Research Projects and Papers

RESEARCH PROJECTS

We have projects in the following areas:

  • Imaging and treating chronic inflammation in multiple sclerosis
  • Understanding and imaging the development and repair of lesions in multiple sclerosis
  • Cerebrospinal fluid dynamics in aging and neuroinflammation
  • The “central vein sign” (CVS) in multiple sclerosis
  • Cortical lesions in multiple sclerosis
  • New methods for image acquisition and analysis — from ultra-low to ultra-high-field MRI
  • Identifying people at risk for developing multiple sclerosis
  • Imaging of functional systems in neurological disease

Scroll down to see our published work in these areas (last updated April 4, 2024).

IMAGING AND TREATING CHRONIC INFLAMMATION IN MULTIPLE SCLEROSIS

We have helped to define: (1) the paramagnetic rim lesion as an MRI biomarker of chronic focal inflammation in the white matter; and (2) gadolinium enhancement as an MRI biomarker of chronic inflammation in the leptomeninges. We are embarking on proof-of-concept clinical trials to see whether we can reduce the inflammation, preserve brain tissue, and initiate repair.

  • Borrelli S, Martire MS, Stölting A, Vanden Bulcke C, Guisset F, Bugli C, Yildiz H, Pothen L, Elands S, Martinelli V, Smith BR, Jacobson S, Du Pasquier R, van Pesch V, Filippi M, Reich DS, Absinta M, Maggi P. Central vein sign, cortical lesions, and paramagnetic rim lesions for the diagnostic and prognostic workup of multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 2024; in press. PMCID: in progress.
  • Maggi P, Vanden Bulcke C, Pedrini E, Bugli C, Sellimi A, Wynen M, Stölting A, Mullins WA, Kalaitzidis G, Lolli V, Perrotta G, El Sankari S, Duprez T, Li X, Calabresi PA, van Pesch V, Reich DS, Absinta M. B-cell depletion therapy does not resolve chronic active multiple sclerosis lesions. EBioMedicine 2023; 94:10471. Epub 2023 Jul 10. PMID: 37437310, PMCID: 10436266, DOI: 10.1016/j.ebiom.2023.104701.
  • Hemond C, Baek J, Ionete C, Reich DS. Paramagnetic rim lesions are associated with pathogenic CSF profiles and worse clinical outcomes in multiple sclerosis: a retrospective cross-sectional study. Mult Scler J 2022; 28:2046-2056. Epub 2022 Jun 24. PMID: 35748669, PMCID: 9588517, DOI: 10.1177/13524585221102921.
  • Hemond CC, Reich DS, Dundamadappa SK. Paramagnetic rim lesions in multiple sclerosis: comparison of visualization at 1.5-T and 3-T MRI. AJR Am J Roentgenology 2021; 219:120-131. Epub 2021 Dec 1. PMID: 34851712, PMCID: 9416872, DOI: 10.2214/AJR.21.26777. (Selected for AJR Journal Club, July 2022.)
  • Absinta M, Maric D, Gharagozloo M, Garton T, Smith MD, Jin J, Fitzgerald KC, Song A, Liu P, Lin JP, Wu T, Johnson KR, McGovern DB, Schafer DP, Calabresi PA, Reich DS. A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis. Nature 2021; 597:709-714. Epub 2021 Sep 8. PMID: 34497421, PMCID: 8719282, DOI: 10.1038/s41586-021-03892-7.
  • Maggi P, Kuhle J, Schädelin S, van der Meer F, Weigel M, Galbusera R, Mathias A, Lu PJ, Rahmanzadeh R, Benkert P, La Rosa F, Bach Cuadra M, Sati P, Théaudin M, Pot Ca, Van Pesch V, Leppert D, Stadelmann C, Du Pasquier RA, Reich DS, ✉︎Absinta M, ✉︎Granziera C. Chronic white matter inflammation and serum neurofilament levels in multiple sclerosis. Neurology 2021; 97:e543-e553. Epub 2021 Jun 4. PMID: 34088875, PMCID: 8424501, DOI: 10.1212/WNL.0000000000012326.
  • Barquero García G, La Rosa F, Kebiri H, Lu PJ, Rahmanzadeh R, Weigel M, Fartaria MJ, Kober T, Théaudin M, Du Pasquier R, Sati P, Reich DS, Absinta M, Granziera C, ✉︎Maggi P, ✉︎Bach Cuadra M. RimNet: A deep 3D multimodal MRI architecture for paramagnetic rim lesions assessment in multiple sclerosis. Neuroimage Clin 2020; 28:102412. Epub 2020 Sep 4. PMID: 32961401, PMCID: 7509077, DOI: 10.1016/j.nicl.2020.102412.
  • Maggi P, Sati P, Nair G, Cortese I, Jacobson S, Smith BR, Nath A, Ohayon J, van Pesch V, Perrotta G, Pot C, Théaudin M, Martinelli V, Scotti R, Wu T, Du Pasquier R, Calabresi PA, Filippi M, Reich DS, Absinta M. Paramagnetic rim lesions are specific to multiple sclerosis: an international multicenter 3T MRI study. Ann Neurol 2020; 88:1034-1042. Epub 2020 Aug 15. PMID: 32799417, PMCID: 9943711, 10.1002/ana.25877.
  • Suthiphosuwan S, Sati P, Absinta M, Guenette M, Reich DS, Bharatha A, Oh J. The paramagnetic rim sign in radiologically isolated syndrome: chronic active demyelinating lesions in asymptomatic individuals. JAMA Neurol 2020 77:653-655. Epub 2020 Mar 9. PMID: 32150224, PMCID: 7063543, DOI: 10.1001/jamaneurol.2020.0124.
  • Absinta M, Sati P, Masuzzo F, Nair G, Sethi VV, Kolb H, Ohayon J, Wu T, Cortese I, Reich DS. Association of chronic active multiple sclerosis lesions with disability in vivo. JAMA Neurol 2019; 76:1474-1483. Epub 2019 Aug 12. PMID: 31403674, PMCID: 6692692, DOI: 10.1001/jamaneurol.2019.2399.
  • Bhargava P, Wicken S, Smith M, Cortese I, Reich DS, Calabresi PA, Mowry EM. Trial of intrathecal rituximab in progressive multiple sclerosis patients with evidence of leptomeningeal contrast enhancement. Mult Scler Relat Disord 2019; 30:136-140. Epub 2019 Feb 11. PMID: 30771580, PMCID: 7325522, DOI: 10.1016/j.msard.2019.02.013.
  • Absinta M, Sati P, Fechner A, Schindler MK, Nair G, Reich DS. Identification of chronic active multiple sclerosis lesions at 3T MRI. AJNR Am J Neuroradiol 2018; 39:1233-1238. Epub 2018 May 3. PMID: 29724768, PMCID: 6039266, DOI: 10.3174/ajnr.A5660.
  • Absinta M, Cortese I, Vuolo L, Nair G, de Alwis PM, Ohayon J, Meani A, Martinelli V, Scotti R, Falini A, Smith BR, Nath A, Jacobson S, Filippi M, Reich DS. Leptomeningeal gadolinium enhancement across the spectrum of chronic neuroinflammatory diseases. Neurology 2017; 15:1439-1444. Epub 2017 Mar 10. PMID: 28283598, PMCID: 5386437, DOI: 10.1212/WNL.0000000000003820.
  • Sethi V, Nair G, Absinta M, Sati P, Venkataraman A, Ohayon J, Wu T, Yang K, Shea CD, Dewey BE, Cortese I, Reich DS. Slowly eroding lesions in multiple sclerosis. Mult Scler 2017; 23:464-472. Epub 2016 Jun 23. PMID: 27339071, PMCID: 5182188, DOI: 10.1177/1352458516655403.
  • Absinta M, Sati P, Schindler MK, Leibovitch E, Ohayon J, Wu T, Meani A, Filippi M, Jacobson S, Cortese I, Reich DS. Persistent 7-tesla phase rim predicts poor outcome in new MS patient lesions. J Clin Invest 2016; 126:2597-2609. Epub 2016 Jun 6. PMID: 27270171, PMCID: 4922708, DOI: 10.1172/JCI86198.
  • *Absinta M, *Vuolo L, Rao A, Nair G, Sati P, Cortese I, Ohayon J, Fenton K, Reyes-Mantilla MI, Maric D, Calabresi PA, Butman JA, Pardo CA, Reich DS. Gadolinium-based MRI characterization of leptomeningeal inflammation in multiple sclerosis. Neurology 2015; 85:18-28. Epub 2015 Apr 17. PMID: 25888557, PMCID: 4501940, DOI: 10.1212/WNL.0000000000001587. 

