Macrophagic enhancement in optical coherence tomography imaging by means of superparamagnetic iron oxide nanoparticles
Abstract
Background: The ability of optical coherence tomography (OCT) to visualise macrophages in vivo in coronary arteries is still controversial. We hypothesise that imaging of macrophages in OCT could be enhanced by means of superparamagnetic nanoparticles.
Methods: We compared the optical backscattering and attenuation of cell pellets containing RAW 264.7 macrophages with those of macrophagic cell pellets labelled with very small superparamagnetic oxydised nanoparticles (VSOP) by means of light intensity analysis in OCT. The labelled macrophages were incubated with VSOP at a concentration of 1 mM Fe, corresponding to intracellular iron concentrations of 8.8 pg/cell. To study the effect of intracellular accumulation on the backscattering, VSOP dilutions without cells were also compared. OCT pullbacks of the PCR tubes containing the cell pellets were obtained and light intensity analysis was performed on raw OCT images in polar view, after normalisation by the backscattering of the PCR tube. The backscattering was estimated by the peak normalised intensity, whilst the attenuation was estimated by the number of pixels between the peak and the normalised intensity 1 (peak-to-one).
Results: VSOP-loaded macrophages have higher backscattering than the corresponding unlabelled macrophages (peak normalised intensity 6.30 vs. 3.15) with also slightly higher attenuation (peak-toone 61 vs. 66 pixels). The backscattering of the nanoparticles in suspension was negligible in the light intensity analysis.
Conclusions: VSOP increase significantly the optical backscattering of macrophages in the nearinfrared region, with minimal increase in signal attenuation. This finding enables the enhancement of macrophages in conventional OCT imaging with an easily implementable methodology
Keywords: plaqueatheroscleroticcoronary artery disease/physiopathologyinflammationmacrophagesferrosoferricoxide/diagnostic usevery small iron oxide particlestomographyoptical coherence
References
- Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet. 1997; 349(9061): 1269–1276.
- Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet. 1997; 349(9064): 1498–1504.
- Mathers CD, Boerma T, Ma Fat D. Global and regional causes of death. Br Med Bull. 2009; 92: 7–32.
- Falk E, Shah PK, Fuster V. Coronary Plaque Disruption. Circulation. 1995; 92(3): 657–671.
- Burke AP, Farb A, Malcom GT, et al. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med. 1997; 336(18): 1276–1282.
- Lendon CL, Davies MJ, Born GV, et al. Atherosclerotic plaque caps are locally weakened when macrophages density is increased. Atherosclerosis. 1991; 87(1): 87–90.
- Moreno PR, Falk E, Palacios IF, et al. Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture. Circulation. 1994; 90(2): 775–778.
- Libby P, Geng YJ, Aikawa M, et al. Macrophages and atherosclerotic plaque stability. Curr Opin Lipidol. 1996; 7(5): 330–335.
- Dirksen MT, van der Wal AC, van den Berg FM, et al. Distribution of inflammatory cells in atherosclerotic plaques relates to the direction of flow. Circulation. 1998; 98(19): 2000–2003.
- Moreno PR, Bernardi VH, Lopez-Cuellar J, et al. Macrophages, smooth muscle cells, and tissue factor in unstable angina: implications for cell-mediated thrombogenicity in acute coronary syndromes. Circulation. 1996; 94(12): 3090–3097.
- Libby P, Tabas I, Fredman G, et al. Inflammation and its resolution as determinants of acute coronary syndromes. Circ Res. 2014; 114(12): 1867–1879.
- Davies MJ, Richardson PD, Woolf N, et al. Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J. 1993; 69(5): 377–381.
- van der Wal AC, Becker AE, van der Loos CM, et al. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation. 1994; 89(1): 36–44.
- Galis ZS, Sukhova GK, Kranzhöfer R, et al. Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. Proc Natl Acad Sci U S A. 1995; 92(2): 402–406.
