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1.  Creation of Computerized 3D MRI-Integrated Atlases of the Human Basal Ganglia and Thalamus 
Functional brain imaging and neurosurgery in subcortical areas often requires visualization of brain nuclei beyond the resolution of current magnetic resonance imaging (MRI) methods. We present techniques used to create: (1) a lower resolution 3D atlas, based on the Schaltenbrand and Wahren print atlas, which was integrated into a stereotactic neurosurgery planning and visualization platform (VIPER); and (2) a higher resolution 3D atlas derived from a single set of manually segmented histological slices containing nuclei of the basal ganglia, thalamus, basal forebrain, and medial temporal lobe. Both atlases were integrated to a canonical MRI (Colin27) from a young male participant by manually identifying homologous landmarks. The lower resolution atlas was then warped to fit the MRI based on the identified landmarks. A pseudo-MRI representation of the high-resolution atlas was created, and a non-linear transformation was calculated in order to match the atlas to the template MRI. The atlas can then be warped to match the anatomy of Parkinson's disease surgical candidates by using 3D automated non-linear deformation methods. By way of functional validation of the atlas, the location of the sensory thalamus was correlated with stereotactic intraoperative physiological data. The position of subthalamic electrode positions in patients with Parkinson's disease was also evaluated in the atlas-integrated MRI space. Finally, probabilistic maps of subthalamic stimulation electrodes were developed, in order to allow group analysis of the location of contacts associated with the best motor outcomes. We have therefore developed, and are continuing to validate, a high-resolution computerized MRI-integrated 3D histological atlas, which is useful in functional neurosurgery, and for functional and anatomical studies of the human basal ganglia, thalamus, and basal forebrain.
PMCID: PMC3167101  PMID: 21922002
brain atlas; Parkinson's disease; stereotactic neurosurgery; image guidance
2.  A Digital Framework to Build, Visualize and Analyze a Gene Expression Atlas with Cellular Resolution in Zebrafish Early Embryogenesis 
PLoS Computational Biology  2014;10(6):e1003670.
A gene expression atlas is an essential resource to quantify and understand the multiscale processes of embryogenesis in time and space. The automated reconstruction of a prototypic 4D atlas for vertebrate early embryos, using multicolor fluorescence in situ hybridization with nuclear counterstain, requires dedicated computational strategies. To this goal, we designed an original methodological framework implemented in a software tool called Match-IT. With only minimal human supervision, our system is able to gather gene expression patterns observed in different analyzed embryos with phenotypic variability and map them onto a series of common 3D templates over time, creating a 4D atlas. This framework was used to construct an atlas composed of 6 gene expression templates from a cohort of zebrafish early embryos spanning 6 developmental stages from 4 to 6.3 hpf (hours post fertilization). They included 53 specimens, 181,415 detected cell nuclei and the segmentation of 98 gene expression patterns observed in 3D for 9 different genes. In addition, an interactive visualization software, Atlas-IT, was developed to inspect, supervise and analyze the atlas. Match-IT and Atlas-IT, including user manuals, representative datasets and video tutorials, are publicly and freely available online. We also propose computational methods and tools for the quantitative assessment of the gene expression templates at the cellular scale, with the identification, visualization and analysis of coexpression patterns, synexpression groups and their dynamics through developmental stages.
Author Summary
We propose a workflow to map the expression domains of multiple genes onto a series of 3D templates, or “atlas”, during early embryogenesis. It was applied to the zebrafish at different stages between 4 and 6.3 hpf, generating 6 templates. Our system overcomes the lack of significant morphological landmarks in early development by relying on the expression of a reference gene (goosecoid, gsc) and nuclear staining to guide the registration of the analyzed genes. The proposed method also successfully maps gene domains from partially imaged embryos, thus allowing greater microscope magnification and cellular resolution. By using the workflow to construct a spatiotemporal database of zebrafish, we opened the way to a systematic analysis of vertebrate embryogenesis. The atlas database, together with the mapping software (Match-IT), a custom-made visualization platform (Atlas-IT), and step-by-step user guides are available from the Supplementary Material. We expect that this will encourage other laboratories to generate, map, visualize and analyze new gene expression datasets.
PMCID: PMC4063669  PMID: 24945246
3.  The SRI24 Multi-Channel Atlas of Normal Adult Human Brain Structure 
Human brain mapping  2010;31(5):798-819.
