Overview

In the Translational Neuroradiology Section, we study multiple sclerosis (MS) through the lens of the focal inflammatory demyelinating lesion. How do these lesions arise? How do they evolve? What accompanies them? What follows them? How do they repair?

To answer these questions, we integrate radiological (MRI) and clinical observations in MS and a pathologically realistic animal model to form hypotheses, and then test and constrain those hypotheses using a range of imaging, histopathological, and molecular studies.

Our vision is that pathophysiology-driven, imaging-based categorization of MS tissue damage at the lesion level will identify practical targets for therapeutic intervention while providing the substrate for identifying patient-level factors (age, sex, genetics, infections, other exposures, etc.) that strongly modify lesion outcomes and thereby the overall disease course.

The NINDS Intramural Research Program has been studying MS using MRI since the 1980s, and the results have informed the current diagnostic criteria, defined the natural history of the disease, and helped to screen and test new therapies. But the era of MRI in MS is far from over. Now, more than ever before, MRI enables investigation of MS on a spatiotemporal scale relevant for uncovering disease mechanisms — an investigation made possible by new developments including ultra-high-field clinical and animal magnets, phased-array radiofrequency coils, and robust 3D imaging sequences. At the TNS, we take full advantage of all of these.

Reviews

  • Reich DS, Lucchinetti C, Calabresi PA. Multiple sclerosis. New Engl J Med 2018; 378:169-180. Epub 2018 Jan 11. PMID: 29320652. PMC6942519. 10.1056/NEJMra1401483
  • Schindler MK, Sati P, Reich DS. Insights from ultra-high-field imaging in multiple sclerosis. Neuroimag Clin N Am 2017; 27:356-366. Epub 2017 Jan 26. PMID: 28391792. PMC5453514. 10.1016/j.nic.2016.12.006
  • 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. 10.1038/nrneurol.2016.166
  • Reich DS. Imag(in)ing multiple sclerosis: time to take better pictures. J Neuroimmunol 2017; 304:72-80. Epub 2016 Oct 3. PMID: 27742080. Epub 2016 Oct 3. PMC5316494. 10.1016/j.jneuroim.2016.09.015
  • Absinta M, Sati P, Reich DS. Advanced MRI and staging of multiple sclerosis lesions. Nature Rev Neurol 2016; 12:358-368. Epub 2016 Apr 29. PMID: 27125632. PMC5074769. 10.1038/nrneurol.2016.59
  • Absinta M, Reich DS, Filippi M. Spring cleaning: time to rethink imaging research lines in MS? J Neurol 2016; 263:1893-1902. Epub 2016 Feb 17. PMID: 26886204. PMC5079426. 10.1007/s00415-016-8060-0
  • Research Themes

    IMAGING 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.

    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.

