Assessment of left ventricular function with gated myocardial perfusion SPECT and gated myocardial FDG PET in patients with left ventricular mechanical dyssynchrony.

BACKGROUND: Left ventricular mechanical dyssynchrony (LVMD) and left ventricular function are intertwined. Gated myocardial perfusion SPECT (MPS) and gated fluorodeoxyglucose positron emission computed tomography (FDG PET) is an elegant way for repeated assessment of myocardial dyssynchrony and myocardial function. To the knowledge of the authors at the time this manuscript was prepared, there was no comprehensive evaluation of the interplay of LVMD and left ventricular function as measured by gated MPS and gated FDG PET; as well as no evaluation of the agreement between the two methods. METHODS: Patients were assigned to the reference cohort (RC) and the dyssynchrony cohort (DC) based on the phase analysis results of gated MPS datasets. Subsequently left ventricular function was analyzed. RESULTS: We demonstrated that LVMD as detected by gated MPS is associated with a significantly higher end-diastolic volume (EDV) and end-systolic volume (ESV) as well as a significantly reduced left ventricular ejection fraction (LVEF) both in gated MPS and gated FDG PET imaging. In the RC and the DC SPECT and PET showed good agreement and generally high linear correlations with regard to left ventricular volumes and LVEF. In the combined cohort (RC and DC) increasing amounts of LVMD were associated with increasing left ventricular volumes as well as a decreasing LVEF. The association was strongest for the dyssynchrony parameter Entropy. CONCLUSIONS: We demonstrated that gated SPECT and gated PET are useful tools in the evaluation of left ventricular function in patients with LVMD as detected by gated MPS. Increasing amounts of dyssynchrony were associated with an increasingly reduced myocardial function. For repeated measurements or therapy monitoring, the methods should not be used interchangeably.

[68Ga]DOTA-TATE PET for the detection of early transplant rejection in a heterotopic allograft heart transplantation model of the rat: a pilot study.

BACKGROUND: The most important cause of heart transplant loss is early acute allograft rejection, caused by the infiltration of lymphocytes, development of edema and myocardial necrosis. It has been propagated that [68Ga]DOTA-TATE PET might be suitable to quantify the presence of SSTR over-expressing lymphocytes. With heterotopic allogenic heart transplant models in the rat readily available, we aimed to investigate, if monitoring and quantification of acute allograft rejection after heterotopic allogenic heart transplantation was feasible by non-invasive serial [68Ga]DOTA-TATE PET. METHODS: Seventeen Lewis rats (9 for serial PET imaging, 8 for histological correlation) received allogenic heterotopic heart transplants from 17 Brown-Norway rats. On days 4, 6 and 7 a [68Ga]DOTA-TATE PET scan was performed. RESULTS: Imaging of acute transplant rejection until 7 days after allogenic heart transplantation in the rat is feasible. Heterotopic allografts showed significantly increased tracer uptake on day 4 until day 7 after transplantation, reflecting the process of histologically detected myocardial lymphocytic infiltration. Both the area of infarction and the amount of necrosis increased over the course of 7 days, with necrosis reaching statistical significance. CONCLUSIONS: We purport that the detected PET signal is primarily a specific marker of lymphocyte infiltration and only to a lesser extent an unspecific marker of infarction and necrosis. Thus, [68Ga]DOTA-TATE PET might be a suitable tool for serial imaging and quantification of lymphocyte infiltration as a direct mediator of acute allograft rejection at an early stage after heart transplantation.

The assessment of left ventricular mechanical dyssynchrony from gated 99mTc-tetrofosmin SPECT and gated 18F-FDG PET by QGS: a comparative study.

BACKGROUND: Due to partly conflicting studies, further research is warranted with the QGS software package, with regard to the performance of gated FDG PET phase analysis as compared to gated MPS as well as the establishment of possible cut-off values for FDG PET to define dyssynchrony. METHODS: Gated MPS and gated FDG PET datasets of 93 patients were analyzed with the QGS software. BW, Phase SD, and Entropy were calculated and compared between the methods. The performance of gated PET to identify dyssynchrony was measured against SPECT as reference standard. ROC analysis was performed to identify the best discriminator of dyssynchrony and to define cut-off values. RESULTS: BW and Phase SD differed significantly between the SPECT and PET. There was no significant difference in Entropy with a high linear correlation between methods. There was only moderate agreement between SPECT and PET to identify dyssynchrony. Entropy was the best single PET parameter to predict dyssynchrony with a cut-off point at 62%. CONCLUSION: Gated MPS and gated FDG PET can assess LVMD. The methods cannot be used interchangeably. Establishing reference ranges and cut-off values is difficult due to the lack of an external gold standard. Further prospective research is necessary.

