Intramyocardial hemorrhage commonly occurs in large reperfused myocardial infarctions. However, its long-term fate remains unexplored. We hypothesized that acute reperfusion intramyocardial hemorrhage leads to chronic iron deposition

Cokic, Ivan

Dharmakumar, Rohan

Friedrich, Matthias G

Kali, Avinash

Kumar, Andreas

Tang, Richard

Tsaftaris, Sotirios A.

Journal of Cardiovascular Magnetic Resonance

English

PubMed

Kali Avinash

Cokic Ivan

Kumar Andreas

Tsaftaris Sotirios

Tang Richard L

Friedrich Matthias G

Dharmakumar Rohan

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Acute reperfusion intramyocardial hemorrhage leads to regional chronic iron deposition in the heart

IMT Institutional Repository

POSTER PRESENTATION Open AccessAcute reperfusion intramyocardial hemorrhageleads to regional chronic iron deposition in theheartAvinash Kali1,2*, Ivan Cokic1, Andreas Kumar3, Sotirios Tsaftaris4, Richard L Tang1, Matthias G Friedrich5,6,Rohan Dharmakumar1From 16th Annual SCMR Scientific SessionsSan Francisco, CA, USA. 31 January - 3 February 2013BackgroundIntramyocardial hemorrhage commonly occurs in largereperfused myocardial infarctions. However, its long-termfate remains unexplored. We hypothesized that acutereperfusion intramyocardial hemorrhage leads to chroniciron deposition.MethodsFifteen patients (mean age = 58±8 years; 3 women), whounderwent successful angioplasty for first STEMI, wererecruited following informed consent. CardiovascularMagnetic Resonance (CMR) imaging (1.5T) was performedon day 3 and month 6 post-angioplasty. 2D T2* maps (6TEs = 2.6-13.7 ms; ΔTE=2.2ms) and Late GadoliniumEnhancement (LGE) images of the entire left ventricle(LV) were acquired. Threshold-based image analysis wasperformed to identify remote, hemorrhagic (Hemo+) andnon-hemorrhagic (Hemo-) myocardium.Fourteen canines, subjected to ischemia-reperfusion (I-R)injury (3 hours of LAD occlusion followed by reperfusion),underwent CMR (1.5T) on days 3 and 56 post-I-R injury.Three sham-operated animals (Shams) were also studiedusing CMR at similar time points. 2D T2* maps (6 TEs =3.4-18.4 ms; ΔTE=3.0ms) and LGE images of the entire LVwere acquired. Threshold-based image analysis was per-formed to identify remote, Hemo+ and Hemo- myocar-dium. Subsequently, animals were euthanized (day 56),hearts were excised and imaged ex-vivo. Sections of Hemo+, Hemo-, remote and Sham myocardium were isolatedand histology was performed. The concentration of iron([Fe]) within each type of tissue was measured using massspectrometry.ResultsSix months post-angioplasty, mean T2* of the scar tissuein patients with Hemo+ infarctions (n=11 as determinedby T2* losses within the infarct on day 3 CMR; Figure 1)was 40% lower than that of remote myocardium, suggest-ing chronic iron deposition (p<0.001). In contrast, meanT2* of Hemo- infarctions (n=4) was not significantlydifferent from that of remote myocardium at both 3 daysand 6 months post-angioplasty (p=0.51).In canines, in-vivo mean T2* of Hemo+ myocardiumwas 40% lower than those of Sham, remote and Hemo-myocardium (p<0.001) at both 3 days and 56 days post-I-Rinjury (Figure 2B). Similarly, mean ex-vivo T2* of Hemo+myocardium was 40% lower than those of Sham, remote1Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, LosAngeles, CA, USAFull