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01-04-2012 | Review

The role of advanced magnetic resonance imaging techniques in primary progressive MS

Authors: Maria A. Rocca, Martina Absinta, Massimo Filippi

Published in: Journal of Neurology | Issue 4/2012

Abstract

Primary progressive multiple sclerosis (PPMS) is characterized by a steady progression of irreversible disability from the onset of the disease. Although magnetic resonance imaging (MRI) is a valuable tool to quantify the disease burden in the brain and spinal cord of patients with MS, measures derived from conventional MRI, including T2-visible lesions, gadolinium-enhancing lesions and atrophy, are correlated only weakly with the clinical manifestations of PPMS. On the contrary, advanced MRI techniques are contributing significantly to the understanding of the mechanisms underlying the irreversible accumulation of disability in PPMS patients. Data from quantitative MRI studies suggest that the extent and topography of “diffuse” damage in different central nervous system (CNS) compartments (i.e. normal-appearing brain white matter and grey matter and the spinal cord) is associated with the severity of disability in PPMS and can predict subsequent medium-term disease evolution. Functional MRI studies have shown that the impairment of the adaptive capacity of the cortex to limit the clinical consequences of structural CNS damage is yet another factor contributing to the manifestations of this condition.

Agosta F, Benedetti B, Rocca MA, Valsasina P, Rovaris M, Comi G, Filippi M (2005) Quantification of cervical cord pathology in primary progressive MS using diffusion tensor MRI. Neurology 64:631–635PubMedCrossRef

Agosta F, Absinta M, Sormani MP, Ghezzi A, Bertolotto A, Montanari E, Comi G, Filippi M (2007) In vivo assessment of cervical cord damage in MS patients: a longitudinal diffusion tensor MRI study. Brain 130:2211–2219PubMedCrossRef

Agosta F, Valsasina P, Absinta M, Sala S, Caputo D, Filippi M (2009) Primary progressive multiple sclerosis: tactile-associated functional MR activity in the cervical spinal cord. Radiology 253:209–215PubMedCrossRef

Anderson VM, Fisniku LK, Khaleeli Z, Summers MM, Penny SA, Altmann DR, Thompson AJ, Ron MA, Miller DH (2010) Hippocampal atrophy in relapsing-remitting and primary progressive MS: a comparative study. Mult Scler 16:1083–1090PubMedCrossRef

Bakshi R, Thompson AJ, Rocca MA, Pelletier D, Dousset V, Barkhof F, Inglese M, Guttmann CR, Horsfield MA, Filippi M (2008) MRI in multiple sclerosis: current status and future prospects. Lancet Neurol 7:615–625PubMedCrossRef

Barkhof F, Bruck W, De Groot CJ, Bergers E, Hulshof S, Geurts J, Polman CH, van der Valk P (2003) Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance. Arch Neurol 60:1073–1081PubMedCrossRef

Basser PJ, Mattiello J, LeBihan D (1994) MR diffusion tensor spectroscopy and imaging. Biophys J 66:259–267PubMedCrossRef

Bodini B, Khaleeli Z, Cercignani M, Miller DH, Thompson AJ, Ciccarelli O (2009) 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 30:2852–2861PubMedCrossRef

Bodini B, Battaglini M, De Stefano N, Khaleeli Z, Barkhof F, Chard D, Filippi M, Montalban X, Polman C, Rovaris M, Rovira A, Samson R, Miller D, Thompson A, Ciccarelli O (2011) T2 lesion location really matters: a 10 year follow-up study in primary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 82:72–77PubMedCrossRef

10.

Bozzali M, Cercignani M, Sormani MP, Comi G, Filippi M (2002) Quantification of brain gray matter damage in different MS phenotypes by use of diffusion tensor MR imaging. AJNR Am J Neuroradiol 23:985–988PubMed

11.

Bradl M, Lassmann H (2009) Progressive multiple sclerosis. Semin Immunopathol 31:455–465PubMedCrossRef

12.

