Abstract
Magnetic resonance imaging (MRI) is a valuable in vivo imaging method for investigating experimental spinal cord injury (SCI). In this chapter a variety of MRI techniques will be described including anatomical, functional, and cellular MRI. The benefits and challenges of each technique are addressed and examples of the application of these imaging tools are presented for mouse and rat SCI.
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Ma M, Basso DM, Walters P, Stokes BT, Jakeman LB (2001) Behavioral and histological outcomes following graded spinal cord contusion injury in the C57Bl/6 mouse. Exp Neurol 169(2):239–254
Joshi M, Fehlings MG (2002) Development and characterization of a novel, graded model of clip compressive spinal cord injury in the mouse: Part 1. Clip design, behavioral outcomes, and histopathology. J Neurotrauma 19(2):175–190
Siegenthaler MM, Tu MK, Keirstead HS (2007) The extent of myelin pathology differs following contusion and transection spinal cord injury. J Neurotrauma 24(10):1631–1646
Jacob JE, Pniak A, Weaver LC, Brown A (2001) Autonomic dysreflexia in a mouse model of spinal cord injury. Neuroscience 108(4):687–693
Onifer SM, Rabchevsky AG, Scheff SW (2007) Rat models of traumatic spinal cord injury to assess motor recovery. ILAR J 48(4):385–395
Fleming JC, Norenberg MD, Ramsay DA, Dekaban GA, Marcillo AE, Saenz AD et al (2006) The cellular inflammatory response in human spinal cords after injury. Brain 129(Pt 12):3249–3269
Inman DM, Steward O (2003) Physical size does not determine the unique histopathological response seen in the injured mouse spinal cord. J Neurotrauma 20(1):33–42
Guertin PA (2005) Paraplegic mice are leading to new advances in spinal cord injury research. Spinal Cord 43(8):459–461
Johnson GA, Cofer GP, Gewalt SL, Hedlund LW (2002) Morphologic phenotyping with MR microscopy: the visible mouse. Radiology 222(3):789–793
Blight AR (2002) Miracles and molecules–progress in spinal cord repair. Nat Neurosci 5(Suppl):1051–1054
Ohta K, Fujimura Y, Nakamura M, Watanabe M, Yato Y (1999) Experimental study on MRI evaluation of the course of cervical spinal cord injury. Spinal Cord 37(8):580–584
Mihai G, Nout YS, Tovar CA, Miller BA, Schmalbrock P, Bresnahan JC et al (2008) Longitudinal comparison of two severities of unilateral cervical spinal cord injury using magnetic resonance imaging in rats. J Neurotrauma 25(1):1–18
Bilgen M, Rumboldt Z (2008) Neuronal and vascular biomarkers in syringomyelia: investigations using longitudinal MRI. Biomark Med 2(2):113–124
Narayana PA, Grill RJ, Chacko T, Vang R (2004) Endogenous recovery of injured spinal cord: longitudinal in vivo magnetic resonance imaging. J Neurosci Res 78(5):749–759
Weber T, Vroemen M, Behr V, Neuberger T, Jakob P, Haase A et al (2006) In vivo high-resolution MR imaging of neuropathologic changes in the injured rat spinal cord. AJNR Am J Neuroradiol 27(3):598–604
Brown A, Jacob JE (2006) Genetic approaches to autonomic dysreflexia. Prog Brain Res 152:299–313
Sroga JM, Jones TB, Kigerl KA, McGaughy VM, Popovich PG (2003) Rats and mice exhibit distinct inflammatory reactions after spinal cord injury. J Comp Neurol 462(2):223–240
Bilgen M, Al-Hafez B, Alrefae T, He YY, Smirnova IV, Aldur MM et al (2007) Longitudinal magnetic resonance imaging of spinal cord injury in mouse: changes in signal patterns associated with the inflammatory response. Magn Reson Imaging 25(5):657–664
