Abstract
Current multiple sclerosis (MS) is generally thought to consist of two general pathological processes; acute inflammation and degeneration. The relationship between these two components is not understood. What is clear, however, is that the measures of acute inflammation are a poor predictor of long-term disability. Although some have suggested that inflammation may not contribute directly to the essential pathology in MS or that it is secondary to tissue degeneration, most students of the disease believe that the two processes are linked. Therefore, applications of MRI to measure both components of the disease are important. As most readers know, considerable success has been achieved in measuring acute inflammation and very little success has been obtained in identifying measures that correlate with disability and the prediction of future disability has not been achieved. In this review, we will examine the successes and failures of MRI in measuring these two components of the disease process. Consequently, we will not attempt to provide a detailed review of each MRI technique or sequence that has been applied to MS (a number of excellent reviews are available) but rather discuss how these techniques have been applied to answer specific questions. We will provide some comments on the use of MRI in clinical trials as well as in clinical practice. Finally, we will end with a brief discussion of future challenges.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Albert PS, McFarland HF, Smith ME, Frank JA (1994) Time series for modelling counts from a relapsing-remitting disease: application to modelling disease activity in multiple sclerosis. Stat Med 13:453–466
Allen IV, Glover G, Anderson R (1981) Abnormalities in the macroscopically normal white matter in cases of mild or spinal multiple sclerosis (MS). Acta Neuropathol Suppl 7:176–178
Altmann DR, Jasperse B, Barkhof F et al (2009) Sample sizes for brain atrophy outcomes in trials for secondary progressive multiple sclerosis. Neurology 72:595–601
Bagnato F, Jeffries N, Richert ND et al (2003) Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years. Brain 126:1782–1789
Bagnato F, Butman JA, Gupta S et al (2006) In vivo detection of cortical plaques by MR imaging in patients with multiple sclerosis. AJNR Am J Neuroradiol 27:2161–2167
Bagnato F, Yao B, Cantor F et al (2009) Multisequence-imaging protocols to detect cortical lesions of patients with multiple sclerosis: Observations from a post-mortem 3 Tesla imaging study. J Neurol Sci
Barkhof F, Valk J, Hommes OR et al (1992) Gadopentetate dimeglumine enhancement of multiple sclerosis lesions on long TR spin-echo images at 0.6 T. AJNR Am J Neuroradiol 13:1257–1259
Barkhof F, Filippi M, Miller DH et al (1997) Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 120(Pt 11):2059–2069
Bendszus M, Ladewig G, Jestaedt L et al (2008) Gadofluorine M enhancement allows more sensitive detection of inflammatory CNS lesions than T2-w imaging: a quantitative MRI study. Brain 131:2341–2352
Benedict RH, Weinstock-Guttman B, Fishman I et al (2004) Prediction of neuropsychological impairment in multiple sclerosis: comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden. Arch Neurol 61:226–230
Bielekova B, Lincoln A, McFarland H, Martin R (2000a) Therapeutic potential of phosphodiesterase-4 and -3 inhibitors in Th1-mediated autoimmune diseases. J Immunol 164:1117–1124
Bielekova B, Goodwin B, Richert N et al (2000b) Encephalitogenic potential of the myelin basic protein peptide (amino acids 83–99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand. Nat Med 6:1167–1175
Bielekova B, Richert N, Howard T et al (2004) Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon beta. Proc Natl Acad Sci USA 101:8705–8708
Bielekova B, Howard T, Packer AN et al (2009) Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis. Arch Neurol 66:483–489
Bo L, Geurts JJ, van der Valk P et al (2007) Lack of correlation between cortical demyelination and white matter pathologic changes in multiple sclerosis. Arch Neurol 64:76–80
Coles A, Deans J, Compston A (2004) Campath-1H treatment of multiple sclerosis: lessons from the bedside for the bench. Clin Neurol Neurosurg 106:270–274
