on factors such as the specific imaging modality (e.g., PET; e.g., SPECT) and the specific area (e.g., organ) of the patient to be imaged. For example, certain radionuclide-labeled PSMA binding agents are suitable for PET imaging, while others are suitable for SPECT imaging. For example, certain radionuclide-labeled PSMA binding agents are convenient for imaging the patient's prostate and are primarily used when the disease is localized, while others are convenient for imaging organs and regions throughout the patient's body and can be used to evaluate metastatic prostate cancer.

[0089] Various PSMA-binding agents and radionuclide-labeled versions thereof are described in U.S. Patent Nos. 8,778,305, 8,211,401, and 8,962,799, each of which is incorporated herein by reference in its entirety. Several PSMA-binding agents and radionuclide-labeled versions thereof are also described in PCT application PCT / US2017 / 058418, filed October 26, 2017, the contents of which are incorporated herein by reference in their entirety.

[0090] B. Bone scan images

[0091] In a scintigraphy image, the intensity value of an image pixel represents a count, which is the number of photons registered by the decay of a radiopharmaceutical injected into a patient prior to the scan. As described herein, for example, in Section A above, radiopharmaceuticals accumulate in various structures in the body based on, for example, their biochemical properties, and the intensity (e.g., count) of image pixels corresponding to physical locations in those structures varies with the accumulation of radiopharmaceutical therein. Higher accumulation results in high levels of radioactivity, which in turn results in high count values. A pixel with zero intensity or count value indicates zero or very low radioactivity at the corresponding physical location in the patient's body, and therefore indicates lower accumulation of radiopharmaceutical.

[0092] However, non-zero intensity values ​​are not comparable between different scintigraphy image scans because they depend on a complex combination of factors, such as dose, scan time, patient characteristics, and camera hardware. These factors can vary from scan to scan and affect the accumulation level of the radiopharmaceutical itself as well as the efficiency of measuring the emitted photon counts. To account for this variability between scans, healthcare professionals who read bone scan images therefore display bone scan images using intensity windowing so that similar areas are displayed at similar brightness and / or color levels. This facilitates comparison and analysis of displayed images, such as Figure 1 and Figure 2 , they show that without intensity window setting ( Figure 1 ) and with intensity window settings ( Figure 2 ) in the same patient but at different times.

[0093] As used herein, the term "intensity window" refers to a range (window) of pixel intensity values ​​within which the brightness and / or color levels of the rendering vary with the underlying image pixel intensity. Outside the intensity window, the brightness and / or color levels used to render the image pixels for display remain constant even if the underlying pixel intensity values ​​change. Intensity windows are typically defined based on minimum and maximum threshold values. Pixel intensities from 0 to the minimum threshold are all displayed using the same minimum brightness or color level value, and pixel intensities above the maximum threshold are all displayed using the same maximum brightness or color level value. Pixel intensities from the minimum threshold to the maximum threshold fall within the intensity window and are displayed using brightness or color levels that vary with the pixel intensity.

[0094] For example, the pixel intensities of medical images (e.g., nuclear medicine images) typically represent physical values, such as counts. Such pixel intensities can vary over a wide range of values ​​and have integer or floating point units. For display, these underlying pixel values ​​are mapped to available colormap (e.g., grayscale; e.g., RGB) values. Using an intensity window allows the use of a full range of grayscale or color levels to represent the portion of the pixel intensities that fall within the intensity window. Because the full range of grayscale and / or color levels is used to represent a limited range of pixel intensities, this approach can make pixel intensity variations within the intensity window easier to observe. However, intensity variations outside the window are not observable because a single minimum and / or maximum grayscale and / or color level is used to represent all intensities above and / or below the window.

[0095] Figure 3 A diagram is shown which illustrates the use of two different intensity windows to display an image using 256 gray levels. As shown in the figure, the first intensity window has minimum and maximum thresholds T1 and T2, respectively. min and T1 max , and the second intensity window has minimum and maximum thresholds T2 respectively min and T2 max When the first intensity window is used, the full range of gray levels from 0 to 255 is used to represent T1 min To T1 max Pixel intensity changes. Below T1 min The intensity is expressed as the minimum gray level 0, and the intensity above T1 maxThe intensity of the image is represented using a maximum grayscale level of 255. The second intensity window has a different threshold and therefore allocates the full range of grayscale levels to represent different parts of the underlying pixel intensity value. In this way, intensity windowing can be used to render and display images in a manner that accounts for non-normalized variations from image to image (e.g., penalizing scale differences and baseline shifts) and thus allows them to be compared when displayed.

