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Biomedical subjects

J C Gore

Publications and source records attributed to J C Gore.

At least 145 records · Page 8Linked to original sources

NMR determination of myocardial pH in vivo: separation of tissue inorganic phosphate from blood 2,3-DPG.

Phosphorus NMR can measure myocardial tissue pH from the chemical shift of inorganic phosphate (Pi) in isolated buffer-perfused hearts, but in vivo the Pi peak originating from the myocardium is obscured by the resonance of 2,3-diphosphoglycerate (DPG) in the blood, making pH difficult to determine. Taking advantage of the fact that most of the interfering DPG is within the cardiac chambers and is rapidly flowing out of the sensitive volume of our coil, we developed a pulse sequence which would separate myocardial Pi signal from interfering DPG. We tested this method on a flow phantom and in living rat heart, using exogenous glycerol phosphate as a blood-pool marker. The results indicated that signal from moving and nonmoving substances could be separated, and derived values for myocardial pH and PCr/Pi ratio were consistent with previous estimates. This method should be useful for studying myocardial acid-base physiology with NMR.

2,3-Diphosphoglycerate↗

Studies of restricted diffusion in heterogeneous media containing variations in susceptibility.

Measurements of water self-diffusion in heterogeneous media by pulsed gradient spin-echo methods depend on the precise choice of experimental parameters. This variation may reflect the presence of restricted or anisotropic diffusion, or the presence of intrinsic magnetic field gradients. In experiments at 2.0 T, restricted diffusion effects have been demonstrated in freshly excised tissues with an effective barrier radius of order 10 microns. In samples with intrinsic susceptibility variations such as tissues or gels containing dispersions of iron oxide particles, the reduction of apparent diffusion coefficient with diffusion interval can be used to estimate the degree of heterogeneity of the magnetic field in the sample. The implications of these effects for diffusion-weighted MRI as well as their use to derive novel tissue parameters are discussed.

Acrylic Resins↗

On the relative importance of paramagnetic relaxation and diffusion-mediated susceptibility losses in tissues.

Susceptibility agents such as dysprosium may reduce the apparent T2 of a tissue by inducing magnetic field gradients so that diffusion of water molecules causes dephasing of the transverse magnetization. Gadolinium has a susceptibility that is about 30% lower than dysprosium, so that diffusion losses are expected to be only half as big, but it also may produce paramagnetic relaxation by dipolar interactions. The relative importance of these two processes is dependent on several parameters, including the metal concentration, pulse sequence timing, field strength, and the permeability of tissue interfaces to water exchange. The conditions under which exchange-mediated dipolar interactions are less important than diffusion losses have been derived for capillary borne contrast agents in realistic situations.

Capillary Permeability↗

In vivo quantitation of water content in muscle tissues by NMR imaging.

The water contents of phantoms and muscle tissues were determined directly from NMR imaging experiments. The method involves the calculation of corrected proton densities using relaxation time determinations and suitable calibration phantoms. Comparison with the values obtained from the oven-dry method yields good agreement in normal rat skeletal tissue and in rats injected with red blood cells from sickle cell patients.

Animals↗

Technical variables influencing the detection of acute deep vein thrombosis by magnetic resonance imaging.

To establish which technical variables influence the detection of deep vein thrombosis by magnetic resonance imaging, 2 dogs, 5 normal volunteers and 17 patients were studied using a 1.5 T whole-body system. A sequential slice gradient echo acquisition (TR 25, TE 13, 0 = 30 degrees, 2 NEX, flow compensation rephasing gradients) in the axial plane was found to be optimal for detecting venous thrombosis. Thus, when using appropriate technique, MRI may identify deep venous thrombosis accurately. It may also allow the diagnosis of conditions which may simulate venous thrombosis clinically since the most common of these, ruptured Baker's cyst, cellulitis, muscle tear, hematoma and external venous compression are all readily identified by MRI.

Acute Disease↗

Analysis of vocal tract shape and dimensions using magnetic resonance imaging: vowels.

