Biomedical subjects

H Shinar

Publications and source records attributed to H Shinar.

17 recordsLinked to original sources

PubMed2001

Multiquantum filters and order in tissues.

In ordered systems, where the molecular motion is anisotropic, quadrupolar and dipolar interactions are not averaged to zero. In such cases, double quantum (DQ) coherences can be formed. This review deals mainly with the effect of anisotropic motion of water molecules and sodium ions in intact biological tissues on (2)H, (1)H and (23)Na NMR spectroscopy and its application to NMR imaging (MRI). Double quantum filtered (DQF) spectra of water molecules and sodium ions were detected in a variety of ordered biological tissues. In collagen-containing tissues such as ligaments, tendons, cartilage, skin, blood vessels and nerves, the DQ coherences are formed as a result of the interaction with the collagen fibers. In red blood cells and presumably also in nerve axons it stems from the interaction with the cytoskeleton. For (23)Na, an I = 3/2 nucleus, the DQ coherences can also be formed in isotropic media. By a judicial choice of the pulse angle in the DQ pulse sequence only the DQ coherences arising from anisotropic motion are detected. For I = 1 nuclei such as 2H, DQF spectra can be observed only in ordered structures. Thus, the observation of 2H DQF spectra is an indication of order. The same is true for pairs of equivalent 1H nuclei. The dependence of the DQF signal on the creation time of the double quantum coherences is characteristic to each tissue and allows signals to be resolved from different tissues by performing the measurements at different creation times. In this way, the 2H DQF signals of the different compartments of sciatic nerve were resolved and water diffusion in each compartment was studied independently. In the axon, the diffusion was heavily restricted perpendicular to the axon's long axis, a result from which the axon diameter could be deduced. In blood vessel walls, this characteristic enabled the different layers of the vessel to be viewed and studied under strain. For 2H, a DQF spectroscopic imaging sequence was used to study the orientation of the collagen fibers in the different zones of articular cartilage and bone plug. The effect of pressure on the fibers and their return to equilibrium was studied as well. In blood vessels, a DQF image was obtained and strain maps of the different layers were calculated. The efficiency of the 1H DQF imaging technique was demonstrated on a phantom of rat tail where only the four tendons were detected at short creation times. 1H DQF imaging and spectroscopy followed the healing of a rabbit's ruptured Achilles tendon and the results were far more sensitive to the process than conventional imaging. Finally, the method was implemented on a commercial whole body MRI spectrometer. Images of human wrist and ankle showed a positive contrast for the tendons and ligaments, indicating the potential of the method for clinical imaging. (c) 2001 John Wiley & Sons, Ltd.

Animals↗

PubMed2000

Slice-selective proton double quantum filtered MRI of joint connective tissues.

1H double quantum filtered (DQF) imaging has been shown to highlight tendons. In this work the DQF magnetic resonance imaging pulse sequence is extended to include slice selection. The short transverse relaxation time of the 1H nuclear magnetic resonance in connective tissues, presents a stringent demand on the application of gradients and soft radiofrequency pulse lengths needed for slice selection. In the present work a slice selection pulse sequence is implemented by postponing the application of the slice refocusing gradient to the period after the last pulse just before the acquisition. Slice-selective DQF images of rat lower leg and knee are given to demonstrate the efficacy of the technique.

Animals↗

PubMed2000

Interaction of hyaluronic acid-linked phosphatidylethanolamine (HyPE) with LDL and its effect on the susceptibility of LDL lipids to oxidation.

The amphiphilic polysaccharide hyaluronic acid-linked phosphatidylethanolamine (HyPE), synthesized by covalently binding dipalmitoyl-phosphatidylethanolamine (DPPE) to short chain hyaluronic acid (mol. wt. approximately = 30 000), interacts with low-density lipoproteins (LDL), to form a 'sugar-decoration' of the LDL surface. This results in an increase in the apparent size of the LDL particles, as studied by photon correlation spectroscopy, and in broadening of the 1H NMR signals of the LDL's phospholipids. Experiments conducted with fluorescently-labeled HyPE indicate that the interaction of HyPE with LDL involves incorporation of the hydrocarbon chains of this amphiphilic polysaccharide into the outer monolayer of the LDL. This interaction also inhibits the copper-induced oxidation of the LDL polyunsaturated fatty acids, avoiding oxidation altogether when the concentration of HyPE is higher than a tenth of the concentration of the LDL's phospholipids. This can not be attributed to competitive binding of copper by HyPE. We propose that the protection of LDL lipids against copper-induced oxidation is due to formation of a sugar network around the LDL.

