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(Circulation. 1996;93:463-473.)
© 1996 American Heart Association, Inc.
Articles |
Simultaneous Transmission/Emission Myocardial Perfusion Tomography
Diagnostic Accuracy of Attenuation-Corrected 99mTc-SestamibiSingle-Photon Emission Computed Tomography
From the Department of Internal Medicine, Division of Nuclear Medicine, University of Michigan Medical Center (Ann Arbor).
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background The purpose of the present study was to assess the diagnostic performance of attenuation-corrected (AC) stress 99mTc-sestamibi cardiac single-photon emission computed tomography (SPECT) for the identification of coronary heart disease (CHD).
Methods and Results With a triple-detector SPECT system with
a 241Am transmission line source, simultaneous
transmission/emission tomography (TCT/ECT) was performed on 60 patients
with angiographic coronary disease and 59 patients with 
5%
likelihood of CHD. Iteratively reconstructed AC stress
99mTc-sestamibi perfusion images were compared with
uncorrected (NC) filtered-backprojection images. Normal
database polar maps were constructed from AC and NC images for
quantitative analyses. From the low-likelihood patients,
the visual and quantitative normalcy rates increased from 0.88 and 0.76
for NC to 0.98 and 0.95 for AC (P<.05). For the detection
of CHD, the receiver operating characteristic curves for the AC
images demonstrated improved discrimination capacity
(P<.05), and sensitivity/specificity values increased from
0.78/0.46 (NC) to 0.84/0.82 (AC) with visual analysis and from
0.84/0.46 (NC) to 0.88/0.82 (AC) with quantitative analysis.
For localization of stenosed vessels, visual and quantitative
sensitivity values were 0.51 and 0.63 for NC and 0.64 and 0.78 for AC
images (P<.05), respectively.
Conclusions TCT/ECT myocardial perfusion imaging significantly improves the diagnostic accuracy of cardiac SPECT for the detection and localization of CHD. Clinical use of TCT/ECT imaging deserves serious consideration.
Key Words: cardiovascular disease • coronary disease • imaging • radioisotopes • tomography
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Myocardial stress perfusion imaging is widely used to noninvasively detect the presence and extent of CHD. Although perfusion imaging with SPECT has been shown to be highly sensitive in the detection of CHD, its specificity in assessing the absence of disease has been suboptimal.1 2 3 It has been hypothesized that the suboptimal specificity of myocardial SPECT perfusion imaging is due to the inhomogeneous attenuation of photons in the thorax, which produces artifactual heterogeneous radionuclide activity distributions in the myocardium of patients without evidence of CHD. Although guidelines have been adopted to distinguish attenuation artifacts from real perfusion abnormalities,4 5 6 7 photon attenuation reduces the discriminating capacity of myocardial perfusion SPECT, resulting in lowered test specificity.
Recent research efforts have resulted in the commercial availability of SPECT imaging systems that are capable of TCT.8 9 10 11 Whether performed sequentially or simultaneously, TCT provides anatomically specific density maps of the thorax that can be used to correct SPECT image data for photon attenuation. We developed a system that uses a triple-detector system with a 241Am transmission line source (activity, 230 MBq/cm) opposite a fan-beam collimator (focal length, 65 cm) on one detector to collect transmission and emission projection data.12 13 An Americium-241 line source was chosen based on its low photon energy (60 keV), which permits its use with both 201Tl and 99mTc radiotracers with minimal cross-talk contamination of the emission data. Parallel-hole collimators instead of fan-beam collimators were used on the "emission-only" detectors to minimize the truncation of emission data caused by the inherent magnification of fan-beam collimators and the image artifacts that can result.
