Integration of Infarct Size, Tissue Perfusion, and

Metabolism by Hybrid Cardiac Positron Emission

Tomography/Computed Tomography
Evaluation in a Porcine Model of Myocardial Infarction
Riikka Lautamäki, MD, PhD; Karl H. Schuleri, MD; Tetsuo Sasano, MD; Mehrbod S. Javadi, MD;
Amr Youssef, MD; Jennifer Merrill, MSc; Stephan G. Nekolla, PhD; M. Roselle Abraham, MD;
Albert C. Lardo, PhD; Frank M. Bengel, MD

Background—Hybrid positron emission tomography/computed tomography (PET-CT) allows for combination of PET
perfusion/metabolism imaging with infarct detection by CT delayed contrast enhancement. We used this technique to
obtain biomorphological insights into the interrelation between tissue damage, inflammation, and microvascular
obstruction early after myocardial infarction.
Methods and Results—A porcine model of left anterior descending coronary artery occlusion/reperfusion was studied.
Seven animals underwent PET-CT within 3 days of infarction, and a control group of 3 animals was scanned at ⬎4
weeks. Perfusion and glucose uptake were assessed by [13N]-ammonia/[18F]-deoxyglucose (FDG), and 64-slice CT
delayed contrast enhancement was measured. In the acute infarct model, CT revealed a no-reflow phenomenon
suggesting microvascular obstruction in 80% of all infarct segments. PET showed increased FDG uptake in 68% of the
CT-defined infarct segments. Ex vivo staining and histology showed active inflammation in the acute infarct area as an
explanation for increased glucose uptake. In chronic infarction, CT showed no microvascular obstruction and agreed
well with matched perfusion/metabolism defects on PET.
Conclusions—Perfusion/metabolism PET and delayed enhancement CT can be combined within a single hybrid PET-CT
session. Increased regional FDG uptake in the acute infarct area is frequently observed. In contrast to the chronic infarct
setting, this indicates tissue inflammation that is commonly associated with microvascular obstruction as identified by
Downloaded from http://ahajournals.org by on January 11, 2022

no reflow on CT. The consequences of these pathophysiological findings for subsequent ventricular remodeling should
be explored in further studies. (Circ Cardiovasc Imaging. 2009;2:299-305.)
Key Words: myocardial infarction 䡲 hybrid imaging 䡲 PET 䡲 CT

I nfarct size and tissue viability are related to outcome after

myocardial infarction, and noninvasive imaging is being
used for risk stratification in this setting.1 Contrast-enhanced
PET-CT environment, where it can be combined with PET-
derived biological information.12

MRI (ceMRI) has been successfully used to identify location,

extent, and transmurality of myocardial infarction via delayed
enhancement.2 It has also been used to detect microvascular
obstruction by a no-reflow pattern of absent enhancement.3
Results of ceMRI have been linked to patient prognosis,4 and
they are used to predict functional recovery after revascular-
ization.5,6 More recently, multidetector CT has been used to
measure delayed contrast enhancement in a manner similar to
ceMRI. This technique has been validated against MRI and
against ex vivo measurements of infarct size.7–11 Although
there is less clinical experience with multidetector CT than
with ceMRI, it is a technique that can be used in the hybrid
Clinical Perspective on p 305
PET is still considered a gold standard for clinical evalu-
ation of myocardial viability.13,14 In chronic ischemic heart
disease, the metabolic tracer [18F]-deoxyglucose (FDG) dis-
tinguishes ischemically compromised but viable “hibernating
myocardium,” which shows increased myocardial glucose
uptake in a hypoperfused region from nonviable scar that
shows a matched reduction of perfusion and metabolism.15
The situation, however, is less clear in the setting of acute
infarction. Early after reperfusion, tissue inflammation may
occur. This may result in increased regional glucose uptake,
and a pattern similar to hibernating myocardium may be

Received December 30, 2008; accepted April 13, 2009.

