Marjatta Strandberg

Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs☆

PURPOSE We evaluated four potential gallium-68 (68Ga)-labeled tracers for positron emission tomography (PET) imaging of myocardial perfusion in comparison with oxygen-15-labeled water ([15O]water) in healthy pigs. Four hexadentate salicylaldimine ligands derived from bis(3-aminopropyl)ethylenediamine (BAPEN) that showed promise in previous rat experiments were selected for this study. METHODS Following an evaluation of myocardial blood flow with [15O]water PET, the pigs (total n=14) underwent a dynamic 90-min PET study with one of four 68Ga-labeled BAPEN derivatives (n=3-5 per tracer) either at rest or under adenosine stress. Serial arterial blood samples were collected during the imaging for the measurements of total radioactivity, radiometabolites, plasma protein binding and blood-to-plasma ratio for the 68Ga chelates. Time-activity curves of the left ventricular blood pool and myocardium were derived from PET images, and metabolite-corrected arterial input function was used for kinetic modeling. Also, ex vivo biodistribution of 68Ga radioactivity was analyzed. RESULTS All four 68Ga tracers showed undesirably slow myocardial accumulation over time, but their in vivo stability, clearance from blood and the kinetics of the myocardium uptake varied. [68Ga][Ga-(sal)2BAPDMEN]1+ showed the highest myocardial uptake in PET images and tissue samples (myocardium-to-blood ratio 7.63±1.89, myocardium-to-lung ratio 3.03±0.33 and myocardium-to-liver ratio 1.80±0.82). However, there was no correlation between the myocardial perfusion measured with [15O]water and the net uptake rates or K1 values of the 68Ga chelates. CONCLUSION Our results revealed that myocardial accumulation of the 68Ga chelates proposed for myocardial perfusion imaging with PET was slow and not determined by myocardial perfusion in a large animal model. These findings suggest that the studied tracers are not suitable for clinical imaging of myocardial perfusion.

Transoesophageal echocardiography should be considered in patients with ischaemic stroke or transient ischaemic attack.

Background and purpose:  In this present study, we tried to find out if there is a subgroup of patients that should not undergo transoesophageal echocardiography (TEE) after an ischaemic stroke or transient ischaemic attack (TIA).

Predicting the outcome of hip fracture patients by using N-terminal fragment of pro-B-type natriuretic peptide

Objective To examine the prognostic value of perioperative N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in hip fracture patients. Design Blinded prospective cohort study. Setting Single centre trial at Turku University Hospital in Finland. Participants Inclusion criterion was admittance to the study hospital due to hip fracture during the trial period of October 2009—May 2010. Exclusion criteria were the patients refusal and inadequate laboratory tests. The final study population consisted of 182 patients. Primary and secondary outcome measures NT-proBNP was assessed once during the perioperative period and later if clinically indicated, and troponin T (TnT) and ECG recordings were evaluated repeatedly. The short-term (30-day) and long-term (1000 days) mortalities were studied. Results Median (IQR) follow-up time was 3.1 (0.3) years. The median (IQR) NT-proBNP level was 1260 (2298) ng/L in preoperative and 1600 (3971) ng/L in postoperative samples (p=0.001). TnT was elevated in 66 (36%) patients, and was significantly more common in patients with higher NT-proBNP. Patients with high (>2370 ng/L) and intermediate (806–2370 ng/L) NT-proBNP level had significantly higher short-term mortality compared with patients having a low (<806 ng/L) NT-proBNP level (15 vs 11 vs 2%, p=0.04), and the long-term mortality remained higher in these patients (69% vs 49% vs 27%, p<0.001). Intermediate or high NT-proBNP level (HR 7.8, 95% CI 1.03 to 59.14, p<0.05) was the only independent predictor of short-term mortality, while intermediate or high NT-proBNP level (HR 2.27, 95% CI 1.30 to 3.96, p=0.004), the presence of dementia (HR 1.74, 95% CI 1.13 to 2.66, p=0.01) and higher preoperative American Society of Anesthesiologists’ (ASA) classification (HR 1.59, 95% CI 1.06 to 2.38, p=0.02) were independent predictors of long-term mortality. Conclusion An elevated perioperative NT-proBNP level is common in hip fracture patients, and it is an independent predictor of short-term and long-term mortality superior to the commonly used clinical risk scores. Trial registration number NCT01015105; Results.

