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ACC/AHA 2008 Performance Measures for Adults With ST-Elevation and Non-ST-Elevation Myocardial Infarction

ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease
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J Am Coll Cardiol, 1998; 32:927-935
© 1998 by the American College of Cardiology Foundation
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CLINICAL STUDIES

Attenuation-corrected 99mTc-tetrofosmin single-photon emission computed tomography in the detection of viable myocardium: comparison with positron emission tomography using 18F-fluorodeoxyglucose

Ichiro Matsunari, MD*, Guido Böning*, Sibylle I. Ziegler, PhD*, Stephan G. Nekolla, PhD*, Jens C. Stollfuss, MD*, Istvan Kosa, MD*, Edward P. Ficaro, PhD{dagger} and Markus Schwaiger, MD, FACC*

* Nuklearmedizinische Klinik und Poliklinik der Technischen Universität München, Klinikum rechts der Isar, Munich, Germany
{dagger} Department of Internal Medicine, Division of Nuclear Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA

Manuscript received January 2, 1998; revised manuscript received May 27, 1998, accepted June 4, 1998.

Address for correspondence: Dr. Markus Schwaiger, Nuklearmedizinische Klinik und Poliklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675 München, Germany


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
Objectives. The purpose of this study was to assess the efficacy of attenuation-corrected (AC) technetium-99m (99mTc)-tetrofosmin single-photon emission computed tomography (SPECT) in detecting viable myocardium compared to 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET).

Background. The role of 99mTc-labeled perfusion tracers in the assessment of myocardial viability remains controversial. Attenuation artifacts affect the diagnostic accuracy of SPECT images.

Methods. Twenty-four patients with coronary artery disease (mean left ventricular ejection fraction 30%) underwent resting 99mTc-tetrofosmin SPECT and FDG PET imaging. Both AC and non–attenuation-corrected (NC) SPECT images were generated.

Results. Using a 50% threshold for viability by FDG PET, the percentage of concordant segments of viability between 99mTc-tetrofosmin and FDG on the patient basis increased from 79.8% ± 14.0% (mean ± SD) on the NC images to 90.8% ± 10.6% on the AC images (p = 0.002). The percentage of 99mTc-tetrofosmin defect segments within PET-viable segments, an estimate for the degree of underestimation of viability, decreased from 19.8% ± 15.2% on the NC images to 9.7% ± 12.6% on the AC images (p = 0.01). Similar results were obtained when a 60% threshold was used to define viability by FDG PET. When the anterior-lateral and inferior-septal regions were separately analyzed, the effect of attenuation correction was significant only in the inferior-septal region.

Conclusions. The results indicate that AC 99mTc-tetrofosmin SPECT improves the detection of viable myocardium mainly by decreasing the underestimation of viability particularly in the inferior-septal region, although some underestimation/overestimation of viability may still occur even with attenuation correction.

Abbreviations and Acronyms
  AC = attenuation-corrected
  CAD = coronary artery disease
  FDG = 18F-fluorodeoxyglucose
  LV = left ventricular
  NC = non–attenuation-corrected
  PET = positron emission tomography
  SPECT = single-photon emission computed tomography

Myocardial viability assessment represents an important clinical issue in patients with coronary artery disease (CAD) and severe left ventricular (LV) dysfunction in deciding whether to proceed with revascularization (1). Viable myocardial areas are likely to benefit from revascularization, whereas revascularization of scarred myocardium will not lead to an improvement in contractile function. A number of studies have shown that metabolic imaging with positron emission tomography (PET) and 18F-fluorodeoxyglucose (FDG) is an accurate noninvasive diagnostic tool to distinguish viable from scarred myocardium (2–6). Availability and high cost, however, limit the wide clinical use of PET imaging. Therefore, efforts have been made to assess the efficacy of single-photon emission computed tomography (SPECT) to identify viable myocardium (7).

