Skip to main content

Advertisement

SpringerLink
Log in

MR Imaging of Inflammation during Myelin-Specific T Cell-Mediated Autoimmune Attack in the EAE Mouse Spinal Cord

  • Research Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study is to detect myelin-specific T cells, key pathological mediators in early multiple sclerosis, and the corresponding animal model, experimental autoimmune encephalomyelitis (EAE), in the mouse spinal cord.

Procedures

T cells were labeled with the iron-based, magnetic resonance (MR) contrast reagent, Feridex, and the transfection reagent, protamine sulfate, resulting in ∼100% iron-labeling efficiency. Feridex-labeling did not alter the induction of EAE by T cells, and recipients were imaged by a 12-T MR instrument.

Results

Focal hypointense lesions were resolvable to gray or white matter of the lumbar spinal cord in T2-weighted images of the recipients of Feridex-labeled T cells. Lesions corresponded to histological evidence of inflammatory lesions and iron-labeled cells in eight-of-eight mice. In contrast, hypointense lesions were not observed eight-of-eight recipients of unlabeled T cells.

Conclusions

These results demonstrate and provide methodologies for labeling, detecting, and extracting MRI-detectable foci of iron-labeled cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50(1):121-127

    Article  CAS  PubMed  Google Scholar 

  2. Barkhof F (2002) The clinico-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol 15(3):239-245

    Article  PubMed  Google Scholar 

  3. Wuerfel J, Tysiak E, Prozorovski T, Smyth M, Mueller S, Schnorr J, Taupitz M, Zipp F (2007) Mouse model mimics multiple sclerosis in the clinico-radiological paradox. Eur J Neurosci 26(1):190-198

    Article  PubMed  Google Scholar 

  4. Chopp M, Li Y, Zhang J (2008) Plasticity and remodeling of brain. J Neurol Sci 265(1-2):97-101

    Article  CAS  PubMed  Google Scholar 

  5. MacKenzie-Graham A, Tinsley MR, Shah KP, Aguilar C, Strickland LV, Boline J, Martin M, Morales L, Shattuck DW, Jacobs RE, Voskuhl RR, Toga AW (2006) Cerebellar cortical atrophy in experimental autoimmune encephalomyelitis. NeuroImage 32(3):1016-1023

    Article  PubMed  Google Scholar 

  6. Oweida AJ, Dunn EA, Karlik SJ, Dekaban GA, Foster PJ (2007) Iron-oxide labeling of hematogenous macrophages in a model of experimental autoimmune encephalomyelitis and the contribution to signal loss in fast imaging employing steady state acquisition (FIESTA) images. J Magn Reson Imaging 26(1):144-151

    Article  PubMed  Google Scholar 

  7. Arbab AS, Yocum GT, Kalish H, Jordan EK, Anderson SA, Khakoo AY, Read EJ, Frank JA (2004) Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI. Blood 104(4):1217-1223

    Article  CAS  PubMed  Google Scholar 

  8. Arbab AS, Yocum GT, Rad AM, Khakoo AY, Fellowes V, Read EJ, Frank JA (2005) Labeling of cells with ferumoxides-protamine sulfate complexes does not inhibit function or differentiation capacity of hematopoietic or mesenchymal stem cells. NMR Biomed 18(8):553-559

    Article  CAS  PubMed  Google Scholar 

  9. Sykova E, Jendelova P (2005) Magnetic resonance tracking of implanted adult and embryonic stem cells in injured brain and spinal cord. Ann N Y Acad Sci 1049:146-160

    Article  PubMed  Google Scholar 

  10. Anderson SA, Shukaliak-Quandt J, Jordan EK, Arbab AS, Martin R, McFarland H, Frank JA (2004) Magnetic resonance imaging of labeled T-cells in a mouse model of multiple sclerosis. Ann Neurol 55(5):654-659

    Article  PubMed  Google Scholar 

  11. Suzuki Y, Zhang S, Kundu P, Yeung AC, Robbins RC, Yang PC (2007) In vitro comparison of the biological effects of three transfection methods for magnetically labeling mouse embryonic stem cells with ferumoxides. Magn Reson Med 57(6):1173-1179

    Article  CAS  PubMed  Google Scholar 

  12. Sorgi FL, Bhattacharya S, Huang L (1997) Protamine sulfate enhances lipid-mediated gene transfer. Gene Ther 4(9):961-968

    Article  CAS  PubMed  Google Scholar 

  13. Montet-Abou K, Montet X, Weissleder R, Josephson L (1997) Cell internalization of magnetic nanoparticles using transfection agents. Mol Imaging 6(1):1-9

