Value of PET ECG gating in a cross-validation study of cardiac function assessment by PET/MR imaging.

BACKGROUND: This work investigated the impact of different cardiac gating methods on the assessment of cardiac function by FDG-PET in a cross-validation PET/MR study. METHODS AND RESULTS: MR- and PET-based left ventricular end-diastolic, end-systolic volumes, and ejection fraction (EDV, ESV, and EF) were delineated in 30 patients with a PET/MR examination. Cardiac PET imaging was performed using three ECG gating methods: fixed number of gates per beat (STD), STD with a beat acceptance window (STD-BR), and fixed gate duration (FW). High MR-PET correlations were found in all the values. ESVs correlated better than EDVs and EFs: Pearson's r coefficient [0.92, 0.92, 0.92] in ESV vs [0.75, 0.81, 0.80] in EDV and [0.79, 0.91, 0.87] in EF, for each method [STD, STD-BR, FW]. Biases with respect to MRI for all the evaluated PET methods were less than 13% in EDV, 5% in ESV, and 14% in EF, but with wide limits of agreements, in the range (59-68)% in EDV, (65-70)% in ESV, and (49-71)% in EF. STD showed the strongest disagreement, while there were no marked differences between STD-BR and FW. CONCLUSION: Based on these findings, PET- and MR-based cardiac function parameters were highly correlated but in substantial disagreement with variabilities introduced by the selected PET ECG gating method. The most significant differences were associated with the ECG gating method susceptible to highly irregular beats, while similar performance was observed in the methods using uniform adjustment of gates width per beat with the beat acceptance window, and fixed gate width along all the beats. Thus, strict quality controls of R peak detection are needed to minimize its impact on the function assessment.

Multimodal assessment of right ventricle overload-metabolic and clinical consequences in pulmonary arterial hypertension.

BACKGROUND: In pulmonary arterial hypertension (PAH) increased afterload leads to adaptive processes of the right ventricle (RV) that help to maintain arterio-ventricular coupling of RV and preserve cardiac output, but with time the adaptive mechanisms fail. In this study, we propose a multimodal approach which allows to estimate prognostic value of RV coupling parameters in PAH patients. METHODS: Twenty-seven stable PAH patients (49.5 ± 15.5 years) and 12 controls underwent cardiovascular magnetic resonance (CMR). CMR feature tracking analysis was performed for RV global longitudinal strain assessment (RV GLS). RV-arterial coupling was evaluated by combination of RV GLS and three proposed surrogates of RV afterload-pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR) and pulmonary artery compliance (PAC). 18-FDG positron emission tomography (PET) analysis was used to assess RV glucose uptake presented as SUVRV/LV. Follow-up time of this study was 25 months and the clinical end-point was defined as death or clinical deterioration. RESULTS: Coupling parameters (RV GLS/PASP, RV GLS/PVR and RV GLS*PAC) significantly correlated with RV function and standardized uptake value (SUVRV/LV). Patients who experienced a clinical end-point (n = 18) had a significantly worse coupling parameters at the baseline visit. RV GLS/PASP had the highest area under curve in predicting a clinical end-point and patients with a value higher than (-)0.29%/mmHg had significantly worse prognosis. It was also a statistically significant predictor of clinical end-point in multivariate analysis (adjusted R2 = 0.68; p < 0.001). CONCLUSIONS: Coupling parameters are linked with RV hemodynamics and glucose metabolism in PAH. Combining CMR and hemodynamic measurements offers more comprehensive assessment of RV function required for prognostication of PAH patients. TRIAL REGISTRATION: NCT03688698, 09/26/2018, retrospectively registered; Protocol ID: 2017/25/N/NZ5/02689.

Clinical quantitative cardiac imaging for the assessment of myocardial ischaemia.

Cardiac imaging has a pivotal role in the prevention, diagnosis and treatment of ischaemic heart disease. SPECT is most commonly used for clinical myocardial perfusion imaging, whereas PET is the clinical reference standard for the quantification of myocardial perfusion. MRI does not involve exposure to ionizing radiation, similar to echocardiography, which can be performed at the bedside. CT perfusion imaging is not frequently used but CT offers coronary angiography data, and invasive catheter-based methods can measure coronary flow and pressure. Technical improvements to the quantification of pathophysiological parameters of myocardial ischaemia can be achieved. Clinical consensus recommendations on the appropriateness of each technique were derived following a European quantitative cardiac imaging meeting and using a real-time Delphi process. SPECT using new detectors allows the quantification of myocardial blood flow and is now also suited to patients with a high BMI. PET is well suited to patients with multivessel disease to confirm or exclude balanced ischaemia. MRI allows the evaluation of patients with complex disease who would benefit from imaging of function and fibrosis in addition to perfusion. Echocardiography remains the preferred technique for assessing ischaemia in bedside situations, whereas CT has the greatest value for combined quantification of stenosis and characterization of atherosclerosis in relation to myocardial ischaemia. In patients with a high probability of needing invasive treatment, invasive coronary flow and pressure measurement is well suited to guide treatment decisions. In this Consensus Statement, we summarize the strengths and weaknesses as well as the future technological potential of each imaging modality.

