Biomedical subjects

U Eliav

Publications and source records attributed to U Eliav.

15 recordsLinked to original sources

PubMed2005

Self-diffusion anisotropy of water in sheep Achilles tendon.

The principal values of the diffusion tensor of free water in the pores of sheep Achilles tendon were determined. For this purpose, the azimuthally angular dependence of the self-diffusion coefficient was measured using a radiofrequency tilt coil and pulsed-field-gradient stimulated-echo (PFGSE) NMR. Combining the PFGSE with multiple acquisitions of Hahn echoes using the Carr-Purcell-Meiboom-Gill pulse sequence reduced the measuring time. The diffusion measurements revealed two diffusion process characterized by a fast and a slow effective diffusion coefficient. A model which describes the stimulated-echo amplitude, encoded by the water diffusion and magnetization transfer, was used for evaluation of the fast diffusion coefficients. The fast diffusion process characterizes the water molecules in pores surrounding the collagen fibrils. The diffusion coefficients characterizing the fast process show a well-defined anisotropy. The principal values of the diffusion tensors were determined assuming the elongated pores to be oriented parallel to the tendon fibrils and thus the orientation distribution function of the pores followed that of the collagen fibrils. The average aspect ratio of pores was estimated from the principal values of the water diffusion tensor and is suitable to characterize quantitatively the changes in tendon morphology due to healing or aging. The methods in this investigation can also be applied to measurements of the diffusion anisotropy using ex situ NMR sensors.

Achilles Tendon↗

PubMed2003

Anisotropy of collagen fiber orientation in sheep tendon by 1H double-quantum-filtered NMR signals.

The anisotropy of the angular distribution of collagen fibrils in a sheep tendon was investigated by 1H double-quantum (DQ) filtered NMR signals. Double-quantum build-up curves generated by the five-pulse sequence were measured for different angles between the direction of the static magnetic field and the axis of the tendon plug. Proton residual dipolar couplings determined from the DQ build-up curves in the initial excitation/reconversion time regime which mainly represent the bound water are interpreted in terms of a model of spin-1/2 pairs with their internuclear axes oriented on average along the fibril direction in the presence of proton exchange. The angular distribution of collagen fibrils around the symmetry axis of the tendon measured by the anisotropy of the residual dipolar couplings was described by a Gaussian function with a standard deviation of 12 degrees +/-1 degrees and with the center of the distribution at 4 degrees +/-1 degrees. The existence of this distribution is directly reflected in the finite value of the residual dipolar couplings at the magic angle, the value of the angular contrast, and the oscillatory behavior of the DQ build-up curves. The 1H residual dipolar couplings were also measured from the doublets recorded by the DQ-filtered signals. From the angular dependence of the normalized splitting the angular distribution of the collagen fibrils was evaluated using a Gaussian function with a standard deviation of 19 degrees +/-1 degrees and with the center of distribution at 2 degrees +/-1 degrees. The advantages and disadvantages of these approaches are discussed.

Achilles Tendon↗

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↗

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↗

PubMed1999

A study of dipolar interactions and dynamic processes of water molecules in tendon by 1H and 2H homonuclear and heteronuclear multiple-quantum-filtered NMR spectroscopy.

