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Characterization of late radiation effects in the rat thoracolumbar spinal cord by MR imaging using USPIO

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Abstract

The aim of this study was to detect late radiation effects in the rat spinal cord using MR imaging with ultra-small particles of iron oxide (USPIO) contrast agent to better understand the development of late radiation damage with emphasis on the period preceding neurological signs. Additionally, the role of an inflammatory reaction was assessed by measuring macrophages that internalized USPIO. T2-weighted spin echo MR measurements were performed at 7T in six rats before paresis was expected (130–150 days post-irradiation, early group), and in six paretic rats (150–190 days post-irradiation, late group). Measurements were performed before, directly after and, only in the early group, 40 h after USPIO administration and compared with histology. In the early group, MR images showed focal regions in grey matter (GM) and white matter (WM) with signal intensity reduction after USPIO injection. Larger lesions with contrast enhancement were located in and around edematous GM of three animals of the early group and five of the late group. Forty hours after injection, additional lesions in WM, GM and nerve roots appeared in animals with GM edema. In the late paretic group, MR imaging showed WM necrosis adjacent to areas with large contrast enhancement. In conclusion, detection of early focal lesions was improved by contrast administration. In the animals with extended radiation damage, large hypo-intense regions appeared due to USPIO, which might be attributed to blood spinal cord barrier breakdown, but the involvement of blood-derived iron-loaded macrophages could not be excluded.

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References

  1. Schultheiss TE, Higgins EM, El-Mahdi AM (1984) The latent period in clinical radiation myelopathy. Int J Radiat Oncol Biol Phys 10:1109–1115

    PubMed  CAS  Google Scholar 

  2. Powers BE, Beck ER, Gillette EL, Gould DH, LeCouter RA (1992) Pathology of radiation injury to the canine spinal cord. Int J Radiat Oncol Biol Phys 23:539–549

    PubMed  CAS  Google Scholar 

  3. van den Aardweg GJ, Hopewell JW, Whitehouse EM, Calvo W (1994) A new model of radiation-induced myelopathy: a comparison of the response of mature and immature pigs. Int J Radiat Oncol Biol Phys 29:763–770

    Google Scholar 

  4. Schultheiss TE, Stephens LC, Maor MH (1988) Analysis of the histopathology of radiation myelopathy. Int J Radiat Oncol Biol Phys 14:27–32

    PubMed  CAS  Google Scholar 

  5. van der Kogel AJ (1991) Central nervous system radiation injury in small animal models. In: PH Gutin, SA Leibel and GF Sheline (eds.) Radiation injury to the nervous system. Raven, New York, pp. 91–111

  6. Chiang CS, McBride WH (1991) Radiation enhances tumor necrosis factor alpha production by murine brain cells. Brain Res 566:265–269

    PubMed  CAS  Google Scholar 

  7. Kureshi SA, Hofman FM, Schneider JH, Chin LS, Apuzzo ML, Hinton DR (1994) Cytokine expression in radiation-induced delayed cerebral injury. Neurosurgery 35:822–829; discussion 829–830

    PubMed  CAS  Google Scholar 

  8. Rubin P, Whitaker JN, Ceckler TL, Nelson D, Gregory PK, Baggs RB, Constine LS, Herman PK (1988) Myelin basic protein and magnetic resonance imaging for diagnosing radiation myelopathy. Int J Radiat Oncol Biol Phys 15:1371–1381

    PubMed  CAS  Google Scholar 

  9. Koehler PJ, Verbiest H, Jager J, Vecht CJ (1996) Delayed radiation myelopathy: serial MR-imaging and pathology. Clin Neurol Neurosurg 98:197–201

    PubMed  CAS  Google Scholar 

  10. Beschet A, Drouet A (1994) Late post-irradiation cervical spinal cord disease. A case. Rev Med Interne 15:734–739

    Article  PubMed  CAS  Google Scholar 

  11. Melki PS, Halimi P, Wibault P, Masnou P, Doyon D (1994) MRI in chronic progressive radiation myelopathy. J Comput Assist Tomogr 18:1–6

    PubMed  CAS  Google Scholar 

  12. Komachi H, Tsuchiya K, Ikeda M, Koike R, Matsunaga T, Ikeda K (1995) Radiation myelopathy: a clinicopathological study with special reference to correlation between MRI findings and neuropathology. J Neurol Sci 132:228–232

    PubMed  CAS  Google Scholar 

  13. Wang PY, Shen WC, Jan JS (1995) Serial MRI changes in radiation myelopathy. Neuroradiology 37:374–377

    PubMed  CAS  Google Scholar 

  14. Wang PY, Shen WC, Jan JS (1992) MR imaging in radiation myelopathy. AJNR Am J Neuroradiol 13:1049–1055; discussion 1056–1048