Coles AJ, Cox A, Le Page E et al (2006) The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol 253:98–108
Coles AJ, Compston DA, Selmaj KW et al (2008) Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 359:1786–1801
Filippi M, Rocca MA, Martino G et al (1998) Magnetization transfer changes in the normal appearing white matter precede the appearance of enhancing lesions in patients with multiple sclerosis. Ann Neurol 43:809–814
Filippi M, Rocca MA, Sormani MP et al (1999) Short-term evolution of individual enhancing MS lesions studied with magnetization transfer imaging. Magn Reson Imaging 17:979–984
Fisher E, Lee JC, Nakamura K, Rudick RA (2008) Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol 64:255–265
Fisniku LK, Brex PA, Altmann DR et al (2008a) Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 131:808–817
Fisniku LK, Chard DT, Jackson JS et al (2008b) Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol 64:247–254
Frank JA, Stone LA, Smith ME et al (1994) Serial contrast-enhanced magnetic resonance imaging in patients with early relapsing-remitting multiple sclerosis: implications for treatment trials. Ann Neurol 36 Suppl:S86–90
Geurts JJ (2008) Is progressive multiple sclerosis a gray matter disease? Ann Neurol 64:230–232
Geurts JJ, Barkhof F (2008) Grey matter pathology in multiple sclerosis. Lancet Neurol 7:841–851
Goodkin DE, Rooney WD, Sloan R et al (1998) A serial study of new MS lesions and the white matter from which they arise. Neurology 51:1689–1697
Griffin CM, Dehmeshki J, Chard DT et al (2002) T1 histograms of normal-appearing brain tissue are abnormal in early relapsing-remitting multiple sclerosis. Mult Scler 8:211–216
Guo AC, MacFall JR, Provenzale JM (2002) Multiple sclerosis: diffusion tensor MR imaging for evaluation of normal-appearing white matter. Radiology 222:729–736
Harris JO, Frank JA, Patronas N et al (1991) Serial gadolinium-enhanced magnetic resonance imaging scans in patients with early, relapsing-remitting multiple sclerosis: implications for clinical trials and natural history. Ann Neurol 29:548–555
Kappos L, Moeri D, Radue EW et al (1999) Predictive value of gadolinium-enhanced magnetic resonance imaging for relapse rate and changes in disability or impairment in multiple sclerosis: a meta-analysis. Gadolinium MRI Meta-analysis Group. Lancet 353:964–969
Katz D, Taubenberger JK, Cannella B et al (1993) Correlation between magnetic resonance imaging findings and lesion development in chronic, active multiple sclerosis. Ann Neurol 34:661–669
Kidd D, Barkhof F, McConnell R et al (1999) Cortical lesions in multiple sclerosis. Brain 122(Pt 1):17–26
Kolind SH, Laule C, Vavasour IM et al (2008) Complementary information from multi-exponential T2 relaxation and diffusion tensor imaging reveals differences between multiple sclerosis lesions. Neuroimage 40:77–85
Kutzelnigg A, Lucchinetti CF, Stadelmann C et al (2005) Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128:2705–2712
Linker RA, Kroner A, Horn T et al (2006) Iron particle-enhanced visualization of inflammatory central nervous system lesions by high resolution: preliminary data in an animal model. AJNR Am J Neuroradiol 27:1225–1229
Losseff NA, Miller DH, Kidd D, Thompson AJ (2001) The predictive value of gadolinium enhancement for long term disability in relapsing-remitting multiple sclerosis–preliminary results. Mult Scler 7:23–25
McDonald WI, Compston A, Edan G et al (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127
McFarland HF, Frank JA, Albert PS et al (1992) Using gadolinium-enhanced magnetic resonance imaging lesions to monitor disease activity in multiple sclerosis. Ann Neurol 32:758–766
McFarland HF, Barkhof F, Antel J, Miller DH (2002) The role of MRI as a surrogate outcome measure in multiple sclerosis. Mult Scler 8:40–51
Miller DH, Barkhof F, Nauta JJ (1993) Gadolinium enhancement increases the sensitivity of MRI in detecting disease activity in multiple sclerosis. Brain 116(Pt 5):1077–1094
Muraro PA, Wandinger KP, Bielekova B et al (2003) Molecular tracking of antigen-specific T cell clones in neurological immune-mediated disorders. Brain 126:20–31
Neema M, Arora A, Healy BC et al (2009) Deep gray matter involvement on brain MRI scans is associated with clinical progression in multiple sclerosis. J Neuroimaging 19:3–8