Thallium-201 (201Tl) myocardial imaging using either a reinjection (8,9) or rest-redistribution (10) protocol is a well-accepted diagnostic technique for the evaluation of myocardial viability. However, despite the excellent physiologic characteristics of 201Tl for assessing viability, its low photon energy of 68 to 80 keV and its relatively long half-life pose limitations. Recently, cationic lipophilic technetium-99m (99mTc)-labeled perfusion tracers such as 99mTc-sestamibi (11) and 99mTc-tetrofosmin (12) have been introduced as an alternative to 201Tl, and their utility in assessing myocardial viability, particularly using a quantitative analysis of regional tracer activity, has been reported (13–18). The use of 99mTc-labeled perfusion agents as a viability marker, however, has been questioned by several studies (14,19–21) in which an underestimation of viable myocardium by 99mTc-labeled perfusion agents has been observed, particularly when compared to FDG PET. Notably, a recent study has shown that underestimation of viable myocardium occurred predominantly in the inferior wall (22), suggesting that the known attenuation of single-photon emitting tracers on conventional SPECT images may play an important role in such underestimation.

Recently, approaches for attenuation correction have been proposed (23,24) and clinical results have shown its utility to improve the detection of CAD (25). We have developed a system for simultaneous transmission/emission measurement using a triple-head SPECT system with an off-set fan beam collimator and Americium 241 (241Am) line source (26,27). We hypothesized that the use of attenuation correction would improve the detection of viable myocardium by SPECT techniques.

This study was therefore designed to assess the efficacy of attenuation-corrected (AC) resting 99mTc-tetrofosmin SPECT for the detection of viable myocardium using FDG PET as the reference method for assessing tissue viability.


   Methods
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 Abstract
 Methods
Results
 Discussion
 References
 
Patients.   The study population consisted of 25 patients with angiographically proved CAD and impaired regional or global LV function. There were 21 men and 3 women with a mean age of 61 years (range from 48 to 82 years). All but two patients had a history of prior myocardial infarction (12 anterior wall infarctions, 4 inferior wall infarctions and 7 anterior and inferior wall infarctions). The inclusion criteria of this study were subnormal left ventricular ejection fraction (LVEF) (<45%) and/or severe regional left ventricular dysfunction (akinesis or dyskinesis). The mean LVEF, which was obtained in 23 of 25 patients by contrast left ventriculography (n = 21) or radionuclide ventriculography (n = 2), was 30% ± 11%, ranging from 13% to 65%. The remaining two patients, in whom LVEF was not measured, had akinetic regions in their infarct-related arterial territories as assessed by left ventriculography. We studied only patients with stable CAD; patients with recent myocardial infarction (≤1 month) were excluded. Two patients had previously undergone revascularization. All but one patient underwent resting 99mTc-tetrofosmin SPECT with simultaneous transmission/emission scan followed by PET imaging with FDG on a single day; in the remaining one patient, PET imaging was performed two days after 99mTc-tetrofosmin SPECT imaging. All patients continued their cardiac medications during the radionuclide studies.

Coronary artery disease was defined as ≥50% reduction in the luminal diameter of at least one major epicardial coronary artery as determined by coronary angiography. Twenty patients had significant stenoses of three vessels, three patients of two vessels and two patients of one vessel (mean 2.7 vessels per patient). All patients gave informed consent in accordance with the institutional Human Clinical Study Committee.

Rest 99mTc-tetrofosmin imaging.   After an overnight fast, each patient was injected with 370 MBq of 99mTc-tetrofosmin at rest. Simultaneous transmission/emission scanning was started 40 min after injection using the SPECT system as described below.

Simultaneous transmission/emission scan.   Simultaneous transmission/emission imaging was performed in a manner as previously described (26,27), using a triple-head SPECT system (MULTISPECT 3, Siemens AG, Erlangen, Germany) equipped with a low-energy, fan-beam collimator with a focal length of 53 cm with its focal line offset by 17 cm for detector 1 and with low-energy, high-resolution, parallel-hole collimators for detector 2 and 3. The transmission line source consisted of a 5.55 GBq (150 mCi) 241Am line source sealed in a stainless-steel tube.

Transmission and emission projection data were acquired in 64 x 64 matrices. Images were acquired in 6° steps over 360° for 20 s/projection. An energy window of 59.0 ± 5.9 keV was used for the 241Am transmission photons and a 15% window centered on the 140 keV peak was used for the emission data. An 80-s transmission "blank" scan was acquired to compute attenuation maps from the transmission data.

