Hyperpolarized [1-C]pyruvate cardiovascular magnetic resonance imaging identifies metabolic phenotypes in patients with heart failure.

Background: Hyperpolarized [1-C]pyruvate cardiovascular magnetic resonance imaging (HP [1-C]pyruvate CMR) visualizes key steps in myocardial metabolism. The present study aimed to examine patients with heart failure (HF) using HP [1-C]pyruvate CMR.

Methods: A cross-sectional study of patients with HF and healthy controls using HP [1-C]pyruvate CMR.

Assessment of focal renal ischemia-reperfusion injury in a porcine model using hyperpolarized [1- C]pyruvate MRI.

Purpose: Ischemic injury in the kidney is a common pathophysiological event associated with both acute kidney injury and chronic kidney disease; however, regional ischemia-reperfusion as seen in thromboembolic renal disease is often undetectable and thus subclinical. Here, we assessed the metabolic alterations following subclinical focal ischemia-reperfusion injury with hyperpolarized [1- C]pyruvate MRI in a porcine model.

Methods: Five pigs were subjected to 60 min of focal kidney ischemia.

Hyperpolarized [1- C]pyruvate combined with the hyperinsulinaemic euglycaemic and hypoglycaemic clamp technique in skeletal muscle in a large animal model.

New Findings: What is the central question of this study? Is it possible to combine the hyperpolarized magnetic resonance technique and the hyperinsulinaemic clamp method in order to evaluate skeletal muscle metabolism in a large animal model? What is the main finding and its importance? The logistical set-up is possible, and we found substantial increments in glucose infusion rates representing skeletal muscle glucose uptake but no differences in ratios of [1- C]lactate to [1- C]pyruvate, [1- C]alanine to [1- C]pyruvate, and C-bicarbonate to [1- C]pyruvate, implying that the hyperpolarization technique might not be optimal for detecting effects of insulin in skeletal muscle of anaesthetized animals, which is of significance for future studies.

Abstract: In skeletal muscle, glucose metabolism is tightly regulated by the reciprocal relationship between insulin and adrenaline, with pyruvate being at the intersection of both pathways. Hyperpolarized magnetic resonance (hMR) is a new approach to gain insights into these pathways, and human trials involving hMR and skeletal muscle metabolism are imminent.

Remodeling after myocardial infarction and effects of heart failure treatment investigated by hyperpolarized [1- C]pyruvate magnetic resonance spectroscopy.

Purpose: Hyperpolarized [1- C]pyruvate MRS can measure cardiac metabolism in vivo. We investigated whether [1- C]pyruvate MRS could predict left ventricular remodeling following myocardial infarction (MI), long-term left ventricular effects of heart failure medication, and could identify responders to treatment.

Methods: Thirty-five rats were scanned with hyperpolarized [1- C]pyruvate MRS 3 days after MI or sham surgery.

The hemodynamic and metabolic effects of spironolactone treatment in acute kidney injury assessed by hyperpolarized MRI.

Renal ischemia-reperfusion injury (IRI) is one of the most common types of acute kidney injury. Spironolactone has shown promising kidney protective effects in renal IRI in rats. We investigated the hemodynamic and metabolic effects of spironolactone (100 mg/kg) administered immediately after 40 min unilateral kidney ischemia in rats.

The impact of the glucagon-like peptide-1 receptor agonist liraglutide on natriuretic peptides in heart failure patients with reduced ejection fraction with and without type 2 diabetes.

Aim: To assess the effect of liraglutide, a glucagon-like peptide-1 receptor agonist, on urinary sodium excretion as well as on circulating adrenomedullin and copeptin levels in patients with type 2 diabetes (T2D).

Materials And Methods: In the LIVE study, patients (n = 241) with left ventricular ejection fraction ≤45% were randomized to liraglutide 1.8 mg daily or placebo for 24 weeks, and 30% had a concomitant diagnosis of T2D.

Visualization of sodium dynamics in the kidney by magnetic resonance imaging in a multi-site study.

Sodium magnetic resonance imaging (MRI) is a powerful, non-invasive technique to assess sodium distribution within the kidney. Here we undertook pre-clinical and clinical studies to quantify the corticomedullary sodium gradient in healthy individuals and in a porcine model of diuresis. The results demonstrated that sodium MRI could detect spatial differences in sodium biodistribution across the kidney.

Heart rate increases in liraglutide treated chronic heart failure patients: association with clinical parameters and adverse events.

