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R H Griffey

Publications and source records attributed to R H Griffey.

At least 55 records · Page 3Linked to original sources
PubMed1991

Three-dimensional gadolinium-enhanced MR imaging of the breast: pulse sequence with fat suppression and magnetization transfer contrast. Work in progress.

A pulse sequence with magnetization transfer contrast and fat suppression was used in three-dimensional magnetic resonance imaging of the breast. Two healthy volunteers, one person with silicone implants, and 12 patients with clinical and/or mammographic findings suspicious for malignancy were evaluated prior to and following infusion of gadopentetate dimeglumine. Imaging time was approximately 7 minutes for each set of data (128 sections). Final voxel dimensions ranged from 1.4 x 0.8 x 0.8 mm to 1.6 x 0.9 x 0.9 mm. All carcinomas, including ductal and lobular types, were enhanced before and after infusion of contrast medium. Multifocal carcinoma and inflammatory carcinoma could be clearly visualized. Enhancement was not evident in patients with fat necrosis (n = 1) or scar (n = 1). Fibrocystic changes in one patient were visible as areas of increased signal intensity on preinfusion images. Resolution and contrast of MR images obtained with this pulse sequence appeared to be improved over that achieved with conventional breast MR imaging techniques. This method has the potential to supplement conventional diagnostic methods in the evaluation of breast disease.

Adult↗
PubMed1991

Effect of hypoxia on cerebral metabolites measured by proton nuclear magnetic resonance spectroscopy in rats.

Proton nuclear magnetic resonance spectroscopy is a unique method to monitor noninvasively the concentrations of cerebral metabolites. N-Acetyl-L-aspartate, the concentration of which is assumed to be stable during hypoxia, has been used to form ratios with lactate. To determine the stability of the signal from N-acetyl-L-aspartate, we used a model of graded hypoxia in rats to monitor the percentage changes from baseline of the peak heights for lactate, lipids, and N-acetyl-L-aspartate. Anesthetized adult rats were exposed sequentially to 15% and 10% O2 while proton nuclear magnetic resonance spectra were collected with a surface coil in a 7-T 89-mm-bore spectrometer. Brain lactate concentration was either increased by feeding or infusion of glucose (n = 9) or lowered by fasting (n = 7). After death the brains were removed and frozen, and the water- and lipid-soluble compounds were extracted to identify the origin of the signals. We analyzed the data both as the percentage change from baseline for heights of the lactate (1.33 ppm), lipids (1.5 ppm), and N-acetyl-L-aspartate (2.02 ppm) peaks and as the ratios of heights of the 1.33 and 2.02 and the 1.5 and 2.02 ppm peaks. Both hypoxic episodes caused a 45% decrease from baseline in the 2.02 ppm peak. During the second hypoxic episode, the 1.33:2.02 ppm peak height ratio increased significantly in hyperglycemic rats (p less than 0.05) but was unchanged in hypoglycemic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Depletion of high-energy phosphates in the central nervous system of patients with systemic lupus erythematosus, as determined by phosphorus-31 nuclear magnetic resonance spectroscopy.

Systemic lupus erythematosus (SLE) can produce profound disturbances in the central nervous system, characterized by encephalopathy, focal neurologic deficits, cerebral infarction, psychosis, and seizures. We used 31P nuclear magnetic resonance (NMR) spectroscopy to determine the in vivo levels of high-energy phosphates in the central nervous system of 10 patients with SLE and 10 age-matched normal controls. 31P NMR spectroscopy was performed on a 1.5-Tesla unit equipped with a dual-tuned 1H-31P surface coil and a software-directed DRESS (depth resolved surface coil spectroscopy) pulse sequence. This procedure detected ADP, ATP, sugar phosphates, phosphocreatine (PCr), inorganic phosphate, phosphomonoesters, and phosphodiesters in the brain tissue of all study subjects. Levels of ATP in the deep white matter of 10 SLE patients were significantly decreased compared with the levels in 10 normal controls, as quantitated by the ratio of ATP:ATP + ADP (mean +/- SD 0.81 +/- 0.11 versus 0.91 +/- 0.05; P less than 0.02). In a subgroup of 4 patients, PCr levels were decreased to a greater extent than the ATP levels. NMR spectroscopic alterations were not related to obvious anatomic lesions, as determined by standard cranial proton magnetic resonance imaging. In 4 SLE patients with markedly abnormal 31P NMR spectra, treatment with prednisone (80 mg/day) normalized the levels of ATP and PCr. Restoration of a normal 31P profile was accompanied by an obvious improvement in the patients' mental status and clinical symptoms. 31P NMR spectroscopy is a powerful new technique for monitoring high-energy phosphate metabolism, and may be particularly useful for characterizing central nervous system disease in patients with neuropsychiatric SLE.

