Patent Publication Number: US-11043296-B2

Title: Systems and methods for semi-automatic tumor segmentation

Description:
RELATED APPLICATIONS 
     This application claims priority to U.S. Provisional Application No. 62/755,873, entitled “SYSTEMS AND METHODS FOR SEMI-AUTOMATIC BRAIN TUMOR SEGMENTATION,” filed Nov. 5, 2018, the entire contents of which is incorporated herein by reference. 
    
    
     FIELD 
     Embodiments of the invention relate to analyzing medical images and, more particularly, to integrating offline analysis with user interaction to segment brain and other types of tumors. 
     BACKGROUND 
     Extracting quantitative variables from medical images contributes more information for decision support in management of cancer patients, helping to improve patient outcomes. Currently, radiological studies are generally limited to detection and staging along with qualitative descriptions. Quantitative descriptors are not yet in the standard of care primarily due to a lack of infrastructure and tools to derive, test, and deploy these quantitative metrics at the point-of-care for all patients. 
     SUMMARY 
     Currently available tools for quantitative analysis lack the speed, precision, and consistency required for wider clinical use. Delineating lesion boundaries correctly is time consuming and inefficient for radiologists. This can be performed by manually drawing the tumor boundary on each image slice, by semi-automatically guiding an algorithm, or by using fully automated methods. Although manual delineation offers complete control to the user, the process is time consuming and may produce variable results due to variable performance among those performing the process. In either the semi-automated or fully automated methods, manual editing is necessary to produce useable results. 
     In particular, embodiments described herein provide systems and methods for volumetric segmentation in a plurality of planar medical images. 
     In one embodiment, a system for volumetric segmentation in a plurality of planar medical images includes a display, a user interface, an electronic processor coupled to the display and the user interface, and a memory coupled to the electronic processor and storing instructions that, when executed by the electronic processor, cause the system to receive the plurality of planar medical images. A boundary of a candidate structure in the plurality of medical images is generated using a segmentation model. A first planar medical image from the plurality of planar medical images is displayed on a display. A user input is received using a user interface indicating a region in the first planar medical image. A first planar contour of the candidate structure is generated. The region is compared to the boundary. Responsive to the region being at least partially within the boundary, the first planar medical image is re-displayed on the display showing the first planar contour of the structure, and a finding record for the candidate structure including the boundary is generated. 
     In another embodiment, a method for volumetric segmentation in a plurality of planar medical images includes, receiving, at an electronic processor, the plurality of planar medical images. A boundary of a candidate structure in the plurality of medical images is generated using a segmentation model. A first planar medical image from the plurality of planar medical images is displayed on a display. A user input is received using a user interface indicating a region in the first planar medical image. A first planar contour of the candidate structure is generated. The region is compared to the boundary. Responsive to the region being at least partially within the boundary, the first planar medical image is re-displayed on the display showing the first planar contour of the structure, and a finding record for the candidate structure including the boundary is generated. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The accompanying figures, where like reference numerals refer to identical or functionally similar elements throughout the separate views, together with the detailed description below, are incorporated in and form part of the specification, and serve to further illustrate embodiments of concepts that include the claimed invention, and explain various principles and advantages of those embodiments. 
         FIG. 1  is a block diagram of one embodiment of a system for performing structure segmentation in medical images, according to some embodiments. 
         FIG. 2  illustrates a flowchart for a method of structure segmentation, according to some embodiments. 
         FIG. 3  illustrates a process flow for performing automatic segmentation, according to some embodiments. 
         FIGS. 4 and 5  illustrate medical images on which visual indications of planar contours are generated responsive to a user input confirming a candidate structure identified by the segmentation in  FIG. 3 , according to some embodiments. 
     
    
    
     Skilled artisans will appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements to help to improve understanding of embodiments of the present invention. 
     The apparatus and method components have been represented where appropriate by conventional symbols in the drawings, showing only those specific details that are pertinent to understanding the embodiments of the present invention so as not to obscure the disclosure with details that will be readily apparent to those of ordinary skill in the art having the benefit of the description herein. 
     DETAILED DESCRIPTION 
     Before any embodiments of the invention are explained in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the accompanying drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways. 
