The diagnostic and prognostic value of ECG-gated SPECT myocardial perfusion imaging.
ABSTRACT Since the development of gated SPECT imaging approximately 10 y ago, this technique is now almost universally used as an adjunct for radionuclide perfusion imaging, enabling the assessment of perfusion along with determination of regional and global left ventricular function in the same examination. The gated SPECT determination of the left ventricular ejection fraction and volumes has been extensively validated. Additionally, this method allows for the improved identification of soft-tissue artifacts and enhances the detection of multivessel coronary artery disease. Furthermore, gated SPECT provides powerful information for the risk assessment of patients with known or suspected coronary artery disease and aids in the assessment of myocardial viability. Gated SPECT imaging has clearly become an integral part of radionuclide myocardial perfusion imaging.
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ABSTRACT: This study was designed to assess the prognostic value of stress myocardial perfusion SPECT with electrocardiographic (ECG) gating in patients undergoing noncardiac surgical treatment. The study included 481 consecutive patients who underwent noncardiac surgery and had been referred for preoperative myocardial perfusion scintigraphy. Myocardial scintigraphy used (99m)Tc-labeled perfusion agents and dipyridamole stress with ECG gating, permitting qualitative and quantitative analyses of both myocardial perfusion and cardiac function. Reconstructed perfusion images were analyzed qualitatively and semiquantitatively. The Quantitative Gated SPECT (QGS) program was used for gated SPECT analysis to calculate global left ventricular ejection fraction and estimate regional wall motion. We assessed the relationships between perioperative cardiac events and various predictors, including clinical risk factors, radionuclide perfusion, and functional variables. Univariate analysis indicated that age (P < 0.001), diabetes mellitus (P < 0.01), history of heart failure (P < 0.05) or perfusion imaging (P < 0.0001), and QGS analysis (P < 0.0001) yielded significant risk stratification. According to multivariate analysis, age, diabetes mellitus, perfusion imaging, and QGS analysis were independent predictors of perioperative cardiac events. The event rate was correlated with quantitative scintigraphic indices of perfusion images (rest perfusion and ischemic scores) and QGS analysis (global ejection fraction and the number of hypokinetic segments). Although QGS functional data offered no significant incremental prognostic value in patients with abnormal perfusion, it classified patients with normal perfusion into 2 risk groups (P < 0.0001). A combination of clinical risk factors, scintigraphic perfusion results, and functional data allowed further detailed risk stratification. Stress myocardial perfusion SPECT with ECG gating has an incremental prognostic value over conventional nongated stress perfusion imaging in predicting perioperative cardiac events.Journal of Nuclear Medicine 03/2003; 44(3):385-90. · 5.77 Impact Factor
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ABSTRACT: In patients who had undergone cardiac surgery (coronary artery bypass graft) and whose hearts showed abnormal movement during the cardiac cycle, we studied the accuracy of functional assessment using ECG-gated single-photon emission tomography (SPET) and the automated software developed by Germano et al. by comparing the findings with magnetic resonance (MR) images acquired three-dimensionally. Sixteen patients who had undergone cardiac surgery underwent 99mTc-sestamibi gated SPET (MIBI-g-SPET) and MRI on the same day. Left ventricular end-diastolic and end-systolic volumes (EDV, ESV) and ejection fraction (LVEF) were measured using MIBI-g-SPET and the aforementioned algorithm. Regional wall thickening was assessed using a four-point scale on MIBI-g-SPET and cine MRI. There was a good correlation between MIBI-g-SPET and MRI in respect of EDV (r=0.89), ESV (r=0.93) and LVEF (r=0.89). A high degree of agreement was found between the wall thickening scores obtained by MIBI-g-SPET and MRI in total segments (kappa=0.62) and in septal segments (kappa=0.67). It is concluded that ECG-gated perfusion SPET can provide regional and global functional information, including absolute volumes, in patients following cardiac surgery.European Journal of Nuclear Medicine 08/1999; 26(7):705-12.