Byrnes KR, Fricke ST, Faden AI (2010) Neuropathological differences between rats and mice after spinal cord injury. J Magn Reson Imaging 32(4):836–846
Gonzalez-Lara LE, Xu X, Hofstetrova K, Pniak A, Brown A, Foster PJ (2009) In vivo magnetic resonance imaging of spinal cord injury in the mouse. J Neurotrauma 26(5):753–762
Brodbelt AR, Stoodley MA (2003) Post-traumatic syringomyelia: a review. J Clin Neurosci 10(4):401–408
Sandner B, Pillai DR, Heidemann RM, Schuierer G, Mueller MF, Bogdahn U et al (2009) In vivo high-resolution imaging of the injured rat spinal cord using a 3.0 T clinical MR scanner. J Magn Reson Imaging 29(3):725–730
Pillai DR, Heidemann RM, Kumar P, Shanbhag N, Lanz T, Dittmar MS et al (2011) Comprehensive small animal imaging strategies on a clinical 3 T dedicated head MR-scanner; adapted methods and sequence protocols in CNS pathologies. PLoS One 6(2):e16091
Henkelman RM, Stanisz GJ, Graham SJ (2001) Magnetization transfer in MRI: a review. NMR Biomed 14(2):57–64
Wolff SD, Balaban RS (1989) Magnetization transfer contrast (MTC) and tissue water proton relaxation in vivo. Magn Reson Med 10(1):135–144
Levesque IR, Giacomini PS, Narayanan S, Ribeiro LT, Sled JG, Arnold DL et al (2010) Quantitative magnetization transfer and myelin water imaging of the evolution of acute multiple sclerosis lesions. Magn Reson Med 63(3):633–640
Harel A, Eliav U, Akselrod S, Navon G (2008) Magnetization transfer based contrast for imaging denatured collagen. J Magn Reson Imaging 27(5):1155–1163
Rausch M, Hiestand P, Baumann D, Cannet C, Rudin M (2003) MRI-based monitoring of inflammation and tissue damage in acute and chronic relapsing EAE. Magn Reson Med 50(2):309–314
Schmierer K, Scaravilli F, Altmann DR, Barker GJ, Miller DH (2004) Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain. Ann Neurol 56(3):407–415
Chen JT, Kuhlmann T, Jansen GH, Collins DL, Atkins HL, Freedman MS et al (2007) Voxel-based analysis of the evolution of magnetization transfer ratio to quantify remyelination and demyelination with histopathological validation in a multiple sclerosis lesion. Neuroimage 36(4):1152–1158
Franconi F, Lemaire L, Marescaux L, Jallet P, Le Jeune JJ (2000) In vivo quantitative microimaging of rat spinal cord at 7 T. Magn Reson Med 44(6):893–898
McGowan JC, Berman JI, Ford JC, Lavi E, Hackney DB (2000) Characterization of experimental spinal cord injury with magnetization transfer ratio histograms. J Magn Reson Imaging 12(2):247–254
Gareau PJ, Weaver LC, Dekaban GA (2001) In vivo magnetization transfer measurements of experimental spinal cord injury in the rat. Magn Reson Med 45(1):159–163
Ogawa S, Menon RS, Kim SG, Ugurbil K (1998) On the characteristics of functional magnetic resonance imaging of the brain. Annu Rev Biophys Biomol Struct 27:447–474
Yoshizawa T, Nose T, Moore GJ, Sillerud LO (1996) Functional magnetic resonance imaging of motor activation in the human cervical spinal cord. Neuroimage 4(3 Pt 1):174–182
Madi S, Flanders AE, Vinitski S, Herbison GJ, Nissanov J (2001) Functional MR imaging of the human cervical spinal cord. AJNR Am J Neuroradiol 22(9):1768–1774
Hyder F, Rothman DL, Shulman RG (2002) Total neuroenergetics support localized brain activity: implications for the interpretation of fMRI. Proc Natl Acad Sci U S A 99(16):10771–10776
Maandag NJ, Coman D, Sanganahalli BG, Herman P, Smith AJ, Blumenfeld H et al (2007) Energetics of neuronal signaling and fMRI activity. Proc Natl Acad Sci U S A 104(51):20546–20551
