Program Project Grant

MRI photo left to right Rob Naismith MD, Ann Cross MD, Victor SongPhD, and Robyn Klein M.D. Shot for Outlook Magazine

Program Project Grant “Biomarkers and pathogenesis of MS: From Mouse to Human”

The Neuroimmunology group was awarded a 5 year Program Project award by the NINDS/ NIH (2008-2013). The overall goal is to develop and validate novel cutting edge imaging techniques to determine underlying pathology of CNS in vivo.

Members of our group developed a novel approach to use diffusion tensor imaging (DTI) for noninvasive detection and differentiation of axon and myelin damage and validated the method in animal models.

The 3 projects of the PO1 are:
“Assessing MRI Biomarkers of White Matter Injury,” PI: Sheng-Kwei (Victor) Song, PhD
“Neuroprotective mechanisms of CXCL12 in CNS Demyelinating Diseases,” PI: Robyn S. Klein MD, PhD
“Directional Diffusivity as a Window into the Pathology MS,” PI: Anne Cross MD

Other investigators integral to the PO1 include: Robert T Naismith MD (Proj 4), Joong Kim PhD (Proj 1), Kathryn (Kim) Trinkaus PhD (Biostatistics Core), Tammie Benzinger MD, PhD (Proj 4), Dr. Junqian (Gordon) Xu PhD (Proj 4).

Recent selected publications from the group include:

