A5072768373- Advanced MRI Techniques and Applications
- Advanced NMR Techniques and Applications
- Medical Imaging Techniques and Applications
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Diet and metabolism studies
- Atomic and Subatomic Physics Research
- Adipose Tissue and Metabolism
- Glioma Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Electron Spin Resonance Studies
- Lanthanide and Transition Metal Complexes
- Anesthesia and Neurotoxicity Research
- Chemical Reactions and Isotopes
- NMR spectroscopy and applications
- Treatment of Major Depression
- Diabetes Management and Research
- Cancer, Hypoxia, and Metabolism
- PARP inhibition in cancer therapy
- Cardiovascular Function and Risk Factors
- Metabolomics and Mass Spectrometry Studies
- Muscle metabolism and nutrition
- Neuroinflammation and Neurodegeneration Mechanisms
- DNA Repair Mechanisms
- ATP Synthase and ATPases Research
Yale University
2016-2025
Resonance Research (United States)
2016-2025
Laboratoire d’Imagerie Biomédicale
2023
University of Minnesota, Duluth
2016
National Center for PTSD
2014
Eindhoven University of Technology
2007-2011
2-Hydroxyglutarate (2HG) exists as two enantiomers, (R)-2HG and (S)-2HG, both are implicated in tumor progression via their inhibitory effects on α-ketoglutarate (αKG)-dependent dioxygenases. The former is an oncometabolite that induced by the neomorphic activity conferred isocitrate dehydrogenase 1 (IDH1) IDH2 mutations, whereas latter produced under pathologic processes such hypoxia. We report IDH1/2 mutations induce a homologous recombination (HR) defect renders cells exquisitely...
DMI shows metabolism of acetate and glucose in the brain liver reveals Warburg effect patients with tumors.
Research on novel treatments for major depressive disorder focuses quite deeply glutamate function, and this research would benefit from a brain-imaging technique that precisely quantified function. Signs of specific form glutamate-related dysfunction could be targeted by therapies were found using novel, state-of-the-art techniques to address issue.
When a person consumes ethanol, the body quickly begins to convert it acetic acid, which circulates in blood and can serve as source of energy for brain other organs. This study used 13C magnetic resonance spectroscopy test whether chronic heavy drinking is associated with greater uptake oxidation providing potential metabolic reward or adenosinergic effect consequence drinking. Seven drinkers, who regularly consumed at least 8 drinks per week 4 day once week, 7 light fewer than 2 were...
Background.The dependence of tumor cells, particularly those originating in the brain, on glucose is target ketogenic diet, which creates a plasma nutrient profile similar to fasting: increased levels ketone bodies and reduced concentrations.The use diets has been particular interest for therapy brain tumors, reportedly lack ability oxidize therefore would be starved during ketosis.Because studies assessing tumors' are lacking, we investigated vivo extent body oxidation 2 rodent glioma...
To present first highly spatially resolved deuterium metabolic imaging (DMI) measurements of the human brain acquired with a dedicated coil design and fast chemical shift (CSI) sequence at an ultrahigh field strength B0 = 9.4 T. 2H temporal resolution 10 min enabled investigation glucose metabolism in healthy subjects.The study was performed double-tuned TxRx channels for 1H 8TxRx/2Rx Ernst angle 3D CSI nominal spatial 2.97 ml min.The [6,6'-2H2]-labeled due to TCA cycle could be made visible...
Purpose To explore the potential of deuterium metabolic imaging (DMI) in human brain vivo at 7 T, using a multi‐element ( 2 H) RF coil for 3D volume coverage. Methods 1 H‐MR images and localized H MR spectra were acquired 3 healthy subjects to generate DMI maps H‐labeled water, glucose, glutamate/glutamine (Glx). In addition, non‐localized both vitro determine T relaxation times deuterated metabolites T. The performance was assessed through numeric simulations experimentally B + maps....
Several lines of evidence support a potential role skeletal muscle mitochondrial dysfunction in the pathogenesis insulin resistance and/or type 2 diabetes. However, it remains to be established whether represents either cause or consequence disease. We examined vivo function early and advanced stages diabetes, with aim gain insight proposed aetiology diabetes.Ten long-standing, insulin-treated diabetes patients, 11 subjects impaired fasting glucose, glucose tolerance recently diagnosed 12...
