Comprehending the appearance of structure in the developing brain is central to an understanding of its function, yet imaging the key events with any single technique is difficult because the events take place over a wide range of spatial and temporal scales. No one imaging technique combines the needed spatial resolution, field of view temporal resolution, and depth of penetration to follow brain development. The goal of the work proposed is two-fold: 1. To meld the complementary imaging modalities of two-photon laser scanning (TPLS) and magnetic resonance imaging (MRI) microscopies to provide coherent four dimensional (3 space and 1 time) information on the emergence of and changes in biological order. The applicant proposes to capitalize on the strengths of each technique and maximize the quality of the resulting data by integrating the imaging modalities at both the experimental and analysis levels; and 2. To apply this melded technology to follow cell lineages and tissue movements that contribute to morphogenesis of avian forebrain. The experimental aim is to directly test hypotheses that lineage restrictions at neuromere boundaries generate regionalization in the forebrain. Implementing the technology within the context of this problem will assure that the technological developments are truly applicable to brain science by driving them with actual research needs. The research plan will entail technological developments in three specific areas: 1.) Hardware and protocols for time course imaging of the same samples with both TPLS and MRI microscopies; 2.) Cellular labels and labeling techniques that are bifunctional, generating image contrast in both modalities; and 3.) Computational tools for combining the image sequences from each modality into an integrated rendering. Although this combination of TPLS and MR imaging will be directed at brain development, the approach is general and the multimodal imaging instrumentation tools will be readily applicable to other problems in neuroscience and biomedical research.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Project (R01)
Project #
5R01RR013625-03
Application #
6188781
Study Section
Diagnostic Imaging Study Section (DMG)
Program Officer
Levy, Abraham
Project Start
1998-09-30
Project End
2003-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
3
Fiscal Year
2000
Total Cost
$370,895
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
078731668
City
Pasadena
State
CA
Country
United States
Zip Code
91125
Tyszka, J Michael; Readhead, Carol; Bearer, Elaine L et al. (2006) Statistical diffusion tensor histology reveals regional dysmyelination effects in the shiverer mouse mutant. Neuroimage 29:1058-65
Martin, Melanie; Hiltner, Timothy D; Wood, John C et al. (2006) Myelin deficiencies visualized in vivo: visually evoked potentials and T2-weighted magnetic resonance images of shiverer mutant and wild-type mice. J Neurosci Res 84:1716-26
Tyszka, J Michael; Ewald, Andrew J; Wallingford, John B et al. (2005) New tools for visualization and analysis of morphogenesis in spherical embryos. Dev Dyn 234:974-83
Pautler, Robia G; Mongeau, Raymond; Jacobs, Russell E (2003) In vivo trans-synaptic tract tracing from the murine striatum and amygdala utilizing manganese enhanced MRI (MEMRI). Magn Reson Med 50:33-9
Alauddin, Mian M; Louie, Angelique Y; Shahinian, Antranik et al. (2003) Receptor mediated uptake of a radiolabeled contrast agent sensitive to beta-galactosidase activity. Nucl Med Biol 30:261-5
Sadun, Alfredo A; Carelli, Valerio; Bose, Swaraj et al. (2002) First application of extremely high-resolution magnetic resonance imaging to study microscopic features of normal and LHON human optic nerve. Ophthalmology 109:1085-91
Dhenain, Marc; Privat, Nicolas; Duyckaerts, Charles et al. (2002) Senile plaques do not induce susceptibility effects in T2*-weighted MR microscopic images. NMR Biomed 15:197-203
Sendhil Velan, S; Narasimhan, P T; Jacobs, R E (2001) MR imaging with phase encoding of intermolecular multiple quantum coherences. J Magn Reson 152:189-94
Ahrens, E T; Dubowitz, D J (2001) Peripheral somatosensory fMRI in mouse at 11.7 T. NMR Biomed 14:318-24
Neusch, C; Rozengurt, N; Jacobs, R E et al. (2001) Kir4.1 potassium channel subunit is crucial for oligodendrocyte development and in vivo myelination. J Neurosci 21:5429-38

Showing the most recent 10 out of 13 publications