Myocardial glucose suppression may interfere with the detection of inflammatory cells with FDG-PET as suggested in a canine model of myocardial infarction.

BACKGROUND: After myocardial infarction, fibrosis and an ongoing dysregulated inflammatory response have been shown to lead to adverse cardiac remodeling. FDG PET is an imaging modality sensitive to inflammation as long as suppression protocols are observed while gadolinium enhanced MRI can be used to determine extracellular volume (ECV), a measure of fibrosis. In patients, glucose suppression is achieved variously through a high fat diet, fasting and injection of heparin. To emulate this process in canines, a heparin injection and lipid infusion are used, leading to similar fatty acids in the blood. The aim of this study was to examine the effect of glucose suppression on the uptake of FDG in the infarcted myocardial tissue and also on the determination of ECV in both the infarcted tissue and in the myocardium remote to the zone of infarction during a long constant infusion of FDG and Gd-DTPA. RESULTS: Extracellular volume was affected neither by suppression nor the length of the constant infusion in remote and infarcted tissue. Metabolic rate of glucose in infarcted tissue decreased during and after suppression of glucose uptake by lipid infusion and heparin injection. An increase in fibrosis and inflammatory cells was found in the center of the infarct as compared to remote tissue. CONCLUSION: The decrease in the metabolic rate of glucose in the infarcted tissue suggests that inflammatory cells may be affected by glucose suppression through heparin injection and lipid infusion.

Changes in myocardial blood flow in a canine model of left sided breast cancer radiotherapy.

BACKGROUND: Left-sided breast cancer patients receiving adjuvant radiotherapy are at risk for coronary artery disease, and/or radiation mediated effects on the microvasculature. Previously our laboratory demonstrated in canines with hybrid 18FDG/PET a progressive global inflammatory response during the initial one year following treatment. In this study, the objective is to evaluate corresponding changes in perfusion, in the same cohort, where resting myocardial blood flow (MBF) was quantitatively measured. METHOD: In five canines, Ammonia PET (13NH3) derived MBF was measured at baseline, 1-week, 1, 3, 6 and 12-months after cardiac external beam irradiation. MBF measurements were correlated with concurrent 18FDG uptake. Simultaneously MBF was measured using the dual bolus MRI method. RESULTS: MBF was significantly increased at all time points, in comparison to baseline, except at 3-months. This was seen globally throughout the entire myocardium independent of the coronary artery territories. MBF showed a modest significant correlation with 18FDG activity for the entire myocardium (r = 0.51, p = 0.005) including the LAD (r = 0.49, p = 0.008) and LCX (r = 0.47, p = 0.013) coronary artery territories. CONCLUSION: In this canine model of radiotherapy for left-sided breast cancer, resting MBF increases as early as 1-week and persists for up to one year except at 3-months. This pattern is similar to that of 18FDG uptake. A possible interpretation is that the increase in resting MBF is a response to myocardial inflammation.

PET/MRI Assessment of Acute Cardiac Inflammation 1 Month After Left-Sided Breast Cancer Radiation Therapy.

Our purpose was to investigate the utility of 18F-FDG PET/MRI and serial blood work to detect early inflammatory responses and cardiac functionality changes at 1 mo after radiation therapy (RT) in patients with left-sided breast cancer. Methods: Fifteen left-sided breast cancer patients who enrolled in the RICT-BREAST study underwent cardiac PET/MRI at baseline and 1 mo after standard RT. Eleven patients received deep-inspiration breath-hold RT, whereas the others received free-breathing RT. A list-mode 18F-FDG PET scan with glucose suppression was acquired. Myocardial inflammation was quantified by the change in 18F-FDG SUVmean (based on body weight) and analyzed on the basis of the myocardial tissue associated with the left anterior descending, left circumflex, or right coronary artery territories. MRI assessments, including left ventricular functional and extracellular volumes (ECVs), were extracted from T1 (before and during a constant infusion of gadolinium) and cine images, respectively, acquired simultaneously during the PET acquisition. Cardiac injury and inflammation biomarker measurements of high-sensitivity troponin T, high-sensitivity C-reactive protein, and erythrocyte sedimentation rate were measured at the 1-mo follow-up and compared with preirradiation values. Results: At the 1-mo follow-up, a significant increase (10%) in myocardial SUVmean in left anterior descending segments (P = 0.04) and ECVs in slices at the apex (6%) and base (5%) was detected (P ≤ 0.02). Further, a significant reduction in left ventricular stroke volume (-7%) was seen (P < 0.02). No significant changes in any circulating biomarkers were seen at follow-up. Conclusion: Myocardial 18F-FDG uptake and functional MRI, including stroke volume and ECVs, were sensitive to changes at 1 mo after breast cancer RT, with findings suggesting an acute cardiac inflammatory response to RT.