Lee JG, Smith JJ, Hudetz AG, Hillard CJ, Bosnjak ZJ, Kampine JP (1995) Laser-Doppler measurement of the effects of halothane and isoflurane on the cerebrovascular CO2 response in the rat. Anesth Analg 80(4):696–702
Pawela CP, Biswal BB, Hudetz AG, Schulte ML, Li R, Jones SR et al (2009) A protocol for use of medetomidine anesthesia in rats for extended studies using task-induced BOLD contrast and resting-state functional connectivity. Neuroimage 46(4):1137–1147
Weber R, Ramos-Cabrer P, Wiedermann D, van Camp N, Hoehn M (2006) A fully noninvasive and robust experimental protocol for longitudinal fMRI studies in the rat. Neuroimage 29(4):1303–1310
Hutchison RM, Mirsattari SM, Jones CK, Gati JS, Leung LS (2010) Functional networks in the anesthetized rat brain revealed by independent component analysis of resting-state FMRI. J Neurophysiol 103(6):3398–3406
Stroman PW (2005) Magnetic resonance imaging of neuronal function in the spinal cord: spinal FMRI. Clin Med Res 3(3):146–156
Porszasz R, Beckmann N, Bruttel K, Urban L, Rudin M (1997) Signal changes in the spinal cord of the rat after injection of formalin into the hindpaw: characterization using functional magnetic resonance imaging. Proc Natl Acad Sci U S A 94(10):5034–5039
Malisza KL, Stroman PW (2002) Functional imaging of the rat cervical spinal cord. J Magn Reson Imaging 16(5):553–558
Ramu J, Bockhorst KH, Mogatadakala KV, Narayana PA (2006) Functional magnetic resonance imaging in rodents: Methodology and application to spinal cord injury. J Neurosci Res 84(6):1235–1244
Endo T, Spenger C, Westman E, Tominaga T, Olson L (2008) Reorganization of sensory processing below the level of spinal cord injury as revealed by fMRI. Exp Neurol 209(1):155–160
Ostergaard L (2004) Cerebral perfusion imaging by bolus tracking. Top Magn Reson Imaging 15(1):3–9
Paiva FF, Tannus A, Silva AC (2007) Measurement of cerebral perfusion territories using arterial spin labelling. NMR Biomed 20(7):633–642
Duhamel G, Callot V, Cozzone PJ, Kober F (2008) Spinal cord blood flow measurement by arterial spin labeling. Magn Reson Med 59(4):846–854
Duhamel G, Callot V, Decherchi P, Le Fur Y, Marqueste T, Cozzone PJ et al (2009) Mouse lumbar and cervical spinal cord blood flow measurements by arterial spin labeling: sensitivity optimization and first application. Magn Reson Med 62(2):430–439
Koh DM, Collins DJ (2007) Diffusion-weighted MRI in the body: applications and challenges in oncology. AJR Am J Roentgenol 188(6):1622–1635
Hagmann P, Jonasson L, Maeder P, Thiran JP, Wedeen VJ, Meuli R (2006) Understanding diffusion MR imaging techniques: from scalar diffusion-weighted imaging to diffusion tensor imaging and beyond. Radiographics 26(Suppl 1):S205–S223
Ellingson BM, Schmit BD, Kurpad SN (2010) Lesion growth and degeneration patterns measured using diffusion tensor 9.4-T magnetic resonance imaging in rat spinal cord injury. J Neurosurg Spine 13(2):181–192
Schwartz ED, Duda J, Shumsky JS, Cooper ET, Gee J (2005) Spinal cord diffusion tensor imaging and fiber tracking can identify white matter tract disruption and glial scar orientation following lateral funiculotomy. J Neurotrauma 22(12):1388–1398
Cheung MM, Li DT, Hui ES, Fan S, Ding AY, Hu Y et al (2009) In vivo diffusion tensor imaging of chronic spinal cord compression in rat model. Conf Proc IEEE Eng Med Biol Soc 2009:2715–2718
Kim JH, Loy DN, Liang HF, Trinkaus K, Schmidt RE, Song SK (2007) Noninvasive diffusion tensor imaging of evolving white matter pathology in a mouse model of acute spinal cord injury. Magn Reson Med 58(2):253–260
