A method for optimizing intracerebral probe planning and placement via multimodal 3D analysis of brain anatomy

Abstract

The method includes acquiring a first imaging scan and a second imaging scan of a single subject brain. The first imaging scan is transformed into a first data set, and the second imaging scan is transformed into a second data set. A sequence-adaptive multi-modal segmentation algorithm is applied to the first data set and the second data set. The sequence-adaptive multi-modal segmentation algorithm performs automatic intensity-based tissue classification to generate a first labeled data set and a second labeled data set. The first labeled data set and the second labeled data set are automatically co-registered with each other, and a transformation matrix is ​​generated based on the first labeled data set and the second labeled data set. The transformation matrix is ​​applied to align the first data set and the second data set.

Description

[Technical field]

[0001] This application claims priority to U.S. Provisional Patent Application No. 62 / 978,868, filed February 20, 2020, and entitled “Methods of Identifying and Avoiding Visual Deficits After Laser Interstitial Thermal Therapy for Mesial Temporal Lobe Epilepsy,” which is incorporated by reference in its entirety. [Background technology]

[0002] Intracranial electrodes are implanted in patients for recording high spatiotemporal resolution intracranial electroencephalography (icEEG) data and for modulation of neural circuits and systems, most commonly for the evaluation of neurological disorders such as epilepsy, movement disorders, and psychiatric diseases.

[0003] In a subset of patients with medically refractory epilepsy, seizure onset can be localized to a definable lesion, and in such exemplary circumstances, surgical intervention offers the potential for cessation of further seizure activity through direct resection, removal, or destruction of pathological brain tissue, including, but not limited to, minimally invasive approaches, including catheter-based tissue ablation.Unfortunately, in many cases, patients do not have lesions that are identifiable using only non-invasive tests or evaluations, which may include tests of brain activity, including, but not limited to, scalp electroencephalography (EEG) and magnetoencephalography (MEG), as well as anatomical imaging modalities used to identify structural lesions, such as magnetic resonance imaging (MRI) or computed tomography (CT).Electrodes are also placed for neuromodulation of epilepsy, which is currently either in the anterior thalamic nucleus or at the site of seizure onset.

[0004] Movement disorders (Parkinson's disease, dystonia, essential tremor) are also common. Treatment of these disorders is often surgical, as drugs generally have undesirable side effects. The deep basal ganglia (e.g., the subthalamic nucleus, the internal segment of the globus pallidus, and the VIM nucleus of the thalamus) and their associated white matter pathways are routinely targeted for these disorders.

[0005] Psychiatric disorders are rapidly becoming targeted conditions for neuromodulation when pharmaceutical drugs are not effective; these include cases of treatment-resistant depression, obsessive-compulsive disorder, post-traumatic stress disorder, and eating disorders.

[0006] In such exemplary patients, implantation of subdural electrodes (SDE) and / or stereoelectroencephalography (SEEG) electrodes and / or other probes or catheters or recording devices is a common strategy used to precisely define the relationships between healthy and / or eloquent brain regions and pathological brain regions that may underlie putative pathological networks for diagnosis or for stimulation to induce neuromodulation. Summary of the Invention [Means for solving the problem]

[0007] The method includes acquiring a first imaging scan and a second imaging scan of a single subject brain. The first imaging scan is transformed into a first data set and the second imaging scan is transformed into a second data set. A sequence-adaptive multi-modal segmentation algorithm is applied to the first data set and the second data set. The sequence-adaptive multi-modal segmentation algorithm performs an automatic intensity-based tissue classification to generate a first label data set and a second label data set. The first label data set and the second label data set are automatically co-registered with respect to each other to generate a transformation matrix based on the first label data set and the second label data set. The transformation matrix is ​​applied to align the first data set and the second data set.

[0008] A non-transitory computer-readable medium encoded with instructions executable by one or more processors to obtain a first imaging scan and a second imaging scan of a single subject brain and transform the first imaging scan into a first data set and the second imaging scan into a second data set. The instructions are also executable by the one or more processors to apply a sequence-adaptive multi-modal segmentation algorithm to the first data set and the second data set, the sequence-adaptive multi-modal segmentation algorithm performing an automatic intensity-based tissue classification and generating a first label data set and a second label data set. The instructions are further executable by the one or more processors to automatically co-register the first label data set and the second label data set with respect to one another and generate a transformation matrix based on the first label data set and the second label data set. The instructions are still further executable by the one or more processors to apply the transformation matrix to align the first data set and the second data set.

[0009] The system includes one or more processors and a memory. The memory is coupled to the one or more processors and stores instructions. The instructions configure the one or more processors to obtain a first imaging scan and a second imaging scan of a subject's brain and transform the first imaging scan into a first data set and the second imaging scan into a second data set. The instructions also configure the one or more processors to apply a sequence-adaptive multi-modal segmentation algorithm to the first data set and the second data set, the sequence-adaptive multi-modal segmentation algorithm performing an automatic intensity-based tissue classification and generating a first label data set and a second label data set. The instructions further configure the one or more processors to automatically co-register the first label data set and the second label data set with respect to each other and generate a transformation matrix based on the first label data set and the second label data set. The instructions still further configure the one or more processors to apply the transformation matrix to align the first data set and the second data set. The present invention provides, for example, the following: (Item 1) 1. A method comprising: obtaining a first imaging scan and a second imaging scan of a single subject brain; converting the first imaging scan into a first data set and the second imaging scan into a second data set; applying a sequence adaptive multi-modal segmentation algorithm to the first data set and the second data set, the sequence adaptive multi-modal segmentation algorithm performing an automatic intensity-based tissue classification to generate a first label data set and a second label data set; automatically co-registering the first and second sign data sets relative to one another and generating a transformation matrix based on the first and second sign data sets; applying the transformation matrix to align the first data set and the second data set; A method comprising: (Item 2) Item 1, wherein the first imaging scan and the second imaging scan are performed using one or more of magnetic resonance imaging (MRI), computed tomography (CT), magnetoencephalography (MEG), or positron emission tomography (PET). (Item 3) 2. The method of claim 1, wherein the sequence adaptive multi-modal segmentation algorithm assigns a numerical indicator value to each voxel of the first data set or the second data set. (Item 4) Extracting voxels from the first data set having labels corresponding to a subcortical region of interest; forming a third data set containing the voxels extracted from the first data set; Transforming the third data set into a first subcortical surface mesh model; and calculating curvature and sulcus features of the first subcortical surface mesh model; Matching the first subcortical surface mesh model to a subcortical anatomy of the region of interest using the curvature and sulcus features; overlaying the first subcortical surface mesh model aligned to an anatomy of the subcortical region of interest onto a second subcortical surface mesh model having a standardized number of nodes that allows for a one-to-one correspondence between node identification and anatomy location; assigning coordinates of nodes of the first subcortical surface mesh model to the second subcortical structural surface mesh model such that the second subcortical surface mesh model exhibits a topology of the first subcortical structural surface mesh model; The method of claim 1, further comprising: (Item 5) the first imaging scan is a contrast-weighted MRI scan and the first data set is a contrast-weighted data set; The method further comprises: selecting voxels of the first data set that are identified as belonging to a cerebrospinal fluid region based on the labeling data set; applying a multi-scale vascular filtering algorithm to identify voxels of said first data set that represent blood vessels and assigning a vascular enhancement weight to each voxel; Integrating the vascular enhancement weights into the first data set; After aligning the first data set and the second data set, converting the first data set into a surface anatomical mesh model. The method according to item 1, comprising: (Item 6) the first imaging scan is a contrast weighted MRI scan and the second imaging scan is an anatomical MRI scan; The method further comprises: defining expected target and entry point coordinates for the probe based on target and entry point coordinates of previously implanted probes or by user defined target and entry points; defining a trajectory for the probe based on an average target coordinate and an average entry point coordinate; adjusting the trajectory to intersect with a nearest voxel that has been assigned a label in the anatomical region of interest; checking the proximity of said trajectory to a critical structure based on user-defined constraints and / or user-defined modifications of said trajectory to satisfy said user-defined constraints; superimposing the trajectory onto the second data set to form a planning data set; The method according to item 1, comprising: (Item 7) the first imaging scan is an anatomical MRI scan and the second imaging scan is a post-implant CT imaging scan, the first data set is an anatomical MRI data set and the second data set is a post-implant CT imaging data set; The method further comprises: obtaining a third imaging scan for use in guiding electrode implantation during surgery; converting the third imaging scan into a third data set; Aligning a third data set with the first data set; obtaining a trajectory embedding data file generated during said electrode embedding; generating a planning trajectory data set based on the trajectory embedding data file, the planning trajectory data set including dummy objects to be placed at the electrode geometry locations; Aligning the planned trajectory dataset to the CT imaging dataset; automatically identifying and labeling electrodes in the CT electrode data set based on dummy objects in the trajectory-embedded data file; The method according to item 1, comprising: (Item 8) A non-transitory computer readable medium, the non-transitory computer readable medium comprising: obtaining a first imaging scan and a second imaging scan of a single subject brain; converting the first imaging scan into a first data set and the second imaging scan into a second data set; applying a sequence adaptive multi-modal segmentation algorithm to the first data set and the second data set, the sequence adaptive multi-modal segmentation algorithm performing an automatic intensity-based tissue classification to generate a first label data set and a second label data set; automatically co-registering the first and second sign data sets relative to one another and generating a transformation matrix based on the first and second sign data sets; applying the transformation matrix to align the first data set and the second data set; A non-transitory computer-readable medium encoded with instructions executable by one or more processors to perform the steps of: (Item 9) 9. The non-transitory computer-readable medium of claim 8, wherein the first imaging scan and the second imaging scan are performed using one or more of magnetic resonance imaging (MRI), computed tomography (CT), magnetoencephalography (MEG), or positron emission tomography (PET). (Item 10) 9. The non-transitory computer-readable medium of claim 8, wherein the sequence adaptive multi-modal segmentation algorithm assigns a numerical indicator value to each voxel of the first data set or the second data set. (Item 11) The instruction: Extracting voxels from the first data set having labels corresponding to a subcortical region of interest; forming a third data set containing the voxels extracted from the first data set; Transforming the third data set into a first subcortical surface mesh model; and calculating curvature and sulcus features of the first subcortical surface mesh model; Matching the first subcortical surface mesh model to a subcortical anatomy of the region of interest using the curvature and sulcus features; overlaying the first subcortical surface mesh model aligned to an anatomy of the subcortical region of interest onto a second subcortical surface mesh model, the second subcortical surface mesh model having a standardized number of nodes that allows a one-to-one correspondence between node identification and anatomy location; assigning coordinates of nodes of the first subcortical surface mesh model to the second subcortical structural surface mesh model such that the second subcortical surface mesh model exhibits a topology of the first subcortical structural surface mesh model; 9. The non-transitory computer-readable medium of item 8, executable by the one or more processors to perform the steps of: (Item 12) the first imaging scan is a contrast-weighted MRI scan and the first data set is a contrast-weighted data set; The instruction: selecting voxels of the first data set that are identified as belonging to a cerebrospinal fluid region based on the labeling data set; applying a multi-scale vascular filtering algorithm to identify voxels of said first data set that represent blood vessels and assigning a vascular enhancement weight to each voxel; Integrating the vascular enhancement weights into the first data set; After aligning the first data set and the second data set, converting the first data set into a surface anatomical mesh model. 9. The non-transitory computer-readable medium of item 8, executable by the one or more processors to perform the steps of: (Item 13) the first imaging scan is a contrast weighted MRI scan and the second imaging scan is an anatomical MRI scan; The instruction: defining expected target and entry point coordinates for the probe based on target and entry point coordinates of previously implanted probes or by user defined target and entry points; defining a trajectory for the probe based on an average target coordinate and an average entry point coordinate; adjusting the trajectory to intersect with a nearest voxel that has been assigned a label in the anatomical region of interest; checking the proximity of said trajectory to a critical structure based on user-defined constraints and / or user-defined modifications of said trajectory to satisfy said user-defined constraints; superimposing the trajectory onto the second data set to form a planning data set; and wherein the one or more processors are executable to perform Item 9. The non-transitory computer-readable medium of item 8. (Item 14) the first imaging scan is an anatomical MRI scan and the second imaging scan is a post-implant CT imaging scan, the first data set is an anatomical MRI data set and the second data set is a post-implant CT data set; The instruction: obtaining a third imaging scan for use in guiding electrode implantation during surgery; converting the third imaging scan into a third data set; Aligning a third data set with the first data set; obtaining a trajectory embedding data file generated during said electrode embedding; generating a planning trajectory data set based on the trajectory embedding data file, the planning trajectory data set including dummy objects to be placed at the electrode geometry locations; Aligning the planned trajectory dataset to the post-implant CT imaging dataset; automatically identifying and labeling electrodes in the CT electrode data set based on dummy objects in the trajectory-embedded data file; 9. The non-transitory computer-readable medium of item 8, executable by the one or more processors to perform the steps of: (Item 15) 1. A system comprising: one or more processors; a memory coupled to the one or more processors, the memory comprising: obtaining a first imaging scan and a second imaging scan of a subject brain; converting the first imaging scan into a first data set and the second imaging scan into a second data set; applying a sequence adaptive multi-modal segmentation algorithm to the first data set and the second data set, the sequence adaptive multi-modal segmentation algorithm performing an automatic intensity-based tissue classification to generate a first label data set and a second label data set; automatically co-registering the first and second sign data sets relative to one another and generating a transformation matrix based on the first and second sign data sets; applying the transformation matrix to align the first data set and the second data set; a memory storing instructions for configuring the one or more processors to A system comprising: (Item 16) The first imaging scan and the second imaging scan may be performed using a method such as magnetic resonance imaging (MRI), computer 16. The system of item 15, implemented using one or more of computed tomography (CT), magnetoencephalography (MEG), or positron emission tomography (PET). (Item 17) Item 16. The system of item 15, wherein the sequence adaptive multi-modal segmentation algorithm assigns a numerical indicator value to each voxel of the first data set or the second data set. (Item 18) The instruction: Extracting voxels from the first data set having labels corresponding to a subcortical region of interest; forming a third data set containing the voxels extracted from the first data set; Transforming the third data set into a first subcortical surface mesh model; and calculating curvature and sulcus features of the first subcortical surface mesh model; Matching the first subcortical surface mesh model to a subcortical anatomy of the region of interest using the curvature and sulcus features; overlaying the first subcortical surface mesh model aligned to an anatomy of the subcortical region of interest onto a second subcortical surface mesh model, the second subcortical surface mesh model having a standardized number of nodes that allows a one-to-one correspondence between node identification and anatomy location; assigning coordinates of nodes of the first subcortical surface mesh model to the second subcortical structural surface mesh model such that the second subcortical surface mesh model exhibits a topology of the first subcortical structural surface mesh model; 16. The system of claim 15, wherein the one or more processors are configured to: (Item 19) the first imaging scan is a contrast-weighted MRI scan and the first data set is a contrast-weighted data set; The instruction: selecting voxels of the first data set that are identified as belonging to a cerebrospinal fluid region based on the labeling data set; applying a multi-scale vascular filtering algorithm to identify voxels of said first data set that represent blood vessels and assigning a vascular enhancement weight to each voxel; Integrating the vascular enhancement weights into the first data set; After aligning the first data set and the second data set, converting the first data set into a surface anatomical mesh model. 16. The system of claim 15, wherein the one or more processors are configured to: (Item 20) the first imaging scan is a contrast weighted MRI scan and the second imaging scan is an anatomical MRI scan; The instruction: defining expected target and entry point coordinates for the probe based on target and entry point coordinates of previously implanted probes or by user defined target and entry points; defining a trajectory for the probe based on an average target coordinate and an average entry point coordinate; adjusting the trajectory to intersect with a nearest voxel that has been assigned a label in the anatomical region of interest; checking the proximity of said trajectory to a critical structure based on user-defined constraints and / or user-defined modifications of said trajectory to satisfy said user-defined constraints; superimposing the trajectory onto the second data set to form a planning data set; 16. The system of claim 15, wherein the one or more processors are configured to: (Item 21) the first imaging scan is an anatomical MRI scan and the second imaging scan is a post-implant CT imaging scan, the first data set is an anatomical MRI data set and the second data set is a post-implant CT imaging data set; The instruction: obtaining a third imaging scan for use in guiding electrode implantation during surgery; converting the third imaging scan into a third data set; Aligning a third data set with the first data set; obtaining a trajectory embedding data file generated during said electrode embedding; generating a planning trajectory data set based on the trajectory embedding data file, the planning trajectory data set including dummy objects to be placed at the electrode geometry locations; Aligning the planned trajectory dataset to the post-implant CT imaging dataset; identifying electrodes in the CT electrode data set based on dummy objects in the trajectory-embedded data file; 16. The system of claim 15, wherein the one or more processors are configured to: [Brief description of the drawings]

