The emergence of diffusion tensor imaging (DTI) provides a unique means via water diffusion characteristics to investigate the white matter integrity in the human brain and its impact on neuronal functions. Over the past ten years, DTI has seen gradually increased utility in its application in clinical diagnosis. However, the characterization of white matter integrity using DTI, as it stands today, often lacks tissue specificity. For example, one of the most commonly used quantitative indices, the fractional anisotropy (FA), can be the composite result of multiple sources in axons and myelin. As such, the changes in FA (as well as the related axial and radial diffusivity) often cannot be clearly attributed to a particular origin. In an effort to achieve tissue specificity for DTI, and given the crucial role of myelin in brain maturation and development, we propose to develop a new acquisition technique that can differentiate white matter microstructural changes with sensitivity and specificity to myelin, and make plans to demonstrate its applicability in translational human applications. Specifically, we propose a progressive research plan to: 1) develop a parallel spiral acquisition sequence for high SNR, spatial accuracy and low motion sensitivity using k-space acquisition in sparse matrix (kSPA) and energy spectrum analysis (KESA);2) develop a magnetization transfer contrast prepared, stimulated-echo DTI to sensitively image myelin microstructure and validate the myelin selectivity in vitro;3) validate the myelin-specific DTI in vivo in multiple sclerosis, and carry out initial application in pediatric brains to optimize a comprehensive DTI protocol and evaluate its potentially large impact in pediatric developmental neuroimaging. Because this methodology can help specifically quantify the microstructural changes, in addition to the content, of the myelin, a successful completion of this project can have a direct and immediate impact on better understanding the myelination process during healthy brain maturation, as well as the demyelination process in disease and during aging, thereby leading to wider applications in developmental and clinical neurosciences.

Public Health Relevance

Recent emergence of diffusion tensor imaging (DTI) provides researchers a new means to investigate white matter structure through water diffusional characteristics. However, the resultant maps on diffusion anisotropy often lacks tissue specificity, leading to inconclusive assessment of white matter changes and their impact on brain disorders. We propose here a new DTI technique that can differentiate the microstructural, in addition to the content, changes in myelin from that in axon within the white matter, thereby improving the understanding of their respective roles in brain maturation in developmental brains. A successful completion of this project will greatly improve the tissue specificity of the current DTI methodology, broadening its clinical applicability in developmental neuroimaging.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS065344-01A1
Application #
7739624
Study Section
Neurotechnology Study Section (NT)
Program Officer
Babcock, Debra J
Project Start
2009-06-01
Project End
2011-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
1
Fiscal Year
2009
Total Cost
$195,000
Indirect Cost
Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Truong, Trong-Kha; Chen, Nan-kuei; Song, Allen W (2012) Inherent correction of motion-induced phase errors in multishot spiral diffusion-weighted imaging. Magn Reson Med 68:1255-61
Madden, David J; Bennett, Ilana J; Burzynska, Agnieszka et al. (2012) Diffusion tensor imaging of cerebral white matter integrity in cognitive aging. Biochim Biophys Acta 1822:386-400
Chen, Nan-Kuei; Avram, Alexandru V; Song, Allen W (2011) Two-dimensional phase cycled reconstruction for inherent correction of echo-planar imaging Nyquist artifacts. Magn Reson Med 66:1057-66
Truong, Trong-Kha; Chen, Nan-kuei; Song, Allen W (2011) Dynamic correction of artifacts due to susceptibility effects and time-varying eddy currents in diffusion tensor imaging. Neuroimage 57:1343-7
Truong, Trong-Kha; Chen, Nan-Kuei; Song, Allen W (2010) Application of k-space energy spectrum analysis for inherent and dynamic B0 mapping and deblurring in spiral imaging. Magn Reson Med 64:1121-7
Avram, Alexandru V; Guidon, Arnaud; Song, Allen W (2010) Myelin water weighted diffusion tensor imaging. Neuroimage 53:132-8