Multinuclear MRI Can Depict Metabolic and Energetic Changes in Mild Traumatic Brain Injury.

Mild traumatic brain injuries (TBIs) are frequent in the European population. The pathophysiological changes after TBI include metabolic changes, but these are not observable using current clinical tools. We aimed to evaluate multinuclear MRI as a mean of assessing these changes.

Differentiating leukemia subtypes based on metabolic signatures using hyperpolarized C NMR.

Leukemia is a group of blood cancers that are classified in four major classes. Within these four classes, many different subtypes exists with similar origin, genetic mutations, and level of maturity, which can make them difficult to distinguish. Despite their similarities, they might respond differently to treatment, and therefore distinguishing between them is of crucial importance.

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.

Metabolic MRI With Hyperpolarized 13 C-Pyruvate for Early Detection of Fibrogenic Kidney Metabolism.

Objectives: Fibrosis is the final common pathway for chronic kidney disease and the best predictor for disease progression. Besides invasive biopsies, biomarkers for its detection are lacking. To address this, we used hyperpolarized 13 C-pyruvate MRI to detect the metabolic changes associated with fibrogenic activity of myofibroblasts.

A continuous flow bioreactor system for high-throughput hyperpolarized metabolic flux analysis.

Hyperpolarized carbon-13 labeled compounds are increasingly being used in medical MR imaging (MRI) and MR imaging (MRI) and spectroscopy (MRS) research, due to its ability to monitor tissue and cell metabolism in real-time. Although radiological biomarkers are increasingly being considered as clinical indicators, biopsies are still considered the gold standard for a large variety of indications. Bioreactor systems can play an important role in biopsy examinations because of their ability to provide a physiochemical environment that is conducive for therapeutic response monitoring ex vivo.

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.

Gadolinium-enhanced MRI visualizing backflow at increasing intra-renal pressure in a porcine model.

Introduction: Intrarenal backflow (IRB) is known to occur at increased intrarenal pressure (IRP). Irrigation during ureteroscopy increases IRP. Complications such as sepsis is more frequent after prolonged high-pressure ureteroscopy.

Fibrosis imaging with multiparametric proton and sodium MRI in pig injury models.

Chronic kidney disease (CKD) is common and has huge implications for health and mortality. It is aggravated by intrarenal fibrosis, but the assessment of fibrosis is limited to kidney biopsies, which carry a risk of complications and sampling errors. This calls for a noninvasive modality for diagnosing and staging intrarenal fibrosis.

Imaging Neurodegenerative Metabolism in Amyotrophic Lateral Sclerosis with Hyperpolarized [1-C]pyruvate MRI.

The cause of amyotrophic lateral sclerosis (ALS) is still unknown, and consequently, early diagnosis of the disease can be difficult and effective treatment is lacking. The pathology of ALS seems to involve specific disturbances in carbohydrate metabolism, which may be diagnostic and therapeutic targets. Magnetic resonance imaging (MRI) with hyperpolarized [1-C]pyruvate is emerging as a technology for the evaluation of pathway-specific changes in the brain's metabolism.

Detection of increased pyruvate dehydrogenase flux in the human heart during adenosine stress test using hyperpolarized [1-C]pyruvate cardiovascular magnetic resonance imaging.

Background: Hyperpolarized (HP) [1-C]pyruvate cardiovascular magnetic resonance (CMR) imaging can visualize the uptake and intracellular conversion of [1-C]pyruvate to either [1-C]lactate or C-bicarbonate depending on the prevailing metabolic state. The aim of the present study was to combine an adenosine stress test with HP [1-C]pyruvate CMR to detect cardiac metabolism in the healthy human heart at rest and during moderate stress.

Methods: A prospective descriptive study was performed between October 2019 and August 2020.

Lactate saturation limits bicarbonate detection in hyperpolarized C-pyruvate MRI of the brain.

Purpose: To investigate the potential effects of [1- C]lactate RF saturation pulses on [ C]bicarbonate detection in hyperpolarized [1- C]pyruvate MRI of the brain.

Methods: Thirteen healthy rats underwent MRI with hyperpolarized [1- C]pyruvate of either the brain (n = 8) or the kidneys, heart, and liver (n = 5). Dynamic, metabolite-selective imaging was used in a cross-over experiment in which [1- C]lactate was excited with either 0° or 90° flip angles.

Concentration-dependent effects of dichloroacetate in type 2 diabetic hearts assessed by hyperpolarized [1- C]-pyruvate magnetic resonance imaging.

