Automatic Alignment of Myocardial Perfusion Images With Contrast-Enhanced Cardiac Computed Tomography.

Explicit fusion of perfusion data from Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) with coronary artery anatomy from Computed Tomographic Coronary Angiography (CTA) has been shown to improve the diagnostic yield for coronary artery disease (CAD) compared to either modality alone. However, most clinically available methods were developed for multimodal scanners or require interactive alignment prior to display and analysis. A new approach was developed to register the two distributions obtained either from a single multimodal imager or from separate scanners, and a preliminary validation was undertaken to compare the automatic alignment to interactive alignment by two experts.

Automatic Alignment of Myocardial Perfusion Images with Contrast Cardiac Tomography.

Explicit fusion of perfusion data from Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) with coronary artery anatomy from Computed Tomographic Coronary Angiography (CTCA) has been shown to improve the diagnostic yield for coronary artery disease (CAD) compared to either modality alone. However, most clinically available methods were developed for multimodal scanners or require interactive alignment prior to display and analysis. A new approach was developed to register and display the two distributions obtained either from a single multimodal imager or from separate scanners, and a preliminary validation was undertaken using interactive alignment by experts.

Diagnostic performance of fusion of myocardial perfusion imaging (MPI) and computed tomography coronary angiography.

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.

Prognostic performance of quantitative PET tools for stratification of patients with ischemic cardiomyopathy undergoing myocardial viability assessment.

OBJECTIVES: This study was performed to determine the prognostic performance of quantitative PET tools in the stratification of patients with ischemic cardiomyopathy undergoing myocardial viability assessment. METHODS: We applied four different quantitative tools to 104 consecutive patients with coronary artery disease and previous myocardial infarction who had undergone rest Rb/gated F-fluorodeoxyglucose (FDG) PET, to assess myocardial viability for potential revascularization. One of these tools was based on the FDG study alone and the other three tools assessed the extent of match/mismatch defects using FDG in comparison with a perfusion reference database. The four quantitative tools used in this research to define viability were (i) FDG alone, which calculates the percentage of left ventricular myocardium (LVM) that is above the 50% of the maximum LVM FDG counts, (ii) low flow match/mismatch, which determines the area with a 5% increase in normalized FDG counts in relation to defined resting perfusion defects as compared with a reference database, (iii) all regions match/mismatch, which computes the area with a 10% increase in normalized FDG counts in relation to the left ventricle resting perfusion distribution, and (iv) percentage max FDG match/mismatch, which defines the area with FDG uptake greater than 60% of the maximum LVM FDG counts within defined perfusion defects as determined by the reference database. The primary endpoint for this analysis was cardiac death. RESULTS: During the follow-up period (22+/-14 months), 19 patients (18%) died; in 17 of these the cause of death was cardiac. Using univariate analysis, none of the methods were predictive of cardiac death. Receiver operating characteristic analysis defined the optimal thresholds for the extent of myocardial viability for the four tools in the prediction of cardiac death: FDG alone=20%, low flow match/mismatch=15%, all regions match/mismatch=35%, and percentage max FDG match/mismatch=20%. A censored survival analysis using a Kaplan-Meier method showed a statistically significant difference between patients with cardiac death and those with no cardiac death using only the low flow match/mismatch (hazard ratio=0.29, P=0.01) and percentage max FDG match/mismatch criteria (hazard ratio=0.23, P=0.005) tools. CONCLUSION: The low flow match/mismatch and percentage max FDG match/mismatch quantitative PET tools are useful for prognostic stratification of patients with ischemic cardiomyopathy undergoing myocardial viability assessment.

Adenosine stress rubidium-82 PET/computed tomography in patients with known and suspected coronary artery disease.

BACKGROUND: Integrated positron emission tomography/computed tomography (PET/CT) is increasingly being utilized for myocardial perfusion imaging (MPI). However, there is a potential for increased imaging artifact compared with standard PET due to the different temporal resolution of PET and CT. We reviewed the diagnostic accuracy of adenosine stress Rb myocardial perfusion PET/CT to detect obstructive coronary artery disease (CAD) on invasive angiography at our institution. METHODS AND RESULTS: Seventy-five patients were included, 23 (13 men, mean age 55.8+/-11.8 years) with low likelihood of CAD and 52 (28 men, mean age 67.1+/-11.4 years) with intermediate to high pretest probability of disease. Coronary angiography was performed only in the latter 52 patients on average within 17 days of the MPI study. The test characteristics of PET/CT MPI were assessed using a threshold of >or=50 and >or=70% stenosis in one or more major coronary artery on invasive angiography. Dedicated software was used for registration, processing, and interpretation. Consensus interpretation of the tomographic PET slices using a 4-point scale (1=definitely normal, 2=probably normal, 3=probably abnormal, 4=definitely abnormal) was done by two readers blinded to clinical information. RESULTS: All MPI studies in the 23 low likelihood patients were normal. In the remaining 52 patients using a stenosis severity>or=50%, global sensitivity and specificity, negative and positive predictive value for detection of CAD were 86, 100, 57, and 100%. Using a stenosis severity>or=70%, these values changed to 90, 83, 71, and 87%. CONCLUSION: Adenosine stress Rb MPI using PET/CT with manual registration demonstrates diagnostic accuracy comparable with that of traditional PET MPI.