[0096] C. Interactive Selection and Adjustment of Intensity Window

[0097] The selection of an intensity window is very important and can be challenging and time consuming even for trained healthcare professionals responsible for image review and analysis. In particular, the very wide range of intensity values ​​that bone scan image pixels can assume makes it challenging to finely and accurately adjust the intensity window threshold within such a wide range of values. This is particularly problematic in images of patients with metastatic cancer because radiopharmaceuticals accumulate in large quantities in metastases, resulting in extremely high intensities in the corresponding image pixels. The interactive intensity window adjustment tool described herein provides a convenient and user-friendly interface for adjusting the intensity window threshold value. Figure 4 , which allow the user to adjust the position of the display indicator widget along the scale) addresses this challenge. Figure 4 A graphical control element is shown in which the display indicator widget is an adjustable slider along a path. Other controls and widget elements are also possible, for example, the display indicator widget can be a radio button, a circular dial, various simulacrum controls, etc. The graphical control uses a nonlinear scaling function to map increments along the scale to intensity values, so that the intensity window threshold is calculated based on the adjustment of the position of the display indicator widget. A special form of scaling function is selected to amplify the user's adjustment of the intensity threshold at the upper end of the scale where the intensity changes rapidly and reaches extreme values, but still maintains linearity and allows finer adjustments at the lower end of the scale where high fidelity is required.

[0098] In this way, the method described here allows users to easily analyze in detail the high-intensity regions that often represent metastases. Previously, setting up intensity windows to allow for investigation of such high-intensity regions was extremely challenging, time-consuming, tedious, or simply impossible. User-friendly graphical controls and adjustment procedures allow users to make adjustments in a convenient manner without having to consider the challenges addressed by the underlying scaling procedures. To the user, the software tools presented here appear to "just work," allowing them to focus their attention on important tasks such as image review and decision making.

[0099] Figure 5 An exemplary process 500 for interactively adjusting intensity window settings for displaying a nuclear medicine image is shown. In a first step, a nuclear medicine image is accessed and / or received by a processor. Figure 1A set of 100 bone scan images 102, 104, 106 are shown for a particular patient but obtained at different times. The images 102, 104, and 106 are not normalized and are displayed without intensity windowing. Even when similar areas of the patient are compared, the overall intensity, and therefore the displayed grayscale, varies greatly from image to image.

[0100] In order to display such images in a manner that allows them to be compared in a meaningful way, normalization 504 and intensity windowing 506 steps may be performed. Figure 2 Shown with Figure 1 The same set of bone scan images, but displayed after normalization and using intensity windowing. The displayed grayscale is now comparable between the different images 202, 204 and 206, allowing them to be analyzed and compared.

[0101] In some embodiments, the image is first normalized using a normalization factor. The normalization factor can be a multiplicative factor that, when used, scales the intensity of the image pixels so that the average intensity within the region identified as corresponding to healthy bone tissue is a predefined constant. The normalization factor that scales the average healthy pixel intensity to a value of 1000 is used to normalize the image. Figure 2 The images shown in [ 1 ] were normalized. The level of 1000 is arbitrary and needs to be the same across studies and patients. The normalization performed is strictly multiplicative and does not change the known reference level of zero counts—zero counts will remain zero counts after normalization.

[0102] In certain embodiments, to determine the normalization factor, healthy tissue regions within the nuclear medicine image to be normalized are first identified. Such regions can be identified by automatic segmentation to identify a graphical representation of the skeleton in the nuclear medicine image, followed by automatic identification of hot spots corresponding to localized areas of high intensity. Image pixels located within the identified graphical representation of the skeleton but outside any identified hot spots are identified as belonging to healthy tissue regions. The intensities of these pixels are then used to determine the average intensity of healthy bone tissue and, therefore, the normalization factor. An example of an iterative method for normalizing bone scan images in this manner is described in U.S. patent application No. 15 / 282,422 filed on September 30, 2016 and U.S. Patent No. 8,855,387 issued on October 7, 2014 (of which U.S. patent application No. 15 / 282,422 is a reissued patent), the contents of each of which are hereby incorporated by reference in their entirety.

[0103] Rendering and display using a fixed initial intensity window 506 Figure 2In some embodiments, automatic normalization allows the image to be displayed using a fixed initial intensity window suitable for an overview (e.g., a rough, high-level review) of the bone scan image. However, in some embodiments, adjustment of the intensity window setting is performed to select subsequent different intensity windows to allow the image to be displayed so that areas of high or low uptake can be investigated in more detail. A graphical user interface (GUI) for displaying and / or reviewing bone scan images can include a graphical control element that provides for selection of subsequent intensity windows 508.

[0104] Figure 4 4. A screen shot of an exemplary GUI is shown that includes a graphical control element 404 for user selection of a subsequent intensity window. The graphical control element 404 is a slider that allows the user to select the minimum and maximum threshold values ​​for the subsequent intensity window by adjusting the position of the display indicator widgets 406a and 406b along the slider bar. The slider scale ranges from the minimum to the maximum possible intensity window threshold values, and the position along the slider scale is mapped to an intensity value. The minimum and maximum threshold values ​​for the intensity window are calculated based on the position of the display indicator widget, allowing the user to adjust them via interaction with the slider 404. In this way, the user selection of the subsequent intensity window is received 510 via the graphical control element and rendered for graphical display 512 using the subsequent intensity window. The GUI 400 can display the updated bone scan image 402 so that the user can interactively adjust the graphical controls and view the results.

