A5026115452- Advanced NMR Techniques and Applications
- Advanced MRI Techniques and Applications
- Electron Spin Resonance Studies
- Atomic and Subatomic Physics Research
- Solid-state spectroscopy and crystallography
- Enzyme Structure and Function
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Biochemical Acid Research Studies
- Diet and metabolism studies
- Cardiovascular Disease and Adiposity
- Amino Acid Enzymes and Metabolism
- Traumatic Brain Injury and Neurovascular Disturbances
- Liver Disease Diagnosis and Treatment
- Lanthanide and Transition Metal Complexes
- Ultrasound and Hyperthermia Applications
- NMR spectroscopy and applications
- MRI in cancer diagnosis
- Infectious Encephalopathies and Encephalitis
- Cancer-related Molecular Pathways
- Long-Term Effects of COVID-19
- Biochemical and Molecular Research
- Optical Imaging and Spectroscopy Techniques
The University of Texas Southwestern Medical Center
2017-2025
Advanced Imaging Research (United States)
2017-2025
Southwestern Medical Center
2019-2024
The University of Texas at Dallas
2017-2022
Stanford University
2012-2019
Palo Alto University
2013
Applied Sciences Laboratory (United States)
2013
SRI International
2013
Menlo School
2013
Yonsei University
2012
Hyperpolarized [1‐ 13 C]pyruvate ([1‐ C]Pyr) has been used to assess metabolism in healthy and diseased states, focusing on the downstream labeling of lactate (Lac), bicarbonate alanine. Although hyperpolarized [2‐ C]Pyr, which retains labeled carbon when Pyr is converted acetyl‐coenzyme A, successfully mitochondrial heart, application C]Pyr study brain limited date, with Lac being only metabolic product reported previously. In this study, single‐time‐point chemical shift imaging data were...
The metabolic phenotype that derives disproportionate energy via glycolysis in solid tumors, including glioma, leads to elevated lactate labeling imaging using hyperpolarized [1-13C]pyruvate. Although the pyruvate dehydrogenase (PDH)–mediated flux from acetyl coenzyme A can be indirectly measured through detection of carbon-13 (13C)-labeled bicarbonate, it has proven difficult visualize 13C-bicarbonate at high enough levels injected [1-13C]pyruvate for quantitative analysis brain. aim this...
To facilitate diagnosis and staging of liver disease, sensitive non-invasive methods for the measurement metabolism are needed. This study used hyperpolarized 13C-pyruvate to assess metabolic parameters in a CCl4 model damage rats. Dynamic 3D 13C chemical shift imaging data from volume covering kidney were acquired 8 control 10 CCl4-treated At 12 time points at 5 s temporal resolution, we quantified signal intensities established courses pyruvate, alanine, lactate. These measurements...
Hyperpolarized [1‐ 13 C]pyruvate MRS provides a unique imaging opportunity to study the reaction kinetics and enzyme activities of in vivo metabolism because its favorable characteristics critical position cellular metabolic pathway, where it can either be reduced lactate (reflecting glycolysis) or converted acetyl‐coenzyme A bicarbonate oxidative phosphorylation). Cancer tissue is altered such way as result relative preponderance glycolysis phosphorylation (i.e. Warburg effect). Although...
The production of glycolytic end products, such as lactate, usually evokes the concept a cellular shift from aerobic to anaerobic ATP generation and O2 insufficiency. In classical view, muscle lactate must export liver for clearance. Studies, however, indicate that also forms under well-oxygenated conditions have led investigators postulate shuttling non-oxidative oxidative fiber, where it can serve precursor. Indeed, intracellular shuttle glycogen shunt hypotheses expand vision include...