Processing of SPECT data.   Image reconstruction of SPECT data was performed in a manner similar to that previously reported by Ficaro et al. (25) except for the use of filtered back projection to reconstruct transmission data (26,27). The geometry used in the current study provided a transmission imaging field of view of 39 cm, yielding little truncation of the transmission data compared to symmetrical geometry. The attenuation maps were smoothed using a Gaussian function with a 2-pixels (14 mm) full-width half-maximum. The AC emission images were reconstructed using an iterative reconstruction method (penalized weighted least squares algorithm [28]) with reconstructed attenuation maps to correct the emission data for photon attenuation. The non–attenuation-corrected (NC) emission images were reconstructed using filtered back projection with a Butterworth filter of order 5 with a frequency cutoff of 0.25 cycles/pixel.

Positron emission tomography.   Attenuation-corrected static PET images with FDG were acquired 40 min after injection of 370 MBq of FDG using either ECAT 951R/31 (n = 9) or ECAT 921/47 (n = 16) (CTI/Siemens AG, Knoxville, Tennessee). In-plane spatial resolution was 6 mm full-width half maximum for both scanners. In subjects without diabetes mellitus, FDG injection was conducted after an oral glucose load. Short-acting insulin was administered in known or suspected diabetic subjects with hyperglycemia to enhance myocardial uptake of FDG as previously described (5). A transmission scan was acquired for 20 min using three retractable 68Ge/68Ga rod sources. Static PET imaging lasting for 20 min was started 40 min after the injection of FDG.

The transaxial data were reconstructed in a 128 x 128 pixel matrix using a Hanning filter with a cutoff frequency of 0.3 cycles/pixel. The reconstructed transaxial images were transferred to the same workstations used for processing the SPECT data.

Data analysis.   Image data analysis was performed using a semiquantitative polar map approach for both SPECT and PET data, which was developed in our laboratory. This method involved two steps: 1) the long axis of the left ventricle was defined interactively in three dimensions; 2) an automatic volumetric radial search for activity maxima was performed. The LV myocardium was then divided into apical, anterior, septal, lateral and inferior regions. Each of the anterior, septal, lateral and inferior regions was further divided into distal and basal segments, resulting in nine segments per patient. The SPECT images were normalized to the pixel showing maximal value in the LV myocardium. A segment was considered to have a 99mTc-tetrofosmin defect if the mean regional activity was <50% of peak activity. The use of 50% of peak activity to define a defect as a threshold cutoff for viability by 99mTc-tetrofosmin was derived from previous literature using this tracer for assessing myocardial viability (15,18). The regional FDG uptake was normalized to the region with the maximal 99mTc-tetrofosmin uptake on the AC images. A segment was considered viable if the normalized regional FDG activity was ≥50% or ≥60% of the reference region; a segment was considered nonviable if the normalized regional FDG activity was <50% or <60% of the reference region (9,20,21,29,30).

Statistical analysis.   Data were expressed as mean ± SD. Because the behavior of different segments within a given patient is not independent, patients were used as the unit of analysis. For this purpose, we calculated the following three parameters for an individual patient: 1) the percentage of concordant segments regarding viability between 99mTc-tetrofosmin SPECT and FDG PET; 2) the percentage of 99mTc-tetrofosmin defect segments (<50% of peak activity) within viable segments by FDG PET; 3) the percentage of 99mTc-tetrofosmin uptake segments (≥50% of peak) within nonviable segments. The percentage of concordant segments should give an estimate of diagnostic accuracy of 99mTc-tetrofosmin SPECT to detect viable myocardium for a given patient. The percentage of 99mTc-tetrofosmin defect segments within PET viable segments, on the other hand, should give an estimate for the degree of underestimation of viability by 99mTc-tetrofosmin, whereas the percentage of 99mTc-tetrofosmin uptake segments within PET nonviable segments should give an estimate for the degree of overestimation of viability by 99mTc-tetrofosmin. A Wilcoxon signed-rank test was used to compare mean values between the NC and AC images. Statistical significance was defined as p < 0.05.


   Results
Top
 Abstract
 Methods
 Results
Discussion
 References
 
Of 25 patients, one was considered to have an inadequate FDG study due to poor image quality and was excluded from further analysis. The remaining 24 patients had FDG images of diagnostic quality and were considered to be eligible for the study.