Magnetic resonance imaging (MRI) techniques were used to gather basic data to apply in computational models of speech articulation. Two experiments were performed. In experiment 1, voice recordings from two male subjects were obtained simultaneously with axial, coronal, or midsagittal MR images of their vocal tracts while they produced the four point vowels. Area functions describing the individual tract shapes were obtained by measurements performed on the MR images. Digital filters derived from these functions were then used to resynthesize the vowel sounds which were compared, both perceptually and acoustically, with the subjects' original recordings. In experiment 2, axial images of the pharyngeal cavity were collected during the production of an ensemble of nine vowels. Plots of cross-sectional area versus the midsagittal width of the tract at different locations within the pharynx and for different vowel productions were used to derive a functional relationship between the two variables. Data from experiment 1 relating midsagittal width to cross-sectional area within the oral cavity were also examined.

Adult↗

Preferential utilization of lactate in neonatal dog brain: in vivo and in vitro proton NMR study.

In vivo proton nuclear magnetic resonance spectroscopy was utilized to determine whether lactate is preferentially utilized as metabolic fuel by the neonatal dog brain. The data showed that during lactate influx, metabolism of lactate could account for most of the fuel needed for oxidative metabolism. The in vivo nuclear magnetic resonance measurements were corroborated by conventional arteriovenous determinations which showed steep decline of arteriovenous difference of glucose and sharp increase in arteriovenous difference of lactate during lactate infusion.

Animals↗

Brain energy state and lactate metabolism during status epilepticus in the neonatal dog: in vivo 31P and 1H nuclear magnetic resonance study.

The purpose of these experiments was to determine whether flurothyl-induced status epilepticus causes progressive decline of brain high-energy phosphates and progressive increase in brain lactate in neonatal dogs who are paralyzed and oxygenated. In vivo 31P nuclear magnetic resonance spectroscopic measurements showed that the fall in brain pH occurred early in the course of seizure. The decline in phosphocreatine was more gradual, i.e. 50% reduction, during the 1st h of seizure. There was no reduction in ATP during the 3 h of status epilepticus. In vivo 1H nuclear magnetic resonance measurement of brain lactate disclosed a steep rise that stabilized by 60 min. Brain and blood lactate were closely related during the initial phase of seizure, suggesting rapid efflux of lactate from brain or systemic production of lactate. Blood lactate exceeded brain lactate after 1 h of status epilepticus. The new steady state for cerebral phosphocreatine and lactate during status epilepticus was achieved much more slowly during neonatal status epilepticus than has been reported during status epilepticus in the adult experimental animal. The lack of change in ATP during 3 h of seizure indicates that brain energy state is not radically altered during prolonged seizure if oxygenation is maintained.

Adenine Nucleotides↗

Quantitative studies of hydrodynamic effects and cross-relaxation in protein solutions and tissues with proton and deuteron longitudinal relaxation times.

Longitudinal relaxation times T1 of water protons were measured in 5% protein solutions at different static magnetic fields (0.47, 2, and 7 T), for proteins with molecular weight ranging between 1.4 and 480 kDa and in solvents of varying degrees of deuteration. T1 values were also obtained for rat liver soaked with Krebs-Ringer solutions of varying degrees of deuteration at the above fields. For the samples containing D2O, T1 for deuterium was also measured at fields 2 and 7 T. The deuterium measurements were used to estimate water rotational correlation times which were in turn used to estimate the contribution of so-called "hydrodynamic effects" of macromolecules to proton relaxation. The proton relaxation rates at full deuteration were compared with those in protonated solvent (water) to obtain a second, direct measurement of this effect. Both measurements provide quantitation of the hydrodynamic effects, free from the contributions of other effects that are transparent to deuteration, and results from both measurements agree with each other reasonably well. The cross-relaxation rate between solute and solvent protons, and the contribution of paramagnetic impurities in the samples were also obtained from the proton T1 studies. The experimental results show that the hydrodynamic effects (intramolecular and intermolecular water-water interactions) are about the same magnitude in all the proteins studied as well as in rat liver. However, the cross-relaxation rate generally increases with increasing protein molecular weight. Measurements in soaked rat liver indicate that the cross-relaxation rate per unit mass of solute is much higher in tissues than in simple solutions of proteins of similar mean molecular weight. The results challenge the prevailing concept that the relaxation properties of biological tissues may be treated as a simple superposition of the properties of their constituents.

