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DOI: 10.1055/s-0036-1579737
Advanced Structural and Functional Brain MRI in Multiple Sclerosis
Publication History
Publication Date:
26 April 2016 (online)
Abstract
Conventional magnetic resonance imaging (MRI) of the central nervous system is crucial for an early and reliable diagnosis and monitoring of patients with multiple sclerosis (MS). Focal white matter (WM) lesions, as detected by MRI, are the pathological hallmark of the disease and show some relation to clinical disability, especially in the long run. Gray matter (GM) involvement is evident from disease onset and includes focal (i.e., cortical lesions) and diffuse pathology (i.e., atrophy). Both accumulate over time and show close relation to physical disability and cognitive impairment. Using advanced quantitative MRI techniques such as magnetization transfer imaging (MTI), diffusion tensor imaging (DTI), proton MR spectroscopy (1H-MRS), and iron imaging, subtle MS pathology has been demonstrated from early stages outside focal WM lesions in the form of widespread abnormalities of the normal appearing WM and GM. In addition, studies using functional MRI have demonstrated that brain plasticity is driven by MS pathology, playing adaptive or maladaptive roles to neurologic and cognitive status and explaining, at least in part, the clinicoradiological paradox of MS.
Keywords
multiple sclerosis - magnetic resonance imaging lesions - normal-appearing brain - atrophy - magnetization transfer - diffusion tensor imaging - proton magnetic resonance spectroscopy - iron - susceptibility weighted imaging - functional magnetic resonance imaging - resting state networks - brain connectivity - high-field magnetic resonance imaging - demyelination - neurodegeneration-
References
- 1 Montalban X, Tintoré M, Swanton J , et al. MRI criteria for MS in patients with clinically isolated syndromes. Neurology 2010; 74 (5) 427-434
- 2 Rovira A, Wattjes MP, Tintore M , et al. Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process. Nat Rev Neurol 2015; 11 (8) 471-482
- 3 Wattjes MP, Rovira A, Miller D , et al. Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-establishing disease prognosis and monitoring patients. Nat Rev Neurol 2015; 11 (10) 597-606
- 4 Filippi M, Rocca MA, De Stefano N , et al. Magnetic resonance techniques in multiple sclerosis: the present and the future. Arch Neurol 2011; 68 (12) 1514-1520
- 5 Rocca MA, Amato MP, De Stefano N , et al; MAGNIMS Study Group. Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis. Lancet Neurol 2015; 14 (3) 302-317
- 6 Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000; 47 (6) 707-717
- 7 Polman CH, Reingold SC, Banwell B , et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald Criteria. Ann Neurol 2011; 69 (2) 292-302
- 8 Charil A, Yousry TA, Rovaris M , et al. MRI and the diagnosis of multiple sclerosis: expanding the concept of “no better explanation.”. Lancet Neurol 2006; 5 (10) 841-852
- 9 Ormerod IE, Miller DH, McDonald WI , et al. The role of NMR imaging in the assessment of multiple sclerosis and isolated neurological lesions. A quantitative study. Brain 1987; 110 (Pt 6): 1579-1616
- 10 Miller DH, Newton MR, van der Poel JC , et al. Magnetic resonance imaging of the optic nerve in optic neuritis. Neurology 1988; 38 (2) 175-179
- 11 Isaac C, Li DK, Genton M , et al. Multiple sclerosis: a serial study using MRI in relapsing patients. Neurology 1988; 38 (10) 1511-1515
- 12 Willoughby EW, Grochowski E, Li DK, Oger J, Kastrukoff LF, Paty DW. Serial magnetic resonance scanning in multiple sclerosis: a second prospective study in relapsing patients. Ann Neurol 1989; 25 (1) 43-49
- 13 Fisniku LK, Brex PA, Altmann DR , et al. Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 2008; 131 (Pt 3): 808-817
- 14 Brex PA, Ciccarelli O, O'Riordan JI, Sailer M, Thompson AJ, Miller DH. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med 2002; 346 (3) 158-164
- 15 Minneboo A, Barkhof F, Polman CH, Uitdehaag BM, Knol DL, Castelijns JA. Infratentorial lesions predict long-term disability in patients with initial findings suggestive of multiple sclerosis. Arch Neurol 2004; 61 (2) 217-221
- 16 Barkhof F, Filippi M, Miller DH , et al. Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 1997; 120 (Pt 11): 2059-2069
- 17 Swanton JK, Fernando KT, Dalton CM , et al. Early MRI in optic neuritis: the risk for disability. Neurology 2009; 72 (6) 542-550