This paper describes the SRI24 atlas, a new standard reference system of normal human brain anatomy, that was created using template-free population registration of high-resolution magnetic resonance images acquired at 3T in a group of 24 normal control subjects. The atlas comprises anatomical channels (T1, T2, and proton density weighted), diffusion-related channels (fractional anisotropy, mean diffusivity, longitudinal diffusivity, mean diffusion-weighted image), tissue channels (CSF probability, gray matter probability, white matter probability, tissue labels), and two cortical parcellation maps. The SRI24 atlas enables multi-channel atlas-to-subject image registration. It is uniquely versatile in that it is equally suited for the two fundamentally different atlas applications: label propagation and spatial normalization. Label propagation, herein demonstrated using DTI fiber tracking, is enabled by the increased sharpness of the SRI24 atlas compared with other available atlases. Spatial normalization, herein demonstrated using data from a young-old group comparison study, is enabled by its unbiased average population shape property. For both propagation and normalization, we also report the results of quantitative comparisons with seven other published atlases: Colin27, MNI152, ICBM452 (warp5 and air12), and LPBA40 (SPM5, FLIRT, AIR). Our results suggest that the SRI24 atlas, although based on 3T MR data, allows equally accurate spatial normalization of data acquired at 1.5T as the comparison atlases, all of which are based on 1.5T data. Furthermore, the SRI24 atlas is as suitable for label propagation as the comparison atlases and detailed enough to allow delineation of anatomical structures for this purpose directly in the atlas.
PMCID: PMC2915788  PMID: 20017133
brain atlas; multi-spectral magnetic resonance imaging; diffusion tensor imaging; unbiased population registration; spatial normalization; label propagation
4.  Computer-based Learning of Neuroanatomy: A Longitudinal Study of Learning, Transfer, and Retention 
A longitudinal experiment was conducted to evaluate the effectiveness of new methods for learning neuroanatomy with computer-based instruction. Using a 3D graphical model of the human brain, and sections derived from the model, tools for exploring neuroanatomy were developed to encourage adaptive exploration. This is an instructional method which incorporates graphical exploration in the context of repeated testing and feedback. With this approach, 72 participants learned either sectional anatomy alone or whole anatomy followed by sectional anatomy. Sectional anatomy was explored either with perceptually continuous navigation through the sections or with discrete navigation (as in the use of an anatomical atlas). Learning was measured longitudinally to a high performance criterion. Subsequent tests examined transfer of learning to the interpretation of biomedical images and long-term retention. There were several clear results of this study. On initial exposure to neuroanatomy, whole anatomy was learned more efficiently than sectional anatomy. After whole anatomy was mastered, learners demonstrated high levels of transfer of learning to sectional anatomy and from sectional anatomy to the interpretation of complex biomedical images. Learning whole anatomy prior to learning sectional anatomy led to substantially fewer errors overall than learning sectional anatomy alone. Use of continuous or discrete navigation through sectional anatomy made little difference to measured outcomes. Efficient learning, good long-term retention, and successful transfer to the interpretation of biomedical images indicated that computer-based learning using adaptive exploration can be a valuable tool in instruction of neuroanatomy and similar disciplines.
PMCID: PMC3551584  PMID: 23349552
learning; instruction; neuroanatomy; graphics; interactive
5.  Software-based Diffusion MR Human Brain Phantom for Evaluating Fiber-tracking Algorithms 
Fiber tracking provides insights into the brain white matter network and has become more and more popular in diffusion MR imaging. Hardware or software phantom provides an essential platform to investigate, validate and compare various tractography algorithms towards a “gold standard”. Software phantoms excel due to their flexibility in varying imaging parameters, such as tissue composition, SNR, as well as potential to model various anatomies and pathologies. This paper describes a novel method in generating diffusion MR images with various imaging parameters from realistically appearing, individually varying brain anatomy based on predefined fiber tracts within a high-resolution human brain atlas. Specifically, joint, high resolution DWI and structural MRI brain atlases were constructed with images acquired from 6 healthy subjects (age 22–26) for the DWI data and 56 healthy subject (age 18–59) for the structural MRI data. Full brain fiber tracking was performed with filtered, two-tensor tractography in atlas space. A deformation field based principal component model from the structural MRI as well as unbiased atlas building was then employed to generate synthetic structural brain MR images that are individually varying. Atlas fiber tracts were accordingly warped into each synthetic brain anatomy. Diffusion MR images were finally computed from these warped tracts via a composite hindered and restricted model of diffusion with various imaging parameters for gradient directions, image resolution and SNR. Furthermore, an open-source program was developed to evaluate the fiber tracking results both qualitatively and quantitatively based on various similarity measures.
