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In vivo assessment of experimental neonatal excitotoxic brain lesion with USPIO-enhanced MR imaging

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Abstract

Purpose:

To assess the feasibility of magnetic resonance imaging (MRI) enhanced with ultrasmall superparamagnetic particles of iron oxide (USPIO) for assessing excitotoxic brain lesions in an experimental model of neonatal periventricular white matter (PWM) lesions.

Materials and methods:

Brain lesions were induced by intracerebral injection of ibotenate in 14 newborn rats. Pre- and post-USPIO T2-weighted MRI was performed in seven of them (group A) and in five control newborns (group C). In seven newborns with induced cerebral lesions, USPIO-enhanced MRI was not performed (group B). We compared the signal intensity of the lesion to the contralateral unaffected brain (lesion-to-brain contrast, LBC) and the lesion signal-to-noise ratio (SNR) before and after USPIO injection. MR imaging was correlated with histology.

Results:

USPIO injection significantly (P < 0.05) decreased LBC and SNR of brain lesion but induced no changes in normal controls. The densities of macrophages and iron-laden cells were higher on the lesion side than on the contralateral side (P < 0.05). Neither lesion size nor the surrounding macrophage infiltrate was significantly different between groups A and B.

Conclusion:

Post-USPIO T2-weighted MRI demonstrated negative enhancement of neonatal excitotoxic brain lesion. USPIO injection does not appear to exacerbate brain lesions.

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References

  1. Deng W, Pleasure J, Pleasure D (2008) Progress in periventricular leukomalacia. Arch Neurol 65:1291–1295

    Article  PubMed  Google Scholar 

  2. Tahraoui SL, Marret S, Bodenant C, Leroux P, Dommergues MA, Evrard P, Gressens P (2001) Central role of microglia in neonatal excitotoxic lesions of the murine periventricular white matter. Brain Pathol 11:56–71

    Article  CAS  PubMed  Google Scholar 

  3. Rezaie P, Dean A (2002) Periventricular leukomalacia, inflammation and white matter lesions within the developing nervous system. Neuropathology 22:106–132

    Article  PubMed  Google Scholar 

  4. Inder TE, Anderson NJ, Spencer C, Wells S, Volpe JJ (2003) White matter injury in the premature infant: a comparison between serial cranial sonographic and MR findings at term. AJNR Am J Neuroradiol 24:805–809

    PubMed  Google Scholar 

  5. Corot C, Robert P, Idee JM, Port M (2006) Recent advances in iron oxide nanocrystal technology for medical imaging. Adv Drug Deliv Rev 58:1471–1504

    Article  CAS  PubMed  Google Scholar 

  6. 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

    Article  PubMed  Google Scholar 

  7. 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  CAS  PubMed  Google Scholar 

  8. Saleh A, Wiedermann D, Schroeter M, Jonkmanns C, Jander S, Hoehn M (2004) Central nervous system inflammatory response after cerebral infarction as detected by magnetic resonance imaging. NMR Biomed 17:163–169

    Article  PubMed  Google Scholar 

  9. Wiart M, Davoust N, Pialat JB, Desestret V, Moucharaffie S, Cho TH, Mutin M, Langlois JB, Beuf O, Honnorat J, Nighoghossian N, Berthezene Y (2007) MRI monitoring of neuroinflammation in mouse focal ischemia. Stroke 38:131–137

    Article  PubMed  Google Scholar 

  10. Denes A, Vidyasagar R, Feng J, Narvainen J, McColl BW, Kauppinen RA, Allan SM (2007) Proliferating resident microglia after focal cerebral ischaemia in mice. J Cereb Blood Flow Metab 27:1941–1953

    Article  CAS  PubMed  Google Scholar 

  11. Dousset V, Gomez C, Petry KG, Delalande C, Caille JM, Ballarino L, Coussemacq M, Canioni P, Quesson B, Seilhan D, Thiaudiere E, Brochet B (1999) Dose and scanning delay using USPIO for central nervous system macrophage imaging. Magma 8:185–189

    Article  CAS  PubMed  Google Scholar 

  12. 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

    CAS  PubMed  Google Scholar 

  13. 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

    Article  CAS  PubMed  Google Scholar 

  14. Floris S, Blezer EL, Schreibelt G, Dopp E, van der Pol SM, Schadee-Eestermans IL, Nicolay K, Dijkstra CD, de Vries HE (2004) Blood-brain barrier permeability and monocyte infiltration in experimental allergic encephalomyelitis: a quantitative MRI study. Brain 127:616–627