Personalized medicine or individualized therapy promises a paradigm shift in healthcare. This is particularly true in complex and multifactorial diseases such as diabetes and the multitude of related pathophysiological complications. Diabetic cardiomyopathy represents an emerging condition that could be effectively treated if better diagnostic and, in particular, better therapeutic monitoring tools were available.

Hyperpolarized pyruvate to measure the influence of PKM2 activation on glucose metabolism in the healthy kidney.

The purpose of the current study was to investigate if hyperpolarized [1- C]pyruvate can inform us on the metabolic consequences for the kidney glucose metabolism upon treatment with the pyruvate kinase M2 (PKM2) activator TEPP-46, which has shown promise as a novel therapeutic target for diabetic nephropathy. A healthy male Wistar rat model was employed to study the conversion of [1- C]pyruvate to [1- C]lactate in the kidney 2 and 4 h after treatment with TEPP-46. All rats were scanned with hyperpolarized [1- C]pyruvate kidney MR and vital parameters and blood samples were taken after scanning.

Metabolic MRI with hyperpolarized [1-C]pyruvate separates benign oligemia from infarcting penumbra in porcine stroke.

Acute ischemic stroke patients benefit from reperfusion in a short time-window after debut. Later treatment may be indicated if viable brain tissue is demonstrated and this outweighs the inherent risks of late reperfusion. Magnetic resonance imaging (MRI) with hyperpolarized [1-C]pyruvate is an emerging technology that directly images metabolism.

Cardiac pH-Imaging With Hyperpolarized MRI.

Regardless of the importance of acid-base disturbances in cardiac disease, there are currently no methods for clinical detection of pH in the heart. Several magnetic resonance imaging techniques hold translational promise and may enable mapping of pH. We provide a brief overview of these emerging techniques.

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.

Hyperpolarized [1,4-C]fumarate imaging detects microvascular complications and hypoxia mediated cell death in diabetic nephropathy.

Today, there is a general lack of prognostic biomarkers for development of renal disease and in particular diabetic nephropathy. Increased glycolytic activity, lactate accumulation and altered mitochondrial oxygen utilization are hallmarks of diabetic kidney disease. Fumarate hydratase activity has been linked to mitochondrial dysfunction as well as activation of the hypoxia inducible factor, induction of apoptosis and necrosis.

Metabolic reprogramming associated with progression of renal ischemia reperfusion injury assessed with hyperpolarized [1-C]pyruvate.

Acute kidney injury is a major clinical challenge affecting as many as 1 percent of all hospitalized patients. Currently it is not possible to accurately stratify and predict the outcome of the individual patient. Increasing evidence supports metabolic reprogramming as a potential target for new biomarkers.

Hyperpolarized [1- C] alanine production: A novel imaging biomarker of renal fibrosis.

Purpose: Renal tubulointerstitial fibrosis is strongly linked to the progressive decline of renal function seen in chronic kidney disease. State-of-the-art noninvasive diagnostic modalities are currently unable to detect the earliest changes associated with the onset of fibrosis. This study was undertaken to evaluate the potential for detecting the earliest alterations in fibrogenesis using a biofluid-based method and metabolic hyperpolarized [1- C]pyruvate imaging.

Ex Vivo Human Placenta Perfusion, Metabolic and Functional Imaging for Obstetric Research-A Feasibility Study.

Placenta metabolism is closely linked to pregnancy outcome, and few modalities are currently available for studying the human placenta. Here, we aimed to investigate a novel ex vivo human placenta perfusion system for metabolic imaging using hyperpolarized [1-C]pyruvate. The metabolic effects of 3 different human placentas were investigated using functional and metabolic magnetic resonance imaging.

High Intrarenal Lactate Production Inhibits the Renal Pseudohypoxic Response to Acutely Induced Hypoxia in Diabetes.

Intrarenal hypoxia develops within a few days after the onset of insulinopenic diabetes in an experimental animal model (ie, a model of type-1 diabetes). Although diabetes-induced hypoxia results in increased renal lactate formation, mitochondrial function is well maintained, a condition commonly referred to as pseudohypoxia. However, the metabolic effects of significantly elevated lactate levels remain unclear.

Metabolic consequences of lactate dehydrogenase inhibition by oxamate in hyperglycemic proximal tubular cells.

Diabetic kidney disease (DKD) is associated with altered metabolic patterns, leading to increased lactate production even in the presence of sufficient oxygen supply. Studies have shown hyperglycemia to be an important factor in determining development of DKD. Here we explore the metabolic consequences of lactate dehydrogenase (LDH) inhibition exerted by the LDH inhibitor, oxamate, in the isolated rat renal proximal tubular cells (NRK-52E) under hyperglycemic conditions.

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.