The purpose of the present study was to assess the diagnostic performance of this TCT/ECT imaging system for the detection and localization of CHD in patients with angiographically documented CHD and in patients with a very low likelihood of CHD. NC and AC emission tomograms were visually and quantitatively interpreted and compared for the presence or absence of CHD by using ROC curve analysis.14 ROC curve analysis was used to characterize and compare the inherent discriminating capacity of the NC and AC images. Normal NC and AC 99mTc-sestamibi perfusion distribution patterns from a database of patients with a very low likelihood of CHD were used in the quantitative analysis of patients with suspected CHD and to determine normalcy rates in low-likelihood patients. Based on ROC curve analyses from the quantitative interpretation of perfusion images, we determined optimal abnormality thresholds for the AC and NC images.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Patient Population
Simultaneous TCT/ECT was performed on a random selection of 360 patients who were referred for stress myocardial perfusion imaging. From this population, two groups of patients were extracted for this study. Group 1 was composed of 59 consecutive patients (22 men and 37 women; mean age, 53±14 years) who had
5%
pretest likelihood for CHD15 (mean±SD, 2.0±1.5%).
For
quantitative analysis, sex-specific normal databases of 20
male and 20 female patients were constructed from AC and NC images.
Normalcy rates were determined for group 1 patients. Group 2
was composed of 60 consecutive patients (38 men and 22 women; mean age,
63±12 years) who had angiographic verification of disease within 90
days of scintigraphy without any change in cardiac
condition or treatment. The mean time interval between tomography and
catheterization was 15±20 days. Within this group, 25
patients (17 men and 8 women; mean age, 60±16 years) had historical
and ECG evidence of a prior myocardial infarction. From the random
patient population (n=360), no patients were excluded from either group
1 or group 2 due to image quality, patient size, or location and extent
of perfusion defects, and no patient was excluded because of coexisting
hypertensive heart disease, ventricular dysfunction, or
dilation. Patients received 111 MBq (3 mCi) thallous chloride for the resting perfusion study. The stress imaging commenced immediately after rest or redistribution imaging. At peak stress, 1110 MBq 99mTc-sestamibi (DuPont Pharma) was injected. Pharmacological stress testing was performed with adenosine16 (n=61), dipyridamole17 (n=12), or dobutamine18 (n=7). Symptom-limited maximal treadmill exercise was performed using the Bruce protocol (n=39).
Coronary Angiography
Coronary angiography was performed using
standard
percutaneous techniques. Coronary
stenoses were assessed by two experienced angiographers and
expressed as percent luminal diameter stenosis; the
angiographers were unaware of the scintigraphic results. From the
angiographic data, coronary stenosis severity was
scored using the following system: 1, 0% to 49%; 2, 50% to 69%; 3,
70% to 89%; and 4, 90% to 100% reduction in luminal diameter.
For comparison with the scintigrams, left main coronary lesions
were recorded as both LAD and LCx stenoses. Diagonal
branches were included in the LAD, and marginal branches were grouped
with the LCx. Lesions to the posterior lateral and posterior descending
arteries were included with the RCA. Perfusion SPECT data were
analyzed at angiographic thresholds of 
50% and 70%
stenoses of luminal diameter.
Acquisition and Processing of TCT/ECT Data
Each patient
underwent simultaneous TCT/ECT imaging
with a collimated line source positioned opposite and parallel to one
of three detectors on either a PRISM 3000XP or a PRISM 3000 SPECT
imaging system (Picker-Ohio Imaging, Nuclear Medicine Division of
Picker International). This detector was fitted with a low-energy,
high-resolution fan-beam collimator with a focal length of 65
cm. The transmission source consisted of a 5.55-GBq (150 mCi)
Americium-241 line source (Isotope Products Laboratories) sealed in
a 0.3-mm-thick stainless steel tube with an active volume of 2.4 mm
(ID)x240 mm. The motor-driven line source holder provided radial
and axial collimation while enabling noncircular orbit acquisitions.
The remaining two detectors were fitted with low-energy,
high-resolution, parallel-hole collimators to collect
uncontaminated, untruncated emission data.
Transmission and emission
projection data were stored in 64x64
matrices for all detectors. Projection images were acquired at 6°
steps over a 360° orbit for 12 seconds per projection for a total
scan time of 12 minutes. To improve transmission counting statistics,
patients weighing more than 90 kg were imaged for 16 seconds per step.