    PubMed  CAS  Google Scholar 

  15. Alfonso ER, De Gregorio MA, Mateo P, Esco R, Bascon N, Morales F, Bellosta R, Lopez P, Gimeno M, Roca M, Villavieja JL (1997) Radiation myelopathy in over-irradiated patients: MR imaging findings. Eur Radiol 7:400–404

    PubMed  CAS  Google Scholar 

  16. Zweig G, Russell EJ (1990) Radiation myelopathy of the cervical spinal cord: MR findings. AJNR Am J Neuroradiol 11:1188–1190

    PubMed  CAS  Google Scholar 

  17. Kennedy AS, Archambeau JO, Archambeau MH, Holshouser B, Thompson J, Moyers M, Hinshaw D Jr., Slater JM (1995) Magnetic resonance imaging as a monitor of changes in the irradiated rat brain. An aid in determining the time course of events in a histologic study. Invest Radiol 30:214–220

    PubMed  CAS  Google Scholar 

  18. Karger CP, Munter MW, Heiland S, Peschke P, Debus J, Hartmann GH (2002) Dose-response curves and tolerance doses for late functional changes in the normal rat brain after stereotactic radiosurgery evaluated by magnetic resonance imaging: influence of end points and follow-up time. Radiat Res 157:617–625

    PubMed  CAS  Google Scholar 

  19. Miot E, Hoffschir D, Pontvert D, Gaboriaud G, Alapetite C, Masse R, Fetissof F, Le Pape A, Akoka S (1995) Quantitative magnetic resonance and isotopic imaging: early evaluation of radiation injury to the brain. Int J Radiat Oncol Biol Phys 32:121–128

    PubMed  CAS  Google Scholar 

  20. Benczik J, Tenhunen M, Snellman M, Joensuu H, Farkkila M, Joensuu R, Abo Ramadan U, Kallio M, deGritz B, Morris GM, Hopewell JW (2002) Late radiation effects in the dog brain: correlation of MRI and histological changes. Radiother Oncol 63:107–120

    PubMed  Google Scholar 

  21. Gareau PJ, Rutt BK, Bowen CV, Karlik SJ, Mitchell JR (1999) In vivo measurements of multi-component T2 relaxation behaviour in guinea pig brain. Magn Reson Imaging 17:1319–1325

    PubMed  CAS  Google Scholar 

  22. Weissleder R, Cheng HC, Bogdanova A, Bogdanov A Jr. (1997) Magnetically labeled cells can be detected by MR imaging. J Magn Reson Imaging 7:258–263

    CAS  PubMed  Google Scholar 

  23. Dousset V, Ballarino L, Delalande C, Coussemacq M, Canioni P, Petry KG, Caille JM (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 20:223–227

    PubMed  CAS  Google Scholar 

  24. Rausch M, Sauter A, Frohlich J, Neubacher U, Radu EW, Rudin M (2001) Dynamic patterns of USPIO enhancement can be observed in macrophages after ischemic brain damage. Magn Reson Med 46:1018–1022.

    PubMed  CAS  Google Scholar 

  25. Le Duc G, Peoc’h M, Remy C, Charpy O, Muller RN, Le Bas JF, Decorps M (1999) Use of T(2)-weighted susceptibility contrast MRI for mapping the blood volume in the glioma-bearing rat brain. Magn Reson Med 42:754–761

    Google Scholar 

  26. Bulte JW, De Jonge MW, Kamman RL, Go KG, Zuiderveen F, Blaauw B, Oosterbaan JA, The TH, de Leij L (1992) Dextran-magnetite particles: contrast-enhanced MRI of blood-brain barrier disruption in a rat model. Magn Reson Med 23:215–223

    PubMed  CAS  Google Scholar 

  27. Hopewell JW, Morris AD, Dixon-Brown A (1987) The influence of field size on the late tolerance of the rat spinal cord to single doses of X rays. Br J Radiol 60:1099–1108

    Article  PubMed  CAS  Google Scholar 

  28. Stewart PA, Vinters HV, Wong CS (1995) Blood-spinal cord barrier function and morphometry after single doses of x-rays in rat spinal cord. Int J Radiat Oncol Biol Phys 32:703–711

    PubMed  CAS  Google Scholar 

  29. Pop LA, van der Plas M, Skwarchuk MW, Hanssen AE, van der Kogel AJ (1997) High dose rate (HDR) and low dose rate (LDR) interstitial irradiation (IRT) of the rat spinal cord. Radiother Oncol 42:59–67

    PubMed  CAS  Google Scholar 

  30. Tropres I, Grimault S, Vaeth A, Grillon E, Julien C, Payen JF, Lamalle L, Decorps M (2001) Vessel size imaging. Magn Reson Med 45:397–408

