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Biomedical subjects

R L Magin

Publications and source records attributed to R L Magin.

At least 19 recordsLinked to original sources

Design and analysis of microcoils for NMR microscopy.

The signal-to-noise ratio achieved in a nuclear magnetic-resonance microscopy experiment is directly related to the performance of the radiofrequency coil. An accurate determination of coil performance requires that the resistance of the coil be well characterized. Traditional high-frequency electric-circuit models used to describe larger NMR coils are inadequate when the diameter of the conductor is reduced to the dimensions of the electrical skin depth (delta) at the frequency of operation. A more extensive model based on a scaling parameter that includes delta is presented. This model complements other existing circuit models that represent sample losses, ground-loop and parasitic losses, and the signal induced in the RF coil. Experimental verification is accomplished using a series of solenoidal microcoils in 1H NMR microspectroscopy experiments at 4.7 T (200 MHz). This study demonstrates for the first time that a predictable performance enhancement is achieved using microcoils as small as 50 microns in diameter.

Magnetic Resonance Spectroscopy

Selective MR imaging of labeled human peripheral blood mononuclear cells by liposome mediated incorporation of dextran-magnetite particles.

Human peripheral blood mononuclear cells (PBMCs) were incubated with large unilamellar vesicles (LUV) containing encapsulated dextran-magnetite particles (DMP). This resulted in an efficient incorporation of DMP. Electron microscopy revealed the presence of DMP in cells mainly in phagosomes and secondary lysosomes. DMP-labeled PBMCs showed a strong increase of the transverse relaxation rate (up to 16.6 s-1 for 5 x 10(7) cells/ml) and, accordingly, a great loss of signal intensity in MR imaging. The fraction of DMP containing PBMCs could be enriched by magnetic cell separation. The major population of the DMP containing cells proved to be monocytes. When PBMCs depleted of monocytes were used for labeling, DMP uptake was observed also in the peripheral blood lymphocytes. The labeling of PBMCs presented here may be used in future studies of selective MR imaging of in vivo cell migration in a variety of immunologically compromised tissue states, e.g., tumors, transplantations, and abscesses.

Contrast Media

Three-dimensional NMR microscopy of rat spleen and liver.

Three-dimensional microscopic NMR images of spleen and liver specimens from rats injected with dextran magnetite particles and from controls were obtained at 4.7 T, using a specially designed probe in conjunction with a 3D filtered back projection reconstruction algorithm. All of the images were reconstructed as 64(3) arrays with (25 microns) 3 isotropic voxels. With the aid of the MR contrast agent, the red pulp and marginal zone of the spleen and the portal triad of the liver could be distinguished from the surrounding tissue in T2-weighted images. For mature rat spleen, natural contrast in T2-weighted images was found to distinguish the same features. Histological examinations of the tissues with and without contrast agent were also performed using an optical microscope. Microscopic NMR images, despite their lower resolution, clearly revealed many features seen in the optical images.

Aging

Theory of paramagnetic contrast agents in liposome systems.

We develop a theoretical description of nuclear spin relaxation mediated by MRI contrast agents and transport processes in liposome systems. Such systems compartmentalize the physical space such that paramagnetic contrast agents, which enhance relaxation, are trapped in some subvolume. Due to diffusive transport across compartmental barriers, i.e., across liposome membranes, nuclear spins in the whole volume exhibit fast relaxation. The description developed is based on the diffusion-Bloch equations for the nuclear magnetization with appropriate boundary and continuity conditions. From this set of equations a new inhomogeneous differential equation for the local relaxation times is derived. For simple geometries of compartmentalized spaces the equation can be solved analytically. A simple formula for average relaxation times in liposome systems is presented. The resulting relaxation times agree well with observations.

Contrast Media

Specific MR imaging of human lymphocytes by monoclonal antibody-guided dextran-magnetite particles.