Humans↗

PubMed1999

Anisotropic and restricted diffusion of water in the sciatic nerve: A (2)H double-quantum-filtered NMR study.

The signals of water in the different compartments of rat sciatic nerve are resolved in the (2)H double-quantum-filtered NMR spectrum, due to their different quadrupolar splittings and relaxation rates. This resolution allowed the independent measurement of the water diffusion coefficients in the different compartments. The water diffusion in all three compartments, the endoneurium, the epineurium and the axon was found to be anisotropic. Parallel to the nerve fiber the average intraxonal water diffusion coefficient was 1.11 x 10(-5) cm(2)/sec, while in the perpendicular direction the diffusion is heavily restricted. The average perpendicular diffusion coefficient ranged from 0.29 x 10(-5) cm(2)/sec to 0.05 x 10(-5) cm(2)/sec for diffusion times of 7 msec and 50 msec, respectively. Assuming restricted diffusion in nonpermeable cylinders, intra-axonal mean diameters of 6.0, 7.4 and 9.0 microm were obtained for nerves taken from three different rats. Magn Reson Med 42:461-466, 1999.

Animals↗

PubMed1999

1H double-quantum-filtered MR imaging as a new tool for assessment of healing of the ruptured Achilles tendon.

1H double-quantum-filtered magnetic resonance imaging (DQF MRI) was applied to monitor the healing process of the Achilles tendons in rabbits after tenotomy. DQF MRI provides a new contrast, which is based on the non-zero average of the dipolar interaction caused by anisotropic motion of water molecules, determined mainly by their interaction with the ordered collagen fibers. Tissues are characterized by the dependence of their DQF signal on the DQ creation time, tau. With the use of DQF MRI, higher tissue contrast is obtained between tendon, bone, skin, and muscle. The tendons, which give weak signals in standard MRI techniques, are highlighted in the (1)H DQF image. The image changed dramatically during the healing process of the injured Achilles tendon. These changes matched the phases of the healing process. By using a tau-weighted contrast, the DQF images indicate the part of tendon that has not completely healed, even after the conventional MRI appeared normal. Magn Reson Med 42:884-889, 1999.

Achilles Tendon↗

PubMed1998

Observation of a 1H double quantum filtered signal of water in biological tissues.

The observation of a 1H double quantum filtered (DQF) NMR signal of water in bovine sciatic nerve, bovine articular cartilage, rat tail tendon, and rat brain is reported. The origin of this signal in rat tail tendon was found to be a result of residual dipolar interaction between water protons and macromolecular protons. The dependence of the width of the 1H DQF spectra on the orientation indicated that in rat tail tendon the effective director of the residual dipolar interaction is parallel to the collagen fibers. 1H DQF NMR may be applied in imaging where the contrast obtained is related to the degree of order in the tissue.

Animals↗

PubMed1998

Proton double-quantum filtered MRI--a new method for imaging ordered tissues.

The imaging of connective tissues such as cartilage and tendons using standard MRI techniques is hampered by their low signal relative to the surrounding tissues. 1H double-quantum filtered (DQF) MRI is an imaging method that detects molecules associated with ordered structures, while the signal from isotropic fluids is filtered out, thus creating a new type of contrast. The technique is demonstrated on an intact rat tail, where the image of the tendons is highlighted. Although the signal-to-noise ratio is inferior to that in gradient-echo MRI, the contrast between the tendons and the surrounding tissues is significantly better in the DQF MRI. It is demonstrated how, by adjusting the parameters of the DQF imaging pulse sequence, one can modify the contrast and enhance the images of specific compartments within an organ. A comparison with 2H DQF imaging of the same tissue is also given.

Animals↗

PubMed1998

Quantification of the contribution of extracellular sodium to 23Na multiple-quantum-filtered NMR spectra of suspensions of human red blood cells.

23Na double-quantum-filtered (DQF) NMR enables the detection of anisotropic motion of sodium ions due to their interaction with ordered structures in biological tissues. Using the technique, anisotropic motion was found for sodium ions in mammalian red blood cell suspensions (RBC) and the effect was shown to correlate with the integrity of membrane cytoskeleton. In the present study relative contributions to the DQF and triple-quantum-filtered (TQF) spectra of sodium bound to anisotropic and isotropic binding sites in the intra- and extracellular sodium pools (Na content being 15 and 150 mM, respectively) of human RBC were quantified for different hematocrits. DQF spectra were measured by a modified Jeener-Broekaert pulse sequence which enabled exclusive detection of anisotropically moving sodium ions. The relative contributions of the extracellular sodium to the TQF and DQF spectra decreased as the hematocrit increased, but their efficiency relative to the sodium content increased. The contribution of the extracellular sodium to the TQF signal was found to dominate the spectrum of the RBC suspension at all hematocrits studied. The contribution of the extracellular sodium to the DQF was significantly smaller than that to the TQF and was only 22% at a high hematocrit of about 90%.