    Google Scholar 

  14. Robinson KM, Markwardt S, Kitzerow N, Moes N, Estrada M, Jones RE (2008) Bone marrow lacking integrin expression facilitates an enhanced susceptibility to EAE in the xenogeneic bone marrow chimera. J Neuroimmunol 204(1-2):110-117

    Article  CAS  PubMed  Google Scholar 

  15. Nessler S, Boretius S, Stadelmann C, Bittner A, Merkler D, Hartung HP, Michaelis T, Bruck W, Frahm J, Sommer N, Hemmer B (2007) Early MRI changes in a mouse model of multiple sclerosis are predictive of severe inflammatory tissue damage. Brain 130(Pt 8):2186-2198

    Article  PubMed  Google Scholar 

  16. Smorodchenko A, Wuerfel J, Pohl EE, Vogt J, Tysiak E, Glumm R, Hendrix S, Nitsch R, Zipp F, Infante-Duarte C (2007) CNS-irrelevant T-cells enter the brain, cause blood-brain barrier disruption but no glial pathology. Eur J Neurosci 26(6):1387-1398

    Article  PubMed  Google Scholar 

  17. Schellenberg AE, Buist R, Yong VW, Del Bigio MR, Peeling J (2007) Magnetic resonance imaging of blood-spinal cord barrier disruption in mice with experimental autoimmune encephalomyelitis. Magn Reson Med 58(2):298-305

    Article  PubMed  Google Scholar 

  18. Kidd D, Barkhof F, McConnell R, Algra PR, Allen IV, Revesz T (2007) Cortical lesions in multiple sclerosis. Brain 122 ( Pt 1):17-26

    Google Scholar 

  19. Brochet B, Deloire MS, Touil T, Anne O, Caille JM, Dousset V, Petry KG (2006) Early macrophage MRI of inflammatory lesions predicts lesion severity and disease development in relapsing EAE. NeuroImage 32(1):266-274

    Article  CAS  PubMed  Google Scholar 

  20. Dousset V, Ballarino L, Delalande C, Coussemacq M, Canioni P, Petry KG, Caille JM (2006) Comparison of ultrasmall particles of iron oxide (USPIO)-enhanced T2-weighted, conventional T2-weighted, and gadolinium-enhanced T1-weighted MR images in rats with experimental autoimmune encephalomyelitis. AJNR Am J Neuroradiol 20(2):223-227

    Google Scholar 

  21. Bakshi R, Minagar A, Jaisani Z, Wolinsky JS (2006) Imaging of multiple sclerosis: role in neurotherapeutics. NeuroRx 2(2):277-303

    Article  Google Scholar 

  22. Thrower BW (2007) Clinically isolated syndromes: predicting and delaying multiple sclerosis. Neurology 68(24 Suppl 4):S12-S15

    Article  PubMed  Google Scholar 

  23. Pawelczyk E, Arbab AS, Pandit S, Hu E, Frank JA (2006) Expression of transferrin receptor and ferritin following ferumoxides-protamine sulfate labeling of cells: implications for cellular magnetic resonance imaging. NMR Biomed 19(5):581-592

    Article  CAS  PubMed  Google Scholar 

  24. Genove G, DeMarco U, Xu H, Goins WF, Ahrens ET (2006) A new transgene reporter for in vivo magnetic resonance imaging. Nat Med 11(4):450-454

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported in part by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, Oregon Opportunity and NIH-NINDS RO1-NS040801 and R01NS039122. We thank Drs. Ed Neuwelt, MD; Leslie Muldoon, PhD and Jeff Wu, PhD for assistance with the cell-labeling reagents and protocol. This work was supported in part by a grant from the W. M. Keck Foundation.

Author information

Authors and Affiliations

  1. V.A. Medical Center, VA R&D 23, Bldg 101, 3710 SW US Veteran’s Hospital Rd, Portland, OR, 97239, USA

    Kristine M. Robinson, Thomas M. Proctor & Richard E. Jones

  2. Advanced Imaging Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, L452, Portland, OR, 97239, USA

    Jeffrey M. Njus & William D. Rooney

  3. Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA

    Daniel A. Phillips & Richard E. Jones

Authors
  1. Kristine M. Robinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeffrey M. Njus
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel A. Phillips
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas M. Proctor
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. William D. Rooney
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Richard E. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard E. Jones.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Robinson, K.M., Njus, J.M., Phillips, D.A. et al. MR Imaging of Inflammation during Myelin-Specific T Cell-Mediated Autoimmune Attack in the EAE Mouse Spinal Cord. Mol Imaging Biol 12, 240–249 (2010). https://doi.org/10.1007/s11307-009-0272-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-009-0272-6

Key words

Search

Navigation