list of author information is available at the end of the articleFigure 1 Patient Studies - Representative CMR images (A; acquiredfrom a 42-year old patient following successful angioplasty for firstSTEMI) with significant T2* loss (arrows) at the site of acute andchronic myocardial infarction (identified by LGE imaging, arrows) areshown. Mean T2* of Hemo+ (B) was 40% lower than that of Hemo-and remote myocardium (p<0.001) on both acute and chronic CMRstudies.Kali et al. Journal of Cardiovascular MagneticResonance 2013, 15(Suppl 1):P174http://www.jcmr-online.com/content/15/S1/P174© 2013 Kali 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.and Hemo- myocardium (p<0.001; Figure 2C). Perl’s stainconfirmed localized chronic iron deposition only withinHemo+ infarctions. Mean [Fe] of Hemo+ infarctions wasnearly 10-fold higher than those of Sham, remote andHemo- myocardium (p<0.001; Figure 2D). A strong linearrelationship was observed between log(ex-vivo T2*) and-log([Fe]) (R2=0.7; p<0.001; Figure 2E).ConclusionsAcute reperfusion intramyocardial hemorrhage leads toregional chronic iron deposition within the infarctzones. T2* CMR can accurately characterize localizedchronic iron deposition following reperfusion-inducedmyocardial hemorrhage. The clinical significance of thisfinding remains to be investigated.FundingThis work was supported in part by grants from Ameri-can Heart Association (SDG 0735099N) and NationalHeart, Lung, And Blood Institute (HL091989).Author details1Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, LosAngeles, CA, USA. 2Department of Biomedical Engineering, University ofCalifornia, Los Angeles, CA, USA. 3Quebec Heart & Lung Institute, LavalUniversity, Quebec City, QC, Canada. 4Department of Computer Science andApplications, IMT Institutions, Lucca, Italy. 5Montréal Heart Institute, Universitéde Montréal, Montréal, QC, Canada. 6Stephenson CMR Center, University ofCalgary, Calgary, AB, Canada.Published: 30 January 2013doi:10.1186/1532-429X-15-S1-P174Cite this article as: Kali et al.: Acute reperfusion intramyocardialhemorrhage leads to regional chronic iron deposition in the heart.Journal of Cardiovascular Magnetic Resonance 2013 15(Suppl 1):P174.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 2 Animal Studies -Representative CMR images (A; T2* in thetop row and LGE in the bottom row) acquired from an animal withhemorrhagic myocardial infarction in acute and chronic phasesalong the long- and short-axis (along the dashed red line in thelong-axis images), together with corresponding ex-vivo images areshown (A). In-vivo T2* images (both acute and chronic phases)clearly demonstrate the evidence of signal loss in the LAD territory.Both mean in-vivo T2* (B) and ex-vivo T2* (C) of Hemo+ sectionswere 40% lower than those of Shams, Remote, and Hemo- in bothacute and chronic phases (p<0.001). Mass spectrometric analysis (D)showed that iron content of Hemo+ tissue was 10-fold higher thanthat of other tissues (p<0.001). Linear regression analysis (E)between log(ex-vivo T2*) and -log([Fe]) showed a strong correlation(R2 = 0.74; p<0.001).Kali et al. Journal of Cardiovascular MagneticResonance 2013, 15(Suppl 1):P174http://www.jcmr-online.com/content/15/S1/P174Page 2 of 2