    Article  CAS  PubMed  Google Scholar 

  15. 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 50:309–314

    Article  CAS  PubMed  Google Scholar 

  16. Baeten K, Hendriks JJ, Hellings N, Theunissen E, Vanderlocht J, Ryck LD, Gelan J, Stinissen P, Adriaensens P (2008) Visualisation of the kinetics of macrophage infiltration during experimental autoimmune encephalomyelitis by magnetic resonance imaging. J Neuroimmunol 195:1–6

    Article  CAS  PubMed  Google Scholar 

  17. Saleh A, Schroeter M, Jonkmanns C, Hartung HP, Modder U, Jander S (2004) In vivo MRI of brain inflammation in human ischaemic stroke. Brain 127:1670–1677

    Article  PubMed  Google Scholar 

  18. Nighoghossian N, Wiart M, Cakmak S, Berthezene Y, Derex L, Cho TH, Nemoz C, Chapuis F, Tisserand GL, Pialat JB, Trouillas P, Froment JC, Hermier M (2007) Inflammatory response after ischemic stroke: a USPIO-enhanced MRI study in patients. Stroke 38:303–307

    Article  PubMed  Google Scholar 

  19. Cho TH, Nighoghossian N, Wiart M, Desestret V, Cakmak S, Berthezene Y, Derex L, Louis-Tisserand G, Honnorat J, Froment JC, Hermier M (2007) USPIO-enhanced MRI of neuroinflammation at the sub-acute stage of ischemic stroke: preliminary data. Cerebrovasc Dis 24:544–546

    Article  PubMed  Google Scholar 

  20. Saleh A, Schroeter M, Ringelstein A, Hartung HP, Siebler M, Modder U, Jander S (2007) Iron oxide particle-enhanced MRI suggests variability of brain inflammation at early stages after ischemic stroke. Stroke 38:2733–2737

    Article  PubMed  Google Scholar 

  21. Dousset V, Brochet B, Deloire MS, Lagoarde L, Barroso B, Caille JM, Petry KG (2006) MR imaging of relapsing multiple sclerosis patients using ultra-small-particle iron oxide and compared with gadolinium. AJNR Am J Neuroradiol 27:1000–1005

    CAS  PubMed  Google Scholar 

  22. Marret S, Mukendi R, Gadisseux JF, Gressens P, Evrard P (1995) Effect of ibotenate on brain development: an excitotoxic mouse model of microgyria and posthypoxic-like lesions. J Neuropathol Exp Neurol 54:358–370

    Article  CAS  PubMed  Google Scholar 

  23. Dommergues MA, Gallego J, Evrard P, Gressens P (1998) Iron supplementation aggravates periventricular cystic white matter lesions in newborn mice. Eur J Paediatr Neurol 2:313–318

    Article  CAS  PubMed  Google Scholar 

  24. Harisinghani MG, Dixon WT, Saksena MA, Brachtel E, Blezek DJ, Dhawale PJ, Torabi M, Hahn PF (2004) MR lymphangiography: imaging strategies to optimize the imaging of lymph nodes with ferumoxtran-10. Radiographics 24:867–878

    Article  PubMed  Google Scholar 

  25. Azoulay R, Olivier P, Baud O, Verney C, Santus R, Robert P, Gressens P, Sebag G (2008) USPIO (Ferumoxtran-10)-enhanced MRI to visualize reticuloendothelial system cells in neonatal rats: feasibility and biodistribution study. J Magn Reson Imaging 28:1046–1052

    Article  PubMed  Google Scholar 

  26. Paxinos G, Watson C (2005) The rat brain in sterotaxic coordinates, 5th ed. Academic Press, New York

  27. Wolff SD, Balaban RS (1997) Assessing contrast on MR images. Radiology 202:25–29

    CAS  PubMed  Google Scholar 

  28. Chalard F, Daire JL, Plaisant P, Gressens P, Sebag G (2005) Application of in vivo magnetic resonance to newborn mouse model of excitotoxic periventricular leukomalacia. Pediatr Radiol 35(Suppl 2):101

    Google Scholar 

  29. Berger C, Hiestand P, Kindler-Baumann D, Rudin M, Rausch M (2006) Analysis of lesion development during acute inflammation and remission in a rat model of experimental autoimmune encephalomyelitis by visualization of macrophage infiltration, demyelination and blood-brain barrier damage. NMR Biomed 19:101–107

