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Evaluation of iron oxide nanoparticle micelles for magnetic particle imaging (MPI) of thrombosis.

Starmans LW, Moonen RP, Aussems-Custers E, Daemen MJ, Strijkers GJ, Nicolay K, Grüll H - PLoS ONE (2015)

Bottom Line: ION-Micelles significantly decreased T2 values in the thrombi with respect to pre-injection T2 values (p < 0.01) and significantly increased ex vivo MPS thrombus signal with respect to the noninjured, contralateral carotid (p < 0.01).Functionalization of the ION-Micelles with the FibPep peptides did not result in an increased MPS thrombus signal with respect to the non-fibrin binding ION-Micelles.The lack of a significant increased thrombus uptake for the FibPep-ION-Micelles indicates that (non-fibrin-specific) entrapment of nanoparticles in the mesh-like thrombi is the key contributor to thrombus nanoparticle uptake.

View Article: PubMed Central - PubMed

Affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.

ABSTRACT
Magnetic particle imaging (MPI) is an emerging medical imaging modality that directly visualizes magnetic particles in a hot-spot like fashion. We recently developed an iron oxide nanoparticle-micelle (ION-Micelle) platform that allows highly sensitive MPI. The goal of this study was to assess the potential of the ION-Micelles for MPI-based detection of thrombi. To this aim, an in vivo carotid artery thrombosis mouse model was employed and ex vivo magnetic particle spectrometer (MPS) measurements of the carotid arteries were performed. In addition, we studied the effect of functionalization of the ION-Micelle nanoplatform with fibrin-binding peptides (FibPeps) with respect to nanoparticle thrombus uptake and hence thrombus detection. In vivo quantitative MR imaging pre- and post-ION-Micelle injection was performed as reference for visualization of ION-micelle uptake. ION-Micelles significantly decreased T2 values in the thrombi with respect to pre-injection T2 values (p < 0.01) and significantly increased ex vivo MPS thrombus signal with respect to the noninjured, contralateral carotid (p < 0.01). Functionalization of the ION-Micelles with the FibPep peptides did not result in an increased MPS thrombus signal with respect to the non-fibrin binding ION-Micelles. The lack of a significant increased thrombus uptake for the FibPep-ION-Micelles indicates that (non-fibrin-specific) entrapment of nanoparticles in the mesh-like thrombi is the key contributor to thrombus nanoparticle uptake. Therefore, (nontargeted) ION-Micelles might be of value for noninvasive MPI-based diagnosis, characterization and treatment monitoring of thrombosis.

No MeSH data available.


Related in: MedlinePlus

In vivo MRI.(A) Images of right and left carotid arteries (RCA & LCA) reconstructed from the 3D time of flight (TOF) image. The thrombus can be observed in the RCA just proximal of the bifurcation (arrowheads). Presence of blood flow in the thrombosed carotid was confirmed for all animals. (B) On the TOF image 13 parallel slices were planned perpendicular to the RCA. T1-weighted images from three slices are shown: (1) distal from the bifurcation, (2) in the thrombus and (3) proximal to the thrombus (arrowheads: RCA). (C, D) Pre- and post-injection T1- and T2-weighted images and T2 maps of (C) FibPep-ION-Micelles and (D) NCFibPep-ION-Micelles (arrowheads: RCA). The insets show magnifications of the RCA (open arrowheads: outer vessel wall).
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pone.0119257.g003: In vivo MRI.(A) Images of right and left carotid arteries (RCA & LCA) reconstructed from the 3D time of flight (TOF) image. The thrombus can be observed in the RCA just proximal of the bifurcation (arrowheads). Presence of blood flow in the thrombosed carotid was confirmed for all animals. (B) On the TOF image 13 parallel slices were planned perpendicular to the RCA. T1-weighted images from three slices are shown: (1) distal from the bifurcation, (2) in the thrombus and (3) proximal to the thrombus (arrowheads: RCA). (C, D) Pre- and post-injection T1- and T2-weighted images and T2 maps of (C) FibPep-ION-Micelles and (D) NCFibPep-ION-Micelles (arrowheads: RCA). The insets show magnifications of the RCA (open arrowheads: outer vessel wall).

