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Effect of C1-C2 rotation on canal size.

An anthropometric study of the atlas and axis was undertaken to determine spinal canal diameters, the degree of narrowing with rotation, and odontoid tilt. The mean sagittal diameter of the atlas was 30.1 mm and the mean coronal diameter was 28.8 mm. The mean sagittal diameter of the axis was 19.0 mm and the mean coronal diameter was 22.8 mm. Approximately 64 degrees of rotation occurred at the atlantoaxial complex before sufficient narrowing caused spinal cord compression in the average specimen. An average of 63 degrees of rotation was required to cause facet dislocation. Most specimens examined had a posterior odontoid tilt up to 45 degrees and a facet angle between 1 degree and 29 degrees. Bilateral facet dislocation occurred at 63 degrees. Spinal canal narrowing to 1 cm occurred at 64 degrees. This narrowing would probably not damage the cord, which averages 1 cm in diameter; however, if the rotary motion of C1 and C2 progressed, cord damage could occur. Facet angles and posterior odontoid tilts that are not within the normal range indicate pathological changes.

Anthropometry↗

Computer-aided interpretation of SPECT images of the brain using an MRI-derived 3D neuro-anatomical atlas.

Nuclear medicine images have comparatively poor spatial resolution, making it difficult to relate the functional information which they contain to precise anatomical structures. A 3D neuro-anatomical atlas has been generated from the MRI data set of a normal, healthy volunteer to assist in the interpretation of nuclear medicine scans of the brain. Region growing and edge-detection techniques were used to semi-automatically segment the data set into the major tissue types within the brain. The atlas was then labelled interactively by marking points on each 2D slice. Anatomical structures useful in the interpretation of SPECT images were labelled. Additional, more detailed information corresponding to these structures is provided via an interactive index which allows access to images, diagrams and explanations. Registration of patient SPECT studies with the atlas is accomplished by using the position of the skull vertex and four external fiducial markers attached to the skin surface. The 3D coordinates determined from these points are used to calculate the transformation required to rotate, scale and translate the SPECT data, in 3D, to match the atlas. Corresponding 2D slices from the two 3D data sets are then displayed side-by-side on a computer screen. A cursor linking the two images allows the delineation of regions of interest (ROIs) in the SPECT scan based on anatomical structures identified from the atlas. Conversely regions of abnormal isotope distribution in the SPECT image can be localized by reference to corresponding structures in the atlas.

Brain↗

Digital hand atlas and web-based bone age assessment: system design and implementation.

Bone age assessment is a procedure frequently performed in pediatric patients to evaluate their growth disorder. A simple method commonly used in bone age assessment is atlas matching by a radiological examination of a left-hand radiograph against a small reference set of Greulich-Pyle atlas patterns of normal standards. The method however can lead to significant deviation in age assessment, due to a variety of observers with different levels of training. The Greulich-Pyle atlas developed in the 1950s based on middle upper class white populations, is also not fully applicable for children of today, especially regarding the standard development in other racial groups. In this paper, we present our system design and initial implementation of a digital hand atlas and computer-aided diagnostic (CAD) system for Web-based bone age assessment. The CAD system is built on top of existing picture archiving and communication system (PACS), as well as recent advances in Internet technology. It consists of a hand atlas database, a CAD module and a Java-based Web user interface. The digital atlas is based on a large new set of clinically normal hand images of diverse ethnic groups. A relational image database system is used to organize hand images, their extracted quantitative features and patient data. The digital atlas removes the disadvantages of the currently out-of-date Greulich-Pyle atlas and allows the bone age assessment to be computerized. The Java-based Web user interface allows users to interact with the hand image database from browsers. Users can use a Web browser to push a clinical hand image to the CAD server for a bone age assessment. Quantitative features on the examined image, which reflect the skeletal maturity, are then extracted and compared with patterns from the atlas database to assess the bone age. The digital atlas method based on open system Internet technology provides an alternative to supplement or replace the traditional one for a quantitative, accurate and cost-effective assessment of bone age.

Adolescent↗

Areas 3a, 3b, and 1 of human primary somatosensory cortex. Part 2. Spatial normalization to standard anatomical space.