    Article  PubMed  Google Scholar 

  30. Vellinga MM, Oude Engberink RD, Seewann A, Pouwels PJ, Wattjes MP, van der Pol SM, Pering C, Polman CH, de Vries HE, Geurts JJ, Barkhof F (2008) Pluriformity of inflammation in multiple sclerosis shown by ultra-small iron oxide particle enhancement. Brain 131:800–807

    Article  PubMed  Google Scholar 

  31. Manninger SP, Muldoon LL, Nesbit G, Murillo T, Jacobs PM, Neuwelt EA (2005) An exploratory study of ferumoxtran-10 nanoparticles as a blood-brain barrier imaging agent targeting phagocytic cells in CNS inflammatory lesions. AJNR Am J Neuroradiol 26:2290–2300

    PubMed  Google Scholar 

  32. Bierry G, Jehl F, Boehm N, Robert P, Prevost G, Dietemann JL, Desal H, Kremer S (2008) Macrophage activity in infected areas of an experimental vertebral osteomyelitis model: USPIO-enhanced MR imaging–feasibility study. Radiology 248:114–123

    Article  PubMed  Google Scholar 

  33. Hilfiker PR, Debatin JF, Tarlo K, Schmitz HC, Kurrer MO (1999) Assessment of peritoneal tolerance of a new MR blood pool contrast agent in rabbits. Invest Radiol 34:722–727

    Article  CAS  PubMed  Google Scholar 

  34. Reddy DK, Moore HL, Lee JH, Saran R, Nolph KD, Khanna R, Twardowski ZJ (2001) Chronic peritoneal dialysis in iron-deficient rats with solutions containing iron dextran. Kidney Int 59:764–773

    Article  CAS  PubMed  Google Scholar 

  35. Raynal I, Prigent P, Peyramaure S, Najid A, Rebuzzi C, Corot C (2004) Macrophage endocytosis of superparamagnetic iron oxide nanoparticles:mechanisms and comparison of ferumoxides and ferumoxtran-10. Invest Radiol 39(1):56–63

    Article  CAS  PubMed  Google Scholar 

  36. McLachlan SJ, Morris MR, Lucas MA, Fisco RA, Eakins MN, Fowler DR, Scheetz RB, Olukotun AY (1994) Phase I clinical evaluation of a new iron oxide MR contrast agent. J Magn Reson Imaging 4:301–307

    Article  CAS  PubMed  Google Scholar 

  37. Sharma R, Saini S, Ros PR, Hahn PF, Small WC, de Lange EE, Stillman AE, Edelman RR, Runge VM, Outwater EK, Morris M, Lucas M (1999) Safety profile of ultrasmall superparamagnetic iron oxide ferumoxtran-10: phase II clinical trial data. J Magn Reson Imaging 9:291–294

    Article  CAS  PubMed  Google Scholar 

  38. Sigal R, Vogl T, Casselman J, Moulin G, Veillon F, Hermans R, Dubrulle F, Viala J, Bosq J, Mack M, Depondt M, Mattelaer C, Petit P, Champsaur P, Riehm S, Dadashitazehozi Y, de Jaegere T, Marchal G, Chevalier D, Lemaitre L, Kubiak C, Helmberger R, Halimi P (2002) Lymph node metastases from head and neck squamous cell carcinoma: MR imaging with ultrasmall superparamagnetic iron oxide particles (Sinerem MR)—results of a phase-III multicenter clinical trial. Eur Radiol 12:1104–1113

    Article  CAS  PubMed  Google Scholar 

  39. Will O, Purkayastha S, Chan C, Athanasiou T, Darzi AW, Gedroyc W, Tekkis PP (2006) Diagnostic precision of nanoparticle-enhanced MRI for lymph-node metastases: a meta-analysis. Lancet Oncol 7:52–60

    Article  PubMed  Google Scholar 

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Acknowledgments

We are grateful to Mrs. Leslie Schendimann for technical support.

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Correspondence to Marianne Alison.

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Alison, M., Azoulay, R., Chalard, F. et al. In vivo assessment of experimental neonatal excitotoxic brain lesion with USPIO-enhanced MR imaging. Eur Radiol 20, 2204–2212 (2010). https://doi.org/10.1007/s00330-010-1793-8

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  • DOI: https://doi.org/10.1007/s00330-010-1793-8

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