Biomedical subjects

D M Doddrell

Publications and source records attributed to D M Doddrell.

64 records · Page 4Linked to original sources

PubMed1986

In vivo determination of 31P spin relaxation times (T1, T2, T1 rho) in rat leg muscle. Use of an off-axis solenoid coil.

A probe using a solenoid coil tilted 45 degrees off-axis has been used to study the 31P NMR relaxation characteristics of the resonances arising from phosphorus metabolites in rats in vivo. T1, T1 rho and T2 values have been determined for phosphocreatine and ATP in leg muscle. The ratio of 31P T1(1700ms) to T2(12ms) for ATP was in excess of 200:1 compared with a ratio of 5:1 for 1H T1:T2. Of major significance was the observation that T2 values for phosphocreatine (230ms) were markedly longer than T2 values for ATP (12ms). Thus by use of appropriate delay times in spin echo sequences ATP signals can be nulled, and discrete 31P imaging of phosphocreatine in muscle may be possible provided the overall signal-to-noise is satisfactory.

Animals↗

PubMed1986

Use of inversion spin transfer to monitor creatine kinase kinetics in rat skeletal muscle in vivo.

A simple multipulse sequence has been used to monitor creatine kinase kinetics in rat skeletal muscle in vivo. Using these procedures, the forward (ATP synthesis) and reverse fluxes (phosphocreatine synthesis) have been calculated to be 8.98 +/- 0.6 and 10.7 +/- 0.8 mumoles/g wet wt/s (n = 5) respectively. These results suggest that in resting skeletal muscle most of the gamma ATP observed in 31P NMR spectra is cytosolic and rapidly exchanging with phosphocreatine. The high flux rates reflect the high catalytic capacity of creatine kinase in skeletal muscle.

Adenosine Triphosphate↗

PubMed1985

In vitro metabolism of [2-13C]-ethanol by 1H NMR spectroscopy using 13C decoupling with the reverse dept polarization-transfer pulse sequence.

The metabolism of [2-13C]-ethanol by alcohol dehydrogenase purified from Drosophila melanogaster has been observed by proton nuclear magnetic resonance spectroscopy (NMR). The reverse-DEPT pulse sequence, with composite pulse 13C decoupling to simplify and increase the signal-to-noise of spectra, has been used to eliminate the strong water signal while still observing the proton signals of metabolites of interest. Using these techniques the rates of synthesis of acetaldehyde, its diol and acetate from [2-13C] ethanol by alcohol dehydrogenase were measured simultaneously.

Acetaldehyde↗

PubMed1985

Application of the reverse dept polarization-transfer pulse sequence to monitor in vitro and in vivo metabolism of 13C-ethanol by 1H-NMR spectroscopy.

Using the reverse 13C----1H DEPT polarization-transfer pulse sequence the metabolism of 13C ethanol in vitro and in vivo has been monitored by 1H-NMR spectroscopy. Using yeast alcohol dehydrogenase, acetaldehyde, the hydrated form of acetaldehyde and acetate were identified as metabolites of [2-13C]-ethanol. The ratio of hydrated to free acetaldehyde was dependent upon the protein concentration of the reaction mixture. Binding of acetaldehyde in an irreversible Schiffs base resulted in optimal enzyme activity. Hepatocytes from rats fasted for 20 h, metabolised [1-13C] and [2-13C]ethanol in a linear fashion, but no [13C]acetaldehyde was detected. Metabolic integrity of the hepatocytes was confirmed with [2-13C]acetate. The addition of disulfiram (50 micron) to hepatocyte suspensions which had been incubated with [1-13C]ethanol, resulted in the resynthesis of [13C]ethanol. The amount of [13C]ethanol resynthesized under these conditions represents intracellular acetaldehyde whose concentration was in the range of 400-800 mumol/g wet weight of hepatocytes when 50 mM ethanol had been originally incubated with the hepatocyte suspension. These studies show how NMR-polarization transfer pulse sequences can be used to monitor the metabolism of 13C-ethanol in vivo, and provide a unique tool to measure in vivo concentrations of acetaldehyde. The studies also suggest that cytoplasmic aldehyde dehydrogenase may play a major role in hepatic ethanol metabolism.

Acetaldehyde↗

PubMed1985

Use of high-resolution 31P-labeled topical magnetic resonance spectroscopy to monitor in vivo tumor metabolism in rats.