An energy window of 59.0±5.9 keV was used for the 241Am
transmission images. Typical transmission count rates varied from 6 to
30 1000 counts/s (kcps) depending on patient size, positioning, and
density. For the 99mTc-sestamibi stress study, an
energy window of 140±10.5 keV was set to collect emission data. The
projection data from the three detectors were acquired
simultaneously in both the transmission and emission
windows. A 20-minute transmission "blank" scan (
30 million
counts acquired once per week) was acquired to compute attenuation line
length sinograms from the transmission data. To minimize potential dead
time effects during the blank scan, the source was shielded to reduce
the beam intensity to less than 60 kcps.
After removal of cross-talk
contamination from the transmission and
emission data, attenuation maps were reconstructed from the truncated
transmission data using a penalized, weighted, least-squares
algorithm.19 20 The boundary constraint for the
reconstruction was the patient outline and the known position of the
imaging table. The patient outline was estimated from the emission
projection data. The initial estimate to the algorithm was
constructed from a FBP reconstruction of the transmission data with the
truncation ring artifact removed and the area between the FBP image and
patient outline assigned the attenuation coefficient of tissue. Before
reconstruction of the emission data, the uncontaminated emission
projection data from the parallel collimated detectors were summed.
The fan-beam emission data were not included in the reconstruction
to minimize possible truncation artifacts in large patients whose
fan-beam emission data would be severely truncated. AC emission
images were constructed using a penalized, weighted, least-squares
algorithm with the reconstructed attenuation maps to correct the
emission data for photon attenuation. The initial estimate for
the reconstruction of the AC emission images was a first-order
Chang-corrected FBP image.21 From this initial
estimate, transaxial emission images were reconstructed in 12
iterations. The average processing time for 18 AC emission images was
2.5 minutes.
NC emission images were reconstructed using conventional FBP with a ramp filter having a cutoff equal to the Nyquist frequency fn. Negative image pixels were not zeroed. Before reslicing, the NC and AC images were filtered with a three-dimensional Butterworth filter of order 5 with a frequency cutoff of 0.6*fn. NC and AC emission images were reformatted into short-axis and horizontal and vertical long-axis slices for visual and quantitative analyses. To normalize the resliced images for visual display, voxel counts outside of the heart were truncated to the maximum pixel count within the myocardium.
Visual Interpretation
All NC and AC images were interpreted
by two observers who
were blinded to the angiographic results. The resliced image sets from
group 1 and 2 patients were pooled and randomly presented to
the observer. The NC and AC image sets were presented to the
observers on separate days. While interpreting the images, the
observers were aware of patient sex and the type of reconstruction but
were unaware of the interpretation of the paired study (AC and NC). In
scoring the images, the basal, mid, and distal short-axis slices
were divided into six evenly spaced segments, and a single segment
representing the apex was scored from the long-axis
sections. Tracer uptake in each sector was scored as 1=normal,
2=equivocal, 3=abnormal, or 4=severely abnormal or
absent. Each
vascular territory was assigned the maximum score of the segments
within its range. Territories with discordant readings were reread and
assigned a consensus value. A vascular territory was considered
abnormal if one of the sectors within its boundaries received a score
2. Likewise, the study was considered abnormal if any vascular
territory was scored as abnormal.
Quantitative Analysis
Quantitative results were generated
from the tracer
distributions in polar map format compared with a database of normal
distributions.1 22 23 The distal-to-basal
rings of
the polar maps were constructed from maximum-count circumferential
profiles of short-axis slices. The apex was similarly sampled from
vertical long-axis slices. The polar maps were normalized to the
maximum count within each map. To account for differences in the photon
attenuation patterns of male and female patients, gender-specific
databases (n=20) were constructed for the quantitative analysis
of NC images. Gender-specific (n=20) and gender-composite
normal databases (10 men and 10 women) were constructed for the AC
analyses. Polar map pixels 2.5 SD below the normal mean of
the appropriate database values were scored as abnormal. The vascular
territories used to determine the localization and extent of the
perfusion defects in these maps were defined as described by Maddahi et
al.23 ROC analysis was used to determine the
abnormal extent thresholds in each vascular territory of the AC and NC
polar maps.