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ABSTRACT: We hypothesized that combining functional assessment to perfusion enhances the ability of electrocardiographic gating Tc-99m sestamibi single photon emission computed tomography (gated SPECT) myocardial perfusion imaging (MPI) to detect defects in multiple vascular territories in patients with severe three-vessel coronary artery disease (3VD). In patients with 3VD, perfusion defects in multiple vascular territories may not always be evident due to globally reduced perfusion. Gated SPECT MPIs were interpreted sequentially with perfusion first, followed by combined perfusion/function, in 143 patients with angiographic 3VD and a control group of 112 non-3VD patients. All patients underwent coronary arteriography within one month of MPI. In 3VD patients, combined perfusion/function analysis yielded significantly greater numbers of abnormal segments/patient (6.2 +/- 4.7 vs. 4.1 +/- 2.8, p < 0.001) and more defects in multiple vascular territories (60% vs. 46%, p < 0.05) than perfusion alone. In the control group, there were no differences between the combined perfusion/function and perfusion alone interpretations. Multivariate analysis of 15 different clinical, stress, and scintigraphic variables in all patients revealed age (p < 0.0001) and number of abnormal vascular territories by combined perfusion/function (p < 0.0001) to be the most powerful predictors of 3VD. Addition of functional data to clinical, stress, and perfusion yielded a significant increase in the predictive value of 3VD (global chi-square: 131.7 vs. 89.8, p < 0.00001). Specificity of combined perfusion/function analysis was not lower than perfusion alone (72% vs. 69%, p = NS). CONCLUSIONS; Adjunctive assessment of function with perfusion by gated SPECT MPI enhances the detection of defects in multiple vascular territories in patients with severe 3VD, without adversely affecting its specificity.Journal of the American College of Cardiology 08/2003; 42(1):64-70. · 14.09 Impact Factor
The Diagnostic and Prognostic Value of
ECG-Gated SPECT Myocardial Perfusion Imaging
Vanessa Go, MD; Mehul R. Bhatt, MD; and Robert C. Hendel, MD
Section of Cardiology, Department of Medicine, Rush University Medical Center, Chicago, Illinois
Since the development of gated SPECT imaging approximately
10 y ago, this technique is now almost universally used as an
adjunct for radionuclide perfusion imaging, enabling the assess-
ment of perfusion along with determination of regional and
global left ventricular function in the same examination. The
gated SPECT determination of the left ventricular ejection frac-
tion and volumes has been extensively validated. Additionally,
this method allows for the improved identification of soft-tissue
artifacts and enhances the detection of multivessel coronary
artery disease. Furthermore, gated SPECT provides powerful
information for the risk assessment of patients with known or
suspected coronary artery disease and aids in the assessment
of myocardial viability. Gated SPECT imaging has clearly be-
come an integral part of radionuclide myocardial perfusion
J Nucl Med 2004; 45:912–921
Electrocardiographically (ECG)-gated myocardial per-
fusion SPECT was developed in the late 1980s and has
rapidly evolved into a standard for myocardial perfusion
imaging in the United States. The American Society of
Nuclear Cardiology in its position paper from March 1999
recommended the routine incorporation of ECG gating dur-
ing SPECT cardiac perfusion scintigraphy (1,2). Gated
SPECT studies allow simultaneous assessment of perfusion
and function in a single-injection, single-acquisition se-
The development of new radioisotopes and improve-
ments in imaging hardware and computer technology have
contributed significantly to the growth of gated SPECT. The
99mTc-based perfusion tracers, because of their higher count
rates and stable myocardial distribution with time, permit
evaluation of regional myocardial wall motion and wall
thickening throughout the cardiac cycle. The development
of automated algorithms to quantitatively measure left ven-
tricular (LV) volume and ejection fraction (EF), and even
regional myocardial wall motion and thickening from gated
SPECT, rapidly and accurately, and with minimal operator
interaction, has also contributed to its widespread use.
