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01-10-2013 | Research Article

Synchrotron Radiation X-Ray Phase Micro-computed Tomography as a New Method to Detect Iron Oxide Nanoparticles in the Brain

Authors: M. Marinescu, M. Langer, A. Durand, C. Olivier, A. Chabrol, H. Rositi, F. Chauveau, T. H. Cho, N. Nighoghossian, Y. Berthezène, F. Peyrin, M. Wiart

Published in: Molecular Imaging and Biology | Issue 5/2013

Abstract

Purpose

The purpose of this study was to introduce synchrotron radiation X-ray phase computed tomography (SR-PCT) as a new method of visualizing ultrasmall superparamagnetic particles of iron oxide (USPIO) distribution into the brains of mice with neuroinflammation.

Procedures

The sensitivity of the technique was assessed by performing back-to-back SR-PCT and magnetic resonance imaging (MRI) in mice stereotaxically injected with a range of USPIO concentrations. Eight mice with cerebral ischemia were then intravenously injected with USPIOs and imaged back-to-back with MRI and SR-PCT.

Results

SR-PCT proved sensitive enough to detect iron in nanomolar quantities. In stroke-induced animals, SR-PCT showed hyperintense areas in the regions of MR signal loss and immunostaining for macrophages. SR-PCT, moreover, identified brain anatomy as clearly as histology, without the need for sectioning or staining, with an examination time of 44 min per brain at an isotropic spatial resolution of 8 μm.

Conclusion

SR-PCT has potential for cellular imaging in intact brain, with unequaled neuroanatomy.

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Pendlebury ST, Rothwell PM (2009) Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis. Lancet Neurol 8(11):1006–1018PubMedCrossRef

Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB, Flegal K et al (2009) Heart disease and stroke statistics—2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 119(3):e21–e181PubMedCrossRef

Iadecola C, Anrather J (2011) The immunology of stroke: from mechanisms to translation. Nat Med 17(7):796–808PubMedCrossRef

Stoll G, Bendszus M (2009) Imaging of inflammation in the peripheral and central nervous system by magnetic resonance imaging. Neuroscience 158(3):1151–1160PubMedCrossRef

Chauveau F, Marinescu M, Cho TH, Wiart M, Berthezene Y, Nighoghossian N (2012) MRI assessment of post-ischemic neuroinflammation in stroke: Experimental and clinical studies. Neuroimaging—methods, Bright P (ed) InTech, doi:10.5772/25150, http://www.intechopen.com/books/neuroimaging-methods/mri-assessment-of-post-ischemic-neuroinflammation-in-stroke-experimental-and-clinical-studies

Cloetens P, Pateyron-Salomé M, Buffière J, Peix G, Baruchel J, Peyrin F et al (1997) Observation of microstructure and damage in materials by phase sensitive radiography and tomography. J Appl Phys 81:5878–5886CrossRef

Giuliani A, Frati C, Rossini A, Komlev VS, Lagrasta C, Savi M et al (2011) High-resolution X-ray microtomography for three-dimensional imaging of cardiac progenitor cell homing in infarcted rat hearts. J Tissue Eng Regen Med 5(8):e168–e178PubMedCrossRef

Torrente Y, Gavina M, Belicchi M, Fiori F, Komlev V, Bresolin N et al (2006) High-resolution X-ray microtomography for three-dimensional visualization of human stem cell muscle homing. FEBS Lett 580(24):5759–5764PubMedCrossRef

Sigovan M, Bessaad A, Alsaid H, Lancelot E, Corot C, Neyran B et al (2010) Assessment of age modulated vascular inflammation in ApoE^−/− mice by USPIO-enhanced magnetic resonance imaging. Investig Radiol 45(11):702–707CrossRef

10.

Marinescu M, Chauveau F, Durand A, Riou A, Cho TH, Dencausse A et al (2012) Monitoring therapeutic effects in experimental stroke by serial USPIO-enhanced MRI. Eur Radiol 23(1):37–47PubMedCrossRef

11.

Sigovan M, Boussel L, Sulaiman A, Sappey-Marinier D, Alsaid H, Desbleds-Mansard C et al (2009) Rapid-clearance iron nanoparticles for inflammation imaging of atherosclerotic plaque: initial experience in animal model. Radiology 252(2):401–409PubMedCrossRef

12.

Desestret V, Brisset JC, Moucharrafie S, Devillard E, Nataf S, Honnorat J et al (2009) Early-stage investigations of ultrasmall superparamagnetic iron oxide-induced signal change after permanent middle cerebral artery occlusion in mice. Stroke 40(5):1834–1841PubMedCrossRef

13.

Chauveau F, Moucharrafie S, Wiart M, Brisset JC, Berthezene Y, Nighoghossian N et al (2010) In vivo MRI assessment of permanent middle cerebral artery occlusion by electrocoagulation: pitfalls of procedure. Exp Transl Stroke Med 2(1):4–8PubMedCrossRef

14.

Wiart M, Davoust N, Pialat JB, Desestret V, Moucharaffie S, Cho TH et al (2007) MRI monitoring of neuroinflammation in mouse focal ischemia. Stroke 38(1):131–137PubMedCrossRef

15.

