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Biomedical subjects

R G Bryant

Publications and source records attributed to R G Bryant.

At least 55 records · Page 3Linked to original sources

The magnetic field dependence of proton spin relaxation in tissues.

The magnetic field dependence of water-proton relaxation is reported for a simple protein solution, a cross-linked protein solution, and a series of rat tissues, fresh, dried and rehydrated. The shape of the magnetic field dependence associated with water proton relaxation in tissues is accounted for by magnetic dipole-dipole interactions between the mobile water spins and the immobile spin populations of the nonrotating components of the tissue coupling the behavior of the immobilized spin system to that of the mobile water spin system. The effect of this coupling is to impart the field dependence of the relaxation associated with the immobilized spin population to that of the mobile water spins that are observed in most relaxation and imaging experiments.

Animals↗

Water-proton nuclear magnetic relaxation in heterogeneous systems: hydrated lysozyme results.

Spin-lattice relaxation rates of water protons in hydrated immobilized lysozyme are measured as a function of magnetic field strength. The dependence of water relaxation versus hydration is presented from 35 to 55% by weight water content. The water-proton relaxation is directly coupled to that of the protein and the coupling exists in the absence of chemical exchange. A model is applied where relaxation within the two proton phases is coupled through a dipolar cross-relaxation mechanism as well as chemical exchange. The observed amplitudes of the water-proton relaxation profiles scale with the ratio of protein to water protons as well as the protein-proton relaxation rate. The field dependence of the protein-proton spin-lattice relaxation is presented in the presence of D2O where a cross-relaxation coupling is absent. The coupled relaxation model accounts well for the NMR relaxation data as a function of magnetic field strength which is similar to measurements on other heterogeneous systems such as tissues.

Magnetic Resonance Spectroscopy↗

Comparison of agarose and cross-linked protein gels as magnetic resonance imaging phantoms.

Measurements of the magnetic field dependence of spin-lattice relaxation rates and the response of the water-proton signal intensity to off-resonance radio frequency fields show that the commonly used agarose phantom provides a less faithful representation for the magnetic response of tissue than does a cross-linked protein system. The origin of these differences lies in the structure and intramolecular dynamics of the macromolecular system used to make the gel. These distinctions will also cause differences in the magnetic response of the water spin system when paramagnetic relaxation agents or contrast agents are incorporated. Use of a thermally cross-linked bovine serum albumin phantom is suggested.

Animals↗

Hetergeneous tumour response to photodynamic therapy assessed by in vivo localised 31P NMR spectroscopy.

Photodynamic therapy (PDT) is efficacious in the treatment of small malignant lesions when all cells in the tumour receive sufficient drug, oxygen and light to induce a photodynamic effect capable of complete cytotoxicity. In large tumours, only partial effectiveness is observed presumably because of insufficient light penetration into the tissue. The heterogeneity of the metabolic response in mammary tumours following PDT has been followed in vivo using localised phosphorus NMR spectroscopy. Alterations in nucleoside triphosphates (NTP), inorganic phosphate (Pi) and pH within localised regions of the tumour were monitored over 24-48 h following PDT irradiation of the tumour. Reduction of NTP and increases in Pi were observed at 4-6 h after PDT irradiation in all regions of treated tumours. The uppermost regions of the tumours (those nearest the skin surface and exposed to the greatest light fluence) displayed the greatest and most prolonged reduction of NTP and concomitant increase in Pi resulting in necrosis. The metabolite concentrations in tumour regions located towards the base of the tumour returned a near pre-treatment levels by 24-48 h after irradiation. The ability to follow heterogeneous metabolic responses in situ provides one means to assess the degree of metabolic inhibition which subsequently leads to tumour necrosis.

Animals↗

Oxygen consumption and diffusion effects in photodynamic therapy.

