OBJECTIVE: The analysis of the MR phase provides additional information on the tissue microstructure. In multiple sclerosis (MS) lesions phase alterations may reflect different stages of inflammatory activity. Here we investigated lesion morphology in MS patients with short and long disease duration on T2* weighted, phase, magnitude and susceptibility weighted imaging (SWI) at 7 Tesla (T). METHODS: 17 MS or clinically isolated syndrome patients with short (<60 months) and 11 with long (>60 months) disease duration underwent 7 T MRI. Lesions were subsequently analyzed side-by-side with regard to morphology and visibility on T2* weighted, SWI, magnitude and SWI-filtered phase images. RESULTS: 126 of 192 T2* weighted lesions (65.6%) were characterized by a phase alteration pattern, and hence could be differentiated on phase images. In detail, a significantly reduced proportion of lesions showing phase alterations was detectable in patients with longer disease duration (mean±SD 51 ± 37%, range 0-100%) compared to patients with short disease duration (mean ± SD 90 ± 19.5%, range 50-100%, p = 0.003). CONCLUSION: This cross-sectional study identified different patterns of phase changes in lesions of MS patients with short and long standing disease. Longitudinal studies are warranted to prove that MR phase imaging is useful in determining the activity and the developmental stage of individual MS plaques.

Berlin Ultrahigh Field Facility Max Delbrueck Center for Molecular Medicine Berlin Germany; Experimental and Clinical Research Center Charité Universitaetsmedizin Berlin and Max Delbrueck Center for Molecular Medicine Berlin Germany

Clinical and Experimental Multiple Sclerosis Research Center Charité Universitaetsmedizin Berlin Berlin Germany; Department of Neurology Charité Universitaetsmedizin Berlin Berlin Germany

Department of Radiology NYU School of Medicine New York New York United States of America

Institute of Neuroradiology Universitaetsmedizin Goettingen Goettingen Germany; Department of Neurology and Center of Clinical Neuroscience Charles University Prague 1st Faculty of Medicine and General University Hospital Prague Prague Czech Republic

Multiple Sclerosis Care Center Department of Neurology NYU School of Medicine New York New York United States of America

NeuroCure Clinical Research Center Charité Universitaetsmedizin Berlin Berlin Germany

NeuroCure Clinical Research Center Charité Universitaetsmedizin Berlin Berlin Germany; Clinical and Experimental Multiple Sclerosis Research Center Charité Universitaetsmedizin Berlin Berlin Germany; Department of Neurology Charité Universitaetsmedizin Berlin Berlin Germany; Experimental and Clinical Research Center Charité Universitaetsmedizin Berlin and Max Delbrueck Center for Molecular Medicine Berlin Germany

NeuroCure Clinical Research Center Charité Universitaetsmedizin Berlin Berlin Germany; Department of Neurology Asklepios Fachklinikum Teupitz Teupitz Germany

NeuroCure Clinical Research Center Charité Universitaetsmedizin Berlin Berlin Germany; Institute of Neuroradiology Universitaetsmedizin Goettingen Goettingen Germany; Berlin Ultrahigh Field Facility Max Delbrueck Center for Molecular Medicine Berlin Germany; Experimental and Clinical Research Center Charité Universitaetsmedizin Berlin and Max Delbrueck Center for Molecular Medicine Berlin Germany

Zobrazit více v PubMed

Polman CH, Reingold SC, Banwell B. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Annals of neurology. 2011;69: 292–302. 10.1002/ana.22366 PubMed DOI PMC

Sinnecker T, Mittelstaedt P, Dörr J, Pfueller CF, Harms L, Niendorf T, et al. Multiple sclerosis lesions and irreversible brain tissue damage: a comparative ultrahigh-field strength magnetic resonance imaging study. Arch Neurol. 2012;69: 739–745. 10.1001/archneurol.2011.2450 PubMed DOI

Nielsen AS, Kinkel RP, Tinelli E, Benner T, Cohen-Adad J, Mainero C. Focal cortical lesion detection in multiple sclerosis: 3 Tesla DIR versus 7 Tesla FLASH-T2. J Magn Reson Imaging. 2012;35: 537–542. 10.1002/jmri.22847 PubMed DOI PMC

de Graaf WL, Zwanenburg JJ, Visser F, Wattjes MP, Pouwels PJ, Geurts JJ, et al. Lesion detection at seven Tesla in multiple sclerosis using magnetisation prepared 3D-FLAIR and 3D-DIR. Eur Radiol. 2012;22: 221–231. 10.1007/s00330-011-2242-z PubMed DOI PMC

