Our objective is to develop new methods for analysis of brain MRIs to gain a better understanding of multiple sclerosis (MS). MS is an autoimmune disease that affects the brain and spinal cord and causes progressive disability. Brain MRIs show regions that have been damaged by MS inflammatory attacks. Neurologists often use MRI to help with diagnosis, to assess disease progression, and to decide whether specific therapies are working. However, standard MRIs are difficult to interpret because there are several different types of tissue damage that all appear the same, plus there are some types of tissue damage that cannot be seen at all. One example is tissue loss, or brain atrophy, which happens too slowly to be seen by eye, so specialized image analysis software is needed to measure it. Another example is that although MS affects both tissue types, white matter and gray matter, only white matter lesions can be seen on standard MRIs. Current methods only provide a partial picture of MS. Therefore, we are interested in developing techniques to distinguish and quantify the different MS pathologic processes, to accurately measure small changes over time, and to assess damage in gray matter as well as in white matter. These new tools will not only help us understand MS better, but they can help the doctors make treatment decisions with their patients and they can help pharmaceutical companies determine if new drugs are effective.
In other words ...
Multiple sclerosis (MS) causes progressive disability due to tissue damage in the central nervous system. Many aspects of MS pathogenesis are not well understood. Magnetic resonance imaging (MRI) provides a window to observe MS pathology in-vivo, but standard methods of MRI are not specific enough to provide a complete picture of disease progression. Accurate and precise image analysis tools are required to be able to track MS disease processes in individuals over time. 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 for quantification of specific MS pathologic processes; and (3) Apply these new measurement techniques in MS patients to improve understanding of the disease. The new methods for quantitative MRI analysis developed in our lab are tested both in MS patients to determine clinical correlations, and in post-mortem brain tissue to determine pathologic correlations. A major focus of our work has been the measurement and characterization of brain atrophy in MS. We have been following a group of patients and controls for 6-15 years in order to gain insight on the pathologic mechanisms of irreversible tissue destruction in MS brains. We envision that this research will not only lead to a better understanding of irreversible tissue destruction in MS, but also that the new MRI analysis techniques may be beneficial for evaluating new drug therapies, monitoring patients, and predicting long-term disease severity.
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.
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