Quantitative assessment of brain iron by R 2 * relaxometry in patients with clinically isolated syndrome and relapsing–remitting multiple sclerosis M Khalil, C Enzinger, C Langkammer, M Tscherner, M Wallner-Blazek, M Jehna, S Ropele, S Fuchs and F Fazekas Background Increased iron deposition has been implicated in the pathophysiology of multiple scle- rosis (MS), based on visual analysis of signal reduction on T 2 -weighted images. R 2 * relaxometry allows to assess brain iron accumulation quantitatively. Objective To investigate regional brain iron deposition in patients with a clinically isolated syn- drome (CIS) or relapsing–remitting MS (RRMS) and its associations with demographical, clinical, and conventional magnetic resonance imaging (MRI) parameters. Methods We studied 69 patients (CIS, n = 32; RRMS, n = 37) with 3T MRI and analyzed regional R 2 * relaxation rates and their correlations with age, disease duration, disability, T 2 lesion load, and normalized brain volumes. Results Basal ganglia R 2 * relaxation rates increased in parallel with age (r = 0.3–0.6; P < 0.01) and were significantly higher in RRMS than in CIS (P < 0.05). Using multivariate linear regression analysis, the rate of putaminal iron deposition was independently predicted by the patients’ age, disease duration, and gray matter atrophy. Conclusions Quantitative assessment by R 2 * relaxometry suggests increased iron deposition in the basal ganglia of MS patients, which is associated with disease duration and brain atrophy. This tech- nique together with long-term follow-up thus appears suited to clarify whether regional iron accu- mulation contributes to MS morbidity or merely reflects an epiphenomenon. Multiple Sclerosis 2009; 15: 1048–1054. http://msj.sagepub.com Key words: 3T MRI; brain atrophy; deep gray matter; iron deposition; multiple sclerosis; R 2 * mapping Introduction With normal aging, regions of the brain, particu- larly the basal ganglia, tend to accumulate nonhe- min iron, primarily in the form of ferritin. Ferritin is a storage protein that contains up to 5000 ferric (Fe3+) ions and does not cross the blood–brain bar- rier. Abnormal iron deposition in the brain has been implicated in the pathophysiology of various neurodegenerative CNS disorders [1]. Although iron is essential for normal neuronal metabolism, exces- sive iron levels can exert neurotoxic effects by the formation of free radicals [2,3]. From several obser- vations, excessive iron deposition has also been pro- posed to play a role in multiple sclerosis (MS). Drayer [4] and Grimaud [5] were the first to report on a regionally specific signal reduction on T 2 -weighted brain magnetic resonance imaging (MRI) images in MS, which was believed to indicate increased iron deposition. Bakshi et al. analyzed in more detail the frequency, location, and clinical sig- nificance of T 2 shortening in a larger cohort of MS patients [6]. In this study, T 2 hypointensity was found to be more pronounced in the thalamus, putamen, caudate nuclei, and in the rolandic cor- tex, and moreover to be associated with advanced disability. Further studies of this group, linked gray Department of Neurology and Department of Radiology (Division of Neuroradiology), Medical University of Graz, Graz, Austria Correspondence to: Franz Fazekas, MD, Department of Neurology, Medical University of Graz, Graz, Austria. Email: franz.fazekas@medunigraz.at Received 11 January 2009; accepted 26 April 2009 RESEARCH PAPER Multiple Sclerosis 2009; 15: 1048–1054 © The Author(s), 2009. 10.1177/1352458509106609 Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav at UNIV CALGARY LIBRARY on November 4, 2009 http://msj.sagepub.com Downloaded from