CT-based SPECT attenuation correction and assessment of infarct size: results from a cardiac phantom study.

RATIONALE: Myocardial perfusion SPECT is a commonly performed, well established, clinically useful procedure for the management of patients with coronary artery disease. However, the attenuation of photons from myocardium impacts the quantification of infarct sizes. CT-Attenuation Correction (AC) potentially resolves this problem. This contention was investigated by analyzing various parameters for infarct size delineation in a cardiac phantom model. METHODS: A thorax phantom with a left ventricle (LV), fillable defects, lungs, spine and liver was used. The defects were combined to simulate 6 infarct sizes (5-20% LV). The LV walls were filled with 100120 kBq/ml 99mTc and the liver with 10-12 kBq/ml 99mTc. The defects were filled with water of 50% LV activity to simulate transmural and non-transmural infarction, respectively. Imaging of the phantom was repeated for each configuration in a SPECT/CT system. The defects were positioned in the anterior as well as in the inferior wall. Data were acquired in two modes: 32 views, 30 s/view, 180° and 64 views, 15 s/view, 360° orbit. Images were reconstructed iteratively with scatter correction and resolution recovery. Polar maps were generated and defect sizes were calculated with variable thresholds (40-60%, in 5% steps). The threshold yielding the best correlation and the lowest mean deviation from the true extents was considered optimal. RESULTS: AC data showed accurate estimation of transmural defect extents with an optimal threshold of 50% [non attenuation correction (NAC): 40%]. For the simulation of non-transmural defects, a threshold of 55% for AC was found to yield the best results (NAC: 45%). The variability in defect size due to the location (anterior versus inferior) of the defect was reduced by 50% when using AC data indicating the benefit from using AC. No difference in the optimal threshold was observed between the different orbits. CONCLUSION: Cardiac SPECT/CT shows an improved capability for quantitative defect size assessment in phantom studies due to the positive effects of attenuation correction.

Exploring New Multimodal Quantitative Imaging Indices for the Assessment of Osseous Tumor Burden in Prostate Cancer Using 68Ga-PSMA PET/CT.

PET combined with CT and prostate-specific membrane antigen (PSMA) ligands has gained significant interest for staging prostate cancer (PC). In this study, we propose 2 multimodal quantitative indices as imaging biomarkers for the assessment of osseous tumor burden using 68Ga-PSMA PET/CT and present preliminary clinical data. Methods: We defined 2 bone PET indices (BPIs) that incorporate anatomic information from CT and functional information from 68Ga-PSMA PET: BPIVOL is the percentage of bone volume affected by tumor and BPISUV additionally considers the level of PSMA expression. We describe a semiautomatic computation method based on segmentation of bones in CT and of lesions in PET. Data from 45 patients with castration-resistant PC and bone metastases during 223Ra-dichloride were retrospectively analyzed. We evaluated the computational stability and reproducibility of the proposed indices and explored their relation to the prostate-specific antigen blood value, the bone scan index (BSI), and disease classification using PERCIST. Results: On the technical side, BPIVOL and BPISUV showed an interobserver maximum difference of 3.5%, and their computation took only a few minutes. On the clinical side, BPIVOL and BPISUV showed significant correlations with BSI (r = 0.76 and 0.74, respectively, P < 0.001) and prostate-specific antigen values (r = 0.57 and 0.54, respectively, P < 0.01). When the proposed indices were compared against expert rating using PERCIST, BPIVOL and BPISUV showed better agreement than BSI, indicating their potential for objective response evaluation. Conclusion: We propose the evaluation of BPIVOL and BPISUV as imaging biomarkers for 68Ga-PSMA PET/CT in a prospective study exploring their potential for outcome prediction in patients with bone metastases from PC.