[0105] The previous method uses a slider scale of 0 to 100, where the minimum scale increment of 0 represents a count of 0, and the maximum scale increment of 100 represents a reference value r, which is set proportional to the normalization factor. Changing the position of the display indicator widget along this slider scale produces a corresponding proportional (e.g., linear) change in the threshold value of the intensity window.

[0106] An exemplary reference value is r = 7000 / f, where f is the normalization factor, and the initial intensity window is set from 0 to r. Therefore, previous methods do not allow the maximum threshold to be increased above the reference value. Because the pixel intensity corresponding to the metastatic area may be higher than the reference value, previous methods do not allow detailed investigation of these areas.

[0107] Allowing the slider scale to represent pixel intensity values ​​from 0 to the maximum intensity found in each image would cover the entire range of intensities that might be of interest, but would sacrifice the control over how far the user can adjust the threshold below a reference value. Since this range, at the bottom of the scale, is most useful in practice, simply expanding the slider scale range is not a viable approach.

[0108] In contrast, the systems and methods described herein utilize a custom slider with a range from 0 (left) to a maximum value (right), but use a non-linear scale with a reference level located at 2 / 3 of the distance from the maximum value.

[0109] The proposed bottom scale places the reference value at 2 / 3 of the way from 0 to the maximum value. To ensure a familiar user experience, the size of the window increases linearly between 0 and the reference value. A nonlinear (e.g., quadratic) function is used between the reference value and the maximum value, where the derivative is equal to the derivative of the linear curve at the reference point. The curve then increases towards the maximum value in a nonlinear (e.g., quadratic) manner. This approach allows exploration of the entire intensity window without losing the important fidelity in the 0 to reference range.

[0110] Figure 6 The custom slider 606 described herein is shown in comparison with the two other approaches described above. Figure 6 As shown in FIG, a limited linear slider 602 from 0 to a reference value prevents the user from adjusting the threshold above the reference level and prohibits exploration of high-intensity regions. However, a larger linear slider (slider 604) from 0 to the maximum intensity value provides an unmanageably small 0 to reference portion, making meaningful adjustment of the intensity window threshold within the important 0 to reference range impossible. Custom slider 606 uses a nonlinear function over a portion of the scale (the higher end) and addresses the shortcomings of other approaches, thereby providing new functionality.

[0111] An exemplary method for determining a slider scaling function is as follows, where r is a reference value and the maximum intensity value found in the image is denoted as m. The scale increments are from 0 to 1.5, where an increment of 1 corresponds to a reference increment that is mapped to a reference value. For intensity values ​​from 0 to r, the scaling function that maps a position x on the scale to an intensity value f(x) is:

[0112] f1(x)=rx,

[0113] where f1(0) = 0 and f1(1) = r. The derivative f1′(x) is f1′(x) = r, indicating that the slope of the curve is r. For the upper range of the scale, corresponding to increments from 1 to 1.5, which map to intensity values ​​from r to m, a nonlinear quadratic function f2(x) is used. This is of the form f2(x) = a + bx + cx 2 A quadratic function where the values ​​of the constants a, b, and c are such that f2(1) = r, f2′(1) = r, and f2(1.5) = m. In other words, the nonlinear part of the scaling function should have the value r at 1, the slope r at 1, and the value m at 1.5. This system of three equations with three unknowns (a, b, and c) has a unique solution. Solving for a, b, and c yields:

[0114] a=c=4m–6r, and

[0115] b=13r–8m.

[0116] Therefore, the equation for the nonlinear part of the resulting scaling function is,

[0117] f2(x)=4m–6r+(13r–8m)x+(4m–6r)x 2

[0118] Figure 7 A graph of the scaling function is shown for typical values ​​of r and m. As can be seen from graph 700, the scaling function has a linear portion 702 from 0 to 1 (corresponding to intensity values ​​from 0 to r) and a non-linear quadratic portion 704 from 1 to 1.5 (corresponding to intensity values ​​from r to m).

[0119] In some embodiments, the maximum value m is less than 1.5 r. In these cases, a linear function can be used over the entire range of 0 to m (eg, the use of a nonlinear function is not required and may introduce unexpected complexity to this simple case).