Bramow S, Frischer JM, Lassmann H, Koch-Henriksen N, Lucchinetti CF, Sorensen PS, Laursen H (2010) Demyelination versus remyelination in progressive multiple sclerosis. Brain 133:2983–2998PubMedCrossRef

13.

Calabrese M, Rocca MA, Atzori M, Mattisi I, Bernardi V, Favaretto A, Barachino L, Romualdi C, Rinaldi L, Perini P, Gallo P, Filippi M (2009) Cortical lesions in primary progressive multiple sclerosis: a 2-year longitudinal MR study. Neurology 72:1330–1336PubMedCrossRef

14.

Calabrese M, Battaglini M, Giorgio A, Atzori M, Bernardi V, Mattisi I, Gallo P, De Stefano N (2010) Imaging distribution and frequency of cortical lesions in patients with multiple sclerosis. Neurology 75:1234–1240PubMedCrossRef

15.

Ceccarelli A, Rocca MA, Valsasina P, Rodegher M, Pagani E, Falini A, Comi G, Filippi M (2009) A multiparametric evaluation of regional brain damage in patients with primary progressive multiple sclerosis. Hum Brain Mapp 30:3009–3019PubMedCrossRef

16.

Ceccarelli A, Rocca MA, Valsasina P, Rodegher M, Falini A, Comi G, Filippi M (2010) Structural and functional magnetic resonance imaging correlates of motor network dysfunction in primary progressive multiple sclerosis. Eur J Neurosci 31:1273–1280PubMedCrossRef

17.

Cercignani M, Bozzali M, Iannucci G, Comi G, Filippi M (2001) Magnetisation transfer ratio and mean diffusivity of normal appearing white and grey matter from patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 70:311–317PubMedCrossRef

18.

Cercignani M, Inglese M, Pagani E, Comi G, Filippi M (2001) Mean diffusivity and fractional anisotropy histograms of patients with multiple sclerosis. AJNR Am J Neuroradiol 22:952–958PubMed

19.

Cercignani M, Bozzali M, Iannucci G, Comi G, Filippi M (2002) Intra-voxel and inter-voxel coherence in patients with multiple sclerosis assessed using diffusion tensor MRI. J Neurol 249:875–883PubMedCrossRef

20.

Ciccarelli O, Werring DJ, Wheeler-Kingshott CA, Barker GJ, Parker GJ, Thompson AJ, Miller DH (2001) Investigation of MS normal-appearing brain using diffusion tensor MRI with clinical correlations. Neurology 56:926–933PubMed

21.

Ciccarelli O, Toosy AT, Marsden JF, Wheeler-Kingshott CM, Miller DH, Matthews PM, Thompson AJ (2006) Functional response to active and passive ankle movements with clinical correlations in patients with primary progressive multiple sclerosis. J Neurol 253:882–891PubMedCrossRef

22.

Cottrell DA, Kremenchutzky M, Rice GP, Koopman WJ, Hader W, Baskerville J, Ebers GC (1999) The natural history of multiple sclerosis: a geographically based study. 5. The clinical features and natural history of primary progressive multiple sclerosis. Brain 122(Pt 4):625–639PubMedCrossRef

23.

Cucurella MG, Rovira A, Rio J, Pedraza S, Tintore MM, Montalban X, Alonso J (2000) Proton magnetic resonance spectroscopy in primary and secondary progressive multiple sclerosis. NMR Biomed 13:57–63PubMedCrossRef

24.

Davie CA, Barker GJ, Thompson AJ, Tofts PS, McDonald WI, Miller DH (1997) 1H magnetic resonance spectroscopy of chronic cerebral white matter lesions and normal appearing white matter in multiple sclerosis. J Neurol Neurosurg Psychiatry 63:736–742PubMedCrossRef

25.

