Quantitative and qualitative comparison of Rubidium-82 and Oxygen-15 water cardiac PET.

BACKGROUND: Differences in tracer characteristics may influence the interpretation of positron emission tomography myocardial perfusion imaging (MPI). We compare the reading of MPIs with a low-extraction retention tracer (82Rb) and a high-extraction non-retention tracer (15O-water) in a selected cohort of patients with known coronary artery disease (CAD). METHODS: Thirty-nine patients with known CAD referred to 82Rb MPI due to angina underwent rest and stress imaging with both tracers and experienced MPI readers provided blinded consensus reads of all studies. In addition, a comparison of regional and global quantitative measures of perfusion was performed. RESULTS: The results showed 74 % agreement in the reading of 82Rb and 15O-water MPI for regional reversible ischemia and global disease, and 82 % agreement for regional irreversible ischemia. The 15O-water MPI identified more cases of global disease (n = 12 (15O-water) vs n = 4 (82Rb), p = 0.03), whereas differences in reversible ischemia (n = 22 vs n = 16, p = 0.11) and, irreversible ischemia (n = 8 vs n = 11, p = 0.45) were not significant. The correlation between myocardial blood flow measured using the two tracers was similar to previous studies (R2 = 0.78) with wide limits of agreement (-0.93 to 0.84 ml/g/min). CONCLUSIONS: Agreement between consensus readings of 82Rb and 15O-water MPI was good in patients with known CAD. In this limited size study, no significant differences in the identification of reversible and irreversible ischemia found, whereas 15O-water MPI had a higher positive rate for suspected global disease.

Outcome prediction by myocardial external efficiency from 11 C-acetate positron emission tomography in cardiac amyloidosis.

AIMS: This study aimed to study the prognostic value of myocardial oxygen consumption (MVO2 ) and myocardial external efficiency (MEE) from 11 C-acetate positron emission tomography (PET) in cardiac amyloidosis (CA) patients. METHODS AND RESULTS: Forty-eight CA patients, both transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis, and 20 controls were included. All subjects were examined with 11 C-acetate PET and echocardiography. MVO2 , forward stroke volume (FSV), and left ventricular mass (LVM) were derived from 11 C-acetate PET and used to calculate MEE. CA patients were followed for survival and the prognostic impact of clinical, echocardiographic, and 11 C-acetate PET parameters was analysed. MVO2 and MEE were reduced in CA compared with controls, but without significant difference between deceased and surviving CA patients. The ratio of 11 C-acetate PET-derived FSV and LVM was also reduced in CA and significantly lowered in deceased patients compared with survivors. In univariate analysis, New York Heart Association class, N-terminal pro-brain natriuretic peptide, and the 11 C-acetate PET parameters FSV/LVM and MEE were the strongest prognostic factors. Of the 11 C-acetate PET parameters, FSV/LVM was the strongest survival predictor with hazard ratio of 0.56 per 0.1 mL/g (95% confidence interval 0.39-0.81, P = 0.002) and independently prognostic in a multivariate model. MEE significantly separated deceased from surviving CA patients with the cut-off of 15.7% (P = 0.032). Survival was significantly shorter with FSV/LVM below 0.27 mL/g (P < 0.001), also when separating AL- and ATTR-CA. CONCLUSIONS: Reduced MEE was associated with shorter survival in CA patients, but FSV/LVM was the strongest survival predictor and the only independently prognostic 11 C-acetate PET parameter in multivariate analysis.

Accelerometer derived physical activity and subclinical coronary and carotid atherosclerosis: cross-sectional analyses in 22 703 middle-aged men and women in the SCAPIS study.