Assessment of the 18F-labeled PET tracer LMI1195 for imaging norepinephrine handling in rat hearts.

UNLABELLED: A novel (18)F-labeled tracer, LMI1195 (N-[3-bromo-4-(3-(18)F-fluoro-propoxy)-benzyl]-guanidine), is being developed for sympathetic nerve imaging; its high specificity for neural uptake-1 mechanism has previously been demonstrated in cell associative studies and in rabbit and nonhuman primate studies assessing heart uptake. The aim of this study was to investigate the mechanisms of (18)F-LMI1195 cardiac uptake in the rat, which is known to contain norepinephrine uptake mechanisms beyond uptake-1. METHODS: Tracer accumulation in the heart was studied over time after intravenous administration of (18)F-LMI1195 in healthy male Wistar rats by quantitative in vivo PET imaging. The uptake mechanism was assessed by pretreatment with the nonselective norepinephrine uptake-1 and norepinephrine uptake-2 inhibitor phenoxybenzamine (50 mg/kg intravenously; n = 4), the selective norepinephrine uptake-1 inhibitor desipramine (2 mg/kg intravenously; n = 4), or saline control (intravenously; n = 4). RESULTS: (18)F-LMI1195 produced high and sustained heart uptake allowing clear delineation of the left ventricular wall over 60 min after tracer administration. Pretreatment with phenoxybenzamine markedly reduced the (18)F-LMI1195 cardiac uptake when compared with controls. In contrast, there was preserved (18)F-LMI1195 uptake after desipramine pretreatment. CONCLUSION: In rats, cardiac uptake of (18)F-LMI1195 was significantly inhibited by phenoxybenzamine but not desipramine, suggesting (18)F-LMI1195 is a substrate for the uptake-2 mechanism and is consistent with the rat heart having a dominant level of the mechanism.

Multimodal assessment of in vivo metabolism with hyperpolarized [1-13C]MR spectroscopy and 18F-FDG PET imaging in hepatocellular carcinoma tumor-bearing rats.

UNLABELLED: Abnormalities of tumor metabolism can be exploited for molecular imaging. PET imaging of (18)F-FDG is a well-established method using the avid glucose uptake of tumor cells. (13)C MR spectroscopic imaging (MRSI) of hyperpolarized [1-(13)C]pyruvate and its metabolites, meanwhile, represents a new method to study energy metabolism by visualizing, for example, the augmented lactate dehydrogenase activity in tumor cells. Because of rapid signal loss, this method underlies strict temporal limitations, and the acquisition of data-encoding spatial, temporal, and spectral information within this time frame-is challenging. The object of our study was to compare spectroscopic images with (18)F-FDG PET images for visualizing tumor metabolism in a rat model. METHODS: (13)C MRSI with IDEAL (Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation) chemical shift imaging in combination with single-shot spiral acquisition was used to obtain dynamic data from 23 rats bearing a subcutaneous hepatocellular carcinoma and from reference regions of the same animals. Static and dynamic analysis of (18)F-FDG PET images of the same animals was performed. The data were analyzed qualitatively (visual assessment) and quantitatively (magnitude and dynamics of (18)F-FDG uptake, (13)C MRSI dynamics, and physiologic parameters). RESULTS: In most animals increased [1-(13)C]lactate signals in the tumor could be detected by simple display of integrated [1-(13)C]lactate images with corresponding enhanced (18)F-FDG uptake. Low [1-(13)C]pyruvate or [1-(13)C]lactate signals did not correlate with histologic or physiologic parameters. Significantly less pyruvate reached the tumors than the gastrointestinal tract, but in tumors a significantly higher amount of pyruvate was converted to lactate and alanine within seconds after intravenous administration. CONCLUSION: This study reveals that PET and (13)C MRSI can be used to visualize increased glycolytic flux in malignant tissue. The combination of signals will allow the quantitative dissection of substrate metabolism, with respect to uptake and downstream metabolic pathways. Although hyperpolarized [1-(13)C]pyruvate increases the sensitivity of MR imaging, signal-to-noise ratio constraints still apply for spatially and temporally resolved (13)C MRSI, emphasizing the need for further MR methodologic development. These first imaging data suggest the feasibility of (13)C MRSI for future clinical use.

Assessment of myocardial perfusion and viability by positron emission tomography.

