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Biomedical subjects

C T Moonen

Publications and source records attributed to C T Moonen.

At least 73 records · Page 4Linked to original sources

In vivo measurement of cerebral oxygen consumption and blood flow using 17O magnetic resonance imaging.

We used 17O NMR imaging techniques to measure the H2(17)O concentration in a 0.8-ml voxel in the cat brain following injection of an arterial bolus of enriched H2(17)O and during inhalation of enriched 17O2. We also measured the H2(17)O concentration in arterial blood during 17O2 inhalation. The data from the first measurement were used to calculate the blood flow in the voxel. The data from all three measurements were combined to calculate the oxygen consumption in the voxel. The values of cerebral blood flow and oxygen consumption calculated with 17O NMR techniques agree reasonably well with values calculated for a similar region of the cat brain using autoradiographic techniques.

Administration, Inhalation↗

Echo-planar time course MRI of cat brain oxygenation changes.

When deoxygenated, blood behaves as an effective susceptibility contrast agent. Changes in brain oxygenation can be monitored using gradient-echo echo-planar imaging. With this technique, difference images also demonstrate that blood oxygenation is increased during periods of recovery from respiratory challenge.

Animals↗

Biotransformation of 2-fluoroaniline in rats studied by in vivo 19F NMR.

The present study describes results from an in vivo 19F NMR study on rats exposed to the xenobiotic compound 2-fluoroaniline. Qualitative pharmacokinetics and the biotransformation of 2-fluoroaniline were studied after exposure to 50 mg/kg body wt 2-fluoroaniline. Accumulation and elimination of the parent compound in and from the liver of exposed animals were readily observed. Metabolites formed in the liver were shown to be efficiently excreted from the liver, as the amount of metabolites in this organ was always less than 10% of the maximum amount of the parent compound observed. In the bladder, rapid accumulation of 2-fluoroaniline-derived metabolites was detected. The metabolite pattern was shown to change in time, with the parent compound being dominantly present during the first hours of exposure. N-acetylated products (4-acetamido-3-fluorophenyl sulphate and 4-acetamido-3-fluorophenyl glucuronide) were observed to accumulate more slowly in the bladder than the non-acetylated products (4-amino-3-fluorophenyl sulphate and 4-amino-3-fluorophenyl glucuronide). Urine metabolite patterns obtained from the bladder in vivo were compared to those obtained during metabolic cage experiments.

Administration, Oral↗

Functional magnetic resonance imaging in medicine and physiology.

Magnetic resonance imaging (MRI) is a well-established diagnostic tool that provides detailed information about macroscopic structure and anatomy. Recent advances in MRI allow the noninvasive spatial evaluation of various biophysical and biochemical processes in living systems. Specifically, the motion of water can be measured in processes such as vascular flow, capillary flow, diffusion, and exchange. In addition, the concentrations of various metabolites can be determined for the assessment of regional regulation of metabolism. Examples are given that demonstrate the use of functional MRI for clinical and research purposes. This development adds a new dimension to the application of magnetic resonance to medicine and physiology.

Animals↗

In vivo NMR diffusion spectroscopy: 31P application to phosphorus metabolites in muscle.

Apparent diffusion coefficients (Da) of individual metabolites can be studied in vivo by diffusion NMR spectroscopy using an echo sequence sensitized to molecular motion. The methods are based on the echo attenuation due to phase dispersion resulting from incoherent displacement during the diffusion time. As the displacement of metabolites by diffusion in vivo can be affected by compartment size, temperature, adsorption processes, etc., the presented methods are potentially useful in studying such phenomena in vivo. Here, the methods are applied to phosphocreatine in the rat quadriceps muscle. It is demonstrated that the displacement of phosphocreatine resembles free diffusion for short diffusion times but becomes limited as a result of boundaries due to compartmentation for longer diffusion times. The limit of the displacement indicates an apparent average size of 44 microns of the compartment in the direction of the diffusion gradient. As the gradient was applied approximately parallel (angle less than 25 degrees) to the muscle fiber, this result indicates that phosphocreatine moves freely in the cytosol but is limited by the boundaries of the muscle cells. Error analyses are performed with regard to motion artifacts and gradient performance. The methods were tested extensively for distilled water and free metabolites.