Regional Differences in the Ghrelin-Growth Hormone Secretagogue Receptor Signalling System in Human Heart Disease.

BACKGROUND: The hormone ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR) are expressed in myocardium. GHSR binding activates signalling pathways coupled to cardiomyocyte survival and contractility. These properties have made the ghrelin-GHSR axis a candidate for a biomarker of cardiac function. The dynamics of ghrelin-GHSR are altered significantly in late stages of heart failure (HF) and cardiomyopathy, when left ventricular (LV) function is failing. We examined the relationship of GHSR with ghrelin in cardiac tissue from patients with valvular disease with no detectable changes in LV function. METHODS: Biopsy samples from the left ventricle and left atrium were obtained from 25 patients with valvular disease (of whom 13 also had coronary artery disease) and preserved LV ejection fraction, and compared to control samples obtained via autopsy. Using quantitative confocal fluorescence microscopy, levels of GHSR were determined using [Dpr3(n-octanoyl),Lys19(sulfo-Cy5)]ghrelin(1-19), and immunofluorescence determined ghrelin, the heart failure marker natriuretic peptide type-B (BNP), and contractility marker sarcoplasmic reticulum ATPase pump (SERCA2a). RESULTS: A positive correlation between GHSR and ghrelin was apparent in only diseased tissue. Ghrelin and BNP significantly correlated in the left ventricle and strongly colocalized to the same intracellular compartment in diseased and control tissue. GHSR, ghrelin, and BNP all strongly and significantly correlated with SERCA2a in the left ventricle of diseased tissue only. CONCLUSIONS: Our results suggest that the dynamics of the myocardial ghrelin-GHSR axis is altered in cardiovascular disease in the absence of measurable changes in heart function, and might accompany a regional shift in endocrine programming.

CONTEXTE: L'hormone ghréline et son récepteur, le récepteur sécrétagogue de l'hormone de croissance (GHSR, de l'anglais growth hormone secretagogue receptor), sont exprimés dans le myocarde. La liaison au récepteur GHSR active les voies de signalisation associées à la survie et à la contractilité des cardiomyocytes. Ces propriétés font de l'axe ghréline-récepteur GHSR un bon candidat biomarqueur de la fonction cardiaque. En effet, la dynamique de cet axe est considérablement altérée aux stades avancés de l'insuffisance cardiaque et de la cardiomyopathie, lorsque la fonction ventriculaire gauche décline. Nous avons donc étudié la relation entre le récepteur GHSR et la ghréline dans le tissu cardiaque de patients présentant une valvulopathie sans changements détectables dans la fonction ventriculaire gauche. MÉTHODOLOGIE: Des échantillons de tissus du ventricule et de l'oreillette gauches ont été prélevés par biopsie chez 25 patients présentant une valvulopathie (dont 13 avaient aussi une coronaropathie) et une fraction d'éjection ventriculaire gauche préservée, puis comparés avec des échantillons témoins prélevés à l'autopsie. Les taux du récepteur GHSR ont été mesurés par microscopie en fluorescence confocale quantitative à l'aide de [Dpr3(n-octanoyl),Lys19(sulfo-Cy5)] ghréline(1-19); les taux de ghréline, de peptide natriurétique de type B (BNP, un marqueur de l'insuffisance cardiaque), et de pompe ATPase du réticulum sarcoplasmique (SERCA2a; un marqueur de la contractilité) ont quant à eux été mesurés par immunofluorescence. RÉSULTATS: Nous avons noté une corrélation positive entre le récepteur GHSR et la ghréline uniquement dans les tissus lésés. Il existe une corrélation significative entre les taux de ghréline et de BNP dans le ventricule gauche, les deux substances étant fortement localisées dans le même compartiment intracellulaire, tant dans les tissus malades que dans les tissus témoins. Le récepteur GHSR, la ghréline et le BNP sont tous fortement et significativement corrélés avec la SERCA2a SERCA2a dans le tissu ventriculaire gauche malade seulement. CONCLUSIONS: Nos résultats semblent indiquer que la dynamique de l'axe ghréline-récepteur GHSR dans le myocarde est altérée en cas de maladie cardiovasculaire même en l'absence de changements mesurables de la fonction cardiaque, et que cette altération pourrait être attribuable à une modification régionale de la programmation endocrinienne.

