J Neurol (2003) 250 : 924 – 931 DOI 10.1007/s00415-003-1115-z ORIGINAL COMMUNICATION Cornelia Laule Irene M.Vavasour Kenneth P.Whittall Joel Oger Donald W. Paty David K. B. Li Alex L. MacKay Douglas L. Arnold Evolution of focal and diffuse magnetisation transfer abnormalities in multiple sclerosis JON 1115 Introduction Multiple Sclerosis (MS) is an autoimmune disease char- acterized by inflammation, gliosis, oedema, demyelina- tion and axonal loss in the central nervous system white matter [31].The temporal evolution of these pathologies is still unclear. Conventional MRI has greatly facilitated the visualization of focal white matter pathology and its evolution. There is, however, a poor correlation between lesion load and measures of clinical disability [12, 17, 19, 39, 40, 42]. These data, and the dissociation of new lesion for- mation and the progression of disability in secondary progressive MS patients treated with interferon [8], have forced a re-evaluation of the significance of lesion ver- sus non-lesion pathology in the progression of MS. This has fuelled interest in the use of other MRI techniques to investigate the pathogenesis underlying the chronic, ir- reversible disability that occurs in MS [3, 34]. Conventional MRI measures signal from mobile pro- tons present primarily in water. It is not feasible to di- rectly image the signal from less mobile, semi-solid pro- tons attached to macromolecules and lipids because of their very short T 2 relaxation time, which is several or- ders of magnitude shorter than that of water. However, the examination of the semi-solid protons is of interest because it can provide information about tissue struc- Received: 29 July 2002 Received in revised form: 17 January 2003 Accepted: 14 March 2003 Cornelia Laule, MSc () · A. L. MacKay, DPhil Dept. of Physics & Astronomy University of British Columbia 2211 Wesbrook Mall Vancouver BC,V6T 2B5, Canada Tel.: +1-604/822-1650 Fax: +1-604/822-0702 E-Mail: claule@physics.ubc.ca I. M. Vavasour, PhD · K. P. Whittall, PhD · D. K. B. Li, MD · A. L. MacKay, DPhil Dept. of Radiology University of British Columbia Vancouver BC, Canada J. Oger, MD · D. W. Paty, MD Dept. of Medicine University of British Columbia Vancouver BC, Canada D. L. Arnold, MD Montreal Neurological Institute McGill University Montreal QU, Canada ■ Abstract Magnetisation transfer (MT) imaging provides indirect in- formation on tissue structure ab- normalities in areas that otherwise may appear normal on conven- tional MRI.We determined the evolution of MT changes in normal appearing white matter (NAWM) and lesion on serial examination of 9 multiple sclerosis (MS) patients and age matched controls. The mean NAWM MT ratio (MTR) was found to correlate strongly (R = 0.93) with the length of time since the patient’s first clinical pre- sentation and was well character- ized by a linear decrease of –0.16 %/year (p < 0.0001). The time zero intercept of the NAWM MTR regression was 30.7 ± 0.2 %, not different from the average MTR of white matter from controls (30.4 ± 0.2 %). An additional grad- ual decrease in NAWM MTR was observed 6 to 12 months before the appearance of a new lesion on con- ventional MRI, while a more pre- cipitous decrease in MTR was seen 2 to 6 months before the lesion ap- peared. Those lesions that exhib- ited pre-lesion MTR decreases showed less MTR recovery than le- sions which had no pre-lesion MTR decrease. The data suggest that the MTR of NAWM in MS undergoes a slow progressive decrease that starts at disease onset and acceler- ates rapidly in focal areas just prior to lesion appearance on conven- tional MRI. ■ Key words magnetisation transfer · multiple sclerosis · brain · lesion · normal appearing white matter