- Lee RT, Schoen FJ, Loree HM, et al. Circumferential stress and matrix metalloproteinase 1 in human coronary atherosclerosis. Implications for plaque rupture. Arterioscler Thromb Vasc Biol. 1996; 16(8): 1070–1073.
- Gutiérrez-Chico JL, Alegría-Barrero E, Teijeiro-Mestre R, et al. Optical coherence tomography: from research to practice. Eur Heart J Cardiovasc Imaging. 2012; 13(5): 370–384.
- Tearney GJ, Yabushita H, Houser SL, et al. Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography. Circulation. 2003; 107(1): 113–119.
- Tearney GJ, Regar E, Akasaka T, et al. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. J Am Coll Cardiol. 2012; 59(12): 1058–1072.
- Herborn CU, Vogt FM, Lauenstein TC, et al. Magnetic resonance imaging of experimental atherosclerotic plaque: comparison of two ultrasmall superparamagnetic particles of iron oxide. J Magn Reson Imaging. 2006; 24(2): 388–393.
- Wagner S, Schnorr J, Ludwig A, et al. Contrast-enhanced MR imaging of atherosclerosis using citrate-coated superparamagnetic iron oxide nanoparticles: calcifying microvesicles as imaging target for plaque characterization. Int J Nanomedicine. 2013; 8: 767–779.
- Scharlach C, Kratz H, Wiekhorst F, et al. Synthesis of acid-stabilized iron oxide nanoparticles and comparison for targeting atherosclerotic plaques: evaluation by MRI, quantitative MPS, and TEM alternative to ambiguous Prussian blue iron staining. Nanomedicine. 2015; 11(5): 1085–1095.
- Wagner M, Wagner S, Schnorr J, et al. Coronary MR angiography using citrate-coated very small superparamagnetic iron oxide particles as blood-pool contrast agent: initial experience in humans. J Magn Reson Imaging. 2011; 34(4): 816–823.
- Taupitz M, Wagner S, Schnorr J, et al. Phase i clinical evaluation of citrate-coated monocrystalline very small superparamagnetic iron oxide particles as a new contrast medium for magnetic resonance imaging. Invest Radiol. 2004; 39(7): 394–405.
- Gregory J. Monitoring particle aggregation processes. Adv Colloid Interface Sci. 2009; 147-148: 109–123.
- Scharlach C, Warmuth C, Schellenberger E. Determination of blood circulation times of superparamagnetic iron oxide nanoparticles by T2* relaxometry using ultrashort echo time (UTE) MRI. Magn Reson Imaging. 2015; 33(9): 1173–1177.
- Khalafalla S, Reimers G. Preparation of dilution-stable aqueous magnetic fluids. IEEE Transactions on Magnetics. 1980; 16(2): 178–183.
- Tearney GJ, Waxman S, Shishkov M, et al. Three-dimensional coronary artery microscopy by intracoronary optical frequency domain imaging. JACC Cardiovasc Imaging. 2008; 1(6): 752–761.
- Saw J, Ricci D, Starovoytov A, et al. Spontaneous coronary artery dissection: prevalence of predisposing conditions including fibromuscular dysplasia in a tertiary center cohort. JACC Cardiovasc Interv. 2013; 6(1): 44–52.
- Mehra MR, Crespo-Leiro MG, Dipchand A, et al. International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010. J Heart Lung Transplant. 2010; 29(7): 717–727.
- Moreno PR, Bernardi VH, López-Cuéllar J, et al. Macrophage infiltration predicts restenosis after coronary intervention in patients with unstable angina. Circulation. 1996; 94(12): 3098–3102.
- Scharlach C, Müller L, Wagner S, et al. LA-ICP-MS Allows Quantitative Microscopy of Europium-Doped Iron Oxide Nanoparticles and is a Possible Alternative to Ambiguous Prussian Blue Iron Staining. J Biomed Nanotechnol. 2016; 12(5): 1001–1010.