[0120] D. Example 1: Improved Intensity Windowing for Image Review in a Cloud-Based Processing, Display, and Quality Control Workflow for Calculating Bone Scan Index Values

[0121] In certain embodiments, the graphical control and interactive intensity window setting methods described herein facilitate the review of the automated analysis of bone scan images as part of a GUI-based automated analysis workflow to determine an index that provides a measurement of the disease state in a patient. Example 1 demonstrates the use of graphical control elements to facilitate an automated image review and reporting workflow as part of an image analysis and reporting workflow used in a cloud-based system for analyzing medical images and determining a risk index representing the disease state and / or progression in a patient. In particular, the example illustrates software developed and incorporating the intensity window setting methods described herein to calculate an automated bone scan index (aBSI) value based on a whole-body bone scan image. BSI calculations are described in U.S. patent application No. 15 / 282,422, filed September 30, 2016, and U.S. Patent No. 8,855,387, issued October 7, 2014 (of which U.S. patent application No. 15 / 282,422 is a reissued patent), the contents of each of which are hereby incorporated by reference in their entirety. A cloud-based platform including cloud-based BSI computing is described in PCT application number PCT / US17 / 58418, filed on October 26, 2017, the contents of which are hereby incorporated by reference in their entirety.

[0122] Figure 8Ais a block flow diagram illustrating a quality control and reporting workflow for generating a BSI report according to one illustrative embodiment. In certain embodiments, the intensity window adjustment tool described herein is implemented as part of a GUI for guiding a user (e.g., a healthcare professional) through reviewing and analyzing patient image data to calculate an automatic BSI value and generate a report.

[0123] A first GUI window may be presented to the user, such as Figure 8B The window shown in Figure 1 allows the user to select a specific patient from the list for review / analysis. Figure 8B When a specific patient's row is found in the list, a window showing the patient's information is displayed. Figure 8C New and / or updated windows are shown in .

[0124] Steering Figure 8D , the user can then access the review page of the guided analysis software. The review page provides a GUI for the user (e.g., a healthcare professional, such as a doctor), which allows them to review the image data and the automatic hotspot identification performed by the software backend in order to calculate the patient's automatic BSI index. As described above, the automatic BSI calculation technology is described in U.S. patent application No. 15 / 282,422 filed on September 30, 2016 and U.S. Patent No. 8,855,387 issued on October 7, 2014 (of which U.S. patent application No. 15 / 282,422 is a reissue patent) and PCT application No. PCT / US17 / 58418 filed on October 26, 2017, the contents of each of which are hereby incorporated by reference in their entirety.

[0125] The user can use the Review page GUI to edit the set of regions identified as hotspots and must confirm that the image quality, bone segmentation (as outlined in the screenshot), and the set of identified hotspots have been reviewed in order to proceed with report generation. Once the user's review and quality control are confirmed, a report can be generated, such as one containing the final BSI calculation. Figure 8E The report shown in .

[0126] The intensity window adjustment graphical control described herein is incorporated into the review page GUI and allows the user to adjust the intensity window used to render and display bone scan images. Figure 9A -D demonstrates a significant improvement in image rendering provided by the techniques described herein over previous methods. Figure 9A An image 902 is shown rendered and displayed using a previous software version, which implemented a conventional linear slider with a limited range - Figure 6 Even with the slider indicator widget set to the far end of the scale, the maximum threshold is too low and the patient's pelvic region is clearly saturated. Figure 9BThe new custom slider described herein (e.g., Figure 6 6) which can be used to increase the intensity window threshold above a reference value, up to the maximum intensity value encountered in the image. The rendered and displayed image 906 is free of saturation, and the user can easily explore high intensity fluctuations in the patient's pelvic region. Although the image is shown using inverted grayscale, other coloring schemes (often referred to as colormaps) are possible, with window 904 showing an earlier version of a set of colormap options and window 908 showing an updated set of colormap options. Figure 9C and 9D Various embodiments of graphical control elements for adjusting an indicator widget to select an intensity window threshold are shown. Figure 9B and 9D The slider shown in FIG is an elegant user-friendly graphical control, but variations and other types of controls are possible (e.g., a control using multiple sliders, such as Figure 9C and other controls, such as a circular dial, various skeuomorphic controls, etc.).

[0127] Steering Figure 9E and 9F Once a subsequent intensity window is selected, it can be used to render a single image or applied to multiple images simultaneously. For example, bone scan images are often collected in a set that includes anterior and posterior bone scan images. Therefore, a single intensity window can be used to render and display both the anterior and posterior images in a bone scan image set. Figure 9E shows the front and back images rendered and displayed using different intensity windows, while Figure 9F Shown are the front and back images rendered and displayed using the same intensity window.

[0128] E. Computer system and network environment

[0129] Figure 10 An illustrative network environment 1000 for use in the methods and systems described herein is shown. Briefly, reference is now made to Figure 10, a block diagram of an exemplary cloud computing environment 1000 is shown and described. The cloud computing environment 1000 may include one or more resource providers 1002a, 1002b, 1002c (collectively referred to as 1002). Each resource provider 1002 may include computing resources. In some embodiments, computing resources may include any hardware and / or software for processing data. For example, computing resources may include hardware and / or software capable of executing algorithms, computer programs, and / or computer applications. In some embodiments, exemplary computing resources may include application servers and / or databases with storage and retrieval capabilities. Each resource provider 1002 may be connected to any other resource provider 1002 in the cloud computing environment 1000. In some embodiments, the resource providers 1002 may be connected via a computer network 1008. Each resource provider 1002 may be connected via a computer network 1008 to one or more computing devices 1004a, 1004b, 1004c (collectively referred to as 1004).

