Spin‐spin relaxation in experimental allergic Encephalomyelitis. Analysis of CPMG data using a non‐linear least squares method and linear inverse theory

Abstract

We have used the CPMG pulse sequence to measure proton T₂ values and water content in spinal cord and brain samples from Hartley guinea pigs inoculated to produce experimental allergic encephalomyelitis (EAE). Relaxation data were fitted using minuit, a non-linear curve fitting routine. Three exponentials provided the best fit to spinal cord data (10 ms (13%), 76 ms (57%), 215 ms (30%)) and two exponentials for brain tissue (10 ms (4%), 92 ms (96%)). Least squares algorithms were also used to analyse the spinal cord data in terms of discrete and smooth distributions of relaxation times. The discrete least squares solutions consisted of three to five isolated spikes between 0.010 and 0.300 s. This type of solution was difficult to interpret in terms of water reservoirs. Smooth solutions consisted of two broad peaks, a small peak with a T₂ near 0.010 s and a larger peak near 0.100 s. The integral ratio of the larger to the smaller peak was 7.092 ± 1.782 for normal tissue, and increased to a maximum of 16 with increasing parenchymal cellular infiltration and demyelination. The short T₂ peak has been assigned to water in the hydration layers of the myelin sheath. The width of the longer T₂ peak was sensitive to tissue heterogeneity. The least squares and smooth distribution analysis models could be used to distinguish samples with extensive parenchymal infiltration from normal tissue, even though only a maximum of 60% of the tissue was affected. The short T₂ component could provide a direct method of measuring intact myelin, which would have a profound effect on the understanding of the evolution of pathology in multiple sclerosis.