Figures & data
Figure 1 Illustration of D-USPIO and DM-USPIO.
Note: DM-USPIO was prepared in-house by adding alkali-treated mannan to D-USPIO.
Abbreviations: D-USPIO, dextran-coated ultrasmall superparamagnetic iron oxide; DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide.
![Figure 1 Illustration of D-USPIO and DM-USPIO.Note: DM-USPIO was prepared in-house by adding alkali-treated mannan to D-USPIO.Abbreviations: D-USPIO, dextran-coated ultrasmall superparamagnetic iron oxide; DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide.](/cms/asset/445ac4ec-0894-4290-b2a9-46b53f886cee/dijn_a_29417_f0001_c.jpg)
Figure 2 In vivo MRA of the thoracic aorta of WHHL rabbits, (A) before, and (B) after the administration of D-USPIO, and (C) before, and (D) after the administration of DM-USPIO.
Notes: Irregularities, seen as spotty signal voids in the aortic wall, are present on the images obtained after administration of D- or DM-USPIO. The graph compares pre- and post-administration SNR measurements in the ROI in the aortic wall of WHHL rabbits subjected to in vivo MRI (n = 6), after injection with D- or DM-USPIO (n = 3, respectively). The SNR values were significantly lower on all post-contrast images. In rabbits injected with DM-USPIO, the difference between the pre- and post-administration SNR values was significantly greater than in those treated with D-USPIO *P < 0.05.
Abbreviations: D-USPIO, dextran-coated ultrasmall superparamagnetic iron oxide; DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide; MRA, magnetic resonance angiography; SNR, signal-to-noise ratio; ROI, region of interest; MRI, magnetic resonance imaging; WHHL, Watanabe heritable hyperlipidemic.
![Figure 2 In vivo MRA of the thoracic aorta of WHHL rabbits, (A) before, and (B) after the administration of D-USPIO, and (C) before, and (D) after the administration of DM-USPIO.Notes: Irregularities, seen as spotty signal voids in the aortic wall, are present on the images obtained after administration of D- or DM-USPIO. The graph compares pre- and post-administration SNR measurements in the ROI in the aortic wall of WHHL rabbits subjected to in vivo MRI (n = 6), after injection with D- or DM-USPIO (n = 3, respectively). The SNR values were significantly lower on all post-contrast images. In rabbits injected with DM-USPIO, the difference between the pre- and post-administration SNR values was significantly greater than in those treated with D-USPIO *P < 0.05.Abbreviations: D-USPIO, dextran-coated ultrasmall superparamagnetic iron oxide; DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide; MRA, magnetic resonance angiography; SNR, signal-to-noise ratio; ROI, region of interest; MRI, magnetic resonance imaging; WHHL, Watanabe heritable hyperlipidemic.](/cms/asset/258a8731-2ba9-457f-80d4-5c9ba9b34d63/dijn_a_29417_f0002_b.jpg)
Figure 3 Graph showing the SNR of the aortic wall specimens on in vitro MRI scans.
Notes: Aortic specimens from WHHL rabbits (A) Controls; (B) dose 1, (C) dose 2, (D) dose 3 of D-USPIO; (E) dose 1, (F) dose 2, (G) dose 3 of DM-USPIO (dose 1: n = 1; dose 2: n = 1; dose 3: n = 3). Compared to the controls, the signal from the aortic wall decreased in rabbits injected with D- or DM-USPIO, in a dose-dependent manner. At dose 3, the SNR tended to be lower (*P < 0.1) in rabbits treated with DM-USPIO. The SNR value obtained from three ROIs on three different aortic images was significantly lower (**P < 0.05) in the rabbit treated with dose 2 DM-USPIO than in the rabbit treated with an equivalent dose of D-USPIO. There was no significant difference at dose 1 (P > 0.1).
Abbreviations: D-USPIO, dextran-coated ultrasmall superparamagnetic iron oxide; DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide; SNR, signal-to-noise ratio; ROI, region of interest.
![Figure 3 Graph showing the SNR of the aortic wall specimens on in vitro MRI scans.Notes: Aortic specimens from WHHL rabbits (A) Controls; (B) dose 1, (C) dose 2, (D) dose 3 of D-USPIO; (E) dose 1, (F) dose 2, (G) dose 3 of DM-USPIO (dose 1: n = 1; dose 2: n = 1; dose 3: n = 3). Compared to the controls, the signal from the aortic wall decreased in rabbits injected with D- or DM-USPIO, in a dose-dependent manner. At dose 3, the SNR tended to be lower (*P < 0.1) in rabbits treated with DM-USPIO. The SNR value obtained from three ROIs on three different aortic images was significantly lower (**P < 0.05) in the rabbit treated with dose 2 DM-USPIO than in the rabbit treated with an equivalent dose of D-USPIO. There was no significant difference at dose 1 (P > 0.1).Abbreviations: D-USPIO, dextran-coated ultrasmall superparamagnetic iron oxide; DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide; SNR, signal-to-noise ratio; ROI, region of interest.](/cms/asset/323fa8e6-2ef7-41ee-8e74-657abdd749af/dijn_a_29417_f0003_b.jpg)
Figure 4 Prussian blue staining of histopathological sections.
