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A digital brain atlas and its application to the visceral neuraxis.

We describe the details and application of a digital brain atlas for the comparison and integration of graphical neurobiological data. The atlas consists of multiple sets of high-resolution video images acquired from histological tissue sections representing a 3-dimensional (3D) volume of an exemplar rat brain. Through an interactive graphical interface running on a standard computer workstation, experimental data is brought into register with the atlas. Once in the atlas, coordinate reference frame data can be compared, analyzed, and visualized in 3 dimensions. We demonstrate the validity and usefulness of the digital brain atlas with a series of results on the visceral neuraxis in the rat.

Animals↗

Brain atlases--a new research tool.

Conventional brain atlases are collections of micrographs or schematic drawings of brain sections from one or a few brains in which anatomical structures are identified, for example, nuclei, cortical areas and fibre tracts. Conventional brain maps have now been replaced with modern computer-based brain atlases. The structures in computerized atlases are deformable so as to fit the sizes and shapes of individual brains, and transform three-dimensional reconstructions or images of brains into a standard brain format. In order to make generalizations about localization of function and structure at both the macroscopical and microscopical level computerized brain atlases are needed. Computerized brain atlases are also used to compensate for the shrinkage and distortions during sectioning and embedding of post-mortem brains, to study structural-functional relationships in the human brain at both the macroscopical and microscopical level, and variations in gross morphology and microstructure of the human brain, and for establishing a three-dimensional human-brain database for all of the above and also for topographically defined data from the literature.

Animals↗

Comparison of three automated urinalysis systems--Bayer Clinitek Atlas, Roche Urisys 2400 and Arkray Aution Max for testing urine chemistry and detection of bacteriuria.

BACKGROUND: Our study is aimed to determine the performance of 3 automated urinalysis systems-Clinitek Atlas, Urisys 2400 and Aution Max. METHODS: One thousand urine specimens were analyzed with the 3 automated systems. The results of the 3 assays were compared for testing urine chemistry and evaluating the capacity of leukocyte esterase and nitrite to detect bacteriuria. RESULTS: The correlation between the 3 instruments represented as within 1 grading difference was better between the Atlas and Aution Max systems for pH, blood, glucose, urobilinogen, ketone and specific gravity. For protein and nitrite, better correlation was observed between the Atlas and Urisys 2400, while the Aution Max and Urisys 2400 conveyed better correlation for bilirubin and white blood cells. The sensitivity and specificity of both the leukocyte esterase and nitrite in screening for significant bacteriuria were 71.7, 58.9, 70.8% and 99.1, 99.1 and 97.2%, for the Clinitek Atlas, Aution Max and Urisys 2400, respectively. CONCLUSIONS: The automated urinalysis systems demonstrate acceptable correlations with each other in urine chemistries, especially between the Clinitek Atlas and Aution Max systems on the majority of items. The specificity and negative predictive value of leukocyte esterase and nitrite of the 3 instruments for screening of significant bacteriuria were sufficient to avoid unnecessary urine culture.

Bacteriuria↗

Detection of diffuse abnormal perfusion in SPECT using a normal brain atlas.

Visual assessment, with significant inter- or intraobserver variability, is still the norm for the evaluation of Single Photon Emission Computerized Tomography (SPECT) cerebral perfusion studies. We present in this paper an automated method for screening SPECT studies to detect diffuse disseminated abnormalities based on a computerized atlas of normal regional cerebral blood flow (rCBF). To generate the atlas, a set of normal brain SPECT studies are registered together. The atlas contains the intensity mean, the nonlinear displacement mean, and the variance of the activity pattern. A patient is then evaluated by registering his or her SPECT volume to the atlas and computing the nonlinear 3-D displacement of each voxel needed for the best shape fit to it. A voxel is counted as "abnormal" if the intensity difference between the atlas and the registered patient (or if the 3-D motion necessary to move the voxel to its registered position) is superior to 3 SD of normal mean. The number of abnormal voxels is used to classify studies. We validated this approach on 24 SPECT perfusion studies selected visually for having clear diffuse anomalies and 21 normal studies. A Markovian segmentation algorithm is also used to identify the white and gray matters for regional analysis. Based on the number of abnormal voxels, two supervised classifiers were tested: (1) minimum distance-to-mean and (2) Bayesian. The analysis of the intensity and displacement "abnormal" voxels allow one to achieve an 80% correct classification rate for the whole brain and a 93% rate if we consider only voxels in the segmented gray matter region.