[0010] For a detailed description of various embodiments, reference will now be made to the accompanying drawings.

[0011] [Figure 1] FIG. 1 shows a flow diagram for a method for co-registration of brain imaging scans in accordance with the present disclosure.

[0012] [Diagram 2] FIG. 2 shows a flow diagram for a method for the generation of surface models of cortical and subcortical brain regions in accordance with the present disclosure.

[0013] [Diagram 3]FIG. 3 shows a flow diagram for a method for automated segmentation of cerebral vasculature in accordance with the present disclosure.

[0014] [Figure 4] FIG. 4 shows a flow diagram for a method for visualizing underlying brain structures according to the present disclosure.

[0015] [Diagram 5] FIG. 5 shows a flow diagram for a method for automated planning of electrode or probe implantation in accordance with the present disclosure.

[0016] [Figure 6] FIG. 6 shows a flow diagram for a method for automated localization, naming, and visualization of previously implanted electrodes or penetrating brain probes in accordance with the present disclosure.

[0017] [Figure 7] FIG. 7 shows a pictorial representation of co-registration of different neuroimaging modalities performed on a single subject in accordance with the present disclosure.

[0018] [Figure 8] 8A-8F show pictorial representations depicting the generation of 2D / 3D surface models of the hippocampus and thalamus in accordance with the present disclosure.

[0019] [Figure 9] 9A-9D show exemplary steps for segmenting the human brain vasculature according to the present disclosure.

[0020] [Figure 10-1] 10A-10W illustrate the use of cutting planes to intersect surface and volumetric models at arbitrary angles to optimize visualization of cortical and subcortical structures and / or functional representations in accordance with the present disclosure. [Figure 10-2]10A-10W illustrate the use of cutting planes to intersect surface and volumetric models at arbitrary angles to optimize visualization of cortical and subcortical structures and / or functional representations in accordance with the present disclosure. [Figure 10-3] 10A-10W illustrate the use of cutting planes to intersect surface and volumetric models at arbitrary angles to optimize visualization of cortical and subcortical structures and / or functional representations in accordance with the present disclosure.

[0021] [Figure 11-1] 11A-11R show certain examples of population-derived anatomical targeting for implantation of electrodes or penetrating probes in accordance with the present disclosure. [Figure 11-2] 11A-11R show certain examples of population-derived anatomical targeting for implantation of electrodes or penetrating probes in accordance with the present disclosure.

[0022] [Figure 12] 12A-12E show pictorial representations of automated electrode localization and targeting.

[0023] [Figure 13] FIG. 13 illustrates a block diagram of a computing system suitable for implementing the methods disclosed herein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] Detailed Description A certain term is used throughout this description and the claims to refer to a characteristic system component. As will be understood by those skilled in the art, different parties may refer to components by different names. This document is not intended to distinguish between components that have different names but the same function. In this disclosure and the claims, the terms "including" and "comprising" are used in a non-limiting manner and should therefore be construed to mean "including, but not limited to...". Also, the term "couple" or "couples" is intended to mean either an indirect or direct wired or wireless connection. Thus, when a first device is coupled to a second device, the connection may be through a direct connection or through an indirect connection via other devices and connections. The recitation "based on" is intended to mean "based at least in part on". Thus, when X is based on Y, X may be a function of Y and any number of other factors.

[0025] There are several clinical reasons for implanting electrodes or other medical devices in the brain, and focal epilepsy provides a single exemplary condition that is focused on here for illustrative purposes. In all such patients who meet the criteria for invasive monitoring or interventional procedures, the patient's clinical course can be broadly categorized into three stages: 1) planning, 2) data acquisition, and 3) intervention. Typically, during the planning stage, the patient undergoes high-resolution anatomical imaging using MRI, which may also be performed following the injection of contrast into the bloodstream for enhanced imaging of blood vessels. More recently, with improvements in computational modeling techniques, data from these imaging scans can be used to generate 2D and 3D models of the patient's brain anatomy that can better inform surgeons and clinicians planning subsequent surgical interventions, taking into account critical or vital anatomical structures.

[0026] Following planning, the patient undergoes intracranial electrode implantation, following which post-operative imaging is typically obtained (e.g., CT brain scans) to precisely and accurately relate the implanted electrodes to the patient's cortical anatomy. Similarly, 2D and / or 3D computational models of the implanted electrodes or probes are also generated from repeated imaging scans, and once the different (pre- or post-implant) imaging data are brought into co-registration with one another (e.g., fabricated into a common coordinate space), they can be used to relate the acquired electrophysiological data to the underlying cortical anatomy.

[0027] In the intervention phase, data collected from phases 1 and 2 (planning and implantation) are used as part of a comprehensive clinical evaluation of the patient to determine whether the putative pathological focus can be localized and, if applicable, its relationship to critical and non-critical brain structures. This information is used by the surgeon to optimize the final surgical planning for removal of the seizure focus, minimizing damage to healthy or vital brain regions.

[0028] At each of these stages, precision and accuracy are paramount to ensure that patients do not sustain any transient or permanent adverse neurological outcomes that would otherwise be avoided. Despite the numerous technological, imaging, and computational advances developed in the past two decades, significant technical obstacles remain. These include challenges with accurate co-registration of different imaging modalities for automated planning of electrode implantation, for methods that use only non-invasive imaging data to minimize the risk of injury to critical structures (e.g., blood vessels), and for automated and / or semi-automated integration of post-implant imaging data with neuroanatomical and functional data to inform potential surgical interventions. The methods and systems disclosed herein overcome the aforementioned limitations using a novel approach described below.

