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The diagnostic value of iron oxide nanoparticles for imaging of myocardial inflammation--quo vadis?

Bietenbeck M, Florian A, Sechtem U, Yilmaz A - J Cardiovasc Magn Reson (2015)

Bottom Line: After intravenous administration, these nanoparticles are taken up by activated monocytes and macrophages, which predominantly accumulate in regions associated with inflammation as was successfully shown in recent preclinical studies.In this article, we outline the basic features of superparamagnetic iron oxide-based contrast agents and review recent studies using such nanoparticles for cardiac imaging in case of acute myocardial infarction as well as acute myocarditis.Moreover, we highlight the translational potential of these agents and possible research applications with regard to imaging and therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology and Angiology, Albert-Schweitzer-Campus 1, building A1, 48149, Münster, Germany.

ABSTRACT
Cardiovascular magnetic resonance (CMR) is an integral part in the diagnostic work-up of cardiac inflammatory diseases. In this context, superparamagnetic iron oxide-based contrast agents can provide additional diagnostic information regarding the assessment of myocardial infarction and myocarditis. After intravenous administration, these nanoparticles are taken up by activated monocytes and macrophages, which predominantly accumulate in regions associated with inflammation as was successfully shown in recent preclinical studies. Furthermore, first clinical studies with a new iron oxide-complex that was clinically approved for the treatment of iron deficiency anaemia recently demonstrated a superior diagnostic value of iron oxide nanoparticles compared to gadolinium-based compounds for imaging of myocardial inflammation in patients with acute myocardial infarction. In this article, we outline the basic features of superparamagnetic iron oxide-based contrast agents and review recent studies using such nanoparticles for cardiac imaging in case of acute myocardial infarction as well as acute myocarditis. Moreover, we highlight the translational potential of these agents and possible research applications with regard to imaging and therapy.

No MeSH data available.


Related in: MedlinePlus

Comparison of explanted hearts from mice after induced myocardial infarction (top row) and after sham procedure (bottom row). Images a and d show myocardium stained with Evans blue indicating areas with enhanced permeability in the area of myocardial infarction (a, arrows). The corresponding sections display damaged tissue only for infarcted hearts (b vs. e) and corresponding signal void in T2-weighted MR images after infusion of VSPIO (c vs. f). Reproduced with permission from Protti et al. [53]
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Fig3: Comparison of explanted hearts from mice after induced myocardial infarction (top row) and after sham procedure (bottom row). Images a and d show myocardium stained with Evans blue indicating areas with enhanced permeability in the area of myocardial infarction (a, arrows). The corresponding sections display damaged tissue only for infarcted hearts (b vs. e) and corresponding signal void in T2-weighted MR images after infusion of VSPIO (c vs. f). Reproduced with permission from Protti et al. [53]

Mentions: In a recent study, Protti et al. extensively investigated the performance of VSPIOs in a murine model of ischemia-reperfusion [53]. The IONs were administered according to four different experimental setups: one pre-MI protocol that was based on the application of VSPIOs seven days before surgery, and three post-MI protocols that differed in the delay between reperfusion and injection (24 h, 6d, 28d). The first post-MI protocol included MR imaging and T2*-mapping 2 h, 48 h and 7d after VSPIO application while mice in the other setups were imaged solely after 48 h. Image analysis of the pre-MI protocol showed no negative contrast enhancement, but a decrease in functional parameters. While the latter was related to myocardial injury, the absence of a negative contrast enhancement was explained by reperfusion of the infarcted territory. On the contrary, CMR series of the first post-MI protocol showed signal voids associated to VSPIO accumulation (Fig. 3). Moreover, Protti and colleagues found a temporal correlation between the recovery of T2*-values and the decrease of areas with ION-induced signal extinction. This correlation was not consistent with functional and volumetric measurements and did not apply for MR imaging six days post-MI as performed in the second setup. Furthermore, no signal void was seen on CMR scans 28 days after MI indicating the restoration of vascular integrity and/or the endpoint of remodelling. Histological examinations performed 48 h post-injection showed a high iron density at the inner endocardial borders of infarcted areas. In contrast, no or little iron was identified in epicardial borders. However, macrophages were identified on both sites. Consequently, the number of macrophages did not significantly correlate with T2*-values. Hence, the authors argued that other cells apart from monocytes and macrophages internalized VSPIOs. Additional electron microscopy showed an augmented VSPIO compartmentalization in macrophages located in endocardial areas as opposed to epicardial regions. Protti and colleagues assumed that an enhanced VSPIO-leakage into endocardial tissue might explain their findings. Increased leakage in turn might have originated from locally increased vessel permeability along with a decreased tissue perfusion [53].Fig. 3


The diagnostic value of iron oxide nanoparticles for imaging of myocardial inflammation--quo vadis?