  1. Song, SK, Sun S-W, Ramsbottom MJ, Chang C, Russell J, Cross AH: Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage 17: 1429-1436, 2002.
  2. Song SK, Sun SW, Ju WK, Lin SJ, Cross AH, Neufeld AH: Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia. NeuroImage 2003; 20: 1714-1722.
  3. Song SK, Yoshino J, Le TQ, Lin S-J, Sun S-W, Cross AH, Armstrong RC. Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage 2005; 26:132-140.
  4. Sun SW, Liang HF, Trinkaus K, Cross AH, Armstrong RC, Song SK: Noninvasive Detection of Cuprizone Induced Axonal Damage and Demyelination in the Mouse Corpus Callosum” Magn Res Med 2006; 55:302-308.
  5. Kim, JH, Budde MD, Liang HF, Klein RS, Russell JH, Cross AH, Song SK: Detecting Axon Damage in Spinal Cords from a Mouse Model of Multiple Sclerosis Using Diffusion Tensor Imaging. Neurobiol of Disease 2006; 21:626-632.
  6. McCandless DD, Piccio LA, Woerner BM, Schmidt RE, Rubin JB, Cross AH, Klein RS. Pathologic expression of CXCL12 at the blood-brain barrier correlates with severity of multiple sclerosis. Am J Pathol 2008; 172: 799-808
  7. Benzinger TLS, Cross AH, Xu J, Naismith R, Sun SW, Song SK. Directional diffusivity as a magnetic resonance (MR) biomarker in demyelinating disease. Proc. SPIE, 2007; 6759:1-10 2007
  8. J. H. Kim, K. Trinkus, and S.-K. Song, “Postmortem Delay Does Not Change Diffusion Anisotropy Indices in Mouse Spinal Cord White Matter”,NMR Biomed., 20: 1-8 (2007).
  9. D. N. Loy, J. H. Kim, M. Xie, R. E. Schmidt, K. Trinkaus, and S.-K. Song, “Diffusion tensor imaging predicts hyperacute spinal cord injury severity”, J. Neurotrauma, 24, 979 – 990 (2007).
  10. J. H. Kim, D. N. Loy, H.-F. Liang, K. Trinkaus, R. E. Schmidt, and S.-K. Song, “Noninvasive diffusion tensor imaging of evolving white matter pathology in a mouse model of acute spinal cord injury”, Mag. Reson. Med. 57: 253 – 260 (2007).
  11. S.-W. Sun, H.-F. Liang, A. H. Cross, and S.-K. Song, “Selective Vulnerability of Cerebral White Matter in a Mouse Model of Multiple Sclerosis Detected Using Diffusion Tensor Imaging”, Neurobiol. Diseas., 28: 30 – 38 (2007).
  12. C. L. MacDonald, K. Dikranian, S.-K. Song, P. Bayly, D. M. Holtzman, D. Brody, “Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury”, Exper. Neurology, 205(1), 116 – 31 (2007).
  13. S. C. Jost, J. E. Wanebo, S.-K. Song, M. R. Chicoine, K. M. Rich, T. A. Woolsey, J. S. Lewis, R. H. Mach, J. Xu, and J. R. Garbow, “In vivo imaging in a murine model of glioblastoma” Neurosurgery, 60(2), 360 – 370 (2007).
  14. M. D. Budde, J. H. Kim, H.-F. Liang, J. H. Russell, A. H. Cross, and S.-K. Song, . “Axonal injury detected by in vivo diffusion tensor imaging correlates with neurological disability in a mouse model of multiple sclerosis” NMR Biomed., 21(6), 589 – 97 (2008).
  15. S.-W. Sun, H.-F. Liang, A. H. Cross, and S.-K. Song, “Evolving Wallerian degeneration after transient retinal ischemia in mice characterized by diffusion tensor imaging”, Neuroimage, 40: 1 – 10 (2008).
  16. J. Chen, Q. Wang, H. Zhang, X. Yang, J. Wang, B.A Berkowitz, S. A Wickline, S.-K. Song, “In Vivo Quantification of T1, T2, and Apparent Diffusion Coefficient in the Mouse Retina at 11.74T”, Mag. Reson. Med., 59: 731 – 738 (2008).
  17. J. Xu, S.-W. Sun, R. T. Naismith, A. Z. Snyder, A. H. Cross, and S.-K. Song. “Assessing Optic Nerve Pathology with Diffusion MRI: from Mouse to Human”,NMR Biomed., 21(9): 928 – 40 (2008).
  18. R. T. Naismith, J. Xu, N. T. Tutlam, A. Snyder, T. Benzinger, J. Shimony, J. Shepherd, K. Trinkaus, A. H. Cross, and S.-K. Song, “Disability in Optic Neuritis Correlates with Diffusion Tensor Derived Directional Diffusivities”, Neurology, 72(7): 589 – 594 (2009).
  19. J.-H. Kim, P. Bayly, T.-W. Tu, and S.-K. Song. “Impacting speed does not determine the mouse spinal cord injury severity using the displacement driven impactor”, J. Neurotrauma, 26(8), 1395 – 1440 (2009).
  20. J. Xu, P. A. Humphrey, A. S. Kibel, A. Z. Snyder, V. R. Narra, J. J. H. Ackerman, and S.-K. Song, “Magnetic Resonance Diffusion Characteristics of Histologically Defined Prostate Cancer in Humans”, Mag. Reson. Med., 61(4): 842-850 (2009).
  21. R. T. Naismith, N. T. Tutlam, J. Xu, E. Klawiter, J. Shepherd, K. Trinkaus, S.-K. Song, and A. H. Cross, . “Optical Coherence Tomography Differs In Neuromyelitis Optica Compared With Multiple Sclerosis”, Neurology, 72(12):1077 – 82 (2009).
  22. J.-H. Kim, P. Bayly, T.-W. Tu, and S.-K. Song. “Impacting speed does not determine the mouse spinal cord injury severity using the displacement driven impactor”, J. Neurotrauma, 26(8), 1395 – 1440 (2009).
  23. M. Budde, M. Xie, S.-F. Liang, K. Trinkaus, A. H. Cross, S.-K. Song, “Axial Diffusivity is the Primary Correlate of Axonal Injury in the EAE Spinal Cord: A Quantitative Pixelwise Correlation Analysis”, J. Neurosci., 29(9):2805-2813 (2009).
  24. R. T. Naismith, N. T. Tutlam, J. Xu, E. C. Klawiter, J. Shepherd, K. Trinkaus, S.-K. Song, and Anne H. Cross, “Optical coherence tomography is less sensitive than visual evoked potentials in optic neuritis”, Neurology, 73(1): 46 – 52 (2009).
  25. X. Ou, S.-W. Sun, H.-F. Liang, S.-K. Song, and D. Gochberg, “Quantitative magnetization transfer measured pool-size ratio reflects optic nerve myelin content in ex vivo mice”, Magn. Reson. Med., 61(2): 364 – 371 (2009).
  26. R. T. Naismith, N. T. Tutlam, J. Xu, E. C. Klawiter, J. Shepherd, K. Trinkaus, S.-K. Song, and Anne H. Cross, . “Optical coherence tomography is less sensitive than visual evoked potentials in optic neuritis”, Neurology, 73(1), 46 – 52 (2009).
  27. X. Ou, S.-W. Sun, H.-F. Liang, S.-K. Song, and D. Gochberg, “The MT pool size ratio and the DTI radial diffusivity may reflect the myelination in shiverer and control mice”, NMR Biomed., 22(5), 480 – 7 (2009).
  28. A. A. Hofling, J. H. Kim, C. R. Fantz, M. S. Sands, and S.-K. Song, “Diffusion tensor imaging detects axonal injury and demyelination in the spinal cord and brain of a murine model of globoid cell leukodystrophy”, NMR Biomed, 22, 1100 – 1106 (2009).
  29. Xie M, Tobin JE, Budde MD, Chen CI, Trinkaus K, Cross AH, McDaniel DP, Song SK, Armstrong R. “Rostro-Caudal Analysis of Corpus Callosum Demyelination and Axon Damage Across Disease Stages Refines Diffusion Tensor Imaging Correlation with Pathological Features”, J. Neuropath. Exp. Neurol. (2010); 69: 704-716. PMCID: PMC2901930
  30. Klawiter EC, Schmidt RE, Trinkaus K, Liang HF, Budde MD, Naismith RT, Song SK, Cross AH, Benzinger TL. “Radial diffusivity predicts demyelination in ex-vivo multiple sclerosis spinal cords”, NeuroImage (2011); 55:1454-1460. PMCID: PMC3062747
  31. Wang Y, Wang Q, Haldar JP, Yeh FC, Xie M, Sun P, Trinkaus K, Klein RS, Cross AH, Song S-K. “Quantification of increased cellularity during inflammatory demyelination”, Brain (2011);134:3587-9.
  32. Naismith RT, Xu J, Tutlam NT, Lancia S, Trinkaus K, Song SK, Cross AH. “Diffusion Tensor Imaging in Acute Optic Neuropathies Predicts Clinical Outcomes”, Arch Neurol (2012); 69:65-71
  33. Klawiter EC, Xu J, Naismith RT, Benzinger TLS, Shimony JS, Lancia S, Snyder AZ, Trinakaus K, Song SK, Cross AH. “Spinal cord diffusion tensor imaging differentiates neuromyelitis optica from multiple sclerosis”, Mult Scler (in press)