Quantitative myocardial perfusion SPECT/CT for the assessment of myocardial tracer uptake in patients with three-vessel coronary artery disease: Initial experiences and results.

BACKGROUND: To evaluate quantitative myocardial perfusion SPECT/CT datasets for routine clinical reporting and the assessment of myocardial tracer uptake in patients with severe TVCAD. METHODS: MPS scans were reconstructed as quantitative SPECT datasets using CTs from internal (SPECT/CT, Q_INT) and external (PET/CT, Q_EXT) sources for attenuation correction. TPD was calculated and compared to the TPD from non-quantitative SPECT datasets of the same patients. SUVmax, SUVpeak, and SUVmean were compared between Q_INT and Q_EXT SPECT datasets. Global SUVmax and SUVpeak were compared between patients with and without TVCAD. RESULTS: Quantitative reconstruction was feasible. TPD showed an excellent correlation between quantitative and non-quantitative SPECT datasets. SUVmax, SUVpeak, and SUVmean showed an excellent correlation between Q_INT and Q_EXT SPECT datasets, though mean SUVmean differed significantly between the two groups. Global SUVmax and SUVpeak were significantly reduced in patients with TVCAD. CONCLUSIONS: Absolute quantification of myocardial tracer uptake is feasible. The method seems to be robust and principally suitable for routine clinical reporting. Quantitative SPECT might become a valuable tool for the assessment of severe coronary artery disease in a setting of balanced ischemia, where potentially life-threatening conditions might otherwise go undetected.

Clinical impact of follicular oncocytic (Hürthle cell) carcinoma in comparison with corresponding classical follicular thyroid carcinoma.

PURPOSE: There are controversial debates if patients with Hürthle cell carcinoma, also known as oxyphilic or oncocytic cell follicular thyroid carcinoma, have a poorer outcome. In this study, we systematically evaluated the clinical outcome in a large patient cohort following thyroidectomy and initial I-131 radioactive iodine therapy (RIT). METHODS: We retrospectively evaluated a total of 378 patients with diagnosed oncocytic follicular Hürthle cell carcinoma (OFTC) (N = 126) or with classical follicular thyroid carcinoma (FTC) (N = 252). Patients received thyroidectomy and complementary I-131 RIT. Clinical data regarding basic demographic characteristics, tumor grade, persistent disease and recurrence during follow-up, and disease-free, disease-specific, and overall survival were collected during follow-up of 6.9 years (interquartile range 3.7; 11.7 years). Univariate and multivariate analyses were used to identify factors associated with disease-related and overall survival. RESULTS: Before and after matching for risk factors, recurrence was significantly more frequently diagnosed in OFTC patients during follow-up (17% vs. 8%; p value 0.037). Likewise, OFTC patients presented with a reduced mean disease-free survival of 17.9 years (95% CI 16.0-19.8) vs. 20.1 years (95% CI 19.0-21.1) in FTC patients (p value 0.027). Multivariate analysis revealed OFTC (HR 0.502; 95% CI 0.309-0.816) as the only independent prognostic factor for disease-free survival. Distant metastases of OFTC patients were significantly less iodine-avid (p value 0.014). Mean disease-specific and overall survival did not differ significantly (p value 0.671 and 0.687) during follow-up of median 6.9 years (3.7; 11.7 years). CONCLUSIONS: Our study suggests that recurrence is more often seen in OFTC patients. OFTC patients have a poorer prognosis for disease-free survival. Thus, OFTC and FTC behave differently and should be categorized separately. However, patients suffering from OFTC present with the same overall and disease-specific survival at the end of follow-up indifferent to FTC patients after initial RIT.

Molecular imaging of cardiac CXCR4 expression in a mouse model of acute myocardial infarction using a novel 68Ga-mCXCL12 PET tracer.