Interindividual topographical variability of cytoarchitectonically defined somatosensory areas 3a, 3b, and 1 was analyzed in the standard anatomical format of a computerized brain atlas. T1-weighted magnetic resonance images were obtained from 10 postmortem brains. The brains were serially sectioned at 20 mcm, sections were stained for cell bodies, and areas 3a, 3b, and 1 were defined with an observer-independent cytoarchitectonic technique. After correction of the sections for deformations due to histological processing, the 3-D reconstructed histological volumes of the individual brains and the volume representations of the cytoarchitectonic areas were adapted to the reference brain of a computerized atlas. Corresponding areas were superimposed in the 3-D space of the reference brain. These population maps describe, for each voxel, how many brains have a representation of one particular cytoarchitectonic area. Each area's extent is very variable across different brains, but representations of areas 3a, 3b, and 1 in >/=50% of the brains were found in the fundus of the central sulcus, its caudal bank, and on the crown of the postcentral gyrus, respectively. Volumes of interest (VOIs) were defined for each area in which >/=50% of the brains have a representation of that area. Despite close spatial relationship of areas 3a, 3b, and 1 in the postcentral gyrus, the three VOIs overlap by <1% of their volumes. Functional imaging data can now be brought into the same standard anatomical format, and changes in regional cerebral blood flow can be calculated in VOIs of areas 3a, 3b, and 1, which are derived from genuine cytoarchitectonic data.

Adult↗

A unified approach for morphometric and functional data analysis in young, old, and demented adults using automated atlas-based head size normalization: reliability and validation against manual measurement of total intracranial volume.

Atlas normalization, as commonly used by functional data analysis, provides an automated solution to the widely encountered problem of correcting for head size variation in regional and whole-brain morphometric analyses, so long as an age- and population-appropriate target atlas is used. In the present article, we develop and validate an atlas normalization procedure for head size correction using manual total intracranial volume (TIV) measurement as a reference. The target image used for atlas transformation consisted of a merged young and old-adult template specifically created for cross age-span normalization. Automated atlas transformation generated the Atlas Scaling Factor (ASF) defined as the volume-scaling factor required to match each individual to the atlas target. Because atlas normalization equates head size, the ASF should be proportional to TIV. A validation analysis was performed on 147 subjects to evaluate ASF as a proxy for manual TIV measurement. In addition, 19 subjects were imaged on multiple days to assess test-retest reliability. Results indicated that the ASF was (1) equivalent to manual TIV normalization (r = 0.93), (2) reliable across multiple imaging sessions (r = 1.00; mean absolute percentage of difference = 0.51%), (3) able to connect between-gender head size differences, and (4) minimally biased in demented older adults with marked atrophy. Hippocampal volume differences between nondemented (n = 49) and demented (n = 50) older adults (measured manually) were equivalent whether corrected using manual TIV or automated ASF (effect sizes of 1.29 and 1.46, respectively). To provide normative values, ASF was used to automatically derive estimated TIV (eTIV) in 335 subjects aged 15-96 including both clinically characterized nondemented (n = 77) and demented (n = 90) older adults. Differences in eTIV between nondemented and demented groups were negligible, thus failing to support the hypothesis that large premorbid brain size moderates Alzheimer's disease. Gender was the only robust factor that influenced eTIV. Men showed an approximately approximately 12% larger eTIV than women. These results demonstrate that atlas normalization using appropriate template images provides a robust, automated method for head size correction that is equivalent to manual TIV correction in studies of aging and dementia. Thus, atlas normalization provides a common framework for both morphometric and functional data analysis.

Adolescent↗

Occipital-axis posterior wiring and fusion for atlantoaxial dislocation associated with occipitalization of the atlas. Technical note.

The authors present their technique of occipital-axis posterior wiring and fusion for atlantoaxial dislocation associated with an occipitalized atlas. The technique consists of drilling a 3 x 1-cm horizontal groove in the occipital bone 1 cm posterior to the foramen magnum and building up a bony bridge along the posterior margin of the foramen magnum. This bony bridge is referred to as an "artificial atlas." Conventional wiring and fusion is performed between the artificial atlas and the C-2 lamina, interposing a strut bone graft. Since the compression force on tightening the wire is vertical, a very high degree of stability for the occipital-C-2 complex is achieved, facilitating early mobilization without postoperative redislocation.