Cubic-Spline Interpolation for Sparse-View CT Image Reconstruction With Filtered Backprojection in Dynamic Myocardial Perfusion Imaging.

We investigated a projection interpolation method for reconstructing dynamic contrast-enhanced (DCE) heart images from undersampled x-ray projections with filtered backprojecton (FBP). This method may facilitate the application of sparse-view dynamic acquisition for ultralow-dose quantitative computed tomography (CT) myocardial perfusion (MP) imaging. We conducted CT perfusion studies on 5 pigs with a standard full-view acquisition protocol (984 projections). We reconstructed DCE heart images with FBP from all and a quarter of the measured projections evenly distributed over 360°. We interpolated the sparse-view (quarter) projections to a full-view setting using a cubic-spline interpolation method before applying FBP to reconstruct the DCE heart images (synthesized full-view). To generate MP maps, we used 3 sets of DCE heart images, and compared mean MP values and biases among the 3 protocols. Compared with synthesized full-view DCE images, sparse-view DCE images were more affected by streak artifacts arising from projection undersampling. Relative to the full-view protocol, mean bias in MP measurement associated with the sparse-view protocol was 10.0 mL/min/100 g (95%CI: -8.9 to 28.9), which was >3 times higher than that associated with the synthesized full-view protocol (3.3 mL/min/100 g, 95% CI: -6.7 to 13.2). The cubic-spline-view interpolation method improved MP measurement from DCE heart images reconstructed from only a quarter of the full projection set. This method can be used with the industry-standard FBP algorithm to reconstruct DCE images of the heart, and it can reduce the radiation dose of a whole-heart quantitative CT MP study to <2 mSv (at 8-cm coverage).

Dynamics of the Ghrelin/Growth Hormone Secretagogue Receptor System in the Human Heart Before and After Cardiac Transplantation.

Currently, the early preclinical detection of left ventricular dysfunction is difficult because biomarkers are not specific for the cardiomyopathic process. The underlying molecular mechanisms leading to heart failure remain elusive, highlighting the need for identification of cardiac-specific markers. The growth hormone secretagogue receptor (GHSR) and its ligand ghrelin are present in cardiac tissue and are known to contribute to myocardial energetics. Here, we examined tissue ghrelin-GHSR levels as specific markers of cardiac dysfunction in patients who underwent cardiac transplantation. Samples of cardiac tissue were obtained from 10 patients undergoing cardiac transplant at the time of organ harvesting and during serial posttransplant biopsies. Quantitative fluorescence microscopy using a fluorescent ghrelin analog was used to measure levels of GHSR, and immunofluorescence was used to measure levels of ghrelin, B-type natriuretic peptide (BNP), and tissue markers of cardiomyocyte contractility and growth. GHSR and ghrelin expression levels were highly variable in the explanted heart, less in the grafted heart biopsies. GHSR and ghrelin were strongly positively correlated, and both markers were negatively correlated with left ventricular ejection fraction. Ghrelin had stronger positive correlations than BNP with the signaling markers for contractility and growth. These data suggest that GHSR-ghrelin have potential use as an integrated marker of cardiac dysfunction. Interestingly, tissue ghrelin appeared to be a more sensitive indicator than BNP to the biochemical processes that are characteristic of heart failure. This work allows for further use of ghrelin-GHSR to interrogate cardiac-specific biochemical mechanisms in preclinical stages of heart failure (HF).