- 18 Mesaros S, Rocca MA, Sormani MP, Charil A, Comi G, Filippi M. Clinical and conventional MRI predictors of disability and brain atrophy accumulation in RRMS. A large scale, short-term follow-up study. J Neurol 2008; 255 (9) 1378-1383
- 19 Gauthier SA, Mandel M, Guttmann CR , et al. Predicting short-term disability in multiple sclerosis. Neurology 2007; 68 (24) 2059-2065
- 20 Stevenson VL, Ingle GT, Miller DH, Thompson AJ. Magnetic resonance imaging predictors of disability in primary progressive multiple sclerosis: a 5-year study. Mult Scler 2004; 10 (4) 398-401
- 21 Barkhof F, McGowan JC, van Waesberghe JH, Grossman RI. Hypointense multiple sclerosis lesions on T1-weighted spin echo magnetic resonance images: their contribution in understanding multiple sclerosis evolution. J Neurol Neurosurg Psychiatry 1998; 64 (Suppl. 01) S77-S79
- 22 van Waesberghe JH, van Walderveen MA, Castelijns JA , et al. Patterns of lesion development in multiple sclerosis: longitudinal observations with T1-weighted spin-echo and magnetization transfer MR. AJNR Am J Neuroradiol 1998; 19 (4) 675-683
- 23 van Walderveen MA, Kamphorst W, Scheltens P , et al. Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis. Neurology 1998; 50 (5) 1282-1288
- 24 Giorgio A, Stromillo ML, Bartolozzi ML , et al. Relevance of hypointense brain MRI lesions for long-term worsening of clinical disability in relapsing multiple sclerosis. Mult Scler 2014; 20 (2) 214-219
- 25 Summers M, Fisniku L, Anderson V, Miller D, Cipolotti L, Ron M. Cognitive impairment in relapsing-remitting multiple sclerosis can be predicted by imaging performed several years earlier. Mult Scler 2008; 14 (2) 197-204
- 26 Giorgio A, Battaglini M, Rocca MA , et al; MAGNIMS Study Group. Location of brain lesions predicts conversion of clinically isolated syndromes to multiple sclerosis. Neurology 2013; 80 (3) 234-241
- 27 Dalton C, Bodini B, Samson R , et al. Brain lesion location and clinical status 20 years after a diagnosis of clinically isolated syndrome suggestive of multiple sclerosis. Mult Scler 2011; 18 (3) 322-328
- 28 Charil A, Zijdenbos AP, Taylor J , et al. Statistical mapping analysis of lesion location and neurological disability in multiple sclerosis: application to 452 patient data sets. Neuroimage 2003; 19 (3) 532-544
- 29 Rossi F, Giorgio A, Battaglini M , et al. Relevance of brain lesion location to cognition in relapsing multiple sclerosis. PLoS ONE 2012; 7 (11) e44826
- 30 Vellinga MM, Geurts JJ, Rostrup E , et al. Clinical correlations of brain lesion distribution in multiple sclerosis. J Magn Reson Imaging 2009; 29 (4) 768-773
- 31 Kincses ZT, Ropele S, Jenkinson M , et al. Lesion probability mapping to explain clinical deficits and cognitive performance in multiple sclerosis. Mult Scler 2011; 17 (6) 681-689
- 32 Bodini B, Battaglini M, De Stefano N , et al. T2 lesion location really matters: a 10 year follow-up study in primary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 2011; 82 (1) 72-77
- 33 Di Perri C, Battaglini M, Stromillo ML , et al. Voxel-based assessment of differences in damage and distribution of white matter lesions between patients with primary progressive and relapsing-remitting multiple sclerosis. Arch Neurol 2008; 65 (2) 236-243
- 34 Ceccarelli A, Rocca MA, Pagani E , et al. The topographical distribution of tissue injury in benign MS: a 3T multiparametric MRI study. Neuroimage 2008; 39 (4) 1499-1509
- 35 Matthews L, Marasco R, Jenkinson M , et al. Distinction of seropositive NMO spectrum disorder and MS brain lesion distribution. Neurology 2013; 80 (14) 1330-1337
- 36 De Stefano N, Stromillo ML, Rossi F , et al. Improving the characterization of radiologically isolated syndrome suggestive of multiple sclerosis. PLoS ONE 2011; 6 (4) e19452
- 37 Lucchinetti CF, Popescu BF, Bunyan RF , et al. Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med 2011; 365 (23) 2188-2197
- 38 Geurts JJ, Pouwels PJ, Uitdehaag BM, Polman CH, Barkhof F, Castelijns JA. Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging. Radiology 2005; 236 (1) 254-260
- 39 Nelson F, Poonawalla AH, Hou P, Huang F, Wolinsky JS, Narayana PA. 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 2007; 28 (9) 1645-1649
- 40 Calabrese M, Filippi M, Rovaris M , et al. Morphology and evolution of cortical lesions in multiple sclerosis. A longitudinal MRI study. Neuroimage 2008; 42 (4) 1324-1328
- 41 Calabrese M, Agosta F, Rinaldi F , et al. Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis. Arch Neurol 2009; 66 (9) 1144-1150
