Ferumoxytol-enhanced magnetic resonance imaging assessing inflammation after myocardial infarction
Colin G Stirrat, Shirjel R Alam, Thomas J MacGillivray, Calum D Gray, Marc R Dweck, Jennifer Raftis, William Sa Jenkins, William A Wallace, Renzo Pessotto, Kelvin Hh Lim, Saeed Mirsadraee, Peter A Henriksen, Scott Ik Semple, David E Newby, Colin G Stirrat, Shirjel R Alam, Thomas J MacGillivray, Calum D Gray, Marc R Dweck, Jennifer Raftis, William Sa Jenkins, William A Wallace, Renzo Pessotto, Kelvin Hh Lim, Saeed Mirsadraee, Peter A Henriksen, Scott Ik Semple, David E Newby
Abstract
Objectives: Macrophages play a central role in the cellular inflammatory response to myocardial infarction (MI) and predict subsequent clinical outcomes. We aimed to assess temporal changes in cellular inflammation and tissue oedema in patients with acute MI using ultrasmallsuperparamagnetic particles of iron oxide (USPIO)-enhanced MRI.
Methods: Thirty-one patients were recruited following acute MI and followed up for 3 months with repeated T2 and USPIO-enhanced T2*-mapping MRI. Regions of interest were categorised into infarct, peri-infarct and remote myocardial zones, and compared with control tissues.
Results: Following a single dose, USPIO enhancement was detected in the myocardium until 24 hours (p<0.0001). Histology confirmed colocalisation of iron and macrophages within the infarcted, but not the non-infarcted, myocardium. Following repeated doses, USPIO uptake in the infarct zone peaked at days 2-3, and greater USPIO uptake was detected in the infarct zone compared with remote myocardium until days 10-16 (p<0.05). In contrast, T2-defined myocardial oedema peaked at days 3-9 and remained increased in the infarct zone throughout the 3-month follow-up period (p<0.01).
Conclusion: Myocardial macrophage activity can be detected using USPIO-enhanced MRI in the first 2 weeks following acute MI. This observed pattern of cellular inflammation is distinct, and provides complementary information to the more prolonged myocardial oedema detectable using T2 mapping. This imaging technique holds promise as a non-invasive method of assessing and monitoring myocardial cellular inflammation with potential application to diagnosis, risk stratification and assessment of novel anti-inflammatory therapeutic interventions.
Trial registration number: Trial registration number: 14663. Registered on UK Clinical Research Network (http://public.ukcrn.org.uk) and also ClinicalTrials.gov (https://ichgcp.net/clinical-trials-registry/NCT02319278?term=DECIFER&rank=2).
Keywords: Cardiac; Inflammation; MRI; Molecular Imaging; Myocardial Infarction; USPIO.
Conflict of interest statement
Competing interests: None declared.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5629948/bin/heartjnl-2016-311018f01.jpg)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5629948/bin/heartjnl-2016-311018f02.jpg)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5629948/bin/heartjnl-2016-311018f03.jpg)
Figure 4
Examples of myocardial oedema and…
Figure 4
Examples of myocardial oedema and USPIO enhancement in the infarct zone after MI.…
Figure 5
T2 value in the myocardium…
Figure 5
T2 value in the myocardium after MI. Time course variation in infarct and…
Figure 6
USPIO enhancement after single-dose administration…
Figure 6
USPIO enhancement after single-dose administration in the first week following MI. Following single-dose…
- Visualising inflammation after myocardial infarction with the use of iron oxide nanoparticles.Yilmaz A. Yilmaz A. Heart. 2017 Oct;103(19):1479-1480. doi: 10.1136/heartjnl-2017-311484. Epub 2017 Jul 20. Heart. 2017. PMID: 28729284 No abstract available.
- Ferumoxytol-enhanced magnetic resonance imaging in acute myocarditis.Stirrat CG, Alam SR, MacGillivray TJ, Gray CD, Dweck MR, Dibb K, Spath N, Payne JR, Prasad SK, Gardner RS, Mirsadraee S, Henriksen PA, Semple SI, Newby DE. Stirrat CG, et al. Heart. 2018 Feb;104(4):300-305. doi: 10.1136/heartjnl-2017-311688. Epub 2017 Oct 6. Heart. 2018. PMID: 28986407 Free PMC article.
