Monitoring response to a clinically relevant IDH inhibitor in glioma-Hyperpolarized C magnetic resonance spectroscopy approaches.

Background: Mutant isocitrate dehydrogenase (IDHmut) catalyzes 2-hydroxyglutarate (2HG) production and is considered a therapeutic target for IDHmut tumors. However, response is mostly associated with inhibition of tumor growth. Response assessment via anatomic imaging is therefore challenging.

Molecular Diet Analysis of Asian Clams for Supplementary Biodiversity Monitoring: A Case Study of Nakdong River Estuary.

Environmental DNA (eDNA) extracted from the gut contents of filter feeders can be used to identify biodiversity in aquatic ecosystems. In this study, we used eDNA from the gut contents of the Asian clam to examine biodiversity within estuarine ecosystem. Field sampling was conducted at three points in the Nakdong River Estuary, which is characterised by closed estuarine features resulting from the presence of an estuarine barrage.

Hyperpolarized δ-[1- C]gluconolactone imaging visualizes response to TERT or GABPB1 targeting therapy for glioblastoma.

TERT promoter mutations are a hallmark of glioblastoma (GBM). Accordingly, TERT and GABPB1, a subunit of the upstream mutant TERT promoter transcription factor GABP, are being considered as promising therapeutic targets in GBM. We recently reported that the expression of TERT or GABP1 modulates flux via the pentose phosphate pathway (PPP).

A C/P surface coil to visualize metabolism and energetics in the rodent brain at 3 Tesla.

Purpose: We constructed a C/P surface coil at 3 T for studying cancer metabolism and bioenergetics. In a single scan session, hyperpolarized C-pyruvate MRS and P MRS was carried out for a healthy rat brain.

Methods: All experiments were carried out at 3 Tesla.

Deuterium magnetic resonance spectroscopy enables noninvasive metabolic imaging of tumor burden and response to therapy in low-grade gliomas.

Background: The alternative lengthening of telomeres (ALT) pathway is essential for tumor proliferation in astrocytomas. The goal of this study was to identify metabolic alterations linked to the ALT pathway that can be exploited for noninvasive magnetic resonance spectroscopy (MRS)-based imaging of astrocytomas in vivo.

Methods: Genetic and pharmacological methods were used to dissect the association between the ALT pathway and glucose metabolism in genetically engineered and patient-derived astrocytoma models.

Acquisition and quantification pipeline for in vivo hyperpolarized C MR spectroscopy.

Purpose: The goal of this study was to combine a specialized acquisition method with a new quantification pipeline to accurately and efficiently probe the metabolism of hyperpolarized C-labeled compounds in vivo. In this study, we tested our approach on [2- C]pyruvate and [1- C]α-ketoglutarate data in rat orthotopic brain tumor models at 3T.

Methods: We used a multiband metabolite-specific radiofrequency (RF) excitation in combination with a variable flip angle scheme to minimize substrate polarization loss and measure fast metabolic processes.

Early Noninvasive Metabolic Biomarkers of Mutant IDH Inhibition in Glioma.

Approximately 80% of low-grade glioma (LGGs) harbor mutant isocitrate dehydrogenase 1/2 (IDH1/2) driver mutations leading to accumulation of the oncometabolite 2-hydroxyglutarate (2-HG). Thus, inhibition of mutant IDH is considered a potential therapeutic target. Several mutant IDH inhibitors are currently in clinical trials, including AG-881 and BAY-1436032.

Glutamate Is a Noninvasive Metabolic Biomarker of IDH1-Mutant Glioma Response to Temozolomide Treatment.

Although lower grade gliomas are driven by mutations in the isocitrate dehydrogenase 1 (IDH1) gene and are less aggressive than primary glioblastoma, they nonetheless generally recur. IDH1-mutant patients are increasingly being treated with temozolomide, but early detection of response remains a challenge and there is a need for complementary imaging methods to assess response to therapy prior to tumor shrinkage. The goal of this study was to determine the value of magnetic resonance spectroscopy (MRS)-based metabolic changes for detection of response to temozolomide in both genetically engineered and patient-derived mutant IDH1 models.

A comparison of sLASER and MEGA-sLASER using simultaneous interleaved acquisition for measuring GABA in the human brain at 7T.

γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter, is challenging to measure using proton spectroscopy due to its relatively low concentration, J-coupling and overlapping signals from other metabolites. Currently, the prevalent methods for detecting GABA at ultrahigh field strengths (≥ 7 T) are GABA-editing and model fitting of non-editing single voxel spectra. These two acquisition approaches have their own advantages: the GABA editing approach directly measures the GABA resonance at 3 ppm, whereas the fitting approach on the non-editing spectrum allows the detection of multiple metabolites, and has an SNR advantage over longer echo time (TE) acquisitions.

Higher GABA concentration in the medial prefrontal cortex of Type 2 diabetes patients is associated with episodic memory dysfunction.

Type 2 diabetes (T2D) is associated with an accelerated episodic memory decline, but the underlying pathophysiological mechanisms are not well understood. Hallmarks of T2D comprise impairment of insulin secretion and insulin sensitivity. Insulin signaling modulates cerebral neurotransmitter activity, including the excitatory glutamate and inhibitory gamma-aminobutyric acid (GABA) systems.

Effect of linewidth on estimation of metabolic concentration when using water lineshape spectral model fitting for single voxel proton spectroscopy at 7 T.

Good B field homogeneity is considered an essential requirement to obtain high-quality MRS data. Many commonly used spectral fitting methods assume that all metabolite signals have Lorentzian or Gaussian shapes. However, B inhomogeneity can both broaden the linewidth and modify the lineshape.

Implications of the magnetic susceptibility difference between grey and white matter for single-voxel proton spectroscopy at 7 T.

Magnetic susceptibility differences between grey matter (GM) and white matter (WM) can potentially affect lineshapes and chemical shifts in single-voxel spectroscopy. This study aimed to investigate the consequences and potential utility of these effects. Spectroscopy voxels were segmented into GM, WM, and cerebrospinal fluid based on T-weighted images.

MASE-sLASER, a short-TE, matched chemical shift displacement error sequence for single-voxel spectroscopy at ultrahigh field.

B inhomogeneity and chemical shift displacement error (CSDE) increase with the main magnetic field strength and are therefore deleterious for magnetic resonance spectroscopy (MRS) at ultrahigh field. A solution is to use adiabatic pulses which operate over a broad range of B and thus are insensitive to B inhomogeneity. Moreover, adiabatic pulses usually have a relatively higher bandwidth, which makes CSDE low to negligible.

Myocardial Extracellular Volume Fraction and Change in Hematocrit Level: MR Evaluation by Using T1 Mapping in an Experimental Model of Anemia.

Purpose To evaluate the effect of changes in hematocrit level on myocardial extracellular volume (ECV) fraction, as quantified with cardiac magnetic resonance (MR) imaging in an animal model. Materials and Methods Thirteen adult male Sprague-Dawley rats underwent cardiac MR imaging before and after induction of anemia. MR imaging procedures, including unenhanced and contrast material-enhanced T1 mapping, were performed by using a saturation recovery Look-Locker sequence with a 9.

The increase in medial prefrontal glutamate/glutamine concentration during memory encoding is associated with better memory performance and stronger functional connectivity in the human medial prefrontal-thalamus-hippocampus network.

The classical model of the declarative memory system describes the hippocampus and its interactions with representational brain areas in posterior neocortex as being essential for the formation of long-term episodic memories. However, new evidence suggests an extension of this classical model by assigning the medial prefrontal cortex (mPFC) a specific, yet not fully defined role in episodic memory. In this study, we utilized 1H magnetic resonance spectroscopy (MRS) and psychophysiological interaction (PPI) analysis to lend further support for the idea of a mnemonic role of the mPFC in humans.

Myocardial Characterization Using Dual-Energy CT in Doxorubicin-Induced DCM: Comparison With CMR T1-Mapping and Histology in a Rabbit Model.

Objectives: This study sought to evaluate whether patterns of myocardial change in doxorubicin-induced dilated cardiomyopathy determined using dual-energy computed tomography (CT) were similar to characterization by extracellular volume fraction (ECV) using cardiac magnetic resonance (CMR) T1-mapping and collagen volume fraction (CVF) measured using histology.