Sundberg LM, Herrera JJ, Narayana PA (2010) In vivo longitudinal MRI and behavioral studies in experimental spinal cord injury. J Neurotrauma 27(10):1753–1767
Tu TW, Kim JH, Wang J, Song SK (2010) Full tensor diffusion imaging is not required to assess the white-matter integrity in mouse contusion spinal cord injury. J Neurotrauma 27(1):253–262
Modo M, Hoehn M, Bulte JW (2005) Cellular MR imaging. Mol Imaging 4(3):143–164
Wang YX, Hussain SM, Krestin GP (2001) Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol 11(11):2319–2331
Kim D, Hong KS, Song J (2007) The present status of cell tracking methods in animal models using magnetic resonance imaging technology. Mol Cells 23(2):132–137
Heyn C, Ronald JA, Ramadan SS, Snir JA, Barry AM, MacKenzie LT et al (2006) In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain. Magn Reson Med 56(5):1001–1010
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
Dousset V, Ballarino L, Delalande C, Coussemacq M, Canioni P, Petry KG et al (1999) 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
Kim J, Kim DI, Lee SK, Kim DJ, Lee JE, Ahn SK (2008) Imaging of the inflammatory response in reperfusion injury after transient cerebral ischemia in rats: correlation of superparamagnetic iron oxide-enhanced magnetic resonance imaging with histopathology. Acta Radiol 49(5):580–588
Schmitz SA, Coupland SE, Gust R, Winterhalter S, Wagner S, Kresse M et al (2000) Superparamagnetic iron oxide-enhanced MRI of atherosclerotic plaques in Watanabe hereditable hyperlipidemic rabbits. Invest Radiol 35(8):460–471
Klug K, Gert G, Thomas K, Christan Z, Marco P, Elisabeth B et al (2009) Murine atherosclerotic plaque imaging with the USPIO Ferumoxtran-10. Front Biosci 14:2546–2552
Bendszus M, Stoll G (2003) Caught in the act: in vivo mapping of macrophage infiltration in nerve injury by magnetic resonance imaging. J Neurosci 23(34):10892–10896
Beckmann N, Falk R, Zurbrugg S, Dawson J, Engelhardt P (2003) Macrophage infiltration into the rat knee detected by MRI in a model of antigen-induced arthritis. Magn Reson Med 49(6):1047–1055
Beckmann N, Cannet C, Zurbruegg S, Haberthur R, Li J, Pally C et al (2006) Macrophage infiltration detected at MR imaging in rat kidney allografts: early marker of chronic rejection? Radiology 240(3):717–724
Ye Q, Wu YL, Foley LM, Hitchens TK, Eytan DF, Shirwan H et al (2008) Longitudinal tracking of recipient macrophages in a rat chronic cardiac allograft rejection model with noninvasive magnetic resonance imaging using micrometer-sized paramagnetic iron oxide particles. Circulation 118(2):149–156
Ho C, Hitchens TK (2004) A non-invasive approach to detecting organ rejection by MRI: monitoring the accumulation of immune cells at the transplanted organ. Curr Pharm Biotechnol 5(6):551–566
Dunn EA, Weaver LC, Dekaban GA, Foster PJ (2005) Cellular imaging of inflammation after experimental spinal cord injury. Mol Imaging 4(1):53–62
Cromer Berman SM, Walczak P, Bulte JW (2011) Tracking stem cells using magnetic nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol 3(4):343–355
Tang KS, Shapiro EM (2011) Enhanced magnetic cell labeling efficiency using -NH(2) coated MPIOs. Magn Reson Med 65(6):1564–1569
Walczak P, Kedziorek DA, Gilad AA, Lin S, Bulte JW (2005) Instant MR labeling of stem cells using magnetoelectroporation. Magn Reson Med 54(4):769–774