Animals↗

Measurement of tissue blood flow using intravascular relaxation agents and magnetic resonance imaging.

Simple concepts of indicator-dilution techniques are described, and the theoretical basis of measuring regional blood flow via transit time measurements of a blood pool marker is discussed. Using very fast imaging of the effects of an appropriate and efficient relaxation agent, the concentration-time curve of the agent can be quantified. Preliminary measurements of the transit of superparamagnetic iron oxide through a rat brain at 2.0 T have been obtained. There are problems, however, in relating the NMR signal change to the tissue concentration of an intravascular relaxation agent when there is not fast exchange of the tissue water with the water in the vasculature, or when the precise efficacy of the agent varies with the geometrical arrangement of the capillaries. Studies of the effects of superparamagnetic iron oxide particles in different media confirm that the in vivo efficacy varies among different tissues, which complicates their use as blood flow markers.

Animals↗

Dose-response curves for Fricke-infused agarose gels as obtained by nuclear magnetic resonance.

The radiation-response characteristics of agarose gels prepared with Fricke dosemeter solution have been studied. The response mechanism is an increase in the NMR longitudinal relaxation rate of protons caused by ferric ions. It has been observed that: (i) oxygen saturation assures consistent and maximum sensitivity; (ii) agarose concentrations in the range 1.0-2.0% have no effect upon sensitivity; (iii) the initial G value is 150 Fe3+/100 eV for gels containing 0.5 mM Fe2+ ions; (iv) increasing NMR frequencies only causes a moderate increase in sensitivity; (v) the gel dosemeters are dose rate independent in the range 4.7-24.2 Gy min-1; (vi) sensitivity is pH dependent, being zero at pH 7; (vii) freshly prepared gels are slightly more sensitive than those more than 24 h old; and (ix) the diffusion coefficient for ferric ions in a 1.0% agarose gel containing 0.0125 M H2SO4 is 1.83 x 10(-2) cm2 h-1, and this will require consideration for the NMR imaging of dose distributions.

Dose-Response Relationship, Radiation↗

Pharmacokinetics of superparamagnetic iron-oxide MR contrast agents in the rat.

The in vivo pharmacokinetics and the biodistribution of superparamagnetic iron-oxide particles (AMI25, Advanced Magnetics, Cambridge, MA) were investigated in anesthetized rats. Four different dose concentrations, ranging from 49.8 to 408.9 mumol of Fe (or 2.78-22.84 mg Fe) per kilogram, radiolabeled with 6.0 microCi of 59Fe-AMI25 were injected intravenously into 18 rats. The radioactivity cleared from the circulation with a fast component with a half-life of approximately 10 minutes and a slower component with a half-life of 92 minutes. Both half-lives were independent of the injected dose (ID) in the range of 105.4-408.9 mumol (5.89-22.84 mg) Fe/kg. The relative uptake in the liver, spleen, and kidneys was 57%, 2.9%, and 2.0% of the ID, respectively. At a dose of 52.1 mumol (2.91 mg) of Fe/kg, the relative concentration of iron significantly increased in the liver and decreased in the blood. Within the kidney, autoradiography showed that the iron was selectively taken up by the cortex. In the kidney, a concentration of 0.23 mumol (0.013 mg) Fe/g resulted in a 30% reduction in image intensity in a single echo magnetic resonance image obtained using a spin-echo sequence and an echo time of 70 ms.

Animals↗

A quantitative study of relaxation rate enhancement produced by iron oxide particles in polyacrylamide gels and tissue.