Nelson F, Poonawalla AH, Hou P et al (2007) Improved identification of intracortical lesions in multiple sclerosis with phase-sensitive inversion recovery in combination with fast double inversion recovery MR imaging. AJNR Am J Neuroradiol 28:1645–1649
Nelson F, Poonawalla A, Hou P et al (2008) 3D MPRAGE improves classification of cortical lesions in multiple sclerosis. Mult Scler 14:1214–1219
Peterson JW, Bo L, Mork S et al (2001) Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 50:389–400
Petkau J, Reingold SC, Held U et al (2008) Magnetic resonance imaging as a surrogate outcome for multiple sclerosis relapses. Mult Scler 14:770–778
Polman CH, Reingold SC, Edan G et al (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 58:840–846
Richert ND, Frank JA (1999) Magnetization transfer imaging to monitor clinical trials in multiple sclerosis. Neurology 53:S29–32
Richert ND, Ostuni JL, Bash CN et al (2001) Interferon beta-1b and intravenous methylprednisolone promote lesion recovery in multiple sclerosis. Mult Scler 7:49–58
Riva M, Ikonomidou VN, Ostuni JJ et al (2009) Tissue-specific imaging is a Robust methodology to differentiate in vivo T1 black holes with advanced multiple sclerosis-induced damage. AJNR Am J Neuroradiol 30(7):1394–401
Rocca MA, Agosta F, Sormani MP et al (2008) A three-year, multi-parametric MRI study in patients at presentation with CIS. J Neurol 255:683–691
Roosendaal SD, Geurts JJ, Vrenken H et al (2009) Regional DTI differences in multiple sclerosis patients. Neuroimage 44:1397–1403
Schmierer K, Scaravilli F, Altmann DR et al (2004) Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain. Ann Neurol 56:407–415
Schmierer K, Wheeler-Kingshott CA, Boulby PA et al (2007) Diffusion tensor imaging of post mortem multiple sclerosis brain. Neuroimage 35:467–477
Sicotte NL, Kern KC, Giesser BS et al (2008) Regional hippocampal atrophy in multiple sclerosis. Brain 131:1134–1141
Smith ME, Stone LA, Albert PS et al (1993) Clinical worsening in multiple sclerosis is associated with increased frequency and area of gadopentetate dimeglumine-enhancing magnetic resonance imaging lesions. Ann Neurol 33:480–489
Stone LA, Frank JA, Albert PS et al (1995) The effect of interferon-beta on blood-brain barrier disruptions demonstrated by contrast-enhanced magnetic resonance imaging in relapsing-remitting multiple sclerosis. Ann Neurol 37:611–619
Tintore M, Rovira A, Martinez MJ et al (2000) Isolated demyelinating syndromes: comparison of different MR imaging criteria to predict conversion to clinically definite multiple sclerosis. AJNR Am J Neuroradiol 21:702–706
van den Elskamp IJ, Lembcke J, Dattola V et al (2008) Persistent T1 hypointensity as an MRI marker for treatment efficacy in multiple sclerosis. Mult Scler 14:764–769
van Walderveen MA, Kamphorst W, Scheltens P et al (1998) Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis. Neurology 50:1282–1288
Vellinga MM, Oude Engberink RD, Seewann A et al (2008) Pluriformity of inflammation in multiple sclerosis shown by ultra-small iron oxide particle enhancement. Brain 131:800–807
Vrenken H, Barkhof F, Uitdehaag BM et al (2005) MR spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter. Magn Reson Med 53:256–266
Werring DJ, Clark CA, Barker GJ et al (1999) Diffusion tensor imaging of lesions and normal-appearing white matter in multiple sclerosis. Neurology 52:1626–1632
Yu CS, Lin FC, Liu Y et al (2008) Histogram analysis of diffusion measures in clinically isolated syndromes and relapsing-remitting multiple sclerosis. Eur J Radiol 68:328–334
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer Berlin Heidelberg
About this chapter
Cite this chapter
McFarland, H.F. (2009). Examination of the Role of MRI in Multiple Sclerosis: A Problem Orientated Approach. In: Martin, R., Lutterotti, A. (eds) Molecular Basis of Multiple Sclerosis. Results and Problems in Cell Differentiation, vol 51. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2009_33
Download citation
DOI: https://doi.org/10.1007/400_2009_33
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-14152-2
Online ISBN: 978-3-642-14153-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)