[0130] Cloud computing environment 1000 may include a resource manager 1006. Resource manager 1006 may connect to resource providers 1002 and computing devices 1004 via computer network 1008. In some embodiments, resource manager 1006 may facilitate the provision of computing resources by one or more resource providers 1002 to one or more computing devices 1004. Resource manager 1006 may receive a request for computing resources from a particular computing device 1004. Resource manager 1006 may identify one or more resource providers 1002 that can provide the computing resources requested by computing device 1004. Resource manager 1006 may select a resource provider 1002 to provide the computing resources. Resource manager 1006 may facilitate connections between resource providers 1002 and a particular computing device 1004. In some embodiments, resource manager 1006 may establish a connection between a particular resource provider 1002 and a particular computing device 1004. In some embodiments, resource manager 1006 may redirect a particular computing device 1004 to a particular resource provider 1002 that has the requested computing resources.

[0131] Figure 11An example of a computing device 1100 and a mobile computing device 1150 that can be used in the methods and systems described in the present disclosure is shown. Computing device 1100 is intended to represent various forms of digital computers, such as laptop computers, desktop computers, workstations, personal digital assistants, servers, blade servers, mainframes, and other appropriate computers. Mobile computing device 1150 is intended to represent various forms of mobile devices, such as personal digital assistants, cellular phones, smartphones, and other similar computing devices. The components shown here, their connections and relationships, and their functions are intended to be exemplary only and not limiting.

[0132] The computing device 1100 includes a processor 1102, a memory 1104, a storage device 1106, a high-speed interface 1108 connected to the memory 1104 and a plurality of high-speed expansion ports 1110, and a low-speed interface 1112 connected to a low-speed expansion port 1114 and the storage device 1106. Each of the processor 1102, the memory 1104, the storage device 1106, the high-speed interface 1108, the high-speed expansion port 1110, and the low-speed interface 1112 is interconnected using various buses and can be mounted on a common motherboard or otherwise as appropriate. The processor 1102 can process instructions for execution within the computing device 1100, including instructions stored in the memory 1104 or on the storage device 1106, to display graphical information of a GUI on an external input / output device (e.g., a display 1116 coupled to the high-speed interface 1108). In other embodiments, multiple processors and / or multiple buses, as well as multiple memories and memory types, can be used as appropriate. Furthermore, multiple computing devices may be connected, with each device providing a portion of the necessary operations (e.g., as a server bank, a group of blade servers, or a multi-processor system). Thus, as the terminology is used herein, where multiple functions are described as being performed by a "processor," this encompasses embodiments in which the multiple functions are performed by any number of processor(s) of any number of computing devices (one or more). Furthermore, where a function is described as being performed by a "processor," this encompasses embodiments in which the function is performed by any number of processor(s) of any number of computing devices (one or more) (e.g., in a distributed computing system).

[0133] Memory 1104 stores information within computing device 1100. In some embodiments, memory 1104 is one or more volatile memory units. In some embodiments, memory 1104 is one or more non-volatile memory units. Memory 1104 can also be another form of computer-readable media, such as a magnetic or optical disk.

[0134] Storage device 1106 can provide mass storage for computing device 1100. In some embodiments, storage device 1106 can be or contain a computer-readable medium, such as a floppy disk drive, a hard disk drive, an optical disk drive, or a magnetic tape drive, flash memory or other similar solid-state storage device, or a device array, including devices in a storage area network or other configuration. Instructions can be stored in an information carrier. When executed by one or more processing devices (e.g., processor 1102), the instructions perform one or more methods, such as those described above. Instructions can also be stored by one or more storage devices, such as a computer or machine-readable medium (e.g., memory 1104, storage device 1106, or memory on processor 1102).

[0135] The high-speed interface 1108 manages bandwidth-intensive operations of the computing device 1100, while the low-speed interface 1112 manages less bandwidth-intensive operations. This division of functions is merely an example. In some embodiments, the high-speed interface 1108 is coupled to the memory 1104, the display 1116 (e.g., through a graphics processor or accelerator), and the high-speed expansion port 1110, which can accept various expansion cards (not shown). In an embodiment, the low-speed interface 1112 is coupled to the storage device 1106 and the low-speed expansion port 1114. The low-speed expansion port 1114 can include various communication ports (e.g., USB, Ethernet, wireless Ethernet), which can be coupled to one or more input / output devices, such as a keyboard, pointing device, scanner, or networking device (e.g., a switch or router), for example, through a network adapter.

[0136] Computing device 1100 can be implemented in a variety of different forms, as shown in the figure. For example, it can be implemented as a standard server 1120, or multiple times in a group of such servers. In addition, it can be implemented in a personal computer, such as laptop computer 1122. It can also be implemented as part of a rack server system 1124. Alternatively, components from computing device 1100 can be combined with other components in a mobile device (not shown), such as mobile computing device 1150. Each of these devices can contain one or more of computing device 1100 and mobile computing device 1150, and the entire system can be composed of multiple computing devices communicating with each other.

