MRI biomarkers of disease progression and conversion to secondary-progressive multiple sclerosis

References

• Milo R, Korczyn AD, Manouchehri N, et al. The temporal and causal relationship between inflammation and neurodegeneration in multiple sclerosis. Mult Scler. 2019;4:1352458519886943.
   Google Scholar
• Jokubaitis VG, Spelman T, Kalincik T, et al. Predictors of disability worsening in clinically isolated syndrome. Ann Clin Transl Neurol. 2015 May;2(5):479–491.
   PubMed Web of Science ®Google Scholar
• Deistung A, Schafer A, Schweser F, et al. Toward in vivo histology: A comparison of quantitative susceptibility mapping (QSM) with magnitude-, phase-, and R2*-imaging at ultra-high magnetic field strength. Neuroimage. 2013 Jan 15;65:299–314.
   PubMed Web of Science ®Google Scholar
• Dwyer MG, Bergsland N, Ramasamy DP, et al. Atrophied brain lesion volume: a new imaging biomarker in multiple sclerosis. J Neuroimaging. 2018 Sep;28(5):490–495.
   PubMed Web of Science ®Google Scholar
• Elliott C, Wolinsky JS, Hauser SL, et al. Slowly expanding/evolving lesions as a magnetic resonance imaging marker of chronic active multiple sclerosis lesions. Mult Scler. 2019 Dec;25(14):1915–1925.
   PubMed Web of Science ®Google Scholar
• Zurawski J, Tauhid S, Chu R, et al. 7T MRI cerebral leptomeningeal enhancement is common in relapsing-remitting multiple sclerosis and is associated with cortical and thalamic lesions. Mult Scler. 2019;12:1352458519885106.
   Google Scholar
• Ziemssen T, Akgun K, Bruck W. Molecular biomarkers in multiple sclerosis. J Neuroinflammation. 2019 Dec 23;16(1):272.
   PubMed Web of Science ®Google Scholar
• Lucchinetti CF, Popescu BF, Bunyan RF, et al. Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med. 2011 Dec 8;365(23):2188–2197.
   PubMed Web of Science ®Google Scholar
• Reich DS, Lucchinetti CF, Calabresi PA. Multiple sclerosis. N Engl J Med. 2018 Jan 11;378(2):169–180.
   PubMed Web of Science ®Google Scholar
• Chard D, Trip SA. Resolving the clinico-radiological paradox in multiple sclerosis. F1000Res. 2017;6:1828.
   PubMedGoogle Scholar
• Dekker I, Eijlers AJC, Popescu V, et al. Predicting clinical progression in multiple sclerosis after 6 and 12 years. Eur J Neurol. 2019 Jun;26(6):893–902.
   PubMed Web of Science ®Google Scholar
• Ontaneda D, Tallantyre E, Kalincik T, et al. Early highly effective versus escalation treatment approaches in relapsing multiple sclerosis. Lancet Neurol. 2019 Oct;18(10):973–980.
   PubMed Web of Science ®Google Scholar
• Absinta M, Sati P, Fechner A, et al. Identification of chronic active multiple sclerosis lesions on 3T MRI. AJNR Am J Neuroradiol. 2018 Jul;39(7):1233–1238.
   PubMed Web of Science ®Google Scholar
• Azevedo CJ, Cen SY, Khadka S, et al. Thalamic atrophy in multiple sclerosis: a magnetic resonance imaging marker of neurodegeneration throughout disease. Ann Neurol. 2018 Feb;83(2):223–234.
   PubMed Web of Science ®Google Scholar
• Fisher E, Lee J-C, Nakamura K, et al. Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol. 2008 Sep;64(3):255–265.
   PubMed Web of Science ®Google Scholar
• Turner B, Lin X, Calmon G, et al. Cerebral atrophy and disability in relapsing-remitting and secondary progressive multiple sclerosis over four years. Mult Scler. 2003 Feb;9(1):21–27.
   PubMedGoogle Scholar
• Bergsland N, Horakova D, Dwyer MG, et al. Subcortical and cortical gray matter atrophy in a large sample of patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis. AJNR Am J Neuroradiol. 2012 Sep;33(8):1573–1578.
   PubMed Web of Science ®Google Scholar
• Bergsland N, Horakova D, Dwyer MG, et al. Gray matter atrophy patterns in multiple sclerosis: a 10-year source-based morphometry study. Neuroimage Clin. 2018;17:444–451.
   PubMed Web of Science ®Google Scholar
• Calabrese M, Rinaldi F, Mattisi I, et al. Widespread cortical thinning characterizes patients with MS with mild cognitive impairment. Neurology. 2010 Jan 26;74(4):321–328.
   PubMed Web of Science ®Google Scholar
• Eshaghi A, Prados F, Brownlee WJ, et al. Deep gray matter volume loss drives disability worsening in multiple sclerosis. Ann Neurol. 2018 Feb;83(2):210–222.