    UNDERSTANDING AND IMAGING THE DEVELOPMENT AND REPAIR OF LESIONS IN MULTIPLE SCLEROSIS

    Our translational research has led to a new and much more dynamic view of lesion development and repair, with implications for understanding disease etiology and developing new paradigms for clinical trials in the disease.

    • *Donadieu M, *Lee NJ, Gaitán MI, Ha SK, Luciano NJ, Roy S, Ineichen BV, Leibovitch EC, Yen CC, Pham DL, Silva AC, Johnson M, Jacobson S, ✉︎Sati P, ✉︎Reich DS. In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis. eLife 2023; 12:e73786. Epub 2023 Apr 21. PMID: 37083540, PMCID: 10171859, DOI: 10.7554/eLife.73786.
    • Lin JP, Kelly HM, Song Y, Kawaguchi R, Geschwind DH, Jacobson S, Reich DS. Transcriptomic architecture of nuclei in the marmoset CNS. Nat Commun 2022; 13:5531. Epub 2022 Sep 21. PMID: 36130924, PMCID: 9492672, DOI: 10.1038/s41467-022-33140-z.
    • *Al-Louzi O, *Letchuman V, Manukyan S, Beck ES, Roy S, Ohayon J, Pham DL, Cortese I, Sati P, Reich DS. Central vein sign profile of newly developing lesions in multiple sclerosis: a 3-year longitudinal study. Neurol Neuroimmunol Neuroinflamm 2022; 9:e1120. Epub 2022 Jan 13. PMID: 35027474, PMCID: 8759076, DOI: 10.1212/NXI.0000000000001120.
    • Reich DS, Arnold DL, Vermersch P, Bar-Or A, Fox RJ, Matta A, Turner T, Wallström E, Zhang X, Mareš M, Khabirov FA, Traboulsee A on behalf of the Tolebrutinib Phase 2b Study Group. Safety and efficacy of tolebrutinib, an oral, central nervous system-penetrant Bruton’s tyrosine kinase inhibitor, in relapsing multiple sclerosis: a phase 2, randomized, placebo-controlled trial. Lancet Neurol 2021; 20:729-738. Epub 2021 Aug 18. PMID: 34418400, PMCID: 8434816, DOI: 10.1016/S1474-4422(21)00237-4.
    • Kolb H, Absinta M, Beck ES, Ha SK, Song Y, Norato G, Cortese I, Sati P, Nair G, Reich DS. 7-tesla MRI differentiates remyelinated from demyelinated white matter lesions in multiple sclerosis. Ann Neurol 2021; 90:612-626. Epub 2021 Aug 14. PMID: 34390015, PMCID: 9291186, DOI: 10.1002/ana.26194.
    • Werneburg S, Jung J, Kunjamma RB, Ha SK, Luciano NJ, Willis CM, Gao G, Biscola NP, Havton LA, Crocker SJ, Popko B, Reich DS, Schafer DP. Targeted complement inhibition at synapses prevents microglial synaptic engulfment and synapse loss in demyelinating disease. Immunity 2019; 52:167-182. Epub 2019 Dec 26. PMID: 31883839, PMCID: 6996144, DOI: 10.1016/j.immuni.2019.12.004.
    • Lee NJ, Ha SK, Sati P, Absinta M, Nair G, Luciano NJ, Leibovitch EC, Yen CC, Rouault TA, Silva AC, Jacobson S, Reich DS. Potential role of iron in repair of inflammatory demyelinating lesions. J Clin Invest 2019; 129:4365-4376. Epub 2019 Sep 9. PMID: 31498148, PMCID: 6763243, DOI: 10.1172/JCI126809.
    • Lefeuvre J, Guy JR, Luciano NJ, Ha SK, Leibovitch E, Santin MD, Silva AC, Jacobson S, Lehéricy S, Reich DS, Sati P. The spectrum of spinal cord lesions in a primate model of multiple sclerosis. Mult Scler 2020; 26:284-293. Epub 2019 Feb 7. PMID: 30730246, PMCID: 6685769, DOI: 10.1177/1352458518822408.
    • Lee N, Ha SK, Sati P, Absinta M, Luciano N, Lefeuvre J, Schindler MK, Leibovitch E, Ryu JK, Petersen M, Silva AC, Jacobson S, Akassoglou K, Reich DS. Spatiotemporal distribution of fibrinogen in marmoset and human inflammatory demyelination. Brain 2018; 141:1637-1649. Epub 2018 Apr 20. PMID: 29688408, PMCID: 5972667, DOI: 10.1093/brain/awy082.
    • Absinta M, Sati P, Schindler MK, Leibovitch E, Ohayon J, Wu T, Meani A, Filippi M, Jacobson S, Cortese I, Reich DS. Persistent 7-tesla phase rim predicts poor outcome in new MS patient lesions. J Clin Invest 2016; 126:2597-2609. Epub 2016 Jun 6. PMID: 27270171, PMCID: 4922708, DOI: 10.1172/JCI86198.
    • Absinta M, Nair G, Sati P, Cortese I, Filippi M, Reich DS. Direct MRI detection of impending plaque development in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 2015; 2:e145. Epub 2015 Sep 4. PMID: 26401516, PMCID: 4561231, DOI: 10.1212/NXI.0000000000000145.
    • Reich DS, White R, Cortese I, Vuolo L, Shea CD, Collins TL, Petkau AJ. Sample-size calculations for short-term proof-of-concept studies of tissue protection and repair in multiple sclerosis lesions via conventional clinical imaging. Mult Scler 2015; 21:1693-1704. Epub 2015 Feb 6. PMID: 25662351, PMCID: 4527958, DOI: 10.1177/1352458515569098.
    • Maggi P, Cummings Macri SM, Gaitán MI, Leibovitch E, Wohler JE, Knight HL, Ellis M, Wu T, Silva AC, Massacesi L, Jacobson S, Westmoreland S, Reich DS. The formation of inflammatory demyelinated lesions in cerebral white matter. Ann Neurol 2014; 76:594-608. Epub 2014 Jul 31. PMID: 25088017, PMCID: 4723108, DOI: 10.1002/ana.24242.
    • Absinta M, Sati P, Gaitán MI, Maggi P, Cortese I, Filippi M, Reich DS. 7T phase imaging of acute MS lesions: A new window into the inflammatory process. Ann Neurol 2013; 74:669-678. Epub 2013 Jun 28. PMID: 23813441, PMCID: 3812397, DOI: 10.1002/ana.23959.
    • Gaitán MI, Sati P, Inati S, Reich DS. Initial investigation of the blood-brain barrier in MS lesions at 7 tesla. Mult Scler 2013; 19: 1068-1073. Epub 2012 Dec 17. PMID: 23246799, PMCID: 4744645, DOI: 10.1177/1352458512471093.
    • Shinohara RT, Goldsmith J, Mateen F, Crainiceanu CM, Reich DS. Predicting breakdown of the blood-brain barrier in multiple sclerosis without contrast agents. AJNR Am J Neuroradiol 2012; 33:1586-1590. Epub 2012 Mar 22. PMID: 22442041, PMCID: 3555688, DOI: 10.3174/ajnr.A2997.
    • Gaitán MI, Shea CD, Evangelou IE, Stone RD, Fenton KM, Bielekova B, Massacesi L, Reich DS. Evolution of the blood­brain barrier in newly forming multiple sclerosis lesions. Ann Neurol 2011; 70:22-29. Epub 2011 Jun 27. PMID: 21710622, PMCID: 3143223, DOI: 10.1002/ana.22472. 

      THE “CENTRAL VEIN SIGN” IN MULTIPLE SCLEROSIS

      Working at NIH and in collaboration with groups all around the world, we have developed and tested a new and highly sensitive approach — the “central vein sign” — that can discriminate lesions cause by MS from those caused by other diseases.

