Download Bright-Blood T2-Weighted MRI Has Higher Diagnostic Accuracy

Bright-Blood T2-Weighted MRI Has Higher Diagnostic
Accuracy Than Dark-Blood Short Tau Inversion Recovery
MRI for Detection of Acute Myocardial Infarction and for
Assessment of the Ischemic Area at Risk and
Myocardial Salvage
Alexander R. Payne, MBChB; Matthew Casey, BMedSci; John McClure, PhD;
Ross McGeoch, MBChB; Aengus Murphy, MBChB; Rosemary Woodward, BSc; Andrew Saul, BSc;
Xiaoming Bi, PhD; Sven Zuehlsdorff, PhD; Keith G. Oldroyd, MD(Hons), FRCP, FSCAI;
Niko Tzemos, MD(Hons), FRCP, FASE; Colin Berry, BSc, PhD, FRCP, FACC
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Background—T2-Weighted MRI reveals myocardial edema and enables estimation of the ischemic area at risk and
myocardial salvage in patients with acute myocardial infarction (MI). We compared the diagnostic accuracy of a new
bright-blood T2-weighted with a standard black blood T2-weighted MRI in patients with acute MI.
Methods and Results—A breath-hold, bright-blood T2-weighted, Acquisition for Cardiac Unified T2 Edema pulse
sequence with normalization for coil sensitivity and a breath-hold T2 dark-blood short tau inversion recovery sequence
were used to depict the area at risk in 54 consecutive acute MI patients. Infarct size was measured on gadolinium late
contrast enhancement images. Compared with dark-blood T2-weighted MRI, consensus agreements between independent observers for identification of myocardial edema were higher with bright-blood T2-weighted MRI when evaluated
per patient (P⬍0.001) and per segment of left ventricle (P⬍0.001). Compared with bright-blood T2-weighted MRI,
dark-blood T2-weighted MRI underestimated the area at risk compared with infarct size (P⬍0.001). The 95% limits of
agreement for interobserver agreements for the ischemic area at risk and myocardial salvage were wider with dark-blood
T2-weighted MRI than with bright-blood T2-weighted MRI. Bright blood enabled more accurate identification of the
culprit coronary artery with correct identification in 94% of cases compared with 61% for dark blood (P⬍0.001).
Conclusions—Bright-blood T2-weighted MRI has higher diagnostic accuracy than dark-blood T2-weighted MRI.
Additionally, dark-blood T2-weighted MRI may underestimate area at risk and myocardial salvage. (Circ Cardiovasc
Imaging. 2011;4:210-219.)
Key Words: myocardial infarction 䡲 MRI 䡲 edema 䡲 myocardial ischemia
A
purposes.8 –14 However, dark-blood T2-weighted MRI is
prone to artifact, such as from motion or from blood stasis at
the left ventricular wall leading to subendocardial bright rim
artifacts. Imaging time in the cardiac cycle15 and coil sensitivity issues, which cause signal loss with depth of field,16 can
give rise to diagnostic uncertainty with this method.
Bright-blood T2-weighted MRI techniques have recently
emerged as potential alternatives to dark-blood T2-weighted
MRI. Kellman et al17 developed a bright-blood T2-prepared,
single-shot steady-state free precession (T2-prepared SSFP)
method, which involves surface coil intensity normalization,
parallel imaging techniques, and motion-corrected averaging.
fter acute myocardial infarction (MI), ex vivo1 and in
vivo2 T2-weighted MRI enable estimation of the ischemic area at risk and myocardial salvage.3,4 T2-Weighted
imaging improves the detection of acute MI5 and enables its
discrimination from chronic MI.6 Overall, T2-weighted MRI
method has emerging potential to guide the diagnosis and
treatment of acute MI patients.7
Editorial see p 198
Clinical Perspective on p 219
Dark-blood inversion recovery T2-weighted MRI methods
are well studied and widely used for clinical and research
Received August 27, 2010; accepted March 15, 2011.
From the West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow, Scotland, United Kingdom (A.R.P., R.M., A.M., R.W.,
A.S., K.G.O., N.T., C.B.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow,
Glasgow, Scotland, United Kingdom (A.R.P., M.C., J.M., N.T., C.B.); and Cardiovascular MR R&D, Siemens Healthcare, Erlangen, Germany, (X.B.,
S.Z.).
Correspondence to Colin Berry, BSc, PhD, FRCP, FACC, BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical
Sciences 126 University Place, University of Glasgow, Glasgow, G12 8TA, Scotland, UK. E-mail [email protected]
© 2011 American Heart Association, Inc.
Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org
210
DOI: 10.1161/CIRCIMAGING.110.960450
Payne et al
Bright-Blood T2-Weighted MRI Versus Dark-Blood MRI
211
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Figure 1. A, MRI findings in a patient with acute STEMI. Matched diastolic cardiac MRI (left, cine MRI; middle left, phase-sensitive
inversion recovery image; middle right, T2-weighted ACUT2E; right, dark-blood STIR) obtained in a 66-year-old man admitted with
anterior STEMI. Pain to balloon time was 2 hours, 16 minutes. MRI was performed 15 hours after reperfusion. Anteroseptal transmural
infarction (as revealed by late gadolinium enhancement, left middle) corresponds with transmural edema revealed by both bright-blood
T2-weighted MRI (middle right) and dark-blood T2-weighted MRI (right). B, MRI findings in a 55-year-old female cigarette smoker 5
days after an acute NSTEMI. Coronary angiography 2 days earlier had revealed a culprit second obtuse marginal coronary artery that
treated medically. Cine MRI (left) revealed a lateral left ventricular wall motion abnormality. Lateral nontransmural infarction (as revealed
by late gadolinium enhancement, left middle) corresponds with transmural edema revealed by both bright-blood T2-weighted MRI (middle right) and dark-blood T2-weighted MRI (right).
Aletras et al18 developed another bright-blood T2-weighted
method, ACUT2E (Acquisition for Cardiac Unified T2 Edema),
which is a hybrid of turbo spin-echo (TSE) and SSFP. The
TSE-SSFP method has higher signal-to-noise (SNR) and
contrast-to-noise (CNR) ratio than T2-prepared SSFP.