Algorithms↗

Atlas-based hippocampus segmentation in Alzheimer's disease and mild cognitive impairment.

This study assesses the performance of public-domain automated methodologies for MRI-based segmentation of the hippocampus in elderly subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Structural MR images of 54 age- and gender-matched healthy elderly individuals, subjects with probable AD, and subjects with MCI were collected at the University of Pittsburgh Alzheimer's Disease Research Center. Hippocampi in subject images were automatically segmented by using AIR, SPM, FLIRT, and the fully deformable method of Chen to align the images to the Harvard atlas, MNI atlas, and randomly selected, manually labeled subject images ("cohort atlases"). Mixed-effects statistical models analyzed the effects of side of the brain, disease state, registration method, choice of atlas, and manual tracing protocol on the spatial overlap between automated segmentations and expert manual segmentations. Registration methods that produced higher degrees of geometric deformation produced automated segmentations with higher agreement with manual segmentations. Side of the brain, presence of AD, choice of reference image, and manual tracing protocol were also significant factors contributing to automated segmentation performance. Fully automated techniques can be competitive with human raters on this difficult segmentation task, but a rigorous statistical analysis shows that a variety of methodological factors must be carefully considered to insure that automated methods perform well in practice. The use of fully deformable registration methods, cohort atlases, and user-defined manual tracings are recommended for highest performance in fully automated hippocampus segmentation.

Aged↗

A stereotaxic MRI template set for the rat brain with tissue class distribution maps and co-registered anatomical atlas: application to pharmacological MRI.

We describe a stereotaxic rat brain MRI template set with a co-registered digital anatomical atlas and illustrate its application to the analysis of a pharmacological MRI (phMRI) study of apomorphine. The template set includes anatomical images and tissue class probability maps for brain parenchyma and cerebrospinal fluid (CSF). These facilitate the use of standard fMRI software for spatial normalisation and tissue segmentation of rat brain data. A volumetric reconstruction of the Paxinos and Watson rat brain atlas is also co-localised with the template, enabling the atlas structure and stereotaxic coordinates corresponding to a feature within a statistical map to be interactively reported, facilitating the localisation of functional effects. Moreover, voxels falling within selected brain structures can be combined to define anatomically based 3D volumes of interest (VOIs), free of operator bias. As many atlas structures are small relative to the typical resolution of phMRI studies, a mechanism for defining composite structures as agglomerations of individual atlas structures is also described. This provides a simple and robust means of interrogating structures that are otherwise difficult to delineate and an objective framework for comparing and classifying compounds based on an anatomical profile of their activity. These developments allow a closer alignment of pre-clinical and clinical analysis techniques.

Animals↗

Specification and selection of regions of interest (ROIs) in a computerized brain atlas.

The computerized individually adjustable brain atlas (CBA) has been further developed. The atlas was primarily designed for anatomical localization and quantitative evaluation of data in positron emission tomography (PET), but may also be employed for other neuroimaging modalities, such as transmission computed tomography (CT) and magnetic resonance imaging (MRI). The atlas is based on anatomical information obtained from digitized cryosectioned brains. Using spatially standardized and then averaged MRI images, we demonstrate the high localization accuracy and precision of the brain atlas. This is a prerequisite for obtaining accuracy when using the atlas in the localization and the quantitative evaluation of PET data. The specification and the selection of region of interests (ROIs) by the CBA are presented and discussed.

Brain↗

ATLAS: a system to selectively identify human-specific L1 insertions.

Retrotransposition of L1 LINEs (long interspersed elements) continues to sculpt the human genome. However, because recent insertions are dimorphic, they are not fully represented in sequence databases. Here, we have developed a system, termed "ATLAS" (amplification typing of L1 active subfamilies), that enables the selective amplification and display of DNA fragments containing the termini of human-specific L1s and their respective flanking sequences. We demonstrate that ATLAS is robust and that the resultant display patterns are highly reproducible, segregate in Centre d'Etude du Polymorphisme Humain pedigrees, and provide an individual-specific fingerprint. ATLAS also allows the identification of L1s that are absent from current genome databases, and we show that some of these L1s can retrotranspose at high frequencies in cultured human cells. Finally, we demonstrate that ATLAS also can identify single-nucleotide polymorphisms within a subset of older, primate-specific L1s. Thus, ATLAS provides a simple, high-throughput means to assess genetic variation associated with L1 retrotransposons.

5' Untranslated Regions↗

Digimouse: a 3D whole body mouse atlas from CT and cryosection data.