Atlanto-Axial Joint↗

Establishment of a reference collection of additives and an analytical handbook of reference data to support enforcement of EU regulations on food contact plastics.

A collection has been made of additives that are required as analytical standards for enforcement of European Union legislation on food contact plastics. The 100 additives have been characterized by mass spectrometry, infra-red spectroscopy and proton nuclear magnetic resonance spectroscopy to provide reference spectra. Gas chromatographic retention times have been recorded to facilitate identification by retention index. This information has been further supplemented by physico-chemical data. Finally, chromatographic methods have been used to indicate the presence of any impurities in the commercial chemicals. Samples of the reference substances are available on request and the collection of spectra and other information will be made available in printed format and on-line through the Internet. This paper gives an overview of the work done to establish the reference collection and the spectral atlas, which together will assist enforcement laboratories in the characterization of plastics and the selection of analytical methods for additives that may migrate.

Chromatography, Gas↗

Atlas-based segmentation of bone structures to support the virtual planning of hip operations.

Two 3-D digitised atlases of a female and a male pelvis were generated to support the virtual 3-D planning of hip operations. The anatomical atlases were designed to replace the interactive, time-consuming pre-processing steps for the virtual operation planning. Each atlas consists of a labelled reference CT data set and a set of anatomical point landmarks. The paper presents methods for the automatic transfer of these anatomical labels to an individual patient data set. The labelled patient data are used to generate 3-D models of the patient's bone structures. Besides the anatomical labelling, the determination of measures, like angles, distances or sizes of contact areas, is important for the planning of hip operations. Thus, algorithms for the automatic computation of orthopaedic parameters were implemented. A first evaluation of the presented atlas-based segmentation method shows a correct labelling of 98.5% of the bony voxels.

Algorithms↗

Co-registration of the Schaltenbrand-Wahren microseries with the probabilistic functional atlas.

OBJECTIVE: The Schaltenbrand-Wahren atlas (SWA) is anatomical, sparse and inconsistent in three dimensions. A high-resolution, electrophysiology-based atlas derived from numerous specimens overcomes these limitations. A combined anatomy-physiology atlas leverages the strengths and complementarity of both, which is studied here. METHOD: An electronic version of the SWA was constructed. A probabilistic functional atlas (PFA) was developed from electrophysiological and neuroimaging data with 0.25 mm3 resolution. A combined atlas is constructed by co-registering the PFA with the SWA by applying linear scaling along the intercommissural distance and the height of the thalamus. RESULTS: An anatomy-physiology atlas is superior to its component atlases. When in register, the anatomical and functional atlases are displayed together and used simultaneously. A structure of interest from the PFA can be displayed with high resolution, compensating for its sparseness in the SWA, while its surrounding structures are obtained from the SWA. The best anatomical and functional targets can be compared: for the subthalamic nucleus, the horizontal and lateral coordinates of the SWA-based and PFA- based targets are approximately the same, while the latter is located 1.3-1.5 mm more anteriorly. CONCLUSION: An anatomy-physiology atlas may enhance the accuracy of targeting and increase the neurosurgeon's confidence. It also opens new research avenues to serve as a reference for: (1) constructing an extendable atlas by adding new electrophysiological data, (2) comparing anatomical and functional targets, (3) studying and comparing various symptoms, and (4) comparing image-based targets obtained from various modalities.

Anatomy, Artistic↗

Integration of microstructural and functional aspects of human somatosensory areas 3a, 3b, and 1 on the basis of a computerized brain atlas.