We studied the diagnostic accuracy of bright-blood T2weighted MRI and dark-blood T2-weighted MRI method in
acute MI by analyzing paired axial left ventricular slices. Our
approach differed to that of Kellman et al,17 who used a
delayed inversion recovery fast spin-echo method. We used
the TSE-SSFP method because of its high SNR and CNR and
compared this method with a standard dark-blood short tau
inversion recovery (STIR) T2-weighted MRI method in 54
patients with acute MI.
Methods
Patient Population and Acute MI Management
Fifty-four consecutive patients who underwent invasive treatment for
acute MI at a regional cardiac center and who also had T2-weighted
MRI were analyzed. No patients were excluded because of poor
image quality. Exclusion criteria represented standard contraindications to contrast MRI, including an estimated glomerular filtration
rate ⬍30 mL/min/1.73 m2. Our MRI research in acute MI has been
approved by the West of Scotland Research Ethics Committee.
The inclusion criteria included a diagnosis of acute MI based on a
history of symptoms consistent with acute myocardial ischemia with
supporting changes on the ECG, with or without regional STsegment elevation, associated with a typical rise in troponin I
concentration.19 The culprit coronary artery was identified by coronary angiography.
Acute MI management followed contemporary guidelines.19 Aspiration thrombectomy, direct stenting, antithrombotic drugs, and
other therapies were administered according to clinical judgment.
MRI Acquisition and Analyses
MRI was performed on a Siemens MAGNETOM Avanto (Erlangen,
Germany) 1.5-T scanner with an 8-element phased-array cardiac
surface coil. The MRI protocol included SSFP cine MRI, T2weighted MRI with bright-blood ACUT2E TSE-SSFP,18 and darkblood STIR8 –12 and delayed enhancement phase-sensitive inversion
recovery sequences.20 Axial left ventricular views were sequentially
acquired with dark-blood and bright-blood T2-weighted MRI
matched to the same slice position usually at the midpapillary level.
Sample images are shown in Figure 1.
The breath-hold bright-blood TSE-SSFP (ACUT2E) incorporates
elements of the SSFP17 and TSE methods.8,17 This hybrid method,
which does not involve a T2 preparation, has an SSFP readout gated
during diastole and with a flip angle ␣ of 180°. There is a 90°
preparation followed by 180° refocusing pulses, which is similar to
TSE; however, this method is different from TSE because it involves
gradient moment nulling rather than gradient crushing. TSE-SSFP
creates a coherent train of T2-weighted spin-echos.18 Typical imaging parameters were acquisition time, 7 to 12 seconds; matrix,
192⫻192; flip angle, 180°; echo time (TE), 1.69 ms; and bandwidth,
789 Hz/pixel. Twenty-nine coherent spin-echoes (echo train length)
were obtained per heartbeat, and the time interval (echo spacing)
between the 180° inversion pulses was 3.4 ms. The trigger pulse was
2, such that data were acquired every second R-R interval. The voxel
size was 1.9⫻1.9⫻6 mm3.
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Circ Cardiovasc Imaging
May 2011
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The breath-hold black-blood T2 triple-inversion recovery pulse
sequence (STIR, 8 to 12) involves a pair of slice-selective and
nonselective 180° inversion pulses to null the blood pool signal
followed by a third inversion pulse to null the fat signal. We used an
8-element phased-array surface coil. Surface coil intensity correction
was routinely performed with prescan normalization and slicerelated shimming as appropriate to optimize dark-blood STIR
acquisition. Postprocessing surface coil intensity correction was not
performed. Typical imaging parameters were acquisition time, 8 to
13 seconds; matrix, 166⫻256; flip angle, 180°; effective echo time
(TE), 61 ms; bandwidth, 235 Hz/pixel; turbo factor, 15; and trigger
pulse, 2. The time interval between the 180° inversion pulses for
STIR was 6.74 ms. The voxel size was 2.2⫻1.4⫻8 mm3.
Microvascular obstruction (MVO) was defined as a dark zone on
early delayed enhancement imaging 1, 3, 5, and 7 minutes after
contrast injection and within an area of late gadolinium enhancement. MI was imaged using segmented phase-sensitive inversion
recovery turbo fast low-angle shot,20 starting around 7 minutes after
intravenous injection of 0.10 mmol/kg of gadoterate meglumine
(Gd2⫹-DOTA, Dotarem, Guebert SA). Typical imaging parameters
were matrix, 192⫻256; flip angle, 25°; TE, 3.36 ms; bandwidth, 130
Hz/pixel; echo spacing, 8.7 ms; and trigger pulse, 2. The voxel size
was 1.8⫻1.3⫻8 mm3.
MRI Analyses
The images were analyzed on a Siemens workstation by MRI trained
cardiologists with at least 5 years of experience. In addition, all 3
cardiologists had completed at least 2 years of full-time MRI
research in patients with acute MI, including protocols with T2weighted MRI. A fourth cardiologist independently coordinated the
images and data for the blinded analysis.
Two cardiologists who did not take part in the blinded scoring for
the presence or absence of edema performed quantitative assessments of
infarct area and area at risk as determined by both T2-weighted
methods. Left ventricular dimensions and volumes and ejection fraction
were quantified using computer-assisted planimetry.
Myocardial Edema and Standardized
Measurements of T2-Weighted Area at Risk
One bright-blood and 1 dark-blood T2-weighted MRI image acquired at the same slice position within the infarct zone were
evaluated by each cardiologist.
Hyperintense zones on T2-weighted MRI images were reviewed
independently by 3 MRI-trained cardiologists who were blinded
to the patients’ history and outcomes. Each observer scored for
the presence or absence of edema and for the position and number
of affected regions of the left ventricular slice for each patient.
Segments were defined according to the 17-segment model of the
American Heart Association.21 Disagreement was resolved by
consensus.
Quantitative assessments were performed by 2 independent observers, and their results were averaged. The jeopardized left
ventricular area at risk on each axial image was defined as the
percentage of left ventricular area delineated by the hyperintense
zone on T2-weighted images.4 The window setting was defined as
the sum of the mean myocardial signal intensity (SI) of the
unaffected area plus 2 standard deviations (SD) for this area. The
level setting was set at the mean SI of the unaffected area. This
standardized approach was based on a recent clinical validation
study.4 Myocardial tissue with a signal intensity with at least 2 SD
above the mean signal obtained in the remote noninfarcted myocardium was considered the area at risk.4 Care was taken to exclude
nonsuppressed blood pool signal because of slow flow adjacent to
the subendocardium.3
Infarct Definition and Size
The presence of acute infarction was established with MRI, based on
abnormalities in cine wall motion, rest first-pass myocardial perfusion, and delayed-enhancement imaging. In addition, supporting
changes on the ECG and coronary angiogram were also required.