     One or more embodiments are described and illustrated in the following description and accompanying drawings. These embodiments are not limited to the specific details provided herein and may be modified in various ways. Furthermore, other embodiments may exist that are not described herein. Also, the functionality described herein as being performed by one component may be performed by multiple components in a distributed manner. Likewise, functionality performed by multiple components may be consolidated and performed by a single component. Similarly, a component described as performing particular functionality may also perform additional functionality not described herein. For example, a device or structure that is “configured” in a certain way is configured in at least that way, but may also be configured in ways that are not listed. Furthermore, some embodiments described herein may include one or more electronic processors configured to perform the described functionality by executing instructions stored in non-transitory, computer-readable medium. Similarly, embodiments described herein may be implemented as non-transitory, computer-readable medium storing instructions executable by one or more electronic processors to perform the described functionality. As used herein, “non-transitory computer-readable medium” comprises all computer-readable media but does not consist of a transitory, propagating signal. Accordingly, non-transitory computer-readable medium may include, for example, a hard disk, a CD-ROM, an optical storage device, a magnetic storage device, a ROM (Read Only Memory), a RAM (Random Access Memory), register memory, a processor cache, or any combination thereof. 
     Also, the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. For example, the use of “including,” “containing,” “comprising,” “having,” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. The terms “connected” and “coupled” are used broadly and encompass both direct and indirect connecting and coupling. Further, “connected” and “coupled” are not restricted to physical or mechanical connections or couplings and can include electrical connections or couplings, whether direct or indirect. In addition, electronic communications and notifications may be performed using wired connections, wireless connections, or a combination thereof and may be transmitted directly or through one or more intermediary devices over various types of networks, communication channels, and connections. Moreover, relational terms such as first and second, top and bottom, and the like may be used herein solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. 
     Example systems and methods disclosed and contemplated herein relate to segmentation of structures in medical images. Although the following description focuses on image segmentation in a medical context, it will be appreciated that various systems, methods, and techniques disclosed herein are applicable to other domains, such as autonomous vehicles. For example, with the autonomous vehicle space, images may be segmented to identify a road centerline, a stop sign, or other findings of interested similar to findings of interest in medical images. 
     Fully automated segmentation, especially based on deep neural networks, has shown promising results when used to analyze magnetic resonance scans of brain tumors. However, such Computer Aided Detection (CAD) systems may produce false positive indications. Accordingly, embodiments described herein combine automated segmentation with a real-time user interface that allow a radiologist to make an initial indication regarding a finding that allows a previously identified structure generated by the CAD system to be matched to the radiologist&#39;s finding. Such embodiments provide clinical radiologists with control over the segmentation, real-time feedback, and an algorithm that is ready to run without the need to first be trained on a large database from their site. Such embodiments improve efficiency and accuracy over existing methods, including editing of a fully automated segmentation method. 
     Evidence from cancer researchers suggests that extraction of quantitative variables from medical images can contribute more information for decision support in management of cancer patients. Specifically, quantitative metrics can improve both diagnostic and prognostic accuracy as well as longitudinal monitoring of patient response. Criteria for monitoring radiographic brain tumor progression include the Macdonald criteria, Response Evaluation Criteria in Solid Tumors (RECIST), WHO criteria, and RANO criteria. 
     Volumetric contouring of a structure included in medical images provides advantages, such as inter-observer consistency, while also catering to individual preferences for accuracy and style. Consistency results from initialization strategies that are reproducible. For example, using a user may identify a structure using a straight stroke approach rather than free-form drawing, and the contouring of the structure may be performed automatically. Tailoring to individual preferences is accomplished by editing tools that may be used by a user if the initial contours are unsatisfactory. In some embodiments, there is exactly one tool in a reading room, generally applicable to all organs, yet simultaneously specialized with organ-specific features. The organ is automatically identified upon tool initialization. 
       FIG. 1  schematically illustrates one embodiment of a system  100  for performing segmentation of features on medical images, according to some embodiments. The system  100  may combine one or more of hardware, software, and firmware, to implement a method provided herein. In the example illustrated, the system  100  includes a display  101 , an electronic processor  102 , a user interface  103 , a memory  104 , data storage device  110 , a communication interface  112  and a bus  120 . As illustrated, the memory  104  may store an operating system  106  and software programs  108 . The electronic processor  102  includes at least one processor or microprocessor that interprets and executes a set of instructions stored in the memory  104 . In some embodiments, the software programs  108  include a segmentation application  109 . In some embodiments, the electronic processor  102  includes multiple computing devices that may be distributed across multiple entities. In some embodiments, the electronic processor  102  is implemented by a virtual processor executing on a cloud-based processing service. 