BACKGROUND: The chemokine receptor CXCR4 and its ligand CXCL12 have been shown to be a possible imaging and therapeutic target after myocardial infarction (MI). The murine-based and mouse-specific 68Ga-mCXCL12 PET tracer could be suitable for serial in vivo quantification of cardiac CXCR4 expression in a murine model of MI. METHODS AND RESULTS: At days 1-6 after MI, mice were intravenously injected with 68Ga-mCXCL12. Autoradiography was performed and the infarct-to-remote ratio (I/R) was determined. In vivo PET imaging with 68Ga-mCXCL12 was conducted on days 1-6 after MI and the percentage of the injected dose (%ID/g) of the tracer uptake in the infarct area was calculated. 18F-FDG-PET was performed for anatomical landmarking. Ex vivo autoradiography identified CXCR4 upregulation in the infarct region with an increasing I/R after 12 hours (1.4 ± 0.3), showing a significant increase until day 2 (4.5 ± 0.6), followed by a plateau phase (day 4) and decrease after 10 days (1.3 ± 1.0). In vivo PET imaging identified similar CXCR4 upregulation in the infarct region which peaked around day 3 post MI (9.7 ± 5.0 %ID/g) and then subsequently decreased by day 6 (2.8 ± 1.0 %ID/g). CONCLUSION: Noninvasive molecular imaging of cardiac CXCR4 expression using a novel, murine-based, and specific 68Ga-mCXCL12 tracer is feasible both ex vivo and in vivo.

Assessment of right ventricular sympathetic dysfunction in patients with arrhythmogenic right ventricular cardiomyopathy: An 123I-metaiodobenzylguanidine SPECT/CT study.

PURPOSE: The purpose of the study was to evaluate a novel approach for the quantification of right ventricular sympathetic dysfunction in patients diagnosed with ARVC/D through state-of-the-art functional SPECT/CT hybrid imaging. METHODS: Sympathetic innervation of the heart was assessed using 123I-MIBG-SPECT/CT in 17 patients diagnosed with ARVC according to the modified task force criteria, and in 10 patients diagnosed with idiopathic ventricular fibrillation (IVF). The 123I-MIBG-uptake in the left (LV) and right ventricle (RV) was evaluated separately based on anatomic information derived from the CT scan, and compared to the uptake in the mediastinum (M). RESULTS: There was a significant difference in the LV/M ratio between the ARVC/D and the IVF groups (3.2 ± 0.5 vs. 3.9 ± 0.8, P = 0.014), with a cut-off value of 3.41 (77% sensitivity, 80% specificity, AUC 0.78). There was a highly significant difference in the mean RV/M ratios between both groups (1.6 ± 0.3 vs. 2.0 ± 0.2, P = 0.001), with optimal cut-off for discrimination at 1.86 (88% sensitivity, 90% specificity, AUC 0.93). CONCLUSION: Employing state-of-the-art functional SPECT/CT hybrid imaging, we could reliably assess and quantify right and left ventricular sympathetic innervation. The RV/M ratio was significantly lower in patients diagnosed with ARVC/D and provided sensitive and specific discrimination between patients with ARVC/D and IVF patients.

Long-term outcome of rare oncocytic papillary (Hürthle cell) thyroid carcinoma following (adjuvant) initial radioiodine therapy.

PURPOSE: Oncocytic (Hürthle cell) papillary thyroid carcinoma (OPTC) is a rare variant of the papillary thyroid carcinoma (PTC) which comprises approximately 1 to 11 % of PTC cases. Its clinical course and prognosis have not been comprehensively documented and the clinical outcome remains a controversial issue. Therefore, we investigated the long-term prognosis after thyroidectomy and (adjuvant) initial radioactive iodine therapy (RIT) of OPTC compared to PTC. METHODS: A total of 563 patients (47 with OPTC and 516 with PTC) with a median follow-up of 9.9 (0.3; 23.5) years were studied. All patients underwent thyroidectomy followed by (adjuvant) initial RIT. Data on the patients' demographics, pathology, laboratory findings, imaging studies, treatment, and follow-up including recurrence, and disease-specific survival were collected. Cox's multivariate regression model was used to identify independent prognostic factors for survival. RESULTS: OPTC patients were significantly older (55.2 ± 12.3 years) than PTC patients (50.3 ± 13.5) at the time of initial diagnosis (p value 0.016). Initial tumor size was larger in the OPTC group (2.8 ± 1.8 cm for OPTC patients, 1.5 ± 1.2 cm for PTC patients, p value < 0.001). Before matching, OPTC patients presented more often with evidence of disease at the last visit of follow-up (p value 0.046). However, this difference was not observed anymore after matching for risk factors (p value 0.637). Disease-specific survival did not differ significantly. Age (HR, 1.183; 95% CI, 1.097-1.276) was identified as an independent prognostic factor for disease-specific survival. OPTC patients predominantly showed a recurrence of distant metastasis within a shorter time despite being not statistically significant. CONCLUSION: At initial diagnosis, OPTC shows significant differences in terms of age and initial tumor size compared to PTC. Patients suffering from OPTC present with the same clinical long-term outcome indifferent to PTC after (adjuvant) initial RIT after matching.