From the Department of Radiology (R.L. M.S.J., J.M., F.M.B.), Division of Nuclear Medicine, the Department of Medicine (K.H.S., T.S., A.Y., R.A.,
A.C.L.), Division of Cardiology, and the Department of Biomedical Engineering (A.C.L.), Johns Hopkins Medical Institutions, Baltimore, Md, and
Nuklearmedizinische Klinik und Poliklinik (S.G.N.), Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Correspondence to Frank M. Bengel, MD, Division of Nuclear Medicine, Johns Hopkins University, 601 N Caroline St, JHOC 3225, Baltimore, MD
21210. E-mail fbengel1@jhmi.edu
© 2009 American Heart Association, Inc.
Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org DOI: 10.1161/CIRCIMAGING.108.846253

299
 300 Circ Cardiovasc Imaging July 2009
Figure 1. Illustration of different CT delayed enhancement pat-
terns. Representative short-axis slices of CT delayed enhance-
ment in chronic (top) and acute (bottom) myocardial infarction
(MI) are shown, along with segments showing nontransmural
infarct (yellow), transmural infarct (orange), no-reflow phenome-
non (red), and normal myocardium (green).
observed,16,17 although it represents a different pathophysio-
logical state that may also have different clinical implications.
We hypothesized that postinfarction inflammation occurs
frequently early after ischemia and reperfusion and that it can
be detected by increased FDG uptake on PET images. Also,
we hypothesized that inflammation is associated with micro-
vascular obstruction, as identified by a no-reflow phenome-
non on delayed contrast enhancement imaging. To test both
hypotheses, we made use of the potential of integrated
PET-CT to measure perfusion, metabolism, and contrast
enhancement pattern in a large animal model of acute and
chronic myocardial infarction.
Methods
Downloaded from http://ahajournals.org by on January 11, 2022
Animal Model
Myocardial infarction was induced in 3 young farm pigs and 7 adult
female Göttingen mini swine (weight, 21 to 42 kg). Under general
anesthesia (induction with ketamine/xylazine/telazol, maintenance
with 1.2 to 2.0% isoflurane), balloon occlusion of the mid left
anterior descending coronary artery, immediately distal to the second
diagonal branch, was performed for 120 to 150 minutes under
fluoroscopic guidance. Postoperative treatment included narcotics
and nonsteroidal anti-inflammatory drugs (ketorolac tromethamine).
Hybrid PET-CT imaging was performed either 24 to 72 hours (acute
phase, n⫽7) or ⬎4 weeks (chronic phase, n⫽3, control group) after
the procedure, under general anesthesia. The experimental protocol
was approved by the Institutional Animal Care and Use Committee.
Animals were maintained in accordance with the guiding principles
of the American Physiological Society.
PET-CT Protocol
PET-CT imaging was performed with a GE Discovery Rx VCT
scanner (GE Medical Systems), equipped with a LYSO PET com-
Table 1. Segmental PET and Delayed Enhancement CT
Patterns in Acute Myocardial Infarction
PET
Total Normal Match Mismatch
Total 119 69 14 36
CT
Normal 82 66 5 11
Transmural 35 2 9 24
(No-reflow) (28) (1) (9) (18)
Nontransmural 2 1 0 1
Table 2. Segmental PET and Delayed Enhancement CT
Patterns in Chronic Myocardial Infarction
PET
Total Normal Match Mismatch
Total 51 32 18 1
CT
Normal 33 30 2 1
Transmural 14 1 13 0
(No-reflow) (0) (0) (0) (0)
Nontransmural 4 1 3 0
ponent and a 64-slice CT component. After a minimum of 12 hours
of fasting, animals were positioned supine in a cradle and a CT scout
scan followed by a low-dose CT scan (120 kV, 80 mA) for
attenuation correction were obtained. CT scans were followed by
intravenous [13N]-ammonia infusion (30 seconds, 370 to 555 MBq)
and list-mode perfusion PET data acquisition (VIP, GE Healthcare,
Waukesha, Wis) was continued for 20 minutes.
Immediately after perfusion PET, diagnostic CT was started.
Ventilation was stopped for each acquisition, for breath-hold simu-
lation. Contrast agent (120 mL; Iodixanol 320 g/mL, Visipaque, GE
Healthcare, Princeton, NJ) was injected at a rate of 5 mL/s through
a femoral vein, and a first CT acquisition was conducted with a fixed
delay of 25 seconds for coronary angiography. The same CT
acquisition was then repeated at 10 minutes after contrast injection
for delayed enhancement imaging. Scan parameters were the same
for both acquisitions and were standard parameters used for a
high-resolution coronary angiography (retrospective ECG gating,
helical acquisition; pitch, 0.24; slice thickness, 0.65 mm; rotation
time, 350 ms; 120 kV, 600 mA).
After CT, myocardial glucose uptake was studied with [18F]FDG.
In the first 2 animals, preparation was performed using simplified
glucose/insulin loading (20 g of dextrose intravenously with simul-
taneous intravenous and subcutaneous insulin to adjust blood glu-
cose to 5 mmol/L; [18F]FDG injection after 60 minutes; 20 minutes
list-mode PET acquisition after 60 minutes of uptake). In the
remaining 8 animals, euglycemic hyperinsulinemic clamping was
performed according to a standard protocol,18 and at 90 minutes, 185
MBq [18F]FDG was injected and list-mode PET data acquisition-
(VIP, GE Healthcare) was started for 40 minutes.
List-mode PET data were resampled to attenuation corrected,