   PubMed Web of Science ®Google Scholar
• Jacobsen C, Hagemeier J, Myhr K-M, et al. Brain atrophy and disability progression in multiple sclerosis patients: a 10-year follow-up study. J Neurol Neurosurg Psychiatry. 2014 Oct;85(10):1109–1115.
   PubMed Web of Science ®Google Scholar
• Zivadinov R, Havrdova E, Bergsland N, et al. Thalamic atrophy is associated with development of clinically definite multiple sclerosis. Radiology. 2013 Sep;268(3):831–841.
   PubMed Web of Science ®Google Scholar
• Frischer JM, Weigand SD, Guo Y, et al. Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque. Ann Neurol. 2015 Nov;78(5):710–721.
   PubMed Web of Science ®Google Scholar
• Lucchinetti C, Bruck W, Parisi J, et al. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol. 2000 Jun;47(6):707–717.
   PubMed Web of Science ®Google Scholar
• Bo L, Vedeler CA, Nyland HI, et al. Subpial demyelination in the cerebral cortex of multiple sclerosis patients. J Neuropathol Exp Neurol. 2003 Jul;62(7):723–732.
   PubMed Web of Science ®Google Scholar
• Calabrese M, Filippi M, Gallo P. Cortical lesions in multiple sclerosis. Nat Rev Neurol. 2010 Aug;6(8):438–444.
   PubMed Web of Science ®Google Scholar
• Peterson JW, Bo L, Mork S, et al. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol. 2001 Sep;50(3):389–400.
   PubMed Web of Science ®Google Scholar
• Geurts JJG, Bo L, Pouwels PJW, et al. Cortical lesions in multiple sclerosis: combined postmortem MR imaging and histopathology.. AJNR Am J Neuroradiol. 2005 Mar;26(3):572–577.
   PubMed Web of Science ®Google Scholar
• Vercellino M, Masera S, Lorenzatti M, et al. Demyelination, inflammation, and neurodegeneration in multiple sclerosis deep gray matter. J Neuropathol Exp Neurol. 2009 May;68(5):489–502.
   PubMed Web of Science ®Google Scholar
• Treaba CA, Granberg TE, Sormani MP, et al. Longitudinal characterization of cortical lesion development and evolution in multiple sclerosis with 7.0-T MRI. Radiology. 2019 Jun;291(3):740–749.
   PubMed Web of Science ®Google Scholar
• Trapp BD, Peterson J, Ransohoff RM, et al. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998 Jan 29;338(5):278–285.
   PubMed Web of Science ®Google Scholar
• Kornek B, Storch MK, Weissert R, et al. Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am J Pathol. 2000 Jul;157(1):267–276.
   PubMed Web of Science ®Google Scholar
• Friese MA, Schattling B, Fugger L. Mechanisms of neurodegeneration and axonal dysfunction in multiple sclerosis. Nat Rev Neurol. 2014 Apr;10(4):225–238.
   PubMed Web of Science ®Google Scholar
• Dziedzic T, Metz I, Dallenga T, et al. Wallerian degeneration: a major component of early axonal pathology in multiple sclerosis.. Brain Pathol. 2010 Sep;20(5):976–985.
   PubMed Web of Science ®Google Scholar
• Correale J, Marrodan M, Ysrraelit MC. Mechanisms of neurodegeneration and axonal dysfunction in progressive multiple sclerosis. Biomedicines. 2019 Feb 20;7(1):14.
   PubMed Web of Science ®Google Scholar
• Frischer JM, Bramow S, Dal-Bianco A, et al. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain. 2009 May;132(5):1175–1189.
   PubMedGoogle Scholar
• Jongen PJ, Ter Horst AT, Brands AM. Cognitive impairment in multiple sclerosis. Minerva Med. 2012 Apr;103(2):73–96.
   PubMed Web of Science ®Google Scholar
• Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) advisory committee on clinical trials of new agents in multiple sclerosis. Neurology. 1996 Apr;46(4):907–911.
   PubMed Web of Science ®Google Scholar
• University of California SFMSET, Cree BAC, Gourraud P-A, Oksenberg JR, et al. Long-term evolution of multiple sclerosis disability in the treatment era. Ann Neurol. 2016 Oct;80(4):499–510.
   PubMed Web of Science ®Google Scholar
• Segal BM. Stage-specific immune dysregulation in multiple sclerosis. J Interferon Cytokine Res. 2014 Aug;34(8):633–640.
   PubMed Web of Science ®Google Scholar
• Kutzelnigg A, Lucchinetti CF, Stadelmann C, et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain. 2005 Nov;128(11):2705–2712.
   PubMed Web of Science ®Google Scholar
• Magliozzi R, Howell OW, Reeves C, et al. A gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol. 2010 Oct;68(4):477–493.
   PubMed Web of Science ®Google Scholar
• Magliozzi R, Howell O, Vora A, et al. Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain. 2006 Apr;130(4):1089–1104.