Avinash Kali

Ivan Cokic

Andreas Kumar

Sotirios Tsaftaris

Richard L Tang

Matthias G Friedrich

Rohan Dharmakumar

Crossref

Springer - Publisher Connector

POSTER PRESENTATION Open Access
Acute reperfusion intramyocardial hemorrhage
leads to regional chronic iron deposition in the
heart
Avinash Kali1,2*, Ivan Cokic1, Andreas Kumar3, Sotirios Tsaftaris4, Richard L Tang1, Matthias G Friedrich5,6,
Rohan Dharmakumar1
From 16th Annual SCMR Scientific Sessions
San Francisco, CA, USA. 31 January - 3 February 2013
Background
Intramyocardial hemorrhage commonly occurs in large
reperfused myocardial infarctions. However, its long-term
fate remains unexplored. We hypothesized that acute
reperfusion intramyocardial hemorrhage leads to chronic
iron deposition.
Methods
Fifteen patients (mean age = 58±8 years; 3 women), who
underwent successful angioplasty for first STEMI, were
recruited following informed consent. Cardiovascular
Magnetic Resonance (CMR) imaging (1.5T) was performed
on day 3 and month 6 post-angioplasty. 2D T2* maps (6
TEs = 2.6-13.7 ms; ΔTE=2.2ms) and Late Gadolinium
Enhancement (LGE) images of the entire left ventricle
(LV) were acquired. Threshold-based image analysis was
performed to identify remote, hemorrhagic (Hemo+) and
non-hemorrhagic (Hemo-) myocardium.
Fourteen canines, subjected to ischemia-reperfusion (I-R)
injury (3 hours of LAD occlusion followed by reperfusion),
underwent CMR (1.5T) on days 3 and 56 post-I-R injury.
Three sham-operated animals (Shams) were also studied
using CMR at similar time points. 2D T2* maps (6 TEs =
3.4-18.4 ms; ΔTE=3.0ms) and LGE images of the entire LV
were acquired. Threshold-based image analysis was per-
formed to identify remote, Hemo+ and Hemo- myocar-
dium. Subsequently, animals were euthanized (day 56),
hearts were excised and imaged ex-vivo. Sections of Hemo
+, Hemo-, remote and Sham myocardium were isolated
and histology was performed. The concentration of iron
([Fe]) within each type of tissue was measured using mass
spectrometry.
Results
Six months post-angioplasty, mean T2* of the scar tissue
in patients with Hemo+ infarctions (n=11 as determined
by T2* losses within the infarct on day 3 CMR; Figure 1)
was 40% lower than that of remote myocardium, suggest-
ing chronic iron deposition (p<0.001). In contrast, mean
T2* of Hemo- infarctions (n=4) was not significantly
different from that of remote myocardium at both 3 days
and 6 months post-angioplasty (p=0.51).
In canines, in-vivo mean T2* of Hemo+ myocardium
was 40% lower than those of Sham, remote and Hemo-
myocardium (p<0.001) at both 3 days and 56 days post-I-R
injury (Figure 2B). Similarly, mean ex-vivo T2* of Hemo+
myocardium was 40% lower than those of Sham, remote
1Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los
Angeles, CA, USA
Full list of author information is available at the end of the article
Figure 1 Patient Studies - Representative CMR images (A; acquired
from a 42-year old patient following successful angioplasty for first
STEMI) with significant T2* loss (arrows) at the site of acute and
chronic myocardial infarction (identified by LGE imaging, arrows) are
shown. Mean T2* of Hemo+ (B) was 40% lower than that of Hemo-
and remote myocardium (p<0.001) on both acute and chronic CMR
studies.
Kali et al. Journal of Cardiovascular Magnetic
Resonance 2013, 15(Suppl 1):P174
http://www.jcmr-online.com/content/15/S1/P174
© 2013 Kali 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.
and Hemo- myocardium (p<0.001; Figure 2C). Perl’s stain
confirmed localized chronic iron deposition only within
Hemo+ infarctions. Mean [Fe] of Hemo+ infarctions was
nearly 10-fold higher than those of Sham, remote and
Hemo- myocardium (p<0.001; Figure 2D). A strong linear
relationship was observed between log(ex-vivo T2*) and
-log([Fe]) (R2=0.7; p<0.001; Figure 2E).
Conclusions
Acute reperfusion intramyocardial hemorrhage leads to
regional chronic iron deposition within the infarct
zones. T2* CMR can accurately characterize localized
chronic iron deposition following reperfusion-induced
myocardial hemorrhage. The clinical significance of this
finding remains to be investigated.
Funding
This work was supported in part by grants from Ameri-
can Heart Association (SDG 0735099N) and National
Heart, Lung, And Blood Institute (HL091989).
Author details
1Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los
Angeles, CA, USA. 2Department of Biomedical Engineering, University of
California, Los Angeles, CA, USA. 3Quebec Heart & Lung Institute, Laval
University, Quebec City, QC, Canada. 4Department of Computer Science and
Applications, IMT Institutions, Lucca, Italy. 5Montréal Heart Institute, Université
de Montréal, Montréal, QC, Canada. 6Stephenson CMR Center, University of
Calgary, Calgary, AB, Canada.
Published: 30 January 2013
doi:10.1186/1532-429X-15-S1-P174
Cite this article as: Kali et al.: Acute reperfusion intramyocardial
hemorrhage leads to regional chronic iron deposition in the heart.
Journal of Cardiovascular Magnetic Resonance 2013 15(Suppl 1):P174.
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 2 Animal Studies -Representative CMR images (A; T2* in the
top row and LGE in the bottom row) acquired from an animal with
hemorrhagic myocardial infarction in acute and chronic phases
along the long- and short-axis (along the dashed red line in the
long-axis images), together with corresponding ex-vivo images are
shown (A). In-vivo T2* images (both acute and chronic phases)
clearly demonstrate the evidence of signal loss in the LAD territory.
Both mean in-vivo T2* (B) and ex-vivo T2* (C) of Hemo+ sections
were 40% lower than those of Shams, Remote, and Hemo- in both
acute and chronic phases (p<0.001). Mass spectrometric analysis (D)
showed that iron content of Hemo+ tissue was 10-fold higher than
that of other tissues (p<0.001). Linear regression analysis (E)
between log(ex-vivo T2*) and -log([Fe]) showed a strong correlation
(R2 = 0.74; p<0.001).
Kali et al. Journal of Cardiovascular Magnetic
Resonance 2013, 15(Suppl 1):P174
http://www.jcmr-online.com/content/15/S1/P174
Page 2 of 2


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Acute reperfusion intramyocardial hemorrhage leads to regional chronic iron deposition in the heart

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