[0137] Mobile computing device 1150 includes a processor 1152, memory 1164, input / output devices such as a display 1154, a communication interface 1166, and a transceiver 1168, among other components. Mobile computing device 1150 may also be provided with a storage device, such as a microdrive or other device, to provide additional storage. Each of processor 1152, memory 1164, display 1154, communication interface 1166, and transceiver 1168 is interconnected using various buses, and several components may be mounted on a common motherboard or in other ways as appropriate.

[0138] The processor 1152 can execute instructions within the mobile computing device 1150, including instructions stored in the memory 1164. The processor 1152 can be implemented as a chipset including a single or multiple analog and digital processors. The processor 1152 can provide, for example, coordination of other components of the mobile computing device 1150, such as control of a user interface, execution of applications by the mobile computing device 1150, and wireless communications by the mobile computing device 1150.

[0139] The processor 1152 can communicate with the user through a control interface 1158 and a display interface 1156 coupled to a display 1154. The display 1154 can be, for example, a TFT (thin film transistor liquid crystal display) display or an OLED (organic light emitting diode) display or other suitable display technology. The display interface 1156 may include appropriate circuitry for driving the display 1154 to present graphics and other information to the user. The control interface 1158 can receive commands from the user and convert them for submission to the processor 1152. In addition, an external interface 1162 can provide communication with the processor 1152 to enable the mobile computing device 1150 to communicate with other devices in a near-area manner. The external interface 1162 can provide, for example, wired communication in some embodiments or wireless communication in other embodiments, and multiple interfaces can also be used.

[0140] Memory 1164 stores information within mobile computing device 1150. Memory 1164 can be implemented as one or more of a computer-readable medium or media, a volatile memory unit, or a non-volatile memory unit. Expansion memory 1174 can also be provided and connected to mobile computing device 1150 via expansion interface 1172, which can include, for example, a SIMM (Single In-Line Memory Module) card interface. Expansion memory 1174 can provide additional storage space for mobile computing device 1150 or store applications or other information for mobile computing device 1150. Specifically, expansion memory 1174 can include instructions for executing or supplementing the processes described above and can also include security information. Thus, for example, expansion memory 1174 can be provided as a security module for mobile computing device 1150 and can be programmed with instructions that enable secure use of mobile computing device 1150. Furthermore, security applications can be provided via a SIMM card along with additional information, such as identifying information placed on the SIMM card in an unhackable manner.

[0141] As discussed below, the memory may include, for example, flash memory and / or NVRAM memory (non-volatile random access memory). In some embodiments, the instructions are stored in an information carrier and, when executed by one or more processing devices (e.g., processor 1152), perform one or more methods, such as those described above. The instructions may also be stored by one or more storage devices, such as one or more computer or machine-readable media (e.g., memory 1164, expansion memory 1174, or memory on processor 1152). In some embodiments, the instructions may be received in a propagated signal, such as via transceiver 1168 or external interface 1162.

[0142] The mobile computing device 1150 may communicate wirelessly via a communication interface 1166, which may include digital signal processing circuitry, if necessary. The communication interface 1166 may provide for communication in various modes or protocols, such as GSM voice calls (Global System for Mobile Communications), SMS (Short Message Service), EMS (Enhanced Message Service), or MMS messages (Multimedia Message Service), CDMA (Code Division Multiple Access), TDMA (Time Division Multiple Access), PDC (Personal Digital Cellular), WCDMA (Wideband Code Division Multiple Access), CDMA2000, or GPRS (General Packet Radio Service). For example, such communication may be performed using radio frequencies via a transceiver 1168. In addition, short-range communications may be performed, such as using Wi-Fi TMOr other such transceiver (not shown). In addition, a GPS (Global Positioning System) receiver module 1170 can provide additional navigation- and location-related wireless data to the mobile computing device 1150, which can be used as appropriate by applications running on the mobile computing device 1150.

[0143] The mobile computing device 1150 may also communicate audibly using an audio codec 1160 that can receive spoken information from a user and convert it into usable digital information. The audio codec 1160 may similarly generate audible sounds for the user, such as through a speaker, such as in the handset of the mobile computing device 1150. Such sounds may include sounds from voice phone calls, may include recorded sounds (e.g., voice messages, music files, etc.), and may also include sounds generated by applications operating on the mobile computing device 1150.

[0144] Mobile computing device 1150 can be implemented in many different forms, as shown in the figure. For example, it can be implemented as a cellular phone 1180. It can also be implemented as part of a smart phone 1182, a personal digital assistant, or other similar mobile device.