Walczak P, Ruiz-Cabello J, Kedziorek DA, Gilad AA, Lin S, Barnett B et al (2006) Magnetoelectroporation: improved labeling of neural stem cells and leukocytes for cellular magnetic resonance imaging using a single FDA-approved agent. Nanomedicine 2(2):89–94
Tai JH, Foster P, Rosales A, Feng B, Hasilo C, Martinez V et al (2006) Imaging islets labeled with magnetic nanoparticles at 1.5 Tesla. Diabetes 55(11):2931–2938
Smith CA, de la Fuente J, Pelaz B, Furlani EP, Mullin M, Berry CC (2010) The effect of static magnetic fields and tat peptides on cellular and nuclear uptake of magnetic nanoparticles. Biomaterials 31(15):4392–4400
Baeten K, Adriaensens P, Hendriks J, Theunissen E, Gelan J, Hellings N et al (2010) Tracking of myelin-reactive T cells in experimental autoimmune encephalomyelitis (EAE) animals using small particles of iron oxide and MRI. NMR Biomed 23(6):601–609
Heyn C, Ronald JA, Mackenzie LT, MacDonald IC, Chambers AF, Rutt BK et al (2006) In vivo magnetic resonance imaging of single cells in mouse brain with optical validation. Magn Reson Med 55(1):23–29
Jirak D, Kriz J, Strzelecki M, Yang J, Hasilo C, White DJ et al (2009) Monitoring the survival of islet transplants by MRI using a novel technique for their automated detection and quantification. MAGMA 22(4):257–265
Sykova E, Jendelova P (2007) In vivo tracking of stem cells in brain and spinal cord injury. Prog Brain Res 161:367–383
Dunning MD, Lakatos A, Loizou L, Kettunen M, ffrench-Constant C, Brindle KM et al (2004) Superparamagnetic iron oxide-labeled Schwann cells and olfactory ensheathing cells can be traced in vivo by magnetic resonance imaging and retain functional properties after transplantation into the CNS. J Neurosci 24(44):9799–9810
Lee IH, Bulte JW, Schweinhardt P, Douglas T, Trifunovski A, Hofstetter C et al (2004) In vivo magnetic resonance tracking of olfactory ensheathing glia grafted into the rat spinal cord. Exp Neurol 187(2):509–516
Gonzalez-Lara LE, Xu X, Hofstetrova K, Pniak A, Chen Y, McFadden CD et al (2011) The use of cellular magnetic resonance imaging to track the fate of iron-labeled multipotent stromal cells after direct transplantation in a mouse model of spinal cord injury. Mol Imaging Biol 13(4):702–711
Pawelczyk E, Jordan EK, Balakumaran A, Chaudhry A, Gormley N, Smith M et al (2009) In vivo transfer of intracellular labels from locally implanted bone marrow stromal cells to resident tissue macrophages. PLoS One 4(8):e6712
Terrovitis J, Stuber M, Youssef A, Preece S, Leppo M, Kizana E et al (2008) Magnetic resonance imaging overestimates ferumoxide-labeled stem cell survival after transplantation in the heart. Circulation 117(12):1555–1562
Amsalem Y, Mardor Y, Feinberg MS, Landa N, Miller L, Daniels D et al (2007) Iron-oxide labeling and outcome of transplanted mesenchymal stem cells in the infarcted myocardium. Circulation 116(11 Suppl):I38–I145
Coyne TM, Marcus AJ, Woodbury D, Black IB (2006) Marrow stromal cells transplanted to the adult brain are rejected by an inflammatory response and transfer donor labels to host neurons and glia. Stem Cells 24(11):2483–2492
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Gonzalez-Lara, L.E., Jawan, F., Foster, P.J. (2013). Magnetic Resonance Imaging of Experimental Spinal Cord Injury. In: Aldskogius, H. (eds) Animal Models of Spinal Cord Repair. Neuromethods, vol 76. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-197-4_12
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DOI: https://doi.org/10.1007/978-1-62703-197-4_12
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