OBJECTIVES: The aim included investigation of the associations between sedentary (SED), low-intensity physical activity (LIPA), moderate-to-vigorous intensity PA (MVPA) and the prevalence of subclinical atherosclerosis in both coronaries and carotids and the estimated difference in prevalence by theoretical reallocation of time in different PA behaviours. DESIGN: Cross-sectional. SETTING: Multisite study at university hospitals. PARTICIPANTS: A total of 22 670 participants without cardiovascular disease (51% women, 57.4 years, SD 4.3) from the population-based Swedish CArdioPulmonary bioImage study were included. SED, LIPA and MVPA were assessed by hip-worn accelerometer. PRIMARY AND SECONDARY OUTCOMES: Any and significant subclinical coronary atherosclerosis (CA), Coronary Artery Calcium Score (CACS) and carotid atherosclerosis (CarA) were derived from imaging data from coronary CT angiography and carotid ultrasound. RESULTS: High daily SED (>70% ≈10.5 hours/day) associated with a higher OR 1.44 (95% CI 1.09 to 1.91), for significant CA, and with lower OR 0.77 (95% CI 0.63 to 0.95), for significant CarA. High LIPA (>55% ≈8 hours/day) associated with lower OR for significant CA 0.70 (95% CI 0.51 to 0.96), and CACS, 0.71 (95% CI 0.51 to 0.97), but with higher OR for CarA 1.41 (95% CI 1.12 to 1.76). MVPA above reference level, >2% ≈20 min/day, associated with lower OR for significant CA (OR range 0.61-0.67), CACS (OR range 0.71-0.75) and CarA (OR range 0.72-0.79). Theoretical replacement of 30 min of SED into an equal amount of MVPA associated with lower OR for significant CA, especially in participants with high SED 0.84 (95% CI 0.76 to 0.96) or low MVPA 0.51 (0.36 to 0.73). CONCLUSIONS: MVPA was associated with a lower risk for significant atherosclerosis in both coronaries and carotids, while the association varied in strength and direction for SED and LIPA, respectively. If causal, clinical implications include avoiding high levels of daily SED and low levels of MVPA to reduce the risk of developing significant subclinical atherosclerosis.

Detection and correction of patient motion in dynamic 15O-water PET MPI.

BACKGROUND: Patient motion constitutes a limitation to 15O-water cardiac PET imaging. We examined the ability of image readers to detect and correct patient motion using simulated motion data and clinical patient scans. METHODS: Simulated data consisting of 16 motions applied to 10 motion-free scans were motion corrected using two approaches, pre-analysis and post-analysis for motion identification. Both approaches employed a manual frame-by-frame correction method. In addition, a clinical cohort was analyzed for assessment of prevalence and effect of motion and motion correction. RESULTS: Motion correction was performed on 94% (pre-analysis) and 64% (post-analysis) of the scans. Large motion artifacts were corrected in 91% (pre-analysis) and 74% (post-analysis) of scans. Artifacts in MBF were reduced in 56% (pre-analysis) and 58% (post-analysis) of the scans. The prevalence of motion in the clinical patient cohort (n = 762) was 10%. Motion correction altered exam interpretation in only 10 (1.3%) clinical patient exams. CONCLUSION: Frame-by-frame motion correction after visual inspection is useful in reducing motion artifacts in cardiac 15O-water PET. Reviewing the initial results (parametric images and polar maps) as part of the motion correction process, reduced erroneous corrections in motion-free scans. In a large clinical cohort, the impact of motion correction was limited to few patients.

Association of Right Ventricular Myocardial Blood Flow With Pulmonary Pressures and Outcome in Cardiac Amyloidosis.