- Ferumoxytol-enhanced magnetic resonance imaging methodology and normal values at 1.5 and 3T.Stirrat CG, Alam SR, MacGillivray TJ, Gray CD, Forsythe R, Dweck MR, Payne JR, Prasad SK, Petrie MC, Gardner RS, Mirsadraee S, Henriksen PA, Newby DE, Semple SI. Stirrat CG, et al. J Cardiovasc Magn Reson. 2016 Jul 27;18(1):46. doi: 10.1186/s12968-016-0261-2. J Cardiovasc Magn Reson. 2016. PMID: 27465647 Free PMC article.
- Imaging of myocardial infarction using ultrasmall superparamagnetic iron oxide nanoparticles: a human study using a multi-parametric cardiovascular magnetic resonance imaging approach.Yilmaz A, Dengler MA, van der Kuip H, Yildiz H, Rösch S, Klumpp S, Klingel K, Kandolf R, Helluy X, Hiller KH, Jakob PM, Sechtem U. Yilmaz A, et al. Eur Heart J. 2013 Feb;34(6):462-75. doi: 10.1093/eurheartj/ehs366. Epub 2012 Oct 26. Eur Heart J. 2013. PMID: 23103659 Clinical Trial.
- Ultrasmall superparamagnetic particles of iron oxide in patients with acute myocardial infarction: early clinical experience.Alam SR, Shah AS, Richards J, Lang NN, Barnes G, Joshi N, MacGillivray T, McKillop G, Mirsadraee S, Payne J, Fox KA, Henriksen P, Newby DE, Semple SI. Alam SR, et al. Circ Cardiovasc Imaging. 2012 Sep 1;5(5):559-65. doi: 10.1161/CIRCIMAGING.112.974907. Epub 2012 Aug 8. Circ Cardiovasc Imaging. 2012. PMID: 22875883
- Ferumoxytol-enhanced MRI in patients with prior cardiac transplantation.Stirrat CG, Alam S, MacGillivray TJ, Gray C, Dweck MR, Jones V, Wallace W, Payne JR, Prasad SK, Gardner RS, Petrie MC, Mirsadraee S, Henriksen P, Newby DE, Semple S. Stirrat CG, et al. Open Heart. 2019 Oct 3;6(2):e001115. doi: 10.1136/openhrt-2019-001115. eCollection 2019. Open Heart. 2019. PMID: 31673393 Free PMC article.
- Magnetic resonance imaging contrast-enhancement with superparamagnetic iron oxide nanoparticles amplifies macrophage foam cell apoptosis in human and murine atherosclerosis.Segers FME, Ruder AV, Westra MM, Lammers T, Dadfar SM, Roemhild K, Lam TS, Kooi ME, Cleutjens KBJM, Verheyen FK, Schurink GWH, Haenen GR, van Berkel TJC, Bot I, Halvorsen B, Sluimer JC, Biessen EAL. Segers FME, et al. Cardiovasc Res. 2023 Jan 18;118(17):3346-3359. doi: 10.1093/cvr/cvac032. Cardiovasc Res. 2023. PMID: 35325057 Free PMC article.
- Myocardial inflammation and energetics by cardiac MRI: a review of emerging techniques.Tsampasian V, Swift AJ, Assadi H, Chowdhary A, Swoboda P, Sammut E, Dastidar A, Cabrero JB, Del Val JR, Nair S, Nijveldt R, Ryding A, Sawh C, Bucciarelli-Ducci C, Levelt E, Vassiliou V, Garg P. Tsampasian V, et al. BMC Med Imaging. 2021 Nov 8;21(1):164. doi: 10.1186/s12880-021-00695-0. BMC Med Imaging. 2021. PMID: 34749671 Free PMC article. Review.
- Iron Oxide Nanoparticles as Theranostic Agents in Cancer Immunotherapy.Canese R, Vurro F, Marzola P. Canese R, et al. Nanomaterials (Basel). 2021 Jul 29;11(8):1950. doi: 10.3390/nano11081950. Nanomaterials (Basel). 2021. PMID: 34443781 Free PMC article. Review.