Acute infarction was considered present only if myocardial
enhancement was confirmed on both the axial and long axis
acquisitions. The myocardial mass of myocardial enhancement
(grams) was quantified by a semiautomatic detection method using
an SI threshold of ⬎2 SD above a remote reference region and
expressed as a percentage of total left ventricular mass.22,23 MVO
regions were included within the infarct area.
Myocardial Salvage
Myocardial salvage, as estimated by MRI, was calculated by
subtraction of percent infarct size from percent area at risk.3,4
Biochemical Assessment of Infarct Size
Troponin I was measured (AxSYM; Abbott) as a biochemical
measure of infarct size. A blood sample was routinely obtained 12 to
24 hours after hospital admission. The troponin I protocol used in our
hospital has an upper threshold of 22.8 ␮g/L.
Angiographic Jeopardy Scores
The Lesion Score from the Alberta Provincial Project for Outcome
Assessment in Coronary Heart Disease (APPROACH)24 was used to
provide angiographic estimates of the area at risk.4 The angiograms
were analyzed by a cardiologist who was independent of the MRI
analyses.
Statistical Analyses
Normality was confirmed or excluded using the Shapiro-Francia test.
Mean (SD) values and medians (interquartile range) were calculated.
Correlations (r) between values for area at risk measured by MRI and
the APPROACH Lesion Score were tested by Pearson or Spearman
methods for normally and nonnormally distributed variables, respectively. All tests were 2-tailed. Comparisons of normally distributed
continuous data between ST-segment–MI (STEMI) and non–STsegment–MI (NSTEMI) patient groups were undertaken using a
Student t test. Between-group comparisons of nonnormally distributed data were performed with a Mann-Whitney test. Differences in
the frequencies and proportions of clinical characteristics between
patients with STEMI and NSTEMI were assessed with either a
Fisher exact test or a ␹2 test with continuity correction, as appropriate. The McNemar exact test was used to compare observer agreement for the presence of regional myocardial edema with brightblood and dark-blood T2-weighted MRI methods. The level of
agreement between area at risk and salvage estimated by brightblood and dark-blood T2-weighted MRI methods were assessed
using Bland-Altman plots and 95% limits of agreement. The 95%
limits of agreement are calculated using the mean difference
between the 2 observers plus/minus twice the standard deviation
of these differences and will contain approximately 95% of all
such differences.
Results
Patient Characteristics
Fifty-four patients with acute MI (44 (81%) STEMI) underwent MRI 2⫾2 days after initial treatment between October
1, 2009, and July 8, 2010 (Tables 1, 2, and 3). All patients had
a history of acute ischemic symptoms, acute changes on the
ECG, a typical rise in troponin I concentrations, a culprit
coronary artery identified by coronary angiography, and
typical findings on the contrast-enhanced MRI scan.
MRI Findings
The cardiac MRI findings are summarized in Tables 2, 3, 4,
and 5. All patients had MRI evidence of segmental acute MI
based on the presence of reduced wall motion and late
gadolinium enhancement in the culprit artery territory. Five
(9%) of these patients (4 STEMI, 1 NSTEMI) did not have
Payne et al
Table 1.
Bright-Blood T2-Weighted MRI Versus Dark-Blood MRI
Clinical Characteristics of Acute STEMI and NSTEMI Patients
All
(n⫽54)
Mean⫾SD age, y
Male sex, n (%)
58⫾10
38 (70)
Acute STEMI
(n⫽44, 81%)
Acute NSTEMI
(n⫽10, 19%)
P
59⫾9
58⫾12
0.79
31 (70)
7 (70)
1.00
History, n (%)
Previous MI
3 (6)
1 (2)
2 (20)
0.08
History of previous angina
7 (13)
2 (5)
2 (20)
0.15
History of PCI or CABG
0 (0)
0 (0)
0 (0)
1.00
History of chronic heart failure
1 (2)
0 (0)
1 (10)
0.18
38 (70)
33 (75)
5 (50)
0.14
2 (4)
1 (2)
1 (10)
0.34
1
46 (85)
38 (86)
8 (80)
2
5 (9)
3 (7)
2 (20)
3
3 (6)
3 (7)
0 (0)
4
0 (0)
0 (0)
0 (0)
54 (100%)
44 (100)
10 (100)
...
3.13 (2.37, 5.43)
...
History of cigarette smoking
Diabetes mellitus
Presenting characteristics
Heart failure, Killip class*
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Troponin-I elevation, n (%)
⬎upper limit of normal (threshold
for positivity) (⬎0.04 ␮g/L)
0.63
...
Cardiac catheter laboratory findings
Median (IQR) time from onset of
symptoms to primary PCI, h
Infarct-related coronary artery
Right
18 (33)
18 (41)
0 (0)
Left anterior descending
28 (52)
20 (45)
8 (80)
8 (15)
6 (14)
2 (20)
0.045
27 (50)
22 (50)
5 (50)
1.00
...
37 (10)
...
...
23 (43)
23 (52)
0 (0)
Circumflex
Multivessel coronary artery disease†
APPROACH score25
TIMI flow grade at initial angiography
0
1
4 (7)
4 (9)
0 (0)
2
6 (11)
6 (14)
0 (0)
3
21 (39)
11 (25)
10 (100)
0.001
Treatment‡
PCI
46 (85)
43 (98)
3 (30)
CABG
1 (2)
0 (0)
1 (10)
Angiography and medical therapy
7 (13)
1 (2)
6 (60)
⬍0.001
Drug therapy during hospital
admission, n (%)
Aspirin
54 (100)
44 (100)
10 (100)
1.00
Glycoprotein IIbIIIa inhibitor
42 (78)
42 (95)
0 (0)
⬍0.001
Clopidogrel
48 (89)
43 (98)
5 (50)
⬍0.001
CABG indicates coronary artery bypass surgery; IQR, interquartile range; PCI, percutaneous coronary intervention;
and TIMI, Thrombolysis In Myocardial Infarction.
