On presentation of cerebral arteries via cortical openings.

The presentation of cortical arteries is challenging, as most of their course is hidden in the depth of the sulci. Despite that, demonstrating the arteries on the cortical surface is a standard way of their presentation. To keep advantages of surface presentation while lessening its limitation, we propose a novel context-related method of cerebrovasculature presentation by cortical openings consisting in the removal of a selected region from the cortical mantle and exposing underlying structures. We also introduce a reverse than standard vessel-to-context mapping from a gyrus/lobule to vessels supplying it.The method has the following steps: define a cortical opening, develop a tool to perform them, create cortical openings for gyri and lobules with underlying white matter and intracranial arteries, generate labeled and parcellated images for the created openings, and integrate the cortical opening images with the NOWinBRAIN public repository of 8600 3D neuroimages.The cortical openings are created for 64 gyri and six lobules for the left and right cerebral hemispheres resulting in 210 images arranged in triples as spatially corresponding non-parcellated and unlabeled, parcellated by color and unlabeled, and parcellated and labeled images.The cortical opening approach, generally, increases vessel exposure in a higher number of depicted branches, revealing arteries otherwise hidden deep in sulci, a more complete vessel course, and a lower number of required views.The gyrus/lobule-to-arteries mapping facilitates exploration of a studied region, encapsulates all local arteries, and reduces vascular complexity by decomposing the entire vascular system into smaller sets involved in the studied region.

Taxonomy of Acute Stroke: Imaging, Processing, and Treatment.

Stroke management employs a variety of diagnostic imaging modalities, image processing and analysis methods, and treatment procedures. This work categorizes methods for stroke imaging, image processing and analysis, and treatment, and provides their taxonomies illustrated by a state-of-the-art review. Imaging plays a critical role in stroke management, and the most frequently employed modalities are computed tomography (CT) and magnetic resonance (MR). CT includes unenhanced non-contrast CT as the first-line diagnosis, CT angiography, and CT perfusion. MR is the most complete method to examine stroke patients. MR angiography is useful to evaluate the severity of artery stenosis, vascular occlusion, and collateral flow. Diffusion-weighted imaging is the gold standard for evaluating ischemia. MR perfusion-weighted imaging assesses the penumbra. The stroke image processing methods are divided into non-atlas/template-based and atlas/template-based. The non-atlas/template-based methods are subdivided into intensity and contrast transformations, local segmentation-related, anatomy-guided, global density-guided, and artificial intelligence/deep learning-based. The atlas/template-based methods are subdivided into intensity templates and atlases with three atlas types: anatomy atlases, vascular atlases, and lesion-derived atlases. The treatment procedures for arterial and venous strokes include intravenous and intraarterial thrombolysis and mechanical thrombectomy. This work captures the state-of-the-art in stroke management summarized in the form of comprehensive and straightforward taxonomy diagrams. All three introduced taxonomies in diagnostic imaging, image processing and analysis, and treatment are widely illustrated and compared against other state-of-the-art classifications.

On presentation of the human cerebral sulci from inside of the cerebrum.

The human cerebral cortex is highly convoluted forming patterns of gyri separated by sulci. The cerebral sulci and gyri are fundamental in cortical anatomy as well as neuroimage processing and analysis. Narrow and deep cerebral sulci are not fully discernible either on the cortical or white matter surface. To cope with this limitation, I propose a new sulci presentation method that employs the inner cortical surface for sulci examination from the inside of the cerebrum. The method has four steps, construct the cortical surface, segment and label the sulci, dissect (open) the cortical surface, and explore the fully exposed sulci from the inside. The inside sulcal maps are created for the left and right lateral, left and right medial, and basal hemispheric surfaces with the sulci parcellated by color and labeled. These three-dimensional sulcal maps presented here are probably the first of this kind created. The proposed method demonstrates the full course and depths of sulci, including narrow, deep, and/or convoluted sulci, which has an educational value and facilitates their quantification. In particular, it provides a straightforward identification of sulcal pits which are valuable markers in studying neurologic disorders. It enhances the visibility of sulci variations by exposing branches, segments, and inter-sulcal continuity. The inside view also clearly demonstrates the sulcal wall skewness along with its variability and enables its assessment. Lastly, this method exposes the sulcal 3-hinges introduced here.