iteratively reconstructed, static, ECG-gated (8 bins for the cardiac
cycle), and dynamic images (21 frames for [13N]-ammonia: 12⫻10
seconds, 6⫻30 seconds, 3⫻300 seconds, and 19 frames for
[18F]FDG: 8⫻15 seconds, 2⫻30 seconds, 2⫻120 seconds, 1⫻180
seconds, 6⫻300 seconds). Because misalignment of CT and PET
affects tracer uptake, alignment for attenuation correction was
checked using fusion software in all studies. It was excellent in all
cases (due to lack of motion in the anesthetized animals); thus, no
realignment was necessary.19
PET Data Analysis
PET data were volumetrically sampled, and polar maps of left
ventricular myocardial activity were generated by using previously
validated software.20 Static tomographic images and polar maps
were normalized to their maximum and used for visual analysis of
regional perfusion/metabolism patterns using the American Heart
Association 17-segment model. Visual classification was done by 2
independent observers blinded to CT data as normal, matched defect,
or mismatch segments. Discrepancies were resolved by consensus. A
threshold of 60% of the individual maximal ammonia uptake was
used to define perfusion defect.21 Normal segments had no perfusion
defect in the [13N]-ammonia polar maps. Segments with a perfusion
defect were visually defined as matched defect segments if [18F]FDG
uptake was concordantly reduced and as mismatch segments if
[18F]FDG uptake was higher than perfusion tracer uptake.
 Lautamäki et al
Figure 2. Representative midventricular short-axis slices of CT
delayed enhancement (left), resting PET perfusion (measured by
N-13 ammonia, NH3) and metabolism (measured by FDG) (right),
and PET-CT fusion (middle) in animals studied in the chronic
and acute phases after myocardial infarction. Images of chronic
infarction show transmural delayed enhancement in anteroseptal
wall, associated with a perfusion/metabolism matched defect on
PET. Images of acute infarction show a no-reflow phenomenon
in anteroseptal wall, associated with reduced perfusion but
enhanced metabolism (mismatch) on PET.
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From gated [13N]-ammonia datasets, resting left ventricular ejec-
tion fraction was measured as previously reported.22
Additionally, from dynamic imaging sequences, absolute myocar-
dial blood flow at rest was quantified from myocardial and arterial
blood time activity curves using a validated 3-compartment model
for [13N]-ammonia,23 and Patlak graphical analysis for [18F]FDG,
assuming a lumped constant of 1.0.24 –26 To determine whole-body
PET-CT Characterization of MI 301
insulin resistance, glucose deposition was measured from plasma
samples in the animals receiving hyperinsulinemic euglycemic
clamp, using a previously described method.18
CT Data Analysis
All CT datasets were reformatted to short-axis images with a
thickness of 3.3 mm. Short-axis slices were divided into 17 segments
to match PET data analysis. Segments were visually classified by 2
independent observers, blinded to PET results, as remote with no
enhancement pattern, nontransmural, or transmural infarct. Infarct
segments were further analyzed for the no-reflow phenomenon, with
a signal void as a sign for microvascular obstruction (Figure 1).7
Pathology and Histology for Ex Vivo Analysis
Five pigs of the acute myocardial infarction group were immediately
euthanized after the imaging study. Hearts were arrested in diastole
by slow retrograde infusion of an ice-cold solution of 4 mmol/L
potassium chloride (KCl) in phosphate-buffered saline, and hearts
were excised for ex vivo tissue analysis. The other animals were kept
alive for the purpose of other scientific projects. In those 5 animals,
12.5 mL/kg 2% triphenyltetrazolium-chloride (TTC)-containing sa-
line was infused immediately before the animals were euthanized.
After fixation of excised hearts in 10% formaldehyde, gross macro-
scopic left ventricular (LV) short-axis slices were created. Three
midventricular/apical rings were analyzed for presence of TTC-
stained infarct tissue in segments that were matched with in vivo
PET-CT images. Additionally, 1 representative short-axis slice was
embedded in paraffin; 5-␮m sections were cut and stained for
hematoxylin and eosin staining. Light microscopy images were
obtained on a Zeiss Axiophot microscope (Carl Zeiss NTS GmbH,
Oberkochen, Germany).
Infarct and remote regions were semiquantitatively analyzed for
the amount of inflammatory cells. Similar sizes of regions of interest
(rectangle of 0.040 mm2) were placed on the mid infarct region and
on the mid remote region on the histological sample with ⫻64
magnification, and the amount of inflammatory cells were calculated
per millimeter squared.
Statistical Analysis
Kappa statistics were used for calculation of interobserver agreement
and agreement in segmental characteristics between PET, CT, and ex
vivo results. The Kruskall-Wallis test with the exact test was used to
compare continuous variables between chronic and acute-phase
Figure 3. Bar charts of PET-derived quantitative
myocardial blood flow (FLOW) (A) and glucose
uptake (MGU) (B) in the entire myocardium and