We have constructed a three-dimensional (3D) whole body mouse atlas from coregistered x-ray CT and cryosection data of a normal nude male mouse. High quality PET, x-ray CT and cryosection images were acquired post mortem from a single mouse placed in a stereotactic frame with fiducial markers visible in all three modalities. The image data were coregistered to a common coordinate system using the fiducials and resampled to an isotropic 0.1 mm voxel size. Using interactive editing tools we segmented and labelled whole brain, cerebrum, cerebellum, olfactory bulbs, striatum, medulla, masseter muscles, eyes, lachrymal glands, heart, lungs, liver, stomach, spleen, pancreas, adrenal glands, kidneys, testes, bladder, skeleton and skin surface. The final atlas consists of the 3D volume, in which the voxels are labelled to define the anatomical structures listed above, with coregistered PET, x-ray CT and cryosection images. To illustrate use of the atlas we include simulations of 3D bioluminescence and PET image reconstruction. Optical scatter and absorption values are assigned to each organ to simulate realistic photon transport within the animal for bioluminescence imaging. Similarly, 511 keV photon attenuation values are assigned to each structure in the atlas to simulate realistic photon attenuation in PET. The Digimouse atlas and data are available at http://neuroimage.usc.edu/Digimouse.html.

Anatomy, Cross-Sectional↗

A multimodal, multidimensional atlas of the C57BL/6J mouse brain.

Strains of mice, through breeding or the disruption of normal genetic pathways, are widely used to model human diseases. Atlases are an invaluable aid in understanding the impact of such manipulations by providing a standard for comparison. We have developed a digital atlas of the adult C57BL/6J mouse brain as a comprehensive framework for storing and accessing the myriad types of information about the mouse brain. Our implementation was constructed using several different imaging techniques: magnetic resonance microscopy, blockface imaging, classical histology and immunohistochemistry. Along with raw and annotated images, it contains database management systems and a set of tools for comparing information from different techniques. The framework allows facile correlation of results from different animals, investigators or laboratories by establishing a canonical representation of the mouse brain and providing the tools for the insertion of independent data into the same space as the atlas. This tool will aid in managing the increasingly complex and voluminous amounts of information about the mammalian brain. It provides a framework that encompasses genetic information in the context of anatomical imaging and holds tremendous promise for producing new insights into the relationship between genotype and phenotype. We describe a suite of tools that enables the independent entry of other types of data, facile retrieval of information and straightforward display of images. Thus, the atlas becomes a framework for managing complex genetic and epigenetic information about the mouse brain. The atlas and associated tools may be accessed at http://www.loni.ucla.edu/MAP.

Anatomy, Artistic↗

Atlas-based identification of targets for functional radiosurgery.

Functional disorders of the brain, such as Parkinson's disease, dystonia, epilepsy, and neuropathic pain, may exhibit poor response to medical therapy. In such cases, surgical intervention may become necessary. Modern surgical approaches to such disorders include radio-frequency lesioning and deep brain stimulation (DBS). The subthalamic nucleus (STN) is one of the most useful stereotactic targets available: STN DBS is known to induce substantial improvement in patients with end-stage Parkinson's disease. Other targets include the Globus Pallidus pars interna (GPi) for dystonia and Parkinson's disease, and the centromedian nucleus of the thalamus (CMN) for neuropathic pain. Radiosurgery is an attractive noninvasive alternative to treat some functional brain disorders. The main technical limitation to radiosurgery is that the target can be selected only on the basis of magnetic resonance anatomy without electrophysiological confirmation. The aim of this work is to provide a method for the correct atlas-based identification of the target to be used in functional neurosurgery treatment planning. The coordinates of STN, CMN, and GPi were identified in the Talairach and Tournoux atlas and transformed to the corresponding regions of the Montreal Neurological Institute (MNI) electronic atlas. Binary masks describing the target nuclei were created. The MNI electronic atlas was deformed onto the patient magnetic resonance imaging-T1 scan by applying an affine transformation followed by a local nonrigid registration. The first transformation was based on normalized cross correlation and the second on optimization of a two-part objective function consisting of similarity criteria and weighted regularization. The obtained deformation field was then applied to the target masks. The minimum distance between the surface of an implanted electrode and the surface of the deformed mask was calculated. The validation of the method consisted of comparing the electrode-mask distance to the clinical outcome of the treatments in ten cases of bilateral DBS implants. Electrode placement may have an effect within a radius of stimulation equal to 2 mm, therefore the registration process is considered successful if error is less than 2 mm. The registrations of the MNI atlas onto the patient space succeeded in all cases. The comparison of the distance to the clinical outcome revealed good agreement: where the distance was high (at least in one implant), the clinical outcome was poor; where there was a close correlation between the structures, clinical outcome revealed an improvement of the pathological condition. In conclusion, the proposed method seems to provide a useful tool for the identification of the target nuclei for functional radiosurgery. Also, the method is applicable to other types of functional treatment.