Effects of oxygen consumption in photodynamic therapy (PDT) are considered theoretically and experimentally. A mathematical model of the Type II mechanism of photooxidation is used to compute estimates of the rate of therapy-dependent in vivo oxygen depletion resulting from reactions of singlet oxygen (1O2) with intracellular substrate. Calculations indicate that PDT carried out at incident light intensities of 50 mW/cm2 may consume 3O2 at rates as high as 6-9 microM s-1. An approximate model of oxygen diffusion shows that these consumption rates are large enough to decrease the radius of oxygenated cells around an isolated capillary. Thus, during photoirradiation, cells sufficiently remote from the capillary wall may reside at oxygen tensions that are low enough to preclude or minimize 1O2-mediated damage. This effect is more pronounced at higher power densities and accounts for an enhanced therapeutic response in tumors treated with 360 J/cm2 delivered at 50 mW/cm2 compared to the same light dose delivered at 200 mW/cm2. The analysis further suggests that the oxygen depletion could be partially overcome by fractionating the light delivery. In a transplanted mammary tumor model, a regimen of 30-s exposures followed by 30-s dark periods produced significantly longer delays in tumor growth when compared to the continuous delivery of the same total fluence.

Animals↗

Structural effects of hydration: studies of lysozyme by 13C solids NMR.

13C-nmr spectra of lysozyme obtained at 50.3 MHz using both static and magic-angle-spinning-cross-polarization methods are reported at several water contents. The line widths and consequent resolution in the hydrated material is substantially improved over that in the lyophilized protein. The line narrowing is not commensurate with loss of a proton-carbon dipole-dipole coupling or dramatic changes in the relaxation parameters characterizing magnetization transfer from protons to carbon in the Hartmann-Hahn cross-polarization experiment. We interpret these data in terms of the water inducing a decrease in the distribution of local conformations sampled by the protein, although the magnitude of the conformational reorientations required to account for the data are not necessarily large nor do they imply a major unfolding of the protein on dehydration.

Carbon Isotopes↗

Hydration effects on dynamics of polyglycine and sodium poly(L-glutamate).

Solid state nmr methods were applied to the study of the motions and structural heterogeneity in polyglycine, sodium poly(L-glutamate), and poly(L-alanine). The response of both the main-chain and side-chain resonances to the addition of water was studied using static and magic-angle sample-spinning line shapes as well as the carbon spin-lattice relaxation times, the proton spin-lattice relaxation time in the rotating frame, and the proton-carbon cross-polarization time. The polyglycine motions are not drastically affected by the addition of water when the polymer is in the 3(1)-helix or the beta-sheet structure. The sodium poly(L-glutamate), however, responds to increased hydration with little motion in the main-chain carbon atoms, but considerable flexibility of the side-chain atoms. The greatest motions are reported for the C5 carbon with rotational amplitudes about the C4-C5 bond of about of 50 degrees. In addition, motions somewhat less than half this size are required closer to the main chain.

Peptides↗

Magnetic relaxation in blood and blood clots.

Nuclear magnetic relaxation rates are measured for whole blood, blood plasma, whole blood clots, and plasma clots in vitro. Relaxation rates are linear in the hematocrit and transverse relaxation rates are significantly greater than longitudinal relaxation rates. Longitudinal relaxation rates measured from 0.01 to 42 MHz for proton Larmor frequencies are found to decline monotonically with increasing magnetic field strength; however, the dispersion curves do not follow a simple Lorentzian behavior, which is anticipated in a suspension of particles in a solution of proteins having a distribution of molecular weights. The transverse relaxation rate is a function of the acquisition parameters, in particular, the choice of TE in either Hahn echo experiments or in echo-train experiments. The origin of this dependence of T2 on TE or the interpulse spacing in an echo train is identified with the exchange of water from inside the red blood cell to the outside and is only an important relaxation mechanism in the case where the blood cell membrane is intact and the cell contains deoxygenated hemoglobin. The dependence of the apparent transverse relaxation rate on the interpulse spacing in a Meiboom-Gill-Carr-Purcell pulse sequence provides the estimate that the mean residence time of water inside the blood cell is about 10 ms. These data provide a sound basis for understanding the dependence of magnetic images on magnetic field strength and the choices of the image acquisition parameters, TE and TR.