PMCID: PMC3865235  PMID: 24357914
Diffusion-weighted MRI; Atlas; Fiber tracking; Tractography; Phantom; Validation
6.  Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system 
Nucleic Acids Research  2012;41(Database issue):D996-D1008.
The Allen Brain Atlas ( provides a unique online public resource integrating extensive gene expression data, connectivity data and neuroanatomical information with powerful search and viewing tools for the adult and developing brain in mouse, human and non-human primate. Here, we review the resources available at the Allen Brain Atlas, describing each product and data type [such as in situ hybridization (ISH) and supporting histology, microarray, RNA sequencing, reference atlases, projection mapping and magnetic resonance imaging]. In addition, standardized and unique features in the web applications are described that enable users to search and mine the various data sets. Features include both simple and sophisticated methods for gene searches, colorimetric and fluorescent ISH image viewers, graphical displays of ISH, microarray and RNA sequencing data, Brain Explorer software for 3D navigation of anatomy and gene expression, and an interactive reference atlas viewer. In addition, cross data set searches enable users to query multiple Allen Brain Atlas data sets simultaneously. All of the Allen Brain Atlas resources can be accessed through the Allen Brain Atlas data portal.
PMCID: PMC3531093  PMID: 23193282
7.  Anatomical Atlas-Guided Diffuse Optical Tomography of Brain Activation 
NeuroImage  2009;49(1):561-567.
We describe a neuro imaging protocol that utilizes an anatomical atlas of the human head to guide Diffuse optical tomography of human brain activation. The protocol is demonstrated by imaging the hemodynamic response to median nerve stimulation in three healthy subjects, and comparing the images obtained using a head atlas with the images obtained using the subject-specific head anatomy. The results indicate that using the head atlas anatomy it is possible to reconstruct the location of the brain activation to the expected gyrus of the brain, in agreement with the results obtained with the subject-specific head anatomy. The benefits of this novel method derive from eliminating the need for subject-specific head anatomy and thus obviating the need for a subject-specific MRI to improve the anatomical interpretation of Diffuse optical tomography images of brain activation.
PMCID: PMC2858333  PMID: 19643185
Diffuse Optical Tomography; NIRS; anatomical atlas; MRI; segmentation; registration; inverse problem; human study; somatosensory; PACS: 87.19.lf; PACS: 87.19.lh
8.  Ethics and access to teaching materials in the medical library: the case of the Pernkopf atlas* 
Conflicts can occur between the principle of freedom of information treasured by librarians and ethical standards of scientific research involving the propriety of using data derived from immoral or dishonorable experimentation. A prime example of this conflict was brought to the attention of the medical and library communities in 1995 when articles claiming that the subjects of the illustrations in the classic anatomy atlas, Eduard Pernkopf's Topographische Anatomie des Menschen, were victims of the Nazi holocaust. While few have disputed the accuracy, artistic, or educational value of the Pernkopf atlas, some have argued that the use of such subjects violates standards of medical ethics involving inhuman and degrading treatment of subjects or disrespect of a human corpse. Efforts were made to remove the book from medical libraries. In this article, the history of the Pernkopf atlas and the controversy surrounding it are reviewed. The results of a survey of academic medical libraries concerning their treatment of the Pernkopf atlas are reported, and the ethical implications of these issues as they affect the responsibilities of librarians is discussed.
PMCID: PMC31704  PMID: 11209801
9.  Disease-Specific Probabilistic Brain Atlases 
Atlases of the human brain, in health and disease, provide a comprehensive framework for understanding brain structure and function. The complexity and variability of brain structure, especially in the gyral patterns of the human cortex, present challenges in creating standardized brain atlases that reflect the anatomy of a population. This paper introduces the concept of a population-based, disease-specific brain atlas that can reflect the unique anatomy and physiology of a particular clinical subpopulation. Based on well-characterized patient groups, disease-specific atlases contain thousands of structure models, composite maps, average templates, and visualizations of structural variability, asymmetry and group-specific differences. They correlate the structural, metabolic, molecular and histologic hallmarks of the disease. Rather than simply fusing information from multiple subjects and sources, new mathematical strategies are introduced to resolve group-specific features not apparent in individual scans. High-dimensional elastic mappings, based on covariant partial differential equations, are developed to encode patterns of cortical variation. In the resulting brain atlas, disease-specific features and regional asymmetries emerge that are not apparent in individual anatomies. The resulting probabilistic atlas can identify patterns of altered structure and function, and can guide algorithms for knowledge-based image analysis, automated image labeling, tissue classification, data mining and functional image analysis.