In this study we analyzed structural and functional aspects of the human primary somatosensory areas 3a, 3b, and 1 on the basis of a computerized brain atlas. The approach overcomes many of the problems associated with subjective architectonic parcellations of the cortex and with 'classical" brain maps published in a "rigid" print format. Magnetic resonance (MR) scans were obtained from ten postmortem brains. The brains were serially sectioned at 20 microm, and sections were stained for cell bodies. Areas 3a, 3b, and 1 were delineated statistically on the basis of differences in the laminar densities of neuronal cell bodies. The borders of the areas were topographically variable across different brains and did not match macroanatomical landmarks of the postcentral gyrus. After correction of the sections for deformations due to histological processing, each brain's 3-D reconstructed histological volume and the volume representations of areas 3a, 3b, and 1 were adapted to the reference brain of a computerized atlas and superimposed in 3-D space. For each area, a population map was generated that described, for each voxel, how many brains had a representation of that area. Despite considerable interindividual variability, representations of areas 3a, 3b, and 1 in > or = 50% of the brains were found in the fundus of the central sulcus, in the rostral bank, and on the crown of the postcentral gyrus, respectively. For each area, a volume of interest (VOI) was defined that encompassed that area's representation in > or = 50% of the brains. Despite close spatial relationship in the postcentral gyrus, the three VOIs overlapped by < 1% of their volumes. Changes in regional cerebral blood flow (rCBF) were measured with positron emission tomography when six right-handed subjects discriminated differences in the speed of a rotating brush stimulating the palmar surface of the right hand. With co-registered MR images, the rCBF data were adapted to the same reference brain and superimposed with the microstructural VOIs. Discrimination of moving stimuli, contrasted to rest, increased the rCBF in the VOIs of areas 3b and 1, but not in area 3a. This approach opens up the possibility of (1) defining VOIs of cortical areas which are not based on macroanatomical landmarks but instead on observer-independent cytoarchitectonic mapping of postmortem brains and of (2) determining in these VOIs changes in rCBF data obtained from functional imaging experiments.

Adult↗

3D and 4D atlas system of living human body structure.

A reference system for accessing anatomical information from a complete 3D structure of the whole body "living human", including 4D cardiac dynamics, was reconstructed with 3D and 4D data sets obtained from normal volunteers. With this system, we were able to produce a human atlas in which sectional images can be accessed from any part of the human body interactively by real-time image generation.

Anatomy, Cross-Sectional↗

Human somatosensory area 2: observer-independent cytoarchitectonic mapping, interindividual variability, and population map.

We analyzed the topographical variability of human somatosensory area 2 in 10 postmortem brains. The brains were serially sectioned at 20 microm, and sections were stained for cell bodies. Area 2 was delineated with an observer-independent technique based on significant differences in the laminar densities of cell bodies. The sections were corrected with an MR scan of the same brain obtained before histological processing. Each brain's histological volume and representation of area 2 was subsequently reconstructed in 3-D. We found that the borders of area 2 are topographically variable. The rostral border lies between the convexity of the postcentral gyrus and some millimeters deep in the rostral wall of the postcentral sulcus. The caudal border lies between the fundus of the postcentral sulcus and some millimeters above it in the rostral wall. In contrast to Brodmann's map, area 2 does not extend onto the mesial cortical surface or into the intraparietal sulcus. When the postcentral sulcus is interrupted by a gyral bridge, area 2 crosses this bridge and is not separated into two segments. After cytoarchitectonic analysis, the histological volumes were warped to the reference brain of a computerized atlas and superimposed. A population map was generated in 3-D space, which describes how many brains have a representation of area 2 in a particular voxel. This microstructurally defined population map can be used to demonstrate activations of area 2 in functional imaging studies and therefore help to further understand the role of area 2 in somatosensory processing.

Adult↗

The microstructural border between the motor and the cognitive domain in the human cerebral cortex.