Notes: (A) dose 1, (B) dose 2, (C) dose 3 of D-USPIO; (D) dose 1, (E) dose 2, (F) dose 3 of DM-USPIO. There was a marked iron uptake in the arterial walls of all rabbits injected with either D- or DM-USPIO. The Prussian blue-stained area increased in both the D- and DM-USPIO group in a dose-dependent manner.
Abbreviations: D-USPIO, dextran-coated ultrasmall superparamagnetic iron oxide; DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide.
![Figure 4 Prussian blue staining of histopathological sections.Notes: (A) dose 1, (B) dose 2, (C) dose 3 of D-USPIO; (D) dose 1, (E) dose 2, (F) dose 3 of DM-USPIO. There was a marked iron uptake in the arterial walls of all rabbits injected with either D- or DM-USPIO. The Prussian blue-stained area increased in both the D- and DM-USPIO group in a dose-dependent manner.Abbreviations: D-USPIO, dextran-coated ultrasmall superparamagnetic iron oxide; DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide.](/cms/asset/7e02388c-264c-4ba8-b08b-e5c185d968fa/dijn_a_29417_f0004_c.jpg)
Figure 5 (A) Prussian blue and (B) immunohistochemical (RAM11) staining of histopathological sections from WHHL rabbits injected with DM-USPIO at dose 3 (0.8 mmol Fe/Kg).
Note: The localization of iron and macrophages was correlated.
Abbreviations: DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide; WHHL, Watanabe heritable hyperlipidemic.
![Figure 5 (A) Prussian blue and (B) immunohistochemical (RAM11) staining of histopathological sections from WHHL rabbits injected with DM-USPIO at dose 3 (0.8 mmol Fe/Kg).Note: The localization of iron and macrophages was correlated.Abbreviations: DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide; WHHL, Watanabe heritable hyperlipidemic.](/cms/asset/e01e6a38-a75a-4c4a-b873-83e256550fa5/dijn_a_29417_f0005_c.jpg)
Figure 6 Iron-positive areas in the aortic wall of rabbits injected with D- or DM-USPIO.
Notes: At dose 3 (0.8 mmol Fe/Kg), the iron-positive areas were significantly larger in rabbits treated with DM- than in those treated with D-USPIO (*P < 0.05). The areas were significantly larger in different sections of the aorta from the rabbit injected with dose 1 or dose 2 DM- than in that treated with an equivalent dose of D-USPIO (*P < 0.05).
Abbreviations: D-USPIO, dextran-coated ultrasmall superparamagnetic iron oxide; DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide.
![Figure 6 Iron-positive areas in the aortic wall of rabbits injected with D- or DM-USPIO.Notes: At dose 3 (0.8 mmol Fe/Kg), the iron-positive areas were significantly larger in rabbits treated with DM- than in those treated with D-USPIO (*P < 0.05). The areas were significantly larger in different sections of the aorta from the rabbit injected with dose 1 or dose 2 DM- than in that treated with an equivalent dose of D-USPIO (*P < 0.05).Abbreviations: D-USPIO, dextran-coated ultrasmall superparamagnetic iron oxide; DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide.](/cms/asset/982be070-2105-4c20-9e4c-4cdc0502aa4f/dijn_a_29417_f0006_b.jpg)
Figure 7 Iron content per unit weight of aortic specimen from rabbits injected with D- or DM-USPIO at dose 3 (0.8 mmol Fe/Kg).
Note: There was no significant difference between the two groups.
Abbreviations: D-USPIO, dextran-coated ultrasmall superparamagnetic iron oxide; DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide.
![Figure 7 Iron content per unit weight of aortic specimen from rabbits injected with D- or DM-USPIO at dose 3 (0.8 mmol Fe/Kg).Note: There was no significant difference between the two groups.Abbreviations: D-USPIO, dextran-coated ultrasmall superparamagnetic iron oxide; DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide.](/cms/asset/dcdc60b3-534d-433d-89c2-2b12368c65cb/dijn_a_29417_f0007_b.jpg)
Figure 8 Iron uptake in cultured J774.1 macrophage cells, measured by atomic absorption photometry.
Note: The amount of intracellular iron was significantly higher in cells treated with DM-USPIO than with D-USPIO (*P < 0.05).
Abbreviations: D-USPIO, dextran-coated ultrasmall superparamagnetic iron oxide; DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide.
![Figure 8 Iron uptake in cultured J774.1 macrophage cells, measured by atomic absorption photometry.Note: The amount of intracellular iron was significantly higher in cells treated with DM-USPIO than with D-USPIO (*P < 0.05).Abbreviations: D-USPIO, dextran-coated ultrasmall superparamagnetic iron oxide; DM-USPIO, mannan–dextran-coated ultrasmall superparamagnetic iron oxide.](/cms/asset/70217dcf-e300-4a08-956b-a19efee102f6/dijn_a_29417_f0008_b.jpg)