- 42 Calabrese M, Rocca MA, Atzori M , et al. Cortical lesions in primary progressive multiple sclerosis: a 2-year longitudinal MR study. Neurology 2009; 72 (15) 1330-1336
- 43 Calabrese M, Rocca MA, Atzori M , et al. A 3-year magnetic resonance imaging study of cortical lesions in relapse-onset multiple sclerosis. Ann Neurol 2010; 67 (3) 376-383
- 44 Giorgio A, Stromillo ML, Rossi F , et al. Cortical lesions in radiologically isolated syndrome. Neurology 2011; 77 (21) 1896-1899
- 45 Calabrese M, Filippi M, Gallo P. Cortical lesions in multiple sclerosis. Nat Rev Neurol 2010; 6 (8) 438-444
- 46 Filippi M, Rocca MA, Calabrese M , et al. Intracortical lesions: relevance for new MRI diagnostic criteria for multiple sclerosis. Neurology 2010; 75 (22) 1988-1994
- 47 Calabrese M, Grossi P, Favaretto A , et al. Cortical pathology in multiple sclerosis patients with epilepsy: a 3 year longitudinal study. J Neurol Neurosurg Psychiatry 2012; 83 (1) 49-54
- 48 Calabrese M, Poretto V, Favaretto A , et al. Cortical lesion load associates with progression of disability in multiple sclerosis. Brain 2012; 135 (Pt 10): 2952-2961
- 49 Pouwels PJ, Kuijer JP, Mugler III JP, Guttmann CR, Barkhof F. Human gray matter: feasibility of single-slab 3D double inversion-recovery high-spatial-resolution MR imaging. Radiology 2006; 241 (3) 873-879
- 50 Klaver R, De Vries HE, Schenk GJ, Geurts JJ. Grey matter damage in multiple sclerosis: a pathology perspective. Prion 2013; 7 (1) 66-75
- 51 Geurts JJ, Roosendaal SD, Calabrese M , et al; MAGNIMS Study Group. Consensus recommendations for MS cortical lesion scoring using double inversion recovery MRI. Neurology 2011; 76 (5) 418-424
- 52 Filippi M, Rocca MA. Magnetization transfer magnetic resonance imaging of the brain, spinal cord, and optic nerve. Neurotherapeutics 2007; 4 (3) 401-413
- 53 Schmierer K, Scaravilli F, Altmann DR, Barker GJ, Miller DH. Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain. Ann Neurol 2004; 56 (3) 407-415
- 54 Fazekas F, Ropele S, Enzinger C, Seifert T, Strasser-Fuchs S. Quantitative magnetization transfer imaging of pre-lesional white-matter changes in multiple sclerosis. Mult Scler 2002; 8 (6) 479-484
- 55 Laule C, Vavasour IM, Whittall KP , et al. Evolution of focal and diffuse magnetisation transfer abnormalities in multiple sclerosis. J Neurol 2003; 250 (8) 924-931
- 56 Chen JT, Collins DL, Atkins HL, Freedman MS, Arnold DL ; Canadian MS/BMT Study Group. Magnetization transfer ratio evolution with demyelination and remyelination in multiple sclerosis lesions. Ann Neurol 2008; 63 (2) 254-262
- 57 Chen JT, Kuhlmann T, Jansen GH , et al; Canadian MS/BMT Study Group. Voxel-based analysis of the evolution of magnetization transfer ratio to quantify remyelination and demyelination with histopathological validation in a multiple sclerosis lesion. Neuroimage 2007; 36 (4) 1152-1158
- 58 Rocca MA, Mastronardo G, Rodegher M, Comi G, Filippi M. Long-term changes of magnetization transfer-derived measures from patients with relapsing-remitting and secondary progressive multiple sclerosis. AJNR Am J Neuroradiol 1999; 20 (5) 821-827
- 59 Agosta F, Rovaris M, Pagani E, Sormani MP, Comi G, Filippi M. Magnetization transfer MRI metrics predict the accumulation of disability 8 years later in patients with multiple sclerosis. Brain 2006; 129 (Pt 10): 2620-2627
- 60 Basser PJ. Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. NMR Biomed 1995; 8 (7–8) 333-344
- 61 Bammer R, Augustin M, Strasser-Fuchs S , et al. Magnetic resonance diffusion tensor imaging for characterizing diffuse and focal white matter abnormalities in multiple sclerosis. Magn Reson Med 2000; 44 (4) 583-591
- 62 Filippi M, Cercignani M, Inglese M, Horsfield MA, Comi G. Diffusion tensor magnetic resonance imaging in multiple sclerosis. Neurology 2001; 56 (3) 304-311
- 63 Werring DJ, Clark CA, Barker GJ, Thompson AJ, Miller DH. Diffusion tensor imaging of lesions and normal-appearing white matter in multiple sclerosis. Neurology 1999; 52 (8) 1626-1632
- 64 Filippi M, Iannucci G, Cercignani M, Assunta Rocca M, Pratesi A, Comi G. A quantitative study of water diffusion in multiple sclerosis lesions and normal-appearing white matter using echo-planar imaging. Arch Neurol 2000; 57 (7) 1017-1021
- 65 Nusbaum AO, Lu D, Tang CY, Atlas SW. Quantitative diffusion measurements in focal multiple sclerosis lesions: correlations with appearance on TI-weighted MR images. AJR Am J Roentgenol 2000; 175 (3) 821-825
- 66 Rovaris M, Gallo A, Valsasina P , et al. Short-term accrual of gray matter pathology in patients with progressive multiple sclerosis: an in vivo study using diffusion tensor MRI. Neuroimage 2005; 24 (4) 1139-1146