Bietenbeck M, Florian A, Sechtem U, Yilmaz A - J Cardiovasc Magn Reson (2015)

Comparison of explanted hearts from mice after induced myocardial infarction (top row) and after sham procedure (bottom row). Images a and d show myocardium stained with Evans blue indicating areas with enhanced permeability in the area of myocardial infarction (a, arrows). The corresponding sections display damaged tissue only for infarcted hearts (b vs. e) and corresponding signal void in T2-weighted MR images after infusion of VSPIO (c vs. f). Reproduced with permission from Protti et al. [53]
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4495803&req=5

Fig3: Comparison of explanted hearts from mice after induced myocardial infarction (top row) and after sham procedure (bottom row). Images a and d show myocardium stained with Evans blue indicating areas with enhanced permeability in the area of myocardial infarction (a, arrows). The corresponding sections display damaged tissue only for infarcted hearts (b vs. e) and corresponding signal void in T2-weighted MR images after infusion of VSPIO (c vs. f). Reproduced with permission from Protti et al. [53]
Mentions: In a recent study, Protti et al. extensively investigated the performance of VSPIOs in a murine model of ischemia-reperfusion [53]. The IONs were administered according to four different experimental setups: one pre-MI protocol that was based on the application of VSPIOs seven days before surgery, and three post-MI protocols that differed in the delay between reperfusion and injection (24 h, 6d, 28d). The first post-MI protocol included MR imaging and T2*-mapping 2 h, 48 h and 7d after VSPIO application while mice in the other setups were imaged solely after 48 h. Image analysis of the pre-MI protocol showed no negative contrast enhancement, but a decrease in functional parameters. While the latter was related to myocardial injury, the absence of a negative contrast enhancement was explained by reperfusion of the infarcted territory. On the contrary, CMR series of the first post-MI protocol showed signal voids associated to VSPIO accumulation (Fig. 3). Moreover, Protti and colleagues found a temporal correlation between the recovery of T2*-values and the decrease of areas with ION-induced signal extinction. This correlation was not consistent with functional and volumetric measurements and did not apply for MR imaging six days post-MI as performed in the second setup. Furthermore, no signal void was seen on CMR scans 28 days after MI indicating the restoration of vascular integrity and/or the endpoint of remodelling. Histological examinations performed 48 h post-injection showed a high iron density at the inner endocardial borders of infarcted areas. In contrast, no or little iron was identified in epicardial borders. However, macrophages were identified on both sites. Consequently, the number of macrophages did not significantly correlate with T2*-values. Hence, the authors argued that other cells apart from monocytes and macrophages internalized VSPIOs. Additional electron microscopy showed an augmented VSPIO compartmentalization in macrophages located in endocardial areas as opposed to epicardial regions. Protti and colleagues assumed that an enhanced VSPIO-leakage into endocardial tissue might explain their findings. Increased leakage in turn might have originated from locally increased vessel permeability along with a decreased tissue perfusion [53].Fig. 3

Bottom Line: After intravenous administration, these nanoparticles are taken up by activated monocytes and macrophages, which predominantly accumulate in regions associated with inflammation as was successfully shown in recent preclinical studies.In this article, we outline the basic features of superparamagnetic iron oxide-based contrast agents and review recent studies using such nanoparticles for cardiac imaging in case of acute myocardial infarction as well as acute myocarditis.Moreover, we highlight the translational potential of these agents and possible research applications with regard to imaging and therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology and Angiology, Albert-Schweitzer-Campus 1, building A1, 48149, Münster, Germany.

ABSTRACT
Cardiovascular magnetic resonance (CMR) is an integral part in the diagnostic work-up of cardiac inflammatory diseases. In this context, superparamagnetic iron oxide-based contrast agents can provide additional diagnostic information regarding the assessment of myocardial infarction and myocarditis. After intravenous administration, these nanoparticles are taken up by activated monocytes and macrophages, which predominantly accumulate in regions associated with inflammation as was successfully shown in recent preclinical studies. Furthermore, first clinical studies with a new iron oxide-complex that was clinically approved for the treatment of iron deficiency anaemia recently demonstrated a superior diagnostic value of iron oxide nanoparticles compared to gadolinium-based compounds for imaging of myocardial inflammation in patients with acute myocardial infarction. In this article, we outline the basic features of superparamagnetic iron oxide-based contrast agents and review recent studies using such nanoparticles for cardiac imaging in case of acute myocardial infarction as well as acute myocarditis. Moreover, we highlight the translational potential of these agents and possible research applications with regard to imaging and therapy.

No MeSH data available.


Related in: MedlinePlus