Kunio Nakamura, Ph.D.
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Phone: (216) 444-4789
Our objective is to develop new methods of analyzing medical images to gain a better understanding of diseases such as multiple sclerosis (MS). Traditional image processing and machine learning algorithms are used to quantify lesion burden and classify and predict prognosis.
Standard MRIs are difficult to interpret because several different types of tissue damage all appear the same, and some types cannot be seen at all. One example is brain atrophy, which happens too slowly to be seen by the eye, and requires specialized image analysis software to measure. In addition, although MS affects both white matter and gray matter, only white matter lesions can be seen on standard MRIs.
Therefore, we are developing techniques to quantify the different MS pathologic processes, to accurately measure small changes over time, and to assess damage in gray matter and white matter. These new tools can help us understand MS better, help doctors make treatment decisions, and help pharmaceutical companies determine if new drugs are effective.
Multiple sclerosis (MS) causes increasing disability caused by tissue damage in the central nervous system. Magnetic resonance imaging (MRI) allows us to observe MS disease in humans, but standard MRI methods are not specific enough to provide a complete picture of disease progression. The main goals of our research are to: (1) develop software to automatically perform reliable measurements from brain MRIs; (2) investigate new imaging and analysis methods to assess how MS develops; and (3) apply these new techniques in MS patients to improve understanding of the disease. We envision that this research will lead to a better understanding of MS, and may be beneficial for evaluating new drug therapies, monitoring patients, and predicting long-term disease severity.
Alasdair J Coles, Douglas L Arnold, Ann D Bass, Aaron L Boster, D Alastair S Compston, Óscar Fernández, Eva Kubala Havrdová, Kunio Nakamura, Anthony Traboulsee, Tjalf Ziemssen, Alan Jacobs, David H Margolin, Xiaobi Huang, Nadia Daizadeh, Madalina C Chirieac, Krzysztof W Selmaj. Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial. Ther Adv Neurol Disord. 2021 Apr 23;14:1756286420982134. doi: 10.1177/1756286420982134. eCollection 2021.
Zheng Y, Dudman J, Chen JT, Mahajan KR, Herman D, Fox RJ, Ontaneda D, Trapp BD, Nakamura K. Sensitivity of T1/T2-weighted ratio in detection of cortical demyelination is similar to magnetization transfer ratio using post-mortem MRI. Mult Scler. 2021 May 20:13524585211014760. doi: 10.1177/13524585211014760
Mahajan KR, Amin M, Poturalski M, Lee J, Herman D, Zheng Y, Androjna C, Howell M, Fox RJ, Trapp BD, Jones SE, Nakamura K, Ontaneda D. Juxtacortical susceptibility changes in progressive multifocal leukoencephalopathy at the gray-white matter junction correlates with iron-enriched macrophages. Mult Scler. 2021 Mar 22:1352458521999651. doi: 10.1177/1352458521999651. Online ahead of print. PMID: 33749379
Conway DS, Planchon SM, Oh SH, Nakamura K, Thompson NR, Sakaie K, Ontaneda D. Measures of Thalamic Integrity are Associated with Cognitive Functioning in Fingolimod-treated Multiple Sclerosis Patients. Mult Scler Relat Disord. 2021 Jan;47:102635. doi: 10.1016/j.msard.2020.102635. Epub 2020 Nov 22. PMID: 33260053
Abbatemarco JR, Ontaneda D, Nakamura K, Husak S, Wang Z, Alshehri E, Bermel RA, Conway DS. Comorbidity effect on processing speed test and MRI measures in multiple sclerosis patients. Mult Scler Relat Disord. 2020 Nov;46:102593. doi: 10.1016/j.msard.2020.102593. Epub 2020 Oct 21. PMID: 33296988
Pulido-Valdeolivas I, Andorrà M, Gómez-Andrés D, Nakamura K, Alba-Arbalat S, Lampert EJ, Zubizarreta I, Llufriu S, Martinez-Heras E, Solana E, Sola-Valls N, Sepulveda M, Tercero-Uribe A, Blanco Y, Camos-Carreras A, Sanchez-Dalmau B, Villoslada P, Saiz A, Martinez-Lapiscina EH. Retinal and brain damage during multiple sclerosis course: inflammatory activity is a key factor in the first 5 years. Sci Rep. 2020 Aug 7;10(1):13333. doi: 10.1038/s41598-020-70255-z. PMID: 32770013 Free PMC article.
Mahajan KR, Nakamura K, Cohen JA, Trapp BD, Ontaneda D. Intrinsic and Extrinsic Mechanisms of Thalamic Pathology in Multiple Sclerosis. Ann Neurol. 2020 Jul;88(1):81-92. doi: 10.1002/ana.25743. Epub 2020 May 1. PMID: 32286701
Ontaneda D, Tallantyre EC, Raza PC, Planchon SM, Nakamura K, Miller D, Hersh C, Craner M, Bale C, Chaudhry B, Gunzler DD, Love TE, Gerry S, Coles A, Cohen JA, Evangelou N. Determining the effectiveness of early intensive versus escalation approaches for the treatment of relapsing-remitting multiple sclerosis: The DELIVER-MS study protocol. Contemp Clin Trials. 2020 Aug;95:106009. doi: 10.1016/j.cct.2020.106009. Epub 2020 Apr 19. PMID: 32320842
Anand A, Nakamura K, Spielberg JM, Cha J, Karne H, Hu B. Integrative analysis of lithium treatment associated effects on brain structure and peripheral gene expression reveals novel molecular insights into mechanism of action. Transl Psychiatry. 2020 Apr 6;10(1):103. doi: 10.1038/s41398-020-0784-z. PMID: 32251271 Free PMC article.