Bridging neuroradiology and neuroanatomy: NOWinBRAIN-a repository with sequences of correlated and labeled planar-surface neuroimages.

Purpose: Integrating neuroradiology with neuroanatomy is essential in medical neuroeducation and neuroimage interpretation. To bridge 2D neuroradiology and 3D neuroanatomy, spatially correlated pairs of labeled images were employed, planar radiologic, and planar-surface combined. Research design: The method employs a 3D fully parcellated and labeled brain atlas extended to the head and neck with about 3000 3D components to create planar radiologic and surface neuroanatomic images. The atlas handles reformatted radiologic images as 3D objects using texture mapping which provides consistency with polygonal 3D neuroanatomic structures. This ensures a precise spatial correspondence of dual 2D-2D/3D images for any composed 3D scene reformatted in arbitrary orientation. The sequences of labeled dual images were created spanning a structure/system of interest in multiple orientations. To facilitate image searching, the image name encodes its content, orientation, and stereotactic location. Results: Labeled dual 2D-2D/3D neuroimage sequences in multiple orientations were created for the cerebrum, brainstem, deep nuclei, cerebral ventricles, intracranial arteries, dural sinuses, extracranial arteries, extracranial veins, trigeminal nerve, head muscles, glands, bones of cranium, and visual system. They all were hierarchically organized as a planar-surface gallery with 42 folders and 502 neuroimages. This gallery was integrated with a public NOWinBRAIN repository at www.nowinbrain.org with more than 7700 neuroimages. Conclusions: Owing to its advantages, simplicity, and free availability, this resource is useful for medical students, residents, educators, and clinicians to study the brain, head, and neck as well as to prepare presentations and teaching materials. The approach might potentially enhance image interpretation by integrating brain atlases with radiologic workstations.

On the definition, construction, and presentation of the human cerebral sulci: A morphology-based approach.

Although the term sulcus is known for almost four centuries, its formal, precise, consistent, constructive, and quantitative definition is practically lacking. As the cerebral sulci (and gyri) are vital in cortical anatomy which, in turn, is central in neuroeducation and neuroimage processing, a new sulcus definition is needed. The contribution of this work is threefold, namely to (1) propose a new, morphology-based definition of the term sulcus (and consequently that of gyrus), (2) formulate a constructive method for sulcus calculation, and (3) provide a novel way for the presentation of sulci. The sulcus is defined here as a volumetric region on the cortical mantle between adjacent gyri separated from them at the levels of their gyral white matter crest lines. Consequently, the sulcal inner surface is demarcated by the crest lines of the gyral white matter of its adjacent gyri. Correspondingly, the gyrus is defined as a volumetric region on the cortical mantle separated from its adjacent sulci at the level of its gyral white matter crest line. This volumetric sulcus definition is conceptually simple, anatomy-based, educationally friendly, quantitative, and constructive. Considering the sulcus as a volumetric object is a major differentiation from other works. Based on the introduced sulcus definition, a method for volumetric sulcus construction is proposed in two, conceptually straightforward, steps, namely, sulcal intersection formation followed by its propagation which steps are to be repeated for every sulcal segment. These sulcal and gyral constructions can be automated by applying existing methods and public tools. As a volumetric sulcus forms an imprint into the white matter, this enables prominent sulcus presentation. Since this type of presentation is novel yet unfamiliar to the reader, also a dual surface presentation was proposed here by employing the spatially co-registered white matter and cortical surfaces. The results were presented as dual surface labeled sulci on eight standard orthogonal views, anterior, left lateral, posterior, right lateral, superior, inferior, medial left, and medial right by using a 3D brain atlas. Moreover, additional 108 labeled images were created with sulcus-oriented views for 27 individual left and right sulci forming 54 dual white matter-cortical surface images strengthening in this way the educational value of the proposed approach. These images were included for public use in the NOWinBRAIN neuroimage repository with over 7700 3D images available at www.nowinbrain.org. The results demonstrated the superiority of white matter surface sulci presentation over the standard cortical surface and cross-sectional presentations in terms of sulcal course, continuity, size, shape, width, depth, side branches, and pattern. To my best knowledge, this is the first work ever presenting the labeling of sulci on all cerebral white matter surfaces as well as on dual white matter-cortical surfaces. Additionally to neuroeducation, three other applications of the proposed approach were discussed, sulcal reference maps, sulcus quantification in terms of new parameters introduced here (sulcal volume, wall skewness, and the number of white matter basins), and an atlas-assisted tool for exploration and studying of cerebral sulci and gyri .