Comparison of activities between 99mTc-tetrofosmin and FDG.   Figure 1 displays NC and AC 99mTc-tetrofosmin SPECT images as well as corresponding FDG PET images from a patient with three-vessel CAD and LV dysfunction. The NC 99mTc-tetrofosmin SPECT images show defects in the apex and inferior wall. The AC images reveal 99mTc-tetrofosmin activity in the inferior wall, while the apical wall still shows a defect, suggesting the presence of viable myocardium in the inferior wall. The FDG PET images confirm the presence of viable myocardium in that region. The transmission images show there was no truncation with the SPECT system used in this study.



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  		Figure 1 An 82-year-old man with three-vessel coronary artery disease. (A) The non–attenuation-corrected 99mTc-tetrofosmin images (left), attenuation-corrected 99mTc-tetrofosmin images (center) and positron emission tomography with 18F-fluorodeoxyglucose (right). (B) Reconstructed transmission images of the patient.

 
Percentage of viable myocardium in relation to 99mTc-tetrofosmin activity is shown in Table 1. All 216 segments were evaluable on both NC and AC images. Of a total of 216 segments, 201 (93%) and 182 (84%) segments, respectively, were viable using 50% and 60% thresholds to define viability by FDG PET. Most of the segments with preserved 99mTc-tetrofosmin activity (≥70% of peak activity) on both NC and AC images showed evidence of tissue viability by FDG PET regardless of the cutoff value applied. Conversely, none of the segments with very low 99mTc-tetrofosmin activity (<30% of peak activity) showed evidence of tissue viability. On the other hand, segments with mildly (50% to 70% of peak) to severely (30% to 50% of peak) reduced 99mTc-tetrofosmin activity showed various patterns of tissue viability.


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  		Table 1 Percentage of Viable Myocardium in Relation to 99mTc-Tetrofosmin Activity (Number of Segments)

 
All segments
Figure 2 shows the percentages of concordant segments regarding viability between 99mTc-tetrofosmin SPECT and FDG PET, the percentages of 99mTc-tetrofosmin defect segments within PET viable segments and the percentages of 99mTc-tetrofosmin uptake segments within PET nonviable segments on the patient basis from a total of 216 segments. Using a 50% threshold for viability by FDG PET, the percentage of concordant segments of viability between 99mTc-tetrofosmin SPECT and FDG PET, an estimate of diagnostic accuracy of 99mTc-tetrofosmin SPECT for the detection of viable myocardium, significantly increased from 79.8% ± 14.0% on the NC images to 90.8% ± 10.6% on the AC images (p = 0.002). The percentage of 99mTc-tetrofosmin defect segments within viable segments, an estimate for the degree of underestimation of viability by 99mTc-tetrofosmin, decreased from 19.8% ± 15.2% on the NC images to 9.7% ± 12.6% on the AC images (p = 0.01). The percentage of 99mTc-tetrofosmin uptake segments within PET nonviable segments, an estimate for the degree of overestimation of viability by 99mTc-tetrofosmin, tended to decrease from 35.2% ± 44.5% on the NC images to 3.7% ± 11.0% on the AC images, but with marginal statistical significance (p = 0.066) because of the high standard deviation and low patient number included in this analysis; only 9 of 24 patients had nonviable segments based on FDG activity. Similar results were obtained when a 60% threshold was used to define viability by FDG PET. The percentage of concordant segments between 99mTc-tetrofosmin and FDG increased from 83.0% ± 12.1% on the NC images to 90.3% ± 13.3% on the AC images (p = 0.028). The percentage of 99mTc-tetrofosmin defect segments within viable segments decreased from 14.1% ± 13.5% on the NC images to 5.7% ± 8.0% on the AC images (p = 0.014). The percentages of 99mTc-tetrofosmin uptake segments within PET nonviable segments, on the other hand, did not differ significantly between the NC and AC images (41.0% ± 41.4% vs. 25.6% ± 34.3%, respectively, p = 0.357). Thus, attenuation correction improved the concordance of viability between 99mTc-tetrofosmin SPECT and FDG PET, and decreased the underestimation of viability by 99mTc-tetrofosmin. Additionally, there was a trend towards improved overestimation of viability by attenuation correction. However, some underestimation and/or overestimation of viability by 99mTc-tetrofosmin still occurred even on the AC images.



