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Large-scale genomic studies have recently identified genetic variants causative for major neurodevelopmental disorders, such as intellectual disability and autism. However, determining how underlying developmental processes are affected by these mutations remains a significant challenge in the field. Zebrafish is an established model system in developmental neurogenetics that may be useful in uncovering the mechanisms of these mutations. Here we describe the use of voxel-intensity, deformation field, and volume-based morphometric techniques for the systematic and unbiased analysis of gene knock-down and environmental exposure-induced phenotypes in zebrafish. We first present a computational method for brain segmentation based on transgene expression patterns to create a comprehensive neuroanatomical map. This map allowed us to disclose statistically significant changes in brain microstructure and composition in neurodevelopmental models. We demonstrate the effectiveness of morphometric techniques in measuring changes in the relative size of neuroanatomical subdivisions in atoh7 morphant larvae and in identifying phenotypes in larvae treated with valproic acid, a chemical demonstrated to increase the risk of autism in humans. These tools enable rigorous evaluation of the effects of gene mutations and environmental exposures on neural development, providing an entry point for cellular and molecular analysis of basic developmental processes as well as neurodevelopmental and neurodegenerative disorders.
Pubmed ID: 29936090 RIS Download
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Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on January 11, 2023. Software package designed to enable researchers with advanced tools for brain and image mapping. Many of the ANTS registration tools are diffeomorphic*, but deformation (elastic and BSpline) transformations are available. Unique components of ANTS include multivariate similarity metrics, landmark guidance, the ability to use label images to guide the mapping and both greedy and space-time optimal implementations of diffeomorphisms. The symmetric normalization (SyN) strategy is a part of the ANTS toolkit as is directly manipulated free form deformation (DMFFD). *Diffeomorphism: a differentiable map with differentiable inverse. In general, these maps are generated by integrating a time-dependent velocity field. ANTS Applications: * Gray matter morphometry based on the jacobian and/or cortical thickness. * Group and single-subject optimal templates. * Multivariate DT + T1 brain templates and group studies. * Longitudinal brain mapping -- special similarity metric options. * Neonatal and pediatric brain segmentation. * Pediatric brain mapping. * T1 brain mapping guided by tractography and connectivity. * Diffusion tensor registration based on scalar or connectivity data. * Brain mapping in the presence of lesions. * Lung and pulmonary tree registration. * User-guided hippocampus labeling, also of sub-fields. * Group studies and statistical analysis of cortical thickness, white matter volume, diffusion tensor-derived metrics such as fractional anisotropy and mean diffusion.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on January 11, 2023. Software package designed to enable researchers with advanced tools for brain and image mapping. Many of the ANTS registration tools are diffeomorphic*, but deformation (elastic and BSpline) transformations are available. Unique components of ANTS include multivariate similarity metrics, landmark guidance, the ability to use label images to guide the mapping and both greedy and space-time optimal implementations of diffeomorphisms. The symmetric normalization (SyN) strategy is a part of the ANTS toolkit as is directly manipulated free form deformation (DMFFD). *Diffeomorphism: a differentiable map with differentiable inverse. In general, these maps are generated by integrating a time-dependent velocity field. ANTS Applications: * Gray matter morphometry based on the jacobian and/or cortical thickness. * Group and single-subject optimal templates. * Multivariate DT + T1 brain templates and group studies. * Longitudinal brain mapping -- special similarity metric options. * Neonatal and pediatric brain segmentation. * Pediatric brain mapping. * T1 brain mapping guided by tractography and connectivity. * Diffusion tensor registration based on scalar or connectivity data. * Brain mapping in the presence of lesions. * Lung and pulmonary tree registration. * User-guided hippocampus labeling, also of sub-fields. * Group studies and statistical analysis of cortical thickness, white matter volume, diffusion tensor-derived metrics such as fractional anisotropy and mean diffusion.
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