The diagnostic value of [(18)F]FDG PET for the detection of chronic osteomyelitis and implant-associated infection.

PURPOSE: The diagnosis of osteomyelitis and implant-associated infections in patients with nonspecific laboratory or radiological findings is often unsatisfactory. We retrospectively evaluated the contributions of [(18)F]FDG PET and [(18)F]FDG PET/CT to the diagnosis of osteomyelitis and implant-associated infections, enabling timely and appropriate decision-making for further therapy options. METHODS: [(18)F]FDG PET or PET/CT was performed in 215 patients with suspected osteomyelitis or implant-associated infections between 2000 and 2013. We assessed the diagnostic accuracy of both modalities together and separately with reference to intraoperative microbial findings, with a mean clinical follow-up of 69 ± 49 months. RESULTS: Infections were diagnosed clinically in 101 of the 215 patients. PET and PET/CT scans revealed 87 true-positive, 76 true-negative, 38 false-positive, and 14 false-negative results, indicating a sensitivity of 86 %, a specificity of 67 %, a positive predictive value (PPV) of 70 %, a negative predictive value (NPV) of 84 % and an accuracy of 76 %. The sensitivity of PET/CT was 88 %, but specificity, PPV, NPV and accuracy (76 %, 76 %, 89 % and 82 %, respectively) were higher than those of stand-alone PET. CONCLUSION: [(18)F]FDG PET is able to identify with high sensitivity the presence of osteomyelitis in orthopaedic surgery patients with nonspecific clinical symptoms of infection.

Derivation of a respiration trigger signal in small animal list-mode PET based on respiration-induced variations of the ECG signal.

BACKGROUND: Raw PET list-mode data contains motion artifacts causing image blurring and decreased spatial resolution. Unless corrected, this leads to underestimation of the tracer uptake and overestimation of the lesion size, as well as inaccuracies with regard to left ventricular volume and ejection fraction (LVEF), especially in small animal imaging. METHODS AND RESULTS: A respiratory trigger signal from respiration-induced variations in the electro-cardiogram (ECG) was detected. Original and revised list-mode PET data were used for calculation of left ventricular function parameters using both respiratory gating techniques. For adequately triggered datasets we saw no difference in mean respiratory cycle period between the reference standard (RRS) and the ECG-based (ERS) methods (1120 ± 159 ms vs 1120 ± 159 ms; P = n.s.). While the ECG-based method showed somewhat higher signal noise (66 ± 22 ms vs 51 ± 29 ms; P < .001), both respiratory triggering techniques yielded similar estimates for EDV, ESV, LVEF (RRS: 387 ± 56 µL, 162 ± 34 µL, 59 ± 5%; ERS: 389 ± 59 µL, 163 ± 35 µL, 59 ± 4%; P = n.s.). CONCLUSIONS: This study showed that respiratory gating signals can be accurately derived from cardiac trigger information alone, without the additional requirement for dedicated measurement of the respiratory motion in rats.

Suspected pulmonary embolism in patients with pulmonary fibrosis: Discordance between ventilation/perfusion SPECT and CT pulmonary angiography.