- 67 Oreja-Guevara C, Rovaris M, Iannucci G , et al. Progressive gray matter damage in patients with relapsing-remitting multiple sclerosis: a longitudinal diffusion tensor magnetic resonance imaging study. Arch Neurol 2005; 62 (4) 578-584
- 68 Barker PB, Bizzi A, De Stefano N, Gullapalli R, Lin DDM. Clinical MR Spectroscopy Techniques and Applications. New York: Cambridge University Press; 2010
- 69 De Stefano N, Giorgio A. Multiple sclerosis and inflammatory diseases. In: Stagg CJ, Rothman DL, eds. Magnetic Resonance Spectroscopy: Tools for Neuroscience Research and Emerging Clinical Applications. Amsterdam: Elsevier; 2013: 162-171
- 70 Srinivasan R, Sailasuta N, Hurd R, Nelson S, Pelletier D. Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T. Brain 2005; 128 (Pt 5): 1016-1025
- 71 Werner P, Pitt D, Raine CS. Multiple sclerosis: altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage. Ann Neurol 2001; 50 (2) 169-180
- 72 De Stefano N, Matthews PM, Arnold DL. Reversible decreases in N-acetylaspartate after acute brain injury. Magn Reson Med 1995; 34 (5) 721-727
- 73 Ciccarelli O, Toosy AT, De Stefano N, Wheeler-Kingshott CA, Miller DH, Thompson AJ. Assessing neuronal metabolism in vivo by modeling imaging measures. J Neurosci 2010; 30 (45) 15030-15033
- 74 Sinnecker T, Dörr J, Pfueller CF , et al. Distinct lesion morphology at 7-T MRI differentiates neuromyelitis optica from multiple sclerosis. Neurology 2012; 79 (7) 708-714
- 75 Haacke EM, Mittal S, Wu Z, Neelavalli J, Cheng YC. Susceptibility-weighted imaging: technical aspects and clinical applications, part 1. AJNR Am J Neuroradiol 2009; 30 (1) 19-30
- 76 Kilsdonk ID, Wattjes MP, Lopez-Soriano A , et al. Improved differentiation between MS and vascular brain lesions using FLAIR* at 7 Tesla. Eur Radiol 2014; 24 (4) 841-849
- 77 Quinn MP, Kremenchutzky M, Menon RS. Venocentric lesions: an MRI marker of MS?. Front Neurol 2013; 4: 98
- 78 Kau T, Taschwer M, Deutschmann H, Schönfelder M, Weber JR, Hausegger KA. The “central vein sign”: is there a place for susceptibility weighted imaging in possible multiple sclerosis?. Eur Radiol 2013; 23 (7) 1956-1962
- 79 Chen W, Gauthier SA, Gupta A , et al. Quantitative susceptibility mapping of multiple sclerosis lesions at various ages. Radiology 2014; 271 (1) 183-192
- 80 Mehta V, Pei W, Yang G , et al. Iron is a sensitive biomarker for inflammation in multiple sclerosis lesions. PLoS ONE 2013; 8 (3) e57573
- 81 Stankiewicz JM, Neema M, Ceccarelli A. Iron and multiple sclerosis. Neurobiol Aging 2014; 35 (Suppl. 02) S51-S58
- 82 Stephenson E, Nathoo N, Mahjoub Y, Dunn JF, Yong VW. Iron in multiple sclerosis: roles in neurodegeneration and repair. Nat Rev Neurol 2014; 10 (8) 459-468
- 83 Filippi M, Rocca MA, Barkhof F , et al; Attendees of the Correlation between Pathological MRI findings in MS workshop. Association between pathological and MRI findings in multiple sclerosis. Lancet Neurol 2012; 11 (4) 349-360
- 84 Giorgio A, De Stefano N. Clinical use of brain volumetry. J Magn Reson Imaging 2013; 37 (1) 1-14
- 85 Coffey CE, Wilkinson WE, Parashos IA , et al. Quantitative cerebral anatomy of the aging human brain: a cross-sectional study using magnetic resonance imaging. Neurology 1992; 42 (3 Pt 1): 527-536
- 86 Pfefferbaum A, Mathalon DH, Sullivan EV, Rawles JM, Zipursky RB, Lim KO. A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Arch Neurol 1994; 51 (9) 874-887
- 87 De Stefano N, Stromillo ML, Giorgio A , et al. Establishing pathological cut-offs of brain atrophy rates in multiple sclerosis. J Neurol Neurosurg Psychiatry 2016; 87 (1) 93-99
- 88 Giorgio A, Battaglini M, Smith SM, De Stefano N. Brain atrophy assessment in multiple sclerosis: importance and limitations. Neuroimaging Clin N Am 2008; 18 (4) 675-686 , xi
- 89 De Stefano N, Giorgio A, Battaglini M , et al. Assessing brain atrophy rates in a large population of untreated multiple sclerosis subtypes. Neurology 2010; 74 (23) 1868-1876
- 90 Minneboo A, Jasperse B, Barkhof F , et al. Predicting short-term disability progression in early multiple sclerosis: added value of MRI parameters. J Neurol Neurosurg Psychiatry 2008; 79 (8) 917-923
- 91 Khaleeli Z, Ciccarelli O, Manfredonia F , et al. Predicting progression in primary progressive multiple sclerosis: a 10-year multicenter study. Ann Neurol 2008; 63 (6) 790-793
- 92 Popescu V, Agosta F, Hulst HE , et al; MAGNIMS Study Group. Brain atrophy and lesion load predict long term disability in multiple sclerosis. J Neurol Neurosurg Psychiatry 2013; 84 (10) 1082-1091