NOWinBRAIN: a Large, Systematic, and Extendable Repository of 3D Reconstructed Images of a Living Human Brain Cum Head and Neck.

Despite the tremendous development of various brain-related resources, a large, systematic, comprehensive, extendable, and beautiful repository of 3D reconstructed images of a living human brain expanded to the head and neck is not yet available. I have created such a novel repository and populated it with images derived from a 3D atlas constructed from 3/7 Tesla MRI and high-resolution CT scans. This web-based repository contains 6 galleries hierarchically organized in 444 albums and sub-albums with 5,156 images. Its original features include a systematic design in terms of multiple standard views, modes of presentation, and spatially co-registered image sequences; multi-tissue class galleries constructed from 26 primary tissue classes and 199 sub-classes; and a unique image naming syntax enabling image searching based solely on the image name. Anatomic structures are displayed in 6 standard views (anterior, left, posterior, right, superior, inferior), all views having the same brain size, and optionally with additional arbitrary views. In each view, the images are shown as sequences in three standard modes of presentation, non-parcellated unlabeled, parcellated unlabeled, and parcellated labeled. There are two types of spatially co-registered image sequences (imitating image layers and enabling animation creation), the appearance image sequence (for standard views) and the context image sequence (with a growing number of tissue classes). Color-coded neuroanatomic content makes the brain beautiful and facilitates its learning and understanding. This unique repository is freely available and easily accessible online at www.nowinbrain.org for a wide spectrum of users in medicine and beyond. Its future extensions are in progress.

Towards an Architecture of a Multi-purpose, User-Extendable Reference Human Brain Atlas.

Human brain atlas development is predominantly research-oriented and the use of atlases in clinical practice is limited. Here I introduce a new definition of a reference human brain atlas that serves education, research and clinical applications, and is extendable by its user. Subsequently, an architecture of a multi-purpose, user-extendable reference human brain atlas is proposed and its implementation discussed. The human brain atlas is defined as a vehicle to gather, present, use, share, and discover knowledge about the human brain with highly organized content, tools enabling a wide range of its applications, massive and heterogeneous knowledge database, and means for content and knowledge growing by its users. The proposed architecture determines major components of the atlas, their mutual relationships, and functional roles. It contains four functional units, core cerebral models, knowledge database, research and clinical data input and conversion, and toolkit (supporting processing, content extension, atlas individualization, navigation, exploration, and display), all united by a user interface. Each unit is described in terms of its function, component modules and sub-modules, data handling, and implementation aspects. This novel architecture supports brain knowledge gathering, presentation, use, sharing, and discovery and is broadly applicable and useful in student- and educator-oriented neuroeducation for knowledge presentation and communication, research for knowledge acquisition, aggregation and discovery, and clinical applications in decision making support for prevention, diagnosis, treatment, monitoring, and prediction. It establishes a backbone for designing and developing new, multi-purpose and user-extendable brain atlas platforms, serving as a potential standard across labs, hospitals, and medical schools.

Evolution of Human Brain Atlases in Terms of Content, Applications, Functionality, and Availability.