Adenosine Diphosphate↗
PubMed1990

Triple-quantum-coherence-filtered imaging of sodium ions in vivo at 4.7 tesla.

The tissue distribution of sodium ions which generate triple-quantum coherence (TQC) in vivo is determined from images. A technique for filtering conventional sodium images, so that signal is obtained only from sodium ions which have a correlation time appropriate for producing TQC, is described. The utility of TQC-filtered sodium images is demonstrated in a study of tumors implanted in a nude rat model, where the intensity of the TQC signal from sodium ions in the growing margin of the tumor is observed to be 200-250% greater than that from surrounding tissue.

Animals↗
PubMed1990

Velocity imaging of slow coherent flows using stimulated echoes.

We measure the velocity distribution of slow fluid flow in model systems using stimulated echoes and velocity phase encoding. We show velocity images of slow coherent flow with velocities of the order of 0.1 mm/s which is slower than can be obtained by the bolus-tracking method. The eddy current errors were compensated by phase correction.

Humans↗
PubMed1989

Senescence-induced alteration in cell surface carbohydrates correlated using proton NMR spectroscopy and a lectin-based affinity-binding assay.

Changes in the cell surface oligosaccharides in human fetal lung fibroblasts (IMR-90) are studied as the cells progress to senescence using nuclear magnetic resonance spectroscopy (NMR) and a biochemical assay. A lectin-based affinity-binding technique is used which measures the organization of carbohydrates on the cell surface. Proton NMR studies of the water in samples of frozen cell suspensions of young and old cells provide information on the local dynamics of the cell surface by monitoring the motion of bound water. Changes in the lectin binding density and affinity class distribution correlate with a decrease in the water proton linewidth in frozen cells. These observations reflect alterations in the conformation or structure of the cell surface oligosaccharides and local constituent water.

Butanols↗
PubMed1989

Myocardial creatine kinase exchange rates and 31P NMR relaxation rates in intact pigs.

In this study, we used 31P NMR to investigate the relationship between cardiac workload and creatine kinase flux in intact pigs. NMR measurements were performed on anesthetized miniature swine in which a surface coil was surgically implanted on the surface of the left ventricle. Cardiac workload was varied by infusion of norepinephrine. Phosphate exchange between creatine phosphate and ATP was measured by a combined saturation transfer, saturation recovery pulse sequence. Exchange measurements showed that creatine kinase flux and concentrations of PCr and ATP were independent of workload for a 2.5-fold range of cardiac rate-pressure products. It appears that, if creatine kinase flux is coupled to work load, the pig heart operates in a regime where small changes in metabolite concentrations or creatine kinase flux are sufficient to maintain elevated workloads. Exchange and relaxation measurements, at 2.0 and 4.7 T, yielded T1 relaxation times for creatine phosphate and ATP which are longer than most reported values. Analysis of the T1 data indicates that chemical-shift anisotropy is a plausible mechanism for a portion of the spin-lattice relaxation rate at high field strengths.

Animals↗
PubMed1989

Glucose inhibition of human fibroblast proliferation and response to growth factors is prevented by inhibitors of aldose reductase.

Diabetes mellitus is associated with premature senescence of cultured dermal fibroblasts. The present study investigated the effect of elevated glucose concentrations on cultured human fibroblasts from normal donors. Mean population doubling times, population doublings until senescence, saturation density at confluence (cells/cm2), tritiated thymidine incorporation, and response to platelet-derived growth factor (PDGF) were inhibited with the increasing glucose concentrations (11.0, 22, 44, or 55 mM glucose) (P less than 0.05). Replicative life span was markedly diminished by multiple passages in high glucose medium (5.5 mM glucose: 62.4 +/- 7.9 population doublings; 22 mM glucose: 22.8 +/- 3.4 population doublings: P less than 0.05). Aldose reductase activity was present in the cultured fibroblasts (3.9 +/- 0.5 nmol/min per mg protein), and inhibitors of aldose reductase, including sorbinil (10(-4) M--10(-6) M) and tolrestat (10(-6) M--10(-8) M), completely prevented glucose-mediated inhibition of fibroblast proliferation, restored the response to PDGF, and allowed a normal replicative life span. Myo-inositol (11 microM--5.5 mM) also reversed the adverse effects of glucose. These in vitro data demonstrate that elevated concentrations of glucose inhibit cell growth and promote premature senescence, effects which can be prevented with inhibitors of aldose reductase or supplemental myo-inositol. These aldose reductase-related effects may explain the impaired growth and premature senescence of cultured connective tissue from diabetic patients.