- Physiological and Pathological Factors Affecting Drug Delivery to the Brain by Nanoparticles.Islam Y, Leach AG, Smith J, Pluchino S, Coxon CR, Sivakumaran M, Downing J, Fatokun AA, Teixidò M, Ehtezazi T. Islam Y, et al. Adv Sci (Weinh). 2021 Jun;8(11):e2002085. doi: 10.1002/advs.202002085. Epub 2021 Mar 15. Adv Sci (Weinh). 2021. PMID: 34105297 Free PMC article. Review.
- Ferumoxytol-enhanced magnetic resonance T1 reactivity for depiction of myocardial hypoperfusion.Colbert CM, Le AH, Shao J, Currier JW, Ajijola OA, Hu P, Nguyen KL. Colbert CM, et al. NMR Biomed. 2021 Jul;34(7):e4518. doi: 10.1002/nbm.4518. Epub 2021 Apr 8. NMR Biomed. 2021. PMID: 33830561 Free PMC article.
- Observational Study
- Research Support, Non-U.S. Gov't
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Female
- Ferrosoferric Oxide / pharmacology*
- Follow-Up Studies
- Hematinics / pharmacology
- Humans
- Inflammation / diagnosis*
- Macrophages / pathology
- Magnetic Resonance Imaging, Cine / methods*
- Male
- Middle Aged
- Myocardial Infarction / diagnosis*
- Myocardium / pathology*
- Reproducibility of Results
- Young Adult
- Hematinics
- Ferrosoferric Oxide
- ClinicalTrials.gov/NCT02319278
- Full Text Sources
- Other Literature Sources
- Medical
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![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5629948/bin/heartjnl-2016-311018f04.jpg)
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5629948/bin/heartjnl-2016-311018f05.jpg)
Figure 6
USPIO enhancement after single-dose administration…
Figure 6
USPIO enhancement after single-dose administration in the first week following MI. Following single-dose…
- Visualising inflammation after myocardial infarction with the use of iron oxide nanoparticles.Yilmaz A. Yilmaz A. Heart. 2017 Oct;103(19):1479-1480. doi: 10.1136/heartjnl-2017-311484. Epub 2017 Jul 20. Heart. 2017. PMID: 28729284 No abstract available.
- Ferumoxytol-enhanced magnetic resonance imaging in acute myocarditis.Stirrat CG, Alam SR, MacGillivray TJ, Gray CD, Dweck MR, Dibb K, Spath N, Payne JR, Prasad SK, Gardner RS, Mirsadraee S, Henriksen PA, Semple SI, Newby DE. Stirrat CG, et al. Heart. 2018 Feb;104(4):300-305. doi: 10.1136/heartjnl-2017-311688. Epub 2017 Oct 6. Heart. 2018. PMID: 28986407 Free PMC article.
- Ferumoxytol-enhanced magnetic resonance imaging methodology and normal values at 1.5 and 3T.Stirrat CG, Alam SR, MacGillivray TJ, Gray CD, Forsythe R, Dweck MR, Payne JR, Prasad SK, Petrie MC, Gardner RS, Mirsadraee S, Henriksen PA, Newby DE, Semple SI. Stirrat CG, et al. J Cardiovasc Magn Reson. 2016 Jul 27;18(1):46. doi: 10.1186/s12968-016-0261-2. J Cardiovasc Magn Reson. 2016. PMID: 27465647 Free PMC article.
- Imaging of myocardial infarction using ultrasmall superparamagnetic iron oxide nanoparticles: a human study using a multi-parametric cardiovascular magnetic resonance imaging approach.Yilmaz A, Dengler MA, van der Kuip H, Yildiz H, Rösch S, Klumpp S, Klingel K, Kandolf R, Helluy X, Hiller KH, Jakob PM, Sechtem U. Yilmaz A, et al. Eur Heart J. 2013 Feb;34(6):462-75. doi: 10.1093/eurheartj/ehs366. Epub 2012 Oct 26. Eur Heart J. 2013. PMID: 23103659 Clinical Trial.