[0145] Various embodiments of the systems and techniques described herein can be implemented in digital electronic circuitry, integrated circuitry, specially designed ASICs (application specific integrated circuits), computer hardware, firmware, software, and / or combinations thereof. These various embodiments can include implementations in one or more computer programs that are executable and / or interpreted on a programmable system comprising at least one programmable processor, which can be special purpose or general purpose, coupled to receive data and instructions from and transmit data and instructions to a storage system, at least one input device, and at least one output device.

[0146] These computer programs (also referred to as programs, software, software applications, or code) contain machine instructions for a programmable processor and may be implemented in high-level procedural and / or object-oriented programming languages ​​and / or assembly / machine languages. As used herein, the terms machine-readable medium and computer-readable medium refer to any computer program product, apparatus, and / or device (e.g., a magnetic disk, an optical disk, a memory, a programmable logic device (PLD)) for providing machine instructions and / or data to a programmable processor, including machine-readable media that receive machine instructions as machine-readable signals. The term machine-readable signal refers to any signal used to provide machine instructions and / or data to a programmable processor.

[0147] To provide for interaction with a user, the systems and techniques described herein can be implemented on a computer having a display device (e.g., a CRT (cathode ray tube) or LCD (liquid crystal display) monitor) to display information to the user; and a keyboard and pointing device (e.g., a mouse or trackball) through which the user can provide input to the computer. Other types of devices can also be used to provide for interaction with the user; for example, the feedback provided to the user can be any form of sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback); and input from the user can be received in any form, including acoustic, voice, or tactile input.

[0148] The systems and techniques described herein can be implemented in a computing system that includes a back-end component (e.g., as a data server), or includes a middleware component (e.g., an application server), or includes a front-end component (e.g., a client computer with a graphical user interface or a web browser through which a user can interact with an embodiment of the systems and techniques described herein), or any combination of such back-end, middleware, or front-end components. The components of the system can be interconnected by any digital data communication form or medium (e.g., a communication network). Examples of communication networks include a local area network (LAN), a wide area network (WAN), and the Internet.

[0149] A computing system may include a client and a server. The client and server are typically remote from each other and typically interact via a communication network. The relationship between the client and the server arises from computer programs that run on the respective computers and have a client-server relationship with each other. In some embodiments, the modules and / or services described herein may be separated, combined, or incorporated into a single or combined module and / or service. The modules and / or services depicted in the figures are not intended to limit the system described herein to the software architecture shown therein.

[0150] While the present invention has been particularly shown and described with reference to certain preferred embodiments, it will be understood by those skilled in the art that various changes in form and details may be made without departing from the spirit and scope of the invention as defined by the following claims.

Claims

1. A method for interactively adjusting an intensity window threshold for displaying a nuclear medicine image, the method comprising: (a) accessing, by a processor of a computing device, the nuclear medicine image, the image comprising a plurality of pixels, each pixel having an intensity representing a level of a detected signal; (b) rendering, by the processor, the nuclear medicine image for graphical display according to the initial intensity window, the rendering comprising visually representing the pixel intensities using a set of available color map values ​​such that a full range of available color map values ​​is assigned to a subset of the pixel intensities within a range from a minimum threshold value of the initial intensity window to a maximum threshold value of the initial intensity window; (c) causing display, by the processor, of a graphical control element to enable user selection of a subsequent intensity window different from the initial intensity window via user adjustment of one or two display indicator widgets according to which one or two thresholds for the subsequent intensity window are determined, wherein the display indicator widget is adjustable along a scale having increments mapped to intensity values ​​via a scaling function, wherein the scaling function is non-linear for at least a portion of the increments; (d) receiving, by the processor, a user selection of the subsequent intensity window corresponding to an adjusted position of the one or two display indicator widgets of the graphical control element; (e) in response to receipt of the user selection of the subsequent intensity window, rendering, by the processor, the nuclear medicine image for graphical display according to the subsequent intensity window, the rendering comprising visually representing the pixel intensities using the set of available color map values ​​such that the full range of available color map values ​​is assigned to a subset of the pixel intensities within a range from a minimum threshold value of the subsequent intensity window to a maximum threshold value of the subsequent intensity window, thereby creating an updated rendering; and (f) causing, by the processor, the updated rendered display from step (e), thereby dynamically updating the display of the nuclear medicine image as the user adjusts selection of the one or two display indicator widgets to make selections of the subsequent intensity windows.

2. The method of claim 1, comprising repeating steps (d)-(f) to update and display the nuclear medicine image in real time as the user adjusts the subsequent intensity window. 3 . The method of claim 1 , wherein the graphical control element comprises a visual representation of the scale as a path, wherein the display indicator widget has an adjustable position along the path. 4 . The method of claim 3 , wherein the scale includes reference increments mapped to reference intensity values, and the graphical control element includes a visual indication of the reference increments along the path.

5. The method of any one of claims 1 or 2, wherein a minimum increment of the scale maps to an intensity value of 0 and a maximum increment of the scale maps to a maximum intensity value in the nuclear medicine image.

