The overall goal of the research proposed is to develop and validate a quantitative, multi-parametric set of magnetic resonance imaging (MRI) techniques for the assessment of pathological and functional changes accompanying human peripheral neuropathy in vivo. Quantitative MRI metrics of diffusion (primarily sensitive to axonal structure), magnetization transfer (primarily sensitive to myelin), and multiexponential T2 (primarily sensitive to water compartment sizes) have provided valuable information on tissue microstructure and pathological changes in the brain. However, no studies have applied these methods to study peripheral neuropathies in humans in vivo. This can be attributed to the technical challenges associated with MRI of peripheral nerves, including the need for higher spatial resolution, a lack of contrast on standard anatomical images, and the influence of surrounding fat. We propose to address these technical challenges with a program of innovative, technical developments that will provide a set of multiple MRI parameters for characterizing peripheral nerves that in turn will be evaluated as potential biomarkers of nerve pathology. More specifically, the research proposed would focus on development and validation of robust, clinically feasible, high-resolution, quantitative MRI methods (diffusion, MT, MET2) of tibial (from ankle to knee) and sciatic nerves (from knee to hip) to access the length dependent nature of certain neuropathies. As an initial application, the developed methods will be applied in patients with Charcot-Marie-Tooth disease, a slowly progressing group of inherited neuropathies with well-defined genetic causes. Clinically, CMT is divided on the basis of nerve conduction studies (NCS) into CMT1 (primary demyelination with secondary axonal degeneration) and CMT2 (primary axonal degeneration). Our initial studies will assess the ability of quantitative MRI to detect and distinguish pathology in and between CMT subtypes. For validation, correlations between MRI metrics and clinical measures that report of pathological (NCS, skin biopsy) and functional (neuropathy disability score) changes in CMT patients will also be determined. If successful, these studies may yield biomarkers of treatment responses and tissue status for use in clinical trials and drug discovery. Additionally, the developed methods may have broader implications in a number of other peripheral neuropathies (e.g., diabetic neuropathy) as well as in diseases that affect myelin and/or axons within the central nervous system (e.g., multiple sclerosis).

Public Health Relevance

The overall goal of this research is to develop and validate quantitative magnetic resonance imaging (MRI) techniques to assess diseases that affect the peripheral nervous system, or peripheral neuropathies. To date, no studies have applied quantitative MRI to study peripheral neuropathies in humans in vivo because of the technical challenges associated with imaging peripheral nerves. We propose to address these technical challenges with a program of innovative, technical developments that will provide a set of MRI parameters for characterizing peripheral nerves, which will in turn be evaluated as potential biomarkers of nerve pathology in neuropathy patients.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Mentored Quantitative Research Career Development Award (K25)
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Special Emphasis Panel (ZEB1-OSR-D (J2))
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Erim, Zeynep
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Vanderbilt University Medical Center
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Dortch, Richard D; Bagnato, Francesca; Gochberg, Daniel F et al. (2018) Optimization of selective inversion recovery magnetization transfer imaging for macromolecular content mapping in the human brain. Magn Reson Med 80:1824-1835
Bagnato, Francesca; Hametner, Simon; Franco, Giulia et al. (2018) Selective Inversion Recovery Quantitative Magnetization Transfer Brain MRI at 7T: Clinical and Postmortem Validation in Multiple Sclerosis. J Neuroimaging 28:380-388
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Gore, John C; Zu, Zhongliang; Wang, Ping et al. (2017) ""Molecular"" MR imaging at high fields. Magn Reson Imaging 38:95-100
Smith, Alex K; Dortch, Richard D; Dethrage, Lindsey M et al. (2017) Incorporating dixon multi-echo fat water separation for novel quantitative magnetization transfer of the human optic nerve in vivo. Magn Reson Med 77:707-716
Arlinghaus, Lori R; Dortch, Richard D; Whisenant, Jennifer G et al. (2016) Quantitative Magnetization Transfer Imaging of the Breast at 3.0 T: Reproducibility in Healthy Volunteers. Tomography 2:260-266
Clark, Daniel James; Smith, Alex K; Dortch, Richard D et al. (2016) Investigating hydroxyl chemical exchange using a variable saturation power chemical exchange saturation transfer (vCEST) method at 3 T. Magn Reson Med 76:826-37
Damon, Bruce M; Li, Ke; Dortch, Richard D et al. (2016) Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease. J Vis Exp :
Towse, Theodore F; Elder, Christopher P; Bush, Emily C et al. (2016) Post-contractile BOLD contrast in skeletal muscle at 7?T reveals inter-individual heterogeneity in the physiological responses to muscle contraction. NMR Biomed 29:1720-1728
Whisenant, Jennifer G; Dortch, Richard D; Grissom, William et al. (2016) Bloch-Siegert B1-Mapping Improves Accuracy and Precision of Longitudinal Relaxation Measurements in the Breast at 3 T. Tomography 2:250-259

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