Human brain atlases have been evolving tremendously, propelled recently by brain big projects, and driven by sophisticated imaging techniques, advanced brain mapping methods, vast data, analytical strategies, and powerful computing. We overview here this evolution in four categories: content, applications, functionality, and availability, in contrast to other works limited mostly to content. Four atlas generations are distinguished: early cortical maps, print stereotactic atlases, early digital atlases, and advanced brain atlas platforms, and 5 avenues in electronic atlases spanning the last two generations. Content-wise, new electronic atlases are categorized into eight groups considering their scope, parcellation, modality, plurality, scale, ethnicity, abnormality, and a mixture of them. Atlas content developments in these groups are heading in 23 various directions. Application-wise, we overview atlases in neuroeducation, research, and clinics, including stereotactic and functional neurosurgery, neuroradiology, neurology, and stroke. Functionality-wise, tools and functionalities are addressed for atlas creation, navigation, individualization, enabling operations, and application-specific. Availability is discussed in media and platforms, ranging from mobile solutions to leading-edge supercomputers, with three accessibility levels. The major application-wise shift has been from research to clinical practice, particularly in stereotactic and functional neurosurgery, although clinical applications are still lagging behind the atlas content progress. Atlas functionality also has been relatively neglected until recently, as the management of brain data explosion requires powerful tools. We suggest that the future human brain atlas-related research and development activities shall be founded on and benefit from a standard framework containing the core virtual brain model cum the brain atlas platform general architecture.

Human Brain Atlases in Stroke Management.

Stroke is a leading cause of death and a major cause of permanent disability. Its management is demanding because of variety of protocols, imaging modalities, pulse sequences, hemodynamic maps, criteria for treatment, and time constraints to promptly evaluate and treat. To cope with some of these issues, we propose novel, patented solutions in stroke management by employing multiple brain atlases for diagnosis, treatment, and prediction. Numerous and diverse CT and MRI scans are used: ARIC cohort, ischemic and hemorrhagic stroke CT cases, MRI cases with multiple pulse sequences, and 128 stroke CT patients, each with 170 variables and one year follow-up. The method employs brain atlases of anatomy, blood supply territories, and probabilistic stroke atlas. It rapidly maps an atlas to scan and provides atlas-assisted scan processing. Atlas-to-scan mapping is application-dependent and handles three types of regions of interest (ROIs): atlas-defined ROIs, atlas-quantified ROIs, and ROIs creating an atlas. An ROI is defined by atlas-guided anatomy or scan-derived pathology. The atlas defines ROI or quantifies it. A brain atlas potential has been illustrated in four atlas-assisted applications for stroke occurrence prediction and screening, rapid and automatic stroke diagnosis in emergency room, quantitative decision support in thrombolysis in ischemic stroke, and stroke outcome prediction and treatment assessment. The use of brain atlases in stroke has many potential advantages, including rapid processing, automated and robust handling, wide range of applications, and quantitative assessment. Further work is needed to enhance the developed prototypes, clinically validate proposed solutions, and introduce them to clinical practice.

Ischemic infarct detection, localization, and segmentation in noncontrast CT human brain scans: review of automated methods.

Noncontrast Computed Tomography (NCCT) of the brain has been the first-line diagnosis for emergency evaluation of acute stroke, so a rapid and automated detection, localization, and/or segmentation of ischemic lesions is of great importance. We provide the state-of-the-art review of methods for automated detection, localization, and/or segmentation of ischemic lesions on NCCT in human brain scans along with their comparison, evaluation, and classification. Twenty-two methods are (1) reviewed and evaluated; (2) grouped into image processing and analysis-based methods (11 methods), brain atlas-based methods (two methods), intensity template-based methods (1 method), Stroke Imaging Marker-based methods (two methods), and Artificial Intelligence-based methods (six methods); and (3) properties of these groups of methods are characterized. A new method classification scheme is proposed as a 2 × 2 matrix with local versus global processing and analysis, and density versus spatial sampling. Future studies are necessary to develop more efficient methods directed toward deep learning methods as well as combining the global methods with a high sampling both in space and density for the merged radiologic and neurologic data.

A 3D stereotactic atlas of the adult human skull base.

BACKGROUND: The skull base region is anatomically complex and poses surgical challenges. Although many textbooks describe this region illustrated well with drawings, scans and photographs, a complete, 3D, electronic, interactive, realistic, fully segmented and labeled, and stereotactic atlas of the skull base has not yet been built. Our goal is to create a 3D electronic atlas of the adult human skull base along with interactive tools for structure manipulation, exploration, and quantification. METHODS: Multiple in vivo 3/7 T MRI and high-resolution CT scans of the same normal, male head specimen have been acquired. From the scans, by employing dedicated tools and modeling techniques, 3D digital virtual models of the skull, brain, cranial nerves, intra- and extracranial vasculature have earlier been constructed. Integrating these models and developing a browser with dedicated interaction, the skull base atlas has been built. RESULTS: This is the first, to our best knowledge, truly 3D atlas of the adult human skull base that has been created, which includes a fully parcellated and labeled brain, skull, cranial nerves, and intra- and extracranial vasculature. CONCLUSION: This atlas is a useful aid in understanding and teaching spatial relationships of the skull base anatomy, a helpful tool to generate teaching materials, and a component of any skull base surgical simulator.