Dehmeshki J, Chard DT, Leary SM, Watt HC, Silver NC, Tofts PS, Thompson AJ, Miller DH (2003) The normal appearing grey matter in primary progressive multiple sclerosis: a magnetisation transfer imaging study. J Neurol 250:67–74PubMedCrossRef

26.

Di Perri C, Battaglini M, Stromillo ML, Bartolozzi ML, Guidi L, Federico A, De Stefano N (2008) 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 65:236–243PubMedCrossRef

27.

Droogan AG, Clark CA, Werring DJ, Barker GJ, McDonald WI, Miller DH (1999) Comparison of multiple sclerosis clinical subgroups using navigated spin echo diffusion-weighted imaging. Magn Reson Imaging 17:653–661PubMedCrossRef

28.

Evangelou N, DeLuca GC, Owens T, Esiri MM (2005) Pathological study of spinal cord atrophy in multiple sclerosis suggests limited role of local lesions. Brain 128:29–34PubMedCrossRef

29.

Filippi M, Rocca MA (2009) Functional MR imaging in multiple sclerosis. Neuroimaging Clin N Am 19:59–70PubMedCrossRef

30.

Filippi M, Iannucci G, Tortorella C, Minicucci L, Horsfield MA, Colombo B, Sormani MP, Comi G (1999) Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI. Neurology 52:588–594PubMed

31.

Filippi M, Cercignani M, Inglese M, Horsfield MA, Comi G (2001) Diffusion tensor magnetic resonance imaging in multiple sclerosis. Neurology 56:304–311PubMed

32.

Filippi M, Rocca MA, Falini A, Caputo D, Ghezzi A, Colombo B, Scotti G, Comi G (2002) Correlations between structural CNS damage and functional MRI changes in primary progressive MS. Neuroimage 15:537–546PubMedCrossRef

33.

Gass A, Barker GJ, Kidd D, Thorpe JW, MacManus D, Brennan A, Tofts PS, Thompson AJ, McDonald WI, Miller DH (1994) Correlation of magnetization transfer ratio with clinical disability in multiple sclerosis. Ann Neurol 36:62–67PubMedCrossRef

34.

Ingle GT, Sastre-Garriga J, Miller DH, Thompson AJ (2005) Is inflammation important in early PPMS? A longitudinal MRI study. J Neurol Neurosurg Psychiatry 76:1255–1258PubMedCrossRef

35.

Khaleeli Z, Cercignani M, Audoin B, Ciccarelli O, Miller DH, Thompson AJ (2007) Localized grey matter damage in early primary progressive multiple sclerosis contributes to disability. Neuroimage 37:253–261PubMedCrossRef

36.

Khaleeli Z, Sastre-Garriga J, Ciccarelli O, Miller DH, Thompson AJ (2007) Magnetisation transfer ratio in the normal appearing white matter predicts progression of disability over 1 year in early primary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 78:1076–1082PubMedCrossRef

37.

Khaleeli Z, Altmann DR, Cercignani M, Ciccarelli O, Miller DH, Thompson AJ (2008) Magnetization transfer ratio in gray matter: a potential surrogate marker for progression in early primary progressive multiple sclerosis. Arch Neurol 65:1454–1459PubMedCrossRef

38.

Khaleeli Z, Ciccarelli O, Manfredonia F, Barkhof F, Brochet B, Cercignani M, Dousset V, Filippi M, Montalban X, Polman C, Rovaris M, Rovira A, Sastre-Garriga J, Vellinga M, Miller D, Thompson A (2008) Predicting progression in primary progressive multiple sclerosis: a 10-year multicenter study. Ann Neurol 63:790–793PubMedCrossRef

39.

Khaleeli Z, Ciccarelli O, Mizskiel K, Altmann D, Miller DH, Thompson AJ (2010) Lesion enhancement diminishes with time in primary progressive multiple sclerosis. Mult Scler 16:317–324PubMedCrossRef

40.

