Alam, Shirjel R

Dweck, Marc R

Henriksen, Peter

Lang, Ninian

Macgillivray, Tom J

Mckillop, Graham

Mirsadraee, Saeed

Newby, David

Pessotto, Renzo

Richards, Jenny

Semple, Scott

Shah, Anoop S

Wang, Chengjia

Zamvar, Vipin

PubMed

Scott Semple

Shirjel R Alam

Tom J MacGillivray

Marc R Dweck

Anoop S Shah

Jenny Richards

Chengjia Wang

Ninian Lang

Graham McKillop

Saeed Mirsadraee

Renzo Pessotto

Vipin Zamvar

Peter Henriksen

David Newby

Crossref

Journal of Cardiovascular Magnetic Resonance

Quantitative myocardial inflammation assessed using a novel USPIO-Magnetic Resonance Imaging acquisition and analysis protocol

Springer - Publisher Connector

ORAL PRESENTATION Open Access
Quantitative myocardial inflammation assessed
using a novel USPIO-Magnetic Resonance
Imaging acquisition and analysis protocol
Scott Semple1,2*, Shirjel R Alam1, Tom J MacGillivray1,2, Marc R Dweck1,3, Anoop S Shah1, Jenny Richards1,4,
Chengjia Wang1,2, Ninian Lang1,3, Graham McKillop5, Saeed Mirsadraee2,5, Renzo Pessotto6, Vipin Zamvar6,
Peter Henriksen1,3, David Newby1,3
From 16th Annual SCMR Scientific Sessions
San Francisco, CA, USA. 31 January - 3 February 2013
Background
Ultrasmall superparamagnetic particles of iron-oxide
(SUPIO) particles can be used as a magnetic resonance
imaging contrast (MRI) agent. Due to their dextran coating
and small diameter (<30 nm), they are phagocytised by
inflammatory cells [1].
The aim of this study was to assess whether a novel
acquisition/registration USPIO-MRI protocol could be
used to assess myocardial cellular inflammation. Myocar-
dial infarction and cardiac surgery was used to model
myocardial inflammation [2]. An influx of macrophages
can be seen in post-mortem histology, however the
dynamics of in vivo patho-physiology is uncertain [3].
Methods
16 patients underwent MRI 2-4 days after ST-elevation
myocardial infarction (STEMI) at baseline and 24-hours
after intravenous USPIO infusion (4 mg/kg; Ferumoxytol,
AMAG; n=10) or no infusion (n=6). Between 5 and
28-days following on-pump coronary artery bypass graft
(CABG) surgery, 32 patients underwent the same protocol
with all patients receiving USPIO.
3T-MRI (Siemens Medical) was performed to optimise
USPIO sensitivity. Baseline and 24-hour multi-echo T2*-
weighted sequences were spatially registered to generate
an R2* (1/T2*) map to assess USPIO uptake. R2* maps
were spatially registered using custom software (Matlab/
Analyze) to late gadolinium enhancement (LGE) images to
confirm USPIO localisation in the infarct zone. CABG R2*
maps were analysed using a standard 17-segment model.
Data comparing CABG to MI cohorts was analysed by
one-way and repeated measures ANOVA with Dunn’s
post-test. Data comparing change in R2* values within
cohorts was analysed by Wilcoxon matched pairs test.
Results
Consistent with reticuloendothelial uptake, R2* values
increased in the liver & spleen following USPIO adminis-
tration. In the myocardial infarct, there was a large R2*
increase from 41.0±12.0 (baseline) to 155±45.0 s-1
(p<0.001) at 24h. A lower magnitude response was seen in
the remote myocardium from 39±3.2 to 80±14.9 s-1
(p<0.002), consistent with myocardial inflammation that
occurs post infarction [4].
In CABG patients the R2* signal increased: 45±7s-1 to
118± 22 s-1 at 24h (p<0001). The increase in myocardial
R2* values was greater than in the remote myocardium of
patients with STEMI, but lower than the infarct zone itself
(p<0.001 and p<0.05 respectively).
Conclusions
USPIO are taken up into inflamed myocardial tissue and
can be quantitatively assessed using a multi-parameter
MRI acquisition protocol with optimised spatial registra-
tion analysis based on a custom mutual information
algorithm.
This represents a novel imaging technique of assessing
myocardial inflammation, as well as providing a useful
research tool in investigating tissue inflammation.
1Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK
Full list of author information is available at the end of the article
Semple et al. Journal of Cardiovascular Magnetic
Resonance 2013, 15(Suppl 1):O114
http://www.jcmr-online.com/content/15/S1/O114
© 2013 Semple et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Funding
Funding was provided by the Medical Research Council,
Chest Heart & Stroke Scotland, the British Heart Founda-
tion and the Scottish Universities Physics Alliance.
The Welcome Trust Clinical Research Facility and the
Clinical Research Imaging Centre are supported by NHS
Research Scotland (NRS) through NHS Lothian.
Author details
1Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK.
2Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK.
3Department of Cardiology, Royal Infirmary of Edinburgh, Edinburgh, UK.
4Department of Vascular Surgery, Royal Infirmary of Edinburgh, Edinburgh,
UK. 5Department of Radiology, Royal Infirmary of Edinburgh, Edinburgh, UK.
6Department of Cardiac Surgery, Royal Infirmary of Edinburgh, Edinburgh,
UK.
Published: 30 January 2013
doi:10.1186/1532-429X-15-S1-O114
Cite this article as: Semple et al.: Quantitative myocardial inflammation
assessed using a novel USPIO-Magnetic Resonance Imaging acquisition
and analysis protocol. Journal of Cardiovascular Magnetic Resonance 2013
15(Suppl 1):O114.
Submit your next manuscript to BioMed Central
and take full advantage of: 
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at 
www.biomedcentral.com/submit
Figure 1 Increase in R2* values in control STEMI patients (no USPIO) (blue, n=6), STEMI patients given USPIO (red, n=10) and CABG patients
(green, n=32). Most significant R2* increase (and hence myocardial inflammation) observed in infarct zones, with CABG myocardial R2* increase
between infarct and myocardium remote to infarction. The spatially registered regions of interests (ROI) for quantifying R2* value for STEMI and
CABG patients are shown in the MRI images at the bottom of the figure.
Semple et al. Journal of Cardiovascular Magnetic
Resonance 2013, 15(Suppl 1):O114
http://www.jcmr-online.com/content/15/S1/O114
Page 2 of 2