scar and remote regions as defined by CT delayed
enhancement.
 302 Circ Cardiovasc Imaging July 2009
animals. To compare quantitative PET data between scar and remote
regions, the Wilcoxon signed-rank test was used. Correlation be-
tween the amount of inflammatory cells and quantitative PET data
are reported with Spearman correlation coefficients. A probability
value of ⬍0.05 was considered statistically significant. Statistical
analyses were performed with SAS 8.2 (SAS Institute, Cary, NC)
and MedCalc version 9.3.0.0 (Medcalc Software, Mariakerke,
Belgium).
Results
Animal Characteristics
In the acute and chronic infarct models, resting left ventric-
ular ejection fraction was 48⫾12% and 41⫾9% (P⫽0.31),
and PET perfusion defect size was 36⫾9% and 31⫾9% of the
LV (P⫽0.43), respectively. In all animals, PET perfusion
defect and CT hyperenhanced region were located in the
anteroseptal area supplied by the left anterior descending
coronary artery. Whole-body glucose uptake as a measure of
insulin resistance was significantly lower in the acute model
compared with chronic infarction (25.6⫾13.5 versus
91.6⫾0.6 ␮mol/kg/min, P⫽0.046, respectively).
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Gross Segmental PET and CT Analysis
Overall, the 2 independent observers were in good agreement
for segmental analysis of PET (␬⫽0.74) and CT (␬⫽0.81)
data. When analyzed separately, interobserver agreement was
still good for animals with chronic (␬⫽0.62 and ␬⫽0.87 for
PET and CT, respectively) and acute infarction (␬⫽0.78 and
␬⫽0.78).
Segmental results for PET and CT in both groups are
shown in Tables 1 and 2. In the chronic infarct model, PET
and CT were in good agreement for distinguishing normal
segments from abnormal segments (␬⫽0.76). Of the 51
segments, 32 (63%) were normal on PET. Of these normal
PET segments, 30 of 32 (94%) were also normal on CT.
Conversely, of the 19 segments with a PET perfusion defect,
16 (84%) showed delayed enhancement on CT. An example
of integrated PET-CT image patterns in the chronic infarct
model is shown in Figure 2.
In the acute infarct model, 69 of 119 segments (58%) were
normal on PET. Of these, 66 of 69 (96%) were also normal on
CT. Among the abnormal segments, a variety of combina-
tions of CT and PET patterns was observed (Table 1). Of
note, the combination of transmural infarct with no-reflow
pattern and PET mismatch was most frequent. An example of
integrated PET-CT image patterns in the acute infarct model
is shown in Figure 2.
PET and CT Patterns in the Acute Infarct Area
In the group of animals imaged early after infarction, 37 of
119 segments (31%) showed evidence of infarction on CT
(Table 1). Of those, 28 (76%) showed a no-reflow phenom-
Figure 4. Correlation of ex vivo infarct detec-
tion with in vivo images. Shown are represen-
tative matching short-axis slices for TTC stain
(A), CT delayed contrast enhancement (B),
PET perfusion (C), and PET-CT fusion (D) in
an animal imaged early after acute myocardial
infarction.
enon, indicating microvascular obstruction. On PET, 50 of
119 segments (42%) were abnormal. Of those, 36 (72%)
showed a mismatch with reduced perfusion but increased
FDG uptake. Eighteen segments (50% of all mismatch
segments and 64% of all segment with no reflow) showed
both a PET mismatch as well as a CT no-reflow phenomenon.
This combination was the most frequent pattern of abnormal-
ity in acute infarct animals.
Quantitative PET Data
Global myocardial blood flow at rest (0.69⫾0.35 for chronic
versus 0.58⫾0.39 mL/g/min for acute infarction, P⫽0.52) and
global myocardial glucose uptake (6.8⫾2.2 versus
4.7⫾0.9 ␮mol/100 g/min, P⫽0.25) were not different between
both animal models. Regional analysis expectedly showed a
significant flow reduction in the CT-defined infarct area
versus remote myocardium in acute infarcts (Figure 3A). In
chronic animals, there was a similar trend which fell short of
significance, probably due to the low number of animals
(Figure 3A). Glucose uptake tended to be higher in the acute
infarct area compared with the remote region, whereas such a
trend was not observed in chronic animals.
Postmortem Analysis
Fifty midventricular segments of acute infarct animals were
available for ex vivo TTC staining analysis. Overall, there
was a good agreement of TTC staining with abnormal PET
(␬⫽0.64) and CT (␬⫽0.75) for infarct detection (Figure 4;
Tables 3 and 4). On histology, hematoxylin and eosin staining
consistently confirmed myocyte damage and revealed a high
content of inflammatory cells in all acute infarct segments
(3535⫾1880 cells/mm2; Figure 5). Semiquantitatively, the
amount of inflammatory cells correlated significantly with
myocardial glucose uptake in the infarct region (r⫽0.90,
P⫽0.037) but not in the remote region (r⫽0.56, P⫽0.32).
Discussion
In summary, this is the first study to our knowledge to use a
hybrid PET-CT approach for integrated assessment of infarct
Table 3. Segmental PET Patterns and Ex Vivo Data in Acute
Myocardial Infarction
PET
Total Normal Match Mismatch
Total 50 24 6 20
Ex vivo (TTC)
Normal 31 23 3 5
Infarct 19 1 3 15
Histology 17 9 0 8
Normal 9 8 0 1
Inflammation 8 1 0 7
 Lautamäki et al PET-CT Characterization of MI 303

