MRI OF MARMOSETS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Progress in the study and treatment of human brain disease in development and aging can be greatly facilitated through the use of appropriate research animal models. This proposal seeks to build an extensive primate brain database of the common marmoset (Callithrix jacchus) that will define the evolving changes in anatomical structure, biochemical processes and neuronal activation patterns across the animal's entire life cycle. The marmoset brain is remarkably complex and is an archetype of human neurological and psychiatric disorders, yet has advantages over other old-world primate species such as its smaller size, is shorter-lived (6-12yrs), thereby having a more compressed rate of development and repopulates rapidly. Validation of this model first requires establishing the temporal course of normal tissue changes from birth through maturation and into senescence. Neuroimaging methods offer key advantages of being non-invasive and survivable, supporting an essentially unlimited number of sequential measurements over a prolonged period. Thus we will evaluate neonatal, juvenile, adult and aged marmoset groups in 4 specific aims by: [1] Describing the morphological development of global and regional brain structures by volumetric quantification of whole-brain, gray matter, white matter, gyri and sulci using T1-weighted anatomical magnetic resonance imaging (MRI). [2] Profiling white-matter area formation by employing multi-parametric T1- and T2- weighted MRI. [3] Characterizing gray-matter metabolic patterns in maturation and pruning phases using high-resolution 18F-FDG positron emission tomography (PET). [4] Defining the cytoarchitectonic microstructure of cortical layers and subcortical regions in immature, adult and aged marmoset brains by building a histologically-based stereotaxic atlas to include the taxonomical classification of individual features (e.g., nuclei, white matter tracts). This atlas will also be used to co-register the PET and MRI images for accurate mapping of topographical boundaries and substructures. Our overarching hypothesis is that the complex temporal profiles of age-related changes observed with multi-modality imaging in the human brain will be closely mirrored in the marmoset brain, but with shortened time constants reflecting its shorter life span. Fulfilling this mission will generate several comprehensive, descriptive developmental datasets and a translational neuroimaging toolkit that will be made broadly available to other investigators for application in a variety of biomedical research paradigms.