Contrast-enhanced magnetic resonance imaging (MRI) is becoming increasingly important in the evaluation of multiple sclerosis (MS) based on its sensitivity to acute, often subclinical events in the brain and its ability to measure the accumulation of the disease over time. However, to date there are conflicting reports concerning the number and volume of these lesions, """"""""the load of the disease"""""""" and the neurological severity. To resolve these conflicts, recent studies employed proton (1H) magnetic resonance spectroscopy (MRS) to investigate the lesions underlying metabolism. They showed that it may be possible to assess the irreversibility of central nervous system injury, discern between edematous and demyelination lesions and (perhaps) predict the time course of their evolution. However, these studies employed the current art of single voxel or small 2D arrays of few tens voxels, which, due to their limited observable volume(s) of interest, must be image-guided onto the pathologies of interest. This restricted them to the study of (i) MRI detectable existing lesions; and (ii) few foci in a single clinical session due to time and voxel-size constraints. The applicants proposed to overcome both these problems with their new three dimensional (3D) 1H-MRS hybrids to achieve simultaneous coverage of most the white-matter volume in clinically feasible time: ~45 min. The 3D hybrids yield ~1000 high resolution, <0.8 cm3 , voxels per exam from 0.5-0.75 liter of brain tissue. Such extensive coverage will enable us to examine: (i) whether lesions develop in white matter regions which are already metabolically abnormal; and (ii) whether 1H-MRS-detected local metabolic changes, primarily neuronal loss in conjunction with demyelination, can predict the onset of a lesion before contrast-enhanced MRI, determining its type and course. These two hypotheses will be investigated by following cohort of 12 relapsing-remitting MS patients over three years with 3D 1H-MRS every 3 months. The MRS data will be compared with (i) localized 1H metabolic levels in age, sex and race matched healthy volunteers; (ii) the contrast enhanced MRI which they undergo every 6 months during that period; and (iii) their own previous local metabolic levels. The 1H-MRS data will be obtained both at the highest, 4 Tesla, magnetic field approved for human use, for maximal sensitivity and at the common clinical filed of 1.5 Tesla.
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