Sinnecker T, Dörr J, Pfueller CF, Harms L, Ruprecht K, Jarius S, et al. Distinct lesion morphology at 7-T MRI differentiates neuromyelitis optica from multiple sclerosis. Neurology. 2012;79: 708–714. 10.1212/WNL.0b013e3182648bc8 PubMed DOI

Wuerfel J, Sinnecker T, Ringelstein EB, Jarius S, Schwindt W, Niendorf T, et al. Lesion morphology at 7 Tesla MRI differentiates Susac syndrome from multiple sclerosis. Mult Scler. 2012;18: 1592–1599. 10.1177/1352458512441270 PubMed DOI

Tallantyre EC, Dixon JE, Donaldson I, Owens T, Morgan PS, Morris PG, et al. Ultra-high-field imaging distinguishes MS lesions from asymptomatic white matter lesions. Neurology. 2011;76: 534–539. 10.1212/WNL.0b013e31820b7630 PubMed DOI PMC

Mistry N, Dixon JE, Tallantyre EC, Tench C, Abdel-Fahim R, Jaspan T, et al. Central veins in brain lesions visualized with high-field magnetic resonance imaging: a pathologically specific diagnostic biomarker for inflammatory demyelination in the brain. JAMA Neurol. 2013;70: 623–628. 10.1001/jamaneurol.2013.1405 PubMed DOI

Pitt D, Boster A, Pei W, Wohleb E, Jasne A, Zachariah CR, et al. Imaging cortical lesions in multiple sclerosis with ultra-high-field magnetic resonance imaging. Arch Neurol. 2010;67: 812–818. 10.1001/archneurol.2010.148 PubMed DOI

Bagnato F, Hamenter S, Yao B, van Gelderen P, Merkle H, Cantor FK, et al. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. Brain. 2011;134: 3602–3615. 10.1093/brain/awr278 PubMed DOI PMC

Hametner S, Wimmer I, Haider L, Pfeifenbring S, Brück W, Lassmann H. Iron and neurodegeneration in the multiple sclerosis brain. Ann Neurol. 2013;74: 848–861. 10.1002/ana.23974 PubMed DOI PMC

Stephenson E, Nathoo N, Mahjoub Y, Dunn JF, Yong VW. Iron in multiple sclerosis: roles in neurodegeneration and repair. Nat Rev Neurol. 2014;10: 459–468. 10.1038/nrneurol.2014.118 PubMed DOI

Absinta M, Sati P, Gaitan MI, Maggi P, Cortese IC, Fillipi M, et al. 7T Phase Imaging of acute MS lesions: A new window into the inflammatory process Annals of neurology. Ann Neurol. 2013;74: 669–678. 10.1002/ana.23959 PubMed DOI PMC

Yablonskiy DA, Luo J, Sukstanskii AL, Iyer A, Cross AH. Biophysical mechanisms of MRI signal frequency contrast in multiple sclerosis. Proc Natl Acad Sci USA. 2012;109: 14212–7. 10.1073/pnas.1206037109 PubMed DOI PMC

Kuchling J, Sinnecker T, Bozin I, Dörr J, Madai V, Sobesky J, et al. Identical lesion morphology in primary progressive and relapsing-remitting MS-an ultrahigh field MRI study. Mult Scler. 2014; 10.1177/1352458514531084 PubMed DOI

Mueller K, Kuchling J, Dörr J, Harms L, Ruprecht K, Niendorf T, et al. Detailing intra-lesional venous lumen shrinking in multiple sclerosis investigated by sFLAIR MRI at 7-T. J Neur. 2014;261: 2032–2036. PubMed

Sinnecker T, Oberwahrenbrock T, Metz I, Zimmermann H, Pfueller CF, Harms L, et al. Optic radiation damage in multiple sclerosis is associated with visual dysfunction and retinal thinning—an ultrahigh-field MR pilot study. Eur Radiol. 2014; 10.1007/s00330-014-3358-8 PubMed DOI

Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33: 1444–1452. PubMed

Haacke EM, Makki M, Ge Y, Maheshwari M, Sehgal V, Hu J, et al. Characterizing iron deposition in multiple sclerosis lesions using susceptibility weighted imaging. J Magn Reson Imaging. 2009;29: 537–544. 10.1002/jmri.21676 PubMed DOI PMC

Wuerfel J, Haertle M, Waiczies H, Tysiak E, Bechmann I, Wernecke KD, et al. Perivascular spaces—MRI marker of inflammatory activity in the brain? Brain. 2008;131: 2332–40. 10.1093/brain/awn171 PubMed DOI