PMCID: PMC2678017  PMID: 19424457
10.  Atlas-based Segmentation of Developing Tissues in the Human Brain with Quantitative Validation in Young Fetuses 
Human Brain Mapping  2010;31(9):1348-1358.
Imaging of the human fetus using magnetic resonance (MR) is an essential tool for quantitative studies of normal as well as abnormal brain development in utero. However, because of fundamental differences in tissue types, tissue properties and tissue distribution between the fetal and adult brain, automated tissue segmentation techniques developed for adult brain anatomy are unsuitable for this data. In this paper, we describe methodology for automatic atlas-based segmentation of individual tissue types in motion-corrected 3D volumes reconstructed from clinical MR scans of the fetal brain. To generate anatomically correct automatic segmentations, we create a set of accurate manual delineations and build an in utero 3D statistical atlas of tissue distribution incorporating developing grey and white matter as well as transient tissue types such as the germinal matrix. The probabilistic atlas is associated with an unbiased average shape and intensity template for registration of new subject images to the space of the atlas. Quantitative whole brain 3D validation of tissue labeling performed on a set of 14 fetal MR scans (20.57–22.86 weeks gestational age) demonstrates that this atlas-based EM segmentation approach achieves consistently high DSC performance for the main tissue types in the fetal brain. This work indicates that reliable measures of brain development can be automatically derived from clinical MR imaging and opens up possibility of further 3D volumetric and morphometric studies with multiple fetal subjects.
PMCID: PMC3306251  PMID: 20108226
11.  Segmentation of Brain Images Using Adaptive Atlases with Application to Ventriculomegaly 
Segmentation of brain images often requires a statistical atlas for providing prior information about the spatial position of different structures. A major limitation of atlas-based segmentation algorithms is their deficiency in analyzing brains that have a large deviation from the population used in the construction of the atlas. We present an expectation-maximization framework based on a Dirichlet distribution to adapt a statistical atlas to the underlying subject. Our model combines anatomical priors with the subject’s own anatomy, resulting in a subject specific atlas which we call an “adaptive atlas”. The generation of this adaptive atlas does not require the subject to have an anatomy similar to that of the atlas population, nor does it rely on the availability of an ensemble of similar images. The proposed method shows a significant improvement over current segmentation approaches when applied to subjects with severe ventriculomegaly, where the anatomy deviates significantly from the atlas population. Furthermore, high levels of accuracy are maintained when the method is applied to subjects with healthy anatomy.
PMCID: PMC3478153  PMID: 21761641
12.  Interactive Atlas of Histology 
An interactive atlas of histology was developed for online use by chiropractic students to enable them to practice and self-assess their ability to identify various histological structures. This article discusses the steps in the development, implementation, and usefulness of an interactive atlas of histology for students who take histology examinations.
The atlas was developed by digitizing images imported through a video-microscope using actual microscope slides. Leica EWS 2100 and PowerPoint software were used to construct the atlas. The usefulness of the atlas was assessed through a comparison of histology exam scores between four classes before and four classes after the use of the atlas. Analysis of admissions data, including overall grade point average (GPA), science and nonscience GPA, and a number of course units, was done initially to avoid any identifiable differences in the academic competency between the two being compared. A survey of the students was also done to assess atlas usefulness and students' satisfaction with the atlas.
Analysis of histology exam scores showed that the average scores in the lab exam were significantly higher for the classes that used the atlas. Survey results showed a high level of student satisfaction with the atlas.
The development and use of an online interactive atlas of histology for chiropractic students helped to improve lab exams scores. In addition, students were satisfied with the features and usefulness of this atlas.