[0029] The embodiments of the present disclosure relate to robust and accurate co-registration of different brain imaging modalities. In particular, the present disclosure describes a novel application of a sequence-adaptive multi-modal segmentation algorithm to the same and / or different imaging modalities used to obtain brain images to accurately achieve intra-subject multi-modal co-registration of these imaging modalities in a robust and automated manner. The sequence-adaptive multi-modal segmentation algorithm is applied to a 3D data set generated from an original brain imaging scan performed on a patient, which may include, but is not limited to, data formats such as those described by the Neuroimaging Informatics Technology Initiative (NIFTI), generated from the imaging file of the patient's brain scan, an exemplary embodiment of which may be an image stored according to the standard defined by the Digital Imaging and Communications in Medicine (DICOM) standard. A sequence-adaptive multi-modal segmentation algorithm is applied to the dataset without the need for further or additional pre-processing (including but not limited to intensity normalization and / or volumetric structure) to generate a new labeled segmented dataset of identical volume and geometry of the original dataset, but with each voxel (i.e., 3D pixel) replaced by a number whose original intensity value is associated with a unique anatomical region and / or the probability that the voxel belongs to various brain regions (an exemplary embodiment of which may include a probabilistic distribution of brain regions as defined by a template or reference anatomical map). The segmented dataset is then utilized as a "go" input to a co-registration algorithm to be aligned to an equivalently segmented "target" dataset generated from the same and / or different imaging modality in the same patient.The co-registration algorithm will also generate, as part of the computational output, a transformation matrix that describes the mathematical operations required to exactly replicate the alignment between the input "moving" and "target" datasets in a symmetrical manner, both in a forward (i.e., aligning the "moving" dataset to the "target" dataset) and backward (i.e., aligning the "target" dataset to the "forward" dataset) manner. Once the transformation matrix is ​​generated, it can be applied to any dataset that shares the volume geometry of the original moving dataset to align it with the original target dataset. The present disclosure describes an entirely new application of the segmentation algorithm to co-register imaging datasets obtained within the same subject using the same or different imaging modalities (e.g., MRI and CT) based on transformation matrices generated using segmentation, providing technical improvements that significantly advance the previous state of the art for intra-subject multi-modal co-registration of brain images. Implementations of the present disclosure provide satisfactory outcomes despite the presence of imaging features that would be common causes of failure of other currently existing co-registration methods, including, but not limited to, anatomical defects, lesions, and / or masses, foreign bodies, hemorrhage, and / or intensity differences between imaging data sets, and / or differences in the imaging pulse sequences used, and / or scanning device platform parameters based on which the images were obtained.

[0030] The disclosed embodiments relate to a method of using extracranial boundary layers generated by a sequence-adaptive multimodal segmentation algorithm to generate anatomically accurate skin and skull models to facilitate pre-surgical planning and post-implant localization of sEEG electrodes. The segmentation of extracranial boundary elements directly from CT imaging is a completely novel approach that is an improvement over previous methods. The generation of skull boundary layers using a method applied to a T1-weighted MRI dataset is also a completely new approach to the field that demonstrates improvements over current methods of boundary element modeling used to estimate these layers. These improvements provide tangible benefits to planning of surgical electrode implantation by providing skull / brain and skin / skull boundary layers for electrode implantation.

[0031] Embodiments of the present disclosure relate to methods of using cerebrospinal fluid (CSF) volumes and segmentation of gray and white matter cortex as a mask to aid in segmenting blood vessels from 3D brain imaging datasets, including but not limited to contrast-weighted T1 MR imaging. In some exemplary embodiments, the MR imaging datasets may have their intensity values ​​upscaled to better separate high-intensity voxels that are likely to reflect blood vessels (e.g., from white matter tracts or partial volume averaging) from surrounding tissue with similar (but lower) intensity values. The use of a CSF boundary layer to mask and constrain the parameter space for blood vessel segmentation using upscaled contrast MRI is a novel approach to facilitate segmentation of the cerebral vasculature.

[0032] Embodiments of the present disclosure relate, in some exemplary embodiments, to a method for applying a multi-scale Hessian-based filter to segment blood vessels from the aforementioned CSF mask dataset, gray matter mask dataset, and white matter mask dataset.

[0033] Embodiments of the present disclosure relate to methods for generating 2D / 3D anatomical mesh models of a patient's hippocampus, amygdala, and other subcortical structures, and for generating standardized versions of these anatomical meshes derived from high-resolution template volumes.

[0034] Embodiments of the present disclosure relate to methods for determining optimal trajectories for implantation of electrodes or penetrating probes into the brain using loss functions and / or risk metrics defined in relation to segmented vascular volumes.

[0035] The embodiments of the present disclosure relate to a method of 2D / 3D visualization of the cerebral vasculature. In some exemplary embodiments, such visualization will require a step of reconstructing discontinuities in the vascular volume. In some exemplary embodiments, this visualization is achieved using algorithms originally developed for diffusion tensor imaging. In such exemplary embodiments, digital image intensity modulation is applied to the vascular volume, constrained to specific directional gradients in 3D space, which in some embodiments is implemented using Hessian-based or tensor-based decomposition to mimic anisotropic diffusion in the 3D imaging volume. These data sets can then be processed by the diffusion tensor imaging toolbox to model and predict connections between similar but discontinuous imaging features. In this manner, likely connections between similar voxels that are becoming discontinuous due to, for example, low signal-to-noise ratios or processing artifacts can be remodeled and visualized (e.g., for blood vessels in the 3D imaging volume). In this manner, for example, continuous blood vessels can be reconstructed from discontinuous data sets.

[0036] The presently disclosed embodiments relate to a method for generating topologically accurate 2D / 3D surface-based representations and / or anatomical mesh models of the hippocampus, amygdala, thalamus, basal ganglia, and other subcortical structures for use in surgical planning. Parcellations of cortical regions are also generated, and any one of these structures can be visualized and manipulated independently with respect to adjacent and contralateral structures. Furthermore, using population-based anatomical charts and templates, standardized surface models of these subcortical and / or other deep structures can also be generated, which will enable the translation and application of surface-based co-registration and analysis techniques originally developed for cortical-based inter-subject analysis and shown to result in significant improvements to accuracy and results. These methods are entirely new contributions to the field that will provide significant improvements in modeling hippocampal and / or other subcortical region pathology, as well as understanding of hippocampal / amygdala or other deep brain structure pathology through direct visualization or through representation of functional or electrographic data on mesh surface models, or modeling of electrode or penetrating probe or catheter implantation into these regions.

[0037] An embodiment of the present disclosure relates to a method for aligning a trajectory obtained from a robotic, mechanical, or human implanted device or process to an anatomical T1 MR imaging of a subject using volume geometry and a transformation matrix obtained from contrast-weighted T1 MR imaging of the subject.

[0038] Embodiments of the present disclosure relate to methods for precisely identifying anatomical targets to be implanted or targeted using automated parcellation techniques and linear and / or non-linear deformation algorithms to warp a subject brain into a standard template space (or vice versa) in which targets have been previously defined based on anatomical structure.

[0039] Embodiments of the present disclosure relate to methods for precisely identifying anatomical targets to be implanted or targeted using prior probability distributions derived from a previously implanted population.

[0040] An embodiment of the present disclosure relates to assigning anatomical targets to facilitate unsupervised design of implantation trajectories using depth electrodes placed for epilepsy identification as dictated by specific seizure semiology or epilepsy characterization. This may apply to placement of laser probes, recording or modulation brain electrodes, stereotactic biopsy probes, injection of biological, cellular, genetic, or chemical materials into the brain via trajectories using anatomical constraints and previous implantation cases.

[0041] An embodiment of the present disclosure relates to a method for generating a 3D surface model of predicted ablation volumes (i.e., expected volumes of hippocampal tissue that may be affected) using prior probability distributions derived from previous laser ablation volumes across a population. This is a novel contribution to the field that will improve pre-surgical planning and informed trajectory modeling for subsequent laser ablation or other similar catheter-based therapies.

[0042] Embodiments of the present disclosure relate to automated techniques for identifying and avoiding damage to white matter pathways (identified either via deterministic or probabilistic tractography derived from diffusion imaging) involved in vital functions such as motor, sensory, auditory, or visual processes.

[0043] An embodiment of the present disclosure relates to a method for automated segmentation and localization of sEEG electrodes using intensity upscaling of post-implant CT brain imaging datasets and a volume-based clustering algorithm of the resulting metal artifacts. Trajectories from robotic implant devices previously aligned to the same imaging space are fitted using linear regression modeling to facilitate discrimination of metal electrode artifacts from noise. A line-fit model allows an automated method to account for deviations in electrode locations. Artifact clusters identified using a 3D volumetric clustering search algorithm are iteratively searched while masking any cortical regions that are not within the cluster of interest to ensure that overlapping or composite artifacts can be resolved. Identified clusters are matched to the robot trajectory using information about the parallelism between the trajectory path and the trajectory of the identified cluster, as well as information about the center of mass of the cluster to re-fit the trajectory once a sufficient number of electrodes have been identified. Real-time visualization of the search algorithm allows for simultaneous updates of cluster search results for informational and debugging purposes.

[0044] An embodiment of the present disclosure relates to a method for validation of implant planning of multiple stereotactic depth probes along oblique trajectories aided by simultaneous visualization of a cortical mesh model of surface topology and deep anatomical structures revealed by structural magnetic resonance imaging sliced ​​along a plane collinear with the proposed trajectory. Slicing the brain surface in any given plane allows visualization of the deeply buried cortex in 3D and also allows rapid confirmation of surgical planning by the clinician.

[0045] Embodiments of the present disclosure relate to a method of manipulating 3D spatial geometry to selectively visualize or interact with different surface models (e.g., skin, skull, blood vessels, brain, hippocampus, amygdala, etc.) along any plane. Surfaces can be rendered selectively traversable along any plane. Visualization of compartmentalization or intracranial EEG activity can also be rendered deep along or against the visualized surface along any plane.

[0046] Embodiments of the present disclosure relate to methods for converting intracranial electroencephalography (icEEG) activity from a surface-based representation into a DICOM or 3D dataset format depicting user-defined activations of interest constrained to underlying cortical ribbons reflecting gray matter regions likely to be involved in this activation.

[0047] Embodiments of the present disclosure relate to methods for performing empirical source localization estimation to model unique neural generators of recorded icEEG data.

[0048] Using the methods disclosed herein, implanted structures are automatically resolved using template matching search in post-surgical imaging along a known planned trajectory. This provides clinical staff with the final location of all implanted materials in an automated fashion (e.g., without manually identifying each electrode), allowing for a rigorous measurement of surgical accuracy. In one specific application, the methods disclosed herein help avoid visual impairment following laser interstitial thermal therapy for mesial temporal lobe epilepsy.

[0049] 1 shows a flow diagram for a method 100 for co-registration of brain imaging scans acquired of a subject by different imaging modalities. Although depicted sequentially for convenience, at least some of the operations shown can be performed in a different order and / or in parallel. In addition, some implementations may perform only some of the operations shown. The operations of method 100 may be performed by a computing system as disclosed herein.

[0050] One or more imaging scans of the subject's brain are obtained in block 102. The imaging scans may be performed using scanning modalities such as magnetic resonance imaging sequences (MRI), computed tomography (CT) sequences, magnetoencephalography (MEG), positron emission tomography (PET), or any combination thereof.

[0051] At block 104, the imaging scan is converted into a file format / data set that can be used for storage, analysis, and manipulation of the brain imaging data contained within the imaging scan. For example, the imaging scan may be converted into the NIFTI format.