Journal Article↗

An ethnographic, controlled study of the use of a computer-based histology atlas during a laboratory course.

OBJECTIVE: To evaluate the use and effect of a computer-based histology atlas during required laboratory sessions in a medical school histology course. DESIGN: Ethnographic observation of students' interactions in a factorial, controlled setting. MEASUREMENTS: Ethnographer's observations; student and instructor self-report survey after each laboratory session with items rated from 1 (least) to 7 (best); microscope practicum scores at the end of the course. RESULTS: Between groups assigned the atlas and those not, the ethnographer found qualitative differences in the semantic categories used by students in communicating with each other and with the faculty. Differences were also found in the quality of the interactions and in the learning styles used with and without the computer present in the laboratory. The most interactive learning style was achieved when a pair of students shared a computer and a microscope. Practicum grades did not change with respect to historical controls. Students assigned the atlas, compared with those not assigned, reported higher overall satisfaction (a difference in score of 0.1, P = 0.003) and perceived their fellow students to be more helpful (a difference of 0.11, P = 0.035). They rated the usefulness of the microscope lower (a difference of 0.23, P<0.001). CONCLUSION: A computer-based histology atlas induces qualitative changes in the histology laboratory environment. Most students and faculty reacted positively. The authors did not measure the impact on learning, but they found that there are aspects of using the atlas that instructors must manipulate to make learning optimal. Ethnographic techniques can be helpful in delineating the context and defining what the interventions might be.

Analysis of Variance↗

Quantification and visualization of the three-dimensional inconsistency of the subthalamic nucleus in the Schaltenbrand-Wahren brain atlas.

The Schaltenbrand-Wahren (SW) brain atlas has many limitations: the major two are three-dimensional (3D) inconsistency and spatial sparseness. In this work, we quantify and visualize the 3D inconsistency of the subthalamic nucleus (STN). The STN 3D models, 3D-A, 3D-C and 3D-S, are reconstructed from the SW axial, coronal, and sagittal microseries, respectively, by using a shape-based (NURBS) approach. All three models are placed in the SW coordinate system and compared quantitatively in terms of location (centroids), size (volumes), shape (normalized eigenvalues), orientation (eigenvectors), and mutual spatial relationships (overlaps and inclusions). Analysis is done in 3D within each orientation and across them. A dedicated tool is developed for quantitative validation of 3D modeling. The average error achieved is 0.088 mm, which is at the resolution limit of the digital SW atlas. The reconstructed 3D STN models differ in location, size, shape, orientation, overlap size, and inclusion rate. The 3D-S volume is 1.27 times larger than that of 3D-A and 1.38 times larger than that of 3D-C. The highest overlap size is found between 3D-A and 3D-S. The highest inclusion rates of 52.5 and 66.6% are for 3D-A and 3D-S. 3D-C has the lowest overlap size and results in the lowest inclusion rates (around 20-30%), meaning that 3D-C is substantially displaced in comparison to 3D-A and 3D-S. The lateral centroid coordinate of 3D-C is 9.18 mm while that of 3D-S is 12.17 mm. Each of the 3D models has some limitation: 3D-A in orientation, 3D-C in location, and 3D-S in shape realism. The STN in comparison to the actual almond is smaller, and relatively (i.e. normalized to the same height) 2.2-2.4 times wider and 3.7-5.5 times longer. 3D-C becomes more similar to 3D-S by scaling the SW coronal microseries laterally by 1.3257. Then the lateral coordinates of their centroids coincide, the difference between them in orientation is 0.11 mm, and 3D-S is only 1.06 times larger than the scaled 3D-C. This operation substantially improves registration of the SW atlas with the probabilistic functional atlas. However, 3D visualization shows that both 3D-S and scaled 3D-C models are heavily interwoven resulting in low inclusion rates of about 60%. The STN in the SW atlas shows severe 3D inaccuracy within each orientation and across them, and it has to be employed with great care and understanding of its limitations.

Anatomy, Artistic↗

The symbolic atlas of the brain: handling non-visual information associated with neuroanatomy.