    PubMed  CAS  Google Scholar 

  31. Dousset V, Delalande C, Ballarino L, Quesson B, Seilhan D, Coussemacq M, Thiaudiere E, Brochet B, Canioni P, Caille JM (1999) In vivo macrophage activity imaging in the central nervous system detected by magnetic resonance. Magn Reson Med 41:329–333

    PubMed  CAS  Google Scholar 

  32. Narayana P, Fenyes D, Zacharopoulos N (1999) In vivo relaxation times of gray matter and white matter in spinal cord. Magn Reson Imaging 17:623–626

    Article  CAS  PubMed  Google Scholar 

  33. Dunn JF, Roche MA, Springett R, Abajian M, Merlis J, Daghlian CP, Lu SY, Makki M (2004) Monitoring angiogenesis in brain using steady-state quantification of DeltaR2 with MION infusion. Magn Reson Med 51:55–61

    PubMed  Google Scholar 

  34. Dousset V, Gomez C, Petry KG, Delalande C, Caille JM (1999) Dose and scanning delay using USPIO for central nervous system macrophage imaging. MAGMA 8:185–189

    Article  CAS  PubMed  Google Scholar 

  35. Godwin-Austen RB, Howell DA, Worthington B (1975) Observations on radiation myelopathy. Brain 98:557–568

    PubMed  CAS  Google Scholar 

  36. Rausch M, Baumann D, Neubacher U, Rudin M (2002) In-vivo visualization of phagocytotic cells in rat brains after transient ischemia by USPIO . NMR Biomed 15:278–283

    Article  PubMed  CAS  Google Scholar 

  37. Schroeter M, Saleh A, Wiedermann D, Hoehn M, Jander S (2004) Histochemical detection of ultrasmall superparamagnetic iron oxide (USPIO) contrast medium uptake in experimental brain ischemia. Magn Reson Med 52:403–406

    PubMed  Google Scholar 

  38. Schultheiss TE, Kun LE, Ang KK, Stephens LC (1995) Radiation response of the central nervous system [see comments] [published erratum appears in Int J Radiat Oncol Biol Phys 1995 Jul 15;32(4):1269]. Int J Radiat Oncol Biol Phys 31:1093–1112

    PubMed  CAS  Google Scholar 

  39. Siegal T, Pfeffer MR (1995) Radiation-induced changes in the profile of spinal cord serotonin, prostaglandin synthesis, and vascular permeability. Int J Radiat Oncol Biol Phys 31:57–64

    PubMed  CAS  Google Scholar 

  40. Li YQ, Ballinger JR, Nordal RA, Su ZF, Wong CS (2001) Hypoxia in radiation-induced blood-spinal cord barrier breakdown. Cancer Res 61:3348–3354

    PubMed  CAS  Google Scholar 

  41. Nordal RA, Nagy A, Pintilie M, Wong CS (2004) Hypoxia and hypoxia-inducible factor-1 target genes in central nervous system radiation injury: a role for vascular endothelial growth factor. Clin Cancer Res 10:3342–3353

    PubMed  CAS  Google Scholar 

  42. Ahrens ET, Feili-Hariri M, Xu H, Genove G, Morel PA (2003) Receptor-mediated endocytosis of iron-oxide particles provides efficient labeling of dendritic cells for in vivo MR imaging. Magn Reson Med 49:1006–1013

    PubMed  CAS  Google Scholar 

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Acknowledgments.

We thank Dr. Pieter Wesseling for his expert help on histology, Andor Veltien for the technical support, the Central Animal Laboratory for excellent animal care and Laboratoires Guerbet (Aulnay-Sous-Bois, France) for providing the contrast agent. This study was supported by a grant from the Dutch Cancer Society (KUN 99-2080).

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Authors and Affiliations

  1. Department of Radiation Oncology, University Medical Center Nijmegen, 341 P.O. box 9101, 6500HB, Nijmegen, The Netherlands

    M. E. P. Philippens, W. J. M. Peeters & A. J. van der Kogel

  2. Department of Radiology, University Medical Center Nijmegen, Nijmegen, The Netherlands

    G. Gambarota, J. A. Pikkemaat & A. Heerschap

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  1. M. E. P. Philippens
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  2. G. Gambarota
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  3. J. A. Pikkemaat
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  4. W. J. M. Peeters
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  5. A. J. van der Kogel
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  6. A. Heerschap
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Correspondence to M. E. P. Philippens.

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Philippens, M., Gambarota, G., Pikkemaat, J. et al. Characterization of late radiation effects in the rat thoracolumbar spinal cord by MR imaging using USPIO. MAGMA 17, 303–312 (2004). https://doi.org/10.1007/s10334-004-0085-1

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  • DOI: https://doi.org/10.1007/s10334-004-0085-1

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