[18F]FDG cardiac PET imaging in a canine model of radiation-induced cardiovascular disease associated with breast cancer radiotherapy.

Radiotherapy for the treatment of left-sided breast cancer increases the long-term risk of cardiovascular disease. The purpose of the present study was to noninvasively image the progression of radiation-induced cardiac inflammation in a large animal model using a hybrid PET and MRI system. Five canines were imaged using [18F]fluorodeoxyglucose PET to assess changes in myocardial inflammation. All animals were imaged at baseline, 1 wk, and 1, 3, 6, and 12 mo after focused cardiac external beam irradiation with image guidance. Radiation was delivered in a single fraction. The linear quadratic model was used to convert a typical multifractionated heart dose to a corrected single-fraction biologically equivalent dose. Immunohistochemistry was performed on excised left ventricular tissue samples from all five irradiated canines and one nonirradiated control canine to confirm the presence of inflammation. The mean doses delivered to the entire heart, left ventricle, left anterior descending artery, and left circumflex artery were 1.7 ± 0.2, 2.7 ± 0.2, 5.5 ± 0.9, and 1.1 ± 0.4 Gy, respectively. FDG standard uptake values remained persistently elevated compared with baseline (1.1 ± 0.03 vs. 2.6 ± 0.19, P < 0.05). The presence of myocardial inflammation was confirmed histologically and correlated with myocardial dose. This study suggests a global inflammatory response that is persistent up to 12 mo postirradiation. Inflammation PET imaging should be considered in future clinical studies to monitor the early changes in cardiac function that may play a role in the ultimate development of radiation-induced cardiac toxicity. NEW & NOTEWORTHY Using advanced cardiac PET imaging, we have shown the spatial and quantitative relationship between radiation dose deposition and temporal changes in inflammation. We have shown that the progression of radiation-induced cardiac inflammation is immediate and does not subside for up to 1 yr after radiation. Results are presented in a large animal model that closely resembles the size and vessel architecture of humans. The proposed imaging protocol can be easily replicated for clinical use.

Sensitivity and specificity of chest imaging for sarcoidosis screening in patients with cardiac presentations.

BACKGROUND: Patients with sarcoidosis can present with cardiac symptoms as the first manifestation of disease in any organ. In these patients, the use of chest imaging modalities may serve as an initial screening tool towards the diagnosis of sarcoidosis through identification of pulmonary/mediastinal involvement; however, the use of chest imaging for this purpose has not been well studied. We assessed the utility of different chest imaging modalities for initial screening for cardiac sarcoidosis (CS). METHODS AND RESULTS: All patients were investigated with chest x-ray, chest computed tomography (CT) and/or cardiac/thorax magnetic resonance imaging (MRI). We then used the final diagnosis (CS versus no CS) and adjudicated imaging reports (normal versus abnormal) to calculate the sensitivity and specificity of individual and combinations of chest imaging modalities. We identified 44 patients (mean age 54 (±8) years, 35.4% female) and a diagnosis of CS was made in 18/44 patients (41%). The sensitivity and specificity for screening for sarcoidosis were 35% and 85% for chest x-ray, respectively (AUC 0.60; 95%CI 0.42-0.78; p value=0.27); 94% and 86% for chest CT (AUC 0.90; 95%CI 0.80-1.00; p value <0.001); 100% and 50% for cardiac/thorax MRI (AUC 0.75; 95%CI 0.56-0.94; p value=0.04). CONCLUSIONS: During the initial diagnostic workup of patients with suspected CS, chest x-ray was suboptimal as a screening test. In contrast CT chest and cardiac/thorax MRI had excellent sensitivity. Chest CT has the highest specificity among imaging modalities. Cardiac/thorax MRI or chest CT could be used as an initial screening test, depending on local availability.