Blood↗

In situ assessment of tumor vascularity using fluorine NMR imaging.

In situ fluorine NMR imaging has been used to measure vascularity in subcutaneously implanted mammary tumors. Oxyferol, a perfluorinated blood substitute comprised of an emulsion of 25% w/v perfluorotributylamine, was used as a tracer. Following iv administration, this perfluorocarbon emulsion remains primarily in the vasculature during the image acquisition period. The distribution of the PFTA in the 19F NMR image gives a map of tissue regions with intact vascularity. This technique has been used to demonstrate decreased blood flow in necrotic regions of R3230AC mammary tumors in which vasculature had been damaged either as a result of spontaneous necrosis or by photodynamic therapy (PDT). Damage to tumor vascularity following PDT was observed prior to the development of necrosis.

Animals↗

Magnetic resonance imaging of blood and clots in vitro.

The effects of variations in blood clot composition on magnetic relaxation rates and magnetic resonance (MR) image have been characterized in vitro. Both 1/T1 and 1/T2 were found to be linear functions of hematocrit for blood and clot, with increases in hematocrit resulting in progressive decreases in image signal intensity. Clot formation in fully oxygenated samples produced no change in relaxation rates or MR images compared with unclotted blood, but clot retraction was associated with a significant increase in 1/T2 that resulted in a decreased signal. Retraction resulted in a heterogenous image with appearance of a hypointense peripheral rim; differences in the method of clot preparation resulted in significant image inhomogeneity. The pattern of fibrinolysis was found to depend on the type of plasminogen activator used and its site of initial application. Injection of tissue plasminogen activator into the clot resulted in lysis, primarily in the clot interior, whereas placing the enzyme in the surrounding serum caused degradation from the outside of the clot. Both observations are consistent with the high binding affinity of tissue plasminogen activator for fibrin. By comparison, streptokinase, with low fibrin binding affinity, dissolved thrombi in a peripheral pattern whether injected into the thrombus or introduced in the serum. These findings identify several variables of clot composition and structure that influence MR images of thrombi and should be considered in their interpretation.

Blood↗

Diagnosis of femoropopliteal venous thrombosis with MR imaging: a comparison of four MR pulse sequences.

In a prospective study, MR images were evaluated in seven patients with femoropopliteal venous thrombosis with symptoms of less than 5 days duration. T1-weighted (600/25 [TR/TE]), intermediate (2000/30), and T2-weighted (2000/100) spin-echo series and a gradient-recalled acquisition in the steady state (GRASS) series were compared. Using venography as the standard for diagnosis, we found GRASS to be the most sensitive of the MR techniques, showing thrombi in all patients. It provided good contrast between the low-intensity thrombus and high-intensity flowing blood and also between thrombus and intermediate- or high-intensity perivascular tissues. The T1-weighted series was the least sensitive technique. All thrombi showed heterogeneity in the transaxial image with differences in signal between the peripheral and central regions. A higher intensity signal in the center than in the periphery at some level of the thrombus was found in six of seven T2-weighted or GRASS images. Heterogeneity in the signal intensity was more frequent in distal portions of thrombi, whereas the most proximal extent was homogeneous in appearance in six of seven cases. The heterogeneous appearance may be related to the greater age of the distal thrombus, because deep venous thrombi are known to begin in the calf and extend proximally over time. We conclude, on the basis of our experience with a small number of patients, that the GRASS MR technique is more sensitive for detecting acute deep venous thrombosis than T1-weighted, intermediate, and T2-weighted MR images.

Adult↗

Carbon-13 NMR of glycogen: hydration response studied by using solids methods.