A probe using a single-tuned solenoid coil has been constructed to study in vivo metabolism of rats in a wide-bore Bruker nuclear magnetic resonance spectrometer. Transplantable rat mammary adenocarcinomas (estrogen receptor negative) were implanted into the hind leg muscle of 8-week-old rats. The other leg without tumor was used as a control. Tumor metabolism could be distinguished from that of surrounding muscle by the appearance of inorganic phosphate and sugar phosphate resonances, reflecting tissue necrosis, and increased glycolysis. Tumor growth was accompanied by an increase in the size of these peaks, and the chemical shifts of the inorganic phosphate peak indicated that the intracellular pH became more acidic. Administration of methotrexate (i.v.) reversed these patterns and decreased tumor volume. Changes in the phosphocreatine peaks indicated changes in tumor volume rather than in tumor metabolism. These studies show that topical magnetic resonance not only can monitor the growth of tumors in vivo but can be also used to evaluate the efficacy of chemotherapeutic drugs.

Animals↗

PubMed1984

In vivo 13C nuclear magnetic resonance spectroscopy using a solenoid transmit/receiver coil.

Topical nuclear magnetic resonance spectroscopy (NMR) using a solenoid transmit/receiver coil has been used to monitor the kinetics of intragastric utilization of [1-13C] glucose in mice in vivo. Using a double-tuned solenoid coil, signal to noise response was excellent and the natural abundance in vivo 13C spectra obtained with acquisition times of 10-15 minutes compares more than favourably with comparable studies using surface or saddle coils. This study clearly shows the potential of solenoid coils to monitor the kinetics of 13C-labelled metabolites in vivo.

Animals↗

PubMed1984

A 15N nuclear magnetic resonance study of the biosynthesis of quinoxaline antibiotics.

Uniformly 15N-labelled triostin A and echinomycin have been prepared by growing the producing organisms on enriched media and their 15N nuclear magnetic resonance spectra partially assigned by a combination of nuclear Overhauser effect and scalar coupling constant measurements. Selective feeding experiments using unlabelled L-tryptophan-supplemented media have shown that N-1 and N-4 of the quinoxaline rings have their origins in the indole and amino groups of tryptophan, respectively.

Echinomycin↗

PubMedDate not supplied

A reproducible method for automated extraction of brain volumes from 3D human head MR images.

An automated method for extracting brain volumes from three commonly acquired three-dimensional (3D) MR images (proton density, T1 weighted, and T2-weighted) of the human head is described. The procedure is divided into four levels: preprocessing, segmentation, scalp removal, and postprocessing. A user-provided reference point is the sole operator-dependent input required. The method's parameters were first optimized and then fixed and applied to 30 repeat data sets from 15 normal older adult subjects to investigate its reproducibility. Percent differences between total brain volumes (TBVs) for the subjects' repeated data sets ranged from .5% to 2.2%. We conclude that the method is both robust and reproducible and has the potential for wide application.

Aged↗

PubMedDate not supplied

Application of high field localised in vivo 1H MRS to study biochemical changes in the thiamin deficient rat brain under glucose load.

In vivo, volume-selected 1H NMR spectroscopy employing the SPACE technique was used to monitor biochemical changes in the thiamin deficient rat brain in response to glucose loading. The concentrations of brain N-acetylaspartate, glutamate/glutamine/gamma-aminobutyric acid, lactate and glucose differed significantly from those of control animals. The results are consistent with a metabolic block at the reaction catalyzed by the thiamin dependent enzyme alpha-keto glutarate dehydrogenase soon after the onset of neurological symptoms of thiamin deficiency, and a further block at pyruvate dehydrogenase arising late in the course of thiamin deficiency.

Acidosis, Lactic↗

PubMedDate not supplied

In vivo localized 1H spectroscopy of the rat eye at 7 T: preliminary studies.

Preliminary in vivo proton spectroscopic studies of the posterior chamber of the rat eye have been undertaken at 7 T. The Spatial and Chemical shift encoded Excitation (SPACE) localization sequence was used to acquire signals from 10 microliter voxels and demonstrate the presence of metabolites associated with the vitreous humor, lens, retina, and the optic nerve. Localized T2 and T1 measurements of water in the vitreous humor indicate a relatively fluid environment. Susceptibility maps are used to demonstrate the difficulties of in vivo spectroscopic investigations in the anterior regions of the eye. Comments are made concerning the implications for spectral resolution in these regions.

Animals↗