Reduced R′2 in multiple sclerosis normal appearing white matter and lesions may reflect decreased myelin and iron content

Background R'(2) is an MRI measure of microscopic magnetic field inhomogeneity, and is increased by the paramagnetic effect of iron and the diamagnetic effect of myelin. R'(2) may detect features of multiple sclerosis (MS) not evident with conventional MRI. Methods Multiecho T-2 and T-2* weighted sequences were obtained from 21 healthy controls (nine men, 12 women; mean age 36 years) and 28 MS patients (seven men, 21 women; 18 relapsing remitting, 10 secondary progressive; mean age 42 years). T2 and T2* relaxation time maps were created from the multiecho sequences, and R'(2) maps were created using the formula R'(2) R-2* - R-2 = 1/T-2* - 1/T-2. R'(2) was measured in MS white matter lesions and in regions of interest in normal appearing white matter (NAWM) and grey matter in all subjects. Results R'(2) was reduced in NAWM in MS compared with controls (9.5/s vs 10.1/s, p=0.05). R'(2) was additionally reduced in lesions, both T-1 isointense (8.5/s vs 9.5/s, p=0.02) and T-1 hypointense (7.7/s vs 9.5/s, p=0.003) compared with NAWM. R'(2) tended to be higher in the basal ganglia of MS patients compared with controls, and was significantly higher in the caudate nucleus in secondary progressive MS (12.9/s vs 10.9/s, p=0.03). Increased T-2 lesion volume predicted an increase in R'(2) in the caudate (beta=0.412, p=0.02). Conclusions Reduction in R'(2) in NAWM and lesions is consistent with a decreases in myelin, tissue iron and/or deoxyhaemoglobin. Increased caudate R'(2) in patients with secondary progressive MS is consistent with increased iron deposition, as corroborated by other techniques.