PMCID: PMC2384180  PMID: 18483638
atlases [publication type]; chiropractic; education; histology; technology
13.  Web-based access to an online atlas of anatomy: the Digital Anatomist Common Gateway Interface. 
A World Wide Web Common Gateway Interface package is described for accessing existing online interactive atlases of anatomy. The Web interface accesses the same 2-D and 3-D images of human neuroanatomy, knee anatomy and thoracic viscera that are currently accessed by a custom interactive atlas in distance learning courses. Although the Web interface is too slow to replace the existing atlas, it provides a parallel access path that has much broader potential for development of a distributed distance learning network in anatomy. By maintaining both access methods to the same information sources we continue to satisfy the fast interactivity needs for our local courses, while at the same time providing a migration path to the Web as the capabilities of Web browsers evolve.
PMCID: PMC2579146  PMID: 8563336
14.  Transition from Film to Electronic Media in the First-Year Medical School Gross Anatomy Lab  
Journal of Digital Imaging  2004;16(4):337-340.
For the benefit of the first-year gross anatomy students, we digitized and published on a Web site images that had been collected over a 30-year period. We provided a CD-ROM (compact disk, read-only media) containing the image set in higher quality format to students and faculty. We supplemented basic images with hot topics such as CT angiography, virtual colonography, computer-aided diagnosis, and 3D post-processing. Full motion video and moving JPEG (Joint Photo Expert Group) animations were integrated into the atlas. On the post course questionnaire medical students reported that the images on CD-ROM were helpful during the course and for review prior to examinations. Faculty and medical students used the CD-ROM for problem-based learning sections and facilitator training. The images were clear and easily projected during review sessions and were useful for the small group sessions, where they served as examples of normal anatomy.
PMCID: PMC3044075  PMID: 14749968
Re-engineering; teaching file; Internet-based; CD-ROM
15.  The HUDSEN Atlas: a three-dimensional (3D) spatial framework for studying gene expression in the developing human brain 
Journal of anatomy  2010;217(4):289-299.
We are developing a three-dimensional (3D) atlas of the human embryonic brain using anatomical landmarks and gene expression data to define major subdivisions through 12 stages of development (Carnegie Stages [CS] 12-23; approx 26-56 days post conception [dpc]). Virtual 3D anatomical models are generated from intact specimens using optical projection tomography (OPT). Using MAPaint software, selected gene expression data, gathered using standard methods of in situ hybridisation and immunohistochemistry, are mapped to a representative 3D model for each chosen Carnegie stage. In these models, anatomical domains, defined on the basis of morphological landmarks and comparative knowledge of expression patterns in vertebrates, are linked to a developmental neuroanatomic ontology. Human gene expression patterns for genes with characteristic expression in different vertebrates (e.g. PAX6, GAD65 and OLIG2) are being used to confirm and/or refine the human anatomical domain boundaries. We have also developed interpolation software that digitally generates a full domain from partial data. Currently, the 3D models and a preliminary set of anatomical domains and ontology are available on the atlas pages along with gene expression data from approximately 100 genes in the HUDSEN Human Spatial Gene Expression Database ( The aim is that full 3D data will be generated from expression data used to define a more detailed set of anatomical domains linked to a more advanced anatomy ontology and all of these will be available online, contributing to the long-term goal of the atlas which is to help maximise the effective use and dissemination of data wherever it is generated.
PMCID: PMC2967454  PMID: 20979583
Human embryo; 3D atlas; Gene Expression; OPT; database
16.  The use of thoracoscopy to enhance medical students’ interest and understanding of thoracic anatomy 
Annals of Thoracic Medicine  2012;7(3):145-148.
To develop a video-based educational tool designed for teaching thoracic anatomy and to examine whether this tool would increase students’ stimulation and motivation for learning anatomy.
Our video-based tool was developed by recording different thoracoscopic procedures focusing on intraoperative live thoracic anatomy. The tool was then integrated into a pre-existing program for first year medical students (n = 150), and included cadaver dissection of the thorax and review of clinical problem scenarios of the respiratory system. Students were guided through a viewing of the videotape that demonstrated live anatomy of the thorax (15 minutes) and then asked to complete a 5-point Likert-type questionnaire assessing the video's usefulness. Apart from this, a small group of entirely different set of students was divided into two groups, one group to view the 15-minute video presentation of thoracoscopy and chest anatomy and the other group to attend a 15-minute lecture of chest anatomy using radiological images. Both groups took a 10-item pretest and post-test multiple choice questions examination to assess short-term knowledge gained.