These innovations have made SPECT imaging a premier
method of noninvasive evaluation of myocardial blood flow
and cardiac function in a variety of clinical situations (3).
GATED SPECT ACQUISITION AND PROCESSING
In a gated acquisition, a 3-lead ECG provides the R wave
trigger to the acquisition computer, with 2 successive R
wave peaks on the ECG defining a cardiac cycle. Counts
from each phase of the cardiac cycle are associated with a
temporal frame within the computer (4). Gating of myocar-
dial perfusion is usually performed at 8 frames per R–R
interval per projection, although most manufacturers have
the capability to acquire 16 frames per R–R interval. The
acquired data are then reconstructed and displayed in a
cinematic or multiframe format, allowing the reader to
assess wall motion in all areas of the myocardium, including
the left and right ventricles (Fig. 1) (5).
Changes in heart rate due to a variety of factors can result
in temporal blurring—that is, mixing of counts from adja-
cent frames. To minimize temporal blurring, a beat rejection
Received Jun. 23, 2003; revision accepted Jan. 7, 2004.
For correspondence or reprints contact: Robert C. Hendel, MD, Section of
Cardiology, Department of Medicine, Rush-Presbyterian-St. Luke’s Medical
Center, 1725 W. Harrison St., Suite 020, Chicago, IL 60612-3864.
frames corresponding to different phases of cardiac cycle are
acquired for each angular projection. Perfusion images are ob-
tained from summation of individual frames. (Reprinted with
permission of (5).)
ECG-gated SPECT acquisition. Separate temporal
THE JOURNAL OF NUCLEAR MEDICINE • Vol. 45 • No. 5 • May 2004
window is set by specifying the acceptable deviation of each
R–R interval from the expected value. A 20% window has
historically been applied, although in patients with highly
variable heart rates, up to a 100% acceptance window can
be set. In patients with arrhythmias, it is important to check
for gating errors, as it has been demonstrated that EF
fluctuations, perfusion differences, and, in particular, wall
thickening discordance may occur with arrhythmias (6).
Thus, in cases of extreme variation in heart rate or rhythm,
an ungated SPECT study may be the most appropriate test.
There are a variety of single-day and 2-d protocols that
may be used in conjunction with gated SPECT. Either201Tl
or99mTc perfusion tracers may be used. Most commonly
used is the high-dose technetium stress study because of its
superior myocardial count density.
vides more reproducible volume and LVEF measurements
201Tl (7). In addition, when low- versus high-dose
technetium was compared there was less variability of
LVEF in the high-dosage cohort (8).
Either or both of the acquisitions composing the stress/
rest or rest/stress sequence can be gated. Although the
common practice is to gate only the poststress image, a
small study by Johnson et al. reports that, in 36% of patients
with reversible perfusion defects, the poststress LVEF was
?5% lower than at rest (9). This implies that global and
regional LV function obtained from poststress gated acqui-
sitions are not representative of basal LV function in pa-
tients with stress-induced ischemia and that perhaps both
rest and stress images should be gated routinely, as long as
counts are sufficient.
Overall ventricular function and regional cardiac function
(myocardial wall motion and thickening) are calculated
separately using computer software requiring minimal op-
erator input (Fig. 2). Most of these programs use an edge
Cedars-Sinai). (A) Myocardial contours displaying endocardial and epicardial surfaces overlying end-diastolic (ED) and end-systolic
(ES) frames display 3 short-axis images, a midcavity horizontal image, and a midcavity vertical long-axis image. (B) Quantitative
polar plots measuring regional myocardial wall perfusion (B1, B2), motion (B3), and wall thickening (B4) from gated SPECT. (C)
Three-dimensional display of endocardial (solid) and epicardial (grid) LV surfaces calculated by automatic algorithm. (D) Endocardial
time–volume curve and calculated LVEF from end-systolic and end diastolic volumes.