BACKGROUND AND OBJECTIVE: Pulmonary embolism (PE) is a common differential diagnosis in patients with pulmonary fibrosis presenting with a clinical deterioration. Both ventilation/perfusion (V/Q)-single photon emission computed tomography (SPECT) and computed tomographic pulmonary angiography (CTPA) are routinely used to detect PE. However, the value of V/Q-SPECT and CTPA in this scenario has not been studied so far. We aimed to investigate the concordance of V/Q-SPECT and CTPA in patients with pulmonary fibrosis and suspicion of pulmonary embolism. METHODS: A total of 22 consecutive patients with pulmonary fibrosis and clinical deterioration who underwent both V/Q-SPECT and CTPA were included in the study and analyzed for the presence of pulmonary embolism. RESULTS: Nine of 22 patients (41%) had evidence for pulmonary embolism in V/Q-SPECT, and two of these patients had matching evidence for pulmonary embolism in CTPA. In the other seven patients with positive findings in V/Q-SPECT, no evidence of pulmonary embolism was found in CTPA. None of the 13 patients with a negative V/Q-SPECT had evidence for pulmonary embolism in CTPA. CONCLUSION: In patients with pulmonary fibrosis and suspected pulmonary embolism, pulmonary embolism is detected more frequently by V/Q-SPECT than by CTPA. Thromboembolic disease is identified on CTPA only in a minority of patients with positive findings on V/Q-SPECT. When making treatment decisions, clinicians should be aware of the high rate of discordant findings in V/Q-SPECT and CTPA in this specific patient population.

In vivo monitoring of parathyroid hormone treatment after myocardial infarction in mice with [68Ga]annexin A5 and [18F]fluorodeoxyglucose positron emission tomography.

[68Ga]Annexin A5 positron emission tomography (PET) reveals the externalization of phosphatidylserine as a surrogate marker for apoptosis. We tested this technique for therapy monitoring in a murine model of myocardial infarction (MI) including parathyroid hormone (PTH) treatment. MI was induced in mice, and they were assigned to the saline or the PTH group. On day 2, they received [68Ga]annexin A5 PET or histofluorescence TUNEL staining. Mice had 2-deoxy-2-[18F]fluoro-d-glucose (FDG)-PET examinations on days 6 and 30 for calculation of the left ventricular ejection fraction and infarct area. [68Ga]Annexin A5 uptake was 7.4 ± 1.3 %ID/g within the infarction for the controls and 4.5 ± 1.9 %ID/g for the PTH group (p  =  .013). TUNEL staining revealed significantly more apoptotic cells in the infarct area on day 2 in the controls (64 ± 9%) compared to the treatment group (52 ± 4%; p  =  .045). FDG-PET revealed a significant decrease in infarct size in the treatment group and an increase in the controls. Examinations of left ventricular ejection fraction on days 6 and 30 did not reveal treatment effects. [68Ga]Annexin A5 PET can detect the effects of PTH treatment as a marker of apoptosis 2 days after MI; ex vivo examination confirmed significant rescue of myocardiocytes. FDG-PET showed a small but significant reduction in infarct size but no functional improvement.

In-vivo comparison of the acute retention of stem cell derivatives and fibroblasts after intramyocardial transplantation in the mouse model.

PURPOSE: Various strategies have been applied to increase the engraftment of an intramyocardial cell transplant (Tx) to treat ischemic myocardium. Thereby, co-transplanted fibroblasts (FB) improve the long-term survival of stem cell derivatives (SCD) in a murine model of myocardial infarction. For therapeutic use, the time frame in which FB exert putative supportive effects needs to be identified. Therefore, we tracked the biodistribution and retention of SCD and FB in vivo using highly sensitive positron emission tomography (PET) imaging. METHODS: Murine [(18)F]-fluorodeoxyglucose (FDG) labeled SCD and FB were transplanted after left anterior descending artery (LAD) ligation into the border zone of the ischemic area in female C57BL/6 mice. Cardiac retention and biodistribution during the initial 2 h after injection were measured via PET imaging. RESULTS: Massive initial cell loss occurred independently of the cell type. Thereby, FB were retained slightly, yet significantly better than SCD until 60 min post-injection (7.5 ± 1.7 vs. 5.2 ± 0.7% ID at 25 min and 7.0 ± 1.5 vs. 4.8 ± 0.8% ID at 60 min). Thereafter, a fraction of ∼ 5% that withstood the massive initial washout remained at the site of injection independently of the applied cell type (120 min, SCD vs. FB P = 0.64). Most of the lost cells were detected in the lungs (∼ 30 % ID). CONCLUSIONS: We were able to quantitatively define the retention and biodistribution of different cell types via PET imaging in a mouse model after intramyocardial Tx. The utmost accuracy was achieved through this cell- and organ-specific approach by correcting PET data for cellular FDG efflux. Thereby, we observed a massive initial cell loss of ∼ 95%, causing low rates of long-term engraftment for both SCD and FB. We conclude that FB are not privileged compared to SCD regarding their acute retention kinetics, and therefore exert their beneficial effects at a later time point.