Mentions: 3D fast low-angle shot time-of-flight (3D-FLASH-TOF) MRI images confirmed formation of thrombus in the right carotid artery, which was observed as interruption of the bright blood signal; the thrombus itself has a light gray appearance in the MR image (Fig. 3A). A 2D image of the right carotid artery (RCA) was reconstructed from the 3D dataset and was used for planning subsequent MRI scans (Fig. 3B). T1- and T2-weighted images and T2 maps were successfully acquired repeatedly (Fig. 3C-D). Quantification of T2 was preferred over T2* because imaging in the carotid artery region requires a protocol that is robust for cardiac, respiratory and blood-flow motion. Region of interest (ROI) analysis revealed decreased mean T2 values in the thrombus area after injection with both FibPep-ION-Micelles (22.7 ± 1.5 ms) and NCFibPep-ION-Micelles (22.0 ± 2.6 ms) compared to pre-injection values (26.5 ± 2.6 and 25.0 ± 1.5 ms, respectively) (Fig. 4). Comparison of T2 values between mice injected with FibPep-ION-Micelles or NCFibPep-ION-Micelles revealed no significant differences for pre- or post-injection values (p = 0.388 and p = 0.675, respectively). These findings indicate that the ION-Micelles accumulate in the thrombi and that the functionalization with FibPep did not specifically enhance in vivo uptake of ION-Micelles in the thrombus as compared to the non-fibrin-binding nanoparticles. Statistically, the mice injected with FibPep-ION-Micelles or NCFibPep-ION-Micelles can thus be viewed as a single group. Comparison of the average mean thrombus T2 values revealed a highly significant (p = 0.003) overall decrease of T2 from 25.8 ± 2.3 ms pre-injection to 22.4 ± 2.1 ms post-injection of ION-Micelles (Fig. 4).


Evaluation of iron oxide nanoparticle micelles for magnetic particle imaging (MPI) of thrombosis.

Starmans LW, Moonen RP, Aussems-Custers E, Daemen MJ, Strijkers GJ, Nicolay K, Grüll H - PLoS ONE (2015)

In vivo MRI.(A) Images of right and left carotid arteries (RCA & LCA) reconstructed from the 3D time of flight (TOF) image. The thrombus can be observed in the RCA just proximal of the bifurcation (arrowheads). Presence of blood flow in the thrombosed carotid was confirmed for all animals. (B) On the TOF image 13 parallel slices were planned perpendicular to the RCA. T1-weighted images from three slices are shown: (1) distal from the bifurcation, (2) in the thrombus and (3) proximal to the thrombus (arrowheads: RCA). (C, D) Pre- and post-injection T1- and T2-weighted images and T2 maps of (C) FibPep-ION-Micelles and (D) NCFibPep-ION-Micelles (arrowheads: RCA). The insets show magnifications of the RCA (open arrowheads: outer vessel wall).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4352001&req=5