   Google Scholar
• Ghione E, Bergsland N, Dwyer MG, et al. Brain atrophy is associated with disability progression in patients with MS followed in a clinical routine. AJNR Am J Neuroradiol. 2018 Dec;39(12):2237–2242.
   PubMed Web of Science ®Google Scholar
• Zivadinov R, Jakimovski D, Gandhi S, et al. Clinical relevance of brain atrophy assessment in multiple sclerosis. Implications for its use in a clinical routine. Expert Rev Neurother. 2016 Jul;16(7):777–793.
   PubMed Web of Science ®Google Scholar
• Grajauskas LA, Siu W, Medvedev G, et al. MRI-based evaluation of structural degeneration in the ageing brain: pathophysiology and assessment. Ageing Res Rev. 2019 Jan;49:67–82.
   PubMed Web of Science ®Google Scholar
• Azevedo CJ, Cen SY, Jaberzadeh A, et al. Contribution of normal aging to brain atrophy in MS. Neurology. 2019;6(6):e616.
   Web of Science ®Google Scholar
• Cree BAC, Hollenbach JA, Bove R, et al. Silent progression in disease activity–free relapsing multiple sclerosis. Ann Neurol. 2019 May;85(5):653–666.
   PubMed Web of Science ®Google Scholar
• Sprenger T, Kappos L, Radue EW, et al. Association of brain volume loss and long-term disability outcomes in patients with multiple sclerosis treated with teriflunomide. Mult Scler. 2019;14:1352458519855722.
   Google Scholar
• Tsivgoulis G, Katsanos AH, Grigoriadis N, et al. The effect of disease modifying therapies on disease progression in patients with relapsing-remitting multiple sclerosis: a systematic review and meta-analysis. PLoS One. 2015;10(12):e0144538.
   PubMed Web of Science ®Google Scholar
• Sormani MP, Arnold DL, De Stefano N. Treatment effect on brain atrophy correlates with treatment effect on disability in multiple sclerosis. Ann Neurol. 2014 Jan;75(1):43–49.
   PubMed Web of Science ®Google Scholar
• Guevara C, Garrido C, Martinez M, et al. Prospective assessment of no evidence of disease activity-4 status in early disease stages of multiple sclerosis in routine clinical practice. Front Neurol. 2019;10:788.
   PubMed Web of Science ®Google Scholar
• Goodin DS, Reder AT, Traboulsee AL, et al. Predictive validity of NEDA in the 16- and 21-year follow-up from the pivotal trial of interferon beta-1b. Mult Scler. 2019 May;25(6):837–847.
   PubMed Web of Science ®Google Scholar
• Schweser F, Raffaini Duarte Martins AL, Hagemeier J, et al. Mapping of thalamic magnetic susceptibility in multiple sclerosis indicates decreasing iron with disease duration: a proposed mechanistic relationship between inflammation and oligodendrocyte vitality. Neuroimage. 2018 Feb;167(167):438–452.
   PubMedGoogle Scholar
• Conte A, Gianni C, Belvisi D, et al. Deep grey matter involvement and altered sensory gating in multiple sclerosis. Mult Scler. 2019;13:1352458519845287.
   Google Scholar
• Su JH, Thomas FT, Kasoff WS, et al. Thalamus Optimized Multi Atlas Segmentation (THOMAS): fast, fully automated segmentation of thalamic nuclei from structural MRI. Neuroimage. 2019 Jul;194(194):272–282.
   PubMedGoogle Scholar
• Pontillo G, Cocozza S, Lanzillo R, et al. Determinants of deep gray matter atrophy in multiple sclerosis: a multimodal MRI study. AJNR Am J Neuroradiol. 2019 Jan;40(1):99–106.
   PubMed Web of Science ®Google Scholar
• Minagar A, Barnett MH, Benedict RH, et al. The thalamus and multiple sclerosis: modern views on pathologic, imaging, and clinical aspects. Neurology. 2013 Jan 8;80(2):210–219.
   PubMed Web of Science ®Google Scholar
• Tremblay A, Jobin C, Demers M, et al. Thalamic and hippocampal volume associated with memory functions in multiple sclerosis. Brain Cogn. 2018 Aug;125:61–68.
   PubMed Web of Science ®Google Scholar
• Louapre C, Govindarajan ST, Gianni C, et al. Heterogeneous pathological processes account for thalamic degeneration in multiple sclerosis: insights from 7 T imaging. Mult Scler. 2018 Oct;24(11):1433–1444.
   PubMed Web of Science ®Google Scholar
• Chiang FL, Wang Q, Yu FF, et al. Localised grey matter atrophy in multiple sclerosis is network-based: a coordinate-based meta-analysis. Clin Radiol. 2019 Oct;74(10):816e19–816 e28.
   Web of Science ®Google Scholar
• Fadda G, Brown RA, Magliozzi R, et al. A surface-in gradient of thalamic damage evolves in pediatric multiple sclerosis.. Ann Neurol. 2019 Mar;85(3):340–351.