Of 150 medical students, 119 completed the questionnaires, 88.6% were satisfied with the thoracoscopic video as a teaching tool, 86.4% were satisfied with the quality of the images, 69.2% perceived it to be beneficial in learning anatomy, 96.2% increased their interest in learning anatomy, and 88.5% wanted this new teaching tool to be implemented to the curriculum. Majority (80.7%) of the students increased their interest in surgery as a future career. Post-test scores were significantly higher in the thoracoscopy group (P = 0.0175).
Incorporating live surgery using thoracoscopic video presentation in the gross anatomy teaching curriculum had high acceptance and satisfaction scores from first year medical students. The video increased students’ interest in learning, in clinically applying anatomic fact, and in surgery as a future career.
PMCID: PMC3425046  PMID: 22924072
Medical students; thoracic anatomy; thoracoscopy
17.  A spatiotemporal atlas of MR intensity, tissue probability and shape of the fetal brain with application to segmentation 
NeuroImage  2010;53(2):460-470.
Modeling and analysis of MR images of the developing human brain is a challenge due to rapid changes in brain morphology and morphometry. We present an approach to the construction of a spatiotemporal atlas of the fetal brain with temporal models of MR intensity, tissue probability and shape changes. This spatiotemporal model is created from a set of reconstructed MR images of fetal subjects with different gestational ages. Groupwise registration of manual segmentations and voxelwise nonlinear modeling allow us to capture the appearance, disappearance and spatial variation of brain structures over time. Applying this model to atlas-based segmentation, we generate age-specific MR templates and tissue probability maps and use them to initialize automatic tissue delineation in new MR images. The choice of model parameters and the final performance are evaluated using clinical MR scans of young fetuses with gestational ages ranging from 20.57 to 24.71 weeks. Experimental results indicate that quadratic temporal models can correctly capture growth-related changes in the fetal brain anatomy and provide improvement in accuracy of atlas-based tissue segmentation.
PMCID: PMC2930902  PMID: 20600970
Structural MRI; Fetal imaging; Atlas building; Tissue segmentation
18.  Ontological Labels for Automated Location of Anatomical Shape Differences 
Journal of Biomedical Informatics  2012;45(3):522-527.
A method for automated location of shape differences in diseased anatomical structures via high resolution biomedical atlases annotated with labels from formal ontologies is described. In particular, a high resolution magnetic resonance image of the myocardium of the human left ventricle was segmented and annotated with structural terms from an extracted subset of the Foundational Model of Anatomy ontology. The atlas was registered to the end systole template of a previous study of left ventricular remodeling in cardiomyopathy using a diffeomorphic registration algorithm. The previous study used thresholding and visual inspection to locate a region of statistical significance which distinguished patients with ischemic cardiomyopathy from those with nonischemic cardiomyopathy. Using semantic technologies and the deformed annotated atlas, this location was more precisely found. Although this study used only a cardiac atlas, it provides a proof-of-concept that ontologically labeled biomedical atlases of any anatomical structure can be used to automate location-based inferences.
PMCID: PMC3371096  PMID: 22490168
Ontologies; Medical Atlases; Cardiac Left Ventricle; Computational Anatomy
19.  Age-Specific Average Head Template for Typically Developing 6-Month-Old Infants 
PLoS ONE  2013;8(9):e73821.
Due to the rapid anatomical changes that occur within the brain structure in early human development and the significant differences between infant brains and the widely used standard adult templates, it becomes increasingly important to utilize appropriate age- and population-specific average templates when analyzing infant neuroimaging data. In this study we created a new and highly detailed age-specific unbiased average head template in a standard MNI152-like infant coordinate system for healthy, typically developing 6-month-old infants by performing linear normalization, diffeomorphic normalization and iterative averaging processing on 60 subjects’ structural images. The resulting age-specific average templates in a standard MNI152-like infant coordinate system demonstrate sharper anatomical detail and clarity compared to existing infant average templates and successfully retains the average head size of the 6-month-old infant. An example usage of the average infant templates transforms magnetoencephalography (MEG) estimated activity locations from MEG’s subject-specific head coordinate space to the standard MNI152-like infant coordinate space. We also created a new atlas that reflects the true 6-month-old infant brain anatomy. Average templates and atlas are publicly available on our website (
PMCID: PMC3772014  PMID: 24069234
20.  An Osteological Study of Occipitocervical Synostosis: Its Embryological and Clinical Significance 
Background: Synostosis or fusion of atlas with occipital bone is known as occipitocervical synostosis, occipitalization of the atlas, or atlanto-occipital fusion. This is a rare congenital malformation at craniovertebral junction. Its incidence ranges from 0.08%–3% in general population. Occipitocervical synostosis result in narrowing of foramen magnum which may compress the brain stem, vertebral artery and cranial nerves. Knowledge of occipitocervical synostosis is important for the surgeons during the surgeries in the craniovertebral region. Hence, the present study was undertaken to determine the incidence and to describe the morphology of the occipitocervical synostosis.
