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Objective: Left ventricular (LV) function and dyssynchrony parameters measured from serial gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) using blinded processing had a poorer repeatability than when manual side-by-side processing was used. The objective of this study was to validate whether an automatic alignment tool can reduce the variability of LV function and dyssynchrony parameters in serial gated SPECT MPI., Methods: Thirty patients who had undergone serial gated SPECT MPI were prospectively enrolled in this study. Thirty minutes after the first acquisition, each patient was repositioned and a gated SPECT MPI image was reacquired. The two data sets were first processed blinded from each other by the same technologist in different weeks. These processed data were then realigned by the automatic tool, and manual side-by-side processing was carried out. All processing methods used standard iterative reconstruction and Butterworth filtering. The Emory Cardiac Toolbox was used to measure the LV function and dyssynchrony parameters., Results: The automatic tool failed in one patient, who had a large, severe scar in the inferobasal wall. In the remaining 29 patients, the repeatability of the LV function and dyssynchrony parameters after automatic alignment was significantly improved from blinded processing and was comparable to manual side-by-side processing., Conclusion: The automatic alignment tool can be an alternative method to manual side-by-side processing to improve the repeatability of LV function and dyssynchrony measurements by serial gated SPECT MPI.

Background: Phase analysis has been developed and validated to measure left-ventricular dyssynchrony from gated SPECT myocardial perfusion imaging. The purpose of this study is to evaluate its performance in regions with perfusion defects., Methods: A special version of the eXtended CArdiac Torso digital phantom was developed to track B-spline points in each temporal frame. A region of 35 B-spline points in the inferior wall with normal and abnormal perfusion uptakes were simulated. Phase shifts were simulated in the same region, representing dyssynchronous contraction. Gated SPECT data were analyzed using a modified phase analysis algorithm, which tracked the same 35 B-spline points to calculate their phases., Results: Phases and phase shifts measured in the B-spline points with perfusion uptake in the range of 50%-10% did not significantly differ from those measured in the same B-spline points with normal perfusion uptake., Conclusion: Phase analysis can accurately measure phases in regions with abnormal perfusion uptake as low as 10% of the perfusion uptake in the normal regions, which corresponded to a regional signal-to-noise ratio (SNR) of 12.0 or greater. In 42 consecutive patients with myocardial infarction >20% of the left ventricle, only two patients had a SNR within the perfusion defects below that threshold.

Background: We evaluated the incremental diagnostic value of fusion images of coronary computed tomography angiography (CTA) and myocardial perfusion imaging (MPI) over MPI alone or MPI and CTA side-by-side to identify obstructive coronary artery disease (CAD > 50% stenosis) using invasive coronary angiography (ICA) as the gold standard., Methods: 50 subjects (36 men; 56 +/- 11 years old) underwent rest-stress MPI and CTA within 12-26 days of each other. CTAs were performed with multi-detector CT-scanners (31 on 64-slice; and 19 on 16-slice). 37 patients underwent ICA while 13 subjects did not because of low (<5%) pre-test likelihood (LLK) of disease. Three blinded readers scored the images in sequential sessions using (1) MPI alone (2) MPI and CTA side-by-side, (3) fused CTA/MPI images., Results: One or more critical stenoses during ICA were found in 28 patients and non-critical stenoses were found in 9 patients. MPI, side-by-side MPI-CTA, and fused CTA/MPI showed the same normalcy rate (NR:13/13) in LLK subjects. The fusion technique performed better than MPI and MPI and CTA side-by-side for the presence of CAD in any vessel (overall area under the curve (AUC) for fused images: 0.89; P = .005 vs MPI, P = .04 vs side-by-side MPI-CTA) and for localization of CAD to the left anterior descending coronary artery (AUC: 0.82, P < .001 vs MPI; P = .007 vs side-by-side MPI-CTA). There was a non-significant trend for better detection of multi-vessel disease with fusion., Conclusions: Using ICA as the gold standard, fusion imaging provided incremental diagnostic information compared to MPI alone or side-by-side MPI-CTA for the diagnosis of obstructive CAD and for localization of CAD to the left anterior descending coronary artery.