     The user interface  103  may include one or more input devices, one or more output devices, or a combination thereof. Accordingly, in some embodiments, the user interface  103  allows a user to interact with (for example, provide input to and receive output from) the system  100 . For example, the user interface  103  may include a keyboard, a cursor-control device (for example, a mouse), a touch screen, a scroll ball, a mechanical button, a display device (for example, a liquid crystal display (LCD)), a printer, a speaker, a microphone, or a combination thereof. 
     The memory  104  stores data used during the execution of instructions by the processor  102 . The memory  104  may include volatile memory elements (for example, random access memory (RAM)), nonvolatile memory elements (for example, ROM), and combinations thereof. The memory  104  may have a distributed architecture, where various components are situated remotely from one another, but may be accessed by the electronic processor  102 . The one or more programs  108  may be configured to implement the methods described herein. 
     The data storage device  110  may include a non-transitory, tangible, machine-readable storage medium that stores machine-readable code or instructions. In one example, the data storage device  110  stores a set of instructions detailing a method provide herein that when executed by one or more processors cause the one or more processors to perform the method. The data storage device  110  may also be a database or a database interface for storing an application module. In one example, the data storage device  110  is located external to the system  100 . In some embodiments, the data storage  110  includes a medical image database  111 . 
     The bus  120 , or other component interconnection, may permit communication among the components of the system  100 . The bus  120  may be, for example, one or more buses or other wired or wireless connections, as is known in the art. The bus  120  may have additional elements, which are omitted for simplicity, such as controllers, buffers (for example, caches), drivers, repeaters and receivers, or other similar components, to enable communications. The bus  120  may also include address, control, data connections, or a combination of the foregoing to enable appropriate communications among the aforementioned components. 
     The communication interface  112  provides the system  100  a communication gateway with one or more external networks (for example, a wireless network, the Internet, etc.). The communication interface  112  may include, for example, an Ethernet card or adapter or a wireless local area network (WLAN) card or adapter (for example, operating according to the IEEE standard 802.11a/b/g/n). The communication interface  112  may include address, control, and/or data connections to enable appropriate communications on the external network(s). 
     In some embodiments, the methods provided herein are performed by a software application executed by a server, and a user may access and interact with the software application using a computing device. Also, in some embodiments, functionality provided by the software application may be distributed between a software application executed by a local device and a software application executed by another electronic process or device (for example, a server) external to the local device. 
       FIG. 2  illustrates a flowchart for a method  200  of structure segmentation, according to some embodiments. In block  205 , a plurality of medical images is received. For example, the medical images may be generated by a scanning tool, such as a computed tomography (CT) tool, a positron emission tomography (PET) tool, a magnetic resonance imaging (MRI) tool, etc., and stored in the medical image database  111 . The segmentation application  109  executed by the electronic processor  102  receives the plurality of medical images. 
     In block  210 , the segmentation application  109  employs one or more segmentation models to identify one or more candidate structures depicted in the plurality of medical images and generates a boundary of each candidate structure. Since segmentation models  109 A,  109 B are known to generate false positives, the boundaries identified by the off-line analysis using the segmentation models  109 A,  109 B may be referred to as boundaries for candidate structures.  FIG. 3  illustrates a process flow for performing automatic segmentation by the segmentation application  109 , according to some embodiments. In some embodiments, the segmentation application  109  employs a deep learning segmentation model  109 A or an algorithmic segmentation model  109 B, or both (see  FIG. 1 ). In some embodiments, the segmentation models  109 A,  109 B are relatively computationally intensive (e.g., requiring about one minute of computing time each on a typical minicomputer). The segmentation application  109  performs the segmentation analysis off-line using the segmentation models  109 A,  109 B. For example, the segmentation application  109  may perform the segmentation analysis relatively soon after the medical images are generated, and prior to them being reviewed by a radiologist of other user. In this manner, the segmentation need not be performed in real time coincident with review by the radiologist. In general, the deep learning segmentation model  190 A generates boundaries  305  of one or more candidate structures identified in the plurality of medical images. In some embodiments, the boundaries are three-dimensional boundaries. 