An important evolution has taken place recently in the field of cardiovascular Positron Emission Tomography (PET) imaging. Being originally a highly versatile research tool that has contributed significantly to advance our understanding of cardiovascular physiology and pathophysiology, PET has gradually been incorporated into the clinical cardiac imaging portfolio contributing to diagnosis and management of patients investigated for coronary artery disease (CAD). PET myocardial perfusion imaging (MPI) has an average sensitivity and specificity around 90% for the detection of angiographically significant CAD and it is also a very accurate technique for prognostication of patients with suspected or known CAD. In clinical practice, Rubidium-82 ((82)Rb) is the most widely used radiopharmaceutical for MPI that affords also accurate and reproducible quantification in absolute terms (ml/min/g) comparable to that obtained by cyclotron produced tracers such as Nitrogen-13 ammonia ((13)N-ammonia) and Oxygen-15 labeled water ((15)O-water). Quantification increases sensitivity for detection of multivessel CAD and it may also be helpful for detection of early stages of atherosclerosis or microvascular dysfunction. PET imaging combining perfusion with myocardial metabolism using (18)F-Fluorodeoxyglucose ((18)F FDG), a glucose analog, is an accurate standard for assessment of myocardial hibernation and risk stratification of patients with left ventricular dysfunction of ischemic etiology. It is helpful for guiding management decisions regarding revascularization or medical treatment and predicting improvement of symptoms, exercise capacity and quality of life post-revascularization. The strengths of PET can be increased further with the introduction of hybrid scanners, which combine PET with computed tomography (PET/CT) or with magnetic resonance imaging (PET/MRI) offering integrated morphological, biological and physiological information and hence, comprehensive evaluation of the consequences of atherosclerosis in the coronary arteries and the myocardium.

Quantitative assessment of glucose metabolism in the vessel wall of abdominal aortic aneurysms: correlation with histology and role of partial volume correction.

Inflammatory-proteolytic processes in the vessel wall are essential in the pathophysiology of abdominal aortic aneurysm (AAA). It has been demonstrated that, (18)F-FDG-PET/CT may be useful for detection of pathological wall metabolism and therefore risk stratification. Quantification of the FDG-uptake in AAA wall is hampered by partial-volume (PV)-effects. For correction and accurate quantitative (18)F-FDG-uptake analysis we designed and validated a novel IDL-based software in correlation to phantom studies, histopathology and clinical presentation of AAA patients. For in vivo studies 23 patients with symptomatic and asymptomatic AAA underwent (18)F-FDG-PET/CT before surgery. In areas with (18)F-FDG-uptake the maximum and mean standardized uptake values in the vessel wall with (PVC-SUV(max), PVC-SUV(mean)) and without (SUV(max), SUV(mean)) PV-correction were determined. Results were correlated with clinical presentation, corresponding macrophage-infiltration and MMP-2- and -9-expression in surgical specimens. In patients, SUV(max), SUV(mean) as well as PVC-SUV(max) or PVC-SUV(mean) enabled a highly significant (p < 0.005) discrimination of symptomatic and asymptomatic AAA. Uncorrected and corrected SUVs showed comparable correlations with macrophage-infiltration and MMP-9 expression. No correlation of (18)F-FDG-uptake and MMP-2 was found. In vivo correlations of detected FDG-uptake with clinical and histological results showed comparable results for corrected and uncorrected SUVs. PV-correction is not mandatory for qualitative clinical assessment of glucose metabolism in the vessel wall of AAA-patients but may be necessary to establish quantitative cut off values to stratify patients for aneurysm repair.

Positron emission tomography in the assessment of left ventricular function in healthy rats: a comparison of four imaging methods.

OBJECTIVE: To measure left ventricular (LV) function parameters in heart of healthy rats by three different positron emission tomography (PET) imaging techniques and by magnetic resonance imaging (MRI). METHODS: ECG-gated microPET examinations were obtained in seven healthy rats with 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) for calculation of LV-function from the blood-pool phase of the dynamic recording (FDGBP), and also from the later myocardial uptake (FDGMyo). On subsequent days, we re-measured LV-function using the novel blood-pool tracer (68)Ga-albumin (AlbBP) and again by FDG (FDGMyo2) in one setting. Cine-MRI examination provided the reference standard measurement. RESULTS: The mean LV ejection fractions (LVEF) were 56 ± 3 (FDGBP), 55 ± 3 (FDGMyo), 56 ± 3 (FDGMyo2), 57 ± 3 (AlbBP), and 57 ± 2 (MRI). There were good to excellent correlations found between the LVEF-values as compared to MRI reference standard for FDGBP (r = 0.71), FDGMyo (r = 0.86) and AlbBP (r = 0.88). Both of the blood-pool methods significantly overestimated the magnitudes of end-diastolic-volume and end-systolic-volume, whereas FDGMyo matched closely to the MRI reference standard. There was no significant bias for both blood-pool methods and a minor negative bias for FDGMyo regarding the LV ejection fraction (LVEF) when compared to cine-MRI results. There was no significant difference between the means of FDGMyo and FDGMyo2 (P = .50). CONCLUSIONS: Relative to reference standard MRI measurements of LVEF, there was excellent agreement between PET-based measurements, notably for the novel blood-pool tracer (68)Ga-albumin.