Animals↗

Single-shot localized echo-planar imaging (STEAM-EPI) at 4.7 tesla.

The resolution and homogeneity limitations of echo-planar imaging (EPI) are overcome by zoom imaging of an easily shimmed localized volume. Use of the stimulated echo enables single-shot localization. In vivo 0.5-mm resolution EPI images of selected regions of a cat brain at 4.7 T are presented.

Animals↗

Proton magnetic resonance spectroscopy of small regions (1 mL) localized inside superficial human tumors. A clinical feasibility study.

It is demonstrated that the stimulated echo technique for proton magnetic resonance spectroscopy (MRS) can be used to study metabolites in volumes of interest (VOIs) as small as 1 mL localized within superficial human tumors. Access to these small VOIs is important for characterization of tissue regions within a tumor, before, during and after treatment. Spectral appearance resembles that from studies on extracts, and cell suspensions and perfused cells of several tumor types. For the first time proton MRS was used to study cancer treatment in vivo in humans, for a case of radiation treatment of squamous cell carcinoma. No spectral evidence of changed metabolism prior to reduction in tumor size was found. However, after the first period of radiation (39 Gy, 4 weeks), complete disappearance of the metabolite resonances from the spectrum was observed, while a considerable mass still remained, suggesting effective cell destruction upon treatment. Needle aspiration cytology of this mass showed absence of malignant cells, supporting this result.

Carcinoma, Squamous Cell↗

Metabolism of human gliomas: assessment with H-1 MR spectroscopy and F-18 fluorodeoxyglucose PET.

Localized hydrogen-1 magnetic resonance (MR) spectroscopy and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) were employed to obtain metabolic information from intracranial gliomas. Advantages and difficulties associated with comparison of results from the two modalities were realized. Forty patients were studied with H-1 MR spectroscopy. MR signal intensities from lactate, N-acetylaspartate (NAA), choline, and creatine from a volume of interest containing the tumor and a contralateral volume were obtained and evaluated. NAA signal intensities were generally decreased in the tumor spectra, and choline signal intensities were elevated. H-1 MR spectroscopy was unsuccessful in eight patients, and FDG PET scans were not obtained in four of the patients with successful MR spectroscopic examinations. Lactate signal intensity was detected in 10 of the 28 patients who had successful H-1 MR spectroscopic and FDG PET studies. Lactate signal intensities were observed in lesions shown at FDG PET to be hypermetabolic, as well as in lesions found to be hypometabolic.

Adult↗

High field localized proton spectroscopy in small volumes: greatly improved localization and shimming using shielded strong gradients.

The availability of shielded gradients facilitates accurate single-voxel spectroscopy. Exact localization (90-99%) of volumes as small as 2 x 2 x 2 mm is demonstrated using a modified stimulated echo sequence. Strong gradient pulses (up to 200 mT/m) are employed to clear the stimulated echo of unwanted magnetization, enabling superior (single-scan) shimming of the selected volume. In vivo and in vitro proton NMR results at 4.7 T are presented.

Animals↗

Comparison of single-shot localization methods (STEAM and PRESS) for in vivo proton NMR spectroscopy.

Two single-shot localization techniques, STEAM and PRESS, are analyzed with regard to specifications for in vivo localized proton NMR. In particular, attention is paid to optimum signal intensity per unit volume, sensitivity to motion and diffusion, shortest attainable echo time, water suppression and editing possibilities. Experimental results are shown for cat brain at 4.7 T and human brain at 1.5 T. Both STEAM and PRESS are highly effective localization methods. For long echo times, PRESS is the method of choice, because it offers a factor of two gain in signal intensity. In addition, the method is less sensitive to motion and diffusion, and not susceptible to multiple-quantum effects. STEAM offers advantages for observation of (coupled) metabolites with short T2, because (a) shorter TEs can be attained and (b) effective water suppression sequences can be implemented without penalty in echo time. Differences relating to editing possibilities and B1 dependence, possibly important in choosing a method, are discussed.

