The main goal of this project is to characterize the development of the murine brain, with emphasis on white matter anatomy, using magnetic resonance micro-imaging in conjunction with mathematical methodologies for quantitative image analysis. The traditionally used histological methods for examination of murine brain sections are limited by tissue distortion or loss, by difficulties in constructing a spatially consistent volumetric image from sections, by extensive effort in preparation, and by lack of capability for in vivo examination of the mouse brain. Magnetic resonance imaging (MRI) is emerging as a technology with strengths complementary to histology, with respect to these limitations. In this project, we will develop methods for imaging and analysis of the murine brain, and we will use them to generate normative data for brain development of the C57BL/6J mouse strain. Our emphasis will be on using diffusion tensor imaging (DTI) to characterize the white matter architecture. Building upon current work by several groups in the Human Brain Project, we propose to develop mathematical methodologies for computational anatomy, which complement traditional analysis methods in mainly two ways. First, they can identify very subtle and localized shape characteristics, without the need to know the location of an affected brain region a priori. Second, they are highly automated and quantitative, thus enabling the examination of a large number of animals with minimal effort, using statistical image analysis techniques. Our image analysis methodology will involve shape analysis methods for the reconstruction and spatial normalization of murine brain structures, and it will utilize the well-established framework of stereotaxic space analysis. After mass-preserving spatial normalization of MRI images to a stereotaxic space of the respective developmental stage, the normal anatomic variation of grey and white matter structures will be measured at a number of different developmental stages. This normative data will be useful in subsequent DTI-based studies aiming to identify regions of abnormal development in neurogenetic mice, by finding regions that fall outside this normal range. We will test this methodology on a pilot study of the Emx-1 knockout mouse, a well-characterized strain with abnormal cortical lamination and defasciculated white matter fiber tracts, including the corpus callosum, and we will validate our MR-based measurements using histological sections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH070365-04
Application #
7217544
Study Section
Special Emphasis Panel (ZRG1-SSS-E (55))
Program Officer
Hirsch, Michael D
Project Start
2004-07-15
Project End
2010-03-15
Budget Start
2007-04-01
Budget End
2010-03-15
Support Year
4
Fiscal Year
2007
Total Cost
$485,162
Indirect Cost
Name
University of Pennsylvania
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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