      • Borrelli S, Martire MS, Stölting A, Vanden Bulcke C, Guisset F, Bugli C, Yildiz H, Pothen L, Elands S, Martinelli V, Smith BR, Jacobson S, Du Pasquier R, van Pesch V, Filippi M, Reich DS, Absinta M, Maggi P. Central vein sign, cortical lesions, and paramagnetic rim lesions for the diagnostic and prognostic workup of multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 2024; in press. PMCID: in progress.
      • Daboul L, O’Donnell CM, Amin M, Rodrigues P, Derbyshire JA, Azevedo C, Bar-Or A, Caverzasi E, Calabresi PA, Cree BAC, Freeman L, Henry RG, Longbrake EE, Oh J, Papinutto N, Pelletier D, Prchkovska V, Raza P, Ramos M, Samudralwar RD, Schindler MK, Sotirchos ES, Sicotte NL, Solomon AJ, Shinohara RT, Reich DS, Sati P, Ontaneda D. A multicenter prospective study evaluating a straightforward central vein assessment for the diagnosis of multiple sclerosis. Mult Scler J 2023; in press. Epub 2023 Dec 13. PMID: 38088067. PMCID: in progress, DOI: 10.1177/13524585231214360.
      • Daboul L, O’Donnell C, Cao Q, Moreno-Dominguez D, Rodrigues P, Derbyshire JA, Azevedo C, Bar-Or A, Caverzasi E, Calabresi PA, Cree BAC, Freeman L, Henry RG, Longbrake EE, Oh J, Papinutto N, Pelletier D, Samudralwar RD, Schindler MK, Sotirchos E, Sicotte NL, Solomon AJ, Shinohara RT, Reich DS, ✉︎Ontaneda D, ✉︎Sati P. Effect of GBCA use on detection and diagnostic performance of the central vein sign: evaluation using a 3T FLAIR* sequence in patients with suspected multiple sclerosis. AJR Am J Roentgenology 2022; 220:115-125. Epub 2022 Aug 17. PMID: 35975888, PMCID: 10016223, DOI: 10.2214/AJR.22.27731.
      • Al-Louzi O, Manukyan S, Donadieu M, Absinta M, Letchuman V, Calabresi B, Desai P, Beck ES, Roy S, Ohayon J, Pham DL, Thomas A, Jacobson S, Cortese I, Auluck PK, Nair G, Sati P, Reich DS. Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: an in-vivo and postmortem MRI study. Mult Scler J 2022; 28:1891-1902. Epub 2022 Jun 8. PMID: 35674284, PMCID: 9489648, DOI: 10.1177/13524585221097560.
      • *Al-Louzi O, *Letchuman V, Manukyan S, Beck ES, Roy S, Ohayon J, Pham DL, Cortese I, Sati P, Reich DS. Central vein sign profile of newly developing lesions in multiple sclerosis: a 3-year longitudinal study. Neurol Neuroimmunol Neuroinflamm 2022; 9:e1120. Epub 2022 Jan 13. PMID: 35027474, PMCID: 8759076, DOI: 10.1212/NXI.0000000000001120.
      • Ontaneda D, Sati P, Raza P, Kilbane M, Gombos E, Alvarez E, Azevedo C, Calabresi PA, Cohen JA, Freeman L, Henry RG, Longbrake EE, Mitra N, Illenberger N, Schindler MK, Moreno-Dominguez D, Ramos M, Mowry E, Oh J, Rodrigues P, Chahin S, Kaisey M, Waubant E, Cutter G, Shinohara RT, Reich DS, Solomon A, Sicotte NL. Central vein sign: a diagnostic biomarker in multiple sclerosis (CAVS-MS) study protocol for a prospective multicenter trial. Neuroimage Clin 2021; 32:102834. Epub 2021 Sep 23. PMID: 34592690, PMCID: 8482479, DOI: 10.1016/j.nicl.2021.102834.
      • Maggi P*, Fartaria MJ*, Jorge J, La Rosa F, Absinta M, Sati P, Meuli R, Du Pasquier R, Reich DS, Bach Cuadra M, Granziera C, Richiardi J, Kober T. CVSnet: a machine learning approach for automated central vein sign assessment in multiple sclerosis. NMR Biomed 2020; in press. Epub 2020 Mar 3. PMID: 32125737. PMC — in progress. 10.1002/nbm.4283.
      • *Maggi P, *Fartaria MJ, Jorge J, La Rosa F, Absinta M, Sati P, Meuli R, Du Pasquier R, Reich DS, Bach Cuadra M, Granziera C, Richiardi J, Kober T. CVSnet: a machine learning approach for automated central vein sign assessment in multiple sclerosis. NMR Biomed 2020; 33:e4283. Epub 2020 Mar 3. PMID: 32125737, PMCID: 7754184, DOI: 10.1002/nbm.4283.
      • Dworkin JD, Sati P, Solomon A, Pham DL, Watts R, Martin ML, Ontaneda D, Schindler MK, Reich DS, Shinohara RT. Automated integration of multimodal MRI for the probabilistic detection of the central vein sign in white matter lesions. AJNR Am J Neuroradiol 2018; 39:1806-1813. Epub 2018 Sep 13. PMID: 30213803. PMC6177309. 10.3174/ajnr.A5765
      • Suthiphosuwan S, Sati P, Guenette M, Montalban X, Reich DS, Bharatha A, Oh J. The central vein sign in radiologically isolated syndrome. AJNR Am J Neuroradiol 2019; 40:776-783. Epub 2019 Apr 18. PMID: 31000526, PMCID: 6786901, DOI: 10.3174/ajnr.A6045.
      • Dworkin JD, Sati P, Solomon A, Pham DL, Watts R, Martin ML, Ontaneda D, Schindler MK, Reich DS, Shinohara RT. Automated integration of multimodal MRI for the probabilistic detection of the central vein sign in white matter lesions. AJNR Am J Neuroradiol 2018; 39:1806-1813. Epub 2018 Sep 13. PMID: 30213803, PMCID: 6177309, DOI: 10.3174/ajnr.A5765.
      • Absinta M, Nair G, Monaco MC, Maric D, Lee N, Ha SK, Luciano N, Sati P, Jacobson S, Reich DS. The central vein sign in inflammatory demyelination: the role of fibrillar collagen type I. Ann Neurol 2019; 85:934-942. Epub 2019 Mar 7. PMID: 30847935, PMCID: 6520117, DOI: 10.1002/ana.25461.
      • *Maggi P, *Absinta M, Grammatico M, Vuolo L, Emmi G, Carlucci G, Spagni G, Barilaro A, Repice E, Emmi L, Martinelli V, Scotti R, Sadeghi N, Perrotta G, Sati P, Dachy B, Reich DS, Filippi M, Massacesi L. Central vein sign differentiates multiple sclerosis from central nervous system inflammatory vasculopathies. Ann Neurol 2018; 83:283-294. Epub 2018 Jan 12. PMID: 29328521, PMCID: 5901412, DOI: 10.1002/ana.25146.
      • Sati P, Oh J, Constable RT, Evangelou N, Guttmann C, Henry R, Klawiter E, Mainero C, Massacesi L, McFarland H, Nelson F, Ontaneda D, Rauscher A, Rooney WD, Samaraweera A, Shinohara RT, Sobel R, Solomon A, Treaba C, Wuerfel J, Zivadinov R, Sicotte N, Pelletier D,* Reich DS* on behalf of the NAIMS Cooperative. The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative. Nature Rev Neurol 2016; 12:714-722. Epub 2016 Nov 11. PMID: 27834394, DOI: 10.1038/nrneurol.2016.166.
      • Solomon AJ, Watts R, Ontaneda D, Absinta M, Sati P, Reich DS. Diagnostic performance of central vein sign for multiple sclerosis with a simplified three lesion algorithm. Mult Scler 2018; 24:750-757. Epub 2017 Aug 18. PMID: 28820013, PMCID: 5794670, DOI: 10.1177/1352458517726383.
      • George IC, Sati P, Absinta M, Cortese I, Sweeney EM, Shea CD, Reich DS. Clinical 3-tesla FLAIR* MRI improves diagnostic accuracy in multiple sclerosis. Mult Scler 2016; 22:1578-1586. Epub 2016 Jan 14. PMID: 26769065, PMCID: 4945460, DOI: 10.1177/1352458515624975.
      • Solomon AJ, Schindler MK, Howard DB, Watts R, Sati P, Nickerson JP, Reich DS. “Central vessel sign” on 3T FLAIR* MRI for the differentiation of multiple sclerosis from migraine. Ann Clin Trans Neurol 2015; 3:82-87. Epub 2015 Dec 16. PMID: 26900578, PMCID: 4748312, DOI: 10.1002/acn3.273.
      • Gaitán MI, Maggi P, Wohler JE, Leibovitch E, Sati P, Calandri I, Merkle H, Massacesi L, Silva AC, Jacobson S, Reich DS. Perivenular brain lesions in a primate multiple sclerosis model at 7T-MRI. Mult Scler 2014; 20:64-71. Cover. Epub: 2013 Jun 17. PMID: 23773983, PMCID: 4745928, DOI: 10.1177/1352458513492244.
      • 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; 265:926-932. Epub 2012 Oct 16. PMID: 23074257, PMCID: 3504317, DOI: 10.1148/radiol.12120208.