Potential impact of noncontrast computed tomography as gatekeeper for myocardial perfusion positron emission tomography in patients admitted to the chest pain unit.

We investigated the ability of coronary artery calcium (CAC) to predict a normal adenosine stress rubidium-82 (Rb-82) myocardial perfusion positron emission tomography (PET) in patients admitted to the chest pain unit. Eighty-four consecutive patients (33 men; mean age 62 +/- 14.8 years) with low to intermediate likelihood of coronary artery disease were included. A single noncontrast computed tomogram under shallow breathing was obtained for attenuation correction and to assess the presence of CAC. This was followed by a rest and adenosine stress dynamic Rb-82 emission PET. Computed tomography and PET images were interpreted independently. There was a high prevalence of risk factors (80% hypertension, 30% diabetes, 38% hypercholesterolemia, 13% smoking); prior coronary revascularization and myocardial infarction were present in 21% and 15% of the patients, respectively. The absence of CAC was associated with a normal adenosine stress Rb-82 myocardial perfusion PET in 34 of 34 patients, yielding a negative predictive value of 100%. The presence of CAC (50 of 84) was associated with a higher incidence of myocardial perfusion defects (13 of 50), yielding a positive predictive value of 26%. Sensitivity was 100% (13 of 13) and specificity was 48% (34 of 71). In conclusion, the absence of CAC is predictive of a normal adenosine stress Rb-82 myocardial perfusion PET in patients admitted to the chest pain unit. If these results are confirmed, myocardial perfusion imaging probably can be safely avoided in chest pain patients with negative CAC with low to intermediate pretest likelihood of disease. This approach may decrease overall radiation exposure and hospital time and prove to be cost effective.

Normal values and prospective validation of transient ischaemic dilation index in 82Rb PET myocardial perfusion imaging.

BACKGROUND: The use of Rb positron emission tomography (PET) for the diagnosis of coronary artery disease (CAD) has increased in recent years but the role of some of the traditional parameters used in SPECT for the diagnosis of CAD, such as transient ischaemic dilation index (TID) of the left ventricle, have not been validated in PET studies. METHODS AND RESULTS: We studied 95 patients who had undergone rest/pharmacological stress Rb PET scans. Thirty of these patients (18 female and 12 male) who had less than 5% likelihood of CAD (LLK) based on sequential Bayesian analysis, were used to determine the normal limits of TID index in this protocol. The remaining 65 patients (33 female and 32 male) underwent coronary angiography within 15 days of the cardiac PET scan. This second group of patients was used to validate the TID normal limits determined in the first group. In LLK patients mean TID index was 1.01+/-0.07 and there were no significant differences between genders. The TID index upper normal limit was 1.15 and was calculated as mean+2 SD. Using this cut-off point, TID index had high specificity and PPV in the diagnosis of single vessel CAD (100% and 100% respectively) and multiple vessel CAD (93% and 85%, respectively). CONCLUSION: Our results indicate that elevated TID index is a specific, although not sensitive marker of single and multiple vessel CAD in pharmacologically stressed Rb PET myocardial perfusion studies.

Quantitative (82)Rb PET/CT: development and validation of myocardial perfusion database.