Edinburgh Research Explorer

     Edinburgh Research Explorer                                      Quantitative myocardial inflammation assessed using a novelUSPIO-Magnetic Resonance Imaging acquisition and analysisprotocolCitation for published version:Semple, S, Alam, SR, Macgillivray, TJ, Dweck, MR, Shah, AS, Richards, J, Wang, C, Lang, N, Mckillop, G,Mirsadraee, S, Pessotto, R, Zamvar, V, Henriksen, P & Newby, D 2013, 'Quantitative myocardialinflammation assessed using a novel USPIO-Magnetic Resonance Imaging acquisition and analysisprotocol' Journal of Cardiovascular Magnetic Resonance, vol 15, no. Suppl 1, pp. O114. DOI:10.1186/1532-429X-15-S1-O114Digital Object Identifier (DOI):10.1186/1532-429X-15-S1-O114Link:Link to publication record in Edinburgh Research ExplorerDocument Version:Publisher's PDF, also known as Version of recordPublished In:Journal of Cardiovascular Magnetic ResonancePublisher Rights Statement:Available under Open Access.© 2013 Semple et al; licensee BioMed Central Ltd.General rightsCopyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s)and / or other copyright owners and it is a condition of accessing these publications that users recognise andabide by the legal requirements associated with these rights.Take down policyThe University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorercontent complies with UK legislation. If you believe that the public display of this file breaches copyright pleasecontact openaccess@ed.ac.uk providing details, and we will remove access to the work immediately andinvestigate your claim.Download date: 28. Apr. 2017ORAL PRESENTATION Open AccessQuantitative myocardial inflammation assessedusing a novel USPIO-Magnetic ResonanceImaging acquisition and analysis protocolScott Semple1,2*, Shirjel R Alam1, Tom J MacGillivray1,2, Marc R Dweck1,3, Anoop S Shah1, Jenny Richards1,4,Chengjia Wang1,2, Ninian Lang1,3, Graham McKillop5, Saeed Mirsadraee2,5, Renzo Pessotto6, Vipin Zamvar6,Peter Henriksen1,3, David Newby1,3From 16th Annual SCMR Scientific SessionsSan Francisco, CA, USA. 31 January - 3 February 2013BackgroundUltrasmall superparamagnetic particles of iron-oxide(SUPIO) particles can be used as a magnetic resonanceimaging contrast (MRI) agent. Due to their dextran coatingand small diameter (<30 nm), they are phagocytised byinflammatory cells [1].The aim of this study was to assess whether a novelacquisition/registration USPIO-MRI protocol could beused to assess myocardial cellular inflammation. Myocar-dial infarction and cardiac surgery was used to modelmyocardial inflammation [2]. An influx of macrophagescan be seen in post-mortem histology, however thedynamics of in vivo patho-physiology is uncertain [3].Methods16 patients underwent MRI 2-4 days after ST-elevationmyocardial infarction (STEMI) at baseline and 24-hoursafter intravenous USPIO infusion (4 mg/kg; Ferumoxytol,AMAG; n=10) or no infusion (n=6). Between 5 and28-days following on-pump coronary artery bypass graft(CABG) surgery, 32 patients underwent the same protocolwith all patients receiving USPIO.3T-MRI (Siemens Medical) was performed to optimiseUSPIO sensitivity. Baseline and 24-hour multi-echo T2*-weighted sequences were spatially registered to generatean R2* (1/T2*) map to assess USPIO uptake. R2* mapswere spatially registered using custom software (Matlab/Analyze) to late gadolinium enhancement (LGE) images toconfirm USPIO localisation in the infarct zone. CABG R2*maps were analysed using a standard 17-segment model.Data comparing CABG to MI cohorts was analysed byone-way and repeated measures ANOVA with Dunn’spost-test. Data comparing