- 93 Giorgio A, Stromillo ML, Bartolozzi ML , et al. Combined measures of brain structural damage and clinical relapses correlate with long-term disability changes in relapsing multiple sclerosis. Paper presented at: 65th Annual Meeting of the American Academy of Neurology; March 16–23, 2013; San Diego, CA
- 94 Jasperse B, Vrenken H, Sanz-Arigita E , et al. Regional brain atrophy development is related to specific aspects of clinical dysfunction in multiple sclerosis. Neuroimage 2007; 38 (3) 529-537
- 95 Dalton CM, Chard DT, Davies GR , et al. Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes. Brain 2004; 127 (Pt 5): 1101-1107
- 96 Fisher E, Lee JC, Nakamura K, Rudick RA. Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol 2008; 64 (3) 255-265
- 97 Fisniku LK, Chard DT, Jackson JS , et al. Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol 2008; 64 (3) 247-254
- 98 Jehna M, Pirpamer L, Khalil M , et al. Periventricular lesions correlate with cortical thinning in multiple sclerosis. Ann Neurol 2015; 78 (4) 530-539
- 99 Lavorgna L, Bonavita S, Ippolito D , et al. Clinical and magnetic resonance imaging predictors of disease progression in multiple sclerosis: a nine-year follow-up study. Mult Scler 2014; 20 (2) 220-226
- 100 Filippi M, Preziosa P, Copetti M , et al. Gray matter damage predicts the accumulation of disability 13 years later in MS. Neurology 2013; 81 (20) 1759-1767
- 101 Barkhof F, Calabresi PA, Miller DH, Reingold SC. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol 2009; 5 (5) 256-266
- 102 De Stefano N, Airas L, Grigoriadis N , et al. Clinical relevance of brain volume measures in multiple sclerosis. CNS Drugs 2014; 28 (2) 147-156
- 103 Ranjeva JP, Audoin B, Au Duong MV , et al. Local tissue damage assessed with statistical mapping analysis of brain magnetization transfer ratio: relationship with functional status of patients in the earliest stage of multiple sclerosis. AJNR Am J Neuroradiol 2005; 26 (1) 119-127
- 104 Iannucci G, Tortorella C, Rovaris M, Sormani MP, Comi G, Filippi M. Prognostic value of MR and magnetization transfer imaging findings in patients with clinically isolated syndromes suggestive of multiple sclerosis at presentation. AJNR Am J Neuroradiol 2000; 21 (6) 1034-1038
- 105 Rovira A, Swanton J, Tintoré M , et al. A single, early magnetic resonance imaging study in the diagnosis of multiple sclerosis. Arch Neurol 2009; 66 (5) 587-592
- 106 Rocca MA, Agosta F, Sormani MP , et al. A three-year, multi-parametric MRI study in patients at presentation with CIS. J Neurol 2008; 255 (5) 683-691
- 107 Gallo A, Rovaris M, Benedetti B , et al. A brain magnetization transfer MRI study with a clinical follow up of about four years in patients with clinically isolated syndromes suggestive of multiple sclerosis. J Neurol 2007; 254 (1) 78-83
- 108 De Stefano N, Battaglini M, Stromillo ML , et al. Brain damage as detected by magnetization transfer imaging is less pronounced in benign than in early relapsing multiple sclerosis. Brain 2006; 129 (Pt 8): 2008-2016
- 109 Fernando KT, Tozer DJ, Miszkiel KA , et al. Magnetization transfer histograms in clinically isolated syndromes suggestive of multiple sclerosis. Brain 2005; 128 (Pt 12): 2911-2925
- 110 Audoin B, Ranjeva JP, Au Duong MV , et al. Voxel-based analysis of MTR images: a method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis. J Magn Reson Imaging 2004; 20 (5) 765-771
- 111 Audoin B, Fernando KT, Swanton JK, Thompson AJ, Plant GT, Miller DH. Selective magnetization transfer ratio decrease in the visual cortex following optic neuritis. Brain 2006; 129 (Pt 4): 1031-1039
- 112 Hayton T, Furby J, Smith KJ , et al. Grey matter magnetization transfer ratio independently correlates with neurological deficit in secondary progressive multiple sclerosis. J Neurol 2009; 256 (3) 427-435
- 113 Khaleeli Z, Altmann DR, Cercignani M, Ciccarelli O, Miller DH, Thompson AJ. Magnetization transfer ratio in gray matter: a potential surrogate marker for progression in early primary progressive multiple sclerosis. Arch Neurol 2008; 65 (11) 1454-1459
- 114 Khaleeli Z, Cercignani M, Audoin B, Ciccarelli O, Miller DH, Thompson AJ. Localized grey matter damage in early primary progressive multiple sclerosis contributes to disability. Neuroimage 2007; 37 (1) 253-261
- 115 Tur C, Penny S, Khaleeli Z , et al. Grey matter damage and overall cognitive impairment in primary progressive multiple sclerosis. Mult Scler 2011; 17 (11) 1324-1332
