Analysis of chemical exchange in iridium N-heterocyclic carbene complexes using heteronuclear parahydrogen-enhanced NMR.

The signal amplification by reversible exchange process (SABRE) enhances NMR signals by unlocking hidden polarization in parahydrogen through interactions with to-be-hyperpolarized substrate molecules when both are transiently bound to an Ir-based organometallic catalyst. Recent efforts focus on optimizing polarization transfer from parahydrogen-derived hydride ligands to the substrate in SABRE. However, this requires quantitative information on ligand exchange rates, which common NMR techniques struggle to provide.

Black-blood MRI at 7T using 2D RARE MRI: In vitro testing and in vivo demonstration.

Vessel walls play a crucial role in many inflammatory vascular diseases. Vessel wall imaging (VWI) using mangnetic resonance imaging (MRI) is one of the few methods by which vessel walls and inflammation can be visualized noninvasively, in vivo, and without ionizing radiation. VWI is based on black-blood (BB) MRI, where the signal from flowing blood is suppressed and contrast agent accumulation in the (inflamed) vessel wall is highlighted.

Through-bond and through-space radiofrequency amplification by stimulated emission of radiation.

Radio Amplification by Stimulated Emission of Radiation (RASER) is a phenomenon observed during nuclear magnetic resonance (NMR) experiments with strongly negatively polarized systems. This phenomenon may be utilized for the production of very narrow NMR lines, background-free NMR spectroscopy, and excitation-free sensing of chemical transformations. Recently, novel methods of producing RASER by ParaHydrogen-Induced Polarization (PHIP) were introduced.

Yeast Solutions and Hyperpolarization Enable Real-Time Observation of Metabolized Substrates Even at Natural Abundance.

Metabolic changes in an organism often occur much earlier than macroscopic manifestations of disease, such as invasive tumors. Therefore, noninvasive tools to monitor metabolism are fundamental as they provide insights into in vivo biochemistry. NMR represents one of the gold standards for such insights by observing metabolites.

Nuclear spin polarization of lactic acid via exchange of parahydrogen-polarized protons.

Hyperpolarization has become a powerful tool to enhance the sensitivity of magnetic resonance. A universal tool to hyperpolarize small molecules in solution, however, has not yet emerged. Transferring hyperpolarized, labile protons between molecules is a promising approach towards this end.

Modeling Ligand Exchange Kinetics in Iridium Complexes Catalyzing SABRE Nuclear Spin Hyperpolarization.

Large signal enhancements can be obtained for NMR analytes using the process of nuclear spin hyperpolarization. Organometallic complexes that bind parahydrogen can themselves become hyperpolarized. Moreover, if parahydrogen and a to-be-hyperpolarized analyte undergo chemical exchange with the organometallic complex it is possible to catalytically sensitize the detection of the analyte via hyperpolarization transfer through spin-spin coupling in this organometallic complex.

Temporal and regional expression changes and co-staining patterns of metabolic and stemness-related markers during glioblastoma progression.

Glioblastomas (GBMs) are characterized by high heterogeneity, involving diverse cell types, including those with stem-like features contributing to GBM's malignancy. Moreover, metabolic alterations promote growth and therapeutic resistance of GBM. Depending on the metabolic state, antimetabolic treatments could be an effective strategy.

Incidence of microvascular dysfunction is increased in hyperlipidemic mice, reducing cerebral blood flow and impairing remote memory.

Introduction: The development of cognitive dysfunction is not necessarily associated with diet-induced obesity. We hypothesized that cognitive dysfunction might require additional vascular damage, for example, in atherosclerotic mice.

Methods: We induced atherosclerosis in male C57BL/6N mice by injecting AAV-PCSK9 (2x10 VG) and feeding them a cholesterol-rich Western diet.

C MRI of hyperpolarized pyruvate at 120 µT.

Nuclear spin hyperpolarization increases the sensitivity of magnetic resonance dramatically, enabling many new applications, including real-time metabolic imaging. Parahydrogen-based signal amplification by reversible exchange (SABRE) was employed to hyperpolarize [1-C]pyruvate and demonstrate C imaging in situ at 120 µT, about twice Earth's magnetic field, with two different signal amplification by reversible exchange variants: SABRE in shield enables alignment transfer to heteronuclei (SABRE-SHEATH), where hyperpolarization is transferred from parahydrogen to [1-C]pyruvate at a magnetic field below 1 µT, and low-irradiation generates high tesla (LIGHT-SABRE), where hyperpolarization was prepared at 120 µT, avoiding magnetic field cycling. The 3-dimensional images of a phantom were obtained using a superconducting quantum interference device (SQUID) based magnetic field detector with submillimeter resolution.

Coupling Constants of <1 Hz Enable C Hyperpolarization of Pyruvate via Reversible Exchange of Parahydrogen.

Observing pyruvate metabolism has become a focal point of molecular magnetic resonance imaging. Signal amplification by reversible exchange (SABRE) has recently emerged as a versatile hyperpolarization technique. Tuning of the spin order transfer (SOT) in SABRE is challenging as the small H-C couplings, in the C-pyruvate case, result in SOT being not readily discernible.