- Ultrasmall superparamagnetic particles of iron oxide in patients with acute myocardial infarction: early clinical experience.Alam SR, Shah AS, Richards J, Lang NN, Barnes G, Joshi N, MacGillivray T, McKillop G, Mirsadraee S, Payne J, Fox KA, Henriksen P, Newby DE, Semple SI. Alam SR, et al. Circ Cardiovasc Imaging. 2012 Sep 1;5(5):559-65. doi: 10.1161/CIRCIMAGING.112.974907. Epub 2012 Aug 8. Circ Cardiovasc Imaging. 2012. PMID: 22875883
- Ferumoxytol-enhanced MRI in patients with prior cardiac transplantation.Stirrat CG, Alam S, MacGillivray TJ, Gray C, Dweck MR, Jones V, Wallace W, Payne JR, Prasad SK, Gardner RS, Petrie MC, Mirsadraee S, Henriksen P, Newby DE, Semple S. Stirrat CG, et al. Open Heart. 2019 Oct 3;6(2):e001115. doi: 10.1136/openhrt-2019-001115. eCollection 2019. Open Heart. 2019. PMID: 31673393 Free PMC article.
- Magnetic resonance imaging contrast-enhancement with superparamagnetic iron oxide nanoparticles amplifies macrophage foam cell apoptosis in human and murine atherosclerosis.Segers FME, Ruder AV, Westra MM, Lammers T, Dadfar SM, Roemhild K, Lam TS, Kooi ME, Cleutjens KBJM, Verheyen FK, Schurink GWH, Haenen GR, van Berkel TJC, Bot I, Halvorsen B, Sluimer JC, Biessen EAL. Segers FME, et al. Cardiovasc Res. 2023 Jan 18;118(17):3346-3359. doi: 10.1093/cvr/cvac032. Cardiovasc Res. 2023. PMID: 35325057 Free PMC article.
- Myocardial inflammation and energetics by cardiac MRI: a review of emerging techniques.Tsampasian V, Swift AJ, Assadi H, Chowdhary A, Swoboda P, Sammut E, Dastidar A, Cabrero JB, Del Val JR, Nair S, Nijveldt R, Ryding A, Sawh C, Bucciarelli-Ducci C, Levelt E, Vassiliou V, Garg P. Tsampasian V, et al. BMC Med Imaging. 2021 Nov 8;21(1):164. doi: 10.1186/s12880-021-00695-0. BMC Med Imaging. 2021. PMID: 34749671 Free PMC article. Review.
- Iron Oxide Nanoparticles as Theranostic Agents in Cancer Immunotherapy.Canese R, Vurro F, Marzola P. Canese R, et al. Nanomaterials (Basel). 2021 Jul 29;11(8):1950. doi: 10.3390/nano11081950. Nanomaterials (Basel). 2021. PMID: 34443781 Free PMC article. Review.
- Physiological and Pathological Factors Affecting Drug Delivery to the Brain by Nanoparticles.Islam Y, Leach AG, Smith J, Pluchino S, Coxon CR, Sivakumaran M, Downing J, Fatokun AA, Teixidò M, Ehtezazi T. Islam Y, et al. Adv Sci (Weinh). 2021 Jun;8(11):e2002085. doi: 10.1002/advs.202002085. Epub 2021 Mar 15. Adv Sci (Weinh). 2021. PMID: 34105297 Free PMC article. Review.
- Ferumoxytol-enhanced magnetic resonance T1 reactivity for depiction of myocardial hypoperfusion.Colbert CM, Le AH, Shao J, Currier JW, Ajijola OA, Hu P, Nguyen KL. Colbert CM, et al. NMR Biomed. 2021 Jul;34(7):e4518. doi: 10.1002/nbm.4518. Epub 2021 Apr 8. NMR Biomed. 2021. PMID: 33830561 Free PMC article.
- Observational Study
- Research Support, Non-U.S. Gov't
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Female
- Ferrosoferric Oxide / pharmacology*
- Follow-Up Studies
- Hematinics / pharmacology
- Humans
- Inflammation / diagnosis*
- Macrophages / pathology
- Magnetic Resonance Imaging, Cine / methods*
- Male
- Middle Aged
- Myocardial Infarction / diagnosis*
- Myocardium / pathology*
- Reproducibility of Results
- Young Adult
- Hematinics
- Ferrosoferric Oxide
- ClinicalTrials.gov/NCT02319278
- Full Text Sources
- Other Literature Sources
- Medical
![Figure 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5629948/bin/heartjnl-2016-311018f06.jpg)
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