Workflow and scan protocol considerations for integrated whole-body PET/MRI in oncology.

Integrated PET/MRI systems open exciting possibilities for clinical and research applications. However, compared with PET/CT, PET/MRI is a complex technique resulting in new problems and challenges, especially regarding workflow, scan protocols, and data analysis. This complexity applies in particular to examinations in oncology with partial- or whole-body coverage extending over several bed positions. Unlike diagnostic PET/CT, for which the clinical CT protocols can largely be copied from stand-alone CT, the design of a diagnostic MRI protocol for partial- or whole-body coverage is more complex and has to be adapted to the special requirements of PET/MRI to be both time-efficient and comprehensive. Here, we describe basic considerations concerning workflow, imaging protocols, and image analysis for whole-body PET/MRI in oncology, based on our experience with the first integrated PET/MRI scanner. The aim is to fully and optimally make use of the combined PET/MRI measurements in oncology, including identifying and reducing image artifacts as well as optimizing workflow beyond the mere fusion of 2 image datasets.

Transient ischemic dilation ratio in 82Rb PET myocardial perfusion imaging: normal values and significance as a diagnostic and prognostic marker.

UNLABELLED: In myocardial perfusion SPECT, transient ischemic dilation ratio (TID) is a well-established marker of severe ischemia and adverse outcome. However, its role in the setting of (82)Rb PET is less well defined. METHODS: We analyzed 265 subjects who underwent clinical rest-dipyridamole (82)Rb PET/CT. Sixty-two subjects without a prior history of cardiac disease and with a normal myocardial perfusion study had either a low or a very low pretest likelihood of coronary artery disease or negative CT angiography. These subjects were used to establish a reference range of TID. In the remaining 203 patients with an intermediate or high pretest likelihood, subgroups with normal and abnormal TID were established and compared with respect to clinical variables, perfusion defect scores, left ventricular function, and absolute myocardial flow reserve. Follow-up was obtained for 969 ± 328 d to determine mortality by review of the social security death index. RESULTS: In the reference group, TID ratio was 0.98 ± 0.06. Accordingly, a threshold for abnormal TID was set at greater than 1.13 (0.98 + 2.5 SDs). In the study group, 19 of 203 patients (9%) had an elevated TID ratio. Significant differences between subgroups with normal and abnormal TID ratio were observed for ejection fraction reserve (5.0 ± 6.4 vs. 1.8 ± 7.9; P < 0.05), difference between end-systolic volume (ESV) at rest and stress (ΔESV[stress-rest]; 1.8 ± 7.4 vs. 12.3 ± 13.0 mL; P < 0.0001), difference between end-diastolic volume (EDV) at rest and stress (ΔEDV[stress-rest]; 10.8 ± 11.5 vs. 23.8 ± 14.6 mL; P < 0.0001), summed rest score (1.8 ± 3.8 vs. 3.8 ± 7.6; P < 0.05), summed stress score (3.0 ± 5.4 vs. 7.5 ± 9.8; P < 0.002), summed difference score (1.3 ± 2.6 vs. 3.7 ± 5.3; P < 0.02), and global myocardial flow reserve (2.1 ± 0.8 vs. 1.7 ± 0.6; P < 0.02). Additionally, TID-positive patients had a significantly lower overall survival probability (P < 0.05). In a subgroup analysis of patients without regional perfusion abnormalities, TID-positive patients' overall survival probability was significantly smaller (P < 0.03), and TID was an independent predictor (exponentiation of the B coefficients [Exp(b)] = 6.22; P < 0.009) together with an ejection fraction below 45% (Exp[b] = 6.16; P < 0.002). CONCLUSION: The present study suggests a reference range of TID for (82)Rb PET myocardial perfusion imaging that is in the range of previously established values for SPECT. Abnormal TID in (82)Rb PET is associated with more extensive left ventricular dysfunction, ischemic compromise, and reduced global flow reserve. Preliminary outcome analysis suggests that TID-positive subjects have a lower overall survival probability.