    • Neumann B*, Foerster S*, Zhao C, Bodini B, Reich DS, Bergles DE, Káradóttir RT, Lubetzki C, Lairson LL, Zalc B, Stankoff B, Franklin RJM. Problems and pitfalls of identifying remyelination in multiple sclerosis. Cell Stem Cell 2020; in press. PMC — in progress.
    • 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. PMC6996144. 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. PMC676324. 10.1172/JCI126809
    • Filippi M, Preziosa P, Banwell BL, Barkhof F, Ciccarelli O, De Stefano N, Geurts JJG, Paul F, Reich DS, Toosy AT, Traboulsee A, Wattjes M, Yousry TA, Gass A, Lubetzki C, Weinshenker BH, Rocca MA. Assessment of lesions on magnetic resonance imaging in multiple sclerosis: practical guidelines. Brain 2019; 142:1858-1875. Epub 17 Jun 2019. PMID: 31209474. PMC6598631. 10.1093/brain/awz144
    • 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 collagen type I. Ann Neurol 2019; 85:934-942. Epub 2019 Mar 7. PMID: 30847935. PMC6520117. 10.1002/ana.25461
    • 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 2019; in press. Epub 2019 Feb 7. PMID: 30730246. PMC6685769. 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. PMC5972667. 10.1093/brain/awy082
    • Leibovitch EC, Caruso B, Ha SK, Schindler MK, Lee N, Luciano NJ, Billioux BJ, Li X, Guy JR, Yen C, Sati P, Silva AC, Reich DS, Jacobson S. Herpesvirus trigger accelerates neuroinflammation in a nonhuman primate model of multiple sclerosis. Proc Natl Acad Sci U S A 2018; 152:11292-11297. Epub 2018 Oct 15. PMID: 30322946. PMC6217390. 10.1073/pnas.1811974115
    • Beck ES, Sati P, Sethi VV, Kober T, Dewey BE, Bhargava P, Nair G, Cortese ICM, 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. PMC6082739. 10.3174/ajnr.A5534
    • Petersen MA, Ryu JK, Chung KH, Etxeberria A, Bardehle S, Mendiola AS, Kamau-Devers W, Fancy SPJ, Thor A, Bushong EA, Baeza-Raja B, Syme C, Wu MD, Rios Coronado PE, Meyer-Franke A, Yahn S, Pous L, Lee JK, Schachtrup C, Lassmann H, Huang EJ, Han MH, Absinta M, Reich DS, Ellisman MH, Rowitch DH, Chan JR, Akassoglou K. Fibrinogen activates BMP signaling in oligodendrocyte progenitor cells and inhibits remyelination after vascular damage. Neuron 2017; 96:1003-1012.e7. Epub 2017 Nov 2. PMID: 29103804. PMC5851281. 10.1016/j.neuron.2017.10.008
    • Absinta M, Cortese ICM, 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. PMC5386437. 10.1212/WNL.0000000000003820
    • Absinta M, Sati P, Schindler MK, Leibovitch E, Ohayon J, Wu T, Meani A, Filippi M, Jacobson S, Cortese ICM, 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. PMC4922708. 10.1172/JCI86198
    • Absinta M, Nair G, Sati P, Cortese ICM, Filippi M, Reich DS. Direct MRI detection of impending plaque development in multiple sclerosis. Neurology: Neuroimmunology & Neuroinflammation 2015; 2:e145. Epub 2015 Sep 4. PMID: 26401516. PMC4561231. 10.1212/NXI.0000000000000145
    • Li X, van Gelderen P, Sati P, de Zwart JA, Reich DS, Duyn JH. Detection of demyelination in multiple sclerosis by analysis of T2* relaxation at 7T. Neuroimage Clin 2015; 7:709-714. Epub 2015 Mar 4. PMID: 26594617. PMC4593862. 10.1016/j.nicl.2015.02.021
    • Reich DS, White R, Cortese ICM, 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. PMC4527958. 10.1177/1352458515569098
    • Harrison DM, Oh J, Roy S, Wood ET, Whetstone A, Seigo MA, Jones CK, Pham DL, van Zijl PCM, Reich DS, Calabresi PA. Thalamic lesions in multiple sclerosis by 7T MRI: Clinical implications and relationship to cortical pathology. Mult Scler 2015; 21:1139-1150. Epub 2015 Jan 12. PMID: 25583851. PMC4499502. 10.1177/1352458514558134
    • 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. PMC4723108. 10.1002/ana.24242
    • Absinta M, Sati P, Gaitán MI, Maggi P, Cortese ICM, 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. PMC3812397. 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. PMC4744645. 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. PMC3555688. 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. PMC3143223. 10.1002/ana.22472(Commentary by Hans Lassmann and selected for F1000prime)

    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.

    • 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, Absinta M, Sati P, Perrotte G, Massacesi L, Dachy B, Pot C, Meuli R, Reich DS, Filippi M, Du Pasquier R, Théaudin M. The “central vein sign” in patients with diagnostic “red flags” for multiple sclerosis: a prospective multicenter 3T study. Mult Scler J 2019; in press. Epub 2019 Sep 19. PMID: 31536435. PMC — in progress. 10.1177/1352458519876031
    • 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. PMC6786901. 10.3174/ajnr.A6045
    • 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 collagen type I. Ann Neurol 2019; 85:934-942. Epub 2019 Mar 7. PMID: 30847935. PMC6520117. 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. PMC5901412. 10.1002/ana.25146
    • 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. PMC5794670. 10.1177/1352458517726383
    • Solomon AJ, Watts R, Dewey BE, Reich DS. MRI evaluation of thalamic volume differentiates multiple sclerosis from common mimics. Neurology: Neuroimmunology and Neuroinflammation 2017; 4:e387. Epub 2017 Jul 18. PMID: 28761906. PMC5515603. 10.1212/NXI.0000000000000387
    • 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. 10.1038/nrneurol.2016.166
    • George IC, Sati P, Absinta M, Cortese ICM, 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. PMC4945460. 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. PMC4748312. 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. PMC4745928. 10.1177/1352458513492244

    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.