     In some embodiments, the plurality of images include multispectral images of the same scan region. For example, Mill data may include T1 weighted images, T2 weighted images, T1 contrast enhanced (CE) images, or fluid-attenuated inversion recovery (FLAIR) images. In some embodiments, the segmentation models  109 A,  109 B receive the multispectral images as inputs allowing data from the different spectrums to be factored into the segmentation. In some embodiments, the segmentation models  109 A,  109 B perform whole organ segmentation (e.g., whole brain segmentation) and partitioning of the tissue into its constituent parts: edema, necrosis, and actively enhancing regions. A radiologist or other user may interface with the segmentation application  109  in real-time to review and or modify the segmentation because only a portion of the image is being segmented and the whole organ analysis has already been completed by the segmentation models  109 A,  109 B off-line. 
     In some embodiments, the deep learning segmentation model  109 A employs a convolution neural network (CNN). For example, a CNN based on the 3D U-Net architecture may be used. Briefly, the input image data is set to 128×128×128 voxels, constrained by the limited memory in the GPU. Processing from left to right, the 3D image volume is sequentially reduced in spatial resolution with multiple 3×3×3 convolution layers while increasing the number of filters or feature maps as the levels move deeper. Once the lowest level is reached, the extracted feature maps are then upsampled to sequentially restore the spatial resolution at each level, concatenating with feature maps preserved during the downsampling to help restore lost information. A Softmax function classifies the 3 tumor classes. Dropouts with probability 0.3 are included to minimize overfitting. 
     To account for the class imbalance, where there is much more background pixel data than tumor, other than cropping, a multiclass Jaccard loss function is used in some embodiments. The four classes include 0 for background, 1 for tumor core, 2 for edema, and 4 for enhancing tumor. A loss function is used: 
     
       
         
           
             
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     where u is the prediction of the CNN and v is from the ground truth segmentation value, i is the pixel number, and k is each class in all K=4 classes. The Jaccard coefficient is a measure of similarity between the segmented prediction and truth image volumes, where higher value indicates greater overlap. The multiclass version is the intersection over union of the two volumes averaged over the four classes. A negative term was added to the loss function to ensure the minimum loss function was optimized. In some embodiments, CNN development uses the open-source machine learning library, TensorFlow, and neural networking API, Keras. Other embodiments may use other machine learning libraries, for example, CNTK. 
     In some embodiments, the algorithmic segmentation model  109 B classifies every organ voxel (e.g., brain voxel) as belonging to one of several tissue types to generate a tissue map  310 . For brain tissue, the tissue types include cerebrospinal fluid (CSF), gray matter, white matter, vessels, ventricles, and disease. In some embodiments, gray and white matter are found by performing Bayesian classification of the T1-weighted, contrast-enhanced image using an Expectation Maximization (EM) algorithm. One element of Bayesian classification is the probability that a voxel belongs to a certain tissue class prior to observing its brightness. When this prior probability varies across the image, it is referred to as a spatially-varying prior (SVP). The SVP is estimated through affine registration of the SPM atlas. Rules of logic are applied to the set of all four MR spectra to derive the other tissues. For example, enhancing tumor is described by areas that show hyper-intensity under contrast-enhancement when compared to the non-enhanced image, but also when compared to healthy white matter. The resultant tissue segmentation is used by the segmentation application  109  for anatomic context. For example, the segmentation application  109  may exclude vessels and ventricles from tumor structures. 
     In some embodiments, the tissue map  310  is used by the segmentation application  109  to refine the boundaries  305  identified by the deep learning segmentation model  309 A. 
     Returning to  FIG. 2 , in block  215 , the segmentation application  109  displays a first planar medical image on the display  101 .  FIGS. 4 and 5  illustrate medical images on which visual indication of planar contours are generated responsive to a user confirming a candidate structure identified by the segmentation in  FIG. 3 , according to some embodiments.  FIG. 4  illustrates a first medical image  405  (e.g., an axial plane image), a second medical image  410  (e.g., a coronal plane image, and a third medical image  415  (e.g., a sagittal plane image). Initially, the segmentation application  109  displays the medical images  405 ,  410 ,  415  without any annotations. 