BACKGROUND: Cardiac amyloidosis (CA) is a restrictive and infiltrative cardiomyopathy, characterized by increased biventricular filling pressures and low output. Symptoms are predominantly of right heart origin. The role of right ventricular (RV) myocardial blood flow (MBF) in CA has not been studied. OBJECTIVES: This study aimed to first associate RV MBF measured by using positron emission tomography (PET) with reference standards of RV pressures and then to explore its prognostic value in CA. METHODS: Cardiac PET was performed at rest in 52 patients with CA and 9 healthy control subjects. MBF was quantified from the right and left ventricles by using 11C-acetate, 15O-water, or both (n = 25). RV pressure was measured invasively or by echocardiography. Associations between biventricular MBF toward symptoms, RV function, and outcome (death or acute heart failure) were studied in patients with CA. RESULTS: MBF of the right ventricle (MBFRV) and the ratio of MBFRV and MBF of the left ventricle (MBFRV/LV) for the 2 tracers were significantly correlated (r > 0.92). MBFRV was directly correlated with RV systolic pressures with both tracers (P ≤ 0.005). MBFLV was inversely correlated with wall thickness (P < 0.0001). MBFRV/LV was significantly associated with N-terminal pro-B-type natriuretic peptide levels, NYHA functional class, RV pressures, and RV systolic function (all; P < 0.001). Twenty-six cardiac events (25 deaths) occurred during follow-up (median 44 months). MBFRV/LV higher than 56% was associated with a diagnosis of pulmonary hypertension (AUC: 0.96 [95% CI: 0.91-1.00]; P < 0.0001); and predicted outcome with HR: 9.0 (95% CI: 4.2-14.5), P < 0.0001). CONCLUSIONS: Measurements of MBFRV using PET are feasible, as confirmed with 2 different tracers. Imbalance between RV and LV myocardial perfusion is associated with increased RV load and adverse events in cardiac amyloidosis.

Myocardial External Efficiency in Asymptomatic Severe Primary Mitral Regurgitation Using 11C-Acetate PET.

Subjects with asymptomatic moderate-to-severe or severe primary mitral regurgitation are closely observed for signs of progression or symptoms requiring surgical intervention. The role of myocardial metabolic function in progression of mitral regurgitation is poorly understood. We used 11C-acetate PET to noninvasively measure myocardial mechanical external efficiency (MEE), which is the energetic ratio of external cardiac work and left ventricular (LV) oxygen consumption. Methods: Forty-seven patients in surveillance with mitral regurgitation and no or minimal symptoms prospectively underwent PET, echocardiography, and cardiac MRI on the same day. PET was used to simultaneously measure cardiac output, LV mass, and oxygen consumption to establish MEE. PET findings were compared between patients and healthy volunteers (n = 9). MEE and standard imaging indicators of regurgitation severity, LV volumes, and function were studied as predictors of time to surgical intervention. Patients were followed a median of 3.0 y (interquartile range, 2.0-3.8 y), and the endpoint was reached in 22 subjects (47%). Results: MEE in patients reaching the endpoint (23.8% ± 5.0%) was lower than in censored patients (28.5% ± 4.5%, P = 0.002) or healthy volunteers (30.1% ± 4.9%, P = 0.001). MEE with a cutoff lower than 25.7% was significantly associated with the outcome (hazard ratio, 7.5; 95% CI, 2.7-20.6; P < 0.0001) and retained independent significance when compared with standard imaging parameters. Conclusion: MEE independently predicted time to progression requiring valve surgery in patients with asymptomatic moderate-to-severe or severe primary mitral regurgitation. The study suggests that inefficient myocardial oxidative metabolism precedes clinically observed progression in mitral regurgitation.

Left-ventricular volumes and ejection fraction from cardiac ECG-gated 15O-water positron emission tomography compared to cardiac magnetic resonance imaging using simultaneous hybrid PET/MR.

