Retrospective evaluation of intersubject brain registration.

Although numerous methods to register brains of different individuals have been proposed, no work has been done, as far as we know, to evaluate and objectively compare the performances of different nonrigid (or elastic) registration methods on the same database of subjects. In this paper, we propose an evaluation framework, based on global and local measures of the relevance of the registration. We have chosen to focus more particularly on the matching of cortical areas, since intersubject registration methods are dedicated to anatomical and functional normalization, and also because other groups have shown the relevance of such registration methods for deep brain structures. Experiments were conducted using 6 methods on a database of 18 subjects. The global measures used show that the quality of the registration is directly related to the transformation's degrees of freedom. More surprisingly, local measures based on the matching of cortical sulci did not show significant differences between rigid and non rigid methods.

A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM).

Motivated by the vast amount of information that is rapidly accumulating about the human brain in digital form, we embarked upon a program in 1992 to develop a four-dimensional probabilistic atlas and reference system for the human brain. Through an International Consortium for Brain Mapping (ICBM) a dataset is being collected that includes 7000 subjects between the ages of eighteen and ninety years and including 342 mono- and dizygotic twins. Data on each subject includes detailed demographic, clinical, behavioural and imaging information. DNA has been collected for genotyping from 5800 subjects. A component of the programme uses post-mortem tissue to determine the probabilistic distribution of microscopic cyto- and chemoarchitectural regions in the human brain. This, combined with macroscopic information about structure and function derived from subjects in vivo, provides the first large scale opportunity to gain meaningful insights into the concordance or discordance in micro- and macroscopic structure and function. The philosophy, strategy, algorithm development, data acquisition techniques and validation methods are described in this report along with database structures. Examples of results are described for the normal adult human brain as well as examples in patients with Alzheimer's disease and multiple sclerosis. The ability to quantify the variance of the human brain as a function of age in a large population of subjects for whom data is also available about their genetic composition and behaviour will allow for the first assessment of cerebral genotype-phenotype-behavioural correlations in humans to take place in a population this large. This approach and its application should provide new insights and opportunities for investigators interested in basic neuroscience, clinical diagnostics and the evaluation of neuropsychiatric disorders in patients.

A four-dimensional probabilistic atlas of the human brain.

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype- phenotype-behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders.

Measurement of cortical thickness using an automated 3-D algorithm: a validation study.

A validation study was conducted to assess the accuracy of the algorithm developed by MacDonald et al. (1999) for measuring cortical thickness. This algorithm automatically determines the cortical thickness by 3-D extraction of the inner and outer surfaces of the cerebral cortex from an MRI scan. A manual method of tagging the grey-csf and grey-white interface was used on 20 regions (10 cortical areas found in each hemisphere) in 40 MRIs of the brain to validate the algorithm. The regions were chosen throughout the cortex to get broad assessment of the algorithm's performance. Accuracy was determined by an anatomist tagging the csf-grey and grey-white borders of selected gyri and by allowing the algorithm to determine the csf-grey and grey-white borders and the corresponding cortical thickness of the same region. Results from the manual and automatic methods were statistically compared using overall ANOVA and paired t tests for each region. The manual and automatic methods were in agreement for all but 4 of the 20 regions tested. The four regions where there were significant differences between the two methods were the insula left and right, the right cuneus, and the right parahippocampus. We conclude that the automatic algorithm is valid for most of the cortex and provides a viable alternative to manual methods of determining cortical thickness in vivo. However, caution should be taken when measuring the regions mentioned previously where the results of the algorithm can be biased by surrounding grey structures.

A new anatomical landmark for reliable identification of human area V5/MT: a quantitative analysis of sulcal patterning.