Statistical Analysis
All data are expressed as
mean±SD. The normalcy rate as
determined from group 1 patients was defined as the ratio of the number
of patients with normal tomograms to the total number of patients in
the group. Data from group 2 patients were used to construct ROC curves
and to calculate sensitivity, specificity, and accuracy values.
Sensitivity was defined as the number of true-positive tomograms
divided by the number of patients with angiographic disease.
Specificity was defined as the number of true-negative tomograms
divided by the number of patients without disease. ROC curves were
constructed by plotting the true-positive fraction
(TPF=sensitivity) versus the false-positive fraction
(FPF=1-specificity) for different abnormal thresholds. The
2 test was used to determine the significance of
differences in the normal coronary polar map distributions.
McNemar's test24 was used to determine differences in
paired data samples. The CORROC program25 was
used to fit the ROC curves, calculate the integral areas of the curves,
and estimate the significance of differences between AC and NC
curves.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Normal Tracer Distributions
Gender-specific databases of normal myocardial tracer distributions were computed and displayed in polar map format (Fig 1
) for the AC and NC images. Differences between the NC
patterns of the two sexes were most apparent in the lateral and
posterior walls of the myocardium, where the normalized
male distribution was 7% to 9% lower (P<.001) than the
normalized female distribution due to soft tissue attenuation. Because
there were no significant differences between the male and female AC
distributions, a gender-composite distribution was constructed. The
AC normal polar maps have improved homogeneity in the basal and distal
rings compared with the NC polar maps. The
anterior-to-posterior activity ratio in basal short-axis
sections decreased from 1.34±0.11 for the normal male NC distribution
to 1.00±0.08 for the AC distribution (P<.001).
Compensation for basal attenuation was also demonstrated by a decrease
in the distal-to-basal activity gradient in the posterior wall
from 1.15±0.05 for the NC images to 1.03±0.05 for the AC images
(P<.001). The 10% to 15% reduction in tracer activity at
the apex of the AC distribution is most likely due to the normal
anatomic thinning in this area and the partial volume effect that is
inherent to SPECT imaging.26
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Angiographic Characteristics
The angiographic findings for
the group 2 patients are summarized
in Table 1. Two patients did not have their RCAs
injected; therefore, visual and quantitative radionuclide data for
these distributions were not included in the analysis. Two
patients had dominant left coronary arteries, so the territory
commonly associated with the RCA was assigned to the LCx. Four vascular
territories in patients whose vessels were unstenosed and had had
previous myocardial infarction were omitted from the analysis.
For patients with significant stenoses, the mean number of
diseased vessels was 2.3±0.8 for a stenosis cutoff of 50%
and 2.1±0.8 for a stenosis cutoff of 70%. The mean severity
score for patients with disease was 2.8±0.8. For each coronary
distribution, the mean severity scores were 2.7±1.2 for the LAD,
2.6±1.2 for the LCx, and 3.2±1.2 for the RCA. Differences in
severity
scores were not significant.
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Visual Analysis of Images
Visual interpretation of the group
1 patients demonstrated a
significant increase in the observed normalcy rate (AC, 0.98±0.02; NC,
0.88±0.04; P=.027). In the visual analysis of the
NC images, there were seven false-positive readings, two involving
the LAD and five involving the RCA. Both of the LAD abnormalities were
due to breast attenuation in women. Four of the five false-positive
readings in the RCA territory could be attributed to diaphragmatic
attenuation; the AC images showed normal activity in each case. NC and
AC images from two of these false-positive patients are displayed
in Fig 2. The remaining false-positive study from
the NC images was also read as abnormal from the interpretation of the
AC images (LCx and RCA territories). This patient had a history of
dilated cardiomyopathy, which was the most likely
cause of the inhomogeneity in tracer distributions (NC and AC
images).
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Visual analysis was performed using the AC and NC images from
the group 2 patients, and ROC curves were plotted for the detection of
CHD and for the localization of disease in each of the three main
coronary distributions (Fig 3). Curve fits were
computed for each set of ROC data points and displayed on the ROC
plots. The constant curve fit for the uncorrected LAD data was replaced
with hand-drawn curves. The integral areas
(Az) for the AC and NC curves were calculated
with an estimate of the significance of the difference (P)
between the AC and NC Az values.