*Killip classes 2 through 4 were merged, and a Fisher exact test was used to compare the between group
differences in proportions of patients in Killip class 1 versus Killip class 2 through 4.
†Multivessel coronary artery disease was defined according to the presence of 2 or more arteries with stenoses
of at least 50% of the reference vessel diameter, by visual assessment.
‡Treatment: CABG and PCI were merged and treated as 1 new variable (revascularization) and compared with
medical therapy.
213
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Circ Cardiovasc Imaging
Table 2.
May 2011
Cardiac MRI Findings
All
(n⫽54)
Acute STEMI
(n⫽44, 81%)
Acute
NSTEMI
(n⫽10, 19%)
P
50⫾12
51⫾11
47⫾15
0.44
Men
89⫾26
84⫾17
105⫾42
0.16
Women
76⫾15
76⫾17
75⫾3
0.72
Men
48⫾25
43⫾13
64⫾48
0.20
Women
35⫾15
35⫾17
35⫾1
1.0
54 (100)
44 (100)
10 (100)
LV dimensions and function, mean⫾SD
LV ejection fraction, %
End-diastolic volume index, mL/m2
2
End-systolic volume index, mL/m
Late gadolinium enhancement
Patients with evidence of late gadolinium
enhancement, n(%)*
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Patients categorized according to the No. of coronary
artery territories with late enhancement in the slice
position selected for T2-weighted MRI, n (%)
None
5 (9)
4 (9)
1 (10)
43 (80)
36 (82)
7 (70)
6 (11)
4 (9)
2 (20)
42 (78)
36 (82)
6 (60)
0.20
Mean⫾SD acute infarct size, %
24.4⫾14.9
26.1⫾15.4
16.7⫾9.3
0.02
Microvascular obstruction, n (%)
42 (78)
35 (80)
7 (70)
0.67
Single coronary artery territory
Multiple coronary artery territories
Transmural late enhancement, n (%)
1.0
LV indicates left ventricular.
*Late gadolinium enhancement within the axial slice coregistered to matched edema images; a coronary artery territory
was assigned to the left anterior descending coronary artery, a diagonal branch, the circumflex coronary artery, an obtuse
marginal artery branch or the right coronary artery.
late enhancement on the slice selected for matched T2weighted imaging. MRI images from acute MI patients are
shown in Figure 1 and 2.
Detection of Acute MI by Bright-Blood and
Dark-Blood T2-Weighted MRI
Compared with dark-blood T2-weighted STIR, complete
consensus agreement between 3 independent observers for
recognition of myocardial edema in the infarct territory
occurred in twice as many patients with bright-blood T2weighted TSE-SSFP (P⬍0.001; Table 3). When considered
per segment of left ventricle, complete consensus was found
in 85% of segments for bright blood but only 50% of
segments for dark blood (P⬍0.001). Similar differences were
found per patient and per segment when majority consensus
was used.
Bright-blood T2-weighted MRI had higher diagnostic
accuracy for acute MI (Tables 4 and 5). Similarly, brightblood T2-weighted MRI had higher diagnostic accuracy
(94%) than dark-blood T2-weighted MRI (61%) for identification of the culprit artery as revealed by coronary
angiography (P⬍0.0001; Table 4). Dark-blood STIR had
high sensitivity (96%) but weak specificity (35%) for
detecting anterior MI (Table 5).
Quantitative Assessment of Area at Risk and
Myocardial Salvage
In 19 patients (35%), the area at risk estimated using
dark-blood STIR was less than infarct size (Figure 3). The
average area at risk estimated by 2 independent observers with
dark-blood T2-weighted MRI (28.7%⫾18.6%) was less than
when measured by bright-blood T2-weighted MRI
(37.9⫾13.6%; P⫽0.004). Consequently, myocardial salvage
was also less when measured by dark-blood T2-weighted MRI
(5.0⫾20.6%) compared with when measured by bright-blood
T2-weighted MRI (13.8⫾11.2%; P⫽0.007).
For area at risk estimated by 2 independent observers
using bright-blood T2-weighted MRI, there was good
correlation between observer 1 and observer 2 (r2⫽89%).
The 95% limits of agreement were ⫺8.4% and 9.8%
(Figure 4), and there was no evidence of bias (P⫽0.29).
For area at risk estimated by STIR between these observers, there was poorer correlation (r2⫽59%), with 95%
limits of agreement being ⫺32.8 and 26.2%. There was
some evidence of bias, with observer 2 reporting a higher
area at risk (P⫽0.05).
The 95% limits of agreement for myocardial salvage
(Figure 4) estimated by 2 independent observers using
images obtained with bright-blood T2-weighted MRI were
⫺12% and 12%, respectively. There was no evidence of
bias (P⫽0.96) on Bland-Altman analysis. The 95% limits
of agreement for myocardial salvage estimated by these
observers using images obtained with dark-blood T2weighted MRI were ⫺32% and 22%, respectively. There
was evidence of bias (P⫽0.012) on Bland-Altman analysis
and the confidence intervals for the bias between the 2
observers were ⫺8.7% to ⫺1.1%.
Payne et al
Bright-Blood T2-Weighted MRI Versus Dark-Blood MRI
Table 3. Diagnostic Accuracy of Bright-Blood TSE-SSFP and
Dark-Blood T2-Weighted STIR for Detection of Myocardial
Edema in the Infarct Territory* as Independently Assessed by 3
Observers per Patient and Per Segment† of Left Ventricle
Table 4. Identification of the Culprit Coronary Artery Based on
the Presence of Regional Hyperenhancement on T2-Weighted MRI
According to the Consensus Formed by 3 Independent Observers
Dark Blood STIR MRI
Consensus agreement per patient (n⫽49 with segmental delayed enhancement)*
Full consensus
Complete agreement of all 3 observers
Bright-blood
T2-weighted MRI
Dark-Blood T2-Weighted MRI
Correct
Incorrect
P
⬍0.001
215
Culprit Artery
Territory Identified
Correct
(n⫽33)
Incorrect
(n⫽21)
Correct (n⫽51)
33
18
Incorrect (n⫽3)
51 (94%)
0
3
3 (6%)
33 (61%)
21 (39%)
P⬍0.0001
Bright-blood T2-weighted MRI
Correct
16
20
Incorrect
2
11
Majority consensus
blood STIR (33⫾18%) and ACUT2E (39⫾18%) were similar (P⫽0.2).
