Search PubMed⌕ Search

Biomedical subjects

W J Adams

Publications and source records attributed to W J Adams.

80 records · Page 5Linked to original sources

Simultaneous acquisition of phase-contrast angiograms and stationary-tissue images with Hadamard encoding of flow-induced phase shifts.

A technique for the simultaneous acquisition of three-dimensional phase-contrast angiograms and stationary-tissue images is described. Hadamard multiplexed encoding of flow information permits image acquisition times that are a third shorter than those of previous phase-contrast methods. The encoding scheme described also enables differentiation of flow-induced phase shifts from phase shifts due to resonance offset conditions such as field inhomogeneities and chemical shift. Display strategies that combine this phase information with the flow image are described.

Blood Vessels↗

A method of coronary MR angiography.

Procedures for the in vivo detection of coronary (and pulmonary) vessels using MR angiographic techniques were investigated. The most successful technique used gradient-recalled thin slice acquisitions that were gated to the cardiac cycle. The resulting data sets consist of three spatial dimensions and one time dimension. Acquisition of four dimensions of data proved necessary to obtain useful images of small vessels located on the moving myocardium.

Coronary Vessels↗

Toward an automated analysis system for nuclear magnetic resonance imaging. II. Initial segmentation algorithm.

Image segmentation algorithms based on hierarchical clustering have been developed for analysis of T1 and T2 nuclear magnetic resonance images. Application of these algorithms to simultaneous T1-T2 images of healthy volunteers extracted fundamental tissue types in the brain. These algorithms also were used both to identify the extent of the region of involvement of a subject with a history of a grade 3 astrocytoma of the right frontal lobe of the brain, and to characterize the tissue within the region of involvement. These results suggest that a simple segmentation algorithm can produce reasonable clustering of tissue types within the brain.

Biometry↗

Toward an automated analysis system for nuclear magnetic resonance imaging. I. Efficient pulse sequences for simultaneous T1-T2 imaging.

Simultaneous T1 and T2 images have been obtained using multiple-echo self-normalizing sequences. Differential T1 and T2 discrimination for two of these sequences, double saturation recovery and inversion-saturation recovery, have been explored in detail. The inversion-saturation recovery sequence exhibits T1 discrimination comparable to, and in many cases better than, that of optimal T1 weighted conventional pulse sequences, but is poor for T2 imaging. The double saturation recovery sequence yields comparable tissue discrimination for T1 and T2 imaging, but is poor compared to optimal T1 weighted and T2 weighted conventional pulse sequences. Simultaneous T1 and T2 images represent quantitative maps of intrinsic tissue properties, and hence form a natural basis for an automated image analysis and tissue classification system.

Brain↗

Mechanistic studies on the metabolic chiral inversion of R-ibuprofen in the rat.

Deuterium labeling techniques and stereoselective GC/MS methodology have been employed to investigate the mechanism by which R-ibuprofen undergoes metabolic chiral inversion in the rat in vivo. Following oral administration of a mixture of R-ibuprofen (7.5 mg kg-1) and R-[ring-2H4; 2-2H]ibuprofen (R-[2H5]ibuprofen) (7.5 mg kg-1) to male Sprague-Dawley rats, the enantiomeric composition and deuterium excess of the drug were determined in serial plasma samples and in pooled urine collected over 10 hr. The results demonstrate that: (i) R-ibuprofen undergoes extensive inversion of configuration to its S antipode in the rat; (ii) chiral inversion of R-[2H5]ibuprofen yields S-[2H4]ibuprofen in a process that involves quantitative loss of the deuterium atom present originally at C-2; (iii) labeling of R-ibuprofen with deuterium at C-2 does not introduce a measurable kinetic deuterium isotope effect on the chiral inversion reaction; and (iv) metabolism of R-[2H5]ibuprofen leads to the appearance in plasma and urine of molecules of R-ibuprofen labeled with 4 atoms of deuterium. On the basis of these findings, a mechanism is proposed for the chiral inversion reaction that invokes the stereoselective formation of the coenzyme A thioester of R-ibuprofen as a key metabolite; conversion of this species to the corresponding enolate tautomer affords a symmetrical intermediate through which racemization of ibuprofen occurs in vivo.

Animals↗

Studies on the metabolism and chiral inversion of ibuprofen in isolated rat hepatocytes.

The oxidative metabolism and chiral inversion of ibuprofen in freshly isolated rat hepatocytes was studied with the aid of a stereoselective GC/MS assay procedure. Hydroxylation of the isobutyl side chain at the subterminal carbon (to give hydroxyibuprofen) proved to be the major route of metabolism of both R(-)-ibuprofen and S(+)-ibuprofen, while formation of the corresponding diastereoisomeric 2-methylpropionic acid derivatives (carboxyibuprofen) was of minor quantitative importance. Both oxidative pathways were inhibited in the presence of metyrapone, a cytochrome P-450 inhibitor. R(-)-Ibuprofen underwent metabolic chiral inversion to the S(+) enantiomer, whose formation was dependent on incubation time, cell density, and substrate concentration. S(+)-Ibuprofen, on the other hand, was not converted to R(-)-ibuprofen in rat hepatocytes. When cells were incubated with a mixture of unlabeled R(-)-ibuprofen and R(-)-[3,3,3-2H3]ibuprofen, the resultant S(+) enantiomer consisted only of unlabeled and trideutero molecules (formed in the same ratio as the corresponding species of R(-)-ibuprofen), indicating that 2,3-dehydroibuprofen did not serve as the symmetrical intermediate in the chiral inversion reaction. Collectively, these results demonstrate that freshly isolated rat hepatocytes represent a convenient and reproducible in vitro model system for studies on the metabolism and chiral inversion of ibuprofen.

Animals↗