    • 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
    • Sudarshana DM, Nair G, Dwyer JT, Dewey B, Steele SU, Wu T, Berkowitz BA, Koretsky AP, Cortese ICM, 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. PMC6754109. 10.3174/ajnr.a6152
    • Fartaria MJ, Sati P, Todea A, Radue EW, O’Brien K, Reich DS, Cuadra MB, Kober T, Granziera C. Automated detection and segmentation of multiple sclerosis lesions using ultra-high-field MP2RAGE. Invest Radiol 2019; 54:356-364. Epub 2019 Mar 2. PMID: 30829941. PMC6499666. 10.1097/RLI.0000000000000551
    • 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
    • Brugarolas P, Reich DS, Popko B. Detecting demyelination by PET: the lesion as imaging target. Molecular Imaging 2018; 17:1-4. Epub 2018 Jul 24. PMID: 30039728. PMC6058413. 10.1177/1536012118785471
    • Dworkin JD, Linn KA, Oguz I, Fleishman G, Bakshi R, Tommala S, Yousuf F, Nair G, Calabresi PA, Henry RG, Oh J, Papinutto N, Pelletier D, Rooney W, Stern W, Sicotte NL, Reich DS, Shinohara RT, and the NAIMS Cooperative. An automated statistical technique for counting distinct multiple sclerosis lesions. AJNR Am J Neuroradiol 2018; 39:626-633. Epub 2018 Feb 28. PMID: 29472300. PMC5895493. 10.3174/ajnr.A5556
    • 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. PMC5766510. 10.1038/s41598-017-18747-3
    • Beck ES, Sati P, Sethi VV, Kober T, Dewey BE, Bhargava P, Nair G, Cortese ICM, 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. PMC6082739. 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. PMC5626482. 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 2017; 7:97. Epub 2017 Sep 4. PMID: 28870001. PMC5992582. 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. PMC5226356. 10.3791/54780
    • Sweeney EM, Shinohara RT, Dewey BE, Schindler MK, Muschelli J, Reich DS, Crainiceanu CM, Eloyan A. Relating multi-sequence longitudinal intensity profiles and clinical covariates in incident multiple sclerosis. Neuroimage Clin 2016; 10:1-17. Epub 2015 Nov 11. PMID: 26693397. PMC4660378. 10.1016/j.nicl.2015.10.013
    • Duan Q, Nair G, Gudino N, de Zwart JA, van Gelderen P, Murphy-Boesch J, Reich DS, Duyn JH, Merkle H. A 7T spine array based on electric dipole transmitters. Magn Reson Med 2015; 74:1189-1197. Epub 2015 Jul 20. PMID: 26190585. PMC4575257. 10.1002/mrm.25817
    • *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. PMC5082280. 10.1002/nbm.3340
    • Shinohara RT, Sweeney EM, Goldsmith J, Shiee N, Mateen FJ, Calabresi PA, Jarso S, Pham DL, Reich DS, Crainiceanu CM. Statistical normalization techniques for magnetic resonance imaging. Neuroimage Clin 2014; 6:9-19. Epub 2014 Aug 15. PMID: 25379412. PMC4215426. 10.1016/j.nicl.2014.08.008
    • *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. PMC4144036. 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 ICM, 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. PMC4725580. 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. PMC4167170. 10.1177/1352458514525868
    • Jones BC, Nair G, Shea CD, Crainiceanu CM, Cortese ICM, 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. PMC3791279. 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. PMC4278432. 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. PMC3504317. 10.1148/radiol.12120208
    • Bazin P-L, Ye C, Bogovic JA, Shiee N, Reich DS, Prince JL, Pham D. Direct segmentation of the major white matter tracts in diffusion tensor images. Neuroimage 2011; 58:458-468. Epub 2011 Jun 21. PMID: 21718790. PMC3159825. 10.1016/j.neuroimage.2011.06.020
    • Shiee N, Bazin P-L, Ozturk A, Calabresi PA, Reich DS, Pham D. A topology-preserving approach to the segmentation of brain images with multiple sclerosis lesions. Neuroimage 2010; 49:1524-1535. PMID: 19766196. PMC2806481. 10.1016/j.neuroimage.2009.09.005

    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.

    • Xia Z*, Steele SU*, Bakshi A, Clarkson SR, White CC, Schindler MK, Nair G, Dewey BE, Price LR, Ohayon J, Chibnik LB, Cortese ICM, De Jager PL*, Reich DS*. Assessment of 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. PMC5348267. 10.1001/jamaneurol.2016.5056(Editorial by Fredrik Piehl)
    • Xia Z, White C, Owen E, von Korff A, Clarkson S, McCabe C, Cimpean M, Winn P, Hoesing A, Steele S, Cortese ICM, 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. PMC4778957. 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?

    • Sudarshana DM, Nair G, Dwyer JT, Dewey B, Steele SU, Wu T, Berkowitz BA, Koretsky AP, Cortese ICM, 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. PMC6754109. 10.3174/ajnr.a6152
    • Wood ET, Ercan E, Cortese ICM, Ronen I, Reich DS. Longitudinal MR spectroscopy of neurodegeneration in multiple sclerosis with diffusion of the intra-axonal constituent N-acetylaspartate. NeuroImage: Clinical 2017; 15:780-788. Epub 2017 Jun 22. PMID: 28702353. PMC5496488. 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. PMC4482216. 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. PMC3753185. 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. PMC3360480. 10.1523/jneurosci.0044-12.2012
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