Correlation of Area at Risk Estimated by
T2-Weighted MRI Versus an Angiographic Score
Agreement with ⱖ2 observers
Dark-Blood T2-Weighted MRI
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Correct
Incorrect
Correct
25
21
Incorrect
1
2
Bright-blood T2-weighted MRI
⬍0.001
Consensus agreement per segment of left ventricle (n⫽96 segments with
acute MI)†
Full consensus
Complete agreement of all 3 observers
Dark-Blood T2-Weighted MRI
Correct
Incorrect
P
Bright-blood T2-weighted MRI
Correct
44
38
Incorrect
4
10
⬍0.001
Majority consensus
Agreement with ⱖ2 observers
Dark-Blood T2-Weighted MRI
Correct
Incorrect
Correct
60
33
Incorrect
3
0
Bright-blood T2-weighted MRI
⬍0.001
*The presence and location of acute infarction was established based on the
presence of reduced regional wall motion and a perfusion abnormality on first
pass associated with late gadolinium enhancement, also supported by acute
changes on the ECG and the culprit artery on coronary angiography. Based on
these criteria, there were 96 segments with evidence of acute MI including
evidence of late gadolinium enhancement in 49 patients.
†The left ventricle was segmented according to the American Heart
Association model.21
Comparison of Area at Risk Estimated by
Bright-Blood T2-Weighted MRI Versus
Dark-Blood STIR
In patients who underwent MRI ⬍2 days after MI (n⫽38),
the area at risk estimated by dark-blood STIR was less than
the area at risk estimated by ACUT2E (27⫾19% versus
37⫾12%; P⫽0.002). In patients who underwent MRI ⱖ2
days after MI (n⫽12), the areas at risk estimated by dark-
The area at risk estimated by the APPROACH Lesion Score
(Table 1) was 37⫾10%. The area at risk estimated by brightblood ACUT2E correlated reasonably well with area at risk
estimated by the APPROACH Lesion Score (r⫽0.62, P⬍0.01).
The correlations between the area at risk estimated using a
single matched axial image from the ACUT2E and STIR
methods versus the APPROACH Lesion Score and were
r⫽0.68 and 0.44, both P⬍0.01.
Bright rim artifacts occurred in 9 (17%) patients with
dark-blood T2-weighted MRI; however, these artifacts were
not associated with false-positive or false-negative results.
Discussion
The main findings of this study are that bright-blood T2weighted MRI has higher diagnostic accuracy for detection of
acute MI than dark-blood STIR, which also underestimates
the ischemic area at risk and myocardial salvage. Additionally, interobserver agreement was better with bright-blood
T2-weighted MRI.
Since T2-weighted MRI became available for use clinically,8 dark-blood2,5–14 techniques have become established
for the detection and assessment of myocardial edema.
However, diagnostic uncertainty with dark-blood T2weighted STIR (related mainly to surface coil sensitivity
problems, imaging timing and motion artifact15) has led to
alternative approaches. One development with dark-blood
STIR has been the use of the body coil instead of a chest wall
surface coil,2,13,14 at the expense of reduced SNR. Use of a
surface coil normalization algorithm may also help. More
recently, new bright-blood T2-weighted techniques with
SSFP have been developed,4,17,18 and their emergence has
stimulated us to question the comparative diagnostic accuracy
of bright-blood versus dark-blood T2-weighted MRI.
Our results extend those of Kellman et al,17 who found that
bright-blood T2-prepared SSFP had higher diagnostic accuracy than dark-blood TSE in 22 acute MI patients. We aimed
to provide further information in a larger patient cohort by
comparing another bright-blood T2-weighted method,
ACUT2E TSE-SSFP,18 with a standard black-blood TSE
method. The bright-blood ACUT2E TSE-SSFP method has
higher SNR and CNR compared with T2-prepared SSFP.17
Our study included a larger number of patients with acute
216
Circ Cardiovasc Imaging
May 2011
Table 5. Sensitivity and Specificity of Bright-Blood TSE-SSFP and Dark-Blood STIR MRI for
Detection of Anterior Versus Nonanterior MI
Bright Blood
T2-Weighted MRI
Anterior MI (n⫽28)
Nonanterior MI (n⫽26)
Anterior
Edema
Nonanterior
Edema
27
1
0
26
Dark Blood
T2-Weighted MRI
Anterior
Edema
Nonanterior
Edema
Sensitivity⫽96%
27
1
Sensitivity⫽96%
Specificity⫽100%
17
9
Specificity⫽35%
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coronary syndromes thus extending the observations by
Kellman et al17 to those with non–ST elevation MI.
The dark-blood preparation used in TSE T2-weighted
imaging introduces potential signal loss due reduced surface
coil sensitivity with depth of field and also through-plane
cardiac motion.15–16 Our results indicate that this problem
mainly affects detection of acute myocardial injury in the
basal and mid inferior as well as posterior left ventricular
walls. Indeed, dark-blood T2 STIR had reduced diagnostic
accuracy for nonanterior MI compared with anterior MI.
Another intriguing finding was that in nearly one-third of
acute MI patients, the area at risk estimated by dark-blood
T2-weighted was less than infarct size, suggesting that the
dark-blood T2-weighted may underestimate area at risk in
some patients. Interobserver agreement was better with
bright-blood T2-weighted MRI than dark-blood STIR. Because quantitative assessment of the ischemic area at risk and
myocardial salvage have emerging importance for clinical
and research purposes,3–15 our results call into question the
use of dark-blood STIR even with surface coil normalization
in acute MI patients.
Optimized timing of the TSE read-out can improve problems related to cardiac motion15; however, this is harder to
optimize at higher heart rates, especially with variation in
Figure 2. A, Dark-blood STIR (right) reveals a hyperintense area in the anterolateral left ventricular wall in a patient with inferolateral MI.