The Symbolic Atlas of the brain is a novel software tool which enables the user to store and access non-visual information associated with the brain anatomy. The atlas is potentially capable of storing any information about neuroanatomical objects. The user can construct a number of atlases, each containing a different kind of information related to functionality, pathology, symptoms and other facts. The Prolog database that underpins the storage of knowledge frames provides scope for nearly unconstrained usage and manipulation of the stored data, including reasoning with and about data and complex querying. The access to the stored information is provided in an intuitive way, through a simple 'click' on an anatomical structure either in a two- or three-dimensional atlas, or on an outline of a structure superimposed on a real image slice. A pilot educational and clinical use of the atlas indicates its great potential, especially in the are of education.

Anatomy, Artistic↗

Accuracy of skeletal age assessment in children from birth to 6 years of age with the ultrasonographic version of the Greulich-Pyle atlas.

OBJECTIVES: For the evaluation of skeletal age, the methods of Greulich-Pyle and Tanner-Whitehouse are generally used in clinical practice. Our investigation was undertaken to determine whether the ultrasonographic version of the Greulich-Pyle atlas is capable of assessing skeletal age. If so, we aimed to describe the standards for the ultrasonographic version of the Greulich-Pyle atlas for each year during the first 6 years of life. METHODS: Ninety-seven subjects underwent left hand and wrist radiography and ultrasonographic examination for bone age assessment during a 1.5-year study. Estimated bone ages derived from the plain radiography and "hand and wrist ultrasonography charts" interpreted by use of the Greulich-Pyle atlas were compared statistically. RESULTS: The estimated bone ages from plain radiography and hand and wrist ultrasonography charts interpreted by use of the Greulich-Pyle atlas were significantly correlated; 71.1% of male patients had the same age in both methods, and in 84.4% of patients, the difference was less than 6 months. In 65.5% of female patients, both methods revealed the same age, and in 88.5% of them, the difference was less then 6 months. CONCLUSIONS: The ultrasonographic version of the Greulich-Pyle atlas can be used to estimate bone age even in ultrasonography departments. This method is highly correlated and a valid alternative to plain radiography for bone age estimation. This enables estimation of skeletal age in ultrasonography departments easily without exposing the patient to radiation.

Age Determination by Skeleton↗

3D-VIEWER: an atlas-based system for individual and statistical investigations of the human brain.

3D-VIEWER is a new software tool for neurosurgical planning and population studies. It is based on digitized three-dimensional brain atlases derived from standard stereotactic atlases that can be adapted to an individual's brain and shown as a series of displayed images. If the patient's brain has been imaged in different modalities, the standardized anatomical information can be adapted to the individual images, which will bring the images into registration. The 3D-VIEWER can be used as a tool for combining multimodal information from the same patient. In addition, several tools are available that allow oblique views of anatomical structures or the view along the intended trajectory during a neurosurgical intervention. Furthermore, using the atlas transformation matrices, anatomical information can be determined when comparing an individual's brain to the anatomy of the atlas brain. Thus, standardized anatomical information from the atlas can be introduced into individual images. This standardization is used to perform individual-group and group-by-group comparisons between patients and normal controls in anatomical studies.

Brain Mapping↗

An overview of the methods and data used in the CCORT Canadian Cardiovascular Atlas project.

The Canadian Cardiovascular Atlas project, an initiative of the Canadian Cardiovascular Outcomes Research Team (CCORT), will be published as a series of 20 articles in future issues of the Canadian Journal of Cardiology. Through a wide range of data sources and analyses from a number of collaborators across Canada, the CCORT Atlas will provide a comprehensive overview of the current state of cardiac care and disease in Canada. Administrative data, clinical registries and community survey data will be analyzed at the provincial and health region levels. The purposes of this article are to 1) provide an overview of the data types and sources used in the Atlas project, 2) give a general description of the methods and analyses used to report Atlas data and 3) describe how Atlas maps were created and how they can be interpreted.

Canada↗

A customizable MR brain imaging atlas of structure and function for decision support.

We present a MR brain atlas for structure and function (diffusion weighted images). The atlas is customizable for contrast and orientation to match the current patient images. In addition, the atlas also provides normative values of MR parameters (T1, T2 and ADC values). The atlas is designed on informatics principles to provide context sensitive decision support at the time of primary image interpretation. Additional support for diagnostic interpretation is provided by a list of expert created most relevant 'Image Finding Descriptors' that will serve as cues to the user. The architecture of the atlas module is integrated into the image workflow of a radiology department to provide support at the time of primary diagnosis.

Algorithms↗