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There was
a significant improvement in the discriminating capacity of
the AC images compared with the NC images for the detection of CHD, as
demonstrated by the increase in the Az value
(Fig 3
). For the localization of disease, a significant
increase in
Az was seen in the RCA distribution. This
increase is attributed to a decrease in false-positive and
false-negative readings resulting from diaphragmatic attenuation.
The increased Az value for the LCx distribution
was not significant based on the P value and the statistics
of the study. Because the NC LAD data were not fit by ROC
analysis, the NC Az values were not
calculated for comparison of the LAD territory data.
Sensitivity,
specificity, and accuracy values are given in Table 2 for the
detection of CHD, localization of disease in
general, and localization in the LAD, LCx, and RCA territories
specifically. For patients with SVD and MVD, sensitivity values are
reported for the detection of disease in general in addition to
localization of stenosed vessels in these patients. With the exception
of the specificity values in the LAD territory, there were increases in
each of the variables at both 50% and 70% stenosis
breakpoints. The slight decrease in specificity for the localization of
disease in the LAD territory was not statistically significant.
Statistically significant differences (P<.05) between AC
and NC imaging were apparent in the measured accuracy for the detection
of CHD, localization of stenosed vessels in general, and localization
of disease in the LCx and RCA territories specifically. Significant
improvement with the use of AC images was also demonstrated in
localizing diseased vessels in patients with MVD. Specificity, and
therefore accuracy, values were not reported for the detection of CHD
in patients with SVD and MVD as these patients were a diseased subset
of group 2 and specificity values are based on patients without
disease.
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Quantitative Analysis of Images
From the quantitative
analysis of the AC and NC images
from the group 2 patients, ROC curves were plotted for the detection of
CHD and for the localization of disease in the LAD, LCx, and RCA
territories (Fig 4). Curve fits were computed for each
set of ROC points and displayed on ROC plots with their corresponding
Az and P values. Increases in
Az values were seen with AC in all of the
observed ROC curve pairs for both angiographic criteria. Statistically
significant differences were demonstrated for CHD detection in general
at both angiographic cutoffs and for the localization of disease in
each of the vascular territories using an angiographic cutoff of 50%
stenosis. The LCx territory also demonstrated a significant
improvement at the 70% stenosis cutoff.
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From the quantitative AC and NC ROC data, the optimal defect size for the localization of disease in each vascular territory was computed by maximizing diagnostic accuracy. The computed thresholds for AC images were 12% to 24% for the LAD, 12% to 28% for the LCx, and 8% to 12% for the RCA territories. For the NC images, the computed thresholds were 12% to 20% for the LAD, 12% to 28% for the LCx, and 0% to 8% for the RCA. For each of these threshold ranges, the lower limit had higher sensitivity at the expense of lower specificity. From these ranges, defect thresholds of 12% for the LAD, 12% for the LCx, and 8% for the RCA were selected for the analysis of both AC and NC defect maps. These defect thresholds were chosen from the measured ranges for the following reasons: (1) it is better to operate at higher sensitivities with a marginal decrease in specificity because the prevalence of disease in our clinical population is relatively high, (2) these thresholds are identical to the established cutoffs for NC defect maps commonly used,23 permitting comparisons with published data, and (3) the statistical significance of the results presented in the present study were invariant to the chosen defect thresholds (several threshold combinations in the above ranges were tested).
With the above defect size thresholds in the
quantitative
analysis of the group 1 patients, there was a significant
increase (P=.003) in the observed normalcy rate from the
interpretation of AC images (0.95±0.03) compared with NC images
(0.76±0.06). As seen in the visual analysis, statistically
significant increases in diagnostic accuracy were
demonstrated using AC images for the detection of CHD, for the
localization of disease in general, and for localizing disease in the
LCx and RCA vascular territories specifically (Table 3).