Material and Methods: Two-hundred dry adult human skulls of Indian origin were studied in the Department of anatomy. The base of these skulls was observed for presence of atlanto-occipital fusion. The anteroposterior and transverse diameter of the foramen magnum and diameter of the inferior articular facets were measured in these skulls using digital vernier caliper.
Results: Two skulls showed occipitalization of Atlas (1%). One of the skulls showed partial fusion (0.5%) while the other showed complete occipitalization (0.5%).
Conclusion: The knowledge of bony fusion between the cranial base and the first cervical vertebra is important as such skeletal anomaly may result in sudden unexpected death due to compression of the vital structures such as brain stem and vertebral arteries.
PMCID: PMC3809614  PMID: 24179875
Synostosis; Occipitocervical; Vertebra; Atlas; Proatlas; Sclerotome
21.  Building a Human Brain Atlas Optimized for Normal Adult Anatomy 
Currently no high resolution three-dimensional (3-D) digital atlas exists that is optimized for normal human adult anatomy. We have developed the methods for defining, constructing and evaluating a “minimal deformation target” MDT brain for multi-subject studies, which produces a single reproducible target based on the common features of a group of brain images. We are building a digital brain atlas, based on a high-resolution, high contrast MR study — CH brain. In a preliminary study (N=27) MDT optimization of the CH brain resulted in a significant reduction of its individual features, including changes in the central sulcus, Sylvian fissure, ventricular system and temporal lobe regions. The atlas will be created by optimizing the CH brain to a large population (N>100) of normal subjects
PMCID: PMC2244379
22.  A High-Resolution Anatomical Atlas of the Transcriptome in the Mouse Embryo 
PLoS Biology  2011;9(1):e1000582.
The manuscript describes the “digital transcriptome atlas” of the developing mouse embryo, a powerful resource to determine co-expression of genes, to identify cell populations and lineages and to identify functional associations between genes relevant to development and disease.
Ascertaining when and where genes are expressed is of crucial importance to understanding or predicting the physiological role of genes and proteins and how they interact to form the complex networks that underlie organ development and function. It is, therefore, crucial to determine on a genome-wide level, the spatio-temporal gene expression profiles at cellular resolution. This information is provided by colorimetric RNA in situ hybridization that can elucidate expression of genes in their native context and does so at cellular resolution. We generated what is to our knowledge the first genome-wide transcriptome atlas by RNA in situ hybridization of an entire mammalian organism, the developing mouse at embryonic day 14.5. This digital transcriptome atlas, the Eurexpress atlas (, consists of a searchable database of annotated images that can be interactively viewed. We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures. The quality and the resolution of the data revealed novel molecular domains for several developing structures, such as the telencephalon, a novel organization for the hypothalamus, and insight on the Wnt network involved in renal epithelial differentiation during kidney development. The digital transcriptome atlas is a powerful resource to determine co-expression of genes, to identify cell populations and lineages, and to identify functional associations between genes relevant to development and disease.
Author Summary
In situ hybridization (ISH) can be used to visualize gene expression in cells and tissues in their native context. High-throughput ISH using nonradioactive RNA probes allowed the Eurexpress consortium to generate a comprehensive, interactive, and freely accessible digital gene expression atlas, the Eurexpress transcriptome atlas (, of the E14.5 mouse embryo. Expression data for over 15,000 genes were annotated for hundreds of anatomical structures, thus allowing us to systematically identify tissue-specific and tissue-overlapping gene networks. We illustrate the value of the Eurexpress atlas by finding novel regional subdivisions in the developing brain. We also use the transcriptome atlas to allocate specific components of the complex Wnt signaling pathway to kidney development, and we identify regionally expressed genes in liver that may be markers of hematopoietic stem cell differentiation.