- 116 Penny S, Khaleeli Z, Cipolotti L, Thompson A, Ron M. Early imaging predicts later cognitive impairment in primary progressive multiple sclerosis. Neurology 2010; 74 (7) 545-552
- 117 Chen JT, Easley K, Schneider C , et al. Clinically feasible MTR is sensitive to cortical demyelination in MS. Neurology 2013; 80 (3) 246-252
- 118 Samson RS, Cardoso MJ, Muhlert N , et al. Investigation of outer cortical magnetisation transfer ratio abnormalities in multiple sclerosis clinical subgroups. Mult Scler 2014; 20 (10) 1322-1330
- 119 Derakhshan M, Caramanos Z, Narayanan S, Arnold DL, Louis Collins D. Surface-based analysis reveals regions of reduced cortical magnetization transfer ratio in patients with multiple sclerosis: a proposed method for imaging subpial demyelination. Hum Brain Mapp 2014; 35 (7) 3402-3413
- 120 Inglese M, van Waesberghe JH, Rovaris M , et al. The effect of interferon beta-1b on quantities derived from MT MRI in secondary progressive MS. Neurology 2003; 60 (5) 853-860
- 121 Filippi M, Rocca MA, Pagani E , et al. European study on intravenous immunoglobulin in multiple sclerosis: results of magnetization transfer magnetic resonance imaging analysis. Arch Neurol 2004; 61 (9) 1409-1412
- 122 Schmierer K, Wheeler-Kingshott CA, Boulby PA , et al. Diffusion tensor imaging of post mortem multiple sclerosis brain. Neuroimage 2007; 35 (2) 467-477
- 123 Seewann A, Vrenken H, van der Valk P , et al. Diffusely abnormal white matter in chronic multiple sclerosis: imaging and histopathologic analysis. Arch Neurol 2009; 66 (5) 601-609
- 124 Gallo A, Rovaris M, Riva R , et al. Diffusion-tensor magnetic resonance imaging detects normal-appearing white matter damage unrelated to short-term disease activity in patients at the earliest clinical stage of multiple sclerosis. Arch Neurol 2005; 62 (5) 803-808
- 125 Raz E, Cercignani M, Sbardella E , et al. Clinically isolated syndrome suggestive of multiple sclerosis: voxelwise regional investigation of white and gray matter. Radiology 2010; 254 (1) 227-234
- 126 Rovaris M, Judica E, Ceccarelli A , et al. A 3-year diffusion tensor MRI study of grey matter damage progression during the earliest clinical stage of MS. J Neurol 2008; 255 (8) 1209-1214
- 127 Rovaris M, Judica E, Gallo A , et al. Grey matter damage predicts the evolution of primary progressive multiple sclerosis at 5 years. Brain 2006; 129 (Pt 10): 2628-2634
- 128 Calabrese M, Rinaldi F, Seppi D , et al. Cortical diffusion-tensor imaging abnormalities in multiple sclerosis: a 3-year longitudinal study. Radiology 2011; 261 (3) 891-898
- 129 Giorgio A, Palace J, Johansen-Berg H , et al. Relationships of brain white matter microstructure with clinical and MR measures in relapsing-remitting multiple sclerosis. J Magn Reson Imaging 2010; 31 (2) 309-316
- 130 Roosendaal SD, Geurts JJ, Vrenken H , et al. Regional DTI differences in multiple sclerosis patients. Neuroimage 2009; 44 (4) 1397-1403
- 131 Bodini B, Cercignani M, Khaleeli Z , et al. Corpus callosum damage predicts disability progression and cognitive dysfunction in primary-progressive MS after five years. Hum Brain Mapp 2013; 34 (5) 1163-1172
- 132 Hulst HE, Steenwijk MD, Versteeg A , et al. Cognitive impairment in MS: impact of white matter integrity, gray matter volume, and lesions. Neurology 2013; 80 (11) 1025-1032
- 133 Dineen RA, Vilisaar J, Hlinka J , et al. Disconnection as a mechanism for cognitive dysfunction in multiple sclerosis. Brain 2009; 132 (Pt 1): 239-249
- 134 Shu N, Liu Y, Li K , et al. Diffusion tensor tractography reveals disrupted topological efficiency in white matter structural networks in multiple sclerosis. Cereb Cortex 2011; 21 (11) 2565-2577
- 135 Bodini B, Khaleeli Z, Cercignani M, Miller DH, Thompson AJ, Ciccarelli O. Exploring the relationship between white matter and gray matter damage in early primary progressive multiple sclerosis: an in vivo study with TBSS and VBM. Hum Brain Mapp 2009; 30 (9) 2852-2861
- 136 Steenwijk MD, Daams M, Pouwels PJ , et al. Unraveling the relationship between regional gray matter atrophy and pathology in connected white matter tracts in long-standing multiple sclerosis. Hum Brain Mapp 2015; 36 (5) 1796-1807
- 137 Sbardella E, Petsas N, Tona F , et al. Assessing the correlation between grey and white matter damage with motor and cognitive impairment in multiple sclerosis patients. PLoS ONE 2013; 8 (5) e63250
- 138 Stromillo ML, Giorgio A, Rossi F , et al. Brain metabolic changes suggestive of axonal damage in radiologically isolated syndrome. Neurology 2013; 80 (23) 2090-2094