BACKGROUND: 15O-water PET is the gold standard for noninvasive quantification of myocardial blood flow. In addition to evaluation of ischemia, the assessment of cardiac function and remodeling is important in all cardiac diseases. However, since 15O-water is freely diffusible and standard uptake images show little contrast between the myocardium and blood pool, the assessment of left-ventricular (LV) volumes and ejection fraction (EF) is challenging. Therefore, the aim of the present study was to investigate the feasibility of calculating LV volumes and EF from first-pass analysis of 15O-water PET, by comparison with cardiac magnetic resonance imaging (CMR) using a hybrid PET/MR scanner. METHODS: Twenty-four patients with known or suspected CAD underwent a simultaneous ECG-gated cardiac PET/MR scan. The 15O-water first-pass images (0-50 seconds) were analyzed using the CarPET software and the CMR images were analyzed using the software Segment, for LV volumes and EF calculations. The LV volumes and EF were compared using correlation and Bland-Altman analysis. In addition, inter- and intra-observer variability of LV volumes and EF were assessed for both modalities. RESULTS: The correlation between PET and CMR was strong for volumes (r > 0.84) and moderate for EF (r = 0.52), where the moderate correlation for EF was partly due to the small range of EF values. Agreement was high for all parameters, with a slight overestimation of PET values for end-diastolic volume but with no significant mean bias for other parameters. Inter- and intra-observer agreement of volumes was high and comparable between PET and CMR. For EF, inter-observer agreement was higher for PET and intra-observer agreement was higher for CMR. CONCLUSION: LV volumes and EF can be calculated by first-pass analysis of a 15O-water PET scan with high accuracy and comparable precision as with CMR.

Influence of image reconstruction on quantitative cardiac 15O-water positron emission tomography.

BACKGROUND: The impact on quantitative 15O-water PET/CT of a wide range of different reconstruction settings, including regularized reconstruction by block-sequential regularized expectation maximization (BSREM), was investigated. METHODS: Twenty clinical stress scans from patients referred for assessment of myocardial ischemia were included. Patients underwent a 4-min dynamic stress PET scan with 15O-water on a digital PET/CT scanner. Twenty-two reconstructions were generated from each scan and a clinical reconstruction was used as reference. Varied parameters were number of iterations, filter, exclusion of time-of-flight and point-spread function, and regularization parameter with BSREM. Analyses were performed in aQuant utilizing two different methods and resulting regional myocardial blood flow (MBF), perfusable tissue fraction (PTF), and transmural MBF (MBFt) values were evaluated. RESULTS: Across the two analyses, correlations toward the reference reconstruction were strong for all parameters (ρ ≥ 0.83). Using automated analysis and the diagnostic threshold of hyperemic MBF at 2.3 mL⋅g-1⋅min-1, diagnosis was unchanged irrespective of reconstruction method in all patients except for one, where only four of the most extreme reconstruction methods resulted in a change of diagnosis. CONCLUSION: The low sensitivity of MBF values to reconstruction method and, as previously shown, scanner type and PET/CT misalignment, confirms that diagnostic hyperemic MBF cutoff values can be consistently used for 15O-water.

Effect of PET-CT misalignment on the quantitative accuracy of cardiac 15O-water PET.

BACKGROUND: Quantification of myocardial blood flow (MBF) with PET requires accurate attenuation correction, which is performed using a separate CT. Misalignment between PET and CT scans has been reported to be a common problem. The purpose of the present study was to assess the effect of PET CT misalignment on the quantitative accuracy of cardiac 15O-water PET. METHODS: Ten clinical patients referred for evaluation of ischemia and assessment of MBF with 15O-water were included in the study. Eleven different misalignments between PET and CT were induced in 6 different directions with 10 and 20 mm amplitudes: caudal (+Z), cranial (- Z), lateral (±X), anterior (+Y), and anterior combined with cranial (+ Y and - Z). Blood flow was quantified from rates of washout (MBF) and uptake (transmural MBF, MBFt) for the whole left ventricle and the three coronary territories. The results from all misalignments were compared to the original scan without misalignment. RESULTS: MBF was only minorly affected by misalignments, but larger effects were seen in MBFt. On the global level, average absolute deviation across all misalignments for MBF was 1.7% ± 1.4% and for MBFt 5.4% ± 3.2 Largest deviation for MBF was - 4.8% ± 5.8% (LCX, X + 20) and for MBFt - 19.3% ± 9.6% (LCX, X + 20). In general, larger effects were seen in LAD and LCX compared to in RCA. CONCLUSION: The quantitative accuracy of MBF from 15O-water PET, based on the washout of the tracer, is only to a minor extent affected by misalignment between PET and CT.

