Diffusion Magnetic Resonance Imaging (MRI) is a non-invasive technique for assessing white matter microstructure and long range neuronal connectivity in the brain. It is well known that diffusion tensor imaging (DTI) is sensitive to changes in tissue structure in a wide range of neurological and psychiatric diseases, in many cases detecting changes that are not visible with other imaging methods. In addition, DTI tractography has been used to reconstruct the pathways of major fiber bundles in the living brain and often shows excellent qualitative agreement with expected white matter anatomy, based on dissections of the human brain. While these applications of diffusion MRI are promising, there have been few studies that relate diffusion MRI measurements to the cellular properties they putatively represent. Currently, diffusion anisotropy is thought to reflect axon 'integrity'and/or 'coherence'in white matter. These concepts have no quantitative definition and their relation to actual axon properties have not been established. This project aims to test the correspondence between diffusion MRI and the distribution of myelinated fibers in the primate brain. Specifically, aim 1 involves developing improved methods for comparing axon fiber orientation measurements from diffusion MRI and light microscopy. In addition, the accuracy of spatial registration of the MRI and microscopy data will be quantified.
In aim 2, the principal diffusivities and directions obtained with DTI will be compared to the angular distribution of axon fibers determined from myelin stained tissue sections. Further, MR fiber tracking will be compared to the gold standard of fiber tracts defined using neuroanatomical tracers. These tests will be performed in several of the major motor pathways (e.g., commisural, association, and projection pathways). As a specific application, the ability of DTI to localize and characterize the subthalamic nucleus and surrounding tissues will be tested. The results will inform current efforts to use DTI in the planning, placement, and programing of deep brain stimulators in humans.
In aim 3, the potential advantages of high angular resolution diffusion imaging (HARDI) will be tested by similar comparisons to the true axon orientation distributions and fiber tracts in motor pathways (determined by light microscopy). In summary, this project will test common assumptions about the information provided by diffusion tensor imaging and high angular resolution diffusion imaging, and therefore provide a better basis for intrepreting and improving measurements made with these techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS058639-02
Application #
7537172
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Babcock, Debra J
Project Start
2007-12-15
Project End
2011-11-30
Budget Start
2008-12-01
Budget End
2009-11-30
Support Year
2
Fiscal Year
2009
Total Cost
$327,177
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Schilling, Kurt G; Gao, Yurui; Christian, Matthew et al. (2018) A Web-Based Atlas Combining MRI and Histology of the Squirrel Monkey Brain. Neuroinformatics :
Schilling, Kurt; Gao, Yurui; Janve, Vaibhav et al. (2018) Confirmation of a gyral bias in diffusion MRI fiber tractography. Hum Brain Mapp 39:1449-1466
Schilling, Kurt G; Gao, Yurui; Li, Muwei et al. (2018) Functional tractography of white matter by high angular resolution functional-correlation imaging (HARFI). Magn Reson Med :
Parvathaneni, Prasanna; Nath, Vishwesh; Blaber, Justin A et al. (2018) Empirical reproducibility, sensitivity, and optimization of acquisition protocol, for Neurite Orientation Dispersion and Density Imaging using AMICO. Magn Reson Imaging 50:96-109
Hainline, Allison E; Nath, Vishwesh; Parvathaneni, Prasanna et al. (2018) Empirical single sample quantification of bias and variance in Q-ball imaging. Magn Reson Med 80:1666-1675
Gao, Yurui; Schilling, Kurt G; Stepniewska, Iwona et al. (2018) Tests of cortical parcellation based on white matter connectivity using diffusion tensor imaging. Neuroimage 170:321-331
Gao, Yurui; Schilling, Kurt G; Stepniewska, Iwona et al. (2018) Tests of clustering thalamic nuclei based on various dMRI models in the squirrel monkey brain. Proc SPIE Int Soc Opt Eng 10578:
Schilling, Kurt G; Janve, Vaibhav; Gao, Yurui et al. (2018) Histological validation of diffusion MRI fiber orientation distributions and dispersion. Neuroimage 165:200-221
Schilling, Kurt G; Nath, Vishwesh; Blaber, Justin A et al. (2017) Empirical consideration of the effects of acquisition parameters and analysis model on clinically feasible q-ball imaging. Magn Reson Imaging 40:62-74
Schilling, Kurt; Gao, Yurui; Stepniewska, Iwona et al. (2017) Reproducibility and variation of diffusion measures in the squirrel monkey brain, in vivo and ex vivo. Magn Reson Imaging 35:29-38

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