pone.0119257.g003: In vivo MRI.(A) Images of right and left carotid arteries (RCA & LCA) reconstructed from the 3D time of flight (TOF) image. The thrombus can be observed in the RCA just proximal of the bifurcation (arrowheads). Presence of blood flow in the thrombosed carotid was confirmed for all animals. (B) On the TOF image 13 parallel slices were planned perpendicular to the RCA. T1-weighted images from three slices are shown: (1) distal from the bifurcation, (2) in the thrombus and (3) proximal to the thrombus (arrowheads: RCA). (C, D) Pre- and post-injection T1- and T2-weighted images and T2 maps of (C) FibPep-ION-Micelles and (D) NCFibPep-ION-Micelles (arrowheads: RCA). The insets show magnifications of the RCA (open arrowheads: outer vessel wall).
Mentions: 3D fast low-angle shot time-of-flight (3D-FLASH-TOF) MRI images confirmed formation of thrombus in the right carotid artery, which was observed as interruption of the bright blood signal; the thrombus itself has a light gray appearance in the MR image (Fig. 3A). A 2D image of the right carotid artery (RCA) was reconstructed from the 3D dataset and was used for planning subsequent MRI scans (Fig. 3B). T1- and T2-weighted images and T2 maps were successfully acquired repeatedly (Fig. 3C-D). Quantification of T2 was preferred over T2* because imaging in the carotid artery region requires a protocol that is robust for cardiac, respiratory and blood-flow motion. Region of interest (ROI) analysis revealed decreased mean T2 values in the thrombus area after injection with both FibPep-ION-Micelles (22.7 ± 1.5 ms) and NCFibPep-ION-Micelles (22.0 ± 2.6 ms) compared to pre-injection values (26.5 ± 2.6 and 25.0 ± 1.5 ms, respectively) (Fig. 4). Comparison of T2 values between mice injected with FibPep-ION-Micelles or NCFibPep-ION-Micelles revealed no significant differences for pre- or post-injection values (p = 0.388 and p = 0.675, respectively). These findings indicate that the ION-Micelles accumulate in the thrombi and that the functionalization with FibPep did not specifically enhance in vivo uptake of ION-Micelles in the thrombus as compared to the non-fibrin-binding nanoparticles. Statistically, the mice injected with FibPep-ION-Micelles or NCFibPep-ION-Micelles can thus be viewed as a single group. Comparison of the average mean thrombus T2 values revealed a highly significant (p = 0.003) overall decrease of T2 from 25.8 ± 2.3 ms pre-injection to 22.4 ± 2.1 ms post-injection of ION-Micelles (Fig. 4).

Bottom Line: ION-Micelles significantly decreased T2 values in the thrombi with respect to pre-injection T2 values (p < 0.01) and significantly increased ex vivo MPS thrombus signal with respect to the noninjured, contralateral carotid (p < 0.01).Functionalization of the ION-Micelles with the FibPep peptides did not result in an increased MPS thrombus signal with respect to the non-fibrin binding ION-Micelles.The lack of a significant increased thrombus uptake for the FibPep-ION-Micelles indicates that (non-fibrin-specific) entrapment of nanoparticles in the mesh-like thrombi is the key contributor to thrombus nanoparticle uptake.

View Article: PubMed Central - PubMed

Affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.

ABSTRACT
Magnetic particle imaging (MPI) is an emerging medical imaging modality that directly visualizes magnetic particles in a hot-spot like fashion. We recently developed an iron oxide nanoparticle-micelle (ION-Micelle) platform that allows highly sensitive MPI. The goal of this study was to assess the potential of the ION-Micelles for MPI-based detection of thrombi. To this aim, an in vivo carotid artery thrombosis mouse model was employed and ex vivo magnetic particle spectrometer (MPS) measurements of the carotid arteries were performed. In addition, we studied the effect of functionalization of the ION-Micelle nanoplatform with fibrin-binding peptides (FibPeps) with respect to nanoparticle thrombus uptake and hence thrombus detection. In vivo quantitative MR imaging pre- and post-ION-Micelle injection was performed as reference for visualization of ION-micelle uptake. ION-Micelles significantly decreased T2 values in the thrombi with respect to pre-injection T2 values (p < 0.01) and significantly increased ex vivo MPS thrombus signal with respect to the noninjured, contralateral carotid (p < 0.01). Functionalization of the ION-Micelles with the FibPep peptides did not result in an increased MPS thrombus signal with respect to the non-fibrin binding ION-Micelles. The lack of a significant increased thrombus uptake for the FibPep-ION-Micelles indicates that (non-fibrin-specific) entrapment of nanoparticles in the mesh-like thrombi is the key contributor to thrombus nanoparticle uptake. Therefore, (nontargeted) ION-Micelles might be of value for noninvasive MPI-based diagnosis, characterization and treatment monitoring of thrombosis.

No MeSH data available.


Related in: MedlinePlus