Table 4. Segmental Delayed Enhancement CT Patterns and and postmortem TTC staining. This is important to recognize
Ex Vivo Data in Acute Myocardial Infarction because it may complicate the use of FDG for clinical
CT viability assessment early after infarct reperfusion therapy.
It has previously been suggested that ischemia/reperfusion
Total Normal Infarct No-Reflow Zone is followed by an increased inflammatory response, which
Total 50 29 21 17 improves tissue repair and wound healing.28 Cellular necrosis
Ex vivo (TTC) and reperfusion damage attract inflammatory cells29 that
Normal 31 27 4 3 contribute to regionally increased glucose uptake. Of note,
Infarct 19 2 17 14 many of the acute infarct segments with a PET mismatch in
our study also showed a no-reflow pattern on CT. This is
Histology 17 10 7 4
thought to reflect microvascular obstruction, which may be a
Normal 9 8 1 0
consequence of multiple mechanisms. Free radical formation
Inflammation 8 2 6 4
after ischemia-reperfusion may damage endothelial and mi-
crovascular structure, and microthrombi may contribute to
pathophysiology. In our porcine model, PET frequently occlusion. Compression by tissue swelling as a consequence
revealed increased regional glucose uptake in the hypoper- of inflammation has been discussed as another potential
fused infarct area early after reperfusion. Correlation with contributor to microvascular obstruction,30 which is sup-
histology showed inflammation as the underlying cause. ported by our hybrid imaging data.
Inflammation was frequently but not always associated with Importantly, the no-reflow phenomenon has been related to
microvascular obstruction, as identified by no reflow on CT, worse outcome in the clinical setting.30 It is known to be more
suggesting a pathophysiological interrelation. Finally, in chronic prevalent in the acute infarct phase,9 and its presence appears
infarcts, PET and CT agreed well and showed hypoperfusion, to predict myocardial wall thinning and remodeling later after
reduced glucose uptake, and delayed enhancement without signs infarction.31 Speculatively, the different PET/CT patterns
of no reflow. observed in our study (infarct with/without inflammation and
From multiple clinical studies in chronic ischemic heart with/without microvascular obstruction) may have different
disease with LV dysfunction, it is well known that decreased implications for the subsequent course of LV function,
FDG uptake in combination with a perfusion defect repre- geometry, and remodeling. This hypothesis would need to be
sents nonviable scar tissue. Preserved or increased FDG tested in future studies that include follow-up observations.
uptake in the region of a perfusion defect, the so-called Importantly, for the purpose of detecting pathophysiolog-
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perfusion/metabolism mismatch, is thought to represent hi-
bernating myocardium in this setting, which benefits from the
restoration of blood flow.27 On the contrary, in our model of
acute myocardial infarction induced by ischemia and reper-
fusion, perfusion/metabolism mismatch indicates inflamma-
tion in otherwise nonviable scar regions as identified by CT
ical mechanisms that precede adverse ventricular remodeling,
other more specific radiotracers targeting inflammation or
other key processes such as MMP activity32 or neurohumoral
activation33 may be preferable over the less specific FDG.
Combination with CT as a morphological technique in the
PET-CT environment may be even more attractive for these