   PubMed Web of Science ®Google Scholar
• Hanninen K, Viitala M, Paavilainen T, et al. Thalamic atrophy without whole brain atrophy is associated with absence of 2-year NEDA in multiple sclerosis. Front Neurol. 2019;10:459.
   PubMed Web of Science ®Google Scholar
• Gaetano L, Haring DA, Radue E-W, et al. Fingolimod effect on gray matter, thalamus, and white matter in patients with multiple sclerosis. Neurology. 2018 Apr 10;90(15):e1324–e1332.
   PubMed Web of Science ®Google Scholar
• Schoonheim MM, Ciccarelli O. The value of including thalamic atrophy as a clinical trial endpoint in multiple sclerosis. Neurology. 2018 Apr 10;90(15):677–678.
   PubMed Web of Science ®Google Scholar
• Bergsland N, Schweser F, Dwyer MG, et al. Thalamic white matter in multiple sclerosis: a combined diffusion-tensor imaging and quantitative susceptibility mapping study. Hum Brain Mapp. 2018 Oct;39(10):4007–4017.
   PubMed Web of Science ®Google Scholar
• Benedict RH, Hulst HE, Bergsland N, et al. Clinical significance of atrophy and white matter mean diffusivity within the thalamus of multiple sclerosis patients. Mult Scler. 2013 Oct;19(11):1478–1484.
   PubMedGoogle Scholar
• Schoonheim MM, Hulst HE, Brandt RB, et al. Thalamus structure and function determine severity of cognitive impairment in multiple sclerosis. Neurology. 2015 Feb 24;84(8):776–783.
   PubMed Web of Science ®Google Scholar
• Lin F, Zivadinov R, Hagemeier J, et al. Altered nuclei-specific thalamic functional connectivity patterns in multiple sclerosis and their associations with fatigue and cognition. Mult Scler. 2019 Aug;25(9):1243–1254.
   PubMed Web of Science ®Google Scholar
• Calabrese M, Rinaldi F, Grossi P, et al. Cortical pathology and cognitive impairment in multiple sclerosis. Expert Rev Neurother. 2011 Mar;11(3):425–432.
   PubMed Web of Science ®Google Scholar
• Calabrese M, Poretto V, Favaretto A, et al. Cortical lesion load associates with progression of disability in multiple sclerosis. Brain. 2012 Oct;135(10):2952–2961.
   PubMed Web of Science ®Google Scholar
• Kilsdonk ID, Jonkman LE, Klaver R, et al. Increased cortical grey matter lesion detection in multiple sclerosis with 7 T MRI: a post-mortem verification study. Brain. 2016 May;139(5):1472–1481.
   PubMedGoogle Scholar
• Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb;17(2):162–173.
   PubMed Web of Science ®Google Scholar
• Eijlers AJC, Dekker I, Steenwijk MD, et al. Cortical atrophy accelerates as cognitive decline worsens in multiple sclerosis. Neurology. 2019 Oct 1;93(14):e1348–e1359.
   PubMed Web of Science ®Google Scholar
• Steenwijk MD, Geurts JJ, Daams M, et al. Cortical atrophy patterns in multiple sclerosis are non-random and clinically relevant. Brain. 2016 Jan;139(1):115–126.
   PubMedGoogle Scholar
• Scalfari A, Romualdi C, Nicholas RS, et al. The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis. Neurology. 2018 Jun 12;90(24):e2107–e2118.
   PubMed Web of Science ®Google Scholar
• Zivadinov R, Bergsland N, Dwyer MG. Atrophied brain lesion volume, a magnetic resonance imaging biomarker for monitoring neurodegenerative changes in multiple sclerosis. Quant Imaging Med Surg. 2018 Nov;8(10):979–983.
   PubMed Web of Science ®Google Scholar
• Tavazzi E, Bergsland N, Kuhle J, et al. A multimodal approach to assess the validity of atrophied T2-lesion volume as an MRI marker of disease progression in multiple sclerosis. J Neurol. 2020 Mar;267(3):802-811.
   PubMed Web of Science ®Google Scholar
• Zivadinov R, Horakova D, Bergsland N, et al. A serial 10-year follow-up study of atrophied brain lesion volume and disability progression in patients with relapsing-remitting MS. AJNR Am J Neuroradiol. 2019 Mar;40(3):446–452.
   PubMed Web of Science ®Google Scholar
• Genovese AV, Hagemeier J, Bergsland N, et al. Atrophied brain T2 lesion volume at MRI is associated with disability progression and conversion to secondary progressive multiple sclerosis. Radiology. 2019 Nov;293(2):424–433.
   PubMed Web of Science ®Google Scholar
• Kaunzner UW, Kang Y, Zhang S, et al. Quantitative susceptibility mapping identifies inflammation in a subset of chronic multiple sclerosis lesions. Brain. 2019 Jan 1;142(1):133–145.