change in R2* values withincohorts was analysed by Wilcoxon matched pairs test.ResultsConsistent with reticuloendothelial uptake, R2* valuesincreased in the liver & spleen following USPIO adminis-tration. In the myocardial infarct, there was a large R2*increase from 41.0±12.0 (baseline) to 155±45.0 s-1(p<0.001) at 24h. A lower magnitude response was seen inthe remote myocardium from 39±3.2 to 80±14.9 s-1(p<0.002), consistent with myocardial inflammation thatoccurs post infarction [4].In CABG patients the R2* signal increased: 45±7s-1 to118± 22 s-1 at 24h (p<0001). The increase in myocardialR2* values was greater than in the remote myocardium ofpatients with STEMI, but lower than the infarct zone itself(p<0.001 and p<0.05 respectively).ConclusionsUSPIO are taken up into inflamed myocardial tissue andcan be quantitatively assessed using a multi-parameterMRI acquisition protocol with optimised spatial registra-tion analysis based on a custom mutual informationalgorithm.This represents a novel imaging technique of assessingmyocardial inflammation, as well as providing a usefulresearch tool in investigating tissue inflammation.1Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UKFull list of author information is available at the end of the articleSemple et al. Journal of Cardiovascular MagneticResonance 2013, 15(Suppl 1):O114http://www.jcmr-online.com/content/15/S1/O114© 2013 Semple et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.FundingFunding was provided by the Medical Research Council,Chest Heart & Stroke Scotland, the British Heart Founda-tion and the Scottish Universities Physics Alliance.The Welcome Trust Clinical Research Facility and theClinical Research Imaging Centre are supported by NHSResearch Scotland (NRS) through NHS Lothian.Author details1Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, UK.2Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK.3Department of Cardiology, Royal Infirmary of Edinburgh, Edinburgh, UK.4Department of Vascular Surgery, Royal Infirmary of Edinburgh, Edinburgh,UK. 5Department of Radiology, Royal Infirmary of Edinburgh, Edinburgh, UK.6Department of Cardiac Surgery, Royal Infirmary of Edinburgh, Edinburgh,UK.Published: 30 January 2013doi:10.1186/1532-429X-15-S1-O114Cite this article as: Semple et al.: Quantitative myocardial inflammationassessed using a novel USPIO-Magnetic Resonance Imaging acquisitionand analysis protocol. Journal of Cardiovascular Magnetic Resonance 201315(Suppl 1):O114.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitFigure 1 Increase in R2* values in control STEMI patients (no USPIO) (blue, n=6), STEMI patients given USPIO (red, n=10) and CABG patients(green, n=32). Most significant R2* increase (and hence myocardial inflammation) observed in infarct zones, with CABG myocardial R2* increasebetween infarct and myocardium remote to infarction. The spatially registered regions of interests (ROI) for quantifying R2* value for STEMI andCABG patients are shown in the MRI images at the bottom of the figure.Semple et al. Journal of Cardiovascular MagneticResonance 2013, 15(Suppl 1):O114http://www.jcmr-online.com/content/15/S1/O114Page 2 of 2

Semple Scott

Alam Shirjel R

MacGillivray Tom J

Dweck Marc R

Shah Anoop S

Richards Jenny

Wang Chengjia

Lang Ninian

McKillop Graham

Mirsadraee Saeed

Pessotto Renzo

Zamvar Vipin

Henriksen Peter

Newby David

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Quantitative myocardial inflammation assessed using a novel USPIO-Magnetic Resonance Imaging acquisition and analysis protocol

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