Animals↗

PubMed1997

Discrimination between the different compartments in sciatic nerve by 2H double-quantum-filtered NMR.

The 2H double-quantum-filtered (DQF) NMR spectrum of isolated rat sciatic nerve, equilibrated with deuterated saline, is composed of three quadrupolar-split water signals. On the basis of the time course of their shift by Co-EDTA2- and CoCl2, the signals with quadrupolar splittings of about 120, 470, and 9 Hz were assigned to water in the epineurium, endoneurium, and intra-axonal compartments, respectively. The signal of the bulk water, which experiences isotropic motion, was eliminated by the DQF pulse sequence. As the maximum intensities of the water signals in the three anisotropic compartments occur at different creation times, in the DQF pulse sequence, it is possible to resolve the signals and measure their properties, such as relaxation times, independently, without perturbing the system with shift reagents.

Animals↗

PubMed1996

A 23Na multiple-quantum-filtered NMR study of the effect of the cytoskeleton conformation on the anisotropic motion of sodium ions in red blood cells.

Recently, it has been shown that 23Na double-quantum-filtered NMR spectroscopy can be used to detect anisotropic motion of bound sodium ions in biological systems. The technique is based on the formation of the second-rank tensor when the quadrupolar interaction is not averaged to zero. Using this method, anisotropic motion of bound sodium in human and dog red blood cells was detected, and the effect was shown to depend on the integrity of the membrane cytoskeleton. In the present study, multiple-quantum-filtered techniques were applied in combination with a quadrupolar echo to measure the transverse-relaxation times, T2f and T2s. Line fitting was performed to obtain the values of the residual quadrupolar interaction, which was measured for sodium in a variety of mammalian erythrocytes of different size, shape, rheological properties, and sodium concentrations. Human unsealed white ghosts were used to study sodium bound at the anisotropic sites on the inner side of the RBC membrane. Modulations of the conformation of the cytoskeleton by the variation of either the ionic strength or pH of the suspending medium caused drastic changes in both the residual quadrupolar interaction and T2f due to changes in the fraction of bound sodium ions as well as changes in the structure of the binding sites. By combining the two spectroscopic parameters, structural change can be followed. The changes in the structure of the sodium anisotropic binding sites deduced by this method were found to correlate with known conformational changes of the membrane cytoskeleton. Variations of the medium pH affected both the fraction of bound sodium ions and the structure of the anisotropic binding sites. Sodium and potassium were shown to bind to the anisotropic binding sites with the same affinity.

Algorithms↗

PubMed1996

31P NMR methods for the direct determination of ADP in the presence of ATP.

A new method is presented for the direct measurement of the amount of ADP in the presence of ATP by selectively eliminating the alpha- and gamma-ATP signals. The method is compared with other methods, both experimentally and theoretically, using the product-operator formalism. An analysis of the effect of beta 1 inhomogeneity on the efficiency of the methods is also given. Experimental results obtained using adiabatic pulses to compensate for such effects are shown. The accuracy of this new method is demonstrated by measuring various ADP concentrations in a series of solutions containing ADP and ATP.

Adenosine Diphosphate↗

PubMed1993

Sodium interaction with ordered structures in mammalian red blood cells detected by Na-23 double quantum NMR.

Na-23 double and triple quantum filtered NMR spectra of intact dog and human red blood cells were measured with the pulse sequence 90 degrees-tau/2-180 degrees-tau/2-theta degrees-t1-theta degrees-t2(Acq). For theta = 90 degrees the triple quantum filtered spectra exhibited the typical multiple quantum filtered lineshape, characteristic of isotropic media, while the double quantum filtered ones presented a superposition of two signals, whose proportion depended on the creation time tau. This effect is due to the formation of both second and third rank tensors. The formation of the second rank tensor, T21 results from non-zero residual quadrupolar interaction and is related to the anisotropic motion of sodium ions. Measurements of the double quantum filtered spectra with theta = 54.7 degrees enabled the detection of the contribution of T21 exclusively. No residual quadrupolar interaction was detected for sodium in the cytoplasm, while unsealed ghosts displayed the double quantum filtered spectral pattern, similar to that of intact cells. The anisotropy of motion of the sodium at the plasma membrane of mammalian erythrocytes depended on the integrity of the cytoskeleton network. Theoretical analysis of the double quantum filtered spectra gave a value of residual quadrupolar splitting of approximately 20 Hz for intact unsealed ghosts. The data presented prove that double quantum filtering is a sensitive technique for detection of motional anisotropies in biological systems.