Nakamura K, Rudick RA, Ontaneda D, Fox RJ, Trapp BD, Fisher E. Fourteen-year serial MRIs of patients with mild and severe courses of MS. Neurol Clin Pract. 2020 Feb;10(1):e5-e6. doi: 10.1212/CPJ.0000000000000695. PMID: 32190426 Free PMC article. No abstract available.
Gaj S, Yang M, Nakamura K, Li X. Automated cartilage and meniscus segmentation of knee MRI with conditional generative adversarial networks. Magn Reson Med. 2020 Jul;84(1):437-449. doi: 10.1002/mrm.28111. Epub 2019 Dec 2.
Narayanan S, Nakamura K, Fonov VS, Maranzano J, Caramanos Z, Giacomini PS, Collins DL, Arnold DL. Brain volume loss in individuals over time: Source of variance and limits of detectability. Neuroimage. 2020 Jul 1;214:116737. doi: 10.1016/j.neuroimage.2020.116737. Epub 2020 Mar 21.
Baldassari LE, Nakamura K, Moss BP, Macaron G, Li H, Weber M, Jones SE, Rao SM, Miller D, Conway DS, Bermel RA. Technology-enabled comprehensive characterization of multiple sclerosis in clinical practice. Multiple Sclerosis and Related Disorders. 2020 Feb 1;38:101525.
Baldassari LE, Planchon SM, Bermel RA, Nakamura K, Fisher E, Feng J, Sakaie KE, Ontaneda D, Cohen JA. Serum neurofilament light chain concentration in a phase 1/2 trial of autologous mesenchymal stem cell transplantation. Multiple Sclerosis Journal–Experimental, Translational and Clinical. 2019 Nov;5(4):2055217319887198.
Dutta R, Mahajan KR, Nakamura K, Ontaneda D, Chen J, Volsko C, Dudman J, Christie E, Dunham J, Fox RJ, Trapp BD. Comprehensive Autopsy Program for Individuals with Multiple Sclerosis. Journal of Visualized Experiments: JoVE. 2019 Jul 19(149).
Feng J, Offerman E, Lin J, Fisher E, Planchon SM, Sakaie K, Lowe M, Nakamura K, Cohen JA, Ontaneda D. Exploratory MRI measures after intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis. Multiple Sclerosis Journal–Experimental, Translational and Clinical. 2019 Jun;5(2):2055217319856035.
Lee H, Nakamura K, Narayanan S, Brown RA, Arnold DL, Alzheimer's Disease Neuroimaging Initiative. Estimating and accounting for the effect of MRI scanner changes on longitudinal whole-brain volume change measurements. NeuroImage. 2019 Jan 1;184:555-65.
Trapp BD, Vignos M, Dudman J, et al. Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study. The Lancet Neurology. 2018 Oct 1;17(10):870-84.
Andorra M, Nakamura K, Lampert EJ, Pulido-Valdeolivas I, Zubizarreta I, Llufriu S, Martinez-Heras E, Sola-Valls N, Sepulveda M, Tercero-Uribe A, Blanco Y. Assessing biological and methodological aspects of brain volume loss in multiple sclerosis. JAMA Neurology. 2018 Oct 1;75(10):1246-55.
Fox RJ, Coffey CS, Conwit R, et al. Phase 2 trial of ibudilast in progressive multiple sclerosis. New England Journal of Medicine. 2018 Aug 30;379(9):846-55.
Lee H, Nakamura K, Narayanan S, Brown R, Chen J, Atkins HL, Freedman MS, Arnold DL. Impact of immunoablation and autologous hematopoietic stem cell transplantation on gray and white matter atrophy in multiple sclerosis. Multiple Sclerosis Journal. 2018 Jul;24(8):1055-66.
Nakamura K, Chen JT, Ontaneda D, Fox RJ, Trapp BD, T1-/T2-weighted ratio differs in demyelinated cortex in multiple sclerosis. Ann Neurol. 2017, 82: 635–639.
Fisher E, Nakamura K, Lee JC, You X, Sperling B, Rudick RA. Effect of Intramuscular Interferon Beta-1a on Gray Matter Atrophy in Relapsing Remitting Multiple Sclerosis: A Retrospective Analysis. Multiple Sclerosis Journal 2016; 22(5) 668-76.
Chen JT, Easley K, Schneider C, Nakamura K, Kidd GJ, Chang A, Staugaitis SM, Fox RJ, Fisher E, Arnold DL, Trapp BD, Clinically feasible MTR is sensitive to cortical demyelination in MS. Neurology 2013; Jan 15;80(3):246-52.
Nakamura K, Fox RJ, Fisher E. CLADA: Cortical Longitudinal Atrophy Detection Algorithm. NeuroImage 54(1):278-89. 2011.
Rudick RA, Lee JC, Nakamura K, Fisher E. Gray matter atrophy and disability in multiple sclerosis. Journal of Neurological Sciences 282:106-111, 2009.
Nakamura K and Fisher E, Segmentation of Brain Magnetic Resonance Images for Measurement of Gray Matter Atrophy in Multiple Sclerosis Patients. NeuroImage. 2009; 44(3): 769-776.
Fisher E, Lee J-C, Nakamura K, Rudick R. Gray matter atrophy in multiple sclerosis: a longitudinal study. Annals of Neurology 64:255-265. 2008.
Researchers from the Department of Biomedical Engineering have found that several magnetic resonance imaging (MRI) modalities can be harnessed to better assess the severity and progression of multiple sclerosis (MS) than traditional imaging methods, according to new findings from Kunio Nakamura, PhD, published in Multiple Sclerosis Journal.