The proton relaxation rate enhancements produced by two types of iron oxide particles, M4125 and AM125 (Advanced Magnetics, Cambridge, MA) designed as potential MR contrast agents, have been measured in polyacrylamide gels and in liver and spleen. The organ uptakes, time courses, and biodistributions of these materials have been measured using radiolabeling. The relaxation rate enhancements produced by these particles have been related to the concentration of iron per gram material at different magnetic field strengths. The relaxation rates increase linearly as a function of concentration at field strengths varying from 0.15 to 7 T. The relaxation effects of these particles in tissue are significantly different from the behavior in vitro. These results suggest that several different mechanisms contribute to relaxation effects in the presence of iron oxide particles and they depend strongly on the way the particles are sequestered. Diffusion effects for a specified TE may be enhanced using gradient or single-spin echoes rather than multiple echoes. AM125 is significantly more effective as a relaxation agent than paramagnetic metal ions only at relatively high fields, while M4125 is less effective per unit concentration.

Acrylic Resins↗

NMR relaxation of water in hydrogel polymers: a model for tissue.

The NMR relaxation rates of a class of hydrated polymers (hydrogels) have been investigated over a wide range of frequencies (0.01 to 60 MHz) and compositions. The gels comprise long chains of polytetramethylene oxide diol crosslinked by copolymers of dimethylacrylamide and methylmethacrylate. The longitudinal relaxation rate dispersion curves of these materials are very similar to those shown by human tissues and they can be altered in flexible fashion by changing the polymer content. By substitution of the water by deuterium oxide, the contribution of intermolecular cross-relaxation effects has been shown to account for two-thirds the total water relaxation rate. With their close similarity to tissue relaxation behavior, hydrogels of differing compositions are particularly well-suited to MRI phantoms and test objects.

Hydrogel, Polyethylene Glycol Dimethacrylate↗

An analysis of magnetic cross-relaxation between water and methylene protons in a model system.

Experiments have been performed to demonstrate and quantify cross-relaxation between water and methylene resonances in a simple model system. Inversion recovery experiments on aqueous solutions of polyethylene glycol produce a transient nuclear Overhauser effect that alters the recovery of the methylene resonance. The relevant equations and parameters that describe this effect are identified and their values are explicitly quantified by analyzing the experimental results. It is shown that cross-relaxation is measurable and significant in this system even though there are no strong hydrophilic interactions available to immobilize water. In studies of dog bile, the water and lipid resonances behave in a qualitatively similar fashion, lending support to the contention that cross-relaxation cannot be neglected in solutions of biological macromolecules.

Animals↗

The influence of pulse sequence on the relaxation effects of superparamagnetic iron oxide contrast agents.

The effects of different pulse sequences and timing parameters on the increase in transverse relaxation rate produced by superparamagnetic iron oxide particles have been studied. Gradient-echo, single spin-echo, and multiple-echo images recorded at 2.0 T were used to evaluate the reduction in signal intensity per unit concentration of iron oxide for different echo times and in different media. For the same echo time, gradient-echo sequences were found to be more than twice as sensitive to the effects of the agent as single spin-echo imaging sequences, while multiple-echo sequences were much less affected than either. Using measurements of the relative effects on different sequences, the contributions of different relaxation mechanisms have been quantified.

Contrast Media↗

Relative contributions of chemical exchange and other relaxation mechanisms in protein solutions and tissues.

Transverse relaxation times T2 of water protons were measured in 5% protein solutions and soaked rat liver in different static magnetic fields (0.15 to 11 T). Protein molecular weight varied between 1.4 and 480 kDa in solutions of varying degrees of deuteration. The data obtained are analyzed in terms of a model system consisting of three phases of different relaxation characteristics: protein protons, hydration layer water protons, and bulk water protons. The contributions to relaxation due to hydrodynamic effects on water protons, cross relaxation between the hydration layer water protons and the protein protons, and chemical exchange between the hydration layer water protons and the bulk water protons are separately estimated. The experimental results indicate that the "hydrodynamic interactions" are about the same magnitude in rat liver and all the proteins studied, but the contribution of the cross relaxation differs by several orders in different protein systems. Fast chemical exchange between the hydration layer water and the bulk water causes considerable shortening of T2 at high magnetic fields for all the protein solutions and rat tissue studied. Selected samples were studied at different temperatures (213-318 K) and with different intervals in the CPMG sequence. The rates of chemical exchange and fractional populations of different phases are determined, and the results obtained provide support for the model in which fast exchange among the different water phases is an important feature of the overall relaxation behavior.

Animals↗