Cardiac remodeling in a new pig model of chronic heart failure: Assessment of left ventricular functional, metabolic, and structural changes using PET, CT, and echocardiography

AimsLarge animal models are needed to study disease mechanisms in heart failure (HF). In the present study we characterized the functional, metabolic, and structural changes of myocardium in a novel pig model of chronic myocardial infarction (MI) by using multimodality imaging and histology.Methods and ResultsMale farm pigs underwent a two-step occlusion of the left anterior descending coronary artery with concurrent distal ligation and implantation of a proximal ameroid constrictor (HF group), or sham operation (control group). Three months after the operation, cardiac output and wall stress were measured by echocardiography. Left ventricle (LV) volumes and mass were measured by computed tomography (CT). Myocardial perfusion was evaluated by [15O]water and oxygen consumption using [11C]acetate positron emission tomography, and the efficiency of myocardial work was calculated. Histological examinations were conducted to detect MI, hypertrophy, and fibrosis. Animals in the HF group had a large anterior MI scar. CT showed larger LV diastolic volume and lower ejection fraction in HF pigs than in controls. Perfusion and oxygen consumption in the remote non-infarcted myocardium were preserved in HF pigs as compared to controls. Global LV work and efficiency were significantly lower in HF than control pigs and was associated with increased wall stress. Histology showed myocyte hypertrophy but not increased interstitial fibrosis in the remote segments in HF pigs.ConclusionsThe chronic post-infarction model of HF is suitable for studies aimed to evaluate LV remodeling and changes in oxidative metabolism and can be useful for testing new therapies for HF.

[18F]FDG Accumulation in Early Coronary Atherosclerotic Lesions in Pigs

Objective Inflammation is an important contributor to atherosclerosis progression. A glucose analogue 18F-fluorodeoxyglucose ([18F]FDG) has been used to detect atherosclerotic inflammation. However, it is not known to what extent [18F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [18F]FDG to various stages of coronary plaques in a pig model. Methods First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days) in farm pigs (n = 10). After 6 months on high-fat diet, pigs underwent dual-gated cardiac PET/CT to measure [18F]FDG uptake in coronary arteries. Coronary segments (n = 33) were harvested for ex vivo measurement of radioactivity and autoradiography (ARG). Results Intimal thickening was observed in 16 segments and atheroma type plaques in 10 segments. Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher [18F]FDG accumulation in the intimal thickening and 4.1±2.3 times higher in the atheromas (P = 0.004 and P = 0.003, respectively). Ex vivo mean vessel-to-blood ratio was higher in segments with atheroma than those without atherosclerosis (2.6±1.2 vs. 1.3±0.7, P = 0.04). In vivo PET imaging showed the highest target-to-background ratio (TBR) of 2.7. However, maximum TBR was not significantly different in segments without atherosclerosis (1.1±0.5) and either intimal thickening (1.2±0.4, P = 1.0) or atheroma (1.6±0.6, P = 0.4). Conclusions We found increased uptake of [18F]FDG in coronary atherosclerotic lesions in a pig model. However, uptake in these early stage lesions was not detectable with in vivo PET imaging. Further studies are needed to clarify whether visible [18F]FDG uptake in coronary arteries represents more advanced, highly inflamed plaques.

Effect of levosimendan therapy on myocardial infarct size and left ventricular function after acute coronary occlusion

Background Levosimendan is an inotropic agent with cardioprotective and vasodilating properties used for the management of acutely decompensated heart failure. We studied the effects of levosimendan treatment on the size of myocardial infarction (MI) and left ventricular (LV) function in experimental pig model of post MI heart failure. Methods After occlusion of the left anterior descending (LAD) coronary artery, animals received levosimendan 5 mg/kg/day orally for 8 weeks (n=7) or no treatment (n=18). One week after stopping treatment, transthoracic echocardiography, CT scan and positron emission tomography were performed to evaluate myocardial function, perfusion and oxidative metabolism. Histology was used to confirm the size of MI and features of LV remodelling. Results The size of MI was significantly smaller in the levosimendan group than in the controls (12±13% vs 27±15% of the LV, p=0.03). End-diastolic volume (EDV) and end-systolic volume (ESV) were smaller in the levosimendan than in the control group (EDV 161±29 mL vs 245±84 mL, p=0.06; ESV 81±18 mL vs 149±67 mL, p=0.03), whereas ejection fraction tended to be higher in the levosimendan group (50±6% vs 41±8%, p=0.06). Conclusions Eight weeks of levosimendan therapy after recent LAD occlusion decreases the size of MI and leads to better preservation of LV function as well as reduced LV remodelling.

Reversibility of myocardial metabolism and remodelling in morbidly obese patients 6 months after bariatric surgery

To study myocardial substrate uptake, structure and function, before and after bariatric surgery, to clarify the interaction between myocardial metabolism and cardiac remodelling in morbid obesity.