The effect of proton exchange on the measurement of 1H-1H, 1H-2H, and 2H-2H residual dipolar interactions in water molecules in bovine Achilles tendons was investigated using double-quantum-filtered (DQF) NMR and new pulse sequences based on heteronuclear and homonuclear multiple-quantum filtering (MQF). Derivation of theoretical expressions for these techniques allowed evaluation of the 1H-1H and 1H-2H residual dipolar interactions and the proton exchange rate at a temperature of 24 degrees C and above, where no dipolar splitting is evident. The values obtained for these parameters at 24 degrees C were 300 and 50 Hz and 3000 s-1, respectively. The results for the residual dipolar interactions were verified by repeating the above measurements at a temperature of 1.5 degrees C, where the spectra of the H2O molecules were well resolved, so that the 1H-1H dipolar interaction could be determined directly from the observed splitting. Analysis of the MQF experiments at 1.5 degrees C, where the proton exchange was in the intermediate regime for the 1H-2H dipolar interaction, confirmed the result obtained at 24 degrees C for this interaction. A strong dependence of the intensities of the MQF signals on the proton exchange rate, in the intermediate and the fast exchange regimes, was observed and theoretically interpreted. This leads to the conclusion that the MQF techniques are mostly useful for tissues where the residual dipolar interaction is not significantly smaller than the proton exchange rate. Dependence of the relaxation times and signal intensities of the MQF experiments on the orientation of the tendon with respect to the magnetic field was observed and analyzed. One of the results of the theoretical analysis is that, in the fast exchange regime, the signal decay rates in the MQF experiments as well as in the spin echo or CPMG pulse sequences (T2) depend on the orientation as the square of the second-rank Legendre polynomial.

Achilles Tendon↗

PubMed1999

Detection and characterization of boric acid and borate ion binding to cytochrome c using multiple quantum filtered NMR.

The application of multiple quantum filtered (MQF) NMR to the identification and characterization of the binding of ligands containing quadrupolar nuclei to proteins is demonstrated. Using relaxation times measured by MQF NMR multiple binding of boric acid and borate ion to ferri and ferrocytochrome c was detected. Borate ion was found to have two different binding sites. One of them was in slow exchange, k(diss) = 20 +/- 3 s(-1) at 5 degrees C and D(2)O solution, in agreement with previous findings by (1)H NMR (G. Taler et al., 1998, Inorg. Chim. Acta 273, 388-392). The triple quantum relaxation of the borate in this site was found to be governed by dipolar interaction corresponding to an average B-H distance of 2.06 +/- 0.07 A. Other, fast exchanging sites for borate and boric acid could be detected only by MQF NMR. The binding equilibrium constants at these sites at pH 9.7 were found to be 1800 +/- 200 M(-1) and 2.6 +/- 1.5 M(-1) for the borate ion and boric acid, respectively. Thus, detection of binding by MQF NMR proved to be sensitive to fast exchanging ligands as well as to very weak binding that could not be detected using conventional methods.

Animals↗

PubMed1998

Mapping strain exerted on blood vessel walls using deuterium double-quantum-filtered MRI.

A technique is described for displaying distinct tissue layers of large blood vessel walls as well as measuring their mechanical strain. The technique is based on deuterium double-quantum-filtered (DQF) spectroscopic imaging. The effectiveness of the double-quantum filtration in suppressing the signal of bulk water is demonstrated on a phantom consisting of rat tail tendon fibers. Only intrafibrillar water is displayed, excluding all other signals of water molecules that reorient isotropically. One- and two-dimensional spectroscopic imaging of bovine aorta and coronary arteries show the characteristic DQF spectrum of each of the tissue layers. This property is used to obtain separate images of the outer layer, the tunica adventitia, or the intermediate layer, the tunica media, or both. To visualize the effect of elongation, the average residual quadrupole splitting is calculated for each pixel. Two-dimensional deuterium quadrupolar splitting images are obtained for a fully relaxed and a 55% elongated sample of bovine coronary artery. These images indicate that the strong effect of strain is associated with water molecules in the tunica adventitia whereas the DQF NMR signal of water in the tunica media is apparently strain-insensitive. After appropriate calibration, these average quadrupolar splitting images can be interpreted as strain maps.

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

Determination of the Dipolar Interaction of 23Na in Solution by Triple-Quantum Relaxation Time Measurements

The measurement of the dipolar interaction of 23Na with hydrogen nuclei in glycerol solution is reported. The method, applied previously to 7Li (U. Eliav and G. Navon, J. Magn. Reson. A 123, 32 (1996)), is based on the measurement of the triple-quantum relaxation time of 23Na. Several models of motion are discussed. The analysis of the results yielded 1.9 MHz and 12.5 kHz for the quadrupolar and the 23Na-1H dipolar interaction, respectively. It is shown that under the conditions of long correlation times the triple-quantum relaxation time can be sensitive to dipolar interactions smaller than the quadrupolar interaction by as much as a factor of 5000. This indicates the possibility of measuring interatomic distances for nuclei with sizable quadrupolar moments. Copyright 1998 Academic Press. Copyright 1998 Academic Press

Journal Article↗

PubMed1997

In vivo 23Na NMR studies of myotonic dystrophy.