Human brain atlasing: past, present and future.

We have recently witnessed an explosion of large-scale initiatives and projects addressing mapping, modeling, simulation and atlasing of the human brain, including the BRAIN Initiative, the Human Brain Project, the Human Connectome Project (HCP), the Big Brain, the Blue Brain Project, the Allen Brain Atlas, the Brainnetome, among others. Besides these large and international initiatives, there are numerous mid-size and small brain atlas-related projects. My contribution to these global efforts has been to create adult human brain atlases in health and disease, and to develop atlas-based applications. For over two decades with my R&D lab I developed 35 brain atlases, licensed to 67 companies and made available in about 100 countries. This paper has two objectives. First, it provides an overview of the state of the art in brain atlasing. Second, as it is already 20 years from the release of our first brain atlas, I summarise my past and present efforts, share my experience in atlas creation, validation and commercialisation, compare with the state of the art, and propose future directions.

Computational and mathematical methods in brain atlasing.

Brain atlases have a wide range of use from education to research to clinical applications. Mathematical methods as well as computational methods and tools play a major role in the process of brain atlas building and developing atlas-based applications. Computational methods and tools cover three areas: dedicated editors for brain model creation, brain navigators supporting multiple platforms, and atlas-assisted specific applications. Mathematical methods in atlas building and developing atlas-aided applications deal with problems in image segmentation, geometric body modelling, physical modelling, atlas-to-scan registration, visualisation, interaction and virtual reality. Here I overview computational and mathematical methods in atlas building and developing atlas-assisted applications, and share my contribution to and experience in this field.

Usefulness of brain atlases in neuroradiology: Current status and future potential.

Human brain atlases, although prevalent in medical education and stereotactic and functional neurosurgery, are not yet applied practically in neuroradiology. In a step towards introducing brain atlases to neuroradiology, we discuss nine different situations of potential atlas use: (1) to support interpretation of brain scans with clearly visible structures (to increase confidence of non-neuroradiologists); (2) to delineate and label scans of low anatomical content (with indiscernible or poorly visible anatomy); (3) to assist in generating the structured report; (4) to assist in interpreting small deep lesions, since an atlas's anatomical parcellation is higher than that of the interpreted scan; (5) to approximate distorted due to pathology (and unknown to the interpreter) anatomy and label it; (6) to cope with data explosion; (7) to assist in the interpretation of functional scans (to label the activation foci with the underlying anatomy and Brodmann's areas); (8) to support ischemic stroke image handling by means of atlases of anatomy and blood supply territories; and (9) to communicate image interpretation results (diagnosis) to others. The usefulness of the atlas for automatic structure identification, localisation, delineation, labelling and quantification, as well as for reporting and communication, potentially increases the interpreter's efficiency and confidence, as well as expedites image interpretation.

A Quantitative Method Using Head Noncontrast CT Scans to Detect Hyperacute Nonvisible Ischemic Changes in Patients With Stroke.

PURPOSE: Because clinical evaluation of noncontrast computed tomography (CT) has a poor sensitivity in the evaluation of acute ischemic stroke, computer-aided diagnosis may be able to facilitate the performance. Recently, we introduced a computational method for the detection and localization of visible infarcts. Herein, we aimed to evaluate and extend a previous method, the Stroke Imaging Marker (SIM), to localize nonvisible hyperacute ischemia. MATERIALS AND METHODS: On the basis of the SIM and its components-the ratio of percentile differences in subranges of Hounsfield Unit (HU) distribution (P-ratio), ratio of voxels count in ranges of brain CT intensity, median HU attenuation value-the infarct localization was performed in 140 early and follow-up scans of 70 patients. In none of the early scans was the infarct visible to a radiologist or an experienced stroke neuroradiologist. The infarcted hemisphere detection rate (HDR) and sensitivity of infarct localization were measured by overlapping the region of detected tissue in the initial scan, with the gold standard set for the fully visible stroke in the follow-up scan. RESULTS: The best performance of the algorithm was found for the P-ratio including seven percentile subranges within the range of 35th-75th percentile. The modified SIM provided a 76% ischemic HDR and 54% sensitivity in spatial localization of hyperacute ischemia (68% among properly detected infarct sides). CONCLUSION: The improved SIM is a dedicated and potentially useful tool for hyperacute nonvisible brain infarct detection from CT scans and may contribute to reduction of image-to-needle time in patients eligible for revascularization therapy.

