Effect of temperature on the kinetics of lactate production and clearance in a rat model of forebrain ischemia

1998 ◽  
Vol 76 (2-3) ◽  
pp. 503-509 ◽  
Author(s):  
Hao Lei ◽  
James Peeling
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Rat Model ◽  
Brain Temperature ◽  
Lactate Production ◽  
Effect Of Temperature ◽  
Resonance Spectroscopy ◽  
Forebrain Ischemia ◽  
Vessel Occlusion ◽  
Kinetics Of

To investigate the effect of brain temperature on metabolic perturbations during and following forebrain ischemia, localized 1H magnetic resonance spectroscopy was used to measure the kinetics of lactate production and clearance in a rat model of 12- or 20-min forebrain ischemia (two-vessel occlusion with hypotension) at a brain temperature of either 34.5 ± 0.5°C or 37.5 ± 0.5°C. During ischemia, lactate production was modeled with apparent first order kinetics. Hypothermia did not affect the rate or the extent of lactate production during ischemia. Upon reperfusion, a delay in the decrease of the cerebral lactate level was found in the normothermia groups. Such a delay was absent in hypothermia groups, which may reflect faster resumption of cerebral oxidative metabolism upon reperfusion in the hypothermic animals. The rate constant for lactate clearance postischemia was larger for normothermic animals and for the 20-min ischemia groups, perhaps because of increased blood-brain barrier permeability following more severe ischemia.Key words: forebrain ischemia, temperature, hypothermia, lactate, magnetic resonance spectroscopy.

Forebrain ischemia in diabetic and nondiabetic BB rats studied with 31P magnetic resonance spectroscopy

Diabetes ◽  
1992 ◽  
Vol 41 (10) ◽  
pp. 1328-1334 ◽  
Author(s):  
G. R. Sutherland ◽  
J. Peeling ◽  
E. Sutherland ◽  
R. Tyson ◽  
F. Dai ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Resonance Spectroscopy ◽  
Forebrain Ischemia ◽  
31P Magnetic Resonance Spectroscopy ◽  
Bb Rats

scholarly journals BIMG-08. DEUTERIUM MAGNETIC RESONANCE SPECTROSCOPY USING 2H-PYRUVATE ALLOWS NON-INVASIVE IN VIVO IMAGING OF TERT EXPRESSION IN BRAIN TUMORS

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i2-i2
Author(s):  
Georgios Batsios ◽  
Celine Taglang ◽  
Meryssa Tran ◽  
Anne Marie Gillespie ◽  
Joseph Costello ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
In Vivo Imaging ◽  
Lactate Production ◽  
Telomere Maintenance ◽  
Resonance Spectroscopy ◽  
Low Grade ◽  
Non Invasive ◽  
Tert Expression

Abstract Telomere shortening constitutes a natural barrier to uncontrolled proliferation and all tumors must find a mechanism of maintaining telomere length. Most human tumors, including high-grade primary glioblastomas (GBMs) and low-grade oligodendrogliomas (LGOGs) achieve telomere maintenance via reactivation of the expression of telomerase reverse transcriptase (TERT), which is silenced in normal somatic cells. TERT expression is, therefore, a driver of tumor proliferation and, due to this essential role, TERT is also a therapeutic target. However, non-invasive methods of imaging TERT are lacking. The goal of this study was to identify magnetic resonance spectroscopy (MRS)-detectable metabolic biomarkers of TERT expression that will enable non-invasive visualization of tumor burden in LGOGs and GBMs. First, we silenced TERT expression by RNA interference in patient-derived LGOG (SF10417, BT88) and GBM (GS2) models. Our results linked TERT silencing to significant reductions in steady-state levels of NADH in all models. NADH is essential for the conversion of pyruvate to lactate, suggesting that measuring pyruvate flux to lactate could be useful for imaging TERT status. Recently, deuterium (2H)-MRS has emerged as a novel, clinically translatable method of monitoring metabolic fluxes in vivo. However, to date, studies have solely examined 2H-glucose and the use of [U-2H]pyruvate for non-invasive 2H-MRS has not been tested. Following intravenous injection of a bolus of [U-2H]pyruvate, lactate production was higher in mice bearing orthotopic LGOG (BT88 and SF10417) and GBM (GS2) tumor xenografts relative to tumor-free mice, suggesting that [U-2H]pyruvate has the potential to monitor TERT expression in vivo. In summary, our study, for the first time, shows the feasibility and utility of [U-2H]pyruvate for in vivo imaging. Importantly, since 2H-MRS can be implemented on clinical scanners, our results provide a novel, non-invasive method of integrating information regarding a fundamental cancer hallmark, i.e. TERT, into glioma patient management.