Human lymphocytes were labeled with biotinylated anti-lymphocyte-directed monoclonal antibodies, to which streptavidin and subsequently biotinylated dextran-magnetite particles were coupled. This labeling resulted in a strong and selective negative contrast enhancement of lymphocyte suspensions at 2.0 T, caused predominantly by the specific increase of R2 with a small but significant specific increase of R1. The R1 was found to decrease with increasing field strength. The immunolabeling procedure described here may be used for the selective signal depletion of target cells in MR imaging.

Antibodies, Monoclonal

Detection and quantitation in rat tissues of the superparamagnetic magnetic resonance contrast agent dextran magnetite as demonstrated by electron spin resonance spectroscopy.

RATIONALE AND OBJECTIVES: The compound studies in this article is a superparamagnetic macromolecular complex of magnetite cores coated with hydrophilic dextran, which is under active investigation as a contrast agent for magnetic resonance imaging (MRI) in liver and spleen. The biodistribution of paramagnetic compounds is problematic and is usually studied by histochemical reactions or by radiolabeling the compound under study. The purpose of this article is to show how electron spin resonance (ESR) spectroscopy detects dextran magnetite (DM) particles in tissues. METHODS: DM injected intravenously in the experimental animal was detected in some reticulo-endothelial organs by ESR. The spectroscopic study was validated using electron microscopy and electron-probe microanalysis. RESULTS: DM exhibits an ESR spectrum; ESR delineated the distribution of DM distribution in liver, spleen, bone marrow, and blood as a function of time. The blood clearance was biphasic, dependent on the size of particles. CONCLUSIONS: ESR spectroscopy is a highly sensitive and reproducible method of studying DM distribution.

Animals

Electric-field distribution near rectangular microstrip radiators for hyperthermia heating: theory versus experiment in water.

A rectangular microstrip antenna radiator is investigated for its near-zone radiation characteristics in water. Calculations of a cavity model theory are compared with the electric-field measurements of a miniature nonperturbing diode-dipole E-field probe whose 3 mm tip was positioned by an automatic three-axis scanning system. These comparisons have implications for the use of microstrip antennas in a multielement microwave hyperthermia applicator. Half-wavelength rectangular microstrip patches were designed to radiate in water at 915 MHz. Both low (epsilon r = 10) and high (epsilon r = 85) dielectric constant substrates were tested. Normal and tangential components of the near-zone radiated electric field were discriminated by appropriate orientation of the E-field probe. Low normal to transverse electric-field ratios at 3.0 cm depth indicate that the radiators may be useful for hyperthermia heating with an intervening water bolus. Electric-field pattern addition from a three-element linear array of these elements in water indicates that phase and amplitude adjustment can achieve some limited control over the distribution of radiated power.

Air

Arrays of mutually coupled receiver coils: theory and application.

Specialized receiver coils having a small sensitive region can provide an improvement in SNR for MR imaging and spectroscopy, at the expense of limiting the usable field of view. This work presents a technique for designing coil arrays that allows the size and location of the sensitive region to be selected remotely. Only one element of the coil array is directly connected to the receiver, allowing flexibility in system design and implementation. A method is presented for the analysis and design of mutually coupled coil arrays of any number of elements of arbitrary shape. The analysis includes mutual coupling effects between primary coils, to allow multiple primary coils to be used simultaneously. A controller system allows remote selection of the sensitive region and automatically matches the impedance of the array to the preamplifier. Results obtained using a mutually coupled coil array designed for spine imaging are shown.

Equipment Design

Sucrose polyester: a new oral contrast agent for MRI.

Sucrose polyester (a dietary fat substitute) opacifies the entire gastrointestinal tract of the rat with oral administration in magnetic resonance imaging (MRI). These results suggest the potential use of this material as an oral contrast agent for human abdominal MRI studies.

Animals

Dextran magnetite as a liver contrast agent.