Influence of patient motion on quantitative accuracy in cardiac 15O-water positron emission tomography.

BACKGROUND: Patient motion is a common problem during cardiac PET. The purpose of the present study was to investigate to what extent motions influence the quantitative accuracy of cardiac 15O-water PET/CT and to develop a method for automated motion detection. METHOD: Frequency and magnitude of motion was assessed visually using data from 50 clinical 15O-water PET/CT scans. Simulations of 4 types of motions with amplitude of 5 to 20 mm were performed based on data from 10 scans. An automated motion detection algorithm was evaluated on clinical and simulated motion data. MBF and PTF of all simulated scans were compared to the original scan used as reference. RESULTS: Patient motion was detected in 68% of clinical cases by visual inspection. All observed motions were small with amplitudes less than half the LV wall thickness. A clear pattern of motion influence was seen in the simulations with a decrease of myocardial blood flow (MBF) in the region of myocardium to where the motion was directed. The perfusable tissue fraction (PTF) trended in the opposite direction. Global absolute average deviation of MBF was 3.1% ± 1.8% and 7.3% ± 6.3% for motions with maximum amplitudes of 5 and 20 mm, respectively. Automated motion detection showed a sensitivity of 90% for simulated motions ≥ 10 mm but struggled with the smaller (≤ 5 mm) simulated (sensitivity 45%) and clinical motions (accuracy 48%). CONCLUSION: Patient motion can impair the quantitative accuracy of MBF. However, at typically occurring levels of patient motion, effects are similar to or only slightly larger than inter-observer variability, and downstream clinical effects are likely negligible.

Quantitative myocardial perfusion response to adenosine and regadenoson in patients with suspected coronary artery disease.

BACKGROUND: The aim of the present study was to compare the quantitative flow responses of regadenoson against adenosine using cardiac 15O-water PET imaging in patients with suspected or known coronary artery disease (CAD). METHODS: Hyperemic myocardial blood flow (MBF) after adenosine and regadenoson was compared using correlation and Bland-Altman analysis in 21 patients who underwent rest and adenosine 15O-water PET scans followed by rest and regadenoson 15O-water PET scans. RESULTS: Global mean (± SD) MBF values at rest and stress were 0.92 ± 0.27 and 2.68 ± 0.80 mL·g·min for the adenosine study and 0.95 ± 0.29 and 2.76 ± 0.79 mL·g·min for the regadenoson study (P = 0.55 and P = 0.49). The correlations between global and regional adenosine- and regadenoson-based stress MBF were strong (r = 0.80 and r = 0.77). The biases were small for both global and regional MBF comparisons (0.08 and 0.09 mL·min·g), but the limits of agreement were wide for stress MBF. CONCLUSION: The correlation between regadenoson- and adenosine-induced hyperemic MBF was strong but the agreement was only moderate indicating that established cut-off values for 150-water PET should be used cautiously if using regadenoson as vasodilator.

Diagnosis of left ventricular hypertrophy using non-ECG-gated 15O-water PET.

AIM: To develop a method for diagnosing left ventricular (LV) hypertrophy from cardiac perfusion 15O-water positron emission tomography (PET). METHODS: We retrospectively pooled data from 139 subjects in four research cohorts. LV remodeling patterns ranged from normal to severe eccentric and concentric hypertrophy. 15O-water PET scans (n = 197) were performed with three different PET devices. A low-end scanner (66 scans) was used for method development, and remaining scans with newer devices for a blinded evaluation. Dynamic data were converted into parametric images of perfusable tissue fraction for semi-automatic delineation of the LV wall and calculation of LV mass (LVM) and septal wall thickness (WT). LVM and WT from PET were compared to cardiac magnetic resonance (CMR, n = 47) and WT to 2D-echocardiography (2DE, n = 36). PET accuracy was tested using linear regression, Bland-Altman plots, and ROC curves. Observer reproducibility were evaluated using intraclass correlation coefficients. RESULTS: High correlations were found in the blinded analyses (r ≥ 0.87, P < 0.0001 for all). AUC for detecting increased LVM and WT (> 12 mm and > 15 mm) was ≥ 0.95 (P < 0.0001 for all). Reproducibility was excellent (ICC ≥ 0.93, P < 0.0001). CONCLUSION: 15O-water PET might detect LV hypertrophy with high accuracy and precision.