Hyperpolarized 129Xe Magnetic Resonance Spectroscopy in a Rat Model of Bronchopulmonary Dysplasia

2021 ◽  
Author(s):  
Jordan David Fliss ◽  
Brandon Zanette ◽  
Yonni Friedlander ◽  
Siddharth Sadanand ◽  
Andras A Lindenmaier ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Gas Exchange ◽  
Magnetic Resonance Spectroscopy ◽  
Bronchopulmonary Dysplasia ◽  
Rat Model ◽  
Resonance Spectroscopy ◽  
Gas Exchange Parameters ◽  
Functional Changes ◽  
Non Invasive

Premature infants often require mechanical ventilation and oxygen therapy which can result in bronchopulmonary dysplasia (BPD), characterized by developmental arrest and impaired lung function. Conventional clinical methods for assessing the prenatal lung are not adequate for the detection and assessment of long-term health risks in infants with BPD, highlighting the need for a non-invasive tool for the characterization of lung microstructure and function. Theoretical diffusion models, like the Model of Xenon Exchange (MOXE), interrogate alveolar gas exchange by predicting the uptake of inert Hyperpolarized (HP) 129Xe gas measured with HP 129Xe magnetic resonance spectroscopy (MRS). To investigate HP 129Xe MRS as a tool for non-invasive characterization of pulmonary microstructural and functional changes in vivo, HP 129Xe gas exchange data were acquired in an oxygen exposure rat model of BPD that recapitulates the fewer and larger distal airways and pulmonary vascular stunting characteristics of BPD. Gas exchange parameters from MOXE, including airspace mean chord length (L­m), apparent hematocrit in the pulmonary capillaries (HCT), and pulmonary capillary transit time (tx), were compared with airspace mean axis length and area density (MAL and ρ­A) and percentage area of tissue and air (PTA and PAA) from histology. L­m was significantly larger in the exposed rats (p=0.003) and correlated with MAL, ρ­A, PTA, and PAA (0.59<|ρ|<0.66 and p<0.05). Observed increase in HCT (p=0.012) and changes in tx are also discussed. These findings support the use of HP 129Xe MRS for detecting fewer, enlarged distal airways in this rat model of BPD, and potentially in humans.

BIOM-10. PRECLINICAL PLATFORM FOR THE IDENTIFICATION OF DEUTERIUM MAGNETIC RESONANCE SPECTROSCOPY-BASED BIOMARKERS OF BRAIN TUMOR METABOLISM

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi12-vi12
Author(s):  
Georgios Batsios ◽  
Meryssa Tran ◽  
Céline Taglang ◽  
Anne Marie Gillespie ◽  
Sabrina Ronen ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Brain Tumors ◽  
Treatment Response ◽  
Lactate Production ◽  
Cell Suspensions ◽  
Response To Therapy ◽  
Resonance Spectroscopy

Abstract Metabolic reprogramming is a fundamental hallmark of cancer, which can be exploited for non-invasive tumor imaging. Deuterium magnetic resonance spectroscopy (2H-MRS) recently emerged as a novel, translational method of interrogating flux from 2H-labeled substrates to metabolic products. However, to date, preclinical studies have been performed in vivo, an endeavor which suffers from low-throughput and potential wastage of animal life, especially when considering studies of treatment response. Developing in vitro assays for monitoring metabolism of 2H-labeled substrates will enhance throughput, lead to the rapid evaluation of new 2H-based probes and enable identification of treatment response biomarkers, thereby allowing the best 2H-based probes to be translated for further in vivo assessment. The goal of this study was to develop a preclinical cell-based platform for quantifying metabolism of 2H-labeled probes in brain tumor models. Since the Warburg effect, which is characterized by elevated glycolytic production of lactate, is a metabolic phenotype of cancer, including brain tumors, we examined metabolism of 2H-glucose or 2H-pyruvate in patient-derived glioblastoma (GBM6) and oligodendroglioma (BT88) cells and compared to normal human astrocytes (NHACONTROL). Following incubation in media containing [6,6’-2H]glucose or [U-2H]pyruvate, 2H-MR spectra obtained from live cell suspensions showed elevated 2H-lactate production in GBM6 and BT88 cells relative to NHACONTROL. Importantly, 2H-lactate production from [6,6’-2H]glucose or from [U-2H]pyruvate was reduced in GBM6 or BT88 cells subjected to irradiation and temozolomide, which is standard of care for glioma patients, pointing to the utility of this method for detecting response to therapy. Collectively, we have, for the first time, demonstrated the ability to quantify metabolism of 2H-MRS probes in live cell suspensions and validated the utility of our assay for differentiating tumor from normal cells and assessing response to therapy. Our studies will expedite the identification of novel 2H-MRS probes for imaging brain tumors and potentially other types of cancer.

A review of in vivo 1H magnetic resonance spectroscopy of cerebral ischemia in rats

1998 ◽  
Vol 76 (2-3) ◽  
pp. 487-496 ◽  
Author(s):  
K L Malisza ◽  
P Kozlowski ◽  
J Peeling
Keyword(s):  
Cerebral Ischemia ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Lactate Concentration ◽  
Dichloroacetic Acid ◽  
Proton Nuclear Magnetic Resonance ◽  
Effect Of Temperature ◽  
Resonance Spectroscopy ◽  
Ischemic Damage

A number of metabolic alterations are initiated by cerebral ischemia including dramatic increases in lactate concentration, decreases in N-acetylaspartate, choline, and creatine concentrations, as well as changes in amino acid levels. A review of proton nuclear magnetic resonance spectroscopy studies of focal and global cerebral ischemia in rats is presented here. In particular, studies in neonatal rats have shown that a continued elevation of lactate levels without recovery after hypoxia-ischemia or a decrease in N-acetylaspartate concentration at any time are indicative of deleterious outcome. Studies of the effect of temperature on ischemic damage in a model of focal ischemia showed that outcome improved with mild hypothermia. Again, lack of recovery of lactate upon reperfusion was shown to be indicative of poor outcome. Dichloroacetic acid was used to treat rats with focal ischemic damage. Animals subjected to transient ischemia that were treated with dichloroacetic acid showed significant decreases in lactate concentration.Key words: NMR, in vivo, rat, cerebral ischemia.

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