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Feasibility of a whole-body 3 T MRI system for detecting macrophages in mouse carotid atherosclerosis using feco/graphite core-shell nanocrystals

Introduction

Novel FeCo/graphite core-shell nanocrystals (FeCo/GC) appear promising for detecting macrophages in mouse arteries with 7 T small-bore MRI, but use of whole-body MRI systems would be advantageous for clinical translation.

Purpose

To evaluate whole-body 3 T MRI for FeCo/GC-enhanced imaging of mouse carotid atherosclerosis with 7 T comparison.

Methods

1) Mice

Seven FVB mice were fed a high-fat diet for 4 weeks and had diabetes induced by streptozotocin injections, followed 2 weeks later by left carotid ligation.

2) FeCo/GC nanocrystals

Composed of an iron-cobalt core encapsulated by a biocompatible graphite shell (size - 7 nm) with Cy5.5 attached for fluorescence imaging. FeCo/GC have superior MRI properties with both cellular imaging and heating attributes. A higher dose (25 mgFe/kg) was used for detection at 3 T than 7 T (6 mgFe/kg).

3) MRI

2 weeks post-ligation, mice (n = 4) were imaged on a whole-body 3 T MRI scanner (Signa HDx, GE Healthcare) with installed gradients (50 mT/m, 150 T/m/s) and a custom 3 cm surface RF coil. As a comparison, another group of mice (n = 3) were imaged on a small-bore 7 T system (30 cm bore magnet, Varian Inc. plus GE "Micro-Signa" environment), with a 9 cm gradient insert (770 mT/m, and 2500 T/m/s, Resonance Research, Inc.) and a custom 6-cm RF coil. Similar gradient echo sequences were used (3 T: TR/TE = 100 ms/10 ms, slice thickness = 1.0 mm, FOV = 3 cm, matrix = 256 × 256, FA = 60; 7 T: TR/TE = 50 ms/4.2 ms, slice thickness = 0.5 mm, FOV = 3 cm, matrix = 256 × 256, FA = 50). MRI was performed pre and 24 and 48 hrs post IV injection of FeCo/GC. FeCo/GC accumulation was assessed by measuring the extent of T2*-induced reduction in carotid lumen size (% reduction of carotid lumen area).

4) Histology

Immunofluorescence staining was performed to confirm co-localization of FeCo/GC and macrophages.

Results

Images prior to FeCo/GC show the left carotid artery (yellow arrow) was smaller than the right (red arrow) due to ligation (Figure 1). After FeCo/GC administration, serial MRI images at 3 T show a further reduction in left carotid lumen area due to T2* signal loss, similar to the findings at 7 T. There was no evidence of lumen area reduction in the non-ligated right carotid arteries (Figure 1). The measured percentage reduction of left carotid lumen area was significant at both 24 and 48 hrs for 3 T and 7 T (Figure 2) and was greater at 3 T, likely due to the larger FeCo/GC dose. Immunofluorescence staining revealed colocalization of FeCo/GC and macrophages (Figure 3).

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Figure 1

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Figure 2

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Figure 3

Conclusion

Whole-body 3 T MRI can detect plaque macrophages using FeCo/graphite nanocrystals in mouse atherosclerosis, encouraging the translation to clinical studies.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Kosuge, H., Sherlock, S., Kitagawa, T. et al. Feasibility of a whole-body 3 T MRI system for detecting macrophages in mouse carotid atherosclerosis using feco/graphite core-shell nanocrystals. J Cardiovasc Magn Reson 12 (Suppl 1), P257 (2010). https://doi.org/10.1186/1532-429X-12-S1-P257

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  • DOI: https://doi.org/10.1186/1532-429X-12-S1-P257

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