Animals↗

Timing of the onset of changes in renal energetics in relation to blood pressure and glomerular filtration in haemorrhagic hypotension in the rat.

The timing and circumstances of changes in renal energetics during the gradual induction of haemorrhagic hypotension were studied in anaesthetised rats by phosphorus-31 nuclear magnetic resonance. Animals were bled at a constant rate of 0.1 ml/min via the femoral artery. Whenever changes in renal energetics were seen, a similar pattern was observed. A decrease in adenosine triphosphate occurred rapidly and was always associated with accumulation of inorganic phosphate and tissue acidosis. Profound oliguria, reflecting a markedly decreased rate of glomerular filtration preceded the changes in metabolite levels. Such a fall in glomerular filtration rate and consequently in the energy requirement for tubular reabsorption could be viewed as a mechanism by which energy demands of the kidney are reduced before a critical limitation of energy supply is reached. During uncomplicated haemorrhage in Wistar rats, mean arterial pressures as low as 25-40 mm Hg were reached before changes in renal energetics developed. In contrast, spontaneously hypertensive rates subjected to uncomplicated haemorrhage, and Wistar rats subjected to haemorrhage during concurrent stimulation of the ipsilateral sciatic nerve, developed changes in renal energetics at higher and more variable blood pressures and in response to the withdrawal of lesser but more variable quantities of blood. The sudden onset and severe degree of energy depletion at varying blood pressures during bleeding and its more ready occurrence in animals in which sympathetic nervous activity could be expected to be increased, suggests that sudden renal vasoconstriction is responsible for the unpredictable occurrence of tubular ischaemia in haemorrhagic hypotension.

Adenosine Triphosphate↗

The noninvasive determination of linoleic acid content of human adipose tissue by natural abundance carbon-13 nuclear magnetic resonance.

A new method to assess noninvasively the proportionate storage of poly- and mono-unsaturated fatty acids in human adipose tissue is described. The method is based on in vivo natural abundance 13C NMR at 1.9 T using a TMR 32/200. Data were acquired with a concentric coil system placed below subcutaneous adipose tissue of the calf or the lower arm. Continuous single-frequency decoupling was used to optimize the signal in the spectral region of interest and minimize potential heating effects. Only adipose triglycerides contributed significantly to the resonance intensities. Typical linewidths for the in vivo 13C resonances were 10-14 Hz resulting in excellent resolution in the region of the unsaturated carbons. Signal-to-noise ratios for the resonance at 128.4 ppm (due to carbon atoms of polyunsaturated fatty acids) were typically 50-90 in 8 min using 0.25s repetition time. The relative storage of polyunsaturated fatty acids was determined by comparing the peak intensity at 128.4 ppm with the intensities of the peaks due to the carbonyl, the glycerol, or the main methyl carbons. High-resolution in vitro NMR of adipose biopsies and various mixtures of triglycerides studied with the in vivo NMR protocols provided further evidence that the described in vivo NMR methods allowed precise information on the relative storage of linoleic acid, the main constituent of the pool of polyunsaturated fatty acids. Conventional gas chromatography was performed on adipose biopsies of two volunteers and resulted in close agreement with the in vivo NMR methods. The average polyunsaturated fatty acid concentration in adipose tissue in seven healthy volunteers was 19.83 mol% +/- 1.74 (SD) as determined by in vivo NMR, consistent with conventional studies based on gas chromatography of biopsied material. Preliminary data on three cystic fibrosis patients showed a decreased polyunsaturated fatty acid concentration of 13.12 mol% +/- 2.73 (SD). The high accuracy of this method and its noninvasive character should be especially valuable in clinical research and diagnosis as repetitive adipose biopsies can be avoided.