Registration of myocardial PET and SPECT for viability assessment using mutual information.

PURPOSE: The combination of sequentially acquired cardiac PET and SPECT data integrating metabolic and perfusion information allows the assessment of myocardial viability, a relevant clinical parameter for the management of patients who have suffered myocardial infarction and are now candidates for complex and cost intensive therapies such as bypass surgery. However, registration of cardiac functional datasets acquired on different imaging systems is limited by the difficulty to define anatomical landmarks and by the relatively poor inherent spatial resolution. In this article, the authors sought to evaluate whether it is possible to automatically register FDG-PET and sestamibi-SPECT cardiac data. METHODS: Automatic rigid registration was implemented with the ITK framework using Mattes mutual information as the similarity measure and a quaternion to represent the rotational component. The goodness of the alignment was evaluated by computing the mean target registration error (mTRE) at the myocardial wall. The registration parameters were optimized for robustness and speed using the data from 11 cardiac patients undergoing both PET and SPECT examinations (training datasets). The optimized algorithm was applied on the PET and SPECT data from 11 further patients (evaluation datasets). Quantitative (mTRE calculation) and visual (scoring method) comparisons were performed between automatic and manual registrations. Moreover, the automatic registration was also compared to the registration implicitly defined in the standard clinical analysis. RESULTS: The registration parameters were successfully optimized and resulted in a mean mTRE of 1.13 mm and 1.2 s average runtime on standard computer hardware for the training datasets. Automatic registration in the 11 validation datasets resulted in an average mTRE of 2.3 mm, with 7.5 mm mTRE in the worst case and an average runtime of 1.6 s. Automatic registration outperformed manual registrations both for the mTRE and for the visual assessment. Automatic registration also resulted in higher accuracy and better visual assessment as compared to the registration implicitly performed in the standard clinical analysis. CONCLUSIONS: The results demonstrate the possibility to successfully perform mutual information based registration of PET and SPECT cardiac data, allowing an improved workflow for the sequentially acquired cardiac datasets, in general, and specifically for the assessment of myocardial viability.

Monte Carlo simulations of the count rate performance of a clinical whole-body MR/PET scanner.

The combination of MR and PET scanners can provide a powerful tool for clinical diagnosis and investigation. Among the existing approaches, the most challenging is that of complete hardware integration of both scanners. Such an integrated tomograph would allow simultaneous acquisition of both modalities, which could help solve issues such as cardiac and respiratory motion. Full integration imposes restrictions on the design of the PET part, such as detector configuration and maximum ring diameter. Furthermore, MR components surrounding the PET detector ring may cause gamma ray interactions, thus affecting PET performance. The purpose of this article is to assess the performance of a hypothetical whole-body integrated MR/PET scanner using Monte Carlo simulation techniques and compare it to state-of-the-art PET/CT devices used in clinical routine. The Monte Carlo simulation toolkit used for this study is the GEANT4 application for emission tomography. A hypothetical whole-body MR/PET tomograph fully integrated at hardware level and positioned between gradient and local coils of the MR scanner has been modeled. The NEMA 2-2001 protocol has been used to configure the simulations in order to measure sensitivity, scatter fraction, count losses, and random detections. Global sensitivity values as a function of the lower-level discriminator (LLD) energy are provided for time resolutions of 5 and 2.25 ns. In addition, the scatter fraction of the system is studied as a function of the LLD for energy resolution values of 10%, 15%, and 20%. Finally, true, scatter, random, and noise equivalent count rate curves as a function of activity concentration are given for dead-time values of 136, 432, and 1150 ns and for time resolution values of 2.25 and 5 ns. The influence on the count rate performance of the integrated PET scanner of the new geometry and interfering MR elements has been measured. The results show that the interference of the MR components has a much lower impact than the reduction in the detector ring diameter. Due to the larger solid angle coverage, the sensitivity is higher than that measured for a clinical PET/CT system (6200-10 900 cps/MBq at the center of the scanner) but not enough to compensate the degradation of the noise equivalent count rate due to increased scatter detection. The simulations prove the viability of an integrated MR/PET system and suggest that priority has to be given to either the improvement of the temporal resolution or the correction of triple coincidences if competitive performance is to be achieved.

Evaluation of a novel (18)F-labeled positron-emission tomography perfusion tracer for the assessment of myocardial infarct size in rats.