In-vivo monitoring of erythropoietin treatment after myocardial infarction in mice with [68Ga]Annexin A5 and [¹8F]FDG PET.

BACKGROUND: Several studies substantiate the cardioprotective effects of erythropoietin (EPO). Our goal was to quantify the effects of EPO treatment on the early expression of the apoptosis marker phosphatidylserine as well as on the left ventricular volumes and function by means of small animal PET. METHODS AND RESULTS: Myocardial infarction (MI) was induced in C57BL/6 mice. Animals were assigned to saline or EPO groups and underwent Annexin PET (day 2) and gated FDG PET (days 6 and 30). Annexin uptake was significantly higher in the infarction than in remote myocardium, with no differences between treatment groups. Infarct size showed a slight decrease in the EPO group and a slight increase in the controls, which did not reach statistical significance. Follow-up analyses revealed a significant increase of end-diastolic and end-systolic volumes in the EPO group, in which a stable left ventricular ejection fraction (LVEF) was maintained. CONCLUSION: We find that deleterious effects of EPO can outweigh cardioprotective effects. The present EPO treatment did not significantly reduce apoptosis after MI, but seemingly provoked significant myocardial dilation while maintaining a stable LVEF. Molecular mechanisms of EPO treatment may need further elucidation to optimize therapy regimens.

Influence of SPECT attenuation correction on the quantification of hibernating myocardium as derived from combined myocardial perfusion SPECT and ¹8F-FDG PET.

BACKGROUND: To evaluate the influence of SPECT attenuation correction on the quantification of hibernating myocardium derived from perfusion SPECT and (18)F-FDG PET. METHODS AND RESULTS: 20 patients underwent rest (99m)Tc-tetrofosmin perfusion SPECT/CT and (18)F-FDG PET/CT. Perfusion images were reconstructed without attenuation correction (NC), with attenuation correction based on the CT from the SPECT/CT (AC_SPECT), and with attenuation correction based on the CT from the PET/CT (AC_PET). Another 56 patients had rest (99m)Tc-tetrofosmin perfusion SPECT and (18)F-FDG PET/CT. Perfusion images were reconstructed as NC and AC_PET. The amounts of hibernating myocardium and scar were quantified with QPS and corresponding AC and NC normative databases. In both cohorts, perfusion in the inferior wall was higher in the AC scans than without AC. Global and regional values for total perfusion deficit (TPD), hibernation and scar areas did not differ between NC, AC_SPECT, and AC_PET scans. In a retrospective evaluation with 7% cut-off of hibernating myocardium as a condition for revascularization, the therapeutic approach would have been altered in 5 of 56 patients, if the AC_PET approach had been used. CONCLUSIONS: AC of SPECT perfusion scans with an attenuation map derived from PET/CT scans is feasible. If AC is unavailable, perfusion scans should be compared to NC normative databases for assessing TPD, hibernation, and mismatch. It should be taken into account that in approximately 10% of the patients, a therapeutic recommendation based on published thresholds for hibernating myocardium would be altered if NC scans were used as compared to AC scans.

Improved machine learning algorithm for predicting ground state properties.

Finding the ground state of a quantum many-body system is a fundamental problem in quantum physics. In this work, we give a classical machine learning (ML) algorithm for predicting ground state properties with an inductive bias encoding geometric locality. The proposed ML model can efficiently predict ground state properties of an n-qubit gapped local Hamiltonian after learning from only [Formula: see text] data about other Hamiltonians in the same quantum phase of matter. This improves substantially upon previous results that require [Formula: see text] data for a large constant c. Furthermore, the training and prediction time of the proposed ML model scale as [Formula: see text] in the number of qubits n. Numerical experiments on physical systems with up to 45 qubits confirm the favorable scaling in predicting ground state properties using a small training dataset.

Positron emission tomography based in-vivo imaging of early phase stem cell retention after intramyocardial delivery in the mouse model.