When we voluntarily interact with our environment, the agranular frontal cortex (Brodmann's areas 4 and 6) plays a pivotal role in cortical motor control. The primary motor cortex (area 4) influences kinematic and dynamic parameters of movements, whereas the rostrally adjoining nonprimary motor cortex (area 6) uses external (e.g., sensory) or internal cues to trigger and guide movements. Once thought to be homogeneous, data from nonhuman primates have shown that area 6 is a mosaic of areas, each with distinct structural and functional properties: the supplementary motor areas "SMA proper" and "pre-SMA" on the mesial cortical surface, and the dorso- and ventrolateral premotor cortex on the cortical convexity. Dorso- and ventrolateral premotor areas are specifically connected with posterior parietal areas. These parieto-frontal circuits work in parallel and tranform different aspects of sensory information into appropriate motor commands. The rostral border of area 6 is very important for functional neuroimaging studies in humans since it separates the "motor domain" of the supplementary motor/premotor cortex from the "cognitive domain" of the prefrontal cortex. Can the topography of this border be inferred from the gyral pattern of the frontal lobe? To answer this, ten postmorterm brains were scanned with a T1-weighted magnetic resonance sequence. The brains were serially sectioned at 20 micro M and area 6 was defined by subjective and objective cytoarchitectonic analysis. Each brain's histological volume (with the representation of area 6) was reconstructed in 3-D and spatially normalized to the reference brain of a computerized atlas. The ten normalized volumes were superimposed and a population map was generated that describes, for each voxel, how many brains have a representation of area 6. On the mesial coetical surface, the rostral border of area 6 lies rostral to the anterior commissure-- though the distance varies across different brains. On the lateral convexity, the border recedes in a caudal direction-- again to a varying degree in different brains-- and lies on the precentral gyrus close to the sylvian fissure. No macroanatomical landmark indicates the border between area 6 and the prefrontal cortex. The question whether a motor task engages only the "motor domain" of the supplementary motor/premotor cortex or in addition the "cognitive domain" of the prefrontal cortex can only be answered by superimposing the functional activation map with the microstructural population map of area 6.

Animals↗

Functional-lesion investigation of developmental stuttering with positron emission tomography.

Positron emission tomographic (PET) H2(15)O measurements of resting-state regional cerebral blood flow (CBF) were obtained in 29 right-handed men, 10 of whom stuttered and 19 of whom did not. PET images were analyzed by sampling 74 regions of interest (ROIs), 37 per hemisphere. ROI placement was guided both physiologically and anatomically. Physiological ROI placement was based on speech motor activations. Anatomical ROIs were positioned by reference to a stereotactic, neurosurgical atlas with positions confirmed and finely adjusted by co-registered magnetic-resonance images (MRIs). For all subjects, PET and MR images were normal to visual inspection. Highly significant (p < 0.0001) between-region and between-hemisphere effects were found for both groups, as have been previously reported for normal subjects, but no significant between-group differences were found for any regional CBF values. Analysis by a laterality index found a weakly significant between-groups effect (p = 0.04) that was isolated to five regions, four of which are implicated in speech or hearing. However, these regional laterality effects showed no consistent directionality, nor did these regions have absolute differences in regional blood flow between groups. Present findings do not support recent suggestions that developmental stuttering is associated with abnormalities of brain blood flow at rest. Rather, our findings indicate an essentially normal functional brain terrain with a small number of minor differences in hemispheric symmetry.

Adult↗

Mapping genetic influences on human brain structure.

Recent advances in brain imaging and genetics have empowered the mapping of genetic and environmental influences on the human brain. These techniques shed light on the 'nature/nurture' debate, revealing how genes determine individual differences in intelligence quotient (IQ) or risk for disease. They visualize which aspects of brain structure and function are heritable, and to what degree, linking these features with behavioral or cognitive traits or disease phenotypes. In genetically transmitted disorders such as schizophrenia, patterns of brain structure can be associated with increased disease liability, and sites can be mapped where non-genetic triggers may initiate disease. We recently developed a large-scale computational brain atlas, including data components from the Finnish Twin registry, to store information on individual variations in brain structure and their heritability. Algorithms from random field theory, anatomical modeling, and population genetics were combined to detect a genetic continuum in which brain structure is heavily genetically determined in some areas but not others. These algorithmic advances motivate studies of disease in which the normative atlas acts as a quantitative reference for the heritability of structural differences and deficits in patient populations. The resulting genetic brain maps isolate biological markers for inherited traits and disease susceptibility, which may serve as targets for genetic linkage and association studies. Computational methods from brain imaging and genetics can be fruitfully merged, to shed light on the inheritance of personality differences and behavioral traits, and the genetic transmission of diseases that affect the human brain.

Algorithms↗

Unraveling Neuronal Identities Using SIMS: A Deep Learning Label Transfer Tool for Single-Cell RNA Sequencing Analysis.