Functional CT assessment of extravascular contrast distribution volume and myocardial perfusion in acute myocardial infarction.

PURPOSE: In a pig model of acute myocardial infarction (AMI), we validated a functional computed tomography (CT) technique for concomitant assessment of myocardial edema and ischemia through extravscualar contrast distribution volume (ECDV) and myocardial perfusion (MP) measurements from a single dynamic imaging session using a single contrast bolus injection. METHODS: In seven pigs, balloon catheter was used to occlude the distal left anterior descending artery for one hour followed by reperfusion. CT and cardiac magnetic resonance (CMR) imaging studies were acquired on 3 days and 12 ±â€¯3 day post ischemic insult. In each CT study, 0.7 ml/kg of iodinated contrast was intravenously injected at 3-4 ml/s before dynamic contrast-enhanced (DCE) cardiac images were acquired with breath-hold using a 64-row CT scanner. DCE cardiac images were analyzed with a model-based deconvolution to generate ECDV and MP maps. ECDV as an imaging marker of edema was validated against CMR T2 weighted imaging in normal and infarcted myocardium delineated from ex-vivo histological staining. RESULTS: ECDV in infarcted myocardium was significantly higher (p < 0.05) than that in normal myocardium on both days post AMI and was in agreement with the findings of CMR T2 weighted imaging. MP was significantly lower (p < 0.05) in the infarcted region compared to normal on both days post AMI. CONCLUSION: This imaging technique can rapidly and simultaneously assess myocardial edema and ischemia through ECDV and MP measurements, and may be useful for delineation of salvageable tissue within at-risk myocardium to guide reperfusion therapy.

Ultra-low dose quantitative CT myocardial perfusion imaging with sparse-view dynamic acquisition and image reconstruction: A feasibility study.

PURPOSE: We implemented and validated a compressed sensing (CS) based algorithm for reconstructing dynamic contrast-enhanced (DCE) CT images of the heart from sparsely sampled X-ray projections. METHODS: DCE CT imaging of the heart was performed on five normal and ischemic pigs after contrast injection. DCE images were reconstructed with filtered backprojection (FBP) and CS from all projections (984-view) and 1/3 of all projections (328-view), and with CS from 1/4 of all projections (246-view). Myocardial perfusion (MP) measurements with each protocol were compared to those with the reference 984-view FBP protocol. RESULTS: Both the 984-view CS and 328-view CS protocols were in good agreements with the reference protocol. The Pearson correlation coefficients of 984-view CS and 328-view CS determined from linear regression analyses were 0.98 and 0.99 respectively. The corresponding mean biases of MP measurement determined from Bland-Altman analyses were 2.7 and 1.2ml/min/100g. When only 328 projections were used for image reconstruction, CS was more accurate than FBP for MP measurement with respect to 984-view FBP. However, CS failed to generate MP maps comparable to those with 984-view FBP when only 246 projections were used for image reconstruction. CONCLUSION: DCE heart images reconstructed from one-third of a full projection set with CS were minimally affected by aliasing artifacts, leading to accurate MP measurements with the effective dose reduced to just 33% of conventional full-view FBP method. The proposed CS sparse-view image reconstruction method could facilitate the implementation of sparse-view dynamic acquisition for ultra-low dose CT MP imaging.

Characterization of 3-Dimensional PET Systems for Accurate Quantification of Myocardial Blood Flow.