[0052] At block 106, each data set produced at block 104 is provided as an input to a sequence-adaptive multimodal segmentation algorithm to generate a labeled parcellated and segmented data set. In general, the segmentation algorithm proceeds by matching a probabilistic anatomical map to a patient data set. The anatomical map, in one exemplary embodiment, serves to assign a probability of a specific brain region label to any voxel of a given data set, the intensity value of the voxel. In one exemplary embodiment, this may be accomplished by using a Bayesian analysis, where the anatomical map provides a prior probability of a voxel belonging to a specific tissue class. The algorithm may then utilize a likelihood distribution to define the relationship between a given brain region label and the distribution of intensity values ​​within the voxels of that data set, as an example. The term "tissue classification" may refer to white matter, gray matter, cerebrospinal fluid, brain tumor, and / or other brain regions. The term "matching" as used herein may refer to either linear or non-linear methods. For an example of the use of segmentation algorithms for sequence-adaptive segmentation of brain MRI, see for example Puonti O., Iglesias JE, Van Leemput K. (2013) Fast, Sequence Adaptive Parcellation of Brain MR Using Parametric Models. In: Mori K., Sakuma I., Sato Y., Barillot C., Navab N. (eds) Medical Image Computing and Computer-Assisted Intervention - MICCAI 2013. MICCAI 2013. Lecture Notes in Computer Science, vol 8149. Springer, Berlin, Heidelberg. https: / / doi.org / 10.1007 / 978-3-642-40811-3_91. The application of sequencing algorithms for the co-registration of different imaging modalities is not known in the art (e.g. between MRI and CT) and is a novel application here.Notably, the application of the present algorithm to achieve fast, accurate and robust co-registration between different imaging modalities (an exemplary embodiment of which may be the co-registration of MRI and CT imaging scans) is a significant improvement over the previous state of the art. In the labeling dataset, the imaging data (the exemplary data unit of the imaging data is a 3D pixel with a resolution of 1 mm×1 mm×1 mm (referred to herein as a voxel)) is replaced by a numerical label assigned according to the extracranial and intracranial structures represented. In various embodiments, the voxels can be of any dimension deemed useful by the user. The term "parcellation" is used to refer to the labeled cortical regions, while the term "segmentation" refers to the labeled subcortical regions. In the present disclosure, these two terms are used synonymously to refer to any labeled cortical or subcortical regions.

[0053] At block 108, the landmark data set is input to a co-registration algorithm whereby any two data sets are registered in each other's coordinate space, and then a mathematical transformation matrix is ​​generated that allows this coordinate transformation to be applied to any other data set that shares the volume geometry of either one of the two input data sets to register this other data set in the coordinate space of the second input data set. The transformation matrix may be a 4×4 matrix M that, in one exemplary embodiment, defines a linear, rigid body, and / or affine transformation from a point p to another point p′, as defined by the equation p′=Mp. In this example, point p defines the location of one voxel in the data set using a column vector consisting of the voxel's x, y, z coordinates and a numerical value 1. For example, p=(x,y,z,1). A matrix / vector product multiplies a vector column from matrix M with the corresponding (x,y,z,1) value from column vector p. Adding up the scalar / vector products generates the output vector p':(x', y', z', 1). In such an embodiment, the upper 3x4 elements of matrix M may contain real numbers that are used to store the combination of transformations, rotations, scaling, and / or shears (among other operations) applied to p. The last row in this exemplar would be (0 0 0 1). Transformation matrices of this form may be generated using one or more of a variety of neuroimaging analysis software. The combined use of the labeling dataset and parcellation / segmentation as input to co-registration, particularly in the case of CT imaging, overcomes many of the limitations of previous state-of-the-art techniques (e.g., related to intensity scaling differences or tissue boundary differences) and ensures accurate co-registration even in the presence of anatomical defects (e.g., strokes), brain lesions (e.g., tumors), or other imaging artifacts.

[0054] In block 110, the data sets generated in block 104 are aligned with each other using a transformation matrix.

[0055] 2 shows a flow diagram for a method 200 for the generation of surface models of cortical and subcortical brain regions according to the present disclosure. Although depicted sequentially for convenience, at least some of the operations shown can be performed in a different order and / or in parallel. In addition, some implementations may perform only some of the operations shown. The operations of method 200 may be performed by a computing system as disclosed herein on a labeling dataset such as produced by method 100.

[0056] The surface model generated by method 200 includes a standardized mesh model derived from a population-level anatomical drawing that allows for point-to-point correspondence between any point on the surface of one object and the same point on the surface in another object.

[0057] In block 202, all voxels that match the labeled values ​​for the cortical or subcortical regions of interest are extracted into a new 3D data set that contains only those voxels of interest. For example, the new data set may include the right hippocampus as identified during the segmentation process of method 100.

[0058] In block 204, the 3D dataset of the segmented cortical or subcortical region of interest formed in block 202 is converted to a surface mesh model using a standard volume / surface conversion. In general, standard volume / surface conversion can be achieved using existing open source neuroimaging software. General and exemplary embodiments of such methods include volume binarization followed by surface tessellation using binarized values ​​to generate a mesh (e.g., as provided by Freesurfer: https: / / surfer.nmr.mgh.harvard.edu / fswiki / mri_tessellate), or the marching cubes algorithm as made available by the open source Vascular Modeling Toolkit software (VMTK: http: / / www.vmtk.org / vmtkscripts / vmtkmarchingcubes.html). In one exemplary embodiment, the surface / anatomical mesh model may be defined as points in 3D space, each of which has a 2D face, joined by lines to form triangles that combine according to a specific volume geometry and form a topologically accurate representation of the modeled object. The surface / anatomical mesh model, in one exemplary embodiment, may be a 2D model (e.g., a plane) that is then folded into 3D space to depict a 3D object (e.g., the brain surface).

[0059] In block 206, the curvature and sulcus features of the resulting surface model are calculated, which are then used to nonlinearly match a stretched version of the surface model to a high-resolution anatomical map of the same region generated from the labeled population data. In this context, "high-resolution anatomical map" may refer to a reference template pattern of cortical curvature data that, in some exemplary embodiments, has been previously prepared as an average pattern calculated from a group of representative subjects and made available as part of a standard repository. In other exemplary embodiments, such template data may be generated using a selected subject population (e.g., patients operated on in a certain manner at a particular institution).

[0060] In block 208, the standardized surface mesh, already aligned with the anatomical map, is overlaid on the subject's original surface model, and the coordinates of this standardized surface mesh are replaced by a resample of the coordinates of the periphery of the subject's native coordinate space. The surface mesh consists of thousands of points in space, called nodes, that are connected by lines to form triangles whose faces form the faces of the surface model. In the context of standardized surfaces, the mesh model consists of a fixed number of nodes, and maintains a specific node / anatomical map region correspondence (i.e., each node corresponds to the same region in the anatomical map), and this correspondence can be preserved across subjects. To preserve this correspondence, for each subject, both the standardized surface mesh and the subject's own original surface mesh are deformed in a nonlinear manner to match a spherical template mesh derived from the aforementioned high-resolution population anatomical map. Both the subject mesh and the standardized mesh are warped to maximize the overlap between the groove pattern and the curvature pattern. Once both the object mesh and the standardized surface mesh are aligned to the template anatomy and therefore aligned to each other, the nodes of the standardized surface mesh are assigned the average of the coordinates of a subset of the surrounding nodes (an exemplary embodiment of which would be the four nearest nodes) from the object's original surface mesh. In this manner, the standardized surface is warped into the object's anatomical coordinate space while both are aligned to the template, thereby preserving the one-to-one correspondence between the standardized surface and the template anatomy. Once contracted from the spherical configuration used during co-registration, the standardized surface mesh subsequently maintains its one-to-one correspondence between nodes and anatomy identifications while assuming the topology of the object's own anatomy. In this manner, surface-based comparisons can be performed across objects with a high level of accuracy by simply comparing specific nodes and identical nodes between surfaces.

[0061] The operations of method 200 may be repeated such that contralateral hemisphere regions and any other additional cortical or subcortical or other labeled / segmented or parceled brain surfaces are generated. For information on generating standardized surfaces for cortical surfaces, see, e.g., Saad, ZS, Reynolds, RC, 2012. Suma. NeuroImage 62, 768-773. http: / / dx.doi.org / 10. 1016 / j.neuroimage.2011.09.016.; Kadipasaoglu CM, Baboyan VG, Conner CR, Chen G, Saad ZS, Tandon N. Surface-based mixed effects multilevel analysis of grouped human electrocorticography. Neuroimage. 2014 Nov 1;101:215-24. doi: 10.1016 / j.neuroimage.2014.07.006. Epub 2014 Jul 12. PMID: 25019677). However, no such method is known for generating standardized surface-based meshes of subcortical regions. Exemplary embodiments of such regions may include the hippocampus, amygdala, thalamic nuclei, and basal ganglia. Such surface models may be used to generate standardized subcortical surfaces for individual anatomical structures, allowing for matching of these subcortical structures between individuals in a manner not previously done.

[0062] The use of method 200 for brain regions not traditionally included in surface-based models or analyses (e.g., hippocampal and / or amygdala and / or subcortical regions), coupled with the use of high-resolution anatomical views of the regions to enable the generation of standardized surface meshes, is a significant improvement over previous state of the art, which previously constrained such methods to only cortical regions (e.g., strictly gray or white matter surfaces).

[0063] 3 shows a flow diagram for a method 300 for automated segmentation of cerebral vasculature and generation of 2D / 3D surface-based and volume-based models according to the present disclosure. Although depicted sequentially for convenience, at least some of the operations shown can be performed in a different order and / or in parallel. In addition, some implementations may perform only some of the operations shown. The operations of method 200 may be performed by a computing system as disclosed herein.

[0064] At block 302, one or more imaging scans of the subject's brain are acquired. The imaging scans include a contrast-weighted MRI scan (e.g., a T1-weighted MRI with contrast, which will be referred to as a contrast MRI data set).

[0065] In block 304, the imaging scan is converted from the original imaging storage format (e.g., DICOM) to a 3D dataset according to method 100. During conversion, the intensity values ​​of the contrast MRI are variably upscaled (e.g., by 100x) to facilitate differentiation of contrast-enhanced structures (e.g., blood vessels) from their surroundings.

[0066] In block 306 , a sequence-adaptive multi-modal segmentation algorithm is used to generate a labeling data set from the contrast MRI, as per method 100 .

[0067] In block 308, a mask from the labeling dataset, generated as described in method 100, for the contrast MRI dataset is used to subselect all voxels identified as belonging to cerebrospinal fluid (CSF) regions. The CSF mask (subselected voxels) provides a novel improvement to the vessel segmentation algorithm, since hyperintense voxels representing blood vessels are most commonly localized adjacent to the pial surface within the CSF. This is especially true for those vessels deemed to pose the greatest risk of clinically significant hemorrhage (typically vessels with a diameter of ≧1.5 mm). Similar masks for the gray matter labelled regions and the white matter labelled regions are also generated.

[0068] In block 310, a multi-scale filtering algorithm designed to enhance tubular features in the imaging data is used to extract blood vessels from adjacent voxels reflecting CSF or background noise. Typically, the filtering algorithm utilizes a Hessian-based eigendecomposition to derive eigenvalues ​​and vectors at each pixel of the data set at various spatial scalings to select tubular structures corresponding to vessels of different diameters (see, e.g., Frangi, Alejandro F., et al. Multiscale vessel enhancement filtering. Medical Image Computing and Computer-Assisted Intervention-MICCAI'98. Springer Berlin Heidelberg, 1998. 130-137). The software algorithm returns an output that assigns a "vascular enhancement" weight to each voxel, for example ranging from 0 to 1, with higher weights representing voxels with more vessel-like features (e.g., being tubular).

[0069] In block 312, information from the vascular enhancement weighted dataset is integrated with the contrast MRI dataset to weight the intensity values ​​of non-zero voxels by their relative "vascular enhancement" weights and to penalize those voxels that overlap with white or gray matter.