UNLABELLED: The use of myocardial perfusion (82)Rb PET/CT studies continues to increase but its accuracy using database quantification methods for the diagnosis of coronary artery disease (CAD) has not been established. METHODS: A sex-independent normal database and criteria for abnormality for rest-stress (82)Rb PET/CT myocardial perfusion imaging were developed and validated by evaluation of 281 patients (136 females: mean age +/- SD, 63.3 +/- 13.3 y; 145 males: mean age +/- SD, 63.9 +/- 12.8 y) who underwent a rest-adenosine stress (82)Rb PET/CT study. These patients were divided into 3 groups: (a) healthy group: 30 patients, with <5% likelihood of CAD (low likelihood [LLK]) based on sequential Bayesian analysis; these patients were used to generate the normal distribution; (b) pilot group: 174 patients; these patients were used to determine the optimal criteria for detecting and localizing the perfusion abnormality; and (c) validation group: 76 patients (23 with LLK of CAD and 53 who underwent coronary angiography; these patients were used for prospective validation. RESULTS: Of the 53 patients who underwent coronary angiography, 8 had <50% stenosis and 45 patients had at least one stenosis > or =50% in one major artery. Fifteen patients had single-vessel disease, 17 had double-vessel disease, and 13 had triple-vessel disease. The prospective validation shows a normalcy rate of 78% (18/23) for global CAD. The analyses by individual arteries show a normalcy rate of 96% (22/23) for the left anterior descending coronary artery, 96% for the left circumflex coronary artery (22/23), and 100% for the right coronary artery (23/23). The overall sensitivity for detection of CAD (> or =50% stenosis) was 93% (42/45). The overall specificity for detection of the absence of CAD (< or =50% stenosis) was 75% (6/8). Also, the positive predictive value for global CAD was 95% (42/44), the negative predictive value was 67% (6/9), and the accuracy was 91% (48/53). CONCLUSION: The quantitative (82)Rb PET/CT database created and validated in this study is highly accurate for the detection and localization of CAD. Physicians should consider using the quantitative output of these algorithms as decision support tools to aid with image interpretation.

Fusion of Myocardial Perfusion Data with CT Coronary Angiography.

Our current approach to fusion of CTCA and PET perfusion data uses the epicardial surface from the perfusion data onto which the CT coronary arteries are aligned and warped. This work was undertaken to improve the alignment and the display realism by using CT epicardial boundary information. PET and CTCA images from a combined scanner were used. Based on the location of the LV detected from PET during standard perfusion processing, the LV chamber of the CT was located. Hounsfield units were used to define an estimated endocardial surface in the CT. Based on the endocardial surface, the epicardial boundary was detected, again using Hounsfield units, or when that failed, by estimating its position based on the detected endocardium. Coronary arteries were detected using a commercial program; the epicardial surface was forced to be congruent with all detected artery points. A confidence factor in each epicardial boundary point was maintained based on how each was detected, whether through threshold, through estimation, or by using he coronary artery points. The epicardial boundary surface points were nonlinearly filtered; erroneous surface points, as defined by local properties and confidence factors, were replaced with values interpolated from the nearest points deemed more accurate. The resulting epicardial surface was linearly aligned to the epicardial boundary detected from the PET, and the CT boundaries were then color-coded based on the PET perfusion. Resulting surfaces were much more realistic than those created using PET epicardial boundaries (Fig 1.) Forcing the CT epicardial surface to lie on the detected coronary arteries eliminated problems with alignment and warping of the coronary arteries onto the PET surface.

Incremental prognostic value of left ventricular function by myocardial ECG-gated FDG PET imaging in patients with ischemic cardiomyopathy.

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.

Quantitative Tc-99m sestamibi attenuation-corrected SPECT: development and multicenter trial validation of myocardial perfusion stress gender-independent normal database in an obese population.

BACKGROUND: A gender-independent stress normal database and criteria for abnormality for attenuation-corrected rest-stress technetium 99m sestamibi same-day myocardial perfusion imaging were developed by evaluation of 112 patients, validated against an obese population of 95 patients from four different clinical sites, and compared with conventional gender-matched database quantification of non-attenuation-corrected studies. METHODS AND RESULTS: These 95 validation patients (63 men) were used for prospective quantitative evaluation (mean weight, 213 +/- 57 lb; mean body mass index, 32 +/- 9 kg/m(2)). This group included 21 patients (12 men) with a lower than 5% likelihood of coronary artery disease (mean weight, 226 +/- 72 lb; mean body mass index, 34 +/- 13 kg/m(2)) and 74 who underwent cardiac catheterization within 2 months (35 with normal coronaries or coronary lesions <70%). These studies were processed twice, once by use of conventional reconstruction and gender-specific database quantification and a second time by use of attenuation correction and a single gender-independent attenuation-corrected normal database. The attenuation-corrected normal database and criteria for abnormality were developed by evaluation of 48 and 78 patients, respectively. No statistically significant differences were found when comparing attenuation-corrected perfusion distributions of normal men and women, whereas significant differences were found in the same uncorrected studies. Compared with quantitative analysis of the uncorrected studies, quantitative analysis of the attenuation-corrected studies by use of a gender-independent normal database demonstrated a significant improvement in normalcy rate (90% vs 52%, P =.006) and specificity (57% vs 29%, P =.015) in this obese population at no significant loss in sensitivity (90% vs 97%, P = not significant). CONCLUSION: Attenuation-corrected studies can be quantified with a single gender-independent normal database and a single criterion for abnormality without loss of sensitivity and with significantly better specificity and normalcy rate.

Three-dimensional fusion of coronary arteries with myocardial perfusion distributions: clinical validation.