   PubMedGoogle Scholar
• Zhang S, Nguyen TD, Hurtado Rua SM, et al. Quantitative susceptibility mapping of time-dependent susceptibility changes in multiple sclerosis lesions. AJNR Am J Neuroradiol. 2019 Jun;40(6):987–993.
   PubMed Web of Science ®Google Scholar
• Dal-Bianco A, Grabner G, Kronnerwetter C, et al. Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging. Acta Neuropathol. 2017 Jan;133(1):25–42.
   PubMed Web of Science ®Google Scholar
• Absinta M, Sati P, Masuzzo F, et al. Association of chronic active multiple sclerosis lesions with disability in vivo. JAMA Neurol. 2019 Aug 12;76(12):1474.
   PubMed Web of Science ®Google Scholar
• Wicken C, Nguyen J, Karna R, et al. Leptomeningeal inflammation in multiple sclerosis: insights from animal and human studies. Mult Scler Relat Disord. 2018 Nov;26:173–182.
   PubMed Web of Science ®Google Scholar
• Absinta M, Vuolo L, Rao A, et al. Gadolinium-based MRI characterization of leptomeningeal inflammation in multiple sclerosis. Neurology. 2015 Jul 7;85(1):18–28.
   PubMed Web of Science ®Google Scholar
• Zivadinov R, Ramasamy DP, Vaneckova M, et al. Leptomeningeal contrast enhancement is associated with progression of cortical atrophy in MS: a retrospective, pilot, observational longitudinal study. Mult Scler. 2017 Sep;23(10):1336–1345.
   PubMed Web of Science ®Google Scholar
• Harrison DM, Wang KY, Fiol J, et al. Leptomeningeal enhancement at 7T in multiple sclerosis: frequency, morphology, and relationship to cortical volume. J Neuroimaging. 2017 Sep;27(5):461–468.
   PubMed Web of Science ®Google Scholar
• Ighani M, Jonas S, Izbudak I, et al. No association between cortical lesions and leptomeningeal enhancement on 7-Tesla MRI in multiple sclerosis. Mult Scler. 2019;1:1352458519876037.
   Google Scholar
• Bevan RJ, Evans R, Griffiths L, et al. Meningeal inflammation and cortical demyelination in acute multiple sclerosis. Ann Neurol. 2018 Dec;84(6):829–842.
   PubMed Web of Science ®Google Scholar
• Bergsland N, Ramasamy D, Tavazzi E, et al. Leptomeningeal contrast enhancement is related to focal cortical thinning in relapsing-remitting multiple sclerosis: a cross-sectional MRI study. AJNR Am J Neuroradiol. 2019 Apr;40(4):620–625.
   PubMed Web of Science ®Google Scholar
• Makshakov G, Magonov E, Totolyan N, et al. Leptomeningeal contrast enhancement is associated with disability progression and grey matter atrophy in multiple sclerosis. Neurol Res Int. 2017;2017:8652463.
   PubMed Web of Science ®Google Scholar
• Zivadinov R, Ramasamy DP, Hagemeier J, et al. Evaluation of leptomeningeal contrast enhancement using pre-and postcontrast subtraction 3D-FLAIR imaging in multiple sclerosis. AJNR Am J Neuroradiol. 2018 Apr;39(4):642–647.
   PubMed Web of Science ®Google Scholar
• Casserly C, Seyman EE, Alcaide-Leon P, et al. Spinal cord atrophy in multiple sclerosis: a systematic review and meta-analysis. J Neuroimaging. 2018 Nov;28(6):556–586.
   PubMed Web of Science ®Google Scholar
• Bernitsas E, Bao F, Seraji-Bozorgzad N, et al. Spinal cord atrophy in multiple sclerosis and relationship with disability across clinical phenotypes. Mult Scler Relat Disord. 2015 Jan;4(1):47–51.
   PubMed Web of Science ®Google Scholar
• Tsagkas C, Magon S, Gaetano L, et al. Spinal cord volume loss: a marker of disease progression in multiple sclerosis. Neurology. 2018 Jul 24;91(4):e349–e358.
   PubMed Web of Science ®Google Scholar
• Rocca MA, Horsfield MA, Sala S, et al. A multicenter assessment of cervical cord atrophy among MS clinical phenotypes. Neurology. 2011 Jun 14;76(24):2096–2102.
   PubMed Web of Science ®Google Scholar
• Rocca MA, Valsasina P, Meani A, et al. Clinically relevant cranio-caudal patterns of cervical cord atrophy evolution in MS.. Neurology. 2019 Nov 12;93(20):e1852–e1866.
   PubMed Web of Science ®Google Scholar
• Dekker I, Sombekke MH, Balk LJ, et al. Infratentorial and spinal cord lesions: cumulative predictors of long-term disability? Mult Scler. 2019;2:1352458519864933.