Background: Emission-transmission misalignment with single-photon emission computed tomography (SPECT)-computed tomography (CT) systems can impair attenuation correction (AC) in myocardial perfusion imaging. This study was performed to develop automated quality control (Auto-QC) to detect critical misalignment that can significantly impact AC., Methods and Results: Auto-QC was developed to segment myocardium and mediastinum from emission and transmission reconstructions, respectively. Myocardium-mediastinum mismatch was used as the quality-control index (QCI). The QCI threshold for acceptable AC was determined with NCAT (NURBS [nonuniform rational B-spline]-based cardiac torso phantom) simulation and verified with 2 patients with minimal misalignment. Compromised data sets, generated by shifting the attenuation maps by 0.5, 1.0, 1.5, and 2.0 pixels along left-right, up-down, and head-foot directions, respectively, were qualitatively and quantitatively compared with the unshifted data sets. Auto-QC was tested with the 2 verification patients and 41 additional patients. Shifts by more than 1 pixel along any direction compromised AC. Auto-QC with the QCI threshold (3%) had highly concordant results with manual quality control in the detection of critical misalignment (sensitivity of 88% and 90% and specificity of 93% and 95% for the tests by use of the 2 verification patients and 41 additional patients, respectively)., Conclusion: QCI quantitatively represented the severity of misalignment. Auto-QC can help clinicians be aware of critical misalignment and can assist in realignment of SPECT and CT images.

Background: A count-based method using technetium-99m sestamibi electrocardiography-gated myocardial perfusion single photon emission computed tomography imaging has been developed to extract the left ventricular (LV) regional phase of contraction (onset of mechanical contraction [OMC]) throughout the cardiac cycle. This study was performed to develop OMC normal databases and dynamic OMC displays for assessment of cardiac mechanic dyssynchrony., Methods and Results: LV regional phases were extracted from 90 enrolled normal subjects (45 men and 45 women) by use of the Emory Cardiac Toolbox and then submitted to statistical analysis to generate the normal databases. The LV OMC wave was dynamically propagated over the perfusion polar map by blackening either sequential phase bins or all past phases. The developed OMC normal databases consisted of peak phase (134.5 degrees +/- 14.3 degrees for men and 140.2 degrees +/- 14.9 degrees for women), phase SD (14.2 degrees +/- 5.1 degrees for men and 11.8 degrees +/- 5.2 degrees for women), and phase histogram bandwidth (38.7 degrees +/- 11.8 degrees for men and 30.6 degrees +/- 9.6 degrees for women), skewness (4.19 +/- 0.68 for men and 4.60 +/- 0.72 for women), and kurtosis (19.72 +/- 7.68 for men and 23.21 +/- 8.16 for women). Both statistical analysis and dynamic OMC displays were incorporated into a user interface as a diagnostic tool., Conclusion: The OMC normal databases and dynamic OMC displays should help clinicians evaluate cardiac mechanic dyssynchrony. Prospective clinical trials are needed to validate whether this tool can be used to select patients with severe heart failure symptoms who might benefit from cardiac resynchronization therapy.

Background: New algorithms were evaluated for their efficacy in detecting and quantifying serial changes in myocardial perfusion from single photon emission computed tomography (SPECT)., Methods and Results: We generated 72 simulations with various left ventricular positions, sizes, count rates, and perfusion defect severities using the nonuniform rational B-splines (NURBs)-based CArdiac Torso (NCAT) phantom. Images were automatically aligned by use of both full linear and rigid transformations and quantified for perfusion by use of the CEqual program. Changes within a given perfusion defect were compared by use of a Student t test before and after registration. Registration approaches were compared by use of receiver operating characteristic analysis. Changes of 5% were not detected well in single patients with or without alignment. Changes of 10% and 15% could be detected with false-positive rates of 15% and 10%, respectively, in single studies if alignment was performed before perfusion analysis. Alignment also reduced the number of studies necessary to demonstrate a significant perfusion change (P < .05) in groups of patients by about half., Conclusion: Comparison of mean uptake by t values in SPECT perfusion defects can be used to detect 10% and greater differences in serial perfusion studies of single patients. Image alignment is necessary to optimize automatic detection of perfusion changes in both single patients and groups of patients.

