Magnetic Resonance Imaging (MRI) has provided an exquisite opportunity to see inside the brain of people living with multiple sclerosis (MS). However, it’s often unclear what pathological processes is represented on MRI. Cleveland Clinic's brain and spinal cord donation program has been active for over 20 years collecting brain and spinal cord from post-mortem donors with MS to help understand the underlying pathology of MS. The program involves obtaining an MRI shortly after death (typically within 6 hours), conducting a 3 tesla MRI of the brain and upper cervical cord, followed by removal of the brain and spinal cord. Half the brain is flash frozen and the other half is placed in long fixation for histological analysis. The program accepts tissues from patients followed at the Mellen Center and from patients who pass away within about a 75 mile radius of Cleveland Clinic. In total, over 160 brains have been collected. The MRI data and tissue obtained has been used by a multidisciplinary research team including neurologists, pathologists, basic science researchers, imaging engineers, and biomedical engineers to conduct transformative research evaluating the connection between MRI and pathology in MS. The brain and spinal cord donation program is directed by neurologist Daniel Ontaneda, MD, MSc and basic neuroscientist Bruce Trapp, PhD.
The Imaging/Pathology Correlation program has enabled several seminal discoveries in the field of MS including:
- Axonal transection in early MS
- Identification and classification of cortical lesions
- Role of premyelinating oligodendrocytes in chronic MS lesions
- Mechanisms of axonal degeneration in MS
- Hippocampal pathology in MS
- Identification of an MS subtype with normal brain white matter myelin content
Currently about a dozen grants research that uses tissue from the MS brain and spinal cord donation program, which remains the only such program in the US that routinely incorporates MRI.
NIH R35NS097303, Pathogenesis of neurological disability in primary diseases of myelin, Trapp (PI) 12/2016 – 11/2024.
Sanofi-Genzyme GENZ1502BT, Rapid autopsy program at the Cleveland Clinic Foundation, Trapp (PI), 02/2015 – 01/2020.
NIH R01NS096148, MicroRNAs as critical regulators of remyelination in multiple sclerosis, Dutta (PI) 05/2016-02/2021.
NMSS RG 5298-A, Pathogenesis of cortical demyelination in progressive multiple sclerosis, Dutta (PI) 02/2015-10/2018.
The relationship between cognitive function and high-resolution diffusion tensor MRI of the cingulum bundle in multiple sclerosis. Mult Scler J 2015;21(14):1794-801. KA, Sakaie KE, Lowe MJ, Lin J, Stone L, Bermel RA, Beall EB, Rao SM, Trapp BD, Phillips MD. PMID: 26106010.
Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol 2015;14(2):183-93. DH, Trapp BD, Lassmann H. PMID: 25772897.
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.
DNA methylation in demyelinated multiple sclerosis hippocampus. Sci Rep 2017;7(1):8696. AM, Volsko C, Tripathi A, Deckard SA, Trapp BD, Fox RJ, Dutta R. PMID: 28821749.
Much, if not all, of the cortical damage in MS can be attributed to the microglial cell – No. Dutta, R., Trapp, B.D., 2018. Mult. Scler. J. 24, 897–899. https://doi.org/10.1177/1352458517743094.
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.
The role of the thalamus and hippocampus in episodic memory performance in patients with multiple sclerosis. Koenig, K.A., Rao, S.M., Lowe, M.J., Lin, J., Sakaie, K.E., Stone, L., Bermel, R.A., Trapp, B.D., Phillips, M.D., 2019. Mult. Scler. 25, 574–584. https://doi.org/10.1177/1352458518760716.
Brain fibrinogen deposition plays a key role in MS pathophysiology - Yes. Davalos, D., Mahajan, K.R., Trapp, B.D., 2019. Mult. Scler. 25, 1434–1435. https://doi.org/10.1177/1352458519852723.
Identifying a new subtype of multiple sclerosis. Neurodegener. Trapp, B.D., Ontaneda, D., 2018. Dis. Manag. 8, 367–369. https://doi.org/10.2217/nmt-2018-0032.
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.
Oligodendrocyte Intrinsic miR-27a Controls Myelination and Remyelination. Tripathi, A., Volsko, C., Garcia, J.P., Agirre, E., Allan, K.C., Tesar, P.J., Trapp, B.D., Castelo-Branco, G., Sim, F.J., Dutta, R., 2019. Cell Rep. 29, 904-919.e9. https://doi.org/10.1016/j.celrep.2019.09.020.
Members & Collaborations
- Harsha Battapady, MS
- Jacqueline Chen, PhD
- Tony Chomyk, BS
- Tara da Silva, PhD
- Jessica Dudman, BS
- Jordon Dunham, PhD
- Ranjan Dutta, PhD
- Robert Fox, MD, MSc
- Kedar Mahajan, MD, PhD
- Kunio Nakamura, PhD
- Daniel Ontaneda, MD, MSc
- Ken Sakaie, PhD
- Susan Staugaitis, MD, PhD
- Bruce Trapp, PhD
External Relationships and Collaborations
- Don Mahad, MD, PhD – University of Edinburgh, Edinburgh, Scotland
- Sverre Mørk MD, PhD (Univ of Bergen, Norway)