Animals↗

PubMed1991

Sodium-23 NMR relaxation times in nucleated red blood cells and suspensions of nuclei.

The relaxation behavior of intracellular 23Na in suspensions of chicken erythrocytes and of their nuclei was investigated. The transverse magnetization was found to decay biexponentially. The average relaxation rates for the nucleated chicken erythrocytes are considerably shorter than the average relaxation rates obtained for dog and human nonnucleated red blood cells. Of particular significance is the twofold decrease in the short component of T2. Calculations based on the measured 23Na NMR relaxation rates in suspensions of nuclei indicate that most of the difference between the relaxation rates in the mammalian as compared to the chicken erythrocytes, can be accounted for by the contribution of the nuclei in the latter.

Animals↗

PubMed1986

Sodium-23 NMR relaxation times in body fluids.

23Na longitudinal and transverse NMR relaxation times were measured in human serum, plasma, cerebrospinal fluid (CSF), and solutions of plasma proteins. The magnetization decay curves could not be resolved into two exponentials. A procedure to extract quantitative information from the measured relaxation rates in such a case was developed. The relaxation times of 23Na in serum and plasma were analyzed in terms of the different contributions from free Na+, Na+ bound to small molecules, and Na+ bound to various protein fractions in these body fluids. While T1 is essentially that of free Na+ in a solution which is slightly more viscous than salt solution, T2 is influenced by binding to proteins with the largest contribution from serum albumin. The effect of binding to small molecules on T1 and T2 is negligible. From measurements of the relaxation times at several magnetic field strengths a rotational correlation time of Na+ bound to serum albumin of 16 +/- 6 ns was obtained. The fraction of bound Na+ in serum and plasma was roughly estimated as 0.02% of the total sodium. The relaxation times in cerebrospinal fluid are very similar to those of NaCl solution.

Blood↗

PubMed1985

The determination of intracellular water space by NMR.

A new method for the determination of intracellular water space using NMR spectroscopy is described. The method is based on the measurement of 59Co NMR signal intensity of an inert, stable and membrane-impermeable cobalt(III) compound such as Co(CN)3-6 or Co(imidazole)3+6 and the 2H or 1H NMR signal intensities of the freely permeable water. As an example of the method, the variation of the intracellular water space of human erythrocytes as a function of osmolality was measured.

Cobalt Radioisotopes↗

PubMed1984

NMR relaxation studies of intracellular Na+ in red blood cells.

The state of intracellular Na+ in human and dog erythrocytes was characterized by 23Na-NMR using dysprosium complexes as shift reagents. Intracellular Na+ concentrations were determined using integration of the inner Na+ NMR signals and measurements of the intracellular volume using 59Co-NMR of extracellular Co(CN)3-6. T2 was found to be significantly shorter than T1, indicating some binding to macromolecules. While the longitudinal magnetization decay follows a single exponential, the transverse magnetization could be fitted with a double-exponential function. It was shown that neither the binding to the inner side of the membrane nor binding to hemoglobin contributes to the relaxation enhancement.

Animals↗

PubMed1979

Kinetic and magnetic properties of cobalt(III) ion in the active site of carbonic anhydrase.

Cobalt(III)bovine carbonic anhydrase B was prepared by the oxidation of the cobalt(II) enzyme with hydrogen peroxide and was purified by affinity chromatography. The oxidation reaction is inhibited by specific inhibitors of carbonic anhydrase. The inhibition is explained by the fact that the Co(II)-enzyme . inhibitor complex cannot be directly oxidized by hydrogen peroxide, but has to dissociate to give free Co(II) enzyme which is then oxidized. The Co(III) ion in Co(III) carbonic anhydrase cannot be directly substituted by zinc ions. It can be reduced by either dithionite or BH-4 ions to give, first, their complexes with the Co(II) enzyme, and upon their removal, a fully active Co(II) enzyme. Cyanide and azide bind to cobalt(III) carbonic anhydrase with similar rate constants of 0.060 +/- 0.005 and 0.070 +/- 0.007 M-1 S-1 respectively. These rates are faster than those found for Co(III) inorganic complexes. The Co(III) ion in both Co(III) carbonic anhydrase and Co(III) carboxypeptidase A was found to be diamagnetic, indicating a near octahedral symmetry.

Animals↗