[0070] In block 314, the vascular dataset is registered to the anatomical MRI dataset using the transformation matrix generated in block 306 (as described in method 100).

[0071] At block 316, the vascular data set is converted into a surface anatomical mesh model (as described with respect to block 204 of method 200) that can be visualized using various levels of transparency and illumination.

[0072] 4 shows a flow diagram for a method 400 for visualizing underlying brain structures according to the present disclosure. Although depicted sequentially for convenience, at least some of the operations shown can be performed in a different order and / or in parallel. In addition, some implementations may perform only some of the operations shown. The operations of method 400 may be performed by a computing system as disclosed herein.

[0073] In block 402, a cutting plane (e.g., a 2D cutting plane) in 3D space in any user-defined axis intersects with a 3D volume or surface. At the intersection of the cutting plane with a given surface mesh model or 3D volume, all components of the mesh on both sides of the cutting plane can be selectively rendered visible, invisible, or semi-transparent. On this plane, any surface and / or volume (structural or functional) data can be visualized simultaneously. In general, the operations of block 402 can be performed by defining the cutting plane along one and / or more of the 2D anatomical imaging planes of the imaging dataset (whose exemplary embodiments include the coronal, sagittal, or axial planes of MRI and / or CT scans). The intersection of the cutting plane and the imaging dataset may be defined along any arbitrary geometric shape (whose embodiments may include orthogonal and / or oblique angles), and the points along the intersection of these two planes identify voxels of the associated 3D volumetric imaging dataset that will be further used for further display and / or analysis. These voxels may then be selectively visualized along with a 3D surface model of the object, and the relationship between the coordinates of the voxels and the coordinates of the 3D surface model (e.g., at their points of intersection) may further be used to selectively render components of the surface model visible, invisible, or semi-transparent on either side of the cut plane, or along the cut plane itself. The coordinates of the voxels along the cut plane may also be used to determine their distance from implanted electrodes within the object, which may then be used to calculate and generate surface and / or volumetric data representations for the cut plane.

[0074] When applied to the extracranial and intracranial anatomical meshes as defined in methods 200 and / or 300 in block 402, qualitative and quantitative analyses of the surfaces or volumes intersected by the cutting plane may be calculated, including, but not limited to, calculation of morphometric features such as the curvature, thickness, and area of ​​the cortical gray / white matter and / or subcortical structures, and the curvature, thickness, and area of ​​the hippocampus and amygdala. Additionally, edges of the intersected surfaces and / or volumes may be selectively raised or lowered to improve the accuracy of visualization. In one exemplary embodiment, the intersection of the cutting plane with specific elements of the 3D surface may include various cortical and / or subcortical surface layers, the exemplary embodiment of which includes the pial and / or white matter surfaces. For these exemplary embodiments, the intersection of the cutting plane with these surfaces will determine the intervening gray matter between these two exemplary surfaces. The intervening gray matter may be otherwise referred to as a cortical ribbon. Also, the thickness of the cortical ribbon can be calculated by calculating the distance between the points of the pial surface and the white matter surface that lie along their intersection with the cutting plane (e.g., the orthogonal distance between these two surfaces at their intersection with the cutting plane). The area can be calculated by integrating the thickness across the length of the cortical ribbon. In another exemplary embodiment, the curvature of a surface (e.g., the pial surface mesh) may be calculated by drawing orthogonal lines outward from the faces of the surface mesh triangles and determining whether these lines intersect with the faces of another mesh triangle. Such intersections occur when the faces of two triangles are oriented towards each other, as in the case of a sulcus. Using the angles and distances of such intersections, local topological features such as surface curvature and sulcal boundaries can then be determined.

[0075] In block 404, when applied to the extracranial anatomical mesh and the intracranial anatomical mesh as defined in methods 200 and / or 300, visualization of brain structural data (including one or more of MRI, CT, PET, fMRI, DTI) and / or brain activity data (including one or more of EEG or MEG or brain stimulation) associated with various anatomical mesh model cut sections may be selectively depicted.

[0076] In block 406, when applied to the extracranial and intracranial anatomical meshes as defined in methods 200 and / or 300, a user can make virtual cuts of arbitrary shapes or geometries (e.g., a dome-shaped surface or a surface that matches a craniotomy) by selecting a path along the surface and the depth within the surface to which the cut should be applied, in a manner that allows the user to model and visualize surgical approaches or various anatomical boundaries for clinical evaluation and / or surgical planning or training and / or educational visualization.

[0077] 5 shows a flow diagram for a method 500 for automated planning of electrode or probe implantation according to the present disclosure. Although depicted sequentially for convenience, at least some of the operations shown can be performed in a different order and / or in parallel. In addition, some implementations may perform only some of the operations shown. The operations of method 500 may be performed by a computing system as disclosed herein.

[0078] The method 500 provides for precise and automated planning of electrode or penetrating probe implantation trajectories using prior probability distributions derived from previously implanted populations for anatomical targets to be implanted or targeted. The prior probability distributions are generated using entry and / or target coordinates of trajectories from previously implanted populations that have been matched to the subject's brain using linear or non-linear deformation algorithms (or vice versa). Furthermore, a general implantation strategy is derived from clinical considerations of likely anatomical regions using a description of a clinical electrical syndrome that links the subject's seizure semiology or other electroclinical characterization of epilepsy. In each case, the trajectories will have the additional goal of avoiding critical structures (e.g., blood vessels) through the use of loss functions and risk metrics. Additionally, these trajectories can be generated, in one embodiment, by a physician or surgeon, skilled in the art of stereotaxy, simply by defining entry points of interest and entry targets.

[0079] At block 502, one or more imaging scans of the subject's brain are acquired. The imaging scans include a targeted anatomical MRI scan (e.g., T1 weighted MRI without contrast) and a contrast weighted scan (e.g., T1 weighted MRI with contrast).

[0080] At block 504, the imaging scans are converted from the original imaging storage format (e.g., DICOM) to a dataset according to method 100. The T1 weighted MRI without contrast is converted to a dataset referred to as the anatomical MRI dataset, and the T1 weighted MRI with contrast is converted to a dataset referred to as the contrast MRI dataset.

[0081] At block 506 , a vascular dataset and mesh model is generated and co-registered to the anatomical MRI dataset and its associated mesh model according to method 100 .

[0082] In block 508, predicted entry and target point coordinates in the subject's own anatomical space are defined using target point coordinates and entry point coordinates curated from a population cohort of previous implanted subjects. The coordinates from the population were previously co-registered to a high-resolution template anatomical map. In an exemplary embodiment, the template coordinate space can be a coordinate space defined as in a standard coordinate space (e.g., Talairach space, Montreal Neuroscience Institute space). Co-registration can be achieved using a non-linear or linear / rigid / affine transformation, such that the template coordinates can be transformed into the patient's coordinate space in a topologically accurate manner, and the inverse transformation can be applied following implantation of the subject's electrodes and further added to the population's previous data set, and calculated in an inversely consistent and symmetric manner.

[0083] In block 510, for each probe, the group of entry and target point coordinates for that probe are averaged to generate an average target and entry point in the subject's anatomical coordinate system from which an average trajectory is defined. For each probe, an anatomical parcellation is further associated with the probe and can be used to further constrain the predicted trajectory in exemplary cases where the anatomical region of interest is small in volume and / or in close proximity to other sensitive anatomical structures and / or the variability of the divergence of the target coordinates from the previous population may be greater than the diameter of the structure. In this manner, in one exemplary embodiment, the anatomical parcellation and the previous implanted trajectory distributions are used and can be used to develop prior information to enable implantation of the penetrating probe. In another exemplary embodiment, the anatomical target may be very large (e.g., as in the cingulate cortex, which extends in a C-shape from the anterior part of the skull to the posterior side), and in such a situation, the target coordinates from the previous population may constrain the desired target location to the anterior, middle, or posterior side of the cingulate bundle (the exemplary trajectory would be here AC=anterior cingulate, MC=middle cingulate, PC=posterior cingulate), while the anatomical parcellation may further constrain the final target coordinates to stay within the boundaries of the cingulate bundle, which is known to curve along its path from inferior to superior and back, and from anterior to posterior and back. In a further exemplary embodiment, the semiology of the patient's seizures may be used by a clinician skilled in the art to derive information about the specific anatomical regions likely to be involved in epilepsy. This understanding can then be translated to inform trajectory planning by constraining the trajectory to the anatomical parcellation of interest. In another embodiment, the surgical trajectories can be created manually by one skilled in the art of stereotaxy by simply defining entry and target points of interest and optimizing these relative to the vessels and other possible trajectories. Alternatively, they can be derived by some combination of derivation from an average population-based trajectory combined with manual optimization.

[0084] In block 512, constraints on the anatomical parcellation may be achieved by adjusting the trajectory so that it intersects with the nearest voxel with an assigned label from the anatomical region of interest, and the distance is determined by calculating the Euclidean distance between the voxels of the probe trajectory and the labeled voxels in the anatomical parcellation of interest.

[0085] At block 514, the intersections of the trajectory with any critical structures, such as blood vessels, are evaluated using a loss function by determining such trajectory intersections with 2D and / or 3D surface and / or volume regions that have been marked or identified as belonging to critical structures, with a penalization of the trajectory for any such intersections. Additionally, the proximity of this trajectory to critical structures, such as blood vessels, is checked against user-determined constraints (e.g., >2 mm from the edge of the vessel, or ≧4 mm from the center of the trajectory of the adjacent probe).

[0086] Automated loss or optimization functions may also be incorporated into the trajectory planning such that, in one exemplary embodiment, total intracranial length is minimized while sampled gray matter is maximized to allow for maximum recording potential.

[0087] Starting from an initial trajectory estimated by prior information (defined by the average entry and target points across the population), method 500 begins a local search surrounding this average point until a trajectory is identified that is as close as possible to the average trajectory that satisfies all safety and optimization criteria. The search region is defined as a frustum with a diameter at each end defined in terms of the standard deviation of the distribution of targets, and a center at each end defined by the average entry and target coordinates from that group population.

[0088] In block 518, the final trajectory is superimposed onto the anatomical MRI dataset, generating a new planning dataset that can be exported in any manner for use with other software or hardware systems to visualize the trajectory planning in relation to the target anatomy.

[0089] When used in conjunction with the visualization techniques of method 400, validation of the implantation planning of multiple stereotactic depth probes along oblique trajectories is aided by simultaneous visualization of a cortical mesh model of the surface topology and deep anatomical structures revealed by structural magnetic resonance imaging sliced ​​along a plane collinear with the proposed trajectory. Slicing the brain surface at any given plane allows visualization of the deeply buried cortex in 3D and also allows the clinician to quickly confirm the surgical planning.

[0090] The integration of the planning operations of method 500 with the anatomical visualization and analysis techniques of methods 100-400 enables clinicians to identify critical extracranial and intracranial structures (including, but not limited to, structures such as the ventricles, white matter pathways, vascular, and eloquent areas) and avoid unwanted iatrogenic outcomes, including, but not limited to, bleeding and / or visual, language, cognitive, spatiotemporal, and / or sensorimotor deficits.

[0091] Incorporating methods 100-500 with white matter pathway analysis using deterministic or probabilistic tractography (derived from diffusion imaging) can further identify risks to pathways involved in critical functions such as motor, sensory, auditory, or visual processes. In a specific application, the approach can be applied to reducing visual deficits after laser interstitial thermotherapy of the hippocampus and / or amygdala for mesial temporal lobe epilepsy. 3D planning of optimal trajectories for targeting the medial temporal lobe combined with visualization of pathways identified by diffusion imaging can be used to expand the therapeutic window of the technique.