Evaluation of quantitative CMR perfusion imaging by comparison with simultaneous 15O-water-PET.

BACKGROUND: We assessed the quantitative accuracy of cardiac perfusion measurements using dynamic contrast-enhanced MRI with simultaneous 15O-water PET as reference with a fully integrated PET-MR scanner. METHODS: 15 patients underwent simultaneous DCE MRI and 15O-water PET scans at rest and adenosine-stress on an integrated PET-MR scanner. Correlation and agreement between MRI- and PET-based global and regional MBF values were assessed using correlation and Bland-Altman analysis. RESULTS: Three subjects were excluded due to technical problems. Global mean (± SD) MBF values at rest and stress were 0.97 ± 0.27 and 3.19 ± 0.70 mL/g/min for MRI and 1.02 ± 0.28 and 3.13 ± 1.16 mL/g/min for PET (P = 0.66 and P = 0.81). The correlations between global and regional MRI- and PET-based MBF values were strong (r = 0.86 and r = 0.75). The biases were negligible for both global and regional MBF comparisons (0.01 and 0.00 mL/min/g for both), but the limits of agreement were wide for both global and regional MBF, with larger variability for high MBF-values. CONCLUSION: The correlation between simultaneous MBF measurements with DCE MRI and 15O-water PET measured in an integrated PET-MRI was strong but the agreement was only moderate indicating that MRI-based quantitative MBF measurements is not ready for clinical introduction.

Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation (4Is)-related cardiovascular diseases: a joint collaboration of the EACVI and the EANM.

With this document, we provide a standard for PET/(diagnostic) CT imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is). This standard should be applied in clinical practice and integrated in clinical (multicenter) trials for optimal procedural standardization. A major focus is put on procedures using [18F]FDG, but 4Is PET radiopharmaceuticals beyond [18F]FDG are also described in this document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicenter trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Finally, PET/MR applications in 4Is cardiovascular diseases are also briefly described. Diagnosis and management of 4Is-related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/MR, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications.

Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation- (4Is) related cardiovascular diseases: a joint collaboration of the EACVI and the EANM: summary.

With this summarized document we share the standard for positron emission tomography (PET)/(diagnostic)computed tomography (CT) imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is) as recently published in the European Journal of Nuclear Medicine and Molecular Imaging. This standard should be applied in clinical practice and integrated in clinical (multicentre) trials for optimal standardization of the procedurals and interpretations. A major focus is put on procedures using [18F]-2-fluoro-2-deoxyglucose ([18F]FDG), but 4Is PET radiopharmaceuticals beyond [18F]FDG are also described in this summarized document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicentre trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Diagnosis and management of 4Is related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/magnetic resonance, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications.

Renography with a semiautomated algorithm for diuretic decision 7 min postradiopharmaceutical administration: a feasibility study.

OBJECTIVE: The F+10 method for diuretic renography (diuretics given 10 min after the radiopharmaceutical) could be a time-conserving method. This method involves a 30-min dynamic acquisition where diuretics are administered only when necessary by the Nuclear Medicine technologist performing the examination. The purpose of this study was to assess the method's performance and to discover the optimal threshold of residual activity for a diuretic administration 7 min into the F+10 renography by reprocessing raw data from prior performed examinations with 20-min acquisitions without diuretics. METHODS: Retrospectively, raw data from 320 original examinations of adult patients performed from 2013 to 2015 were reprocessed into 7-min series and categorized as requiring diuretic or not. The diuretic decisions made by an expert panel were used as a reference. A receiver-operating characteristic curve was drawn to assess the optimal cutoff value for the residual renal activity. Sensitivity, specificity, positive and negative predictive values, as well as the Youden J index were calculated. RESULT: The experts classified 50% (160 examinations) as in need of diuretics. The receiver-operating characteristic curve demonstrated the theoretical optimal cutoff value at 7 min to be 94% of maximum activity (sensitivity 0.93, specificity 0.81, Youden J index 0.73). A clinically acceptable threshold is suggested to be 85% (sensitivity 0.99, specificity 0.59, Youden J index 0.58). CONCLUSION: Tc-mercaptoacetyltriglycine renography with the F+10 method and the threshold 85% for diuretic decision 7 min into the renography is a feasible and acceptable method in clinical practice.