Hyperpolarized 13 C MRS allows the in vivo assessment of pyruvate dehydrogenase complex (PDC) flux, which converts to acetyl‐coenzyme A (acetyl‐CoA). [1‐ C]pyruvate has been used measure changes cardiac PDC with demonstrated increase C‐bicarbonate production after dichloroacetate (DCA) administration. With C]pyruvate, label is released as CO 2 / C‐bicarbonate, and, hence, does not allow us follow fate acetyl‐CoA. Pyruvate labeled position track into TCA (tricarboxylic acid) cycle and [5‐...
Purpose Commonly used anesthetic agents such as isoflurane are known to be potent cerebral vasodilators, with reported dose‐dependent increase in blood flow and volume. Despite the widespread use of hyperpolarized 13 C preclinical research studies, a quantitative assessment its effect on metabolic measurements is limited. This work investigates anesthesia dose MR rat brain for [1‐ C]pyruvate 2‐keto[1‐ C]isocaproate. Methods Dynamic 2D 3D spiral chemical shift imaging was acquire images well...
Abstract In addition to an increased lactate‐to‐pyruvate ratio, altered metabolism of a malignant glioma can be further characterized by its kinetics. Spatially resolved dynamic data pyruvate and lactate from C6‐implanted female Sprague–Dawley rat brain were acquired using spiral chemical shift imaging sequence after bolus injection hyperpolarized [1‐ 13 C]pyruvate. Apparent rate constants for the conversion in three different regions (glioma, normal appearing brain, vasculature) estimated...
In addition to cancer imaging, 13 C‐MRS of hyperpolarized pyruvate has also demonstrated utility for the investigation cardiac metabolism and ischemic heart disease. Although no adverse effects have yet been reported doses commonly used in vivo , high substrate concentrations lead supraphysiological levels that can affect underlying should be considered when interpreting results. With lactate serving as an important energy source physiological one two orders magnitude higher than pyruvate,...
Purpose MRS of hyperpolarized [2‐ 13 C]pyruvate can be used to assess multiple metabolic pathways within mitochondria as the C label is not lost with conversion pyruvate acetyl‐CoA. This study presents first MR spectroscopic imaging in glioma‐bearing brain. Methods Spiral chemical shift spectrally undersampling scheme (1042 Hz) and a hard‐pulse excitation was exploited simultaneously image C]pyruvate, C]lactate, [5‐ C]glutamate, metabolites known produced brain after an injection without...
Purpose In contrast to [1‐ 13 C]pyruvate, hyperpolarized [2‐ C]pyruvate permits the ability follow C label beyond flux through pyruvate dehydrogenase complex and investigate incorporation of acetyl‐coenzyme A into different metabolic pathways. However, chemical shift imaging (CSI) with is challenging owing large spectral dispersion resonances, which also leads severe displacement artifacts for slice‐selective acquisitions. Methods This study introduces a sequence three‐dimensional CSI using...
Abstract Altered branched-chain amino acids (BCAAs) metabolism is a distinctive feature of various cancers and plays an important role in sustaining tumor proliferation aggressiveness. Despite the therapeutic diagnostic potentials, BCAA cancer activities associated enzymes remain unclear. Due to its pivotal rapid cellular transport, hyperpolarized 13 C-labeled α-ketoisocaproate (KIC), α-keto acid corresponding leucine, can assess both aminotransferase (BCAT) dehydrogenase complex (BCKDC) via...
Purpose The intracellular lactate to pyruvate concentration ratio is a commonly used tissue assay biomarker of redox, being proportional free cytosolic [NADH]/[NAD + ]. In this study, we assessed the use hyperpolarized [1‐ 13 C]alanine and subsequent detection products C]pyruvate C]lactate as useful substrate for assessing redox levels in liver vivo. Methods Animal experiments were conducted measure vivo metabolism at baseline after ethanol infusion. A solution 80‐mM was injected...
Reactive oxygen species (ROS) are essential cellular metabolites widely implicated in many diseases including cancer, inflammation, and cardiovascular neurodegenerative disorders. Yet, ROS signaling remains poorly understood, their measurements a challenge due to high reactivity instability. Here, we report the development of 13C-thiourea as probe detect measure H2O2 dynamics with sensitivity spatiotemporal resolution using hyperpolarized 13C magnetic resonance spectroscopic imaging. In...
