This proposal aims to develop 3D anatomical analysis tools of the developing mouse brain, combining the 3D alignment precision of MRI imaging and the higher resolution of serial histological section images. The special new features of the MRI imaging will be the implementation of diffusion tensor imaging (DTI), a new type of MRI that can provide unique image contrast based on measurement of water diffusion. Since water tends to diffuse along oriented structures within a volume, DTI serves effectively to delineate various early structures within the brain. This is a particularly important technical advance for the immature brain which has not yet formed myelin, because the brain at these stages of development has little intrinsic contrast detectable by conventional MRI. In this proposal, we will focus on development of technologies and databases that will be essential components for the long-term goal through the following four aims. First, MRI-based database of developing embryo and neonates will be acquired from days 11 to 19 of gestation, at 3-day intervals postnatally to day 21, and weekly thereafter to 12 weeks of age. Second, the slowness of acquisition of the very large datasets accessible by DTI will be offset by combination of a modified fast spin echo technique that will reduce acquisition time by a factor of 8, and parallel imaging that will reduce the time factor by 2. Third, a large series of serially-sectioned and stained mouse brains at all stages from embryonic day 11 to adulthood are available, and section images will be digitally captured and elastically warped to the MRI standards, based on common anatomical landmarks. From this study, MR-visible structures will be identified and assigned. Then the aligned MRI and histological images will be segmented into cell groups and axonal tracts by a combination of automated """"""""seeding"""""""" algorithms and """"""""neuroanatomical expert"""""""" hand-tracing of contours by modifications of Unix-based 3D software that we have developed for the adult mouse brain. Finally, tools for computational neuroanatomy will be developed for reliable quantitative measures of morphological differences between specimens. This project was made possible through collaboration with Drs. Moil (MRI), Sidman (neuroanatomy), and Miller (computational neuroanatomy).

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB003543-03
Application #
7102803
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Cohen, Zohara
Project Start
2004-09-30
Project End
2008-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
3
Fiscal Year
2006
Total Cost
$502,356
Indirect Cost
Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Aggarwal, Manisha; Gobius, Ilan; Richards, Linda J et al. (2015) Diffusion MR Microscopy of Cortical Development in the Mouse Embryo. Cereb Cortex 25:1970-80
Wu, Dan; Reisinger, Dominik; Xu, Jiadi et al. (2014) Localized diffusion magnetic resonance micro-imaging of the live mouse brain. Neuroimage 91:12-20
Aggarwal, Manisha; Burnsed, Jennifer; Martin, Lee J et al. (2014) Imaging neurodegeneration in the mouse hippocampus after neonatal hypoxia-ischemia using oscillating gradient diffusion MRI. Magn Reson Med 72:829-40
Carver, Alissa R; Andrikopoulou, Maria; Lei, Jun et al. (2014) Maternal pravastatin prevents altered fetal brain development in a preeclamptic CD-1 mouse model. PLoS One 9:e100873
Dada, Tahani; Rosenzweig, Jason M; Al Shammary, Mofeedah et al. (2014) Mouse model of intrauterine inflammation: sex-specific differences in long-term neurologic and immune sequelae. Brain Behav Immun 38:142-50
Miller, Michael I; Younes, Laurent; Trouvé, Alain (2014) Diffeomorphometry and geodesic positioning systems for human anatomy. Technology (Singap World Sci) 2:36
Wu, Dan; Xu, Jiadi; McMahon, Michael T et al. (2013) In vivo high-resolution diffusion tensor imaging of the mouse brain. Neuroimage 83:18-26
Aggarwal, Manisha; Zhang, Jiangyang; Pletnikova, Olga et al. (2013) Feasibility of creating a high-resolution 3D diffusion tensor imaging based atlas of the human brainstem: a case study at 11.7 T. Neuroimage 74:117-27
Li, Xin; Aggarwal, Manisha; Hsu, Johnny et al. (2013) AtlasGuide: software for stereotaxic guidance using 3D CT/MRI hybrid atlases of developing mouse brains. J Neurosci Methods 220:75-84
Ratnanather, J Tilak; Lal, Rakesh M; An, Michael et al. (2013) Cortico-cortical, cortico-striatal, and cortico-thalamic white matter fiber tracts generated in the macaque brain via dynamic programming. Brain Connect 3:475-90

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