6. A method according to any one of claims 1 or 2, wherein the scale includes reference increments mapped to reference intensity values, wherein the scaling function has a greater slope for intensity values ​​above the reference intensity value than for intensity values ​​below the reference increments.

7. The method of claim 6, wherein the scaling function is non-linear above the reference intensity value and linear below the reference intensity value.

8. The method according to claim 4, comprising: Prior to step (b), the processor normalizes the nuclear medicine image using a normalization factor to generate a normalized version of the nuclear medicine image for rendering and display; and The processor calculates the reference intensity value as a function of the normalization factor.

9. The method of claim 4, wherein the reference increment is located more than halfway along the scale from a minimum end to a maximum end of the scale.

10. The method according to any one of claims 1 or 2, comprising: Prior to step (b), the processor normalizes the nuclear medicine image using a normalization factor, thereby generating a normalized version of the nuclear medicine image for rendering and display.

11. The method of claim 10, wherein the normalization factor is determined by the processor identifying a healthy tissue region in the nuclear medicine image that is determined to not contain any hot spots and calculating the normalization factor by the processor so that the product of the normalization factor and the average intensity of the identified healthy tissue region is a predefined intensity level.

12. The method of any one of claims 1 or 2, wherein the nuclear medicine image is a bone scan image.

13. A system for interactively adjusting an intensity window threshold for displaying a nuclear medicine image, the system comprising: a processor of a computing device; and a memory having instructions stored thereon, wherein the instructions, when executed by the processor, cause the processor to: (a) accessing the nuclear medicine image, the image comprising a plurality of pixels, each pixel having an intensity representing a level of a detected signal; (b) rendering the nuclear medicine image for graphical display according to an initial intensity window using a set of available color map values ​​to visually represent the pixel intensities such that the full range of available color map values ​​is assigned to a subset of the pixel intensities within a range from a minimum threshold value of the initial intensity window to a maximum threshold value of the initial intensity window; (c) causing display of a graphical control element to enable user selection of a subsequent intensity window different from the initial intensity window via user adjustment of one or two display indicator widgets according to which one or two thresholds for the subsequent intensity window are determined, wherein the display indicator widgets are adjustable along a scale having increments mapped to intensity values ​​via a scaling function, wherein the scaling function is non-linear for at least a portion of the increments; (d) receiving a user selection of the subsequent intensity window corresponding to an adjusted position of the one or two display indicator widgets of the graphical control element; (e) in response to receipt of the subsequent intensity window, rendering the nuclear medicine image for graphical display according to the subsequent intensity window using the set of available color map values ​​to visually represent the pixel intensities such that the full range of available color map values ​​is assigned to a subset of the pixel intensities within a range from a minimum threshold value of the subsequent intensity window to a maximum threshold value of the subsequent intensity window, thereby creating an updated rendering; and (f) causing the updated rendered display from step (e) to dynamically update the display of the nuclear medicine image as the user adjusts selection of the one or two display indicator widgets to make selections of the subsequent intensity windows.

14. The system of claim 13, wherein the instructions cause the processor to repeat steps (d)-(f) to update and display the nuclear medicine image in real time as the user adjusts the subsequent intensity window. 15 . The system of claim 13 , wherein the graphical control element comprises a visual representation of the scale as a path, wherein the display indicator widget has an adjustable position along the path.

16. The system of claim 15, wherein the scale includes reference increments mapped to reference intensity values, and the graphical control element includes a visual indication of the reference increments along the path.

17. The system of any one of claims 13 or 14, wherein a minimum increment of the scale maps to an intensity value of 0 and a maximum increment of the scale maps to a maximum intensity value in the nuclear medicine image.

18. A system according to any one of claims 13 or 14, wherein the scale includes reference increments mapped to reference intensity values, wherein the scaling function has a greater slope for intensity values ​​above the reference intensity value than for intensity values ​​below the reference increments.

19. The system of claim 18, wherein the scaling function is non-linear above the reference intensity value and linear below the reference intensity value.

20. The system of claim 18, wherein the instructions cause the processor to: Prior to step (b), normalizing the nuclear medicine image using a normalization factor to produce a normalized version of the nuclear medicine image for rendering and display; and The reference intensity value is calculated as a function of the normalization factor.

21. The system of claim 18, wherein the reference increment is located more than halfway along the scale from a minimum end to a maximum end of the scale.

22. The system of any one of claims 13 or 14, wherein the instructions cause the processor, prior to step (b): The nuclear medicine image is normalized using a normalization factor, thereby generating a normalized version of the nuclear medicine image for rendering and display.

23. The system of claim 22, wherein the instructions cause the processor to determine the normalization factor by identifying a healthy tissue region in the nuclear medicine image that is determined to not contain any hot spots and calculating the normalization factor such that the product of the normalization factor and the average intensity of the identified healthy tissue region is a predefined intensity level.

24. The system of any one of claims 13 or 14, wherein the nuclear medicine image is a bone scan image.

Images