     In block  215 , the segmentation application  109  receives, via the user interface  103 , a user input  420  indicating a region in the first planar medical image. In some embodiments, the user provides the user input  420  by drawing an axis through a region of interest. In some embodiments, the axis is a straight line. The axis may be a long axis, a short axis, or a partial axis. In other embodiments, the user provides the user input  420  by clicking within the region, circling the region, circling a portion of the region, drawing a line in a portion of the region, or the like. 
     In block  225 , the segmentation application  109  determines whether the region identified by the user input in the first planar medical image coincides with a boundary  305  of a candidate structure identified by the segmentation models  109 A,  109 B. In some embodiments, the user indicates that the user input  420  is complete (e.g., the long axis is drawn as intended), and the segmentation application  109  proceeds with the determination in block  225 . In some embodiments, the segmentation application  109  determines whether the region identified by the user input in the first planar medical image coincides with a boundary  305  of a candidate structure by determining whether a long axis drawn by the user has endpoints that intersect or are proximal to the boundary  305 . For example, the endpoints of the axis may be within a predetermined distance from the boundary  305 . In some embodiments, the segmentation application  109  determines whether the region identified by the user input in the first planar medical image is within a boundary  305  of a candidate structure by determining whether the indicated region coincides with the boundary  305 . 
     Responsive to determining that the region identified by the user input in the first planar medical image is not within the boundary  305  of a candidate structure in block  225 , the segmentation application performs user-directed segmentation in block  230 . In some embodiments, the tissue map  310  generated by the algorithmic segmentation model  109 B is used to facilitate user-directed segmentation. 
     Responsive to determining that the region identified by the user input in the first planar medical image is within the boundary  305  of a candidate structure in block  225 , the segmentation application generates a planar contour  425  of the candidate structure in block  235 . In some embodiments, the planar contour  425  is generated by projecting the boundary  305  on the plane corresponding to the first medical image  405 . In some embodiments, the segmentation application  109  generates the planar contour  425  prior to determining if the region is within the boundary  305  in block  225  to facilitate the determination. 
     In block  240 , the segmentation application  109  re-displays the first medical image  405  on the display to provide a visual indication of the planar contour  425 , as illustrated in  FIG. 4 . In some embodiments, the segmentation application  109  also generates planar contours  430 ,  435  for the other medical images  410 ,  415  by projecting the boundary  305  into the plane corresponding to the particular medical image  410 ,  415 . The planar contours  430 ,  435  are shown in the medical images  410 ,  415 , as illustrated in  FIG. 5 . In some embodiments, the planar contours  425 ,  430 ,  435  appear more coarsely pixilated because the medical images  405 ,  410 ,  415  displays super-sampled images, whereas the deep learning segmentation model  109 A operates on full resolution images. 
     In some embodiments, the segmentation application generates planar contours for other medical images in the set of medical images after receiving the user input. For example, medical images having the same orientation as the medical image  405 , but in different slices, may be annotated with planar contours to allow the user to scroll through the slices to see the boundaries of the structure throughout its 3D volume. 
     In some embodiments, if the user determines that the planar contours  425 ,  430 ,  435  are unsatisfactory, the user may draw additional axes or move the envelope defined by the planar contours  425 ,  430 ,  435 . Data from the deep learning segmentation model  109 A and the tissue map  310  generated by the algorithmic segmentation model  109  may be used to alter the boundary  305  and the planar contours  425 ,  430 ,  435 . 
     In block  245 , the segmentation application generates a finding record for the candidate structure contained within the boundary  305 . In some embodiments, a finding record includes a 3-D mesh and metadata describing the characteristics of the mesh. In some embodiments, the finding record is a 3-D image volume. In some embodiments, the user indicates that the candidate structure contained within the boundary  305  identified by the segmentation application  109  (e.g., using the deep learning segmentation model  109 A) is a valid finding. 
     If the user identifies multiple structures of interest in the medical images  405 ,  410 ,  415 , the method  200  may be repeated for each structure. Since the candidate structures are not initially provided to the user, the user is not burdened with false positives. Only those candidate structures that correspond to findings indicated by the user are presented. 
     In the foregoing specification, specific embodiments have been described. However, one of ordinary skill in the art appreciates that various modifications and changes may be made without departing from the scope of the invention as set forth in the claims below. Accordingly, the specification and figures are to be regarded in an illustrative rather than a restrictive sense, and all such modifications are intended to be included within the scope of present teachings. 
     Various features and advantages of some embodiments are set forth in the following claims.