Quantitative interpretation of AC images also significantly improved
the diagnostic accuracy in localizing stenosed vessels in
patients with MVD. For patients with SVD, sensitivity and specificity
values were slightly higher using NC images compared with AC images,
but these increases were not significant. Data in this table also
demonstrated that the quantitative interpretation of AC images did not
significantly improve the detection of CHD in patients with SVD or
MVD.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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The simultaneous TCT/ECT imaging system used in the present study demonstrated improved diagnostic accuracy for the identification and localization of CHD. As a result, there were significant improvements in the observed normalcy rates of low-likelihood patients when using AC images compared with NC images. Increases in the observed normalcy rates were evident by both visual and quantitative analyses. With either visual or quantitative analysis of the AC images, there were increases in sensitivity, specificity, and accuracy for the detection and localization of CHD. The most significant increases in accuracy were apparent in the detection and localization of coronary stenoses of intermediate severity (
50% and 70%).
Detection of CHD
Both visual and quantitative ROC curves
demonstrated significant
improvements in the discriminating capacity of AC imaging compared with
NC imaging. This was evident by the larger Az
value for AC images for the detection of CHD. Larger
Az values demonstrate greater separation between
diseased and healthy coronary distributions, resulting in
better discrimination between stenosed and unstenosed states. It is
also important to note that the improvement of the AC curve compared
with the NC curve was greater at the 50% stenoses cutoff
(+20%, P=.005) in comparison to the improvement at the
70% stenoses cutoff (+12%, P=.016). This is
indicative of a significant increase in diagnostic accuracy
of AC imaging compared with NC imaging, especially for coronary
arteries with stenoses in the range of 50% to 70% compared
with more severe stenoses.
The characteristics of the AC data produced
statistically significant
increases in diagnostic accuracy with ROC analysis
for the detection of CHD at both angiographic cutoffs investigated. The
improvement in diagnostic accuracy of AC images compared
with NC images was a result of improved detection specificity
(P<.05) with no loss in detection sensitivity. With an
angiographic cutoff of 50% stenosis, visual interpretation
correctly identified 9 of 11 patients without CHD using AC images but
only 5 of 11 nondiseased patients when using NC images. For the two
false-positive AC studies, one patient had congestive heart failure
and a moderately dilated left ventricle, whereas the other had a large
severe anterior wall myocardial infarction that extended into the LCx
territory. For the latter patient, the LCx was unstenosed, resulting in
a false-positive interpretation of that vascular territory. The six
false-positive readings from the NC interpretations included the
two patients with false-positive readings from the AC
interpretations, three patients (all males) with diaphragmatic
attenuation (abnormal RCA interpretations), and one female patient with
anterior breast attenuation artifact (abnormal LAD interpretation).
Similar patterns of abnormality were demonstrated by quantitative
analysis.
Although visual interpretation of AC images demonstrated
increased
sensitivity for the detection of CHD compared with NC images, the
increase was not statistically significant at either angiographic
stenosis cutoff. Visual interpretation of the AC images with an
angiographic cutoff of 50% stenosis produced eight
false-negative interpretations: three patients had 50%
one-vessel stenoses, two patients had two vessels with 50%
stenoses, and three patients had balanced three-vessel
disease (all vessels 70% stenosed). The same patterns were seen in
the NC images where 5 of the 11 false-negative interpretations
were in patients with mild one-vessel disease (50% to 70%
stenosis). The negative interpretations of the images from
patients with mild SVD may be due to (1) differences between
physiological and angiographic disease
severity27 and (2) interobserver variability in the
interpretations of coronary angiograms.28 The
second most prominent cause of false-negative interpretations was
balanced three-vessel disease. Because the interpretation of SPECT
perfusion tomograms relies on the relative regional distribution of
activity in the myocardium, balanced coronary
disease can present as a uniform distribution. For balanced
coronary disease, absolute quantification of tracer uptake in
the myocardium is necessary to distinguish normal from
impaired coronary reserve. With the ability to correct SPECT
data for photon attenuation and the future implementation of scatter
correction methodology,29 quantification of perfusion may
soon be achievable with the potential for increased sensitivity,
especially in patients with balanced MVD and patients with relatively
mild disease in general.
