Magnetic resonance imaging (MRI) is a uniquely informative soft tissue imaging modality with contrast that is sensitive to a myriad of physical, chemical, and functional characteristics of tissue but often lacks specificity. On the spatial scale relevant to water proton (1H) nuclear magnetic resonance (NMR), tissues are heterogeneous and, consequently, exhibit an NMR signal that is the complex summation of spatially varying characteristics. Most MRI protocols provide contrast between tissues that can be resolved spatially, but yield little or no quantitative information about the variation in NMR signal that exists on a smaller scale, that is, the sub-voxel scale. This quantitative sub-voxel information is alluring because it provides specificity to tissue micro-anatomy. Development of quantitative sub-voxel MRI tissue characterization requires coordinated advancement on two fronts: 1) quantitative models that relate relevant micro-anatomical characteristics to 1H NMR signal characteristics, and 2) practical and effective quantitative MRI methods that can translate these the use of sub-voxel tissue models to widespread utility for researchers and clinicians. The proposed studies address both modeling and method development with the aim to develop practical and quantitative imaging biomarkers for micro-anatomical characteristics of white matter and skeletal muscle, including 1) myelin volume fraction and myelin thickness in normal, developing, and abnormally developing white matter, and 2) myofiber volume fraction and size, in the presence of inflammation and fibrosis. Such biomarkers have the potential to impact research and clinical diagnostics by providing quantitative and specific measures to track changes in disorders associated with abnormal white matter development, such as Schizophrenia and Autism, as well muscle injuries and diseases such as Muscular Dystrophy.

Public Health Relevance

MRI is a widespread diagnostic imaging modality capable of relatively non-invasive visualization of soft tissue. The contrast in MRI results from many complex interactions of water molecules in the body with each other and the physical and chemical characteristics of their local environments. This research program aims to better relate MRI contrast to specific micro-anatomical characteristics in neural tissue and skeletal muscle. This work has broad potential impact the diagnostic and prognostic capabilities of MRI for a wide array of diseases and injuries.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01EB001744-10
Application #
8705514
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Liu, Guoying
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
City
Nashville
State
TN
Country
United States
Zip Code
37212
Lankford, Christopher L; Dortch, Richard D; Does, Mark D (2015) Fast T2 mapping with multiple echo, Caesar cipher acquisition and model-based reconstruction. Magn Reson Med 73:1065-74
Harkins, Kevin D; Horch, R Adam; Does, Mark D (2015) Simple and robust saturation-based slice selection for ultrashort echo time MRI. Magn Reson Med 73:2204-11
Bryant, Nathan D; Li, Ke; Does, Mark D et al. (2014) Multi-parametric MRI characterization of inflammation in murine skeletal muscle. NMR Biomed 27:716-25
Hormuth 2nd, David A; Skinner, Jack T; Does, Mark D et al. (2014) A comparison of individual and population-derived vascular input functions for quantitative DCE-MRI in rats. Magn Reson Imaging 32:397-401
Xu, Junzhong; Li, Hua; Harkins, Kevin D et al. (2014) Mapping mean axon diameter and axonal volume fraction by MRI using temporal diffusion spectroscopy. Neuroimage 103:10-9
Harkins, Kevin D; Does, Mark D; Grissom, William A (2014) Iterative method for predistortion of MRI gradient waveforms. IEEE Trans Med Imaging 33:1641-7
Lankford, Christopher L; Does, Mark D (2013) On the inherent precision of mcDESPOT. Magn Reson Med 69:127-36
Nyman, Jeffry S; Gorochow, Lacey E; Adam Horch, R et al. (2013) Partial removal of pore and loosely bound water by low-energy drying decreases cortical bone toughness in young and old donors. J Mech Behav Biomed Mater 22:136-45
Janve, Vaibhav A; Zu, Zhongliang; Yao, Song-Yi et al. (2013) The radial diffusivity and magnetization transfer pool size ratio are sensitive markers for demyelination in a rat model of type III multiple sclerosis (MS) lesions. Neuroimage 74:298-305
Harkins, Kevin D; Dula, Adrienne N; Does, Mark D (2012) Effect of intercompartmental water exchange on the apparent myelin water fraction in multiexponential T2 measurements of rat spinal cord. Magn Reson Med 67:793-800

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