MRI findings in a patient with acute inferolateral STEMI. A 60-year-old male smoker presented with inferolateral STEMI. Primary percutaneous coronary intervention (PCI) was performed in an occluded dominant left circumflex coronary artery. The pain to balloon time
was 2 hours, 17 minutes. Coronary artery blood flow was mildly reduced (TIMI flow grade 2) at end of the PCI. Cardiac MRI was performed 19 hours after hospital admission. Inferolateral transmural infarction with MVO (as revealed by late gadolinium enhancement, left
middle) corresponds with transmural edema revealed by bright-blood T2-weighted MRI (middle right). A hyperintense zone in the
anterolateral wall on dark-blood T2-weighted MRI (right) incorrectly suggests anterior MI and involvement of the left anterior descending coronary artery. B, Inferior MI that is not apparent with dark-blood STIR (right). A 52-year-old obese male smoker presented with
inferior STEMI. Coronary angiography revealed a distal occlusion of his right coronary artery. The pain to balloon time was 83 minutes.
MRI was performed 14 hours after hospital admission. Inferior nontransmural infarction with MVO (as revealed by late gadolinium
enhancement, left middle) corresponds with transmural edema revealed by bright-blood T2-weighted MRI (middle right) but not by
dark-blood T2-weighted MRI (right). C, Subendocardial bright rim artifact with dark-blood STIR. A 48-year-old male smoker presented
with an anterior STEMI and underwent primary PCI in the culprit left anterior descending coronary artery. MRI was performed 14 hours
after hospital admission and revealed anteroseptal transmural infarction with MVO (as revealed by late gadolinium enhancement, left
middle) corresponds with transmural edema revealed by both bright-blood T2-weighted MRI (middle right) and dark-blood T2-weighted
MRI (right). An anterior subendocardial bright rim artifact is present in the dark-blood STIR image.
Payne et al
Bright-Blood T2-Weighted MRI Versus Dark-Blood MRI
217
For the edema image analyses to enable estimation of the
area at risk, we adopted a standardized approach for window
and level intensity settings that had been previously worked
out in an earlier clinical validation study.4 Standardized
window and level settings were based on the signal intensity
of normal (remote myocardium) and a signal intensity difference of 2 SD was used to discriminate affected (hyperintense)
myocardium from unaffected zones.
Single-shot T2-prepared SSFP can be acquired during free
breathing and multiple images may be motion-corrected and
averaged to enhance the SNR. This method provides a
uniform proton density field map and can be used for T2
mapping to measure absolute values of T2 in the heart.
T2-prepared SSFP is an attractive alternative method for
bright-blood edema imaging.17 In the future, quantitative T2
mapping could help to improve detection of regional myocardial edema compared with visual assessment alone.25
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Limitations
Figure 3. Scatterplots with lines of identity for the relationships
between infarct size measured by MRI versus area at risk
derived with A, bright-blood T2-weighted MRI, and B, darkblood T2-weighted MRI. Average values of area at risk were
obtained from measurements from 2 independent observers.
Because infarct size is physiologically a subset of the area at
risk, the expected relationship between area at risk and infarct
size involves all points at or below the line of identity. This is so
for all cases with bright-blood T2-weighted MRI but only 35
(65%) of cases with dark-blood T2-weighted MRI (P⬍0.001,
Fisher exact test).
R-R intervals. Furthermore, timing optimization complicates
the examination. Motion tracking can further improve image
quality.16
Subendocardial rim artifacts have the potential to be
problematic in acute MI patients because of reduced regional
wall motion, particularly at the left ventricular apex. We
found that bright rim artifacts were fairly common. We also
found that the presence of these artifacts was not associated
with diagnostic accuracy. This could be because the observers
were able to correctly discriminate bright rim artifacts from
edema. It is also possible that meticulous slice-related shimming during dark-blood STIR acquisition reduced their
intensity.
We aimed to use the T2-weighted MRI methods in a way
that closely reflected standard (usual) clinical practice. Therefore, we used the methods as set-up to be used on our scanner.
Furthermore, there are other differences inherent to these
methods (eg, different spatial resolutions) that we chose to
accept rather than modify. For example, shimming was not
routinely used with the ACUT2E method, whereas shimming
is standard practice for image optimization with STIR. Also,
breath-hold duration is shorter with the ACUT2E method
than with STIR, and, because long breath-holds are associated with reduced image quality, this could be one other
source of differences in image quality. Again, we did not
attempt to alter breath-hold durations. Rather, we accepted
the methods as set on the scanner.
Because of time constraints when imaging our acute MI
patients, we focused on 2 T2-weighted MRI methods. All
patients had evidence of late gadolinium enhancement, but 5
of these patients did not have late enhancement in the image
position that had been selected for T2-weighted MRI. This
can be explained by the fact that T2-weighted MRI was
obtained in the culprit area of injured myocardium revealed
by reduced wall motion but before gadolinium contrast
administration. Therefore, the T2 MRI acquisitions in these 5
patients can be interpreted as having been acquired in a
territory of noninfarcted but injured myocardium evidenced
by wall motion and edema.
Coil sensitivity corrections with the ACUT2E method may
be imperfect because of nonuniform proton density field map.
Furthermore, neither ACUT2E nor STIR can be used for T2
mapping and, like STIR, ACUT2E is dependent on subjective
image interpretation.
T2-Dark-blood STIR had lower sensitivity in accurately
identifying the area at risk in patients with acute coronary
syndrome. Whether the addition of coil profile normalization
and/or T2 mapping could have improved its accuracy has not
been addressed in this study.
We suggest that the addition of complicated algorithms to
resolve a potential weakness of a test complicates rather than
facilitates the clinical applicability and appeal of the diagnostic method.
For several reasons, it has not been possible to estimate
CNR and SNR in our analysis. The STIR method does not
compensate for coil sensitivity variation across the imaging
plane and because TSE methods are sensitive to motion, T2
signal differences may arise between injured (reduced motion) and uninjured (normal motion) myocardium in addition
to contributions from T2 differences related to myocardial
edema. Noise measurements are not incorporated in the
ACUT2E method, and retrospective measurements are not
possible with parallel imaging because noise values may be
variable across the field of view.