With an angiographic cutoff of 50%, the
sensitivity (0.84) and
specificity (0.46) from the quantitatively interpreted NC
images agreed well with the sensitivity (0.87) and specificity (0.36)
values from the multicenter trial for NC stress
99mTc-sestamibi studies reported by Van Train et
al.3 From the data presented here, it is apparent
that the principle benefit of AC is a significant increase in test
specificity (0.82 versus 0.46) with no loss or a slight gain in
sensitivity (0.92 versus 0.84).
Localization of CHD
At both angiographic stenoses criteria,
diagnostic accuracy in localizing stenosed coronary
vessels increased with the interpretation of AC compared with NC
images. From the quantitative analyses, the increases in
accuracy for disease localization using AC images resulted from large
increases in sensitivity. The increased sensitivity can be attributed
to the uniformity of the mean and variance distributions of the AC
polarmaps compared with the normal NC maps. The uniform distribution of
the AC polarmaps provides stricter defect thresholds for the detection
of disease, resulting in improved sensitivity with no loss in
specificity. From the visual interpretations, increases in accuracy for
the localization of stenoses resulted from improvements in
vessel sensitivity (LAD and LCx territories) and in specificity (RCA
territory). These changes in sensitivity and specificity depend on the
observer's threshold for abnormal; therefore, other observers may show
increases in sensitivity and specificity directionally opposite to the
results of this study. Regardless of the directional change in
sensitivity and specificity, the ROC data predict that
diagnostic accuracy will increase for the localization of
stenosed vessels using AC images rather than NC images.
Comparison of Visual and Quantitative Results
For the
detection of CHD, the visual and quantitative results
agreed well. Both demonstrated that AC images more clearly
differentiate stenosed from nonstenosed states compared with NC images
and that the improvement in diagnostic accuracy results
primarily from increased specificity. However, in the localization of
stenosed vessels, visual and quantitative interpretations did not agree
as well. The discrepancies between visual and quantitative results are
attributed primarily to differences in the thresholds used for the
detection of disease. For visual analyses, the observer
uses a "learned" normal database to set mental limits for the
presence or absence of disease. Quantitative analyses used
predefined abnormal thresholds for each pixel based on a database of
normal studies. Based on these differences, it was expected that
sensitivity and specificity pairs might differ between visual and
quantitative interpretations. The parameter
"accuracy" is less dependent on the abnormality threshold used
because it combines the results from the diseased and undiseased
states. In comparing the data from Tables 2 and
3, there is good
agreement in the accuracy values between visual and quantitative
analyses. The same agreement is seen in the ROC curves, which
are much more informative regarding the differences between AC and NC
images as they provide all sensitivity and specificity pairs for all
detection thresholds. The minor differences in the significance of the
results between visual and quantitative ROC analyses can be
attributed to the statistical uncertainty from a relatively small
patient population.
Data Truncation and Iterative Reconstruction
A
triple-detector system with a line source positioned
opposite a single fan-beam collimator provides an excellent imaging
geometry for simultaneous TCT/ECT. With this geometry,
cross-talk contamination between the transmission and emission
energy windows is directly measured and corrected, minimizing the
introduction of bias in the reconstructed images. Patient data are
acquired in less than 20 minutes, minimizing artifacts due to patient
movement that are more likely to occur with longer acquisitions. With a
moveable line source, patient contoured orbits are achievable, reducing
the amount of transmission data truncation and maximizing emission
image resolution. The single limitation of this system is the
truncation of the transmission data due to the fan-beam collimator;
this necessitates an iterative reconstruction algorithm to accurately
reconstruct the undersampled regions of the thorax. In an effort to
decrease the computation time required to provide accurate estimates of
the truncated regions of the thorax, we incorporated a quadratic
penalty function in the objective function used in the reconstruction
of the truncated transmission data.20 The quadratic
penalty function constrains the amplitude of reconstructed image pixels
based on their nearest neighbors. As a result, the penalty function
quickly fills in the missing information based on neighboring pixels. A
consequence of the quadratic penalty function is a smoothing effect on
high-contrast edges in the reconstructed attenuation maps. Although
lung-tissue boundaries have high-contrast edges, respiratory
motion during imaging effectively decreases the contrast at these
boundaries. The small loss in contrast due to the quadratic penalty
function used in the reconstruction of the transmission maps is greatly
outweighed by its ability to estimate undersampled regions in the
thorax. The incorporation of nonquadratic penalty functions into the
reconstruction objective function is the basis of future work.
