Deuterium MRI of serine metabolism in mouse models of glioblastoma.

Purpose: Serine is a major source of one-carbon units needed for the synthesis of nucleotides and the production of intramitochondrial nicotinamide adenine dinucleotide phosphate (NADPH), and it plays an important role in cancer cell proliferation. The aim of this study was to develop a deuterium (H) MRS imaging method for imaging tumor serine metabolism.

Methods: Sequential (H) spectra and spectroscopic images were used to monitor the metabolism of [2,3,3-H]serine in patient-derived glioblastoma cells in vitro and in tumors obtained by their orthotopic implantation in mouse brain.

AI as a New Frontier in Contrast Media Research: Bridging the Gap Between Contrast Media Reduction, the Contrast-Free Question and New Application Discoveries.

Artificial intelligence (AI) techniques are currently harnessed to revolutionize the domain of medical imaging. This review investigates 3 major AI-driven approaches for contrast agent management: new frontiers in contrast agent dose reduction, the contrast-free question, and new applications. By examining recent studies that use AI as a new frontier in contrast media research, we synthesize the current state of the field and provide a comprehensive understanding of the potential and limitations of AI in this context.

Assessment of the sensitivity of H MR spectroscopy measurements of [2,3- H ]fumarate metabolism for detecting tumor cell death.

Imaging the metabolism of [2,3- H ]fumarate to produce malate can be used to detect tumor cell death post-treatment. Here, we assess the sensitivity of the technique for detecting cell death by lowering the concentration of injected [2,3- H ]fumarate and by varying the extent of tumor cell death through changes in drug concentration. Mice were implanted subcutaneously with human triple negative breast cancer cells (MDA-MB-231) and injected with 0.

Imaging Glioblastoma Response to Radiotherapy Using 2H Magnetic Resonance Spectroscopy Measurements of Fumarate Metabolism.

Unlabelled: Early detection of tumor cell death in glioblastoma following treatment with chemoradiation has the potential to distinguish between true disease progression and pseudoprogression. Tumor cell death can be detected noninvasively in vivo by imaging the production of [2,3-2H2]malate from [2,3-2H2]fumarate using 2H magnetic resonance (MR) spectroscopic imaging. We show here that 2H MR spectroscopy and spectroscopic imaging measurements of [2,3-2H2]fumarate metabolism can detect tumor cell death in orthotopically implanted glioblastoma models within 48 hours following the completion of chemoradiation.

Deuterium MRSI of tumor cell death in vivo following oral delivery of H-labeled fumarate.

Purpose: There is an unmet clinical need for direct and sensitive methods to detect cell death in vivo, especially with regard to monitoring tumor treatment response. We have shown previously that tumor cell death can be detected in vivo from H MRS and MRSI measurements of increased [2,3- H ]malate production following intravenous injection of [2,3- H ]fumarate. We show here that cell death can be detected with similar sensitivity following oral administration of the H-labeled fumarate.

Genetic algorithm-based optimization of pulse sequences.

Purpose: The performance of pulse sequences in vivo can be limited by fast relaxation rates, magnetic field inhomogeneity, and nonuniform spin excitation. We describe here a method for pulse sequence optimization that uses a stochastic numerical solver that in principle is capable of finding a global optimum. The method provides a simple framework for incorporating any constraint and implementing arbitrarily complex cost functions.

Monitoring tumor cell death in murine tumor models using deuterium magnetic resonance spectroscopy and spectroscopic imaging.

H magnetic resonance spectroscopic imaging has been shown recently to be a viable technique for metabolic imaging in the clinic. We show here that H MR spectroscopy and spectroscopic imaging measurements of [2,3-H]malate production from [2,3-H]fumarate can be used to detect tumor cell death in vivo via the production of labeled malate. Production of [2,3-H]malate, following injection of [2,3-H]fumarate (1 g/kg) into tumor-bearing mice, was measured in a murine lymphoma (EL4) treated with etoposide, and in human breast (MDA-MB-231) and colorectal (Colo205) xenografts treated with a TRAILR2 agonist, using surface-coil localized H MR spectroscopy at 7 T.

Increasing the sensitivity of hyperpolarized [ N ]urea detection by serial transfer of polarization to spin-coupled protons.

Purpose: Hyperpolarized N-labeled molecules have been proposed as imaging agents for investigating tissue perfusion and pH. However, the sensitivity of direct N detection is limited by the isotope's low gyromagnetic ratio. Sensitivity can be increased by transferring N hyperpolarization to spin-coupled protons provided that there is not significant polarization loss during transfer.

Measuring Tumor Glycolytic Flux in Vivo by Using Fast Deuterium MRI.

Background Tumor cells frequently show high rates of aerobic glycolysis, which provides the glycolytic intermediates needed for the increased biosynthetic demands of rapid cell growth and proliferation. Existing clinical methods (fluorodeoxyglucose PET and carbon 13 MRI and spectroscopy) do not allow quantitative images of glycolytic flux. Purpose To evaluate the use of deuterium (hydrogen 2 [H]) MR spectroscopic imaging for quantitative mapping of tumor glycolytic flux and to assess response to chemotherapy.

Glyoxalase activity in human erythrocytes and mouse lymphoma, liver and brain probed with hyperpolarized C-methylglyoxal.

Methylglyoxal is a faulty metabolite. It is a ubiquitous by-product of glucose and amino acid metabolism that spontaneously reacts with proximal amino groups in proteins and nucleic acids, leading to impairment of their function. The glyoxalase pathway evolved early in phylogeny to bring about rapid catabolism of methylglyoxal, and an understanding of the role of methylglyoxal and the glyoxalases in many diseases is beginning to emerge.

Photogenerated Radical in Phenylglyoxylic Acid for in Vivo Hyperpolarized C MR with Photosensitive Metabolic Substrates.

Whether for C magnetic resonance studies in chemistry, biochemistry, or biomedicine, hyperpolarization methods based on dynamic nuclear polarization (DNP) have become ubiquitous. DNP requires a source of unpaired electrons, which are commonly added to the sample to be hyperpolarized in the form of stable free radicals. Once polarized, the presence of these radicals is unwanted.

Metabolic Imaging Detects Low Levels of Glycolytic Activity That Vary with Levels of c-Myc Expression in Patient-Derived Xenograft Models of Glioblastoma.

C MRI of hyperpolarized [1-C]pyruvate metabolism has been used in oncology to detect disease, investigate disease progression, and monitor response to treatment with a view to guiding treatment in individual patients. This technique has translated to the clinic with initial studies in prostate cancer. Here, we use the technique to investigate its potential uses in patients with glioblastoma (GB).

Dynamic H imaging of hyperpolarized [1- C]lactate in vivo using a reverse INEPT experiment.

Purpose: Dynamic magnetic resonance spectroscopic imaging of hyperpolarized C-labeled cell substrates has enabled the investigation of tissue metabolism in vivo. Currently observation of these hyperpolarized substrates is limited mainly to C detection. We describe here an imaging pulse sequence that enables proton observation by using polarization transfer from the hyperpolarized C nucleus to spin-coupled protons.