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  		Figure 2 Bar charts showing the percentage of concordant segments regarding viability between 99mTc-tetrofosmin SPECT and FDG PET (labeled as Concordance), the percentage of 99mTc-tetrofosmin defect segments (<50% of peak activity) within viable segments by FDG PET (labeled as TDV) and the percentage of 99mTc-tetrofosmin uptake segments (≥50% of peak) within nonviable segments (labeled as TUNV) from all 216 segments. Data using a 50% threshold cutoff to define viability by FDG PET are illustrated on the left, and those using a 60% threshold cutoff are on the right. Values are calculated on the patient basis and are expressed as mean ± SD. NC = non–attenuation-corrected image; AC = attenuation-corrected image; n = the number of patients who were eligible for the analysis.

 
Segments with abnormal wall motion
Regional wall motion was abnormal in the majority of segments in this patient population. Fifty segments in 15 patients had normal wall motion, 76 segments in 19 patients were hypokinetic, 75 segments in 21 patients akinetic and 15 segments in 6 patients were dyskinetic by contrast or radionuclide left ventriculography. All patients had at least one dysfunctional myocardial segment.

Figure 3 shows the same comparisons as in Figure 2 for 166 asynergic segments. Similar to the results from all 216 segments, the percentage of concordant segments of viability between 99mTc-tetrofosmin SPECT and FDG PET increased from 74.2% ± 20.5% on the NC images to 88.7% ± 13.7% on the AC images (p = 0.005) using a 50% threshold for viability by FDG PET. The percentage of 99mTc-tetrofosmin defect segments within viable segments decreased from 24.5% ± 21.4% on the NC images to 13.7% ± 22.2% on the AC images (p = 0.036). The percentage of 99mTc-tetrofosmin uptake segments within PET nonviable segments tended to decrease from 35.2% ± 44.5% on the NC images to 3.7% ± 11.0% on the AC images, but did not reach statistical significance (p = 0.066). Using a 60% threshold for viability by FDG PET, the percentage of concordant segments between 99mTc-tetrofosmin and FDG again increased from 77.9% ± 18.5% on the NC images to 89.3% ± 14.6% on the AC images (p = 0.035). The percentage of 99mTc-tetrofosmin defect segments within viable segments decreased from 18.2% ± 19.9% on the NC images to 6.7% ± 10.2% on the AC images (p = 0.010). The percentages of 99mTc-tetrofosmin uptake segments within PET nonviable segments did not differ significantly between the NC and AC images (41.0% ± 41.4% vs. 25.6% ± 34.3%, respectively, p = 0.357). Thus, when only the segments with wall motion abnormality were considered, attenuation correction again improved the concordance of viability between 99mTc-tetrofosmin and FDG, and decreased the underestimation of viability by 99mTc-tetrofosmin.



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  		Figure 3 Bar charts showing the percentage of concordant segments regarding viability between 99mTc-tetrofosmin SPECT and FDG PET (labeled as Concordance), the percentage of 99mTc-tetrofosmin defect segments (<50% of peak activity) within viable segments by FDG PET (labeled as TDV) and the percentage of 99mTc-tetrofosmin uptake segments (≥50% of peak) within nonviable segments (labeled as TUNV) from 166 asynergic segments. Data using a 50% threshold cutoff to define viability by FDG PET are illustrated on the left, and those using a 60% threshold cutoff are on the right. Values are calculated on the patient basis, and are expressed as mean ± SD. NC = non–attenuation-corrected image; AC = attenuation corrected image; n = the number of patients who were eligible for the analysis.

 
Regional analysis.   Because the effect of attenuation correction varies from region to region as demonstrated by Ficaro et al. (25,31), we separately assessed the effect of attenuation correction in two different myocardial regions: the inferior-septal region, where attenuation artifacts are most likely to occur, and the anterior-lateral region, which includes the apex.