Diagnostic Accuracy of [11C]PIB Positron Emission Tomography for Detection of Cardiac Amyloidosis.

OBJECTIVES: This dual-site study evaluated the diagnostic accuracy of the method. BACKGROUND: Pittsburgh compound ([11C]PIB) positron emission tomography (PIB-PET) has shown promise as a specific and noninvasive method for the diagnosis of cardiac amyloidosis (CA). METHODS: The study had 2 parts. In the initial study, 51 subjects were included, 36 patients with known CA and increased wall thickness (15 immunoglobulin light chain [AL] and 21 transthyretin [ATTR] amyloidosis) and 15 control patients (7 were nonamyloid hypertrophic and 8 healthy volunteers). Subjects underwent PIB-PET and echocardiography. Sensitivity and specificity of PIB-PET were established for 2 simple semiquantitative approaches, standardized uptake value ratio (SUVR) and retention index (RI). The second part of the study included 11 amyloidosis patients (5 AL and 6 hereditary ATTR) without increased wall thickness to which the optimal cutoff values of SUVR (>1.09) and RI (>0.037 min-1) were applied prospectively. RESULTS: The diagnostic accuracy of visual inspection of [11C]PIB uptake was 100% in discriminating CA patients with increased wall thickness from controls. Semiquantitative [11C]PIB uptake discriminated CA from controls with a 94% (95% confidence interval [CI]: 80% to 99%) sensitivity for both SUVR and RI and specificity of 93% (95% CI: 66% to 100%) for SUVR and 100% (95% CI: 75% to 100%) for RI. [11C]PIB uptake was significantly higher in AL-CA than in ATTR-CA patients (p < 0.001) and discriminated AL-CA from controls with 100% (95% CI: 88% to 100%) accuracy for both the semiquantitative measures. In the prospective group without increased wall thickness, RI was elevated compared to controls (p = 0.001) and 5 of 11 subjects were evaluated as [11C]PIB PET positive. CONCLUSIONS: In a dual-center setting, [11C]PIB PET was highly accurate in detecting cardiac involvement in the main amyloid subtypes, with 100% accuracy in AL amyloidosis. A proportion of amyloidosis patients without known cardiac involvement were [11C]PIB PET positive, indicating that the method may detect early stages of CA.

Quantification of 11C-PIB kinetics in cardiac amyloidosis.

BACKGROUND: The purpose of this work was to determine the optimal tracer kinetic model of 11C-PIB and to validate the use of the simplified methods retention index (RI) and standardized uptake value (SUV) for quantification of cardiac 11C-PIB uptake in amyloidosis. METHODS AND RESULTS: Single-tissue, reversible and irreversible two-tissue models were fitted to data from seven cardiac amyloidosis patients who underwent 11C-PIB PET scans and arterial blood sampling for measurement of blood radioactivity and metabolites. The irreversible two-tissue model (2Tirr) best described cardiac 11C-PIB uptake. RI and SUV showed high correlation with the rate of irreversible binding (Ki) from the 2Tirr model (r2 =0.95 and r2 =0.94). Retrospective data from 10 amyloidosis patients and 5 healthy controls were analyzed using RI, SUV, as well as compartment modelling with a population-average metabolite correction. All measures were higher in amyloidosis patients than in healthy controls (p=.001), but with an overlap between groups for Ki. CONCLUSION: An irreversible two-tissue model best describes the 11C-PIB uptake in cardiac amyloidosis. RI and SUV correlate well with Ki from the 2Tirr model. RI and SUV discriminate better between amyloidosis patients and controls than Ki based on population-average metabolite correction.

