Reduced R2′ in multiple sclerosis normal appearing white matter and lesions may reflect decreased myelin and iron content
- 1NMR Research Unit, Department of Neuroinflammation, UCL Institute of Neurology, London, UK
- 2NMR Research Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, UK
- Correspondence to Dr D Paling, NMR research Unit, Department of Neuroinflammation, 6th Floor, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK;
Contributors All authors had full access to all of the data in the study and all authors take full responsibility for the integrity of the data and accuracy of the data analysis. DP, DT, DHM and XG contributed to the design/conceptualisation of the study, analysis/interpretation of the data and drafting/revising the manuscript. CW-K and RK contributed to the design/conceptualisation of the study and drafting/revising the manuscript.
- Received 16 February 2012
- Revised 5 April 2012
- Accepted 12 April 2012
- Published Online First 23 May 2012
Background R2′ is an MRI measure of microscopic magnetic field inhomogeneity, and is increased by the paramagnetic effect of iron and the diamagnetic effect of myelin. R2′ may detect features of multiple sclerosis (MS) not evident with conventional MRI.
Methods Multiecho T2 and T2* 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 R2′ maps were created using the formula R2′ = R2*−R2 = 1/T2*−1/T2. R2′ 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 R2′ was reduced in NAWM in MS compared with controls (9.5/s vs 10.1/s, p=0.05). R2′ was additionally reduced in lesions, both T1 isointense (8.5/s vs 9.5/s, p=0.02) and T1 hypointense (7.7/s vs 9.5/s, p=0.003) compared with NAWM. R2′ 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 T2 lesion volume predicted an increase in R2′ in the caudate (β=0.412, p=0.02).
Conclusions Reduction in R2′ in NAWM and lesions is consistent with a decreases in myelin, tissue iron and/or deoxyhaemoglobin. Increased caudate R2′ in patients with secondary progressive MS is consistent with increased iron deposition, as corroborated by other techniques.
Funding This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme, and was supported by grant code 6DFB. The NMR Research Unit is also supported by grants from the UK MS Society, and Philips Healthcare.
Competing interests Dr David Paling has received funding for travel from the European Committee for Treatment and Research in Multiple Sclerosis. Dr Daniel J Tozer position is partially funded by the commercial companies Biogen Idec and Novartis. This funding is for work on clinical trials unconnected with this work. Dr Claudia Wheeler-Kingshott has received funding from the commercial company Biogen Idec for consultancy work, unconnected with this work. Dr Raju Kapoor receives funding for serving on the advisory boards for the commercial companies Biogen Iden, Novartis and Genetech. Dr Kapoor has received funding for travel to medical conferences from the commercial companies Biogen Idec, Merk Serono and TEVA. Dr Kapoor has received research support from National MS Society, The MS society of Great Britain and Northern Ireland and the commercial company Novatis for work unconnected with this work. Professor David Miller has received research grants (held by University College London) from Biogen Idec Inc, GlaxoSmithKline, Schering AG, and Novartis to perform MRI analysis in multiple sclerosis trials. Professor Miller has also received honoraria and travel expenses for advisory committee work or as an invited speaker from Biogen Idec Inc, GlaxoKlineSmith, Bayer Schering, Novartis and the US National Institutes of Health. Professor Xavier Golay receives funding from the commercial company Philips for advisory work unconnected with this work. Professor Xavier Golay holds two patents for arterial spin labelling imaging unconnected with this work. Professor Xavier Golay serves on the journal editorial boards of MAGMA and NMR in biomedicine.
Ethics approval The study was reviewed and approved by the local research ethics committee NRES London–Bentham.
Provenance and peer review Not commissioned; externally peer reviewed.