The location of human area V5 (or MT) has been correlated with the intersection of the ascending limb of the inferior temporal sulcus (ALITS) and the lateral occipital sulcus (LO). This study was undertaken to attempt a replication and quantification of these observations using functional magnetic resonance imaging. V5 was significantly activated in 19 hemispheres with alternating, low contrast, random checkerboard patterns. We confirmed the stereotaxic location of V5 and were able to describe a fairly consistent sulcal pattern in the parieto-temporo-occipital cortex. V5 was usually (95%) buried within a sulcus, most commonly within the inferior temporal sulcus (ITS) (11%), the ascending limb of the ITS (ALITS) (53%) and the posterior continuation of the ITS (26%). The average distance from V5 of two identified anatomical landmarks of V5, the junctions of the LO and the ALITS, and the ITS and ALITS, were both 1 cm. However, the LO-ALITS junction often had to be determined by interpolation (47%), and was not always present even with interpolation (21%). In contrast, the ITS-ALITS junction was always present and V5 was usually (90%) located in a sulcus intersecting with this junction, making it a more reliable landmark for localizing V5 with respect to gross morphological features on individual cortical surfaces.

Statistical sulcal shape comparisons: application to the detection of genetic encoding of the central sulcus shape.

Principal Component Analysis allows a quantitative description of shape variability with a restricted number of parameters (or modes) which can be used to quantify the difference between two shapes through the computation of a modal distance. A statistical test can then be applied to this set of measurements in order to detect a statistically significant difference between two groups. We have applied this methodology to highlight evidence of genetic encoding of the shape of neuroanatomical structures. To investigate genetic constraint, we studied if shapes were more similar within 10 pairs of monozygotic twins than within interpairs and compared the results with those obtained from 10 pairs of dizygotic twins. The statistical analysis was performed using a Mantel permutation test. We show, using simulations, that this statistical test applied on modal distances can detect a possible genetic encoding. When applied to real data, this study highlighted genetic constraints on the shape of the central sulcus. We found from 10 pairs of monozygotic twins that the intrapair modal distance of the central sulcus was significantly smaller than the interpair modal distance, for both the left central sulcus (Z = -2.66; P < 0.005) and the right central sulcus (Z = -2.26; P < 0.05). Genetic constraints on the definition of the central sulcus shape were confirmed by applying the same experiment to 10 pairs of normal young individuals (Z = -1.39; Z = -0.63, i.e., values not significant at the P < 0.05 level) and 10 pairs of dizygotic twins (Z = 0.47; Z = 0.03, i.e., values not significant at the P < 0.05 level).

Automated extraction and variability analysis of sulcal neuroanatomy.

Systematic mapping of the variability in cortical sulcal anatomy is an area of increasing interest which presents numerous methodological challenges. To address these issues, we have implemented sulcal extraction and assisted labeling (SEAL) to automatically extract the two-dimensional (2-D) surface ribbons that represent the median axis of cerebral sulci and to neuroanatomically label these entities. To encode the extracted three-dimensional (3-D) cortical sulcal schematic topography (CSST) we define a relational graph structure composed of two main features: vertices (representing sulci) and arcs (representing the relationships between sulci). Vertices contain a parametric representation of the surface ribbon buried within the sulcus. Points on this surface are expressed in stereotaxic coordinates (i.e., with respect to a standardized brain coordinate system). For each of these vertices, we store length, depth, and orientation as well as anatomical attributes (e.g., hemisphere, lobe, sulcus type, etc.). Each arc stores the 3-D location of the junction between sulci as well as a list of its connecting sulci. Sulcal labeling is performed semiautomatically by selecting a sulcal entity in the CSST and selecting from a menu of candidate sulcus names. In order to help the user in the labeling task, the menu is restricted to the most likely candidates by using priors for the expected sulcal spatial distribution. These priors, i.e., sulcal probabilistic maps, were created from the spatial distribution of 34 sulci traced manually on 36 different subjects. Given these spatial probability maps, the user is provided with the likelihood that the selected entity belongs to a particular sulcus. The cortical structure representation obtained by SEAL is suitable to extract statistical information about both the spatial and the structural composition of the cerebral cortical topography. This methodology allows for the iterative construction of a successively more complete statistical models of the cerebral topography containing spatial distributions of the most important structures, their morphometrics, and their structural components.