[0092] 6 shows a flow diagram for a method 600 for automated localization, naming, and visualization of previously implanted electrodes or penetrating brain probes combined with resolution of implanted structures in post-surgical imaging using a template matching search algorithm and planned trajectories. Although depicted sequentially for convenience, at least some of the operations shown can be performed in a different order and / or in parallel. In addition, some implementations may perform only some of the operations shown. The operations of method 600 may be performed by a computing system as disclosed herein.

[0093] At block 602, one or more imaging scans of the subject's brain are obtained. The imaging scans include a targeted anatomical MRI scan (e.g., T1-weighted MRI without contrast) and a post-implant CT imaging scan obtained after the electrodes are implanted, which is used to localize the location of implementation of each electrode.

[0094] At block 604, the imaging scans are converted from the original imaging storage format (e.g., DICOM) to a dataset according to method 100. T1 weighted MRI without contrast is converted to a dataset referred to as an anatomical MRI dataset, and CT imaging scans are converted to a dataset referred to as a CT electrode dataset.

[0095] In block 606, both data sets are co-registered and the CT electrode data set is registered to the anatomical MRI according to method 100.

[0096] At block 608, a third imaging scan is acquired. The third imaging scan is actually used by the surgeon as an anatomical imaging dataset (referred to herein as an implanted MRI dataset or imaging scan) to guide electrode implantation during surgery. In one exemplary embodiment, this scan may be a T1 weighted MRI with contrast that is used to both provide high resolution anatomical detail and reveal blood vessel locations during implant planning. The implanted MRI imaging scan is imported, co-registered, and aligned to the anatomical MRI according to method 100.

[0097] At block 610, a trajectory embedding data file (referred to herein as an embedding log) is obtained. The embedding log is generated when the embedding is performed, an example embodiment of which is a subject embedding file generated by a robotic sEEG embedding system (e.g., Zimmer ROSA® robot), another example is a stereotactic file generated by a navigation system (e.g., BrainLab® and Medtronic Stealth®). The embedding log includes information about the probe / trajectory name and / or the planned target point coordinates and / or the entry point coordinates and / or the probe trajectory vector, defined relative to the patient coordinate space of the embedded MRI (as described in method 500).

[0098] Method 500 may also include a security / manual verification feature, whereby the user is required to manually key in the probe name, the number of electrodes on each probe, and the number of electrodes to ignore from each probe (e.g., for electrodes in the anchor bolt, outside the brain, or not included in the recording, etc.). An initial list of names and putative electrodes for each probe may be obtained automatically by reading such information directly from the implant log or equivalent, if available, and provided to the user as a template.

[0099] In block 612, the planned target and entry point coordinates provided for each probe from the embedding log, along with the number of electrodes in each probe as verified by the user, are used to calculate an initial list of expected coordinates for each electrode. This calculation is performed using the axes of the trajectories calculated from the entry and target point coordinates, the distance between the entry and target point coordinates, and the spacing between the electrodes. This information is used to generate a "dummy" object at the estimated location of each electrode for each of the probe trajectories. An exemplary embodiment of such a "dummy" object may be a sphere centered around the coordinates with a given geometric shape that matches the electrode geometry (e.g., a cylinder). This new dataset (herein referred to as the planned trajectory dataset) has the same volume geometry and coordinate space as the embedded MRI dataset.

[0100] At block 614, the planned trajectory dataset is registered to the anatomical MRI dataset using the transformation matrix generated by registration of the embedded MRI dataset to the anatomical MRI dataset.

[0101] In block 616, using the CT electrodes, the planned trajectory dataset is co-registered to the subject's anatomical MRI dataset using such as by method 100, and a binarization operation is performed on the CT electrode dataset, where imaging voxels (e.g., potentially dimensions of a 1 mm x 1 mm x 1 mm cube containing intensity information from the image, serving as a 3D pixel equivalent) that are below an automatically determined threshold level are filled with zeros. A 3D clustering algorithm is applied to the remaining voxels to identify voxels with high intensity signals of electrode contacts on the CT scan (sometimes referred to as metal artifacts). An exemplary embodiment of the 3D clustering algorithm can be a standard clustering command provided by the underlying neuroimaging analysis software used. An iterative search is performed by adjusting the threshold until the resulting number of clusters resembles the expected number of electrodes. The coordinates of these clusters are iteratively compared to the coordinates of a spherical "dummy" electrode generated for the planned trajectory dataset. Using 3D space and centroid line / distance for the distance metric, clusters from the CT electrode dataset and trajectory paths and spherical object coordinates from the planning trajectory dataset are iteratively searched and optimized until all expected electrodes are identified and localized.

[0102] At block 618, a clustering algorithm combined with the trajectory path information and number of expected electrodes as provided by the input log and represented in the planned trajectory dataset is used to adjust the final locations of the electrode coordinates. Final coordinate locations (e.g., cluster locations) that best fit the imaging data and the physical constraints of the expected trajectory (locations along a specific line separated by a specific distance from adjacent electrodes on the same path) are thus derived.

[0103] At block 620, after all electrode coordinates have been identified, 2D and / or 3D models of these electrodes are rendered for visualization with appropriate electrode names and numbering schemes assigned. The electrodes are visualized using displayable objects (e.g., cylinders or disks) that reflect the size, spacing, and dimensions of each actual electrode. Having been co-registered to the anatomical MRI dataset, these electrodes can be visualized in relation to the 2D and / or 3D surface- and volume-based representations of the relevant extracranial and intracranial structures generated by methods 200 and / or 300.

[0104] Visible electrode objects may be individually manipulated (e.g., colored, annotated, numbered, made visible using a different shape or representation, turned on or off). They can be rendered transparent, semi-transparent, or invisible, in addition to any functional data (EEG) collected by the electrodes.

[0105] The methods and techniques described herein can be used in conjunction with other methods for surface-based representation of general neural correlates measured using recorded intracranial EEG or other general functional activation or implanted electrodes and / or penetrating probes and / or imaging modalities. The methods disclosed herein for surface-based representations can be applied not only to display representations for cortical structures, but also to display anatomical meshes generated for the hippocampus, amygdala, and / or other general subcortical or brain structures. Such methods are disclosed in U.S. Pat. No. 10,149,618.

[0106] Using the methods disclosed herein, the data representation of interest can be constrained to specific electrodes and exported to a new dataset by superimposing the intensity values ​​of the voxels of interest on the anatomical MRI dataset to generate a new surface or volume activation dataset. In surface-based datasets, activations are assigned to surface nodes using geodesic spread functions as described in a previous publication (Kadipasaoglu CM, Baboyan VG, Conner CR, Chen G, Saad ZS, Tandon N. Surface-based mixed effects multilevel analysis of grouped human electrocorticography. Neuroimage. 2014 Nov 1;101:215-24. doi: 10.1016 / j.neuroimage.2014.07.006. Epub 2014 Jul 12. PMID: 25019677). In volume-based datasets, activations are constrained to voxels located within the boundary between the pial surface membrane and the white matter surface membrane (cortical ribbon) underlying the electrode of interest (Christopher R. Conner, Gang Chen, Thomas A. Pieters, Nitin Tandon, Category Specific Spatial Dissociations of Parallel Processes Underlying Visual Naming, Cerebral Cortex, Volume 24, Issue 10, October 2014, Pages 2741-2750, https: / / doi.org / 10.1093 / cercor / bht130). These datasets can be exported to disk in any manner for use with other software or hardware systems to visualize these activations in relation to the anatomical structures of interest.

[0107] 7 shows a pictorial representation of co-registration of different neuroimaging modalities performed on a single subject in accordance with the present disclosure. In FIG. 7, sequence adaptive segmentation is applied to dataset 702 to produce labeling dataset 706, and sequence adaptive segmentation is applied to dataset 704 to produce labeling dataset 708. Labeling datasets 706 and 708 are co-registered, and a transformation matrix produced by the co-registration is applied to align labeling datasets 706 and 708, as shown in dataset 710.

[0108] 8 shows pictorial representations depicting the generation of 2D / 3D surface models of the hippocampus and thalamus in accordance with the present disclosure: Fig. 8A is an example illustration of an anatomical mesh model of the right hippocampus generated from segmentation of a 3D volumetric dataset of an anatomical T1 MRI of the subject shown in Fig. 8B.

[0109] 8B and 8C depict exemplary views of 2D / 3D surface mesh models of the left hippocampus and amygdala in a subject visualized simultaneously with the right cerebral hemisphere of the same subject following anatomical dissection-based parcellation. In FIG. 8C, the surface models are visualized as distinct structures. The left cortical hemisphere is rendered transparently independent of the right, allowing visualization of the left hippocampus and amygdala. In FIG. 8D, the parcellated right cortical hemisphere is rendered semi-transparently so that a solid-state rendering of the underlying right hippocampus and amygdala can be visualized.

[0110] 8E and 8F illustrate an exemplary surface-based mesh model of a subject's left thalamus and its nuclei, generated using a parcellation derived from a microscopic stereotactic anatomy. In Fig. 8E, the surface model is shown in isolation. In Fig. 8F, the same model is viewed in relation to three principle planes of the subject's original anatomical T1 MRI.

[0111] 9A-9D show exemplary steps for segmenting the human cerebral vasculature according to the present disclosure. FIG. 9A-9C depict the original imaging dataset (FIG. 9A, an exemplary embodiment of which here is T1 MRI with contrast) that is subsequently masked by the cerebrospinal fluid segmentation volume (FIG. 9B) and then processed using a multi-scale Hessian-based filtering algorithm to accurately segment the vascular voxels (FIG. 9C). FIG. 9D depicts the resulting vascular 3D surface model that is generated using the segmented vascular volume (right) as well as an overlay of the (contoured) surface cerebral vascular model across the three major planes of the original contrasted T1 MRI dataset, demonstrating the comprehensive segmentation of the subject's vasculature.

[0112] 10A-10W show pictorial representations using 2D cutting planes ("slicers") to intersect 2D and / or 3D surface models and volume models at arbitrary angles to optimize visualization of cortical and subcortical structures and / or functional representations. FIGs. 10A-10C depict the cutting planes as viewed on a 2D sagittal plan view of a subject's anatomical T1-weighted MRI overlaid with a CT skull shown in FIG. 10A. A 3D surface model of the subject's complete skull is shown in FIG. 10B, and the skull following application of the cutting plane is shown in FIG. 10C. The skull is rendered partially transparent to visualize the underlying compartmentalized cortical surface model to which the same cutting plane has been applied.

[0113] 10D-10F show rotated views of the same subject skull and underlying compartmentalized cortical surface model. Note that the cut planes may be rendered opaque and constrained within the boundaries of the 3D surface model to display the associated 2D MRI planar image (FIG. 10D). Alternatively, the cut planes may be rendered semi-transparent and / or the 2D MRI planar view may extend beyond the boundaries of the underlying surface model (FIG. 10E). Finally, the cut planes may be rendered invisible and the underlying planes of the surface model rendered transparent so that the deep anatomical structures may be visualized (FIG. 10F).

[0114] Figures 10G, 10H, and 10I show sagittal views of the 2D cut plane and the associated 3D parcellated cortical surface model at various rotated angles. In Figure 10I, the edges of the cortical model are extended slightly beyond the boundaries of the cut plane, where gyral and sulcal boundaries are selectively highlighted, providing a more precise visualization of the underlying anatomical features.