Three-dimensional (3D) mode imaging is the current standard for PET/CT systems. Dynamic imaging for quantification of myocardial blood flow with short-lived tracers, such as 82Rb-chloride, requires accuracy to be maintained over a wide range of isotope activities and scanner counting rates. We proposed new performance standard measurements to characterize the dynamic range of PET systems for accurate quantitative imaging. METHODS: 82Rb or 13N-ammonia (1,100-3,000 MBq) was injected into the heart wall insert of an anthropomorphic torso phantom. A decaying isotope scan was obtained over 5 half-lives on 9 different 3D PET/CT systems and 1 3D/2-dimensional PET-only system. Dynamic images (28 × 15 s) were reconstructed using iterative algorithms with all corrections enabled. Dynamic range was defined as the maximum activity in the myocardial wall with less than 10% bias, from which corresponding dead-time, counting rates, and/or injected activity limits were established for each scanner. Scatter correction residual bias was estimated as the maximum cavity blood-to-myocardium activity ratio. Image quality was assessed via the coefficient of variation measuring nonuniformity of the left ventricular myocardium activity distribution. RESULTS: Maximum recommended injected activity/body weight, peak dead-time correction factor, counting rates, and residual scatter bias for accurate cardiac myocardial blood flow imaging were 3-14 MBq/kg, 1.5-4.0, 22-64 Mcps singles and 4-14 Mcps prompt coincidence counting rates, and 2%-10% on the investigated scanners. Nonuniformity of the myocardial activity distribution varied from 3% to 16%. CONCLUSION: Accurate dynamic imaging is possible on the 10 3D PET systems if the maximum injected MBq/kg values are respected to limit peak dead-time losses during the bolus first-pass transit.

Technical Note: Evaluation of a 160-mm/256-row CT scanner for whole-heart quantitative myocardial perfusion imaging.

PURPOSE: The authors investigated the performance of a recently introduced 160-mm/256-row CT system for low dose quantitative myocardial perfusion (MP) imaging of the whole heart. This platform is equipped with a gantry capable of rotating at 280 ms per full cycle, a second generation of adaptive statistical iterative reconstruction (ASiR-V) to correct for image noise arising from low tube voltage potential/tube current dynamic scanning, and image reconstruction algorithms to tackle beam-hardening, cone-beam, and partial-scan effects. METHODS: Phantom studies were performed to investigate the effectiveness of image noise and artifact reduction with a GE Healthcare Revolution CT system for three acquisition protocols used in quantitative CT MP imaging: 100, 120, and 140 kVp/25 mAs. The heart chambers of an anthropomorphic chest phantom were filled with iodinated contrast solution at different concentrations (contrast levels) to simulate the circulation of contrast through the heart in quantitative CT MP imaging. To evaluate beam-hardening correction, the phantom was scanned at each contrast level to measure the changes in CT number (in Hounsfield unit or HU) in the water-filled region surrounding the heart chambers with respect to baseline. To evaluate cone-beam artifact correction, differences in mean water HU between the central and peripheral slices were compared. Partial-scan artifact correction was evaluated from the fluctuation of mean water HU in successive partial scans. To evaluate image noise reduction, a small hollow region adjacent to the heart chambers was filled with diluted contrast, and contrast-to-noise ratio in the region before and after noise correction with ASiR-V was compared. The quality of MP maps acquired with the CT system was also evaluated in porcine CT MP studies. Myocardial infarct was induced in a farm pig from a transient occlusion of the distal left anterior descending (LAD) artery with a catheter-based interventional procedure. MP maps were generated from the dynamic contrast-enhanced (DCE) heart images taken at baseline and three weeks after the ischemic insult. RESULTS: Their results showed that the phantom and animal images acquired with the CT platform were minimally affected by image noise and artifacts. For the beam-hardening phantom study, changes in water HU in the wall surrounding the heart chambers greatly reduced from >±30 to ≤ ± 5 HU at all kVp settings except one region at 100 kVp (7 HU). For the cone-beam phantom study, differences in mean water HU from the central slice were less than 5 HU at two peripheral slices with each 4 cm away from the central slice. These findings were reproducible in the pig DCE images at two peripheral slices that were 6 cm away from the central slice. For the partial-scan phantom study, standard deviations of the mean water HU in 10 successive partial scans were less than 5 HU at the central slice. Similar observations were made in the pig DCE images at two peripheral slices with each 6 cm away from the central slice. For the image noise phantom study, CNRs in the ASiR-V images were statistically higher (p < 0.05) than the non-ASiR-V images at all kVp settings. MP maps generated from the porcine DCE images were in excellent quality, with the ischemia in the LAD territory clearly seen in the three orthogonal views. CONCLUSIONS: The study demonstrates that this CT system can provide accurate and reproducible CT numbers during cardiac gated acquisitions across a wide axial field of view. This CT number fidelity will enable this imaging tool to assess contrast enhancement, potentially providing valuable added information beyond anatomic evaluation of coronary stenoses. Furthermore, their results collectively suggested that the 100 kVp/25 mAs protocol run on this CT system provides sufficient image accuracy at a low radiation dose (<3 mSv) for whole-heart quantitative CT MP imaging.