Automatic calculation of myocardial external efficiency using a single 11C-acetate PET scan.

BACKGROUND: Myocardial external efficiency (MEE) is defined as the ratio of kinetic energy associated with cardiac work [forward cardiac output (FCO)*mean systemic pressure] and the chemical energy from oxygen consumed (MVO2) by the left ventricular mass (LVM). We developed a fully automated method for estimating MEE based on a single 11C-acetate PET scan without ECG-gating. METHODS AND RESULTS: Ten healthy controls, 34 patients with aortic valve stenosis (AVS), and 20 patients with mitral valve regurgitation (MVR) were recruited in a dual-center study. MVO2 was calculated using washout of 11C -acetate activity. FCO and LVM were calculated automatically using dynamic PET and parametric image formation. FCO and LVM were also obtained using cardiac magnetic resonance (CMR) in all subjects. The correlation between MEEPET-CMR and MEEPET was high (r = 0.85, P < 0.001) without significant bias. MEEPET was 23.6 ± 4.2% for controls and was lowered in AVS (17.2 ± 4.3%, P < 0.001) and in MVR (18.0 ± 5.2%, P = 0.004). MEEPET was strongly associated with both NYHA class (P < 0.001) and the magnitude of valvular dysfunction (mean aortic gradient: P < 0.001, regurgitant fraction: P = 0.009). CONCLUSION: A single 11C-acetate PET yields accurate and automated MEE results on different scanners. MEE might provide an unbiased measurement of the phenotypic response to valvular disease.

Calculation of left ventricular volumes and ejection fraction from dynamic cardiac-gated 15O-water PET/CT: 5D-PET.

BACKGROUND: Quantitative measurement of myocardial blood flow (MBF) is of increasing interest in the clinical assessment of patients with suspected coronary artery disease (CAD). 15O-water positron emission tomography (PET) is considered the gold standard for non-invasive MBF measurements. However, calculation of left ventricular (LV) volumes and ejection fraction (EF) is not possible from standard 15O-water uptake images. The purpose of the present work was to investigate the possibility of calculating LV volumes and LVEF from cardiac-gated parametric blood volume (V B) 15O-water images and from first pass (FP) images. Sixteen patients with mitral or aortic regurgitation underwent an eight-gate dynamic cardiac-gated 15O-water PET/CT scan and cardiac MRI. V B and FP images were generated for each gate. Calculations of end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV) and LVEF were performed with automatic segmentation of V B and FP images, using commercially available software. LV volumes and LVEF were calculated with surface-, count-, and volume-based methods, and the results were compared with gold standard MRI. RESULTS: Using V B images, high correlations between PET and MRI ESV (r = 0.89, p < 0.001), EDV (r = 0.85, p < 0.001), SV (r = 0.74, p = 0.006) and LVEF (r = 0.72, p = 0.008) were found for the volume-based method. Correlations for FP images were slightly, but not significantly, lower than those for V B images when compared to MRI. Surface- and count-based methods showed no significant difference compared with the volume-based correlations with MRI. The volume-based method showed the best agreement with MRI with no significant difference on average for EDV and LVEF but with an overestimation of values for ESV (14%, p = 0.005) and SV (18%, p = 0.004) when using V B images. Using FP images, none of the parameters showed a significant difference from MRI. Inter-operator repeatability was excellent for all parameters (ICC > 0.86, p < 0.001). CONCLUSION: Calculation of LV volumes and LVEF from dynamic 15O-water PET is feasible and shows good correlation with MRI. However, the analysis method is laborious, and future work is needed for more automation to make the method more easily applicable in a clinical setting.