Quantification of EF, regional myocardial wall motion, and thickening from gated myocardial perfusion SPECT (QPS;
CLINICAL VALUE OF GATED SPECT • Go et al.
detection method using endocardial and epicardial surface
points and make geometric assumptions (gaussian fit) to
calculate LV end-systolic and end-diastolic volumes. Other
methods seek definition of the same points using the per-
centage systolic count increases because of the partial-
volume effect. Newer programs are usually a hybrid of edge
detection and count-based methods and are 3-dimensional
(10–12). Visually the ventricular wall thickening can be
accentuated with thermal or hot body imaging options.
The 3 most widely distributed software packages for LV
function analysis from gated myocardial perfusion scans are
QGS (Cedars-Sinai), 4D-MSPECT (University of Michi-
gan), and the Emory Cardiac Toolbox or ECTb (Emory
University). The QGS methodology uses gaussian fit to
determine endocardial and epicardial offsets, whereas ECTb
is a count-based method. Although both programs have, in
general, compared favorably with other modalities for de-
termining LVEF and volumes (Tables 1 and 2), it is impor-
tant to keep in mind that the choice of gold standard, as well
as degree of rigorousness in comparing the different meth-
odologies in these validation studies, may vary. Some mo-
dalities used for comparison, including 2-dimensional echo-
cardiography, radionuclide ventriculography, and first-pass
radionuclide angiography have their own inherent inaccu-
racies. It is also important to note that not all reports
provided the statistical analysis of the variability around the
correlation line, such as the SE of estimates, which indicates
the likelihood that the EF measured by the new technique
will be within a certain range of the EF measured by the
gold standard. If there is a large range, this usually indicates
that a study is not as reliable. Perfusion defects, background
activity, time after injection, and the injected dose may have
a confounding effect on the quantitative determination of
LVEF and LV volumes, as demonstrated by a small study
done in canines by Vallejo et al., which showed that the
automated QGS program consistently overestimated LVEF
and LV volumes when compared with MRI (13). Further-
more, since this was a canine study, it is postulated that
perhaps in smaller hearts, the limited spatial resolution of
SPECT makes endocardial border recognition problematic
and that perhaps a count-based method would be more
appropriate. A larger human study by the same author,
comparing gated SPECT with first-pass radionuclide an-
giography, showed a better correlation in studies with low
extracardiac activity, higher counts, and larger hearts (14).
This emphasizes the critical importance of quality control
and optimizing image acquisition, as well as awareness on
the part of the reader to recognize the presence of such
variables. A study by Nakajima et al., specifically examin-
ing pediatric hearts (age, 2 mo to 19 y) with correspondingly
small LV volumes (14–326 mL), also emphasized that in
patients with small ventricular volumes gated SPECT is
valid if appropriate image acquisition parameters are used
Several studies have directly compared the performance
of gated SPECT software packages. A comparison between
QGS and ECTb showed that QGS consistently provided
significantly lower volumes and EFs compared with the
ECTb algorithm for both coronary artery disease (CAD) and
low-likelihood patients (Table 3) but that both methods
showed close correlation with each other (r ? 0.91–0.94)
(16). Lum and Coel demonstrated a correlation coefficient
of ?0.9 in estimating EF and end-diastolic volume among
QGS, ECTb, and 4D-MSPECT (17). Nakajima et al. com-
pared QGS, ECTb, and 4D-MSPECT with gated blood
pool and observed correlation coefficients of 0.89, 0.85,
and 0.90, respectively (18). Although several studies have
shown high correlation between various gated SPECT soft-
ware programs in estimation of ventricular volume, since
each program uses a different algorithm, their LV function
data should be interchangeable only with caution. In the
situation in which the same gated SPECT software applica-
tion is used twice consecutively on the same patient, there is
high correlation for both wall motion (r ? 0.95) and systolic
thickening (r ? 0.88) (19).
