The long-term objective of this research is to develop clinical tools which can be used to effectively evaluate new treatments for multiple sclerosis (MS). There are many new proposed treatments for MS which involve immunotherapy, oral tolerance, and alternative medicine techniques. These treatments need to be tested in animals and humans. Currently, there is a need for non-invasive techniques which can be used to differentiate acute and chronic brain damage as well as functional versus non-functional brain damage in MS patients. This project will be accomplished by sequentially and noninvasively evaluating anatomical, biochemical and functional properties of central nervous system tissue using 1) MR imaging, 2) echoplanar spectroscopic imaging (EPSI), which can be used to measure brain chemicals sensitive to neuronal and membrane damage, 3) electrophysiology, which can be used to measure nerve conduction amplitude and velocity, and 4) neurologic exams, which can be used to measure the Expanded Disability Stats Scale and Ambulatory Index. These exams will be performed on patients with remitting-relapsing MS, chronic progressive MS, MS patients receiving beta-interferon, and normal volunteers. With MS, lesions can occur in many places in the brain (i.e. brain stem, cerebrum, cerebellum) and it would be important to use multi-slice techniques for both MRI and spectroscopy in order to assess the progression of MS. Therefore, we are proposing to use EPSI to cover a large portion of the brain to measure metabolite changes in MS patients. In order to develop EPSI as an endpoint in testing new treatments for MS, we will correlate the electrophysiologic properties and clinical symptoms that accompany the biochemical changes measured by spectroscopy at several different times during a one year period. This correlation would be important in gaining a better understanding of the relationship between the nerve conduction and N-acetyl aspartate, a marker for neuronal damage.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS030722-04
Application #
2268694
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1992-04-01
Project End
1998-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
4
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Washington
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Richards, T L; Dager, S R; Posse, S (1998) Functional MR spectroscopy of the brain. Neuroimaging Clin N Am 8:823-34
Gardner, J C; Yazdani, F (1998) Correlating MR lesions and functional deficits in multiple sclerosis patients. Anatomical atlas registration. Phys Med Rehabil Clin N Am 9:569-86, vi
Richards, T L; Lappin, M S; Lawrie, F W et al. (1998) Bioelectromagnetic applications for multiple sclerosis. Phys Med Rehabil Clin N Am 9:659-74
Heide, A C; Kraft, G H; Slimp, J C et al. (1998) Cerebral N-acetylaspartate is low in patients with multiple sclerosis and abnormal visual evoked potentials. AJNR Am J Neuroradiol 19:1047-54
Posse, S; Dager, S R; Richards, T L et al. (1997) In vivo measurement of regional brain metabolic response to hyperventilation using magnetic resonance: proton echo planar spectroscopic imaging (PEPSI). Magn Reson Med 37:858-65
Korenberg, M J; Sakai, H M; Naka, K I (1997) Complexity and frequency hierarchies in the catfish retina. Front Med Biol Eng 8:87-107
Richards, T L; Lappin, M S; Acosta-Urquidi, J et al. (1997) Double-blind study of pulsing magnetic field effects on multiple sclerosis. J Altern Complement Med 3:21-9
Rose, L M; Richards, T L; Peterson, J et al. (1997) Resolution of CNS lesions following treatment of experimental allergic encephalomyelitis in macaques with monoclonal antibody to the CD18 leukocyte integrin. Mult Scler 2:259-66
Richards, T L; Alvord Jr, E C; Peterson, J et al. (1995) Experimental allergic encephalomyelitis in non-human primates: MRI and MRS may predict the type of brain damage. NMR Biomed 8:49-58
Jimenez, J V; Richards, T L; Heide, A C et al. (1995) Incorporation of a phosphonium analogue of choline into the rat brain as measured by magnetic resonance spectroscopy. Magn Reson Med 33:285-92

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