Kidd D, Thorpe JW, Thompson AJ, Kendall BE, Moseley IF, MacManus DG, McDonald WI, Miller DH (1993) Spinal cord MRI using multi-array coils and fast spin echo. II. Findings in multiple sclerosis. Neurology 43:2632–2637PubMed

41.

Kutzelnigg A, Lucchinetti CF, Stadelmann C, Bruck W, Rauschka H, Bergmann M, Schmidbauer M, Parisi JE, Lassmann H (2005) Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128:2705–2712PubMedCrossRef

42.

Le Bihan D, Breton E, Lallemand D, Grenier P, Cabanis E, Laval-Jeantet M (1986) MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. Radiology 161:401–407PubMed

43.

Leary SM, Davie CA, Parker GJ, Stevenson VL, Wang L, Barker GJ, Miller DH, Thompson AJ (1999) 1H magnetic resonance spectroscopy of normal appearing white matter in primary progressive multiple sclerosis. J Neurol 246:1023–1026PubMedCrossRef

44.

Leary SM, Silver NC, Stevenson VL, Barker GJ, Miller DH, Thompson AJ (1999) Magnetisation transfer of normal appearing white matter in primary progressive multiple sclerosis. Mult Scler 5:313–316PubMed

45.

Lycklama a Nijeholt GJ, Castelijns JA, Lazeron RH, van Waesberghe JH, Polman CH, Uitdehaag BM, Barkhof F (2000) Magnetization transfer ratio of the spinal cord in multiple sclerosis: relationship to atrophy and neurologic disability. J Neuroimaging 10:67–72PubMed

46.

Lycklama G, Thompson A, Filippi M, Miller D, Polman C, Fazekas F, Barkhof F (2003) Spinal-cord MRI in multiple sclerosis. Lancet Neurol 2:555–562PubMedCrossRef

47.

Mesaros S, Rocca MA, Pagani E, Sormani MP, Petrolini M, Comi G, Filippi M (2011) Thalamic damage predicts the evolution of primary-progressive multiple sclerosis at 5 years. AJNR Am J Neuroradiol 32(6):1016–1020PubMedCrossRef

48.

Miller DH, Leary SM (2007) Primary-progressive multiple sclerosis. Lancet Neurol 6:903–912PubMedCrossRef

49.

Mostert JP, Koch MW, Steen C, Heersema DJ, De Groot JC, De Keyser J (2010) T2 lesions and rate of progression of disability in multiple sclerosis. Eur J Neurol 17:1471–1475PubMedCrossRef

50.

Mottershead JP, Schmierer K, Clemence M, Thornton JS, Scaravilli F, Barker GJ, Tofts PS, Newcombe J, Cuzner ML, Ordidge RJ, McDonald WI, Miller DH (2003) High field MRI correlates of myelin content and axonal density in multiple sclerosis – a post-mortem study of the spinal cord. J Neurol 250:1293–1301PubMedCrossRef

51.

Narayana PA, Wolinsky JS, Rao SB, He R, Mehta M (2004) Multicentre proton magnetic resonance spectroscopy imaging of primary progressive multiple sclerosis. Mult Scler 10(Suppl 1):S73–S78PubMedCrossRef

52.

Ogawa S, Menon RS, Tank DW, Kim SG, Merkle H, Ellermann JM, Ugurbil K (1993) Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model. Biophys J 64:803–812PubMedCrossRef

53.

Penny S, Khaleeli Z, Cipolotti L, Thompson A, Ron M (2010) Early imaging predicts later cognitive impairment in primary progressive multiple sclerosis. Neurology 74:545–552PubMedCrossRef

54.

Pierpaoli C, Basser PJ (1996) Toward a quantitative assessment of diffusion anisotropy. Magn Reson Med 36:893–906PubMedCrossRef

55.

Pike GB, de Stefano N, Narayanan S, Francis GS, Antel JP, Arnold DL (1999) Combined magnetization transfer and proton spectroscopic imaging in the assessment of pathologic brain lesions in multiple sclerosis. AJNR Am J Neuroradiol 20:829–837PubMed

56.