Can the inflammatory response be evaluated using 18F-FDG within zones of microvascular obstruction after myocardial infarction?

UNLABELLED: Inflammation that occurs after acute myocardial infarction plays a pivotal role in healing by facilitating the creation of a supportive scar. (18)F-FDG, which is taken up avidly by macrophages, has been proposed as a marker of cell-based inflammation. However, its reliability as an accurate indicator of inflammation has not been established, particularly in the early postinfarction period when regional myocardial perfusion is often severely compromised. METHODS: Nine adult dogs underwent left anterior descending coronary occlusion with or without reperfusion. Animals were imaged between 7 and 21 d after infarction with PET/MR imaging after bolus injection of gadolinium-diethylenetriaminepentaacetic acid (DTPA), bolus injection of (18)F-FDG, bolus injection of (99)Tc-DTPA to simulate the distribution of gadolinium-DTPA (which represents its partition coefficient in well-perfused tissue), and injection of (111)In-labeled white blood cells 24 h earlier. After sacrifice, myocardial tissue concentrations of (18)F, (111)In, and (99)Tc were determined in a well counter. Linear regression analysis evaluated the relationships between the concentrations of (111)In and (18)F and the dependence of the ratio of (111)In/(18)F to the apparent distribution volume of (99m)Tc-DTPA. RESULTS: In 7 of 9 animals, (111)In increased as (18)F increased with the other 2 animals, showing weak negative slopes. With respect to the dependence of (111)In/(18)F with partition coefficient, 4 animals showed no dependence and 4 showed a weak positive slope, with 1 animal showing a negative slope. Further, in regions of extensive microvascular obstruction, (18)F significantly underestimated the extent of the presence of (111)In. CONCLUSION: In the early post-myocardial infarction period, (18)F-FDG PET imaging after a single bolus administration may underestimate the extent and degree of inflammation within regions of microvascular obstruction.

Clinical interpretation standards and quality assurance for the multicenter PET/CT trial rubidium-ARMI.