      CORTICAL LESIONS IN MULTIPLE SCLEROSIS

      We have developed new methods for detecting and characterizing cortical multiple sclerosis lesions and their evolution over time.

      • Beck ES, Mullins WA, dos Santos Silva J, Filippini S, Parvathaneni P, Maranzano J, Morrison M, Suto DJ, Donnay C, Dieckhaus H, Luciano NJ, Sharma K, Gaitán MI, Liu J, de Zwart JA, van Gelderen P, Cortese I, Narayanan S, Duyn JH, Nair G, Sati P, Reich DS. Contribution of new and chronic cortical lesions to disability accrual in multiple sclerosis. Brain Commun 2024; in press.
      • Borrelli S, Martire MS, Stölting A, Vanden Bulcke C, Guisset F, Bugli C, Yildiz H, Pothen L, Elands S, Martinelli V, Smith BR, Jacobson S, Du Pasquier R, van Pesch V, Filippi M, Reich DS, Absinta M, Maggi P. Central vein sign, cortical lesions, and paramagnetic rim lesions for the diagnostic and prognostic workup of multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 2024; in press. PMCID: in progress.
      • La Rosa F, Beck ES, Maranzano J, Todea RA, van Gelderen P, de Zwart JA, Luciano NJ, Duyn JH, Thiran JP, Granziera C, Reich DS, Sati P, Cuadra MB. Multiple sclerosis cortical lesion detection with deep learning at ultra-high-field MRI. NMR Biomed 2022; 25:e4730. Epub 2022 Mar 16. PMID: 35297114, PMCID: 9539569, DOI: 10.1002/nbm.4730.
      • Beck ES, Maranzano J, Luciano NJ, Parvathaneni P, Filippini S, Morrison M, Suto DJ, Wu T, van Gelderen P, de Zwart JA, Antel S, Fetco D, Ohayon J, Andrada F, Mina Y, Thomas C, Jacobson S, Duyn J, Cortese I, Narayanan S, Nair G, Sati P, Reich DS. Cortical lesion hotspots and association of subpial lesions with disability in multiple sclerosis. Mult Scler J 2022; 28:1351-1363. Epub 2022 Feb 10. PMID: 35142571, PMCID: 9256754, DOI: 10.1177/13524585211069167.
      • *Liu J, *Beck ES, FIlippini S, van Gelderen P, de Zwart JA, Norato G, Sati P, Al-Louzi O, Kolb H, Donadieu M, Morrison M, Duyn JH, Reich DS. Navigator-guided motion and B0 correction of T2*-weighted MRI improves multiple sclerosis cortical lesion detection. Invest Radiol 2021; 56:409-416. Epub 2021 Jul 1. PMID: 34086012, PMCID: 8269363, DOI: 10.1097/RLI.0000000000000754.
      • Donadieu M, Kelly H, Szczupak D, Lin JP, Song Y, Yen CCC, Ye FQ, Guy JR, Beck ES, Jacobson S, Silva AC, Sati P, Reich DS. Ultrahigh-resolution MRI reveals extensive cortical demyelination in a nonhuman primate model of multiple sclerosis. Cereb Cortex 2021; 31:439-447. Epub 2020 Sep 8. PMID: 32901254, PMCID: 7947170, DOI: 10.1093/cercor/bhaa235.
      • Beck ES, Gai N, Filippini S, Maranzano J, Nair G, Reich DS. Inversion recovery susceptibility weighted imaging with enhanced T2-weighting (IR-SWIET) at 3 tesla improves visualization of subpial cortical multiple sclerosis lesions. Invest Radiol 2020; 55:727-735. Epub 2020 Jun 22. PMID: 32604385, PMCID: 7541598, DOI: 10.1097/RLI.0000000000000698.
      • Beck ES, Sati P, Sethi VV, Kober T, Dewey BE, Bhargava P, Nair G, Cortese I, Reich DS. Improved visualization of cortical lesions in multiple sclerosis using 7T MP2RAGE. AJNR Am J Neuroradiol 2018; 39:459-466. Epub 2018 Feb 8. PMID: 29439120, PMCID: 6082739, DOI: 10.3174/ajnr.A5534.

        NEW METHODS FOR IMAGE ACQUISITION AND ANALYSIS

        We develop new approaches to acquiring and analyzing MRI for CNS diseases, focusing on detection (e.g. blood vessels within lesions), segmentation (lesion and structure identification), and radiological-pathological correlation. Our imaging-based studies, validated by histopathology, led to the identification of meningeal lymphatic vessels in human and nonhuman primates. We have also pioneered studies of multiple sclerosis with ultra-low-field, portable MRI.