   Google Scholar
• De Stefano N, Giorgio A, Battaglini M, et al. Assessing brain atrophy rates in a large population of untreated multiple sclerosis subtypes. Neurology. 2010 Jun 8;74(23):1868–1876.
   PubMed Web of Science ®Google Scholar
• Singhal T, Tauhid S, Hurwitz S, et al. The effect of glatiramer acetate on spinal cord volume in relapsing-remitting multiple sclerosis. J Neuroimaging. 2017 Jan;27(1):33–36.
   PubMed Web of Science ®Google Scholar
• Dupuy SL, Khalid F, Healy BC, et al. The effect of intramuscular interferon beta-1a on spinal cord volume in relapsing-remitting multiple sclerosis. BMC Med Imaging. 2016 Oct 5;16(1):56.
   PubMed Web of Science ®Google Scholar
• Cawley N, Tur C, Prados F, et al. Spinal cord atrophy as a primary outcome measure in phase II trials of progressive multiple sclerosis. Mult Scler. 2018 Jun;24(7):932–941.
   PubMed Web of Science ®Google Scholar
• Gros C, De Leener B, Badji A, et al. Automatic segmentation of the spinal cord and intramedullary multiple sclerosis lesions with convolutional neural networks. Neuroimage. 2019 Jan 1;184:901–915.
   PubMed Web of Science ®Google Scholar
• Moccia M, Prados F, Filippi M, et al. Longitudinal spinal cord atrophy in multiple sclerosis using the generalized boundary shift integral. Ann Neurol. 2019 Nov;86(5):704–713.
   PubMed Web of Science ®Google Scholar
• Daams M, Weiler F, Steenwijk MD, et al. Mean upper cervical cord area (MUCCA) measurement in long-standing multiple sclerosis: relation to brain findings and clinical disability. Mult Scler. 2014 Dec;20(14):1860–1865.
   PubMed Web of Science ®Google Scholar
• Zurawski J, Glanz BI, Healy BC, et al. The impact of cervical spinal cord atrophy on quality of life in multiple sclerosis. J Neurol Sci. 2019 Aug;403(403):38–43.
   PubMedGoogle Scholar
• Yiannakas MC, Mustafa AM, De Leener B, et al. Fully automated segmentation of the cervical cord from T1-weighted MRI using PropSeg: application to multiple sclerosis. Neuroimage Clin. 2016;10:71–77.
   PubMed Web of Science ®Google Scholar
• Weeda MM, Middelkoop SM, Steenwijk MD, et al. Validation of mean upper cervical cord area (MUCCA) measurement techniques in multiple sclerosis (MS): high reproducibility and robustness to lesions, but large software and scanner effects. Neuroimage Clin. 2019;24:101962.
   PubMed Web of Science ®Google Scholar
• Liptak Z, Berger AM, Sampat MP, et al. Medulla oblongata volume: a biomarker of spinal cord damage and disability in multiple sclerosis. AJNR Am J Neuroradiol. 2008 Sep;29(8):1465–1470.
   PubMed Web of Science ®Google Scholar
• Collorone S, Cawley N, Grussu F, et al. Reduced neurite density in the brain and cervical spinal cord in relapsing-remitting multiple sclerosis: a NODDI study. Mult Scler. 2019;4:1352458519885107.
   Google Scholar
• Spano B, Giulietti G, Pisani V, et al. Disruption of neurite morphology parallels MS progression. Neurol Neuroimmunol Neuroinflamm. 2018 Nov;5(6):e502.
   PubMed Web of Science ®Google Scholar
• De Santis S, Bastiani M, Droby A, et al. Characterizing microstructural tissue properties in multiple sclerosis with diffusion MRI at 7 T and 3 T: the impact of the experimental design. Neuroscience. 2019 Apr 1;403:17–26.
   PubMed Web of Science ®Google Scholar
• Plemel JR, Liu W-Q, Yong VW. Remyelination therapies: a new direction and challenge in multiple sclerosis. Nat Rev Drug Discov. 2017 Sep;16(9):617–634.
   PubMed Web of Science ®Google Scholar
• Wilhelm MJ, Ong HH, Wehrli SL, et al. Direct magnetic resonance detection of myelin and prospects for quantitative imaging of myelin density. Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9605–9610.
   PubMed Web of Science ®Google Scholar
• Sheth V, Shao H, Chen J, et al. Magnetic resonance imaging of myelin using ultrashort echo time (UTE) pulse sequences: phantom, specimen, volunteer and multiple sclerosis patient studies. Neuroimage. 2016 Aug;136(136):37–44.
   PubMedGoogle Scholar
• Guglielmetti C, Boucneau T, Cao P, et al. Longitudinal evaluation of demyelinated lesions in a multiple sclerosis model using ultrashort echo time magnetization transfer (UTE-MT) imaging. Neuroimage. 2019 Dec;4(208):116415.