Li W, Wu B, Liu C. Quantitative susceptibility mapping of human brain reflects spatial variation in tissue composition. Neuroimage. 2011;55: 1645–1656. 10.1016/j.neuroimage.2010.11.088 PubMed DOI PMC

Mehta V, Pei W, Yang G, Swamy E, Boster A, Schmalbrock P, et al. Iron is a sensitive biomarker for inflammation in Multiple Sclerosis. PLoS One. 2013;8: 1–10. PubMed PMC

Haacke EM, Cheng NY, House MJ, Liu Q, Neelavalli J, Ogg RJ, et al. Imaging iron stores in the brain using magnetic resonance imaging. Magn Reson Imaging. 2005;23: 1–25. PubMed

Duyn JH, van Gelderen P, Li TQ, de Zwart JA, Koretsky AP, Fukunaga M. High-field MRI of brain cortical substructure based on signal phase. Proc Natl Acad Sci USA. 2007;104: 11796–801. PubMed PMC

Sukstanskii AL, Yablonskiy DA. On the role of neuronal magnetic susceptibility and structure symmetry on gradient echo MR signal formation. Magn Reson Med. 2014;71: 345–353. 10.1002/mrm.24629 PubMed DOI PMC

He X, Yablonskiy DA. Biophysical mechanisms of phase contrast in gradient echo MRI. Proc Natl Acad Sci USA. 2009;106: 13558–63. 10.1073/pnas.0904899106 PubMed DOI PMC

Sinnecker T, Bozin I, Dörr J, Pfueller CF, Harms L, Niendorf T, et al. Periventricular venous density in multiple sclerosis is inversely associated with T2 lesion count: a 7 Tesla MRI study. Mult Scler. 2013;19: 316–325. 10.1177/1352458512451941 PubMed DOI

Ge Y, Zohrabian VM, Osa EO, Xu J, Jaggi H, Herbert J, et al. Diminished visibility of cerebral venous vasculature in multiple sclerosis by susceptibility-weighted imaging at 3.0 Tesla. J Magn Reson Imaging. 2009;29: 1180–1194. PubMed PMC

Bian W, Harter K, Hammond-Rosenbluth KE, Lupo JM, Xu D, Kelley DA, et al. A serial in vivo 7T magnetic resonance phase imaging study of white matter lesions in multiple sclerosis. Mult Scler. 2013;19: 69–75. 10.1177/1352458512447870 PubMed DOI

Yao B, Bagnato F, Matsuura E, Merkle H, van Gelderen P, Cantor FK, et al. Chronic multiple sclerosis lesions: characterization with high-field-strength MR imaging. Radiology. 2012;262: 206–215. 10.1148/radiol.11110601 PubMed DOI PMC

Craelius W, Migdal MW, Luessenhop CP, Sugar A, Mihalakis I. Iron deposits surrounding multiple sclerosis plaques. Arch Pathol Lab Med. 1982;106: 397–399. PubMed

Adams CW. Perivascular iron deposition and other vascular damage in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1988;51: 260–265. PubMed PMC

Grabner G, Dal-Bianco A, Schernthaner M, Vass K, Lassmann H, Trattnig S. Analysis of multiple sclerosis lesions using a fusion of 3.0 T FLAIR and 7.0 T SWI phase: FLAIR SWI. J Magn Reson Imaging. 2011;33: 543–549. 10.1002/jmri.22452 PubMed DOI

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: 19–30. 10.3174/ajnr.A1400 PubMed DOI PMC

Bakshi R, Benedict RH, Bermel RA, Caruthers SD, Puli SR, Tjoa CW, et al. T2 hypointensity in the deep gray matter of patients with multiple sclerosis: a quantitative magnetic resonance imaging study. Arch Neurol. 2002;59: 62–68. PubMed

Connor JR, Menzies SL. Relationship of iron to oligodendrocytes and myelination. Glia. 1996;17: 83–93. PubMed

Chen W, Gauthier SA, Gupta A, Comunale J, Liu T, Wang S, et al. Quantitative susceptibility mapping of multiple sclerosis lesions at various ages. Radiology. 2014;271: 183–192. 10.1148/radiol.13130353 PubMed DOI PMC

Dixon JE, Simpson A, Mistry N, Evangelou N, Morris PG. In Optimisation of T₂*-weighted MRI for the detection of small veins in multiple sclerosis at 3 T and 7 T. Eur J Radiol. 2013;82: 719–727. 10.1016/j.ejrad.2011.09.023 PubMed DOI

Ultrahigh field MRI in clinical neuroimmunology: a potential contribution to improved diagnostics and personalised disease management