Magnetic resonance imaging (MRI) has revolutionized both the diagnosis and treatment of multiple sclerosis (MS). MRI is used every day as a prognostic marker and in treatment response outcome assessment in clinical practice, and as an outcome measure in clinical trials. Despite the demonstrated utility of MRI, it has limited specificity to the pathological disease process and provides limited insight in the progressive forms of the disease.

At the Mellen Center for MS Treatment and Research, we are investigating several advanced MRI technologies with the aim of providing new insights into disease biology, improving specificity of MRI to pathological processes, and developing biomarkers for neurodegeneration/neural repair. Advanced MRI research is conducted on a 3 tesla Siemens Skyra, a 3 tesla Siemens Prisma, and a 7 tesla Siemens Magnetom, all of which are housed within the Mellen Center. A dozen neuroradiologists, MRI physicists, and MRI technologists leverage a state of the art image analysis laboratory dedicated to MS research. The Mellen Center Imaging group pioneered and implemented the following methods to better understand MS.

Techniques under investigation include:

  • Whole brain and segmented atrophy (i.e. thalamus, cortex)
  • Diffusion tensor imaging
  • Functional MRI (including resting state functional MRI)
  • Magnetic resonance fingerprinting
  • Multi-model myelin imaging
  • Central vein imaging
  • GABA spectroscopy
  • Myelin PET imaging
  • USPIO contrast based imaging


Daniel Ontaneda, MD MSc


NIH U01NS082329, A randomized, double-blind, placebo-controlled study of ibudilast in subjects with progressive multiple Sclerosis, Fox (PI) 07/2013 – 06/2018.

PCORI MS-1610-37047, Determining the effectiveness of early intensive versus escalation approaches for the treatment of relapsing-remitting multiple sclerosis (DELIVER-MS), Ontaneda (PI), 20/2018 – 01/2023.

NIH R01NS091683, Pathogenesis of tissue destruction in multiple sclerosis, Trapp (PI) 07/2016 – 06/2020.

DOD W81XWH-16-1-0446, Longitudinal Evaluation of the Relation of Imaging Measures to Cognitive Decline in Multiple Sclerosi, Koenig (PI), 09/2016 – 09/2019.

Race to Erase MS Foundation Pilot Study, Central vein sign in the early diagnosis of multiple sclerosis (CAVS-MS), Ontaneda (PI) 06/2017 – 06/2018.

NMSS PP-1603-08307, Vitamin D levels in progressive multiple sclerosis, Ontaneda (PI) 09/2016 – 08/2017.



NN102/SPRINT-MS Trial Investigators, 2018. Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis. Fox, R.J., Coffey, C.S., Conwit, R., Cudkowicz, M.E., Gleason, T., Goodman, A., Klawiter, E.C., Matsuda, K., McGovern, M., Naismith, R.T., Ashokkumar, A., Barnes, J., Ecklund, D., Klingner, E., Koepp, M., Long, J.D., Natarajan, S., Thornell, B., Yankey, J., Bermel, R.A., Debbins, J.P., Huang, X., Jagodnik, P., Lowe, M.J., Nakamura, K., Narayanan, S., Sakaie, K.E., Thoomukuntla, B., Zhou, X., Krieger, S., Alvarez, E., Apperson, M., Bashir, K., Cohen, B.A., Coyle, P.K., Delgado, S., Dewitt, L.D., Flores, A., Giesser, B.S., Goldman, M.D., Jubelt, B., Lava, N., Lynch, S.G., Moses, H., Ontaneda, D., Perumal, J.S., Racke, M., Repovic, P., Riley, C.S., Severson, C., Shinnar, S., Suski, V., Weinstock-Guttman, B., Yadav, V., Zabeti, A., N. Engl. J. Med. 379, 846–855. https://doi.org/10.1056/NEJMoa1803583.

Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study.Trapp, B.D., Vignos, M., Dudman, J., Chang, A., Fisher, E., Staugaitis, S.M., Battapady, H., Mork, S., Ontaneda, D., Jones, S.E., Fox, R.J., Chen, J., Nakamura, K., Rudick, R.A., 2018. Lancet. Neurol. 17, 870–884. https://doi.org/10.1016/S1474-4422(18)30245-X.

MOG-related disorders: A new cause of imaging-negative myelitis?Macaron, G., Ontaneda, D., 2019. Mult. Scler. 1352458519840746. https://doi.org/10.1177/1352458519840746.