Evolution of in a mouse model of inflammatory bowel disease leads to a disease-specific bacterial genotype and trade-offs with clinical relevance.

Inflammatory bowel disease (IBD) is a persistent inflammatory condition that affects the gastrointestinal tract and presents significant challenges in its management and treatment. Despite the knowledge that within-host bacterial evolution occurs in the intestine, the disease has rarely been studied from an evolutionary perspective. In this study, we aimed to investigate the evolution of resident bacteria during intestinal inflammation and whether- and how disease-related bacterial genetic changes may present trade-offs with potential therapeutic importance.

Exceptionally Mild and High-Yielding Synthesis of Vinyl Esters of Alpha-Ketocarboxylic Acids, Including Vinyl Pyruvate, for Parahydrogen-Enhanced Metabolic Spectroscopy and Imaging.

Metabolic changes often occur long before pathologies manifest and treatment becomes challenging. As key elements of energy metabolism, α-ketocarboxylic acids (α-KCA) are particularly interesting, e.g.

Current Methods for Hyperpolarized [1-C]pyruvate MRI Human Studies.

MRI with hyperpolarized (HP) C agents, also known as HP C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of hyperpolarized agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with [1-C]pyruvate - by far the most commonly used agent, which sits at a key metabolic junction in glycolysis.

Nitrogen-15 dynamic nuclear polarization of nicotinamide derivatives in biocompatible solutions.

Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance imaging by more than 10,000 times, enabling in vivo metabolic imaging to be performed noninvasively in real time. Here, we are developing a group of dDNP polarized tracers based on nicotinamide (NAM). We synthesized 1-N-NAM and 1-N nicotinic acid and hyperpolarized them with dDNP, reaching (13.

Spying on parahydrogen-induced polarization transfer using a half-tesla benchtop MRI and hyperpolarized imaging enabled by automation.

Nuclear spin hyperpolarization is a quantum effect that enhances the nuclear magnetic resonance signal by several orders of magnitude and has enabled real-time metabolic imaging in humans. However, the translation of hyperpolarization technology into routine use in laboratories and medical centers is hampered by the lack of portable, cost-effective polarizers that are not commercially available. Here, we present a portable, automated polarizer based on parahydrogen-induced hyperpolarization (PHIP) at an intermediate magnetic field of 0.

Resveratrol Mitigates Metabolism in Human Microglia Cells.

The recognition of the role of microglia cells in neurodegenerative diseases has steadily increased over the past few years. There is growing evidence that the uncontrolled and persisting activation of microglial cells is involved in the progression of diseases such as Alzheimer's or Parkinson's disease. The inflammatory activation of microglia cells is often accompanied by a switch in metabolism to higher glucose consumption and aerobic glycolysis.

Establishment of a Rodent Glioblastoma Partial Resection Model for Chemotherapy by Local Drug Carriers-Sharing Experience.

Local drug delivery systems (LDDS) represent a promising therapy strategy concerning the most common and malignant primary brain tumor glioblastoma (GBM). Nevertheless, to date, only a few systems have been clinically applied, and their success is very limited. Still, numerous new LDDS approaches are currently being developed.

LIGHT-SABRE Hyperpolarizes 1-C-Pyruvate Continuously without Magnetic Field Cycling.

Nuclear spin hyperpolarization enables real-time observation of metabolism and intermolecular interactions . 1-C-pyruvate is the leading hyperpolarized tracer currently under evaluation in several clinical trials as a promising molecular imaging agent. Still, the quest for a simple, fast, and efficient hyperpolarization technique is ongoing.

Modern Manufacturing Enables Magnetic Field Cycling Experiments and Parahydrogen-Induced Hyperpolarization with a Benchtop NMR.

Benchtop NMR (btNMR) spectrometers are revolutionizing the way we use NMR and lowering the cost drastically. Magnetic field cycling (MFC) experiments with precise timing and control over the magnetic field, however, were hitherto not available on btNMRs, although some systems exist for high-field, high-resolution NMR spectrometers. Still, the need and potential for btNMR MFC is great─e.

Nanomaterials for hyperpolarized nuclear magnetic resonance and magnetic resonance imaging.

Nanomaterials play an important role in the development and application of hyperpolarized materials for magnetic resonance imaging (MRI). In this context they can not only act as hyperpolarized materials which are directly imaged but also play a role as carriers for hyperpolarized gases and catalysts for para-hydrogen induced polarization (PHIP) to generate hyperpolarized substrates for metabolic imaging. Those three application possibilities are discussed, focusing on carbon-based materials for the directly imaged particles.

Quasi-continuous production of highly hyperpolarized carbon-13 contrast agents every 15 seconds within an MRI system.

Hyperpolarized contrast agents (HyCAs) have enabled unprecedented magnetic resonance imaging (MRI) of metabolism and pH in vivo. Producing HyCAs with currently available methods, however, is typically time and cost intensive. Here, we show virtually-continuous production of HyCAs using parahydrogen-induced polarization (PHIP), without stand-alone polarizer, but using a system integrated in an MRI instead.