UNLABELLED: Clinical decisions regarding diagnosis and effective treatment of coronary artery disease frequently require integration of information from various imaging modalities, which are acquired, processed, and read at different physical locations and times. We have developed methods to integrate the information in 2 cardiac imaging studies, perfusion SPECT and coronary angiography. Three-dimensional (3D) models of the coronary artery tree created from biplane angiograms were automatically aligned with 3D models of the left ventricular epicardial surface created from perfusion SPECT. Myocardial mass at risk was used as a unique measure to validate the accuracy of the unification. METHODS: Thirty patients were injected with the perfusion agent (99m)Tc-tetrosfosmin during balloon occlusion while undergoing percutaneous transluminal coronary angioplasty for single-vessel coronary artery disease. Thus, a single, severe perfusion defect was induced by a single coronary artery occlusion of known severity and placement. The accuracy of the unification was measured by computing the overlap between physiologic area at risk, determined using SPECT perfusion quantification techniques only, and anatomic area at risk, determined using coronary artery anatomy aligned with the epicardial surface of the left ventricle. RESULTS: The unification resulted in an 80% overlap of areas at risk, and an overlap of 84% of normal areas, for all coronary artery distributions. The mass at risk measured based on the unified anatomic information correlated with the physiologically based mass at risk as y = 0.92x + 10.3 g; r = 0.76, SEE = 10.4 g. CONCLUSION: A unification algorithm for automatically registering 3D models of the epicardial surface from perfusion SPECT and 3D coronary artery trees from coronary angiography has been presented and validated in 30 patient studies.

Comparison between ECTb and QGS for assessment of left ventricular function from gated myocardial perfusion SPECT.

BACKGROUND: The most widely distributed software packages to compute left ventricular (LV) volume and ejection fraction (EF) from gated perfusion tomograms are QGS and the Emory Cardiac Toolbox (ECTb). Because LV modeling and time sampling differ between the algorithms, it is necessary to document relationships between values produced by them and to establish normal limits individually for each software package in order to interpret results obtained for individual patients. METHODS AND RESULTS: Gated single photon emission computed tomography technetium 99m sestamibi myocardial perfusion studies were collected and analyzed for 246 patients evaluated for coronary artery disease. QGS and ECTb values of ejection fraction (EF), end-diastolic volume (EDV), and end-systolic volume were found to correlate linearly (r = 0.90, 0.91, and 0.94, respectively), but EF and EDV were significantly lower for QGS than with ECTb (53% +/- 13% vs 61% +/- 13 and 102 +/- 45 mL vs 114 +/- 50 mL, respectively). To compare calculations for healthy subjects between the two software packages, data were also selected for 50 other patients at low likelihood for coronary artery disease, for whom EF and EDV were significantly lower for QGS compared with ECTb (62% +/- 9% vs 67% +/- 8% and 84 +/- 26 mL vs 105 +/- 33 mL, respectively). The ECTb lower limit was 51% for EF and the upper limits were 171 mL for EDV and 59 mL/m(2) for mass-indexed EDV, compared with limits of 44%, 137 mL, and 47 mL/m(2) for QGS. CONCLUSIONS: Although correlations were strong between the two methods of computing LV functional values, statistical scatter was substantial and significant biases and trends observed. Therefore, when both software packages are used at the same site, it will be important to take these differences into consideration and to apply normal limits specific to each set of algorithms.

[Unified three-dimensional images of myocardial perfusion and coronary angiography]. / Superposición en tres dimensiones de las imágenes de perfusión miocárdica y de la coronariografía.

INTRODUCTION AND OBJECTIVES: In everyday clinical practice, the cardiologist needs to integrate anatomical and functional information from patients with coronary artery disease. The aim of this study is to present a way to unify, in three-dimensional images, anatomical information from coronary angiography with physiological information from myocardial perfusion scintigraphy. METHODS: Three patients with one vessel disease (left anterior descending, right coronary and left circumflex arteries, respectively) scheduled for percutaneous coronary revascularization were selected. Two-dimensional angiographic images were obtained before and after revascularization. 99mTc-tetrofosmin was administered during coronary occlusion and tomographic images corresponding to the occlusion were detected after coronary dilatation. Control rest scintigraphic images were obtained after two days. The three-dimensional coronary tree from coronary angiography was superposed on the epicardial contours of the myocardial perfusion images following a method of our own. RESULTS: A correct three-dimensional reconstruction of myocardial contour and coronary tree was achieved for each patient. The three-dimensional unified images showed excellent concordance between the extent of perfusion defects and the anatomic distribution of the occluded vessel. CONCLUSIONS: Three-dimensional unification of myocardial perfusion images and coronary angiography is technically possible. This technology integrates anatomical and functional information to facilitate the cardiologist's decision-making and so improve coronary patient management.