Aldehyde Reductase↗
PubMed1989

Tumor characterization using unconventional MR modalities.

This article reviews many of the promising new magnetic resonance (MR) modalities for the characterization of tumor structure and metabolism, excluding 31P magnetic resonance spectroscopy (MRS). The report focuses on recent work with localized proton MRS, MR imaging of diffusion and perfusion, and work on imaging bound pools of sodium ions. The technical problems associated with these methods are discussed, along with the unique information each provides. Many of these techniques have already been used in studies of human disease, or are of sufficient importance that clinical applications are imminent.

Animals↗
PubMed1989

Carbon-13 magnetic resonance spectroscopy. Problems and promise.

Carbon-13 magnetic resonance spectroscopy (13C MRS) is being used to investigate metabolism in the brain, liver, heart, and skeletal muscle of animals. The tricarboxylic acid cycle, glycolysis, gluconeogenesis, hepatic ketogenesis, and metabolism of ethanol are some of the metabolic processes amenable to 13C MRS. Clinical investigation using 13C in humans will become widespread as improvements in sensitivity, localization, enrichment, and decoupling are realized. Carbon-13 MRS offers potential as a new investigative probe into organ physiology.

Animals↗
PubMed1989

Magnetic resonance and computed tomographic imaging in the evaluation of acute neuropsychiatric disease in systemic lupus erythematosus.

Magnetic resonance (MR) imaging and computed tomography (CT) are useful for the evaluation of central nervous system (CNS) lupus. This report describes the use of cranial MR and CT in 21 patients with systemic lupus erythematosus (SLE) with acute neuropsychiatric symptoms manifested by headache, seizures, focal neurological deficits, psychosis, or organic brain syndrome. Computed tomography was found to be insensitive and detected only diffuse atrophy (two cases), cerebral infarct (one case), and intracerebral haemorrhage (one case) in the 21 patients. Cranial MR images obtained with a General Electric 1.5 tesla Signa unit detected labile and fixed areas of increased proton intensity interpreted as focal oedema (eight cases), infarct (10 cases), haemorrhage (one), atrophy (seven), and acute sinusitis (two). Focal oedema was characterised by labile, high intensity lesions in the gray or white matter of the cerebellum, cerebrum, or brain stem, which completely resolved after aggressive corticosteroid treatment. Most high intensity reversible or fixed lesions evident on MR were not apparent on cranial CT images. In several patients sequential MR images were valuable in monitoring the efforts of treatment. Although histological confirmation of the high intensity brain lesions apparent on MR is desirable, prior necropsy studies suggest that pathological confirmation may be difficult owing to the paucity of recognisable brain lesions in patients with CNS lupus. It is concluded that for the evaluation of acute neuropsychiatric SLE MR is useful and provides more information than cranial CT.

Adolescent↗
PubMed1988

Diabetic neuropathy. Structural analysis of nerve hydration by magnetic resonance spectroscopy.

The water content of the sural nerve of diabetic patients was quantitatively defined by magnetic resonance proton imaging as a putative reflection of activity of the aldose-reductase pathway. Thirty-nine patients were evaluated, comparing group A, symptomatic diabetic men with sensory neuropathy; group B, similarly symptomatic diabetic men treated with aldose-reductase inhibition; group C, neurologically asymptomatic diabetic men; and group D, control nondiabetic men. Marked increase in hydration of the sural nerve was seen in more than half of the symptomatic diabetic patients. Two of 11 neurologically asymptomatic diabetics had increased nerve hydration, suggesting a presymptomatic alteration of the nerve. Symptomatic diabetics treated with aldose-reductase inhibitors had normal nerve water levels. Increased level of peripheral nerve water represents a new finding in diabetes mellitus. It seems to be related to aldose-reductase activity, involved in the development of neuropathy, and similar to events that occur in other target tissue in human diabetes.

Adult↗
PubMed1988

Fluorine-19 NMR imaging of glucose metabolism.

Metabolic imaging reflecting glucose metabolism in the glycolytic and aldose reductase sorbitol (ARS) pathways was performed noninvasively in rat using fluorinated glucose analogs, 2-fluoro-2-deoxy-D-glucose (2-FDG) or 3-fluoro-3-deoxy-D-glucose (3-FDG), and fluorine-19 (19F) nuclear magnetic resonance (NMR) imaging. 19F images of 2-FDG-6-phosphate, a main metabolite of 2-FDG in the glycolytic pathway, showed high glucose utilization in the brain, spinal cord, and heart. Images of 3-fluoro-3-deoxy-D-sorbitol (3-FDSL), a main metabolite of 3-FDG in the ARS pathway, demonstrated the heterogeneous nature of the spatial distribution of aldose reductase activities, being highest in the brain and lens. The extremely low toxicity of 3-FDG indicates promise for clinical application of 3-FDG NMR imaging.