Because all of the patients in our cohort had a confirmed
diagnosis of acute MI, the study design only permits an
evaluation of the sensitivity and not the specificity of the
218
Circ Cardiovasc Imaging
May 2011
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Figure 4. Bland-Altman plots for A, area
at risk, and B, salvage in 54 acute MI
subjects revealed by bright-blood
T2-weighted MRI (upper row) and darkblood T2-weighted MRI (lower row) measured by 2 independent observers. The
95% limits of agreement for area at risk
estimation using images obtained with
bright-blood T2-weighted MRI were
⫺8.5% and 9.9%, respectively. There
was no evidence of bias (P⫽0.29) on
Bland-Altman analysis. The 95% limits of
agreement for area at risk estimation
using images obtained with dark-blood
T2-weighted MRI were ⫺33% and 26%,
respectively. There was no evidence of
bias (P⫽0.113) on Bland-Altman analysis. The 95% limits of agreement for
myocardial salvage estimation using
images obtained with bright-blood
T2-weighted MRI were ⫺12% and 12%,
respectively. There was no evidence of
bias (P⫽0.9) on Bland-Altman analysis.
The 95% limits of agreement for myocardial salvage estimation using images
obtained with dark-blood T2-weighted
MRI were ⫺33% and 23%, respectively.
There was evidence of bias (P⫽0.012)
on Bland-Altman analysis.
methods. Our results demonstrate that bright-blood MRI
increases the rate of detection of acute MI cases therefore
raising sensitivity. Although our results do not provide
definitive information on whether or not bright-blood T2weighted MRI might raise the rate of falsely reporting edema
in patients without acute MI (ie, reducing specificity), the fact
that uninjured segments from myocardium remote from the
injured culprit artery territory were also included in our
analysis provides some reassurance that this may not be the
case.
Anticipated Value
Our findings indicate that the diagnostic utility of dark-blood
STIR has some limitations when used in patients with known
or suspected acute MI. Based on our findings, bright-blood
T2-weighted MRI appears to have acceptable diagnostic
utility.
Acknowledgments
We thank the staff in the Imaging Centre in the Golden Jubilee
National Hospital, and in particular Jennifer Gilchrist and Carolyn
Clark. We also thank the staff in the Cardiac Catheterization
Laboratories and Coronary Care Unit in our hospital. We acknowledge the excellent technical support from Ms Christie McComb and
Dr John Foster, Department of Medical Physics, Greater Glasgow
and Clyde Health Board. We gratefully acknowledge the support of
Dr Patrick Revell and Dr Craig Buckley from MR R&D, Siemens
Healthcare, UK.
Sources of Funding
Dr Berry holds a Senior Fellowship from the Scottish Funding
Council. This research was supported by a grant from the Chief
Scientist Office, Scottish Health Department.
Disclosures
Drs Bi and Zuehlsdorff are employees of Siemens Healthcare, the
manufacturer of the MRI scanner and pulse sequences used in
this study.
References
1. Garcia-Dorado D, Oliveras J, Gili J, Sanz E, Perezvilla F, Barrabes J,
Carreras MJ, Solares J, Soler-Soler J. Analysis of myocardial edema by
magnetic-resonance-imaging early after coronary-artery occlusion with or
without reperfusion. Cardiovasc Res. 1993;27:1462–1469.
2. Aletras AH, Tilak GS, Natanzon A, Hsu LY, Gonzalez FM, Hoyt RF Jr,
Arai AE. Retrospective determination of the area at risk for reperfused
acute myocardial infarction with T2-weighted cardiac magnetic resonance imaging: histopathological and displacement encoding with stimulated echoes (DENSE) functional validations. Circulation. 2006 18;113:
1865–1870.
3. Friedrich MG, Abdel-Aty H, Taylor A, Schulz-Menger J, Messroghli D,
Dietz R. The salvaged area at risk in reperfused acute myocardial
infarction as visualized by cardiovascular magnetic resonance. J Am Coll
Cardiol. 2008;51:1581–1587.
4. Berry C, Kellman P, Mancini C, Chen MY, Bandettini WP, Lowrey T,
Hsu LY, Aletras AH, Arai AE. Magnetic resonance imaging delineates
the ischemic area-at-risk and myocardial salvage in patients with acute
myocardial infarction. Circ Cardiovasc Imaging. 2010;3:527–535.
5. Cury RC, Shash K, Nagurney JT, Rosito G, Shapiro MD, Nomura CH,
Abbara S, Bamberg F, Ferencik M, Schmidt EJ, Brown DF, Hoffmann U,
Brady TJ. Cardiac magnetic resonance with T2-weighted imaging
improves detection of patients with acute coronary syndrome in the
emergency department. Circulation. 2008;118:837– 844.
6. Abdel-Aty H, Zagrosek A, Schulz-Menger J, Taylor AJ, Messroghli D,
Kumar A, Gross M, Dietz R, Friedrich MG. Delayed enhancement and
T2-weighted cardiovascular magnetic resonance imaging differentiate
acute from chronic myocardial infarction. Circulation. 2004;109:
2411–2416.
7. Friedrich MG. Myocardial edema: a new clinical entity? Nat Rev Cardiol.
2010;7:292–296.
Payne et al
Bright-Blood T2-Weighted MRI Versus Dark-Blood MRI
Downloaded from http://circimaging.ahajournals.org/ by guest on May 11, 2017
8. Simonetti OP, Finn JP, White RD, Laub G, Henry DA. “Black blood”
T2-weighted inversion-recovery MR imaging of the heart. Radiology.
1996;199:49 –57.
9. Francone M, Bucciarelli-Ducci C, Carbone I, Canali E, Scardala R,
Calabrese FA, Sardella G, Mancone M, Catalano C, Fedele F, Passariello
R, Bogaert J, Agati L. Impact of primary coronary angioplasty delay on
myocardial salvage, infarct size, and microvascular damage in patients
with ST-segment elevation myocardial infarction: insight from cardiovascular magnetic resonance. J Am Coll Cardiol. 2009;54:2145–2153.
10. O’Regan DP, Ahmed R, Neuwirth C, Tan Y, Durighel G, Hajnal JV,
Nadra I, Corbett SJ, Cook SA. Cardiac MRI of myocardial salvage at the
peri-infarct border zones after primary coronary intervention. Am J
Physiol Heart Circ Physiol. 2009;297:H340 –H346.
11. Ganame J, Messalli G, Dymarkowski S, Rademakers FE, Desmet W, Van
de Werf F, Bogaert J. Impact of myocardial haemorrhage on left ventricular function and remodelling in patients with reperfused acute myocardial infarction. Eur Heart J. 2009;30:1440 –1449.