Figure 5. Ex vivo histological tissue anal-

ysis in a representative animal after acute
myocardial infarction. A short-axis TTC
stain, showing anteroseptal infarct tissue
in white, is shown on the upper left. A
matched hematoxylin and eosin (HE)–s-
tained thin section of the whole short-axis
slice is shown in the center. Two different
magnifications (⫻20, ⫻64) are shown for
3 different myocardial areas: Two areas
from the TTC-positive infarct region,
which showed a PET perfusion/metabo-
lism mismatch and CT no-reflow pattern,
and 1 TTC-negative remote area, which
showed no PET or CT defect, are magni-
fied. In comparison to the remote area,
both mismatched areas from the acute
infarct zone show significant leukocyte
infiltration, suggesting extensive inflam-
mation as the probable reason for the in
vivo increase of glucose uptake.
 304 Circ Cardiovasc Imaging July 2009
compounds, which are expected to show a weaker albeit more
specific molecular signal that would require additional infor-
mation for accurate localization.
In conclusion, our observations suggest that CT and PET
yield information that can be combined into a single hybrid
imaging session for a comprehensive assessment of postis-
chemic tissue damage. Acute inflammation and microvascu-
lar obstruction may coexist early after acute myocardial
infarction, and they can be detected by increased FDG uptake
on PET and no reflow on delayed enhancement CT, respec-
tively. The implications for subsequent changes of ventricular
structure and transition to heart failure should be determined.
Acknowledgments
We thank the staff of the PET-CT center of Johns Hopkins Hospital
for their excellent technical assistance. We also thank Norman J.
Barker, MS, MA, RBP, for his expertise and helpful suggestions
obtaining pathology and histology images.
Sources of Funding
Dr Lautamäki is supported by grants from the Finnish Cardiac
Research Foundation, the Finnish Medical Foundation, the Instru-
mentarium Foundation for Science, and the Paavo Nurmi Foundation
and by the Bracco/SNM Research Fellowship in Cardiovascular
Molecular Imaging kindly provided by the Cardiovascular and
Radiopharmaceutical Sciences Councils, the Society of Nuclear
Medicine, and Bracco.
Disclosures
None.
Downloaded from http://ahajournals.org by on January 11, 2022
References
1. Miller TD, Christian TF, Hopfenspirger MR, Hodge DO, Gersh BJ,
Gibbons RJ. Infarct size after acute myocardial infarction measured by
quantitative tomographic 99mTc sestamibi imaging predicts subsequent
mortality. Circulation. 1995;92:334 –341.
2. Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, Bundy
J, Finn JP, Klocke FJ, Judd RM. Relationship of MRI delayed contrast
enhancement to irreversible injury, infarct age, and contractile function.
Circulation. 1999;100:1992–2002.
3. Gerber BL, Rochitte CE, Melin JA, McVeigh ER, Bluemke DA, Wu KC,
Becker LC, Lima JA. Microvascular obstruction and left ventricular
remodeling early after acute myocardial infarction. Circulation. 2000;
101:2734 –2741.
4. Yan AT, Shayne AJ, Brown KA, Gupta SN, Chan CW, Luu TM, Di Carli
MF, Reynolds HG, Stevenson WG, Kwong RY. Characterization of the
peri-infarct zone by contrast-enhanced cardiac magnetic resonance
imaging is a powerful predictor of post-myocardial infarction mortality.
Circulation. 2006;114:32–39.
5. Kim RJ, Wu E, Rafael A, Chen EL, Parker MA, Simonetti O, Klocke FJ,
Bonow RO, Judd RM. The use of contrast-enhanced magnetic resonance
imaging to identify reversible myocardial dysfunction. N Engl J Med.
2000;343:1445–1453.
6. Selvanayagam JB, Kardos A, Francis JM, Wiesmann F, Petersen SE,
Taggart DP, Neubauer S. Value of delayed-enhancement cardiovascular
magnetic resonance imaging in predicting myocardial viability after
surgical revascularization. Circulation. 2004;110:1535–1541.
7. Nieman K, Shapiro MD, Ferencik M, Nomura CH, Abbara S, Hoffmann
U, Gold HK, Jang IK, Brady TJ, Cury RC. Reperfused myocardial
infarction: contrast-enhanced 64-Section CT in comparison to MR
imaging. Radiology. 2008;247:49 –56.
8. Lardo AC, Cordeiro MA, Silva C, Amado LC, George RT, Saliaris AP,
Schuleri KH, Fernandes VR, Zviman M, Nazarian S, Halperin HR, Wu
KC, Hare JM, Lima JA. Contrast-enhanced multidetector computed
tomography viability imaging after myocardial infarction: character-
ization of myocyte death, microvascular obstruction, and chronic scar.
Circulation. 2006;113:394 – 404.
9. Gerber BL, Belge B, Legros GJ, Lim P, Poncelet A, Pasquet A, Gisellu
G, Coche E, Vanoverschelde JL. Characterization of acute and chronic