Anterior-lateral region
Figure 4 A shows the percentages of concordant segments regarding viability between 99mTc-tetrofosmin SPECT and FDG PET, the percentages of 99mTc-tetrofosmin defect segments within PET viable segments and the percentages of 99mTc-tetrofosmin uptake segments within PET nonviable segments in the anterior-lateral region. Using a 50% threshold for viability by FDG PET, the percentages of concordant segments of viability between 99mTc-tetrofosmin and FDG were similar between the NC and AC images (86.7% ± 14.0% vs. 87.5% ± 16.5%, respectively, p = 0.796). The percentages of 99mTc-tetrofosmin defect segments within viable segments were also similar between the NC and AC images (10.4% ± 13.6% vs. 12.1% ± 17.4%, respectively, p = 0.582). The percentages of 99mTc-tetrofosmin uptake segments within PET nonviable segments tended to decrease from 44.5% ± 50.2% on the NC images to 5.5% ± 13.5% on the AC images, but did not differ significantly (p = 0.102) because only six patients had PET nonviable segments in the anterior-lateral region. Using a 60% threshold for viability by FDG PET, the percentages of concordant segments of viability between 99mTc-tetrofosmin and FDG were again similar between the NC and AC images (85.0% ± 14.7% vs. 87.5% ± 14.2%, respectively, p = 0.366). The percentages of 99mTc-tetrofosmin defect segments within viable segments were also similar between the NC and AC images (7.5% ± 12.9% vs. 9.4% ± 13.3%, respectively, p = 0.380). The percentage of 99mTc-tetrofosmin uptake segments within PET nonviable segments decreased from 62.5% ± 36.5% on the NC images to 18.8% ± 27.4% on the AC images, but did not reach statistical significance (p = 0.056) because only eight patients had PET nonviable segments in this region. Thus, the effect of attenuation correction was not significant in the anterior-lateral region, although there was a trend toward improved overestimation of viable myocardium by 99mTc-tetrofosmin.



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  		Figure 4 Bar charts showing the percentage of concordant segments regarding viability between 99mTc-tetrofosmin SPECT and FDG PET (labeled as Concordance), the percentage of 99mTc-tetrofosmin defect segments (<50% of peak activity) within viable segments by FDG PET (labeled as TDV) and the percentage of 99mTc-tetrofosmin uptake segments (≥50% of peak) within nonviable segments (labeled as TUNV) in the anterior-lateral (A) and inferior-septal regions (B). Data using a 50% threshold cutoff to define viability by FDG PET are illustrated on the left, and those using a 60% threshold cutoff are on the right. Values are calculated on the patient basis, and are expressed as mean ± SD. NC = non–attenuation-corrected image; AC = attenuation corrected image; n = the number of patients who were eligible for the analysis.

 
Inferior-septal region
Figure 4B illustrates the same comparisons for the inferior-septal region. Using a 50% threshold for viability by FDG PET, the percentage of concordant segments of viability between 99mTc-tetrofosmin and FDG significantly increased from 70.8% ± 24.1% on the NC images to 94.8% ± 12.7% on the AC images (p < 0.001). The percentage of 99mTc-tetrofosmin defect segments within viable segments decreased from 29.5% ± 26.5% on the NC images to 5.9% ± 13.9% on the AC images (p = 0.001). The percentages of 99mTc-tetrofosmin uptake segments within PET nonviable segments did not differ significantly between the NC and AC images (12.5% ± 25.0% vs. 0.0% ± 0.0%, respectively, p = 0.317). When a 60% threshold cutoff was used to define viability by FDG PET, the percentage of concordant segments of viability between 99mTc-tetrofosmin and FDG again increased from 80.2% ± 20.8% on the NC images to 93.8% ± 16.9% on the AC images (p = 0.028). The percentage of 99mTc-tetrofosmin defect segments within viable segments decreased from 19.1% ± 22.6% on the NC images to 0.0% ± 0.0% on the AC images (p = 0.002). The percentage of 99mTc-tetrofosmin uptake segments within PET nonviable segments on the NC images (12.5% ± 23.1%) appeared to be lower than that on the NC images (35.4% ± 44.0%), but was not significantly different (p = 0.269). Thus, attenuation correction improved the concordance of viability between 99mTc-tetrofosmin and FDG, and decreased the underestimation of viability by 99mTc-tetrofosmin in the inferior-septal region.