[0115] Figures 10J-10L show three views of the same 2D sagittal cut plane and 3D cortical surface model shown in Figures 10G-10I, where the edges of the model are set back from the cut plane (Figure 10J), coplanar with the plane (Figure 10K), and extended slightly beyond the plane (Figure 10L).

[0116] 10M, 10N, and 10P show three views of a 2D coronal section and a 3D skin and parcellated cortical surface model. The full skin model is intersected by the section plane, and the remaining components of the skin and parcellated cortical model are visualized (FIG. 10M). The parcellated cortical model is shown in isolation in FIG. 10N with the edges slightly extended beyond the plane, and then again in the third view, with the edges constrained only to the gray and white matter boundaries, such that extension of the gray and white matter boundary edges beyond the section plane would isolate the intervening cortical ribbons. In FIG. 10P, an enlarged and slightly rotated view of the third image from FIG. 10N is depicted, with a white arrow indicating an exemplary region of the aforementioned cortical ribbon contained between the gray matter edge and the white matter boundary (FIG. 10P).

[0117] 10Q-10W show the cortex with simultaneous representation of surface and deep anatomical structures in addition to cortical activity, represented as a color scale through slices along planes collinear with the deep trajectory. Visualization of brain structural data (including one or more of MRI, CT, PET, fMRI, DTI) and / or brain activity data (including one or more of EEG or MEG or brain stimulation) associated with various anatomical mesh model cut planes may be selectively depicted to optimize visualization of functional activation in neocortical regions (FIGS. 10Q, 10R, 10S, 10T, and 10U) and / or hippocampal and amygdala regions (FIGS. 10V and 10W) ​​and / or subcortical or other brain regions. Then the relevant surface is visualized (FIGS. 10T-10V), the cut planes and associated viewpoints are depicted by lines 1002 and arrows 1004, respectively.

[0118] 11A-11R show pictorial representations of population-derived anatomical targeting for electrode or penetrating probe implantation that incorporate previous derived using probability distributions and / or anatomical anatomy-based parcellation and segmentation from previously implanted populations. FIGs. 11A-11D depict grouped representations of trajectories into the brain from 130 patients implanted with 2,600 electrodes to explore epilepsy, which are co-registered, aligned to a common brain space, and color-coded by entry and target points (FIG. 11A). Electrodes may further be color-coded based on standard domain terminology applied to them, showing similar entry and target points for specific cortical or subcortical lesions across individuals, an exemplary embodiment of which is depicted for the right amygdala and hippocampus within a single subject (FIG. 11B). Using information of previous trajectories from this population, new trajectories can be derived for any specific brain region for new individuals (not the previous 130). An exemplary illustration of the analysis is provided for the right anterior hippocampus (RAH) of a single subject, where new trajectories are depicted as elongated cylinders while previous trajectories of the population are depicted either using each individual probe (FIG. 11C, shorter cylinders) or by visualizing the mean and variance of this population (FIG. 11D), which in this exemplary illustration is depicted with a truncated cone using the mean and 1.5 times the standard deviation of the entry and exit point coordinates.

[0119] FIG. 11E depicts the integration of oblique cut planes, detailed cerebrovascular anatomical mesh models and compartmentalized anatomical mesh models, and a trajectory planning algorithm to generate automated embedded trajectory planning for 12 brain probes (e.g., sEEG probes). The automated algorithm ensures compliance with multiple safety constraints, an example embodiment of which may be minimum distance from adjacent vessels along the trajectory as well as from adjacent probes. Panel 11E-2 depicts an example diagram of manual trajectory optimization in which two cylinders are visualized, representing the original (i.e., automatically derived) and manually adjusted trajectories for a right anterior hippocampal (RAH) probe.

[0120] 11F depicts a similar population-level derived planning for laser interstitial thermal therapy of the amygdala and / or hippocampus for mesial temporal lobe epilepsy. Visualized is the optimal new trajectory for a new subject along with the population-derived predicted ablation volume expected for the given trajectory.

[0121] 11G and 11H depict exemplary views of new trajectories derived from population data of previous embedded trajectories across multiple regions within the left cingulate gyrus, including the left rostral cingulate (LRC), anterior cingulate (LAC), medial cingulate (LMC), and posterior cingulate (LPC) regions. These views include a lateral view highlighting the entry point (FIG. 11G), and a medial view depicting the proposed trajectories labeled by the aforementioned target brain regions, where the left hemisphere is rendered sufficiently transparent so that the right hemisphere cingulate is visible (and can be used as a visual reference for the contralateral target brain region), and the proposed trajectories are depicted with their associated frustum (derived from the population) rendered as a semi-transparent overlay. Figures 11J-11P depict exemplary views of another subset of exemplary proposed trajectories that may be desired for a subject undergoing stereotactic EEG evaluation for refractory epilepsy using both superior (Figures 11J-11L) and lateral (11M-11P) views of the 3D cortical surface model, with the left hemisphere rendered opaque (11J and 11M) or fully transparent (11K-11L and 11N-11P). The center figures depict the population data of previously implanted trajectories used for the generation of their individual new trajectories, using cylinders colored by the target brain region to visualize each of the previously implanted probes overlaid with their individual new trajectories (Figures 11K and 11N). The mean and 1.5 times the standard deviation from the distribution of coordinates of the population of previously implanted trajectories are used to generate the aforementioned truncated cone, depicted as a semi-transparent overlay with their individual trajectories in the right-most figures (11L and 11P). The bottom row depicts an example schematic of all trajectories from the previous embedding population data visualized with their individual frustums on a 3D cortical surface model of a single example subject, rendered both opaque and fully transparent (11Q and 11R, respectively).

[0122] 12A-12E depict a pictorial representation of automated electrode localization and targeting that incorporates an implant trajectory log from a robotic sEEG implant system to constrain and inform the electrode search algorithm, providing probe names and associated electrode numbers. An initial clustering algorithm applied to the post-implant CT electrode dataset is depicted in 12A, demonstrating how an expanding intensity threshold to zero-fill voxels with intensity below the threshold can be used to identify clusters of high intensity voxels that represent artifacts from electrodes in contact with the CT scanning device. The trajectory implant log from the robotic implant system is also used to further inform the electrode search by constraining the search space of the algorithm to more efficiently separate signals associated with electrode artifacts from noise, and also ensure that the final electrode coordinates are spaced and aligned in a manner consistent with the actual implant as defined by the spherical dummy electrodes (FIG. 12C).

[0123] FIG. 12D depicts a cross-section applied to the subject's skull model at an oblique angle to visualize the electrodes implanted in relation to the right hippocampal surface model and the amygdala surface model of the subject. In this exemplary embodiment, each electrode is rendered as a cylinder with electrode spacing and dimensions as indicated by the implantation trajectory log and the physical dimensions of the actual electrode. The probes and their individual electrodes are color-coded by probe name. A more magnified view of the right hippocampus and amygdala of the same subject is visualized as a displayable object and depicted in FIG. 12E with a subset of the implanted probes color-coded by those probe names annotated in white. This time, the trajectories from the trajectory implantation log are also depicted here as translucent cylinders with smaller dimensions and spacing in order to differentiate them from the true electrode locations. As can be seen by the highlighted electrodes with crosshairs in the upper layer, the final electrode coordinates do not always exactly correspond to the planned trajectory because the probe can be deflected during implantation. The highlighted electrode coordinates correspond to the coordinates of the crosshairs in adjacent 2D coronal and sagittal plane images of the pre-implantation MRI of the same subject overlaid by post-implantation CT.

[0124] FIG. 13 shows a block diagram of a computing system 1300 suitable for implementing the methods disclosed herein (e.g., methods 100, 200, 300, 400, 500, and / or 600). Computing system 1300 includes one or more computing nodes 1302 communicatively coupled (e.g., via network 1318) and a secondary storage device 1316. One or more of the computing nodes 1302 and the associated secondary storage device 1316 can be applied to perform the operations of the methods described herein.

[0125] Each computing node 1302 includes one or more processors 1304 coupled to memory 1306, a network interface 1312, and I / O devices 1314. In various embodiments, the computing node 1302 may be a uniprocessor system including one processor 1304, or a multiprocessor including several (e.g., two, four, eight, or another suitable number) processors 1304. The processor 1304 may be any suitable processor capable of executing instructions. For example, in various embodiments, the processor 1304 may be a general purpose or embedded microprocessor, a graphics processing unit (GPU), or a digital signal processor (DSP) implementing any of a variety of instruction set architectures (ISAs). In a multiprocessor system, each of the processors 1304 may generally, but not necessarily, implement the same ISA.

[0126] The memory 1306 may include a non-transitory computer-readable storage medium configured to store program instructions 1308 and / or data 1310 accessible by the processor 1304. The memory 1306 may be implemented using any suitable memory technology, such as static random access memory (SRAM), synchronous dynamic RAM (SDRAM), non-volatile / flash type memory, or any other type of memory. The program instructions 1308 and data 1310 implementing the functionality disclosed herein are stored within the memory 1306. For example, the instructions 1308 may include instructions that, when executed by the processor 1304, implement one or more of the methods disclosed herein.

[0127] The secondary storage 1316 may include volatile and / or non-volatile storage and devices for storing information such as program instructions and / or data as described herein to implement the methods described herein. The secondary storage 1316 may include various types of computer-readable media accessible by the computing nodes 1302 via the network interface 1312. The computer-readable media may include storage or memory media such as solid-state storage, magnetic media, or optical media, e.g., disks or CD / DVD-ROMs, or other storage technologies.

[0128] Network interface 1312 includes circuitry configured to allow data to be exchanged between computing nodes 1302 and / or other devices coupled to network 1318. For example, network interface 1312 may be configured to allow data to be exchanged between a first instance of computing system 1300 and a second instance of computing system 1300. Network interface 1312 may support communications over wired or wireless data networks.

[0129] The I / O devices 1314 enable the computing nodes 1302 to communicate with various input / output devices, such as one or more display terminals, keyboards, keypads, touch pads, scanning devices, voice or optical recognition devices, or any other device suitable for entry or retrieval by one or more computing nodes 1302. Multiple input / output devices may be present in the computing system 1300.

[0130] The computing system 1300 is illustrative only and is not intended to limit the scope of the embodiments. In particular, the computing system 1300 may include any combination of hardware or software capable of performing the functions disclosed herein. The computing node 1302 may also be connected to other devices, not illustrated in some embodiments. In addition, the functionality provided by the illustrated components may in some embodiments be combined in fewer components or distributed among additional components. Similarly, in some embodiments, the functionality of some of the illustrated components may not be provided and / or other additional functionality may be available.

[0131] The above discussion is intended to illustrate the principles and various embodiments of the present invention. Numerous variations and modifications will become apparent to those skilled in the art once the above disclosure is fully appreciated. It is intended that the following claims be interpreted to embrace all such variations and modifications.

Claims

1. 1. A method comprising: obtaining a first imaging scan and a second imaging scan of a single subject brain; converting the first imaging scan into a first data set and converting the second imaging scan into a second data set; applying a sequence-adaptive multi-modal segmentation algorithm to the first data set and the second data set, the sequence-adaptive multi-modal segmentation algorithm performing an automatic intensity-based tissue classification to generate a first label data set and a second label data set; generating a transformation matrix based on the first and second label data sets by automatically co-registering the first and second label data sets with respect to each other; aligning the first data set and the second data set by applying the transformation matrix; and The method includes:

2. 10. The method of claim 1, wherein the first imaging scan and the second imaging scan are performed using one or more of magnetic resonance imaging (MRI), computed tomography (CT), magnetoencephalography (MEG), or positron emission tomography (PET).