Denes A, Vidyasagar R, Feng J, Narvainen J, McColl BW, Kauppinen RA et al (2007) Proliferating resident microglia after focal cerebral ischaemia in mice. J Cereb Blood Flow Metab 27(12):1941–1953PubMedCrossRef

16.

Paganin D, Mayo SC, Gureyev TE, Miller PR, Wilkins SW (2002) Simultaneous phase and amplitude extraction from a single defocused image of a homogeneous object. J Microsc 206(Pt 1):33–40PubMedCrossRef

17.

Dejus RJ, Sanchez del Rio M (1996) Xop: a graphical user interface for spectral calculations and X-ray optics utilities. Rev Sci Instrum 67:3356CrossRef

18.

Salome M, Peyrin F, Cloetens P, Odet C, Laval-Jeantet AM, Baruchel J et al (1999) A synchrotron radiation microtomography system for the analysis of trabecular bone samples. Med Phys 26(10):2194–2204PubMedCrossRef

19.

Franklin K, Paxinos G (1997) The mouse brain in stereotaxic coordinates. Academic, San Diego

20.

Henning EC, Ruetzler CA, Gaudinski MR, Hu TC, Latour LL, Hallenbeck JM et al (2009) Feridex preloading permits tracking of CNS-resident macrophages after transient middle cerebral artery occlusion. J Cereb Blood Flow Metab 29(7):1229–1239PubMedCrossRef

21.

Kleinschnitz C, Schutz A, Nolte I, Horn T, Frank M, Solymosi L et al (2005) In vivo detection of developing vessel occlusion in photothrombotic ischemic brain lesions in the rat by iron particle enhanced MRI. J Cereb Blood Flow Metab 25(11):1548–1555PubMedCrossRef

22.

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(4):163–169PubMedCrossRef

23.

Byun J, Verardo MR, Sumengen B, Lewis GP, Manjunath BS, Fisher SK (2006) Automated tool for the detection of cell nuclei in digital microscopic images: application to retinal images. Mol Vis 12:949–960PubMed

24.

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(4):278–283PubMedCrossRef

25.

Stroh A, Zimmer C, Werner N, Gertz K, Weir K, Kronenberg G et al (2006) Tracking of systemically administered mononuclear cells in the ischemic brain by high-field magnetic resonance imaging. NeuroImage 33(3):886–897PubMedCrossRef

26.

Jensen TH, Bech M, Bunk O, Menzel A, Bouchet A, Le Duc G et al (2011) Molecular X-ray computed tomography of myelin in a rat brain. NeuroImage 57(1):124–129PubMedCrossRef

27.

Schulz G, Weitkamp T, Zanette I, Pfeiffer F, Beckmann F, David C et al (2010) High-resolution tomographic imaging of a human cerebellum: comparison of absorption and grating-based phase contrast. J R Soc Interface 7(53):1665–1676PubMedCrossRef

28.

Stampanoni M, Reichold J, Weber B, Habertür D, Schittny J, Eller J et al (2010) Deciphering complex, functional structures with synchrotron-based absorption and phase contrast tomographic microscopy. Proc SPIE 7804:L1–L13

29.

Zhu P, Zhang K, Wang Z, Liu Y, Liu X, Wu Z et al (2010) Low-dose, simple, and fast grating-based X-ray phase-contrast imaging. Proc Natl Acad Sci U S A 107(31):13576–13581PubMedCrossRef

30.

Connor DM, Benveniste H, Dilmanian FA, Kritzer MF, Miller LM, Zhong Z (2009) Computed tomography of amyloid plaques in a mouse model of Alzheimer’s disease using diffraction enhanced imaging. NeuroImage 46(4):908–914PubMedCrossRef

31.

Noda-Saita K, Yoneyama A, Shitaka Y, Hirai Y, Terai K, Wu J et al (2006) Quantitative analysis of amyloid plaques in a mouse model of Alzheimer’s disease by phase-contrast X-ray computed tomography. Neuroscience 138(4):1205–1213PubMedCrossRef

32.

Pinzer BR, Cacquevel M, Modregger P, McDonald SA, Bensadoun JC, Thuering T et al (2012) Imaging brain amyloid deposition using grating-based differential phase contrast tomography. NeuroImage 61(4):1336–1346PubMedCrossRef

Title: Synchrotron Radiation X-Ray Phase Micro-computed Tomography as a New Method to Detect Iron Oxide Nanoparticles in the Brain
Authors: M. Marinescu
M. Langer
A. Durand
C. Olivier
A. Chabrol
H. Rositi
F. Chauveau
T. H. Cho
N. Nighoghossian
Y. Berthezène
F. Peyrin
M. Wiart
Publication date: 01-10-2013
Publisher: Springer US
Published in: Molecular Imaging and Biology / Issue 5/2013
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-013-0639-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Synchrotron Radiation X-Ray Phase Micro-computed Tomography as a New Method to Detect Iron Oxide Nanoparticles in the Brain

Abstract

Purpose

Procedures

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusion

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