- 139 Filippi M. Multiple sclerosis: a white matter disease with associated gray matter damage. J Neurol Sci 2001; 185 (1) 3-4
- 140 Sarchielli P, Presciutti O, Tarducci R , et al. Localized (1)H magnetic resonance spectroscopy in mainly cortical gray matter of patients with multiple sclerosis. J Neurol 2002; 249 (7) 902-910
- 141 Sharma R, Narayana PA, Wolinsky JS. Grey matter abnormalities in multiple sclerosis: proton magnetic resonance spectroscopic imaging. Mult Scler 2001; 7 (4) 221-226
- 142 Filippi M, Bozzali M, Rovaris M , et al. Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain 2003; 126 (Pt 2) 433-437
- 143 Adalsteinsson E, Langer-Gould A, Homer RJ , et al. Gray matter N-acetyl aspartate deficits in secondary progressive but not relapsing-remitting multiple sclerosis. AJNR Am J Neuroradiol 2003; 24 (10) 1941-1945
- 144 Wylezinska M, Cifelli A, Jezzard P, Palace J, Alecci M, Matthews PM. Thalamic neurodegeneration in relapsing-remitting multiple sclerosis. Neurology 2003; 60 (12) 1949-1954
- 145 Inglese M, Liu S, Babb JS, Mannon LJ, Grossman RI, Gonen O. Three-dimensional proton spectroscopy of deep gray matter nuclei in relapsing-remitting MS. Neurology 2004; 63 (1) 170-172
- 146 Geurts JJ, Reuling IE, Vrenken H , et al. MR spectroscopic evidence for thalamic and hippocampal, but not cortical, damage in multiple sclerosis. Magn Reson Med 2006; 55 (3) 478-483
- 147 Cawley N, Solanky BS, Muhlert N , et al. Reduced gamma-aminobutyric acid concentration is associated with physical disability in progressive multiple sclerosis. Brain 2015; 138 (Pt 9): 2584-2595
- 148 De Stefano N, Filippi M, Miller D , et al. Guidelines for using proton MR spectroscopy in multicenter clinical MS studies. Neurology 2007; 69 (20) 1942-1952
- 149 Walsh AJ, Blevins G, Lebel RM, Seres P, Emery DJ, Wilman AH. Longitudinal MR imaging of iron in multiple sclerosis: an imaging marker of disease. Radiology 2014; 270 (1) 186-196
- 150 Khalil M, Langkammer C, Pichler A , et al. Dynamics of brain iron levels in multiple sclerosis: a longitudinal 3T MRI study. Neurology 2015; 84 (24) 2396-2402
- 151 Khalil M, Enzinger C, Langkammer C , et al. Quantitative assessment of brain iron by R(2)* relaxometry in patients with clinically isolated syndrome and relapsing-remitting multiple sclerosis. Mult Scler 2009; 15 (9) 1048-1054
- 152 Bermel RA, Puli SR, Rudick RA , et al. Prediction of longitudinal brain atrophy in multiple sclerosis by gray matter magnetic resonance imaging T2 hypointensity. Arch Neurol 2005; 62 (9) 1371-1376
- 153 Khalil M, Langkammer C, Ropele S , et al. Determinants of brain iron in multiple sclerosis: a quantitative 3T MRI study. Neurology 2011; 77 (18) 1691-1697
- 154 Rocca MA, Absinta M, Moiola L , et al. Functional and structural connectivity of the motor network in pediatric and adult-onset relapsing-remitting multiple sclerosis. Radiology 2010; 254 (2) 541-550
- 155 Rocca MA, Mezzapesa DM, Ghezzi A , et al. A widespread pattern of cortical activations in patients at presentation with clinically isolated symptoms is associated with evolution to definite multiple sclerosis. AJNR Am J Neuroradiol 2005; 26 (5) 1136-1139
- 156 Audoin B, Reuter F, Duong MV , et al. Efficiency of cognitive control recruitment in the very early stage of multiple sclerosis: a one-year fMRI follow-up study. Mult Scler 2008; 14 (6) 786-792
- 157 Giorgio A, Portaccio E, Stromillo ML , et al. Cortical functional reorganisation and its relationship with brain structural damage in patients with benign multiple sclerosis. Mult Scler 2010; 16 (11) 1326-1334
- 158 Fox MD, Greicius M. Clinical applications of resting state functional connectivity. Front Syst Neurosci 2010; 4: 19
- 159 Roosendaal SD, Schoonheim MM, Hulst HE , et al. Resting state networks change in clinically isolated syndrome. Brain 2010; 133 (Pt 6): 1612-1621
- 160 Rocca MA, Valsasina P, Martinelli V , et al. Large-scale neuronal network dysfunction in relapsing-remitting multiple sclerosis. Neurology 2012; 79 (14) 1449-1457
- 161 Rocca MA, Valsasina P, Absinta M , et al. Default-mode network dysfunction and cognitive impairment in progressive MS. Neurology 2010; 74 (16) 1252-1259
- 162 Bonavita S, Gallo A, Sacco R , et al. Distributed changes in default-mode resting-state connectivity in multiple sclerosis. Mult Scler 2011; 17 (4) 411-422
- 163 Loitfelder M, Filippi M, Rocca M , et al. Abnormalities of resting state functional connectivity are related to sustained attention deficits in MS. PLoS ONE 2012; 7 (8) e42862