Adipose Tissue↗

Adipose tissue abnormalities in cystic fibrosis: noninvasive determination of mono- and polyunsaturated fatty acids by carbon-13 topical magnetic resonance spectroscopy.

Natural abundance in vivo carbon-13 topical magnetic resonance (TMR) spectroscopy was used to assess human adipose tissue stores of essential (polyunsaturated) fatty acids. TMR spectra were obtained from 17 normal volunteers and nine cystic fibrosis patients using an Oxford TMR-32 with a surface coil that sampled tissue less than 1 cm below the surface of an extremity. Spectra were taken of lower leg adipose tissue. Polyunsaturated fatty acid content was determined by comparing peak heights of the polyunsaturated peak (internal unsaturated carbons, 128 ppm) to C-1 carboxyl groups (173 ppm). Monounsaturated fatty acid content was determined by subtracting the polyunsaturated peak from the peak observed for all unsaturated carbons (external unsaturated carbon, 130 ppm) and dividing this ratio by the carboxyl peak. In vivo TMR of normal volunteers resulted in observed polyunsaturated fatty acid content of 17.8 +/- 2.1% and a monounsaturated content of 44.8 +/- 3.8%. The polyunsaturated and monounsaturated fatty acid content of adipose tissue from the cystic fibrosis patients was 15.0 +/- 2.0% (p less than 0.005 versus normal volunteers) and 47.8 +/- 6.5% (NS), respectively. One cystic fibrosis patient without fat malabsorption had decreased adipose polyunsaturates, whereas another patient on high calorie gastrostomy feeds had normal levels. Carbon-13 TMR spectroscopy is a sensitive, noninvasive technique for determining essential fatty acid status in subcutaneous adipose tissue of patients with cystic fibrosis.

Adipose Tissue↗

23Na rotating frame imaging in the perfused rabbit heart using separate transmitter and receiver coils.

One-dimensional spatial localization of sodium absorption in the perfused rabbit heart was obtained using 23Na rotating frame imaging. A Dadok-type coil was used as the receiver and a circular surface coil as the transmitter allowing regularly shaped slices and homogeneous reception sensitivity. The short time of spatial labeling in this technique results in minimal intensity losses due to relaxation processes.

Animals↗

A comparative carbon-13, nitrogen-15, and phosphorus-31 nuclear magnetic resonance study on the flavodoxins from Clostridium MP, Megasphaera elsdenii, and Azotobacter vinelandii.

The flavodoxins from Megasphaera elsdenii, Clostridium MP, and Azotobacter vinelandii were studied by 13C, 15N, and 31P NMR techniques by using various selectivity enriched oxidized riboflavin 5'-phosphate (FMN) derivatives. It is shown that the pi electron distribution in protein-bound flavin differs from that of free flavin and depends also on the apoflavoprotein used. In the oxidized state Clostridium MP and M. elsdenii flavodoxins are very similar with respect to specific hydrogen bond interaction between FMN and the apoprotein and the electronic structure of flavin. A. vinelandii flavodoxin differs from these flavodoxins in both respects, but it also differs from Desulfovibrio vulgaris flavodoxin. The similarities between A. vinelandii and D. vulgaris flavodoxins are greater than the similarities with the other two flavodoxins. The differences in the pi electron distribution in the FMN of reduced flavodoxins from A. vinelandii and D. vulgaris are even greater, but the hydrogen bond patterns between the reduced flavins and the apoflavodoxins are very similar. In the reduced state all flavodoxins studied contain an ionized prosthetic group and the isoalloxazine ring is in a planar conformation. The results are compared with existing three-dimensional data and discussed with respect to the various possible mesomeric structures in protein-bound FMN. The results are also discussed in light of the proposed hypothesis that specific hydrogen bonding to the protein-bound flavin determines the specific biological activity of a particular flavoprotein.

Azotobacter↗