Large single-cell RNA datasets have contributed to unprecedented biological insight. Often, these take the form of cell atlases and serve as a reference for automating cell labeling of newly sequenced samples. Yet, classification algorithms have lacked the capacity to accurately annotate cells, particularly in complex datasets. Here we present SIMS (Scalable, Interpretable Machine Learning for Single-Cell), an end-to-end data-efficient machine learning pipeline for discrete classification of single-cell data that can be applied to new datasets with minimal coding. We benchmarked SIMS against common single-cell label transfer tools and demonstrated that it performs as well or better than state of the art algorithms. We then use SIMS to classify cells in one of the most complex tissues: the brain. We show that SIMS classifies cells of the adult cerebral cortex and hippocampus at a remarkably high accuracy. This accuracy is maintained in trans-sample label transfers of the adult human cerebral cortex. We then apply SIMS to classify cells in the developing brain and demonstrate a high level of accuracy at predicting neuronal subtypes, even in periods of fate refinement, shedding light on genetic changes affecting specific cell types across development. Finally, we apply SIMS to single cell datasets of cortical organoids to predict cell identities and unveil genetic variations between cell lines. SIMS identifies cell-line differences and misannotated cell lineages in human cortical organoids derived from different pluripotent stem cell lines. When cell types are obscured by stress signals, label transfer from primary tissue improves the accuracy of cortical organoid annotations, serving as a reliable ground truth. Altogether, we show that SIMS is a versatile and robust tool for cell-type classification from single-cell datasets.

Brain organoids↗

Absorbed dose measurements in dual energy X-ray absorptiometry (DXA).

In this study a predominantly film dosimetric method was used to measure the effective dose from posteroanterior (PA) lumbar spine and proximal femur scans performed on a Lunar DPX-L machine. Because of the very low dose rate in scanning mode, the depth dose data were determined using a stationary detector configuration. The characteristic curve for the film (Kodak TMAT-H) was obtained and depth dose measurements were made using slabs of "solid water". The film was calibrated using a superficial X-ray unit (calibrated against a standard traceable to a national standard). To assess the change in film response with beam hardening at depth, the film was exposed to calibration beams of different half value layer (HVL). The HVL of the DXA beam was determined for surface and depth doses using aluminium filters and a diamond detector (an energy independent device). All measurements were performed three times. Beam size was measured using film, and the scan areas and times were determined by scanning phantoms. The dose from a scan was calculated using Dsc = DTscAb/Asc, where D = dose rate (stationary), Tsc = scan time, Ab = beam area, and Asc = scan area. Organ doses were determined using an anatomical atlas and ICRP 23 female reference. All film measurements had good precision (coefficient of variation < 4%). There was little variation in film sensitivity with change in HVL (< 1% change for the first three HVLs) and consequently no corrections were applied to the depth dose data. Skin entrance dose was 11.5 microGy. Effective dose in females was 0.19 microSv for the PA lumbar spine. For the proximal femur scan, the effective dose was 0.14 microSv (ovaries included) and 0.023 microSv (ovaries excluded) for pre-menopausal and pos-menopausal women, respectively.

Absorptiometry, Photon↗

[Application of a semi-automatic ROI setting system for brain PET images to animal PET studies].

ProASSIST, a semi-automatic ROI (region of interest) setting system for human brain PET images, has been modified for use with the canine brain, and the performance of the obtained system was evaluated by comparing the operational simplicity for ROI setting and the consistency of ROI values obtained with those by a conventional manual procedure. Namely, we created segment maps for the canine brain by making reference to the coronal section atlas of the canine brain by Lim et al., and incorporated them into the ProASSIST system. For the performance test, CBF (cerebral blood flow) and CMRglc (cerebral metabolic rate in glucose) images in dogs with or without focal cerebral ischemia were used. In ProASSIST, brain contours were defined semiautomatically. In the ROI analysis of the test image, manual modification of the contour was necessary in half cases examined (8/16). However, the operation was rather simple so that the operation time per one brain section was significantly shorter than that in the manual operation. The ROI values determined by the system were comparable with those by the manual procedure, confirming the applicability of the system to these animal studies. The use of the system like the present one would also merit the more objective data acquisition for the quantitative ROI analysis, because no manual procedure except for some specifications of the anatomical features is required for ROI setting.

Animals↗