3. The method of claim 1 , wherein the sequence-adaptive multi-modal segmentation algorithm assigns a numerical indicator value to each voxel of the first data set or the second data set.

4. The method comprises: Extracting voxels having labels corresponding to a subcortical region of interest from the first data set after applying the transformation matrix; forming a third data set containing the voxels extracted from the first data set after applying the transformation matrix; Transforming the third data set into a first subcortical surface mesh model; and calculating curvature and sulcus features of the first subcortical surface mesh model; using the curvature and sulcus features to match the first subcortical surface mesh model to a subcortical anatomy of the subcortical region of interest; overlaying the first subcortical surface mesh model aligned to the subcortical anatomy of the subcortical region of interest onto a second subcortical surface mesh model, the second subcortical surface mesh model having a standardized number of nodes that allows a one-to-one correspondence between node identification and anatomy location; assigning coordinates of nodes of the first subcortical surface mesh model to the second subcortical surface mesh model such that the second subcortical surface mesh model exhibits a topology of the first subcortical surface mesh model; The method of claim 1 further comprising:

5. the first imaging scan is a contrast-weighted MRI scan and the first data set is a contrast-weighted data set; The method comprises: selecting voxels of the first data set that are identified as belonging to a cerebrospinal fluid region based on the labeling data set; applying a multi-scale vascular filtering algorithm to identify voxels of the first data set that represent blood vessels and assigning a vascular enhancement weight to each voxel; Integrating the vascular enhancement weights into the first data set; converting the first data set into a surface anatomical mesh model after aligning the first data set and the second data set; The method of claim 1 further comprising:

6. the first imaging scan is a contrast-weighted MRI scan and the second imaging scan is an anatomical MRI scan; The method comprises: defining expected target and entry point coordinates for the probe based on target and entry point coordinates of previously implanted probes or by user defined target and entry points; defining a trajectory for the probe based on an average target coordinate and an average entry point coordinate; adjusting the trajectory to intersect with a nearest voxel that has been assigned a label in the anatomical region of interest; checking the proximity of said trajectory to a critical structure based on user-defined constraints and / or user-defined modifications of said trajectory to satisfy said user-defined constraints; forming a planning data set by superimposing the trajectory onto the second data set after applying the transformation matrix; The method of claim 1 further comprising:

7. the first imaging scan is an anatomical MRI scan and the second imaging scan is a post-implant CT imaging scan, the first data set is an anatomical MRI data set and the second data set is a post-implant CT imaging data set; The method comprises: obtaining a third imaging scan for use in guiding electrode implantation during surgery; converting the third imaging scan into a third data set; aligning a third data set to the first data set after applying the transformation matrix; obtaining a trajectory embedding data file generated during said electrode embedding; generating a planning trajectory data set based on the trajectory embedding data file, the planning trajectory data set including dummy objects to be placed at the electrode geometry locations; Aligning the planned trajectory dataset to the post-implant CT imaging dataset; automatically identifying electrodes in the post-embedding CT imaging data set based on dummy objects in the trajectory-embedding data file and labeling the electrodes in the post-embedding CT imaging data set; The method of claim 1 further comprising:

8. A non-transitory computer readable medium, the non-transitory computer readable medium comprising: obtaining a first imaging scan and a second imaging scan of a single subject brain; converting the first imaging scan into a first data set and converting the second imaging scan into a second data set; applying a sequence-adaptive multi-modal segmentation algorithm to the first data set and the second data set, the sequence-adaptive multi-modal segmentation algorithm performing an automatic intensity-based tissue classification to generate a first label data set and a second label data set; generating a transformation matrix based on the first and second label data sets by automatically co-registering the first and second label data sets with respect to each other; aligning the first data set and the second data set by applying the transformation matrix; and A non-transitory computer-readable medium encoded with instructions executable by one or more processors to perform the steps of:

9. 9. The non-transitory computer readable medium of claim 8, wherein the first imaging scan and the second imaging scan are performed using one or more of magnetic resonance imaging (MRI), computed tomography (CT), magnetoencephalography (MEG), or positron emission tomography (PET).

10. 10. The non-transitory computer readable medium of claim 8, wherein the sequence adaptive multi-modal segmentation algorithm assigns a numerical indicator value to each voxel of the first data set or the second data set.

11. The instruction: Extracting voxels having labels corresponding to a subcortical region of interest from the first data set after applying the transformation matrix; forming a third data set containing the voxels extracted from the first data set after applying the transformation matrix; Transforming the third data set into a first subcortical surface mesh model; and calculating curvature and sulcus features of the first subcortical surface mesh model; using the curvature and sulcus features to match the first subcortical surface mesh model to a subcortical anatomy of the subcortical region of interest; overlaying the first subcortical surface mesh model aligned to the subcortical anatomy of the subcortical region of interest onto a second subcortical surface mesh model, the second subcortical surface mesh model having a standardized number of nodes that allows a one-to-one correspondence between node identification and anatomy location; assigning coordinates of nodes of the first subcortical surface mesh model to the second subcortical surface mesh model such that the second subcortical surface mesh model exhibits a topology of the first subcortical surface mesh model; 10. The non-transitory computer-readable medium of claim 8, executable by the one or more processors to:

12. the first imaging scan is a contrast-weighted MRI scan and the first data set is a contrast-weighted data set; The instruction: selecting voxels of the first data set that are identified as belonging to a cerebrospinal fluid region based on the labeling data set; applying a multi-scale vascular filtering algorithm to identify voxels of the first data set that represent blood vessels and assigning a vascular enhancement weight to each voxel; Integrating the vascular enhancement weights into the first data set; converting the first data set into a surface anatomical mesh model after aligning the first data set and the second data set; 10. The non-transitory computer-readable medium of claim 8, executable by the one or more processors to:

13. the first imaging scan is a contrast-weighted MRI scan and the second imaging scan is an anatomical MRI scan; The instruction: defining expected target and entry point coordinates for the probe based on target and entry point coordinates of previously implanted probes or by user defined target and entry points; defining a trajectory for the probe based on an average target coordinate and an average entry point coordinate; adjusting the trajectory to intersect with a nearest voxel that has been assigned a label in the anatomical region of interest; checking the proximity of said trajectory to a critical structure based on user-defined constraints and / or user-defined modifications of said trajectory to satisfy said user-defined constraints; forming a planning data set by superimposing the trajectory onto the second data set after applying the transformation matrix; 10. The non-transitory computer-readable medium of claim 8, executable by the one or more processors to:

14. the first imaging scan is an anatomical MRI scan and the second imaging scan is a post-implant CT imaging scan, the first data set is an anatomical MRI data set and the second data set is a post-implant CT imaging data set; The instruction: obtaining a third imaging scan for use in guiding electrode implantation during surgery; converting the third imaging scan into a third data set; aligning a third data set to the first data set after applying the transformation matrix; obtaining a trajectory embedding data file generated during said electrode embedding; generating a planning trajectory data set based on the trajectory embedding data file, the planning trajectory data set including dummy objects to be placed at the electrode geometry locations; Aligning the planned trajectory dataset to the post-implant CT imaging dataset; automatically identifying electrodes in the post-embedding CT imaging data set based on dummy objects in the trajectory-embedding data file and labeling the electrodes in the post-embedding CT imaging data set; 10. The non-transitory computer-readable medium of claim 8, executable by the one or more processors to:

15. 1. A system comprising: one or more processors; a memory coupled to the one or more processors; Equipped with The memory stores instructions; The instruction: obtaining a first imaging scan and a second imaging scan of a subject brain; converting the first imaging scan into a first data set and converting the second imaging scan into a second data set; applying a sequence-adaptive multi-modal segmentation algorithm to the first data set and the second data set, the sequence-adaptive multi-modal segmentation algorithm performing an automatic intensity-based tissue classification to generate a first label data set and a second label data set; generating a transformation matrix based on the first and second label data sets by automatically co-registering the first and second label data sets with respect to each other; aligning the first data set and the second data set by applying the transformation matrix; and and configuring the one or more processors to:

16. The first imaging scan and the second imaging scan may be performed using magnetic resonance imaging (MRI), computer 16. The system of claim 15, wherein the method is performed using one or more of computed tomography (CT), magnetoencephalography (MEG), or positron emission tomography (PET).

17. The system of claim 15 , wherein the sequence-adaptive multi-modal segmentation algorithm assigns a numerical indicator value to each voxel of the first data set or the second data set.

18. The instruction: Extracting voxels having labels corresponding to a subcortical region of interest from the first data set after applying the transformation matrix; forming a third data set containing the voxels extracted from the first data set after applying the transformation matrix; Transforming the third data set into a first subcortical surface mesh model; and calculating curvature and sulcus features of the first subcortical surface mesh model; using the curvature and sulcus features to match the first subcortical surface mesh model to a subcortical anatomy of the subcortical region of interest; overlaying the first subcortical surface mesh model aligned to the subcortical anatomy of the subcortical region of interest onto a second subcortical surface mesh model, the second subcortical surface mesh model having a standardized number of nodes that allows a one-to-one correspondence between node identification and anatomy location; assigning coordinates of nodes of the first subcortical surface mesh model to the second subcortical surface mesh model such that the second subcortical surface mesh model exhibits a topology of the first subcortical surface mesh model; 20. The system of claim 15, further comprising: configuring the one or more processors to:

19. the first imaging scan is a contrast-weighted MRI scan and the first data set is a contrast-weighted data set; The instruction: selecting voxels of the first data set that are identified as belonging to a cerebrospinal fluid region based on the labeling data set; applying a multi-scale vascular filtering algorithm to identify voxels of the first data set that represent blood vessels and assigning a vascular enhancement weight to each voxel; Integrating the vascular enhancement weights into the first data set; converting the first data set into a surface anatomical mesh model after aligning the first data set and the second data set; 20. The system of claim 15, further comprising: configuring the one or more processors to:

20. the first imaging scan is a contrast-weighted MRI scan and the second imaging scan is an anatomical MRI scan; The instruction: defining expected target and entry point coordinates for the probe based on target and entry point coordinates of previously implanted probes or by user defined target and entry points; defining a trajectory for the probe based on an average target coordinate and an average entry point coordinate; adjusting the trajectory to intersect with a nearest voxel that has been assigned a label in the anatomical region of interest; checking the proximity of said trajectory to a critical structure based on user-defined constraints and / or user-defined modifications of said trajectory to satisfy said user-defined constraints; forming a planning data set by superimposing the trajectory onto the second data set after applying the transformation matrix; 20. The system of claim 15, further comprising: configuring the one or more processors to:

21. the first imaging scan is an anatomical MRI scan and the second imaging scan is a post-implant CT imaging scan, the first data set is an anatomical MRI data set and the second data set is a post-implant CT imaging data set; The instruction: obtaining a third imaging scan for use in guiding electrode implantation during surgery; converting the third imaging scan into a third data set; aligning a third data set to the first data set after applying the transformation matrix; obtaining a trajectory embedding data file generated during said electrode embedding; generating a planning trajectory data set based on the trajectory embedding data file, the planning trajectory data set including dummy objects to be placed at the electrode geometry locations; Aligning the planned trajectory dataset to the post-implant CT imaging dataset; identifying electrodes in the post-embedding CT imaging data set based on dummy objects in the trajectory-embedding data file; 20. The system of claim 15, further comprising: configuring the one or more processors to:

Images