- 164 Faivre A, Rico A, Zaaraoui W , et al. Assessing brain connectivity at rest is clinically relevant in early multiple sclerosis. Mult Scler 2012; 18 (9) 1251-1258
- 165 Hawellek DJ, Hipp JF, Lewis CM, Corbetta M, Engel AK. Increased functional connectivity indicates the severity of cognitive impairment in multiple sclerosis. Proc Natl Acad Sci U S A 2011; 108 (47) 19066-19071
- 166 Giorgio A, Stromillo ML, De Leucio A , et al. Appraisal of brain connectivity in radiologically isolated syndrome by modeling imaging measures. J Neurosci 2015; 35 (2) 550-558
- 167 Richiardi J, Gschwind M, Simioni S , et al. Classifying minimally disabled multiple sclerosis patients from resting state functional connectivity. Neuroimage 2012; 62 (3) 2021-2033
- 168 Wegner C, Filippi M, Korteweg T , et al. Relating functional changes during hand movement to clinical parameters in patients with multiple sclerosis in a multi-centre fMRI study. Eur J Neurol 2008; 15 (2) 113-122
- 169 Mancini L, Ciccarelli O, Manfredonia F , et al. Short-term adaptation to a simple motor task: a physiological process preserved in multiple sclerosis. Neuroimage 2009; 45 (2) 500-511
- 170 Rocca MA, Valsasina P, Hulst HE , et al; MAGNIMS fMRI Study Group. Functional correlates of cognitive dysfunction in multiple sclerosis: A multicenter fMRI Study. Hum Brain Mapp 2014; 35 (12) 5799-5814
- 171 Rocca MA, Absinta M, Valsasina P , et al. Abnormal connectivity of the sensorimotor network in patients with MS: a multicenter fMRI study. Hum Brain Mapp 2009; 30 (8) 2412-2425
- 172 Bosnell R, Wegner C, Kincses ZT , et al. Reproducibility of fMRI in the clinical setting: implications for trial designs. Neuroimage 2008; 42 (2) 603-610
- 173 Nielsen K, Rostrup E, Frederiksen JL , et al. Magnetic resonance imaging at 3.0 tesla detects more lesions in acute optic neuritis than at 1.5 tesla. Invest Radiol 2006; 41 (2) 76-82
- 174 Wattjes MP, Lutterbey GG, Harzheim M , et al. Higher sensitivity in the detection of inflammatory brain lesions in patients with clinically isolated syndromes suggestive of multiple sclerosis using high field MRI: an intraindividual comparison of 1.5 T with 3.0 T. Eur Radiol 2006; 16 (9) 2067-2073
- 175 Wattjes MP, Harzheim M, Lutterbey GG , et al. Does high field MRI allow an earlier diagnosis of multiple sclerosis?. J Neurol 2008; 255 (8) 1159-1163
- 176 Wattjes MP, Harzheim M, Kuhl CK , et al. Does high-field MR imaging have an influence on the classification of patients with clinically isolated syndromes according to current diagnostic MR imaging criteria for multiple sclerosis?. AJNR Am J Neuroradiol 2006; 27 (8) 1794-1798
- 177 Kilsdonk ID, Barkhof F, Wattjes MP. 2010 revisions to McDonald criteria for diagnosis of multiple sclerosis: impact of 3-Tesla magnetic resonance imaging. Ann Neurol 2011; 70 (1) 182-183
- 178 Hammond KE, Metcalf M, Carvajal L , et al. Quantitative in vivo magnetic resonance imaging of multiple sclerosis at 7 Tesla with sensitivity to iron. Ann Neurol 2008; 64 (6) 707-713
- 179 Kilsdonk ID, Lopez-Soriano A, Kuijer JP , et al. Morphological features of MS lesions on FLAIR* at 7 T and their relation to patient characteristics. J Neurol 2014; 261 (7) 1356-1364
- 180 Absinta M, Sati P, Gaitán MI , et al. Seven-tesla phase imaging of acute multiple sclerosis lesions: a new window into the inflammatory process. Ann Neurol 2013; 74 (5) 669-678
- 181 Sati P, George IC, Shea CD, Gaitán MI, Reich DS. FLAIR*: a combined MR contrast technique for visualizing white matter lesions and parenchymal veins. Radiology 2012; 265 (3) 926-932
- 182 Mainero C, Benner T, Radding A , et al. In vivo imaging of cortical pathology in multiple sclerosis using ultra-high field MRI. Neurology 2009; 73 (12) 941-948
- 183 Kangarlu A, Bourekas EC, Ray-Chaudhury A, Rammohan KW. Cerebral cortical lesions in multiple sclerosis detected by MR imaging at 8 Tesla. AJNR Am J Neuroradiol 2007; 28 (2) 262-266
- 184 Kollia K, Maderwald S, Putzki N , et al. First clinical study on ultra-high-field MR imaging in patients with multiple sclerosis: comparison of 1.5T and 7T. AJNR Am J Neuroradiol 2009; 30 (4) 699-702
- 185 Cohen-Adad J, Benner T, Greve D , et al. In vivo evidence of disseminated subpial T2* signal changes in multiple sclerosis at 7 T: a surface-based analysis. Neuroimage 2011; 57 (1) 55-62
- 186 Wattjes MP, Steenwijk MD, Stangel M. MRI in the diagnosis and monitoring of multiple sclerosis: an update. Clin Neuroradiol 2015; 25 (Suppl. 02) 157-165