Background: The purpose of this study was to determine the independent value of left ventricular (LV) functional parameters derived from gated fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to predict prognosis in patients with ischemic cardiomyopathy undergoing myocardial viability assessment., Methods and Results: We studied 90 consecutive patients with coronary artery disease and low LV ejection fraction (26% +/- 7%) undergoing gated FDG PET to assess myocardial viability for potential revascularization. The primary endpoint for this analysis was the occurrence of cardiac death, myocardial infarction, or worsening heart failure (HF) to New York Heart Association class IV. During follow-up (22 +/- 14 months), 21 patients had an event (17 died, 4 had myocardial infarctions, and 4 had worsening HF). On Cox regression analysis, the event-free survival rate at 2 years was lower for patients with an end-diastolic volume (EDV) of 260 mL or greater (relative risk, 2.7; P = .014), end-systolic volume (ESV) of 200 mL or greater (relative risk, 2.5; P = .021), and LV mass of 143 g or greater (relative risk, 1.6; P = .009). In a risk-adjusted model, EDV (chi 2 = 68, P < .0001) and ESV (chi 2 = 75, P = .035) added a significant amount in the estimation of events over the perfusion-FDG mismatch pattern (chi 2 = 40, P < .001). In a stratified Cox model, patients with PET mismatch, LV ejection fraction lower than 25%, and EDV of 260 mL or greater had the lowest survival rate (P = .006). These patients showed an apparent survival benefit with revascularization but without an improvement in HF symptoms., Conclusion: LV functional parameters determined by gated FDG PET have incremental prognostic value over viability information in patients with ischemic cardiomyopathy. Our data suggest that patients with residual viability and advanced cardiac remodeling are at high clinical risk. In these patients the apparent survival benefit of revascularization may not be associated with a measurable improvement in HF symptoms.

Background: Cardiac gating is not routinely used in cardiac positron emission tomography (PET). The aim of this study was to determine the feasibility of assessing regional wall motion, ejection fraction (EF), cardiac volumes, and mass with nitrogen-13 ammonia (N-13 ammonia) at the time of PET myocardial perfusion imaging., Methods: We studied 12 healthy volunteers (mean age, 28 +/- 8 years) and 53 patients with documented coronary artery disease (CAD) (mean age, 59 +/- 11 years). All subjects received a single administration of approximately 600 MBq (16 mCi) of N-13 ammonia intravenously. A 6-minute dynamic scan was performed for quantitative assessment of myocardial perfusion at rest, followed by a separate, 13-minute static scan acquired in the gated mode (8 equal bins). Gated data was imported into the Emory Toolbox. Wall motion was evaluated by dividing the myocardium into 9 anatomic regions graded semiquantitatively., Results: Healthy volunteers had a normal EF (61 +/- 6), end systolic volume (ESV) (37 +/- 15 mL), end diastolic volume (EDV) (89 +/- 25 mL), and cardiac mass (116 +/- 18 g). In contrast, patients with CAD showed reduced EF (32 +/- 13%) and increased ESV (129 +/- 56 mL), EDV (188 +/- 68 mL), and cardiac mass (173 +/- 45 g) (P < 0.001 for each). In patients with CAD, EF measured by gated PET correlated significantly to independent measurements of EF (P < 0.001)., Conclusions: Gating of cardiac perfusion images obtained after administration of N-13 ammonia is feasible and appears to be an accurate means of evaluating regional and global cardiac function. Gating can provide important additional diagnostic and prognostic information.

Background: Two methods of computing left ventricular volumes and ejection fraction (EF) from 8-frame gated perfusion single photon emission computed tomography (SPECT) were compared with each other and with magnetic resonance (MR) imaging., Methods and Results: Thirty-five subjects underwent 8-frame gated dual-isotope SPECT imaging and 12- to 16-frame gated MR imaging. Endocardial boundaries on short-axis MR images were hand traced by experts blinded to any SPECT results. Volumes and EF were computed with the use of Simpson's rule. SPECT images were analyzed for the same functional variables with the use of 2 automatic programs, Quantitative Gated SPECT (QGS) and the Emory Cardiac Toolbox (ECTb). The mean difference between MR and SPECT EF was 0.008 for ECTb and 0.08 for QGS. QGS showed a slight trend toward higher correlation for EF (r = 0.72, SE of the estimate = 0.08) than ECTb (r = 0.70, SE of the estimate = 0.09). For both SPECT methods, left ventricular volumes were similarly correlated with MR, although SPECT volumes were higher than MR values by approximately 30%., Conclusions: QGS and ECTb values of cardiac function computed from 8-frame gated perfusion SPECT correlate very well with each other and correlate well with MR. Averaged over all subjects, ECTb measurements of EF are not significantly different from MR values but QGS significantly underestimates the MR values.