. Liraglutide, a glucagon-like peptide-1 agonist, is used for treatment of type 2 diabetes and has beneficial cardiovascular properties. However, treatment increases heart rate (HR) and possibly the risk of cardiovascular events in chronic heart failure (CHF) patients.

Myocardial strain assessed by feature tracking cardiac magnetic resonance in patients with a variety of cardiovascular diseases - A comparison with echocardiography.

Myocardial deformation assessed by speckle tracking echocardiography (STE) is increasingly used for diagnosis, monitoring and prognosis in patients with clinical and pre-clinical cardiovascular diseases. Feature tracking cardiac magnetic resonance (FT-CMR) also allows myocardial deformation analysis. To clarify whether the two modalities can be used interchangeably, we compared myocardial deformation analysis by FT-CMR with STE in patients with a variety of cardiovascular diseases and healthy subjects.

Hyperpolarized [1- C] pyruvate as a possible diagnostic tool in liver disease.

Introduction of hyperpolarized magnetic resonance in preclinical studies and lately translation to patients provides new detailed in vivo information of metabolic flux in organs. Hyperpolarized magnetic resonance based on C enriched pyruvate is performed without ionizing radiation and allows quantification of the pyruvate conversion products: alanine, lactate and bicarbonate in real time. Thus, this methodology has a promising potential for in vivo monitoring of energetic alterations in hepatic diseases.

Hyperpolarized [1- C]pyruvate MRI can image the metabolic shift in cardiac metabolism between the fasted and fed state in a porcine model.

Purpose: Owing to its noninvasive nature, hyperpolarized MRI may improve delineation of myocardial metabolic derangement in heart disease. However, consistency may depend on the changeable nature of cardiac metabolism in relation to whole-body metabolic state. This study investigates the impact of feeding status on cardiac hyperpolarized MRI in a large animal model resembling human physiology.

C Pyruvate Transport Across the Blood-Brain Barrier in Preclinical Hyperpolarised MRI.

Hyperpolarised MRI with Dynamic Nuclear Polarisation overcomes the fundamental thermodynamic limitations of conventional magnetic resonance, and is translating to human studies with several early-phase clinical trials in progress including early reports that demonstrate the utility of the technique to observe lactate production in human brain cancer patients. Owing to the fundamental coupling of metabolism and tissue function, metabolic neuroimaging with hyperpolarised [1-C]pyruvate has the potential to be revolutionary in numerous neurological disorders (e.g.

Acute hypertensive stress imaged by cardiac hyperpolarized [1- C]pyruvate magnetic resonance.

Purpose: Deranged metabolism is now recognized as a key causal factor in a variety of heart diseases, and is being studied extensively. However, invasive methods may alter metabolism, and conventional imaging techniques measure tracer uptake but not downstream metabolism. These challenges may be overcome by hyperpolarized MR, a noninvasive technique currently crossing the threshold into human trials.

Imaging porcine cardiac substrate selection modulations by glucose, insulin and potassium intervention: A hyperpolarized [1- C]pyruvate study.

Cardiac metabolism has received considerable attention in terms of both diagnostics and prognostics, as well as a novel target for treatment. As human trials involving hyperpolarized magnetic resonance in the heart are imminent, we sought to evaluate the general feasibility of detection of an imposed shift in metabolic substrate utilization during metabolic modulation with glucose-insulin-potassium (GIK) infusion, and thus the limitations associated with this strategy, in a large animal model resembling human physiology. Four [1- C]pyruvate injections did not alter the blood pressure or ejection fraction over 180 min.

Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial.

Aims: To determine the effect of the glucagon-like peptide-1 analogue liraglutide on left ventricular function in chronic heart failure patients with and without type 2 diabetes.

Methods And Results: LIVE was an investigator-initiated, randomised, double-blinded, placebo-controlled multicentre trial. Patients (n = 241) with reduced left ventricular ejection fraction (LVEF ≤45%) were recruited (February 2012 to August 2015).

Renal MR angiography and perfusion in the pig using hyperpolarized water.

Purpose: To study hyperpolarized water as an angiography and perfusion tracer in a large animal model.

Methods: Protons dissolved in deuterium oxide (D O) were hyperpolarized in a SPINlab dissolution dynamic nuclear polarization (dDNP) polarizer and subsequently investigated in vivo in a pig model at 3 Tesla (T). Approximately 15 mL of hyperpolarized water was injected in the renal artery by hand over 4-5 s.