Limitations of AC Cardiac SPECT
The data from this study have
demonstrated the
diagnostic improvements that attenuation corrected SPECT
with TCT/ECT imaging can offer to myocardial perfusion SPECT. However,
from the comparison of AC and NC images, two potential areas of concern
have become apparent. The first concern is the 10% to 15% decrease in
activity in the apex relative to the uniform activity distribution in
the distal and proximal regions of the myocardium of the AC
images. This behavior requires the physician interpreting the AC
perfusion tomographs to recognize mild reductions in apical activity as
normal. Although this internal adjustment by the interpreting physician
is similar to the adjustment in the rules regarding diaphragmatic and
breast attenuation patterns in NC images, the decreased activity at the
apex is a consistent finding not dependent on gender or body
habitus. This independence produces less variability in the activity
distribution of the AC apex compared with the activity variations
resulting from soft tissue attenuation in NC images. As a result, the
AC images demonstrated significant improvements in
diagnostic accuracy compared with NC images. However, it is
important that physicians interpreting AC images familiarize themselves
with the AC normal perfusion distribution as the assumption of a
homogeneous activity distribution throughout the entire
myocardium could lead to false-positive interpretations
in the distal LAD territory.
The second potential problem with interpretation of AC images involves splachnic activity, which can spillover into nearby myocardium. The spillover of activity into the myocardium results from photon scatter in the patient and the dispersion of photons due to the distance between the patient and camera. Photon scatter is the more problematic of the two phenomena. Activity from nearby liver and bowel are the most troublesome source of scattered activity. Although photon scatter from the liver has been known to be a problem in the interpretation of the inferoposteroseptal walls of NC perfusion images in some patients, the effect is more severe in AC images. Because the attenuation correction procedure cannot distinguish scattered from unscattered photons, both components are equally amplified during attenuation correction. As a result, the scattered radiation is more prominently displayed in the AC images and poses a larger problem in the interpretation of AC images compared with the NC images of some patients. From the 119 cases reviewed for this article, liver activity was problematic in 6 NC and 13 AC images. To alleviate this problem, scatter subtraction methods need be implemented and validated. We are working on the implementation of an energy deconvolution method for estimating and removing the scatter component from the measured signal.29 To address the problem of photon dispersion, we are implementing three-dimensional iterative reconstruction methods incorporating the depth-dependent response of the imaging system in the system response matrix of our reconstruction algorithms.
Conclusions
Myocardial SPECT perfusion imaging has been
criticized for
inhomogeneous radiotracer distributions in healthy
individuals. This phenomenon has been attributed to photon attenuation
and has been blamed for reduced test specificity. We have demonstrated
that AC myocardial SPECT perfusion imaging using measured,
patient-specific attenuation maps effectively eliminates
attenuation artifacts from these studies and significantly
increases their specificity for the detection of CHD without a loss in
test sensitivity. The localization of disease was also improved,
evident by a significant increase in stenosed vessel sensitivity. Based
on the increased diagnostic accuracy seen in this study for
AC myocardial perfusion SPECT imaging, serious consideration for the
clinical implementation of this promising new technology in the
diagnosis of CHD is warranted. Intensive further investigation is
necessary before routine clinical use.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This work was supported by NIH grant RO1-HL-41047 (Dr Corbett) and NIH grant R29-CA-60711 (Dr Fessler). The authors thank Robert J. Ackermann and Steven Pitt for their help in data acquisition and processing. The authors also wish to thank the Ohio Imaging Division of Picker International for their engineering and software support.
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Footnotes |
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Reprint requests to Edward P. Ficaro, PhD, University of Michigan Hospitals, B1G412/0028, 1500 E Medical Center Dr, Ann Arbor, MI 48109. E-mail eficaro@umich.edu.
Received May 30, 1995; revision received September 18, 1995; accepted September 24, 1995.
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