Initially, the clinical role of gated SPECT lay in its ability
to enhance artifact identification. Soft-tissue attenuation ar-
tifacts often appear as fixed defects and are difficult to
differentiate from infarct, thereby reducing the test speci-
ficity of SPECT myocardial perfusion imaging. Gated ac-
quisitions may help differentiate scar from artifact as fixed
defects with decreased function likely represent a myocar-
dial infarction (MI), whereas attenuation artifacts will have
a fixed defect with normal or relatively normal wall motion.
DePuey and Rozanski demonstrated that false-positive per-
fusion studies could be reduced from 14% to 3% by incor-
porating regional wall motion data in the interpretation of
perfusion imaging (20). In women, where the false-positive
rate of stress ECGs is relatively high and breast soft-tissue
attenuation artifact is common, ECG gating was shown to
further enhance the diagnostic specificity of99mTc perfusion
imaging from 84% to 94% (21). Subsequently, Smanio et al.
demonstrated that the addition of gated SPECT for the
assessment of regional systolic function reduces the degree
of uncertainty in the interpretation of99mTc-sestamibi per-
fusion studies. The number of “borderline-normal” or “bor-
derline-abnormal” interpretations was significantly reduced.
In patients with a low likelihood of CAD, the normalcy rate
increased from 74% to 93% (Fig. 3). In patients with a high
likelihood of CAD, the trend was also toward a higher
number of unequivocally abnormal interpretations (22).
Diagnosis of CAD
The detection of CAD, particularly multivessel disease, is
also enhanced by the capability to obtain functional infor-
mation through gating. Though proven in various studies
that SPECT myocardial perfusion imaging reliably detects
THE JOURNAL OF NUCLEAR MEDICINE • Vol. 45 • No. 5 • May 2004
CAD, the question of underestimating ischemia in the case
of multivessel disease or left main disease because of bal-
anced global hypoperfusion comes into question. According
to several reports, only 13%–50% of patients with 3-vessel
CAD or left main disease actually have perfusion abnor-
malities in multiple territories (23–25). This could poten-
tially lead clinicians to underestimate risk or incorrectly
predict prognosis. Several studies have clearly demon-
Validation of Quantitative Measurements of LVEF by Different Software Programs for Gated Myocardial Perfusion SPECT
Authors Year Software Gold standard
Ioannidis et al.
Baba et al.
Itti et al.
Vourvouri et al.
Higuchi et al.
Germano et al.
Faber et al.
Vallejo et al.
Tadamura et al.
Yoshioka et al.1999 QGSFPRNA 21
Vallejo et al.
Nichols et al.
Nichols et al.
Atsma et al.
Wright et al.
Bax et al.
Cwajg et al.
201Tl (low dose)
Nichols et al.2000SPECT
2D Echo330.92 overall
0.82 SPECT EF
He et al.1999FPRNA63
Inubushi et al.
Nichols et al.
Nakajima et al.2001QGS
Everaert et al.1997ERNA 40
Chua et al.
Abe et al.
Manrique et al.
* Perfusion and function analysis for gated SPECT.
ERNA ? equilibrium radionuclide angiography; 2D Echo ? 2-dimensional echocardiography; FPRNA ? first-pass radionuclide angiography.
CLINICAL VALUE OF GATED SPECT • Go et al.
strated the incremental value of using both functional and
perfusion data in detecting multivessel disease or high-
grade stenoses over perfusion data alone, although there are
some conflicting data on sensitivity and specificity. Sharir et
al. examined a population of 99 patients who underwent
SPECT with normal resting perfusion. Multivariate regres-
sion analysis showed that both extensive perfusion abnor-
malities and the presence of wall motion abnormalities in
multiple territories were independent predictors of severe
multivessel CAD but that the addition of wall motion vari-
ables to perfusion data resulted in a significant increase in
the global ?2for predicting severe proximal left anterior
descending as well as severe multivessel CAD. For perfu-
sion alone, sensitivity was 49%, whereas combined perfu-
sion and wall motion abnormality yielded a sensitivity of
82% (26). Lima et al. demonstrated that evaluation of seg-
mental poststress thickening abnormalities on gated SPECT
better identified patients with severe angiographic triple-
vessel disease. The addition of functional data derived from
gated SPECT to perfusion data improved detection of mul-
tivessel disease from 46% to 60% (P ? 0.05) and triple-
vessel disease from 10% to 25% (P ? 0.001) (27).