PMCID: PMC3022534  PMID: 21267068
23.  A method of 2D/3D registration of a statistical mouse atlas with a planar X-ray projection and an optical photo 
Medical image analysis  2013;17(4):401-416.
The development of sophisticated and high throughput whole body small animal imaging technologies has created a need for improved image analysis and increased automation. The registration of a digital mouse atlas to individual images is a prerequisite for automated organ segmentation and uptake quantification. This paper presents a fully-automatic method for registering a statistical mouse atlas with individual subjects based on an anterior-posterior X-ray projection and a lateral optical photo of the mouse silhouette. The mouse atlas was trained as a statistical shape model based on 83 organ-segmented micro-CT images. For registration, a hierarchical approach is applied which first registers high contrast organs, and then estimates low contrast organs based on the registered high contrast organs. To register the high contrast organs, a 2D-registration-back-projection strategy is used that deforms the 3D atlas based on the 2D registrations of the atlas projections. For validation, this method was evaluated using 55 subjects of preclinical mouse studies. The results showed that this method can compensate for moderate variations of animal postures and organ anatomy. Two different metrics, the Dice coefficient and the average surface distance, were used to assess the registration accuracy of major organs. The Dice coefficients vary from 0.31±0.16 for the spleen to 0.88±0.03 for the whole body, and the average surface distance varies from 0.54±0.06 mm for the lungs to 0.85±0.10 mm for the skin. The method was compared with a direct 3D deformation optimization (without 2D-registration-back-projection) and a single-subject atlas registration (instead of using the statistical atlas). The comparison revealed that the 2D-registration-back-projection strategy significantly improved the registration accuracy, and the use of the statistical mouse atlas led to more plausible organ shapes than the single-subject atlas. This method was also tested with shoulder xenograft tumor-bearing mice, and the results showed that the registration accuracy of most organs was not significantly affected by the presence of shoulder tumors, except for the lungs and the spleen.
PMCID: PMC3667217  PMID: 23542374
24.  Spatio-Temporal Analysis of Early Brain Development 
Analysis of human brain development is a crucial step for improved understanding of neurodevelopmental disorders. We focus on normal brain development as is observed in the multimodal longitudinal MRI/DTI data of neonates to two years of age. We present a spatio-temporal analysis framework using Gompertz function as a population growth model with three different spatial localization strategies: voxel-based, data driven clustering and atlas driven regional analysis. Growth models from multimodal imaging channels collected at each voxel form feature vectors which are clustered using the Dirichlet Process Mixture Models (DPMM). Clustering thus combines growth information from different modalities to subdivide the image into voxel groups with similar properties. The processing generates spatial maps that highlight the dynamic progression of white matter development. These maps show progression of white matter maturation where primarily, central regions mature earlier compared to the periphery, but where more subtle regional differences in growth can be observed. Atlas based analysis allows a quantitative analysis of a specific anatomical region, whereas data driven clustering identifies regions of similar growth patterns. The combination of these two allows us to investigate growth patterns within an anatomical region. Specifically, analysis of anterior and posterior limb of internal capsule show that there are different growth trajectories within these anatomies, and that it may be useful to divide certain anatomies into subregions with distinctive growth patterns.
PMCID: PMC4199456  PMID: 25328368
Brain development; MRI; Diffusion tensor imaging; Longitudinal analysis; Growth trajectory
25.  Human Brain White Matter Atlas: Identification and Assignment of Common Anatomical Structures in Superficial White Matter 
NeuroImage  2008;43(3):447-457.
Structural delineation and assignment are the fundamental steps in understanding the anatomy of the human brain. The white matter has been structurally defined in the past only at its core regions (deep white matter). However, the most peripheral white matter areas, which are interleaved between the cortex and the deep white matter, have lacked clear anatomical definitions and parcellations. We used axonal fiber alignment information from diffusion tensor imaging (DTI) to delineate the peripheral white matter, and investigated its relationship with the cortex and the deep white matter. Using DTI data from 81 healthy subjects, we identified nine common, blade-like anatomical regions, which were further parcellated into 21 subregions based on the cortical anatomy. Four short association fiber tracts connecting adjacent gyri (U-fibers) were also identified reproducibly among the healthy population. We anticipate that this atlas will be useful resource for atlas-based white matter anatomical studies.
PMCID: PMC2586008  PMID: 18692144
human; white matter; atlas; association fiber; magnetic resonance imaging; diffusion tensor

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