        • Smyth LCD, *Xu D, *Okar SV, Dykstra T, Rustenhoven J, Papadopoulos Z, Bhasiin K, Kim MW, Drieu A, Mamuladze T, Blackburn S, Gu X, Gaitán MI, Nair G, Storck SE, Du S, White MA, Bayguinov P, Smirnov I, Dikranian K, Reich DS, Kipnis J. Identification of direct connections between the dura and the brain. Nature 2024; 627:165-173. Epub 2024 Feb 7. PMID: 38326613, PMCID: in progress, DOI: 10.1038/s41586-023-06993-7.
        • Donnay C, Dieckhaus H, Tsagkas C, Beck ES, Mullins WA, Reich DS, Nair G. Pseudo-label assisted nnU-net (PLAn) enables automatic segmentation of 7T MRI from a single acquisition. Front Neuroimaging 2023; 2:1252261. Epub 2023 Dec 1. PMID: 38107773, PMCID: 10722186, DOI: 10.3389/fnimg.2023.1252261.
        • Okar SV, Dieckhaus H, Beck ES, Gaitán MI, Norato G, Pham DL, Absinta M, Cortese I, Fletcher A, Jacobson S, Nair G, Reich DS. Highly sensitive 3-tesla real inversion recovery MRI detects leptomeningeal contrast enhancement in chronic active multiple sclerosis. Invest Radiol 2023; 59:243-251. Epub 2023 Jul 27. PMID: 37493285, PMCID: 10278242, DOI: 10.1097/RLI.0000000000001011.
        • Arnold TC, Tu D, Okar SV, Nair G, By S, Kawatra K, Robert-Fitzgerald TE, Desiderio LM, Schindler MK, Shinohara RT, ✉︎Reich DS, ✉︎Stein JM. Sensitivity of portable low-field magnetic resonance imaging for multiple sclerosis lesions. Neuroimage Clin 2022; 35:103101. Epub 2022 Jun 27. PMID: 35792417, PMCID: 9421456, DOI: 10.1016/j.nicl.2022.103101.
        • *Liu J, *Beck ES, FIlippini S, van Gelderen P, de Zwart JA, Norato G, Sati P, Al-Louzi O, Kolb H, Donadieu M, Morrison M, Duyn JH, Reich DS. Navigator-guided motion and B0 correction of T2*-weighted MRI improves multiple sclerosis cortical lesion detection. Invest Radiol 2021; 56:409-416. Epub 2021 Jul 1. PMID: 34086012, PMCID: 8269363, DOI: 10.1097/RLI.0000000000000754.
        • Olson J, Pham DL, Reich DS, Butman JA. Making a difference: an integrated PACS workflow for evaluating longitudinal changes across serial imaging. Medical Imaging 2021: Imaging Informatics for Healthcare, Research, and Applications 2021; 1160100. Epub 2021 Feb 15, DOI: 10.1117/12.2582209.
        • Al-Louzi O, Roy S, Osuorah I, Parvathaneni P, Smith BR, Ohayon J, Sati P, Pham DL, Jacobson S, Nath A, Reich DS, Cortese I. Progressive multifocal leukoencephalopathy lesion and brain parenchymal segmentation from MRI using serial deep convolutional neural networks. Neuroimage Clin 2020; 28:102499. Epub 2020 Nov 11. PMID: 33395989, PMCID: 7708929, DOI: 10.1016/j.nicl.2020.102499.
        • Nair G, Dodd S, Ha SK, Koretsky AP, Reich DS. Ex vivo MR microscopy of a human brain with multiple sclerosis: visualizing individual cells in tissue using intrinsic iron. Neuroimage 2020; 223:117285. Epub 2020 Aug 20. PMID: 32828923, PMCID: 7811778, DOI: 10.1016/j.neuroimage.2020.117285.
        • Suto DJ, Nair G, Sudarshana D, Steele SU, Dwyer JT, Beck ES, Ohayon J, McFarland H, Koretsky AP, Cortese I, Reich DS. Manganese-enhanced magnetic resonance imaging in multiple sclerosis. AJNR Am J Neuroradiol 2020; 41:1569-1576. Epub: 2020 Aug 6. PMID: 32763897, PMCID: 7583091, DOI: 10.3174/ajnr.A6665.
        • Beck ES, Gai N, Filippini S, Maranzano J, Nair G, Reich DS. Inversion recovery susceptibility weighted imaging with enhanced T2-weighting (IR-SWIET) at 3 tesla improves visualization of subpial cortical multiple sclerosis lesions. Invest Radiol 2020; 55:727-735. Epub 2020 Jun 22. PMID: 32604385, PMCID: 7541598, DOI: 10.1097/RLI.0000000000000698.
        • Sudarshana DM, Nair G, Dwyer JT, Dewey B, Steele SU, Wu T, Berkowitz BA, Koretsky AP, Cortese I, Reich DS. Manganese-enhanced MRI (MEMRI) of the brain in healthy volunteers. AJNR Am J Neuroradiol 2019; 40:1309-1316. Epub 2019 Aug 1. PMID: 31371354, PMCID: 6754109, DOI: 10.3174/ajnr.a6152.