   Google Scholar
• Ma YJ, Searleman AC, Jang H, et al. Whole-brain myelin imaging using 3D Double-Echo Sliding Inversion Recovery Ultrashort Echo Time (DESIRE UTE) MRI. Radiology. 2019;19:190911.
   Google Scholar
• Hagemeier J, Weinstock-Guttman B, Bergsland N, et al. Iron deposition on SWI-filtered phase in the subcortical deep gray matter of patients with clinically isolated syndrome may precede structure-specific atrophy. AJNR Am J Neuroradiol. 2012 Sep;33(8):1596–1601.
   PubMed Web of Science ®Google Scholar
• Ropele S, Enzinger C, Fazekas F. Iron mapping in multiple sclerosis. Neuroimaging Clin N Am. 2017 May;27(2):335–342.
   PubMed Web of Science ®Google Scholar
• Stephenson E, Nathoo N, Mahjoub Y, et al. Iron in multiple sclerosis: roles in neurodegeneration and repair. Nat Rev Neurol. 2014 Aug;10(8):459–468.
   PubMed Web of Science ®Google Scholar
• Hernández‐Torres E, Wiggermann V, Machan L, et al. Increased mean R2* in the deep gray matter of multiple sclerosis patients: have we been measuring atrophy? J Magn Reson Imaging. 2019 Jul;50(1):201–208.
   PubMed Web of Science ®Google Scholar
• Absinta M, Sati P, Schindler M, et al. Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions. J Clin Invest. 2016 Jul 1;126(7):2597–2609.
   PubMed Web of Science ®Google Scholar
• Lee NJ, Ha S-K, Sati P, et al. Potential role of iron in repair of inflammatory demyelinating lesions. J Clin Invest. 2019 Oct 1;129(10):4365–4376.
   PubMed Web of Science ®Google Scholar
• Zivadinov R, Tavazzi E, Bergsland N, et al. Brain iron at quantitative MRI is associated with disability in multiple sclerosis. Radiology. 2018 Nov;289(2):487–496.
   PubMed Web of Science ®Google Scholar
• Bian W, Harter K, Hammond-Rosenbluth KE, et al. A serial in vivo 7T magnetic resonance phase imaging study of white matter lesions in multiple sclerosis. Mult Scler. 2013 Jan;19(1):69–75.
   PubMed Web of Science ®Google Scholar
• Petzold A, Balcer LJ, Calabresi PA, et al. Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol. 2017 Oct;16(10):797–812.
   PubMed Web of Science ®Google Scholar
• Zivadinov R, Tavazzi E, Hagemeier J, et al. The effect of glatiramer acetate on retinal nerve fiber layer thickness in patients with relapsing–remitting multiple sclerosis: a longitudinal optical coherence tomography study. CNS Drugs. 2018 Aug;32(8):763–770.
   PubMed Web of Science ®Google Scholar
• El Ayoubi NK, Ghassan S, Said M, et al. Retinal measures correlate with cognitive and physical disability in early multiple sclerosis. J Neurol. 2016 Nov;263(11):2287–2295.
   PubMed Web of Science ®Google Scholar
• Villoslada P, Sepulcre J, Toledo J, et al. Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis. Neurology. 2008 Nov 18;71(21):1747. author reply 1747-8.
   PubMed Web of Science ®Google Scholar
• Carotenuto A, Giordano B, Dervenoulas G, et al. [(18)F]Florbetapir PET/MR imaging to assess demyelination in multiple sclerosis. Eur J Nucl Med Mol Imaging. 2020 Feb;47(2):366–378.
   PubMed Web of Science ®Google Scholar
• Auvity S, Tonietto M, Caille F, et al. Repurposing radiotracers for myelin imaging: a study comparing 18F-florbetaben, 18F-florbetapir, 18F-flutemetamol,11C-MeDAS, and 11C-PiB. Eur J Nucl Med Mol Imaging. 2020 Feb;47(2):490–501.
   PubMed Web of Science ®Google Scholar
• Chen BY, Ghezzi C, Villegas B, et al. (18)F-FAC PET visualizes brain-infiltrating leukocytes in a mouse model of multiple sclerosis. J Nucl Med. 2019 Oct 25. DOI:10.2967/jnumed.119.229351.
   Web of Science ®Google Scholar
• Herranz E, Louapre C, Treaba CA, et al. Profiles of cortical inflammation in multiple sclerosis by (11)C-PBR28 MR-PET and 7 Tesla imaging. Mult Scler. 2019;1:1352458519867320.
   Google Scholar
• Singhal T, O’Connor K, Dubey S, et al. Gray matter microglial activation in relapsing vs progressive MS: a [F-18]PBR06-PET study. Neurol Neuroimmunol Neuroinflamm. 2019 Sep;6(5):e587.
   PubMed Web of Science ®Google Scholar
• Singhal T, Weiner HL, Bakshi R. TSPO-PET imaging to assess cerebral microglial activation in multiple sclerosis. Semin Neurol. 2017 Oct;37(5):546–557.