UNLABELLED: Rubidium-ARMI ((82)Rb as an Alternative Radiopharmaceutical for Myocardial Imaging) is a multicenter trial to evaluate the accuracy, outcomes, and cost-effectiveness of low-dose (82)Rb perfusion imaging using 3-dimensional (3D) PET/CT technology. Standardized imaging protocols are essential to ensure consistent interpretation. METHODS: Cardiac phantom qualifying scans were obtained at 7 recruiting centers. Low-dose (10 MBq/kg) rest and pharmacologic stress (82)Rb PET scans were obtained in 25 patients at each site. Summed stress scores, summed rest scores, and summed difference scores (SSS, SRS, and SDS [respectively] = SSS-SRS) were evaluated using 17-segment visual interpretation with a discretized color map. All scans were coread at the core lab (University of Ottawa Heart Institute) to assess agreement of scoring, clinical diagnosis, and image quality. Scoring differences greater than 3 underwent a third review to improve consensus. Scoring agreement was evaluated with intraclass correlation coefficient (ICC-r), concordance of clinical interpretation, and image quality using κ coefficient and percentage agreement. Patient (99m)Tc and (201)Tl SPECT scans (n = 25) from 2 centers were analyzed similarly for comparison to (82)Rb. RESULTS: Qualifying scores of SSS = 2, SDS = 2, were achieved uniformly at all imaging sites on 9 different 3D PET/CT scanners. Patient scores showed good agreement between core and recruiting sites: ICC-r = 0.92, 0.77 for SSS, SDS. Eighty-five and eighty-seven percent of SSS and SDS scores, respectively, had site-core differences of 3 or less. After consensus review, scoring agreement improved to ICC-r = 0.97, 0.96 for SSS, SDS (P < 0.05). The agreement of normal versus abnormal (SSS ≥ 4) and nonischemic versus ischemic (SDS ≥ 2) studies was excellent: ICC-r = 0.90 and 0.88. Overall interpretation showed excellent agreement, with a κ = 0.94. Image quality was perceived differently by the site versus core reviewers (90% vs. 76% good or better; P < 0.05). By comparison, scoring agreement of the SPECT scans was ICC-r = 0.82, 0.72 for SSS, SDS. Seventy-six and eighty-eight percent of SSS and SDS scores, respectively, had site-core differences of 3 or less. Consensus review again improved scoring agreement to ICC-r = 0.97, 0.90 for SSS, SDS (P < 0.05). CONCLUSION: (82)Rb myocardial perfusion imaging protocols were implemented with highly repeatable interpretation in centers using 3D PET/CT technology, through an effective standardization and quality assurance program. Site scoring of (82)Rb PET myocardial perfusion imaging scans was found to be in good agreement with core lab standards, suggesting that the data from these centers may be combined for analysis of the rubidium-ARMI endpoints.

Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) IMAGE HF Project I-A: study protocol for a randomized controlled trial.

BACKGROUND: Ischemic heart disease (IHD) is the most common cause of heart failure (HF); however, the role of revascularization in these patients is still unclear. Consensus on proper use of cardiac imaging to help determine which candidates should be considered for revascularization has been hindered by the absence of clinical studies that objectively and prospectively compare the prognostic information of each test obtained using both standard and advanced imaging. METHODS/DESIGN: This paper describes the design and methods to be used in the Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) multi-center trial. The primary objective is to compare the effect of HF imaging strategies on the composite clinical endpoint of cardiac death, myocardial infarction (MI), cardiac arrest and re-hospitalization for cardiac causes.In AIMI-HF, patients with HF of ischemic etiology (n = 1,261) will follow HF imaging strategy algorithms according to the question(s) asked by the physicians (for example, Is there ischemia and/or viability?), in agreement with local practices. Patients will be randomized to either standard (SPECT, Single photon emission computed tomography) imaging modalities for ischemia and/or viability or advanced imaging modalities: cardiac magnetic resonance imaging (CMR) or positron emission tomography (PET). In addition, eligible and consenting patients who could not be randomized, but were allocated to standard or advanced imaging based on clinical decisions, will be included in a registry. DISCUSSION: AIMI-HF will be the largest randomized trial evaluating the role of standard and advanced imaging modalities in the management of ischemic cardiomyopathy and heart failure. This trial will complement the results of the Surgical Treatment for Ischemic Heart Failure (STICH) viability substudy and the PET and Recovery Following Revascularization (PARR-2) trial. The results will provide policy makers with data to support (or not) further investment in and wider dissemination of alternative 'advanced' imaging technologies. TRIAL REGISTRATION: NCT01288560.

Transcatheter aortic valve implantation in a patient with severe aortic insufficiency and minimal aortic annular calcification.

Severe aortic insufficiency with minimal aortic annular calcification has been considered a relative contraindication to transcatheter aortic valve implantation (TAVI) because of a lack of calcium for fluoroscopic visualization and radial stent fixation. We report a patient with severe aortic insufficiency after previous coronary artery bypass and aortic valve repair who underwent successful TAVI. Intraoperative transesophageal echocardiography was critical to guide valve implantation and previous surgical pledgets were used to seat an oversized TAVI prosthesis within the aortic annulus. In follow-up, the patient remained New York Heart Association class I and echocardiography demonstrated a well-functioning TAVI prosthesis with no aortic insufficiency.