        • Brugarolas P, Sanchez-Rodriguez J, Tsai HM, Basuli F, Cheng SH, Zhang X, Caparaiello A, Lacroix J, Freifelder R, Murali D, DeJesus O, Miller R, Swenson R, Chen CT, Herscovitch P, Reich DS, Bezanilla F, Popko B. Development of a PET radioligand for potassium channels to image CNS demyelination. Sci Rep 2018; 8:607. Epub 2018 Jan 12. PMID: 29330383, PMCID: 5766510, DOI: 10.1038/s41598-017-18747-3.
        • Beck ES, Sati P, Sethi VV, Kober T, Dewey BE, Bhargava P, Nair G, Cortese I, Reich DS. Improved visualization of cortical lesions in multiple sclerosis using 7T MP2RAGE. AJNR Am J Neuroradiol 2018; 39:459-466. Epub 2018 Feb 8. PMID: 29439120, PMCID: 6082739, DOI: 10.3174/ajnr.A5534.
        • *Absinta M, *Ha SK, Nair G, Sati P, Luciano NJ, Palisoc M, Louveau A, Zaghloul KA, Pittaluga S, Kipnis J, Reich DS. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. eLife 2017; 6:e29738. Epub 2017 Oct 3. PMID: 28971799, PMCID: 5626482, DOI: 10.7554/eLife.29738.
        • Basuli F, Zhang X, Brugraolas P, Reich DS, Swenson RE. An efficient new method for the synthesis of [18F]3-fluoro-4-aminopyridine via Yamada-Curtius rearrangement. J Labelled Comp Radiopharm 2018; 61:112-117. Epub 2017 Sep 4. PMID: 28870001, PMCID: 5992582, DOI: 10.1002/jlcr.3560.
        • Luciano NJ, Sati P, Nair G, Guy JR, Ha SK, Absinta M, Chiang WY, Leibovitch EC, Jacobson S, Silva AC, Reich DS. Utilizing 3D printing technology to merge MRI with histology: a protocol for brain sectioning. Journal of Visualized Experiments (JoVE) 2016; 118:e54780. Epub 2016 Nov 4. PMID: 28060281, PMCID: 5226356, DOI: 10.3791/54780.
        • *Wood ET, *Ercan AE, Branzoli F, Webb A, Sati P, Reich DS, Ronen I. Reproducibility of in vivo human diffusion-weighted magnetic resonance spectroscopy of the corpus callosum at 3T and 7T. NMR Biomed 2015; 28:976-987. Epub 2015 Jun 18. PMID: 26084563, PMCID: 5082280, DOI: 10.1002/nbm.3340.
        • *Absinta M, *Nair G, Filippi M, Ray-Chaudhury A, Reyes-Mantilla MI, Pardo CA, Reich DS. Postmortem MRI to guide the pathological cut: Individualized, 3D-printed cutting boxes for fixed brains. J Neuropath Exp Neurol 2014; 73:780-788. Epub 2014 Aug. PMID: 25007244, PMCID: 4144036, DOI: 10.1097/NEN.0000000000000096.
        • Liu W, Nair G, Vuolo L, Bakshi A, Massoud R, Reich DS, Jacobson S. In-vivo imaging of spinal cord atrophy in neuroinflammatory diseases. Ann Neurol 2014; 76:370-378. Epub 2014 Jul 1. PMID: 25042583. PMC4165784. 10.1002/ana.24213
        • Gao KC, Nair G, Cortese I, Koretsky AP, Reich DS. Sub-millimeter imaging of brain-free water for rapid volume assessment in atrophic brains. NeuroImage 2014; 100:370-378. Epub 2014 Jun 16. PMID: 24945671, PMCID: 4725580, DOI: 10.1016/j.neuroimage.2014.06.014.
        • Sati P, Thomasson D, Li N, Pham DL, Biassou N, Reich DS, Butman JA. Rapid, high-resolution, whole-brain, susceptibility-based MRI of multiple sclerosis. Mult Scler 2014; 20:1464-1470. Epub 2014 Mar 17. PMID: 24639479, PMCID: 4167170, DOI: 10.1177/1352458514525868.
        • Jones BC, Nair G, Shea CD, Crainiceanu CM, Cortese I, Reich DS. Quantification of multiple-sclerosis-related brain atrophy in two heterogeneous MRI datasets using mixed-effects modeling. Neuroimage Clin 2013; 3:171-179. Epub 2013 Aug 30. PMID: 24179861, PMCID: 3791279, DOI: 10.1016/j.nicl.2013.08.001.
        • Nair G, Absinta M, Reich DS. Optimized T1-MPRAGE sequence for better visualization of spinal cord MS lesions at 3T. AJNR Am J Neuroradiol 2013; 34:2215-2222. Epub: 2013 Jun 13. PMID: 23764721, PMCID: 4278432, DOI: 10.3174/ajnr.A3637.
        • 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; 265:926-932. Epub 2012 Oct 16. PMID: 23074257, PMCID: 3504317, DOI: 10.1148/radiol.12120208.