myocardial infarcts by multidetector computed tomography: comparison
with contrast-enhanced magnetic resonance. Circulation. 2006;113:
823– 833.
10. Baks T, Cademartiri F, Moelker AD, Weustink AC, van Geuns RJ, Mollet
NR, Krestin GP, Duncker DJ, de Feyter PJ. Multislice computed
tomography and magnetic resonance imaging for the assessment of
reperfused acute myocardial infarction. J Am Coll Cardiol. 2006;48:
144 –152.
11. Schuleri KH, Centola M, George RT, Amado LC, Evers KS, Kitagawa K,
Vavere AL, Evers R, Hare JM, Cox C, McVeigh ER, Lima JAC, Lardo
AC. Characterization of peri-infarct zone heterogeneity by contrast
enhanced multi-detector computed tomography: comparison with
magnetic resonance imaging. J Am Coll Cardiol. 2009;53:1699 –1707.
12. Holz A, Lautamaki R, Sasano T, Merrill J, Nekolla SG, Lardo AC,
Bengel FM. Expanding the versatility of cardiac PET/CT: feasibility of
delayed contrast enhancement CT for infarct detection in a porcine model.
J Nucl Med. 2009;50:259 –265.
13. Machac J, Bacharach SL, Bateman TM, Bax JJ, Beanlands R, Bengel F,
Bergmann SR, Brunken RC, Case J, Delbeke D, DiCarli MF, Garcia EV,
Goldstein RA, Gropler RJ, Travin M, Patterson R, Schelbert HR. Positron
emission tomography myocardial perfusion and glucose metabolism
imaging. J Nucl Cardiol. 2006;13:e121– e151.
14. Le Guludec D, Lautamaki R, Knuuti J, Bax JJ, Bengel FM. Present and
future of clinical cardiovascular PET imaging in Europe-a position
statement by the European Council of Nuclear Cardiology (ECNC). Eur
J Nucl Med Mol Imaging. 2008;35:1709 –1724.
15. Knuuti J, Schelbert HR, Bax JJ. The need for standardisation of cardiac
FDG PET imaging in the evaluation of myocardial viability in patients
with chronic ischaemic left ventricular dysfunction. Eur J Nucl Med Mol
Imaging. 2002;29:1257–1266.
16. Nian M, Lee P, Khaper N, Liu P. Inflammatory cytokines and postmyo-
cardial infarction remodeling. Circ Res. 2004;94:1543–1553.
17. Godino C, Messa C, Gianolli L, Landoni C, Margonato A, Cera M,
Stefano C, Cianflone D, Fazio F, Maseri A. Multifocal, persistent cardiac
uptake of [18-F]-fluoro-deoxy-glucose detected by positron emission
tomography in patients with acute myocardial infarction. Circ J. 2008;
72:1821–1828.
18. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method
for quantifying insulin secretion and resistance. Am J Physiol. 1979;237:
E214 –E223.
19. Lautamaki R, Brown TL, Merrill J, Bengel FM. CT-based attenuation
correction in (82)Rb-myocardial perfusion PET-CT: incidence of mis-
alignment and effect on regional tracer distribution. Eur J Nucl Med Mol
Imaging. 2008;35:305–310.
20. Nekolla SG, Miethaner C, Nguyen N, Ziegler SI, Schwaiger M. Repro-
ducibility of polar map generation and assessment of defect severity and
extent assessment in myocardial perfusion imaging using positron
emission tomography. Eur J Nucl Med. 1998;25:1313–1321.
21. Delbeke D, Lorenz CH, Votaw JR, Silveira ST, Frist WH, Atkinson JB,
Kessler RM, Sandler MP. Estimation of left ventricular mass and infarct
size from nitrogen-13-ammonia PET images based on pathological exam-
ination of explanted human hearts. J Nucl Med. 1993;34:826 – 833.
22. Hattori N, Bengel FM, Mehilli J, Odaka K, Ishii K, Schwaiger M, Nekolla
SG. Global and regional functional measurements with gated FDG PET
in comparison with left ventriculography. Eur J Nucl Med. 2001;28:
221–229.
23. Muzik O, Beanlands RS, Hutchins GD, Mangner TJ, Nguyen N,
Schwaiger M. Validation of nitrogen-13-ammonia tracer kinetic model
for quantification of myocardial blood flow using PET. J Nucl Med.
1993;34:83–91.
24. Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pet-
tigrew KD, Sakurada O, Shinohara M. The [14C]deoxyglucose method
for the measurement of local cerebral glucose utilization: theory, pro-
cedure, and normal values in the conscious and anesthetized albino rat.
J Neurochem. 1977;28:897–916.
25. Patlak CS, Blasberg RG. Graphical evaluation of blood-to-brain transfer
constants from multiple-time uptake data: generalizations J Cereb Blood
Flow Metab. 1985;5:584 –590.
26. Ng CK, Soufer R, McNulty PH. Effect of hyperinsulinemia on myo-
cardial fluorine-18-FDG uptake. J Nucl Med. 1998;39:379 –383.
27. vom Dahl J, Eitzman DT, al Aouar ZR, Kanter HL, Hicks RJ, Deeb GM,
Kirsh MM, Schwaiger M. Relation of regional function, perfusion, and
metabolism in patients with advanced coronary artery disease undergoing
surgical revascularization. Circulation. 1994;90:2356 –2366.
 Lautamäki et al PET-CT Characterization of MI 305