Animals↗
PubMed1988

In vivo 13C NMR spectroscopy of the human prostate.

The metabolism of the normal and hyperplastic human and rat prostate differs from that of other tissues in that this organ supports and secretes high concentrations of citrate. During the dedifferentiation process that is characteristic of neoplasia, the ability of the prostate to maintain these high citrate levels is markedly diminished. We undertook a natural abundance 13C NMR study of the human and rat prostate in vitro and the human organ in vivo in order to determine whether the amounts of citrate in the nonmalignant prostate were sufficiently high to be detected. We report here our success at detecting citrate via 13C NMR in all three of these systems.

Adult↗
PubMed1988

Characterization of the carbamino adducts of insulin.

Carbon-13 (13C) nuclear magnetic resonance spectroscopy (NMR) is performed to characterize the formation of carbamino adducts between insulin and (13C) carbon dioxide over a range of pH values in the presence of a physiological concentration (23 mM) of sodium bicarbonate. The peaks from two of the carbamino adducts resonate at higher frequencies than the signal from bicarbonate, at 164.6 and 165.3 ppm, and are attributed to the adducts with the terminal amino groups of phenylalanine B1 and glycine A1. The intensities of these signals vary with the pH, with unique patterns. Over 6% of each terminal amino group exists as the carbamino adduct at the optimum pH values of 7.8 and 8.3. A unique third adduct resonates at 159.3 ppm, and is attributed to lysine B29. This adduct is present on 2% of the insulin molecules at pH 8.2, but has minimal intensity at pH 7.4. No signals from adducts are detected below pH 6.2, where the amino groups exist predominantly in the protonated form. Creation of the adducts is rapid and they are stable for over 4 wk at 37 degrees C. The narrow bandwidth of the resonance of the adduct (4.0-4.5 Hz) relative to the irreversible cyanate adduct is consistent with molecular forms of the carbamino adduct smaller than the 2-Zn-hexamer which is the preponderate form of clinically utilized U-100 insulin (i.e., 100 U/ml).

Animals↗
PubMed1988

F-19 MR imaging of glucose metabolism in the rabbit.

Noninvasive metabolic magnetic resonance (MR) imaging reflecting glucose metabolism in the aldose-reductase-sorbitol (ARS) pathway was performed in the rabbit head; after administration of the fluorinated glucose analogue 3-fluoro-3-deoxy-D-glucose (3FD-glucose), fluorine-19 images were generated. Images of 3FD-glucose showed significant 3FD-glucose uptake by adipose tissue, indicating its buffering effects in case of excess loads of glucose. Images of 3-fluoro-3-deoxy-D-sorbitol (3FD-sorbitol) demonstrated the spatial distribution of aldose reductase activities and significant sorbitol accumulation in the lens. Images of 3-fluoro-3-deoxy-D-fructose (3FD-fructose) showed preferential uptake of fructose by muscle tissue. The extremely low toxicity of 3FD-glucose indicates promise for its clinical application in metabolic imaging.

Aldehyde Reductase↗
PubMed1987

Proton NMR measurements of bacteriophage T4 lysozyme aided by 15N isotopic labeling: structural and dynamic studies of larger proteins.

A strategy for resolution and assignment of single proton resonances in proteins of molecular mass up to at least 40 kDa is presented. This approach is based on 15N (or 13C) labeling of selected residues in a protein. The resonances from protons directly bonded to labeled atoms are detected in a two-dimensional 1H-15N (or 13C) spectrum. The nuclear Overhauser effects from isotopically tagged protons are selectively observed in one-dimensional isotope-directed measurements. Using this approach, we have observed approximately 160 resonances from 15N-bonded protons in the backbone and sidechains of uniformly 15N-labeled T4 lysozyme (molecular mass = 18.7 kDa). Partial proton-deuterium exchange can be used to simplify the 1H-15N spectrum of this protein. These resonances are identified by amino acid class using selective incorporation of 15N-labeled amino acids and are assigned to specific residues by mutational substitution, multiple 15N and 13C labeling, and isotope-directed nuclear Overhauser effect measurements. For example, using a phenyl[15N]alanine-labeled lysozyme variant containing two consecutive phenylalanine residues in an alpha-helical region, we observe an isotope-directed nuclear Overhauser effect from the amide proton of Phe-66 to that of Phe-67.

Deuterium↗