          IDENTIFYING PEOPLE AT RISK FOR DEVELOPING MS

          We have worked closely with collaborators on the Genes and Environment in MS study. Our goal is to develop and test a new algorithm, based on genetic and environmental risk factors, to identify people at risk for developing MS — and to develop strategies to prevent the disease in the first place.

          • Everest E, Ahangari M, Uygunoglu U, Tutuncu M, Bulbur A, Saip S, Duman T, Sezerman U, Reich DS, Riley B, Siva A, Tahir Turanli E. Investigating the role of common and rare variants in multiplex multiple sclerosis families reveals an increased burden of common risk variation. Sci Rep 2022; 12:16984. Epub 2022 Oct 10. PMID: 36216875, PMCID: 9550807, DOI: 10.1038/s41598-022-21484-x.
          • Oh J, Suthiphosuwan S, Sati P, Absinta M, Dewey B, Guenette M, Selchen D, Bharatha A, Donaldson E, Reich DS, Feinstein A. Cognitive impairment, the central vein sign, and paramagnetic rim lesions in RIS: potential tools to guide clinical management. Mult Scler J 2021; 27:2199-2208. Epub 2021 Mar 23. PMID: 33754887, PMCID: 8458475, DOI: 10.1177/13524585211002097.
          • Suthiphosuwan S, Sati P, Absinta M, Guenette M, Reich DS, Bharatha A, Oh J. The paramagnetic rim sign in radiologically isolated syndrome: chronic active demyelinating lesions in asymptomatic individuals. JAMA Neurol 2020 77:653-655. Epub 2020 Mar 9. PMID: 32150224, PMCID: 7063543, DOI: 10.1001/jamaneurol.2020.0124.
          • Suthiphosuwan S, Sati P, Guenette M, Montalban X, Reich DS, Bharatha A, Oh J. The central vein sign in radiologically isolated syndrome. AJNR Am J Neuroradiol 2019; 40:776-783. Epub 2019 Apr 18. PMID: 31000526, PMCID: 6786901, DOI: 10.3174/ajnr.A6045.
          • *Xia Z, *Steele SU, Bakshi A, Clarkson SR, White CC, Schindler MK, Nair G, Dewey BE, Price LR, Ohayon J, Chibnik LB, Cortese I, ✉︎De Jager PL, ✉︎Reich DS. Early evidence of multiple sclerosis in a prospective study of high-risk family members. JAMA Neurol 2017; 74:293-300. Epub 2017 Jan 17. PMID: 28114441, PMCID: 5348267, DOI: 10.1001/jamaneurol.2016.5056 
          • Xia Z, White C, Owen E, von Korff A, Clarkson S, McCabe C, Cimpean M, Winn P, Hoesing A, Steele S, Cortese I, Chitnis T, Weiner H, Reich DS, Chibnik L, De Jager P. GEMS project: a platform to investigate multiple sclerosis risk. Ann Neurol 2016; 79:178-189. Epub 2015 Nov 19. PMID: 26583565, PMCID: 4778957, DOI: 10.1002/ana.24560.