28. Frangogiannis NG, Smith CW, Entman ML. The inflammatory response
in myocardial infarction. Cardiovasc Res. 2002;53:31– 47.
29. Frangogiannis NG, Mendoza LH, Lindsey ML, Ballantyne CM, Michael
LH, Smith CW, Entman ML. IL-10 is induced in the reperfused myocar-
dium and may modulate the reaction to injury. J Immunol. 2000;165:
2798 –2808.
30. Jaffe R, Charron T, Puley G, Dick A, Strauss BH. Microvascular
obstruction and the no-reflow phenomenon after percutaneous coronary
intervention. Circulation. 2008;117:3152–3156.
31. Koyama Y, Matsuoka H, Mochizuki T, Higashino H, Kawakami H,
Nakata S, Aono J, Ito T, Naka M, Ohashi Y, Higaki J. Assessment of
reperfused acute myocardial infarction with two-phase contrast-enhanced
helical CT: prediction of left ventricular function and wall thickness.
Radiology. 2005;235:804 – 811.
32. Zhang J, Nie L, Razavian M, Ahmed M, Dobrucki LW, Asadi A,
Edwards DS, Azure M, Sinusas AJ, Sadeghi MM. Molecular imaging of
activated matrix metalloproteinases in vascular remodeling. Circulation.
2008;118:1953–1960.
33. Dilsizian V, Eckelman WC, Loredo ML, Jagoda EM, Shirani J. Evidence
for tissue angiotensin-converting enzyme in explanted hearts of ischemic
cardiomyopathy using targeted radiotracer technique. J Nucl Med.
2007;48:182–187.

CLINICAL PERSPECTIVE
Early after myocardial infarction, several pathophysiological mechanisms may be triggered that contribute to subsequent
postinfarction remodeling and transition to heart failure. Early detection of such mechanisms by noninvasive imaging,
along with a better understanding of their interrelations and implications, may improve individual postinfarction therapy.
This study uses innovative hybrid positron emission tomography/computed tomography technology to identify postinfarc-
tion inflammation and microvascular obstruction early after acute myocardial infarction, which appear to be partially
interrelated. The work done in an animal model may stimulate further clinical studies to investigate the clinical role of the
imaging findings.
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