PURPOSE: To establish PET as a tool for in-vivo quantification and monitoring of intramyocardially transplanted stem cells after labelling with FDG in mice with induced myocardial infarction. METHODS: After inducing myocardial infarction in C57BL/6 mice, murine embryonic stem cells were labelled with FDG and transplanted into the border zone of the infarction. Dynamic PET scans were acquired from 25 to 120 min after transplantation, followed by a scan with 20 MBq FDG administered intravenously for anatomical landmarking. All images were reconstructed using the OSEM 3D and MAP reconstruction algorithms. FDG data were corrected for cellular tracer efflux and used as marker for cellular retention. FACS analysis of transplanted cells expressing enhanced green fluorescent protein was performed to validate the PET data. RESULTS: We observed a rapid loss of cells from the site of transplantation, followed by stable retention over 120 min. Amounts of retention were 5.3 ± 1.1 % at 25 min, 5.0 ± 0.9 % at 60 min and 5.7 ± 1.2 % at 120 min. FACS analysis showed a high correlation without significant differences between the groups (P > 0.05). FDG labelling did not have any adverse effects on cell proliferation or differentiation. CONCLUSION: Up-to-date imaging is a powerful method for tracking and quantifying intramyocardially transplanted stem cells in vivo in the mouse model. This revealed a massive cell loss within minutes, and thereafter a relatively stable amount of about 5 % remaining cells was observed. Our method may become crucial for further optimization of cardiac cell therapy in the widely used mouse model of infarction.

The amount of viable and dyssynchronous myocardium is associated with response to cardiac resynchronization therapy: initial clinical results using multiparametric ECG-gated [18F]FDG PET.

PURPOSE: There is still a significant amount of patients who do not sufficiently respond to cardiac resynchronization therapy (CRT). Previous studies demonstrated that the amount of dyssynchronous myocardium was predictive of response to CRT. Otherwise, non-response is frequently associated with high amounts of scar tissue. The combination of these parameters might yield a more accurate prediction of response. We hypothesized that the probability of a CRT response increases with the presence of high amounts of "viable and dyssynchronous" myocardium. METHODS: A total of 19 patients (17 male, 61 ± 10 years) underwent ECG-gated [(18)F]fluorodeoxyglucose (FDG) myocardial positron emission tomography (PET) before CRT device implantation and were followed for 6 months. Response to CRT was defined as clinical improvement of at least one New York Heart Association (NYHA) class in combination with left ventricular (LV) ejection fraction (EF) improvement of >5%. Twelve responders (71%) and seven non-responders (29%) were identified. For each patient bullseye maps of FDG uptake and phase analysis were calculated (QPS/QGS 2012, Cedars-Sinai, Los Angeles, CA, USA) and fused. Amounts of myocardium representing "viable and synchronous", "scar and synchronous", viable and dyssynchronous or "scar and dyssynchronous" myocardium were quantified by planimetric measurements of the fused bullseye maps. RESULTS: Responders by definition showed significant decrease in NYHA class and significant increase of LVEF. Furthermore, a significantly higher amount of viable and dyssynchronous myocardium was found as compared to non-responders (21 ± 13% vs 6 ± 5%; p < 0.05). CONCLUSION: Combined assessment of myocardial viability and LV dyssynchrony is feasible using multiparametric [(18)F]FDG PET and could improve conventional response prediction criteria for CRT.

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.

Association between left ventricular mechanical dyssynchrony with myocardial perfusion and functional parameters in patients with left bundle branch block.

OBJECTIVE: To identify predictors of left ventricular mechanical dyssynchrony (LVMD) in patients with known left bundle branch block (LBBB) using gated single-photon emission computed tomography (SPECT) phase analysis. METHODS: 81 patients (74% male, 70 ± 10 years) with LBBB and suspected or known coronary artery disease underwent ECG-gated myocardial perfusion SPECT. LV perfusion and functional parameters were measured, and phase analysis was performed to quantify LV-dyssynchrony. RESULTS: 35/81 patients (42%) had prior myocardial infarction (MI), and the mean left ventricular ejection fraction (LVEF) was 49% ± 16%. LVMD was present in 58/81 (72%) patients. The summed thickening score (STS) (P < .001; odds ratio 1.22) emerged as independent predictor for the presence of LVMD in a multivariate regression model. In addition, prior MI, low LVEF, summed stress score, summed rest score, summed motion score, and LAD rest extent were identified as predictors of LVMD in a univariate model. Clinical baseline characteristics, cardiac risk factors, and QRS duration (P = .051) had no influence on the presence of LVMD. CONCLUSION: In patients with LBBB, the occurrence of LVMD as assessed by gated SPECT phase analysis is mainly influenced by reduced myocardial contractility as expressed by the STS. Proper discrimination between LVMD arising from known electrical conduction delay as opposed to areas of MI causing reduced regional contractility seems to be mandatory for therapy planning in patients with LVMD.