The carbon-13 NMR spectra of glycogen are reported by using the methods of magic-angle sample spinning and high-power proton decoupling to provide a dynamic report on the glucose monomer behavior as a function of hydration. Although the glycogen behaves as a typical polymer in the dry state, addition of water makes a significant difference in the spectral appearance. Water addition decreases the carbon spin-lattice relaxation times by 2 orders of magnitude over the range from 7% to 70% water by weight. The proton-carbon dipole-dipole coupling, which broadens the carbon spectrum and permits cross-polarization spectroscopy, is lost with increasing hydration over this range. By 60% water by weight, scalar decoupling methods are sufficient to achieve a reasonably high-resolution spectrum. Further, at this concentration, the carbon spin-lattice relaxation times are near their minimum values at a resonance frequency of 50.3 MHz, making acquisition of carbon spectra relatively insensitive to intensity distortions associated with saturation effects. Though motional averaging places the spectrum in the solution phase limit, the static spectrum shows a residual broader component that would not necessarily be detected readily by using high-resolution liquid-state experiments.

Glycogen↗

Magnetic resonance imaging using a ribbonator: hand and wrist.

A modified version of a single-turn solenoid with rectangular symmetry, which we call a ribbonator, provides excellent magnetic resonance images of the hand and wrist when used as both the transmitter and the receiver in a 1.5-T clinical imaging system. The very high RF efficiency provides excellent signal-to-noise and anatomical resolution. Design equations and RF properties of the resonator are discussed.

Copper↗

Magnetic field mapping.

Homogeneous radiofrequency magnetic fields are necessary for production of high-quality magnetic images and for most forms of magnetic resonance spectroscopy. It is often convenient to map the radiofrequency homogeneity associated with a resonant device by measuring the magnetic image intensity of an aqueous phantom placed within the resonator. The rf field intensity is not related trivially to the magnetic image intensity, and the relationship is different for different image acquisition methods. In this report relationships between rf field intensity and magnetic image intensity are derived and radio-frequency field maps presented for comparison using (1) an rf probe moved about within the resonant volume, (2) spin-echo images, and (3) small tip angle gradient refocused echo images.

Magnetic Resonance Spectroscopy↗

MRI of extremities using perforated single-turn solenoids.

A class of single-turn solenoids that permits magnetic imaging of the extremities in horizontal bore magnets with improved coupling between the imaged anatomy and the rf section of the imager is described and demonstrated. These devices differ from more conventional designs primarily by the placement of one or more access holes in the side of the generally cylindrical resonant structure to permit extremity insertion. The image quality is excellent, rf efficiency and homogeneity are good, and signal-to-noise is high, permitting rapid acquisition of magnetic images with small fields of view.

Extremities↗

Gastrointestinal contrast agents: a diamagnetic approach.

The clay minerals kaolin and bentonite are demonstrated as gastrointestinal contrast agents for MRI. Weak field dependence of the relaxation efficiency assures effectiveness of these agents at all field strengths in clinical use. These agents eliminate signals from their immediate environment and are not toxic.

Bentonite↗

Current perspectives on the epidemiology and pathogenesis of clinically significant Vibrio spp.

Recent taxonomic advances have now implicated several different Vibrio species as human pathogens. While the most common clinical presentation of Vibrio infection continues to be gastroenteritis, an increasing number of extraintestinal infections are being reported, particularly in immunocompromised individuals. Detection of Vibrio infections requires a good clinical history and the use of appropriate isolation and identification procedures by the laboratory to confirm illnesses attributed to Vibrio species. Except for Vibrio cholerae O1 and Vibrio parahaemolyticus, there is little direct evidence linking the production of a myriad of cell-associated or extracellular factors produced by each species with human disease and pathogenesis. Many questions regarding pathogenic Vibrio species remain unanswered, including their frequency and distribution in environmental specimens (water, shellfish), infective doses, virulence potential of individual isolates, and markers associated with such strains.

Epidemiologic Methods↗