Cognitive dysfunction in multiple sclerosis (MS) is present in approximately 50% of the patients. Only moderate correlations have been found between cognitive dysfunction and T(2) lesion load, black holes or atrophy. Cognitive dysfunction in MS is probably related to the overall disease burden of the brain including abnormalities in normal appearing white matter (NAWM) and cortical grey matter, which is undetected with conventional magnetic resonance imaging (MRI). Hence, imaging techniques that embrace such abnormalities are needed to achieve better correlation with cognitive dysfunction. MR spectroscopy (MRS) performed with multi-slice echo planar spectroscopic imaging (EPSI) and PET measurements of brain metabolism as the cortical cerebral metabolic rate of glucose are imaging methods that are able to provide information on axonal loss or dysfunction in both MS lesions and in NAWM and cortical grey matter. Measurements of global NAA using multi-slice EPSI is a new promising method for measurement of the global neuron capacity and can be repeated with only little discomfort and without any risk for the patient.