BACKGROUND: The goal of this study was to evaluate a new (18)F-labeled positron-emission tomography (PET) perfusion tracer, (18)F BMS747158-02, for the assessment of myocardial infarct (MI) size. METHODS AND RESULTS: Wistar rats were studied 24 hours after ligation of the left coronary artery either permanently (n=15) or transiently (n=16) for 30 minutes. Seven nonoperated rats were studied as controls. The rats were injected with 37 MBq of (18)F BMS747158-02 and imaged with a small animal PET scanner for 20 minutes. Polar maps were generated for measurement of PET defect size, and left ventricular systolic and diastolic volumes were assessed in gated images. As a reference, MI size was determined by 2,3,5-triphenyltetrazolium chloride staining of left ventricular tissue samples. Permanent or transient ligation of the left coronary artery produced transmural or subendocardial MI of variable sizes, respectively. In normal rats, PET imaging demonstrated intense and homogeneous uptake of (18)F BMS747158-02 throughout the myocardium. After ligation, sharply defined perfusion defects were present. Throughout the imaging period, the defect size correlated closely with the MI size either after permanent (r=0.88; P<0.01; mean difference, 1.86%) or transient (r=0.92; P<0.01; mean difference, 2.16%) ligation of the left coronary artery. Moreover, reduction of left ventricular systolic function measured with PET correlated with the MI size (r=-0.81; P<0.01; n=23). CONCLUSIONS: Myocardial (18)F BMS747158-02 PET imaging provides excellent image quality and uptake properties, enabling accurate evaluation of MI size and left ventricular function in rats. It is a promising technique for evaluation of MI size in clinical trials.

A phantom assessment of cold stomach-related artifacts in myocardial perfusion imaging.

AIM: To study the effect of a 'cold stomach', caused by either air or water, on Tl-201 and Tc-99m myocardial perfusion single-photon emission computed tomography (MPS). MATERIALS AND METHODS: A stomach insert was created in a thorax phantom. MPS was performed with Tl-201 or Tc-99m. MPS was recorded with an empty stomach, a stomach filled with 0.5 or 1 l of water, or with 0.5 or 1 l of air. For Tc-99m, transmission scans for attenuation correction (AC) were also obtained. RESULTS: In Tl-201 MPS, filling the stomach with air caused an increase of activity in the infero-lateral wall, whereas filling the stomach with 1 l of water resulted in a slight decrease of activity in the infero-lateral wall. In Tc-99m MPS, filling the stomach with air also resulted in a higher activity in the infero-lateral wall, which normalized when AC was applied. Filling the stomach with water caused no marked differences in Tc-99m MPS with or without AC. CONCLUSION: A stomach filled with large amounts of water causes (mild) infero-lateral wall defects in Tl-201 MPS; a stomach filled with air causes a strong scintigraphic overexpression of the infero-lateral wall in both Tl-201 and Tc-99m MPS which can be compensated with AC.

Rubidium-82 PET-CT for quantitative assessment of myocardial blood flow: validation in a canine model of coronary artery stenosis.

PURPOSE: Absolute quantification of myocardial blood flow expands the diagnostic potential of PET for assessment of coronary artery disease. (82)Rb has significantly contributed to increasing utilization of PET; however, clinical studies are still mostly analysed qualitatively. The aim of this study was to reevaluate the feasibility of (82)Rb for flow quantification, using hybrid PET-CT in an animal model of coronary stenosis. METHODS: Nine dogs were prepared with experimental coronary artery stenosis. Dynamic PET was performed for 8 min after (82)Rb(1480-1850 MBq) injection during adenosine-induced vasodilation. Microspheres were injected simultaneously for reference flow measurements. CT angiography was used to determine the myocardial regions related to the stenotic vessel. Two methods for flow calculation were employed: a two-compartment model including a spill-over term, and a simplified retention index. RESULTS: The two-compartment model data were in good agreement with microsphere flow (y = 0.84x + 0.20; r = 0.92, p<0.0001), although there was variability in the physiological flow range <3 ml/g per minute (y = 0.54x + 0.53; r = 0.53, p = 0.042). Results from the retention index also correlated well with microsphere flow (y = 0.47x + 0.52; r = 0.75, p = 0.0004). Error increased with higher flow, but the correlation was good in the physiological range (y = 0.62x + 0.29; r = 0.84, p = 0.0001). CONCLUSION: Using current state-of-the-art PET-CT systems, quantification of myocardial blood flow is feasible with (82)Rb. A simplified approach based on tracer retention is practicable in the physiological flow range. These results encourage further testing of the robustness and usefulness in the clinical context of cardiac hybrid imaging.