   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
This study describes for the first time the utility of attenuation correction for assessing myocardial viability with SPECT imaging. The major findings of this study were as follows: 1) attenuation correction increased the percentage of concordant segments regarding viability between 99mTc-tetrofosmin SPECT and FDG PET, and decreased the underestimation of viability by 99mTc-tetrofosmin; 2) when the LV myocardium was divided into two regions, only the inferior-septal region showed such improvements, while the anterior-lateral region did not.

99mTc-tetrofosmin as a myocardial viability marker.   Technetium-99m-tetrofosmin is a newly introduced cationic lipophilic 99mTc-labeled myocardial perfusion tracer as an alternative to 201Tl (12). This agent reportedly has good diagnostic accuracy for detection of CAD when compared with 201Tl (32). It has been shown that the uptake and retention of this tracer depend on cellular metabolism (33), suggesting that cellular viability may be essential for its uptake and retention. A recent animal study has also demonstrated that myocardial 99mTc-tetrofosmin uptake is affected not only by flow but also by viability (34). In clinical studies, it has been reported that regional resting 99mTc-tetrofosmin activity closely correlates with regional reinjection 201Tl activity (15), and that defect size on resting 99mTc-tetrofosmin images is similar to that on reinjection 201Tl images (35), suggesting the potential utility of this tracer as a myocardial viability marker. In another study, using a quantitative approach and receiver operating characteristic analysis, rest 99mTc-tetrofosmin and rest-redistribution 201Tl imaging were found to be comparable in predicting functional recovery after revascularization (18). To date, however, the direct comparison of 99mTc-tetrofosmin activity with metabolic activity as measured by FDG PET has not yet been reported.

Effect of attenuation correction.   The present data indicate that none of the segments with absent 99mTc-tetrofosmin uptake (<30% of peak activity) on both NC and AC images showed evidence of tissue viability by PET. In contrast, most of the segments with preserved 99mTc-tetrofosmin activity (≥70% of peak) were viable. This observation suggests that the determination of myocardial viability may not be difficult in these extreme categories regardless of whether attenuation correction is used. On the other hand, the segments with mildly to severely reduced 99mTc-tetrofosmin activity (30% to 70% of peak) showed various patterns of viability.

We observed that a considerable portion (14.1% to 19.8%) of PET viable segments had 99mTc-tetrofosmin defects (defined as <50% of peak) on the conventional NC images, indicating that the NC 99mTc-tetrofosmin images underestimate tissue viability compared to FDG PET. This is in agreement with published data comparing 99mTc-sestamibi SPECT with FDG PET (14,21,22). Sawada et al. (21) and Altehoefer et al. (19) observed metabolic activity within 99mTc-sestamibi defects and concluded that 99mTc-sestamibi uptake may underestimate the presence of viable myocardium. Dilsizian et al. (14) reported high agreement for viability between reinjection 201Tl and 99mTc-sestamibi imaging using quantitative analysis, but underestimation of viable myocardium still occurred in 4 of 18 regions (22%) with irreversible 99mTc-sestamibi defects (<50% of peak activity). More recently, Soufer et al. (22) have demonstrated that such underestimation of viable myocardium was predominantly observed in the inferior region, where attenuation artifacts are likely to occur. It is well recognized that attenuation artifacts may unfavorably affect the quantification of regional tracer activity on conventional SPECT images. Our data indicate that the AC images increase the concordance of viability between 99mTc-tetrofosmin SPECT and FDG PET, and decrease the underestimation of viable myocardium, which may partially explain the underestimation of viable myocardium with 99mTc-sestamibi observed in the previous studies. When two myocardial regions (i.e., the anterior-lateral region and inferior-septal region) were separately analyzed, only the inferior-septal region showed such significant improvements while the anterior-lateral region did not. Thus, the benefit of attenuation correction appears to be the improved underestimation of viability, particularly in the inferior-septal region, resulting in the improved overall concordance of viability between 99mTc-tetrofosmin SPECT and FDG PET. It should also be noted, however, that even AC images may still underestimate and/or overestimate tissue viability as compared to FDG PET.