Background: Anthracycline chemoagents are effective against a wide range of malignant conditions. However, cardiotoxicity is a well-known adverse effect of these drugs.

Therapeutic dosage assessment based on population pharmacokinetics of a novel single-dose transdermal donepezil patch in healthy volunteers.

Purpose: We performed population pharmacokinetic (PK) analysis of a novel transdermal donepezil patch in healthy subjects who participated in a phase I trial. We also studied the optimal dosage regimen with repeated patch application for achieving a therapeutic range using a PK simulation model.

Methods: This study used data from a randomized, single-dose escalation phase I clinical trial conducted in Korea.

Single dose pharmacokinetics of the novel transdermal donepezil patch in healthy volunteers.

Background: Donepezil is an acetylcholinesterase inhibitor indicated for Alzheimer's disease. The aim of this randomized, single-blind, placebo-controlled, single-dose, dose-escalation study was to investigate the safety, tolerability, and pharmacokinetics of the donepezil patch in healthy male subjects.

Methods: Each healthy male subject received a single transdermal donepezil patch (72 hours patch-on periods) of 43.

H2O2-responsive molecularly engineered polymer nanoparticles as ischemia/reperfusion-targeted nanotherapeutic agents.

The main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury is the overproduction of reactive oxygen species (ROS). Hydrogen peroxide (H2O2), the most abundant form of ROS produced during I/R, causes inflammation, apoptosis and subsequent tissue damages. Here, we report H2O2-responsive antioxidant nanoparticles formulated from copolyoxalate containing vanillyl alcohol (VA) (PVAX) as a novel I/R-targeted nanotherapeutic agent.

Biodegradable polyoxalate and copolyoxalate particles for drug-delivery applications.

Polyoxalate and copolyoxalate were developed in the 1970s and have been used for biomedical applications such as suture coating purposes, owing to their biocompatibility and biodegradability. They are known to degrade into diols and oxalic acid, which are considered biocompatible. One of the advantages of oxalate-based polymer is the ease of control of physicochemical properties, such as biodegradability, crystallinity and mechanical strength.

RpgrORF15 connects to the usher protein network through direct interactions with multiple whirlin isoforms.

Purpose: Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene are a frequent cause of X-linked retinitis pigmentosa. The RPGR transcript undergoes complex alternative splicing to express both constitutive (Rpgr(ex1-19)) and Rpgr(ORF15) variants. Because functional studies of Rpgr suggest a role in intracellular protein trafficking through the connecting cilia, the goal of this study was to identify potential binding partners for Rpgr(ORF15) and to identify the domains on whirlin necessary for Rpgr binding.

Misexpression of the constitutive Rpgr(ex1-19) variant leads to severe photoreceptor degeneration.

Purpose: Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene are a frequent cause of X-linked retinitis pigmentosa. The RPGR transcript undergoes complex alternative splicing to express both constitutive (Rpgr(ex1-19)) and Rpgr(ORF15) variants. Both variants localize to photoreceptor connecting cilia and are believed to play roles in ciliary function.

Reduction of oxidative stress by p-hydroxybenzyl alcohol-containing biodegradable polyoxalate nanoparticulate antioxidant.

The large production of reactive oxygen species (ROS) leads to the oxidative stress and the subsequent functional decline of organ systems. p-Hydroxybenzyl alcohol (HBA) is known to play a pivotal protective role against oxidative stress-related diseases. We have developed biodegradable antioxidant copolyoxalate, in which HBA is chemically incorporated into its backbone for the treatment of oxidative stress-related diseases.

Antioxidant and anti-inflammatory activities of hydroxybenzyl alcohol releasing biodegradable polyoxalate nanoparticles.

p-Hydroxybenzyl alcohol (HBA) is one of phenolic compounds in herbal agents and plays a pivotal role in protection against oxidative damage-related diseases due to anti-inflammatory effects. We have developed a new biodegradable and anti-inflammatory peroxalate copolymer in which HBA is chemically incorporated into its backbone. The HBA-incorporated copolyoxalate (HPOX) was synthesized from a condensation reaction of oxalyl chloride, 1,4-cyclohexamethanol and HBA and was capable of releasing pharmaceutically active HBA during hydrolytic degradation.