   PubMed Web of Science ®Google Scholar
• Hogel H, Rissanen E, Vuorimaa A, et al. Positron emission tomography imaging in evaluation of MS pathology in vivo. Mult Scler. 2018 Oct;24(11):1399–1412.
   PubMed Web of Science ®Google Scholar
• Bauckneht M, Capitanio S, Raffa S, et al. Molecular imaging of multiple sclerosis: from the clinical demand to novel radiotracers. EJNMMI Radiopharm Chem. 2019 Apr 8;4(1):6.
   PubMedGoogle Scholar
• Takano A, Piehl F, Hillert J, et al. In vivo TSPO imaging in patients with multiple sclerosis: a brain PET study with [18F]FEDAA1106. EJNMMI Res. 2013 Apr 24;3(1):30.
   PubMed Web of Science ®Google Scholar
• Datta G, Colasanti A, Kalk N, et al. 11 C-PBR28 and 18 F-PBR111 detect white matter inflammatory heterogeneity in multiple sclerosis. J Nucl Med. 2017 Sep;58(9):1477–1482.
   PubMed Web of Science ®Google Scholar
• Jurgens T, Jafari M, Kreutzfeldt M, et al. Reconstruction of single cortical projection neurons reveals primary spine loss in multiple sclerosis. Brain. 2016 Jan;139(1):39–46.
   PubMedGoogle Scholar
• Friese MA. Widespread synaptic loss in multiple sclerosis. Brain. 2016 Jan;139(1):2–4.
   PubMedGoogle Scholar
• Albert M, Barrantes-Freer A, Lohrberg M, et al. Synaptic pathology in the cerebellar dentate nucleus in chronic multiple sclerosis. Brain Pathol. 2017 Nov;27(6):737–747.
   PubMed Web of Science ®Google Scholar
• Misgeld T, Schwarz TL. Mitostasis in neurons: maintaining mitochondria in an extended cellular architecture. Neuron. 2017 Nov 1;96(3):651–666.
   PubMed Web of Science ®Google Scholar
• Cai Z, Li S, Matuskey D, et al. PET imaging of synaptic density: a new tool for investigation of neuropsychiatric diseases. Neurosci Lett. 2019 Jan;691(691):44–50.
   PubMedGoogle Scholar
• Querol M, Chen JW, Weissleder R, et al. DTPA-bisamide-based MR sensor agents for peroxidase imaging. Org Lett. 2005 Apr 28;7(9):1719–1722.
   PubMed Web of Science ®Google Scholar
• Pulli B, Bure L, Wojtkiewicz GR, et al. Multiple sclerosis: myeloperoxidase immunoradiology improves detection of acute and chronic disease in experimental model. Radiology. 2015 May;275(2):480–489.
   PubMed Web of Science ®Google Scholar
• Kirschbaum K, Sonner JK, Zeller MW, et al. In vivo nanoparticle imaging of innate immune cells can serve as a marker of disease severity in a model of multiple sclerosis. Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13227–13232.
   PubMed Web of Science ®Google Scholar
• Kerbrat A, Combes B, Commowick O, et al. USPIO-positive MS lesions are associated with greater tissue damage than gadolinium-positive-only lesions during 3-year follow-up. Mult Scler. 2017 Oct;1:1352458517736148.
   Google Scholar
• Saar G, Koretsky AP. Manganese enhanced MRI for use in studying neurodegenerative diseases. Front Neural Circuits. 2018;12:114.
   PubMed Web of Science ®Google Scholar
• Lin T-H, Kim JH, Perez-Torres C, et al. Axonal transport rate decreased at the onset of optic neuritis in EAE mice. Neuroimage. 2014 Oct;100(100):244–253.
   PubMedGoogle Scholar
• Ferguson B, Matyszak MK, Esiri MM, et al. Axonal damage in acute multiple sclerosis lesions. Brain. 1997 Mar;120(Pt 3):393–399.
   PubMed Web of Science ®Google Scholar
• Sorbara CD, Wagner NE, Ladwig A, et al. Pervasive axonal transport deficits in multiple sclerosis models. Neuron. 2014 Dec 17;84(6):1183–1190.
   PubMed Web of Science ®Google Scholar
• Splendiani A, Perri M, Marsecano C, et al. Effects of serial macrocyclic-based contrast materials gadoterate meglumine and gadobutrol administrations on gadolinium-related dentate nuclei signal increases in unenhanced T1-weighted brain: a retrospective study in 158 multiple sclerosis (MS) patients. Radiol Med. 2018 Feb;123(2):125–134.
   PubMed Web of Science ®Google Scholar
• Zivadinov R, Bergsland N, Hagemeier J, et al. Cumulative gadodiamide administration leads to brain gadolinium deposition in early MS. Neurology. 2019 Aug 6;93(6):e611–e623.
   PubMed Web of Science ®Google Scholar