Myotonic dystrophy is an inherited multi-system disease. Its pathophysiology leading to muscle malfunction and damage is not well understood. 23Na NMR spectroscopy was applied here for an in vivo comparative study of the calf muscles of 7 myotonic dystrophy patients at various stages of the disease and 11 healthy volunteers. Both the total sodium content, expressed as the ratio of the 23Na and 1H water signals, and the fast transverse relaxation time, T2f, determined from the triple quantum-filtered spectra, increased in correlation with the severity of the disease. The results demonstrate that 23Na NMR enables the quantitation of myotonic dystrophy progression.

Adolescent↗

PubMed1996

Measurement of Dipolar Interaction of Quadrupolar Nuclei in Solution Using Multiple-Quantum NMR Spectroscopy

Relaxation resulting from the modulation of dipolar interaction is commonly used for estimating distances in molecules in solutions. However, for most nuclei with spin I > ½ the single-quantum-transition relaxation by dipolar interaction is masked by quadrupolar relaxation. In the present study, it is shown that even in systems where single-quantum relaxation times are dominated by quadrupolar interaction, dipolar relaxation can be measured by following the -m $\leftrightarrow$ m transitions. This is demonstrated for 7Li in the complex [Li-Kryptofix 211]+X- (X = Cl, Br) dissolved in glycerol at temperatures for which slow motion prevails and no 1H-7Li NOE can be observed. The relaxation times that are most important for the assessment of the dipolar interaction of 7Li are -½ $\leftrightarrow$ ½ and -${{3}\over{2}}$ $\leftrightarrow$ ${{3}\over{2}}$ and they are measured by multiple-quantum-filtration techniques. For estimating the quadrupolar interaction, the relaxation times of the populations and those of the transitions ±½ $\leftrightarrow$ ±${{3}\over{2}}$ were measured. The longitudinal and transverse relaxation times of 6Li as well as the 1H-6Li NOE were also measured and, together with the 7Li measurements, were used to obtain the strengths of dipolar (D) and quadrupolar (chi) interactions. The experimental data were analyzed using several models to describe the motion. The model that gave the best fit and resulted in parameters that were physically meaningful encompassed a whole-body isotropic motion as well as internal anisotropic motion. For this particular model, the following values for the quadrupolar and the dipolar interactions strength were obtained: D(7Li)/2pi = 6.8 kHz, chi(7Li)/2pi = 85 kHz and D(6Li)/2pi = 1.4 kHz, chi(6Li)/2pi = 2.6 kHz. From the value of D, an estimate of the average lithium-proton distance was calculated to be 3.3 Å, which is in fair agreement with crystallographic studies. The sizes of the quadrupolar and dipolar interactions were independently confirmed by the 7Li NMR powder spectra of the complexes that were used for the solution studies.

Journal Article↗

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↗

PubMed1994

Analysis of double-quantum-filtered NMR spectra of 23Na in biological tissues.

Double-quantum-filtered NMR spectra of 23Na in bovine nasal cartilage tissue and its constituents were measured. The presence of even-rank tensors was detected in the cartilage tissue and in a suspension of collagen fibers, indicating anisotropic motion of the sodium ions. Quantitative analysis of the spectra was performed by calculating the time evolution of the second- and third-rank tensors by solving a modified Redfield equation. Analytical expressions for the spectra were obtained. It is shown that the anisotropy stems from local rather than macroscopic order. A good fit to the observed spectra was obtained for several models that assume isotropic distribution of the directors of the locally ordered sites. The local residual quadrupolar interaction was found to be 550 Hz, demonstrating the sensitivity of double-quantum filtration in the detection of anisotropic motion.

Animals↗

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↗