This Award will allow the candidate to have the protected time necessary to focus on new and emerging MRI-based research projects in MS and provide an opportunity to become well-grounded in new areas of study relevant to his research field. Under the guidance of his mentor, co-mentor and Research Advisory Committee, the candidate will develop independent research skills and abilities in longitudinal clinical investigations and advanced magnetic resonance techniques, including diffusion tensor imaging. This mentored training experience will lead to his establishment as an independent, patient-oriented translational investigator in the following years. Multiple Sclerosis (MS) is an inflammatory disorder of the central nervous system which leads to tissue destruction and brain atrophy. Magnetic resonance (MRI) technology allows direct visualization of ongoing disease processes and has been useful in following patients over time and evaluating therapeutic interventions. We will apply advanced magnetic resonance techniques to multiple sclerosis patients in longitudinal clinical studies in order to better understand MS pathogenesis and the effects of therapeutic interventions.
Aim 1 will evaluate if the short-term changes in measures of brain atrophy induced by corticosteroid infusions correlate with the subsequent rate of disease progression. We hypothesize that the short-term decline in brain parenchymal fraction (BPF) following intravenous methylprednisolone predicts increased subsequent disease progression.
In Aim 2 we will describe the diffusion tensor characteristics of multiple sclerosis brain lesions recovering from acute inflammation. This project will lead to greater insights into sensitive monitoring strategies of the pathologic process of brain tissue injury during the course of MS. These insights should lead to methods to provide for more accurate advice to MS patients in the early stages of disease, for better therapeutic decision making, and for monitoring therapeutic responses in individual MS patients. Furthermore, these studies should help develop improved methods for evaluating new therapeutic strategies for neuroprotection and neuroregeneration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23NS047211-05
Application #
7479117
Study Section
NST-2 Subcommittee (NST)
Program Officer
Utz, Ursula
Project Start
2004-08-02
Project End
2009-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
5
Fiscal Year
2008
Total Cost
$169,503
Indirect Cost
Name
Cleveland Clinic Lerner
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195
Ontaneda, Daniel; Sakaie, Ken; Lin, Jian et al. (2014) Identifying the start of multiple sclerosis injury: a serial DTI study. J Neuroimaging 24:569-576
Fox, R J; Sakaie, K; Lee, J-C et al. (2012) A validation study of multicenter diffusion tensor imaging: reliability of fractional anisotropy and diffusivity values. AJNR Am J Neuroradiol 33:695-700
Fox, R J; Cronin, T; Lin, J et al. (2011) Measuring myelin repair and axonal loss with diffusion tensor imaging. AJNR Am J Neuroradiol 32:85-91
Bermel, Robert A; Rae-Grant, Alexander D; Fox, Robert J (2010) Diagnosing multiple sclerosis at a later age: more than just progressive myelopathy. Mult Scler 16:1335-40
Fox, R J; Kivisakk, P; Fisher, E et al. (2008) Multiple sclerosis: chemokine receptor expression on circulating lymphocytes in correlation with radiographic measures of tissue injury. Mult Scler 14:1036-43
Fox, Robert J (2008) Picturing multiple sclerosis: conventional and diffusion tensor imaging. Semin Neurol 28:453-66
Fox, R J; Lee, J-C; Rudick, R A (2007) Optimal reference population for the multiple sclerosis functional composite. Mult Scler 13:909-14
Fox, Robert J; Kivisakk, Pia; Lee, Jar-Chi et al. (2006) Chemokine receptors as biomarkers in multiple sclerosis. Dis Markers 22:227-33
Pelfrey, Clara M; Cotleur, Anne C; Zamor, Natacha et al. (2006) Immunological studies of mitoxantrone in primary progressive MS. J Neuroimmunol 175:192-9
Fox, Robert J; Bethoux, Francois; Goldman, Myla D et al. (2006) Multiple sclerosis: advances in understanding, diagnosing, and treating the underlying disease. Cleve Clin J Med 73:91-102

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