Ramio-Torrenta L, Sastre-Garriga J, Ingle GT, Davies GR, Ameen V, Miller DH, Thompson AJ (2006) Abnormalities in normal appearing tissues in early primary progressive multiple sclerosis and their relation to disability: a tissue specific magnetisation transfer study. J Neurol Neurosurg Psychiatry 77:40–45PubMedCrossRef

57.

Riccitelli G, Rocca MA, Pagani E, Rodegher ME, Rossi P, Falini A, Comi G, Filippi M (2010) Cognitive impairment in multiple sclerosis is associated to different patterns of gray matter atrophy according to clinical phenotype. Hum Brain Mapp. doi:10.1002/hbm.21125 PubMed

58.

Rocca MA, Matthews PM, Caputo D, Ghezzi A, Falini A, Scotti G, Comi G, Filippi M (2002) Evidence for widespread movement-associated functional MRI changes in patients with PPMS. Neurology 58:866–872PubMed

59.

Rocca MA, Riccitelli G, Rodegher M, Ceccarelli A, Falini A, Falautano M, Meani A, Comi G, Filippi M (2010) Functional MR Imaging correlates of neuropsychological impairment in primary-progressive multiple sclerosis. AJNR Am J Neuroradiol 31:1240–1246PubMedCrossRef

60.

Rocca MA, Valsasina P, Absinta M, Riccitelli G, Rodegher ME, Misci P, Rossi P, Falini A, Comi G, Filippi M (2010) Default-mode network dysfunction and cognitive impairment in progressive MS. Neurology 74:1252–1259PubMedCrossRef

61.

Rovaris M, Bozzali M, Santuccio G, Ghezzi A, Caputo D, Montanari E, Bertolotto A, Bergamaschi R, Capra R, Mancardi G, Martinelli V, Comi G, Filippi M (2001) In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis. Brain 124:2540–2549PubMedCrossRef

62.

Rovaris M, Bozzali M, Iannucci G, Ghezzi A, Caputo D, Montanari E, Bertolotto A, Bergamaschi R, Capra R, Mancardi GL, Martinelli V, Comi G, Filippi M (2002) Assessment of normal-appearing white and gray matter in patients with primary progressive multiple sclerosis: a diffusion-tensor magnetic resonance imaging study. Arch Neurol 59:1406–1412PubMedCrossRef

63.

Rovaris M, Gallo A, Falini A, Benedetti B, Rossi P, Comola M, Scotti G, Comi G, Filippi M (2005) Axonal injury and overall tissue loss are not related in primary progressive multiple sclerosis. Arch Neurol 62:898–902PubMedCrossRef

64.

Rovaris M, Gallo A, Valsasina P, Benedetti B, Caputo D, Ghezzi A, Montanari E, Sormani MP, Bertolotto A, Mancardi G, Bergamaschi R, Martinelli V, Comi G, Filippi M (2005) Short-term accrual of gray matter pathology in patients with progressive multiple sclerosis: an in vivo study using diffusion tensor MRI. Neuroimage 24:1139–1146PubMedCrossRef

65.

Rovaris M, Gass A, Bammer R, Hickman SJ, Ciccarelli O, Miller DH, Filippi M (2005) Diffusion MRI in multiple sclerosis. Neurology 65:1526–1532PubMedCrossRef

66.

Rovaris M, Judica E, Gallo A, Benedetti B, Sormani MP, Caputo D, Ghezzi A, Montanari E, Bertolotto A, Mancardi G, Bergamaschi R, Martinelli V, Comi G, Filippi M (2006) Grey matter damage predicts the evolution of primary progressive multiple sclerosis at 5 years. Brain 129:2628–2634PubMedCrossRef

67.

Rovaris M, Judica E, Sastre-Garriga J, Rovira A, Sormani MP, Benedetti B, Korteweg T, De Stefano N, Khaleeli Z, Montalban X, Barkhof F, Miller DH, Polman C, Thompson AJ, Filippi M (2008) Large-scale, multicentre, quantitative MRI study of brain and cord damage in primary progressive multiple sclerosis. Mult Scler 14:455–464PubMedCrossRef

68.