Developing therapeutic strategies to promote myelin repair in multiple sclerosis. Baldassari, L.E., Feng, J., Clayton, B.L.L., Oh, S.-H., Sakaie, K., Tesar, P.J., Wang, Y., Cohen, J.A., 2019. Expert Rev. Neurother. 19, 997–1013. https://doi.org/10.1080/14737175.2019.1632192.

Serum neurofilament light chain concentration in a phase 1/2 trial of autologous mesenchymal stem cell transplantation.Baldassari, L.E., Planchon, S.M., Bermel, R.A., Nakamura, K., Fisher, E., Feng, J., Sakaie, K.E., Ontaneda, D., Cohen, J.A., 2019. Mult. Scler. J. - Exp. Transl. Clin. 5, 2055217319887198. https://doi.org/10.1177/2055217319887198.

Exploratory MRI measures after intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis. Feng, J., Offerman, E., Lin, J., Fisher, E., Planchon, S.M., Sakaie, K., Lowe, M., Nakamura, K., Cohen, J.A., Ontaneda, D., 2019. Mult. Scler. J. - Exp. Transl. Clin. 5, 2055217319856035. https://doi.org/10.1177/2055217319856035.

Comparative discontinuation, effectiveness, and switching practices of dimethyl fumarate and fingolimod at 36-month follow-up.Vollmer, B., Ontaneda, D., Harris, H., Nair, K., Bermel, R.A., Corboy, J.R., Fox, R.J., Vollmer, T., Cohen, J.A., Alvarez, E., Hersh, C.M., 2019. J. Neurol. Sci. 407, 116498. https://doi.org/10.1016/j.jns.2019.116498.

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis.Dutta, R., Mahajan, K.R., Nakamura, K., Ontaneda, D., Chen, J., Volsko, C., Dudman, J., Christie, E., Dunham, J., Fox, R.J., Trapp, B.D., 2019. J. Vis. Exp. https://doi.org/10.3791/59511.

Technology-enabled comprehensive characterization of multiple sclerosis in clinical practice. Baldassari, L.E., Nakamura, K., Moss, B.P., Macaron, G., Li, H., Weber, M., Jones, S.E., Rao, S.M., Miller, D., Conway, D.S., Bermel, R.A., Cohen, J.A., Ontaneda, D., McGinley, M.P., 2019. Mult. Scler. Relat. Disord. 38, 101525. https://doi.org/10.1016/j.msard.2019.101525.

Vitamin D and MRI measures in progressive multiple sclerosis.Abbatemarco, J.R., Fox, R.J., Li, H., Ontaneda, D., 2019. Mult. Scler. Relat. Disord. 35, 276–282. https://doi.org/10.1016/j.msard.2019.08.014.

Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis. Contemp Clin Trials 2016;50:166-77.Fox RJ, Coffey CS, Cudkowicz ME, Gleason T, Goodman A, Klawiter EC, Matsuda K, McGovern M, Conwit R, Naismith R, Ashokkumar A, Bermel R, Ecklund D, Koepp M, Long J, Natarajan S, Ramachandran S, Skaramagas T, Thornell B, Yankey J, Agius M, Bashir K, Cohen B, Coyle P, Delgado S, Dewitt D, Flores A, Giesser B, Goldman M, Jubelt B, Lava N, Lynch S, Miravalle A, Moses H, Ontaneda D, Perumal J, Racke M, Repovic P, Riley C, Severson C, Shinnar S, Suski V, Weinstock-Gutman B, Yadav V, Zabeti A. PMID: 27521810.

Effect of intramuscular interferon beta-1a on gray matter atrophy in relapsing-remitting multiple sclerosis: A retrospective analysis. Mult Scler J 2016;22(5):668-76. Fisher E, Nakamura K, Lee JC, You X, Sperling B, Rudick RA. PMID: 26238463.

 T1-/T2-weighted ratio differs in demyelinated cortex in multiple sclerosis. Ann Neurol 2017;82(4):635-639.  K, Chen JT, Ontaneda D, Fox RJ, Trapp BD.PMID: 28833377.

The role of advanced magnetic resonance imaging techniques in multiple sclerosis clinical trials. Neurotherapeutics 2017;14(4):905-923 KR, Ontaneda D. PMID: 28770481.

Imaging as an outcome measure in multiple sclerosis. Neurotherapeutics 2017;14(1):24-34. D, Fox RJ. PMID: 27699722.

Measuring brain tissue integrity during 4 years using diffusion tensor imaging. AJNR 2017;38(1):31-38.  D, Sakaie K, Lin J, Wang XF, Lowe MJ, Phillips MD, Fox RJ. PMID: 27659189.

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