Although the previous studies have mainly focused on underestimation of viable myocardium using SPECT imaging and 99mTc perfusion tracers, an overestimation of viability may also occur in the clinical setting. Soufer et al. (22) reported that such overestimation of viability by 99mTc-sestamibi imaging predominantly occurred in the apex, which is consistent with our results that, on the NC images, the percentage of 99mTc-tetrofosmin uptake segments within nonviable segments was relatively high in the anterior-lateral region (Fig. 4A). It was not clear from the current data whether attenuation correction would improve such overestimation of viable myocardium by 99mTc-tetrofosmin SPECT imaging, although there was a trend toward improved overestimation of viability. This was partially because only limited number of patients had nonviable segments based on FDG activity, despite the severe CAD in our study population as evidenced by the low LVEF (30% ± 11%) and high prevalence of multivessel disease. However, this reflects the fact that even in patients with severe CAD, the majority of dysfunctional myocardium is metabolically active as measured by FDG PET. In a study by Baer et al. (29), for example, 30 of 42 patients (71%) had FDG activity in their severely dysfunctional and infarct regions. A further study specifically involving patients with a large amount of nonviable myocardium may be necessary to address this issue.

Clinical implications.   We are aware that perfusion imaging alone, in the absence of metabolic information, may not completely resolve the challenging issue of myocardial viability even when attenuation correction is performed. Recent PET studies using flow tracer have shown that perfusion imaging with attenuation correction alone may have a limited value in predicting functional recovery after revascularization (6,36). Although the preserved myocardial perfusion is certainly an important factor for maintaining tissue viability as demonstrated in this study and in others (37,38), it may not necessarily imply the presence of ischemically compromised but viable myocardium. Considering the wide availability of SPECT techniques as compared to PET, and the increasing interest in the potential use of 99mTc-based tracers as a viability marker (13,16,17,39–41), however, it is important to develop and evaluate newer SPECT techniques using 99mTc agents for the detection of viable myocardium. It is also noteworthy that previous viability studies have often pointed out that attenuation artifacts may unfavorably affect the diagnostic accuracy of viability tests using conventional SPECT techniques (14,16,17,19,22,42). In this regard, the results of the current study indicate that attenuation correction represents a useful improvement in the detection of viable myocardium using a quantitative approach and SPECT imaging.

Study limitations.   We directly compared AC and NC 99mTc-tetrofosmin activity using FDG PET as the reference standard; functional outcome data after revascularization were not obtained. Thus, although numerous studies have demonstrated that preserved metabolic activity measured by FDG PET is an accurate maker of tissue viability (2,4,29,30,42), definitive statements regarding the use of AC 99mTc-tetrofosmin SPECT in the management of patients with LV dysfunction are not possible based on the current data. The purpose of this study was, however, to investigate the effect of attenuation correction on myocardial 99mTc-tetrofosmin SPECT for assessing viability using FDG as a biological marker of tissue viability. Further prospective studies involving patients undergoing revascularization are required to determine the clinical significance of AC 99mTc-tetrofosmin SPECT imaging.

We did not perform scatter correction in this study. As described by Ficaro et al. (25) and by our previous study (26), attenuation correction may amplify the scatter spillover into nearby myocardium, typically the inferior-septal wall, from splanchnic activity. Therefore, it is anticipated that the additional use of scatter correction combined with attenuation correction could have further improved the detection of viable myocardium. However, there are no methods for simultaneous attenuation/scatter correction currently available for clinical use. Further work on instrumentation should aim for the incorporation of scatter correction into attenuation correction.

Conclusions.   Our data indicate that AC resting 99mTc-tetrofosmin myocardial SPECT improves the detection of viable myocardium mainly by decreasing the underestimation of viability in the inferior-septal region. The AC 99mTc-tetrofosmin SPECT may, however, still underestimate and/or overestimate myocardial viability compared to FDG PET. Further work should be directed toward the incorporation of scatter correction into attenuation correction.


   Acknowledgments
 
We thank Dr. Claire S. Duvernoy for her suggestions during manuscript preparation. We also thank Dr. Hideji Tanii, Department of Hygiene, Kanazawa University School of Medicine, for expertise in data analysis.


   Footnotes
 
Dr. Matsunari was supported by Mitsubishi Research Institute, Japan.


   References
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 Abstract
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 References
 

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