Assessment of alphavbeta3 integrin expression after myocardial infarction by positron emission tomography.

AIMS: The purpose of this study was to determine the feasibility of a new positron emission tomography (PET) imaging approach using an (18)F-labelled alpha(v)beta(3) integrin antagonist ((18)F-Galacto-RGD) to monitor the integrin expression after myocardial infarction. METHODS AND RESULTS: Male Wister rats were subjected to 20 min transient left coronary artery occlusion followed by reperfusion. Autoradiographic analysis and in vivo PET imaging were used to determine myocardial (18)F-Galacto-RGD uptake at different time points following reperfusion. RESULTS: PET imaging and autoradiography demonstrated no significant focal myocardial (18)F-Galacto-RGD uptake in non-operated control rats and at day 1 after reperfusion. However, focal accumulation in the infarct area started at day 3 (uptake ratio = 1.91 +/- 0.22 vs. remote myocardium), peaked between 1 (3.43 +/- 0.57) and 3 weeks (3.43 +/- 0.95), and decreased to 1.96 +/- 0.40 at 6 months after reperfusion. Pretreatment with alpha(v)beta(3) integrin antagonist c(-RGDfV-) significantly decreased tracer uptake, indicating the specificity of tracer uptake. The time course of focal tracer uptake paralleled vascular density as measured by CD31 immunohistochemical analysis. CONCLUSION: Regional (18)F-Galacto-RGD accumulation suggests up-regulation of alpha(v)beta(3) integrin expression after myocardial infarction, which peaks between 1 and 3 weeks and remains detectable until 6 months after reperfusion. This new PET tracer is promising for the monitoring of myocardial repair processes.

Contrast-enhanced magnetic resonance imaging in the assessment of myocardial infarction and viability.

Contrast-enhanced magnetic resonance imaging (MRI) can be used to visualize the transmural extent of myocardial infarction with high spatial resolution. The aim of this review is to provide an overview of the use of contrast-enhanced MRI for characterization of ischemic myocardial injury in comparison to other imaging methods and its relevance in clinical syndromes related to coronary artery disease. Infarcted myocardium appears hyperenhanced compared with normal myocardium when imaged by a delayed-enhancement MRI technique with the use of an inversion-prepared T(1)-weighted sequence after injection of gadolinium chelates, such as gadolinium-diethylenetriamine pentaacetic acid. Experimental and clinical studies indicate that the extent of delayed enhancement is reproducible and closely correlates with the size of myocardial necrosis or infarct scar as determined by established in vitro and in vivo methods. Furthermore, MRI appears to be more sensitive than other imaging methods in detecting small subendocardial infarctions. The transmural extent of delayed enhancement potentially predicts functional outcome after revascularization in acute myocardial infarction and chronic ischemic heart disease, indicating that it can accurately discriminate between infarction and dysfunctional but viable myocardium. Further experience from clinical trials is needed to understand the association of delayed enhancement with clinical outcomes.

Assessment of global and regional left ventricular function by electrocardiographic gated N-13 ammonia positron emission tomography in patients with coronary artery disease.

BACKGROUND: Electrocardiographic gated 13N-ammonia positron emission tomography (PET) enables simultaneous assessment of myocardial blood flow and left ventricular (LV) function. The aim of this study was to assess the accuracy of gated 13N-ammonia PET for evaluating global and regional LV function in patients with coronary artery disease (CAD) in comparison with conventional left ventriculography (LVG). METHODS AND RESULTS: Fifty-four patients with CAD underwent gated 13N-ammonia PET and LVG. The LV end-diastolic and end-systolic volumes (LVEDV, LVESV) and ejection fraction (LVEF) by gated 13N-ammonia PET were calculated using Cedars-Sinai automated quantitative gated single photon emission computed tomography (QGS) and compared with those obtained by LVG. The regional wall motion (RWM) was visually scored, and compared with that on LVG. There were good correlations between the 2 methods for LVEF, LVEDV and LVESV (R=0.828, R=0.821 and R=0.874 respectively). The RWM assessed by gated 13N-ammonia PET also agreed well with that by LVG (complete agreement was 70.4%, kappa=0.58). CONCLUSIONS: Gated 13N-ammonia PET combined with QGS works reasonably well for the assessment of both global and regional LV function in CAD patients, although additional calibration may be necessary.