Limits...
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

Ex vivo MPS of carotid arteries.MPS measurements of excised injured and contralateral, noninjured carotid arteries following injection with FibPep-ION-Micelles (n = 5) and NCFibPep-ION-Micelles (n = 5) or without injection (n = 3). Data is expressed as magnetic moment of the third harmonic (76 kHz), horizontal lines represent group means. * P < 0.01 versus contralateral carotid (all three groups) and injured carotid of mice which had not received an injection of ION-Micelles.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4352001&req=5

pone.0119257.g005: Ex vivo MPS of carotid arteries.MPS measurements of excised injured and contralateral, noninjured carotid arteries following injection with FibPep-ION-Micelles (n = 5) and NCFibPep-ION-Micelles (n = 5) or without injection (n = 3). Data is expressed as magnetic moment of the third harmonic (76 kHz), horizontal lines represent group means. * P < 0.01 versus contralateral carotid (all three groups) and injured carotid of mice which had not received an injection of ION-Micelles.

Mentions: Mice were euthanized upon completion of the MR scans (ca. 2 h post-injection of ION-Micelles and 4.5 h post-thrombus induction). Subsequently, the injured and noninjured, contralateral carotid arteries were excised and measured using MPS to probe ION-Micelle MPI signal. In addition, the injured and contralateral carotids of three mice that had not undergone nanoparticle injection were measured with MPS to quantify background MPS signal of the thrombosed and noninjured carotids. Specific analysis of the third MPS harmonic (Fig. 5) showed significantly increased signal for the injured carotids of mice injected with FibPep-ION-Micelles or NCFibPep-ION-Micelles (26 ± 7 and 25 ± 8 pAm2, respectively) with respect to the contralateral carotids of these mice (9 ± 3 and 8 ± 2 pAm2, respectively) and also with respect to both the injured and contralateral carotids of mice which did not receive nanoparticle injections (5 ± 2 and 6 ± 4 pAm2, respectively). Thus, the ION-Micelles showed significant accumulation in thrombi. The MPS data indicate that there was no significant difference between iron oxide nanoparticle uptake in the injured carotids of mice injected with FibPep-ION-Micelles or NCFibPep-ION-Micelles, which is in line with the above MRI findings.


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)

Ex vivo MPS of carotid arteries.MPS measurements of excised injured and contralateral, noninjured carotid arteries following injection with FibPep-ION-Micelles (n = 5) and NCFibPep-ION-Micelles (n = 5) or without injection (n = 3). Data is expressed as magnetic moment of the third harmonic (76 kHz), horizontal lines represent group means. * P < 0.01 versus contralateral carotid (all three groups) and injured carotid of mice which had not received an injection of ION-Micelles.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0119257.g005: Ex vivo MPS of carotid arteries.MPS measurements of excised injured and contralateral, noninjured carotid arteries following injection with FibPep-ION-Micelles (n = 5) and NCFibPep-ION-Micelles (n = 5) or without injection (n = 3). Data is expressed as magnetic moment of the third harmonic (76 kHz), horizontal lines represent group means. * P < 0.01 versus contralateral carotid (all three groups) and injured carotid of mice which had not received an injection of ION-Micelles.
Mentions: Mice were euthanized upon completion of the MR scans (ca. 2 h post-injection of ION-Micelles and 4.5 h post-thrombus induction). Subsequently, the injured and noninjured, contralateral carotid arteries were excised and measured using MPS to probe ION-Micelle MPI signal. In addition, the injured and contralateral carotids of three mice that had not undergone nanoparticle injection were measured with MPS to quantify background MPS signal of the thrombosed and noninjured carotids. Specific analysis of the third MPS harmonic (Fig. 5) showed significantly increased signal for the injured carotids of mice injected with FibPep-ION-Micelles or NCFibPep-ION-Micelles (26 ± 7 and 25 ± 8 pAm2, respectively) with respect to the contralateral carotids of these mice (9 ± 3 and 8 ± 2 pAm2, respectively) and also with respect to both the injured and contralateral carotids of mice which did not receive nanoparticle injections (5 ± 2 and 6 ± 4 pAm2, respectively). Thus, the ION-Micelles showed significant accumulation in thrombi. The MPS data indicate that there was no significant difference between iron oxide nanoparticle uptake in the injured carotids of mice injected with FibPep-ION-Micelles or NCFibPep-ION-Micelles, which is in line with the above MRI findings.

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