Conflicting data exist on mitochondrial function and physical activity in type 2 diabetes mellitus (T2DM) development.The aim was to assess at different stages during T2DM development combination with exercise longstanding patients.We performed cross-sectional analysis of skeletal muscle from 12 prediabetic 11 male subjects controls matched by age body mass index.One-year intrasubject controlled supervised training intervention done patients.Extensive ex vivo analyses quality, quantity, were...
Deuterium metabolic imaging (DMI) is a novel MR‐based method to spatially map metabolism of deuterated substrates such as [6,6'‐ 2 H ]‐glucose in vivo. Compared with traditional 13 C‐MR‐based studies, the MR sensitivity DMI high due larger magnetic moment and favorable T 1 relaxation times. Here, field dependence transmit efficiency studied on phantoms rat brain postmortem at 4, 9.4 11.7 T. The spectral resolution human vivo are investigated 4 7 before after an oral dose ]‐glucose. For small...
Introduction There is a lack of robust metabolic imaging techniques that can be routinely applied to characterize lesions in patients with brain tumors. Here we explore an animal model glioblastoma the feasibility detect uptake and metabolism deuterated choline describe tumor-to-brain image contrast. Methods RG2 cells were incubated level intracellular its metabolites measured cell extracts using high resolution 1 H NMR. In rats orthotopically implanted tumors deuterium (DMI) was vivo...
Currently inherited or acquired skeletal muscle mitochondrial dysfunction is linked to dysregulated fatty acid metabolism, resulting in increased levels of intramyocellular lipids (IMCLs) and lipid intermediates, inducing insulin resistance. The present study aimed clarify the order changes IMCL function during development type 2 diabetes Zucker diabetic (ZDF) rats. oxidative capacity were determined vivo, using localized (1)H magnetic resonance spectroscopy (MRS) dynamic (31)P MRS,...
Solid tumors have an acidic extracellular pH (pHe ) but near neutral intracellular (pHi ). Because pHe milieu is conducive to tumor growth and builds resistance therapy, simultaneous mapping of inside outside the (i.e., intratumoral-peritumoral gradient) fulfills important need in cancer imaging. We used Biosensor Imaging Redundant Deviation Shifts (BIRDS), which utilizes shifts non-exchangeable protons from macrocyclic chelates (e.g.,...
Purpose To develop 1 H‐based MR detection of nicotinamide adenine dinucleotide (NAD + ) in the human brain at 7T and validate H results with NAD based on 31 P‐MRS. Methods H‐MR was achieved a one‐dimensional double‐spin‐echo method slice parallel to surface coil transceiver. Perturbation water resonance avoided through use frequency‐selective excitation. P‐MR performed an unlocalized pulse‐acquire sequence. Results Both H‐ P‐MRS allowed signals every subject 16 min. Spectral fitting provided...
Deuterium metabolic imaging (DMI) is a novel, 3D, magnetic resonance (MR)-based method to map metabolism of deuterated substrates in vivo. The replacement protons with deuterons could potentially lead kinetic isotope effects (KIEs) which rates are reduced due the presence heavier isotope. Knowledge extent KIE vivo and 2H label loss exchange reactions required for DMI-based measurements absolute rates. Here deuterium investigated glucose acetate using double substrate/double labeling strategy...
Previous studies have reported that brain metabolism of acetate is increased more than twofold during hypoglycemia in type 1 diabetic (T1D) subjects with unawareness. These data support the hypothesis upregulation blood-brain barrier monocarboxylic acid (MCA) transport may contribute to maintenance energetics Plasma lactate concentrations are ∼10-fold higher concentrations, making most likely alternative MCA as fuel. We therefore examined [3-13C]lactate across and its brains T1D patients...
Purpose Deuterium metabolic imaging (DMI) combined with [6,6’‐ 2 H ]‐glucose has the potential to detect glycogen synthesis in liver. However, similar chemical shifts of and ]‐glycogen NMR spectrum make unambiguous detection separation difficult vivo, contrast comparable approaches using 13 C MRS. Here visibility H‐labeled is investigated better understand its contribution observed signal liver following administration ]‐glucose. Methods Mice were provided drinking water containing glucose....
Increased glucose and choline uptake are hallmarks of cancer. We investigated whether the conversion [2H9]choline alone together with that [6,6′-2H2]glucose can be assessed in tumors via deuterium metabolic imaging (DMI) after administering these compounds. Therefore, human renal carcinoma cells were grown subcutaneously mice. Isoflurane anesthetized mice IV infused MR magnet for ~20 s ~0.2 mL solutions containing either (0.05 g/kg) or (1.3 g/kg). 2H was performed on a 11.7T system...