12. Raman SV, Simonetti OP, Winner MW III, Dickerson JA, He X, Mazzaferri EL Jr, Ambrosio G. Cardiac magnetic resonance with edema
imaging identifies myocardium at risk and predicts worse outcome in
patients with non-ST-segment elevation acute coronary syndrome. J Am
Coll Cardiol. 2010;55:2480 –2488.
13. Larose E, Rodés-Cabau J, Pibarot P, Rinfret S, Proulx G, Nguyen CM,
Déry JP, Gleeton O, Roy L, Noël B, Barbeau G, Rouleau J, Boudreault
JR, Amyot M, De Larochellière R, Bertrand OF. Predicting late myocardial recovery and outcomes in the early hours of ST-segment elevation
myocardial infarction traditional measures compared with microvascular
obstruction, salvaged myocardium, and necrosis characteristics by cardiovascular magnetic resonance. J Am Coll Cardiol. 2010;55:2459 –2469.
14. Eitel I, Desch S, Fuernau G, Hildebrand L, Gutberlet M, Schuler G,
Thiele H. Prognostic significance and determinants of myocardial salvage
assessed by cardiovascular magnetic resonance in acute reperfused myocardial infarction. J Am Coll Cardiol. 2010;55:2470 –2479.
15. Wince WB, Kim RJ. Molecular imaging: T2-weighted CMR of the area
at risk: a risky business? Nature Rev Cardiol. 2010;7:547–549.
16. Keegan J, Gatehouse PD, Prasad SK, Firmin DN. Improved turbo spin
echo imaging of the heart with motion-tracking. J Magn Reson Imaging.
2006;24:563–570.
219
17. Kellman P, Aletras AH, Mancini C, McVeigh ER, Arai AE. T2-prepared
SSFP improves diagnostic confidence in edema imaging in acute myocardial infarction compared to turbo spin echo. Magn Reson Med. 2007;
57:891– 897.
18. Aletras AH, Kellman P, Derbyshire JA, Arai AE. ACUT2E TSE-SSFP: a
hybrid method for T2-weighted imaging of edema in the heart. Magn
Reson Med. 2008;59:229 –235.
19. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M,
Hochman JS, Krumholz HM, Krushner FG, Lamas GA. ACC-AHA
guidelines for the management of patients with ST-elevation myocardial
infarction. J Am Coll Cardiol. 2004;44:E1–E211.
20. Kellman P, Arai AE, McVeigh ER, Aletras AH. Phase-sensitive inversion
recovery for detecting myocardial infarction using gadolinium-delayed
hyperenhancement. Magn Reson Med. 2002;47:372–383.
21. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey
WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS. Standardized
myocardial segmentation and nomenclature for tomographic imaging of
the heart: a statement for healthcare professionals from the Cardiac
Imaging Committee of the Council on Clinical Cardiology of the
American Heart Association. Circulation. 2002;105:539 –542.
22. McGeoch R, Watkins S, Steedman T, Berry C, Davie A, Byrne J, Hillis
WS, Lindsay MM, Robb SD, Dargie HJ, Oldroyd KG. The index of
microvascular resistance measured acutely predicts the severity and
nature of myocardial Infarction in patients with ST segment elevation
myocardial infarction. J Am Coll Cardiol Cardiovasc Interv. 2010;3:
715–722.
23. Weir RA, Murphy CA, Petrie CJ, Martin TN, Balmain S, Clements S,
Steedman T, Wagner GS, Dargie HJ, McMurray JJV. Microvascular
obstruction remains a portent of adverse remodeling in optimally-treated
patients with left ventricular systolic dysfunction after acute myocardial
infarction. Circ Imaging. 2010;3:360 –367.
24. Graham MM, Faris PD, Ghali WA, Galbraith PD, Norris CM, Badry JT,
Mitchell LB, Curtis MJ, Knudtson ML, APPROACH Investigators
(Alberta Provincial Project for Outcome Assessment in Coronary Heart
Disease). Validation of three myocardial jeopardy scores in a population
based cardiac catheterization cohort. Am Heart J. 2001;142:254 –261.
25. Giri S, Chung YC, Merchant A, Mihai G, Rajagopalan S, Raman SV,
Simonetti OP. T2 quantification for improved detection of myocardial
edema. J Cardiovasc Magn Reson. 2009;11:56.
CLINICAL PERSPECTIVE
T2-weighted MRI has diagnostic and clinical utility for detecting myocardial edema in patients with known or suspected
acute myocardial infarction. T2-weighted MRI also enables estimation of the ischemic area at risk and myocardial salvage
in patients with acute myocardial infarction. The T2-weighted MRI method that is most widely used is dark-blood short
tau inversion recovery (STIR). However, dark-blood STIR is prone to artifact from motion, subendocardial blood stasis,
and technical issues with scan timing or surface coil sensitivity. All of these problems with dark-blood STIR may contribute
to diagnostic uncertainty with this method. Based on recent technical developments, an alternative bright-blood
T2-weighted MRI approach has emerged. Therefore, we compared the diagnostic accuracy of a new bright-blood
T2-weighted MRI method with standard dark-blood STIR in patients with acute myocardial infarction. We found that
compared with dark-blood STIR, bright-blood T2-weighted MRI was associated with higher consensus agreements
between observers for identification of myocardial edema and a higher rate of detection of the culprit coronary artery. The
dark-blood method also underestimated the area at risk compared with infarct size. Our results support the use of
bright-blood T2-weighted MRI instead of STIR for the assessment of myocardial edema.
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Bright-Blood T2-Weighted MRI Has Higher Diagnostic Accuracy Than Dark-Blood Short
Tau Inversion Recovery MRI for Detection of Acute Myocardial Infarction and for
Assessment of the Ischemic Area at Risk and Myocardial Salvage
Alexander R. Payne, Matthew Casey, John McClure, Ross McGeoch, Aengus Murphy,
Rosemary Woodward, Andrew Saul, Xiaoming Bi, Sven Zuehlsdorff, Keith G. Oldroyd, Niko
Tzemos and Colin Berry
Circ Cardiovasc Imaging. 2011;4:210-219; originally published online March 22, 2011;
doi: 10.1161/CIRCIMAGING.110.960450
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