The use of rest and stress LVEF may also assist in the
detection of multivessel coronary disease, as demonstrated
in a study by Yamagishi et al., wherein the combination of
perfusion data and worsening of the LVEF significantly
increased sensitivity in detecting multivessel CAD over
201Tl perfusion defects or rest LVEF and postexercise LVEF
alone (43.3% vs. 26.9%, 25.4%, and 25.4%, respectively).
In this study, though sensitivity increased, there was also a
significant decrease in specificity, although this remained
acceptable at approximately 90% (28). Another study
sought to correlate the degree of angiographic stenosis
with the presence of regional wall motion abnormalities
(RWMA) on exercise stress/rest gated99mTc SPECT studies
(29). Reversible RWMA were found to be highly specific
for angiographic stenoses of ?70%, both overall and for
specific vascular territories (94%–100%). Furthermore,
when patients were stratified according to the severity of
angiographic stenoses (50%–79% and 80%–99%), the pres-
ence of reversible RWMA distinguished a higher angio-
graphic severity with positive predictive values between
77% and 88% for specific vascular territories. Of note, these
improvements in specificity were at the expense of sensi-
tivity, which were much less compared with perfusion alone
(53% for reversible RWMA vs. 89% for perfusion alone).
imaging has been shown as an indicator of CAD (30,31).
Poststress diastolic dysfunction is though to be a manifestation
of myocardial ischemia causing increased early filling pres-
sures. Indices of diastolic dysfunction include peak filling rate
(PFR) and time to PFR of the left ventricle. PFR computed by
gated SPECT using 8 frames per R–R interval has a poor
correlation of 0.51 compared with equilibrium radionuclide
angiography (ERNA) (30). The correlation improves if more
frames are used. Paul et al. measured diastolic parameters
through gated SPECT and found that PFR was lower in post-
stress patients with severe reversible scintigraphic perfusion
defects compared with rest images (2.23 s?1and 2.94 s?1; P ?
0.005) (31). Yet, other parameters such as LVEF, end-diastolic
volume, and end-systolic volume were also all significantly
lower in the same patient groups. Although gated SPECT allows
observations of diastolic dysfunction, this parameter does not
currently have incremental diagnostic value over existing stan-
Prognosis and Risk Stratification
As with the case with perfusion imaging in general, gated
SPECT imaging has also found an important role in the risk
assessment of patients with known or suspected CAD. This
is not surprising, given the well-recognized prognostic role
of LV function with regard to long-term survival, as has
been shown using a variety of techniques for LV functional
assessment. Among a large series of 1,690 consecutive
patients who underwent dual-isotope gated SPECT imag-
ing, those whose EFs were ?45% were associated with
Comparison of 2 Software Programs for Quantitation of LV
Function and Volumes in Normal or Low-Risk Subjects
Parameter QGS ECTb
62 ? 9
84 ? 26
33 ? 17
67 ? 8
105 ? 33
35 ? 17
EDV ? end-diastolic volume; ESV ? end-systolic volume.
Values are mean ? SD. Data are from (16).
Assessment of LVEF by 5 Methods: Range and Lower Normal Limits
Mean LVEF ? SD (%)
Lower normal limit (%)
63 ? 10
60 ? 5
65 ? 5
67 ? 8
55 ? 7
ERNA ? equilibrium radionuclide angiography.
Data are from (87).
THE JOURNAL OF NUCLEAR MEDICINE • Vol. 45 • No. 5 • May 2004