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Biomedical subjects

Allan MacKenzie-Graham

Publications and source records attributed to Allan MacKenzie-Graham.

4 recordsLinked to original sources

Cerebellar cortical atrophy in experimental autoimmune encephalomyelitis.

Brain atrophy measured by MRI is an important correlate with clinical disability and disease duration in multiple sclerosis (MS). Unfortunately, neuropathologic mechanisms which lead to this grey matter atrophy remain unknown. The objective of this study was to determine whether brain atrophy occurs in the mouse model, experimental autoimmune encephalomyelitis (EAE). Postmortem high-resolution T2-weighted magnetic resonance microscopy (MRM) images from 32 mouse brains (21 EAE and 11 control) were collected. A minimum deformation atlas was constructed and a deformable atlas approach was used to quantify volumetric changes in neuroanatomical structures. A significant decrease in the mean cerebellar cortex volume in mice with late EAE (48-56 days after disease induction) as compared to normal strain, gender, and age-matched controls was observed. There was a direct correlation between cerebellar cortical atrophy and disease duration. At an early time point in disease, 15 days after disease induction, cerebellar white matter lesions were detected by both histology and MRM. These data demonstrate that myelin-specific autoimmune responses can lead to grey matter atrophy in an otherwise normal CNS. The model described herein can now be used to investigate neuropathologic mechanisms that lead to the development of gray matter atrophy in this setting.

Animals↗

LONI visualization environment.

Over the past decade, the use of informatics to solve complex neuroscientific problems has increased dramatically. Many of these research endeavors involve examining large amounts of imaging, behavioral, genetic, neurobiological, and neuropsychiatric data. Superimposing, processing, visualizing, or interpreting such a complex cohort of datasets frequently becomes a challenge. We developed a new software environment that allows investigators to integrate multimodal imaging data, hierarchical brain ontology systems, on-line genetic and phylogenic databases, and 3D virtual data reconstruction models. The Laboratory of Neuro Imaging visualization environment (LONI Viz) consists of the following components: a sectional viewer for imaging data, an interactive 3D display for surface and volume rendering of imaging data, a brain ontology viewer, and an external database query system. The synchronization of all components according to stereotaxic coordinates, region name, hierarchical ontology, and genetic labels is achieved via a comprehensive BrainMapper functionality, which directly maps between position, structure name, database, and functional connectivity information. This environment is freely available, portable, and extensible, and may prove very useful for neurobiologists, neurogenetisists, brain mappers, and for other clinical, pedagogical, and research endeavors.

Brain Mapping↗

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↗

The informatics of a C57BL/6J mouse brain atlas.

The Mouse Atlas Project (MAP) aims to produce a framework for organizing and analyzing the large volumes of neuroscientific data produced by the proliferation of genetically modified animals. Atlases provide an invaluable aid in understanding the impact of genetic manipulations by providing a standard for comparison. We use a digital atlas as the hub of an informatics network, correlating imaging data, such as structural imaging and histology, with text-based data, such as nomenclature, connections, and references. We generated brain volumes using magnetic resonance microscopy (MRM), classical histology, and immunohistochemistry, and registered them into a common and defined coordinate system. Specially designed viewers were developed in order to visualize multiple datasets simultaneously and to coordinate between textual and image data. Researchers can navigate through the brain interchangeably, in either a text-based or image-based representation that automatically updates information as they move. The atlas also allows the independent entry of other types of data, the facile retrieval of information, and the straight-forward display of images. In conjunction with centralized servers, image and text data can be kept current and can decrease the burden on individual researchers' computers. A comprehensive framework that encompasses many forms of information in the context of anatomic imaging holds tremendous promise for producing new insights. The atlas and associated tools can be found at http://www.loni.ucla.edu/MAP.

Anatomy, Artistic↗