            IMAGING OF FUNCTIONAL SYSTEMS IN NEUROLOGICAL DISEASE

            Can imaging findings in specific functional systems (e.g. white matter tracts) be related to clinical disability?

            • *Mina Y, *Azodi S, Dubuche T, Andrada F, Osuorah I, Ohayon J, Cortese I, Wu T, Johnson KR, Reich DS, Nair G, Jacobson S. Cervical and thoracic cord atrophy in multiple sclerosis phenotypes: quantification and correlation with clinical disability. Neuroimage Clin 2021; 30:102680. Epub 2021 Apr 28. PMID: 34215150, PMCID: 8131917, DOI: 10.1016/j.nicl.2021.102680.
            • Suto DJ, Nair G, Sudarshana D, Steele SU, Dwyer JT, Beck ES, Ohayon J, McFarland H, Koretsky AP, Cortese I, Reich DS. Manganese-enhanced magnetic resonance imaging in multiple sclerosis. AJNR Am J Neuroradiol 2020; 41:1569-1576. Epub: 2020 Aug 6. PMID: 32763897, PMCID: 7583091, DOI: 10.3174/ajnr.A6665.
            • Oh J, Chen M, Cybulsky K, Suthiphosuwan S, Seyman E, Dewey B, Diener-West M, van Zijl P, Prince J, Reich DS, Calabresi PA. Five-year longitudinal changes in quantitative spinal cord MRI in multiple sclerosis. Mult Scler J 2020; 27:549-558. Epub 2020 Jun 1. PMID: 32476593, PMCID: 7704828, DOI: 10.1177/1352458520923970.
            • Wood ET, Ercan E, Cortese I, Ronen I, Reich DS. Longitudinal MR spectroscopy of neurodegeneration in multiple sclerosis with diffusion of the intra-axonal constituent N-acetylaspartate. Neuroimage Clin 2017; 15:780-788. Epub 2017 Jun 22. PMID: 28702353, PMCID: 5496488, DOI: 10.1016/j.nicl.2017.06.028.
            • Oh J, Zackowski KM, Chen M, Newsome S, Saidha S, Smith SA, Diener-West M, Prince JL, Jones CK, van Zijl PCM, Calabresi PA, Reich DS. Multiparametric MRI correlates of sensorimotor function in the spinal cord of multiple sclerosis. Mult Scler J 2013; 19:427-435. Epub 2012 Aug 13. PMID: 22891033, PMCID: 4482216, DOI: 10.1177/1352458512456614.
            • Harrison DM, Shiee N, Bazin P-L, Newsome SD, Ratchford JN, Pham DL, Calabresi PA, Reich DS. Tract-specific quantitative MRI improves disability prediction over conventional MRI in multiple sclerosis. J Neurol 2013; 260:397-406. Epub 2012 Aug 12. PMID: 22886062, PMCID: 3753185, DOI: 10.1007/s00415-012-6638-8.
            • Wood ET, Ronen I, Techawiboonwong A, Jones CK, Barker PB, Calabresi PA, Harrison DM, Reich DS. Investigating axonal damage in multiple sclerosis by diffusion tensor spectroscopy. J Neurosci 2012; 32:6665-6669. Epub 2012 Mar 21. PMID: 22573688, PMCID: 3360480, DOI: 10.1523/jneurosci.0044-12.2012.
            • Goldsmith J, Crainiceanu CM, Caffo BS, Reich DS. Longitudinal penalized functional regression for cognitive outcomes on neuronal tract measurements. J R Stat Soc Ser C Appl Stat 2012; 61:453-469. Epub 2012 Jan 5. PMID: 22679339, PMCID: 3366511, DOI: 10.1111/j.1467-9876.2011.01031.x.
            • Goldsmith J, Bobb J, Crainiceanu CM, Caffo BS, Reich DS. Penalized functional regression. J Computational and Graphical Statistics 2011; 20:830-851. Epub 2011 Dec 1. PMID: 22368438, PMCID: 3285536, DOI: 10.1198/jcgs.2010.10007.
            • Reich DS, Ozturk A, Calabresi PA, Mori S. Automated vs. conventional tractography in multiple sclerosis: Variability and correlation with disability. Neuroimage 2010; 49:3047-3056. PMID: 19944769, PMCID: 2843834, DOI: 10.1016/j.neuroimage.2009.11.043.
            • Reich DS, Smith SA, Gordon-Lipkin EM, Ozturk A, Caffo BS, Balcer LJ, Calabresi PA. Damage to the optic radiation in multiple sclerosis is associated with retinal injury and visual disability. Arch Neurol 2009; 66:998-1006. PMID: 19667222, PMCID: 2784485, DOI: 10.1001/archneurol.2009.107.
            • Reich DS, Zackowski KM, Gordon-Lipkin EM, Smith SA, Chodkowski BA, Cutter GR, Calabresi PA. Corticospinal tract abnormalities are associated with weakness in multiple sclerosis. AJNR Am J Neuroradiol 2008; 29:333-339. PMID: 17974617, PMCID: 2802714, DOI: 10.3174/ajnr.A0788.
            • Reich DS, Smith SA, Zackowski KM, Gordon-Lipkin E, Jones CK, Mori S, van Zijl PCM, Calabresi PA. Multiparametric magnetic resonance imaging analysis of the corticospinal tract in multiple sclerosis. Neuroimage 2007; 38:271-279. PMID: 17870615, PMCID: 2082136, DOI: 10.1016/j.neuroimage.2007.07.049.
            • Reich DS, Smith SA, Jones CK, Zackowski KM, van Zijl PC, Calabresi PA, Mori S. Quantitative characterization of the corticospinal tract at 3T. AJNR Am J Neuroradiol 2006; 27:2168-2178. PMID: 17110689, PMCID: 2802715.