Sajja BR, Narayana PA, Wolinsky JS, Ahn CW (2008) Longitudinal magnetic resonance spectroscopic imaging of primary progressive multiple sclerosis patients treated with glatiramer acetate: multicenter study. Mult Scler 14:73–80PubMedCrossRef

69.

Sajja BR, Wolinsky JS, Narayana PA (2009) Proton magnetic resonance spectroscopy in multiple sclerosis. Neuroimaging Clin N Am 19:45–58PubMedCrossRef

70.

Sastre-Garriga J, Ingle GT, Chard DT, Cercignani M, Ramio-Torrenta L, Miller DH, Thompson AJ (2005) Grey and white matter volume changes in early primary progressive multiple sclerosis: a longitudinal study. Brain 128:1454–1460PubMedCrossRef

71.

Sastre-Garriga J, Ingle GT, Chard DT, Ramio-Torrenta L, McLean MA, Miller DH, Thompson AJ (2005) Metabolite changes in normal-appearing gray and white matter are linked with disability in early primary progressive multiple sclerosis. Arch Neurol 62:569–573PubMedCrossRef

72.

Sepulcre J, Sastre-Garriga J, Cercignani M, Ingle GT, Miller DH, Thompson AJ (2006) Regional gray matter atrophy in early primary progressive multiple sclerosis: a voxel-based morphometry study. Arch Neurol 63:1175–1180PubMedCrossRef

73.

Suhy J, Rooney WD, Goodkin DE, Capizzano AA, Soher BJ, Maudsley AA, Waubant E, Andersson PB, Weiner MW (2000) 1H MRSI comparison of white matter and lesions in primary progressive and relapsing-remitting MS. Mult Scler 6:148–155PubMed

74.

Thompson AJ, Montalban X, Barkhof F, Brochet B, Filippi M, Miller DH, Polman CH, Stevenson VL, McDonald WI (2000) Diagnostic criteria for primary progressive multiple sclerosis: a position paper. Ann Neurol 47:831–835PubMedCrossRef

75.

Tortorella C, Viti B, Bozzali M, Sormani MP, Rizzo G, Gilardi MF, Comi G, Filippi M (2000) A magnetization transfer histogram study of normal-appearing brain tissue in MS. Neurology 54:186–193PubMed

76.

Tur C, Khaleeli Z, Ciccarelli O, Altmann DR, Cercignani M, Miller DH, Thompson AJ (2011) Complementary roles of grey matter MTR and T2 lesions in predicting progression in early PPMS. J Neurol Neurosurg Psychiatry 82:423–428PubMedCrossRef

77.

Valsasina P, Rocca MA, Absinta M, Agosta F, Caputo D, Comi G, Filippi M (2011) Cervical cord fMRI abnormalities differ between the progressive forms of multiple sclerosis. Hum Brain Mapp (in press)

78.

van Waesberghe JH, Kamphorst W, De Groot CJ, van Walderveen MA, Castelijns JA, Ravid R, Lycklama a Nijeholt GJ, van der Valk P, Polman CH, Thompson AJ, Barkhof F (1999) Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann Neurol 46:747–754PubMedCrossRef

79.

Vrenken H, Barkhof F, Uitdehaag BM, Castelijns JA, Polman CH, Pouwels PJ (2005) MR spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter. Magn Reson Med 53:256–266PubMedCrossRef

Title: The role of advanced magnetic resonance imaging techniques in primary progressive MS
Authors: Maria A. Rocca
Martina Absinta
Massimo Filippi
Publication date: 01-04-2012
Publisher: Springer-Verlag
Published in: Journal of Neurology / Issue 4/2012
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-011-6195-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The role of advanced magnetic resonance imaging techniques in primary progressive MS

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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