Traumatic brain injury (TBI) involves complex secondary processes following the primary injury. The is often associated with rapid metabolic shifts and impaired function immediately after initial tissue damage. Magnetic resonance spectroscopic imaging (MRSI) coupled hyperpolarization of 13C-labeled substrates provides a unique opportunity to map changes in traumatic real-time without invasive procedures. In this report, we investigated two patients acute mild TBI (Glasgow coma scale 15) but...
Purpose Noninvasive imaging with hyperpolarized (HP) pyruvate can capture in vivo cardiac metabolism. For proper quantification of the metabolites and optimization parameters, understanding MR characteristics such as s HP signals is critical. This study to measure [1‐ 13 C]pyruvate products rodents humans. Methods A dynamic C multi‐echo spiral sequence that acquires [ C]bicarbonate, C]lactate, images an interleaved manner was implemented for a clinical 3 Tesla system. each metabolite...
Hyperpolarized 13C magnetic resonance spectroscopy (MRS) provides unprecedented opportunities to obtain clinical diagnostic information through in vivo monitoring of metabolic pathways. The continuing advancement this field relies on the identification molecular probes that can effectively interrogate pathways critical disease. In report, we describe synthesis, development, and application sodium [1-13C]-glycerate ([13C]-Glyc) as a novel probe for evaluating glycolysis using hyperpolarized...
To evaluate the utility of hyperpolarized [1-13 C]-l-lactate to detect hepatic pyruvate carboxylase activity in vivo under fed and fasted conditions.[1-13 C]-labeled sodium L-lactate was polarized using a dynamic nuclear polarizer. Polarization level T1 were measured vitro 3 Telsa MR scanner. Two groups healthy rats (fasted vs. fed) prepared for studies. Each rat anesthetized intravenously injected with 60-mM C]-l-lactate, immediately followed by acquisition 13 C (carbon-13) spectra from...
Carbon‐13 magnetic resonance spectroscopy (MRS) following oral intake of 13 C‐labeled glucose is the gold standard for imaging glycogen metabolism in humans. However, temporal resolution previous studies has been >13 minutes. Here, we describe a high‐sensitivity C MRS method hepatic synthesis with 1 minute or less. Nuclear spectra were acquired from liver 3 healthy volunteers, using clamshell radiofrequency transmit and paddle‐shaped array receive coils Tesla system. Following 15‐minute...
Background Pyruvate dehydrogenase (PDH) and lactate are essential for adenosine triphosphate production in skeletal muscle. At the onset of exercise, oxidation glucose glycogen is quickly enabled by dephosphorylation PDH. However, direct measurement PDH flux exercising human muscle daunting, net effect covalent modification other control mechanisms on has not been assessed. Purpose To demonstrate feasibility assessing activation changes pyruvate metabolism after exercise using carbon 13...
Glioblastoma remains incurable despite treatment with surgery, radiation therapy, and cytotoxic chemotherapy, prompting the search for a metabolic pathway unique to glioblastoma cells.13C MR spectroscopic imaging hyperpolarized pyruvate can demonstrate alterations in metabolism these tumors.Three patients diagnostic MRI suggestive of were scanned at 3 T 1-2 days prior tumor resection using 13C/1H dual-frequency RF coil 13C/1H-integrated protocol, which consists series 1H sequences (T2 FLAIR,...
[13 C]Bicarbonate formation from hyperpolarized [1-13 C]pyruvate via pyruvate dehydrogenase, a key regulatory enzyme, represents the cerebral oxidation of and integrity mitochondrial function. The present study is to characterize chronology metabolism during secondary injury associated with acute traumatic brain (TBI) by longitudinally monitoring C]bicarbonate production in rodents.Male Wistar rats were randomly assigned undergo controlled-cortical impact (CCI, n = 31) or sham surgery (n...