Translational Neuroscience
  1. Title: A Neuroimaging Study of Primate Brain Development and Aging in the Marmoset
    Principal Investigator: Michael Duff Davis, Ph.D.
    Funding: NIH 5R01AG029412-02 Project
    Dates: September 15, 2007 - June 30, 2012

    Progress in the study and treatment of human brain disease in development and aging is facilitated by 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, myelination processes and neurochemical 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 old-world primate species, such as its smaller size, frequent reproductive twinning and simple husbandry. Moreover, a short life span (8-12yrs) makes the marmoset particularly attractive in ontogenetic and aging studies by virtue of its compressed rate of maturation. Validation of this model first requires establishing the temporal course of normal tissue changes from birth through adulthood 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 3 specific aims by, [1] Describing the morphological development of global and regional brain structures through volumetric quantification of whole-brain, gray matter, white-matter, gyri and sulci using T1-weighted anatomical MRI, [2] Profiling white-matter tissue formation by employing multi-parametric T1, T2 and DT MRI, and [3] Defining the cytoarchitectonic microstructure of cortical layers in immature, adult and aged marmoset brains by building a histologically- based stereotaxic atlas to include the taxonomic classification of individual features and labeling of key neurochemical markers. Our overarching hypothesis is that the complex temporal profiles of age-related changes observed with imaging in the human brain will be closely mirrored in the marmoset brain, but with shortened time constants reflecting its shorter life span. The net product will provide several comprehensive, descriptive developmental datasets and a translational neuroimaging toolkit that can be broadly disseminated. The findings should not only expand the methodological armamentaria, but also further validate the marmoset as a valuable, primate subject for modeling human developmental and aging brain disorders, including gestational dysmorphology, multiple sclerosis, Parkinson's and Alzheimer's Disease.

  2. Title: A High-Field (7T) MRI System for Translational Imaging Research
    Principal Investigator: Michael Duff Davis, Ph.D.
    Funding: 1S10RR023038-01
    Date: May 1, 2007 - April 30, 2009

    The objective of this proposal is to seek funding for the purchase of a small-bore, 7T MRI scanner to be installed at the UT Health Science Center at San Antonio (UTHSCSA). Commissioning of this instrument will help resolve a cross-institutional demand for a high-resolution animal MRI. It will serve the regional biomedical academic communities located at the UTHSCSA, the Southwest Foundation for Biomedical Research (SFBR), the Audie Murphy Memorial Veterans Hosp. and the UT San Antonio. An advanced Bruker ClinScan MR system has just emerged on the market and represents a much needed leading-edge technology employing a high-performance pulsed magnetic gradient field and 32-channel parallel RF systems. Driven by a Siemens Syngo consol with IDEAMRI pulse sequencing, this instrument will now enable users to perform such demanding studies as dynamic rodent fMRI and cardiac imaging. Scanning modalities yielding superior spatial and temporal resolution not previously achievable with our existing 2T and 3T human MRI's include anatomical MR microscopy (~100um resolution), BOLD (oxygen utilization), MR spectroscopy, contrast-perfusion MRI (blood flow) and diffusion tensor imaging (white matter connectivity). While this proposal will initially serve the more well-established NIH investigator, these powerful features will undoubtedly attract other investigators to acquire pilot data to fuel new NIH grant submissions. Because this MRI can accommodate a wide variety of animal sizes and species from transgenic mice to non-human primates, as well as necropsied human tissue, we expect to generate interest spanning multiple disciplines such as oncology, aging, neurological and psychiatric disorders. We anticipate that this new tool will act as a catalyst in spawning innovative strategies to solve complex hypotheses. The RII is a department-level unit within the UTHSCSA School of Medicine whose charter is to develop non-invasive imaging for basic preclinical and clinical investigation. It has outstanding facilities dedicated exclusively for research. This includes a recent expansion of its animal imaging core, contiguous with a large animal housing satellite, and has already been site-prepped to accommodate the future installation of a new MRI which would allow it to be brought online relatively quickly. Also conveniently nearby are the Southwest National Primate Research Center (SNPRC) and the SFBR that provide non-human primates and other exotic species for imaging at the RII. Put to use, this new MRI will drive high-caliber translatable research directed at improving our understanding and treatment of human diseases, provide an important training environment and, since its use involves survivable testing, at lesser sacrifice of animal subjects.