Three-dimensional stereotactic atlas of the extracranial vasculature correlated with the intracranial vasculature, cranial nerves, skull and muscles.

Our objective was to construct a 3D, interactive, and reference atlas of the extracranial vasculature spatially correlated with the intracranial blood vessels, cranial nerves, skull, glands, and head muscles.The atlas has been constructed from multiple 3T and 7T magnetic resonance angiogram (MRA) brain scans, and 3T phase contrast and inflow MRA neck scans of the same specimen in the following steps: vessel extraction from the scans, building 3D tubular models of the vessels, spatial registration of the extra- and intracranial vessels, vessel editing, vessel naming and color-coding, vessel simplification, and atlas validation.This new atlas contains 48 names of the extracranial vessels (25 arterial and 23 venous) and it has been integrated with the existing brain atlas.The atlas is valuable for medical students and residents to easily get familiarized with the extracranial vasculature with a few clicks; is useful for educators to prepare teaching materials; and potentially can serve as a reference in the diagnosis of vascular disease and treatment, including craniomaxillofacial surgeries and radiologic interventions of the face and neck.

Three-dimensional stereotactic atlas of the adult human skull correlated with the brain, cranial nerves, and intracranial vasculature.

BACKGROUND: Although the adult human skull is a complex and multifunctional structure, its 3D, complete, realistic, and stereotactic atlas has not yet been created. This work addresses the construction of a 3D interactive atlas of the adult human skull spatially correlated with the brain, cranial nerves, and intracranial vasculature. NEW METHOD: The process of atlas construction included computed tomography (CT) high-resolution scan acquisition, skull extraction, skull parcellation, 3D disarticulated bone surface modeling, 3D model simplification, brain-skull registration, 3D surface editing, 3D surface naming and color-coding, integration of the CT-derived 3D bony models with the existing brain atlas, and validation. RESULTS: The virtual skull model created is complete with all 29 bones, including the auditory ossicles (being among the smallest bones). It contains all typical bony features and landmarks. COMPARISON WITH EXISTING METHOD(S): The created skull model is superior to the existing skull models in terms of completeness, realism, and integration with the brain along with blood vessels and cranial nerves. CONCLUSIONS: This skull atlas is valuable for medical students and residents to easily get familiarized with the skull and surrounding anatomy with a few clicks. The atlas is also useful for educators to prepare teaching materials. It may potentially serve as a reference aid in the reading and operating rooms.

Toward the holistic, reference, and extendable atlas of the human brain, head, and neck.

Despite numerous efforts, a fairly complete (holistic) anatomical model of the whole, normal, adult human brain, which is required as the reference in brain studies and clinical applications, has not yet been constructed. Our ultimate objective is to build this kind of atlas from advanced in vivo imaging. This work presents the taxonomy of our currently developed brain atlases and addresses the design, content, functionality, and current results in the holistic atlas development as well as atlas usefulness and future directions. We have developed to date 35 commercial brain atlases (along with numerous research prototypes), licensed to 63 companies and institutions, and made available to medical societies, organizations, medical schools, and individuals. These atlases have been applied in education, research, and clinical applications. Hundreds of thousands of patients have been treated by using our atlases. Based on this experience, the first version of the holistic and reference atlas of the brain, head, and neck has been developed and made available. The atlas has been created from multispectral 3 and 7 Tesla and high-resolution CT in vivo scans. It is fully 3D, scalable, interactive, and highly detailed with about 3,000 labeled components. This atlas forms a foundation for the development of a multi-level molecular, cellular, anatomical, physiological, and behavioral brain atlas platform.