The superparamagnetic particle dextran magnetite was studied as a liver tumor contrast agent for magnetic resonance imaging (MRI). The effects of dextran magnetite on the longitudinal (T1) and transverse (T2) relaxation times in liver, spleen, and an implanted rat liver tumor were measured at 0.47 T (IBM/Bruker PC-20 relaxometer) over the dose range of 23 to 69 mumol Fe/kg. Dextran magnetite substantially reduced the T2 of the liver and spleen, but not of the tumor, thereby providing a basis for improved tumor imaging. The T1 of the tumor was not affected following injection of dextran magnetite in the dose range studied, while the spleen T1 was reduced substantially more than the T1 of the liver. Histological studies using the iron reaction for Prussian blue clearly showed dextran magnetite in the liver and spleen, but not in the tumor. While dextran magnetite was sequestered in macrophages in both liver and spleen, the distribution in the liver was more diffuse (70 microns average particle separation) than that in the spleen (25 microns separation). The lack of a T1 effect in the liver is consistent with the fact that a majority of the water in the tissue cannot diffuse to the relaxational centers on the time scale of the liver's intrinsic T1 (280 ms). In the spleen, however, the dextran magnetite is more densely packed in the red pulp allowing a significant fraction of the water to be relaxed by a T1 mechanism. Spin-echo images of the implanted tumor (mammary adenocarcinoma. R3230AC) in the livers of Fischer 344 rats were obtained at 0.50 T (Siemens Magnetom). The tumor-to-liver contrast was improved for both T1 and T2-weighted spin-echo images after intravenous injection of the dextran magnetite contrast agent. The contrast determined from these images agreed with that predicted by the measured T1 and the T2 (Hahn spin-echo) values. In addition, gradient-echo T2-weighted images with good contrast were obtained in a much shorter imaging time than was needed for T2-weighted spin-echo images. These results demonstrate that the MRI contrast enhancement observed with dextran magnetite is based on its selective uptake and distribution in the macrophages in the liver and spleen and that this agent has substantial potential as a superparamagnetic MR contrast agent.

Adenocarcinoma

Blood clearance of dextran magnetite particles determined by a noninvasive in vivo ESR method.

Dextran magnetite (DM) is a potential MR contrast agent with superparamagnetic properties. Its fast clearance from the blood and selective uptake by tissue macrophages provide advantages for imaging tumors in the liver and spleen. DM consists of a suspension of solid particles with a wide distribution of sizes. In this study we have used ESR spectroscopy to determine the blood clearance of DM injected iv in mice. The spectra are obtained on living animals by inserting the tail of a mice into the waveguide cavity of the ESR spectrometer and recording the ESR spectrum continuously. This procedure allows the direct measurement of the plasma clearance of DM from individual animals, without blood sampling. We applied this method to study the clearance of suspensions of DM particles with different average sizes.

Animals

A programmable data acquisition and control system for magnetic resonance imaging: application to mutually coupled surface coil arrays and temperature monitoring.

A programmable data acquisition and control system was developed for use in conjunction with magnetic resonance imaging (MRI). The controller consists of two functional blocks: a host system and a remote system. The remote system resides inside the shielded room housing the magnet. The host, an IBM compatible personal computer, is located at the technician's console. Communication between these devices is implemented over a fiber optic RS-232 data link. This configuration allows experiments to be performed remotely by using a series of keyboard typed commands, by programming the host to send a series of commands, or by directly programming the remote system. As an example of its capabilities, the controller was used to tune and match arrays of receiver coils for localized imaging and to record the rectal temperature of a sedated rat during image acquisition.

Algorithms

The effects of A23187 on the phospholipid phase transition of large unilamellar vesicles (LUVs) as detected by ultrasound spectroscopy.

The effect of the hydrophobic Ca2+ ionophore, A23187, on the phospholipid dynamics of large unilamellar vesicle (LUVs: 4: 1 (w/w) mixture of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG] membranes, as a function of A23187 content, was investigated using techniques sensitive to the phospholipid phase transition. The ultrasonic absorption per wavelength, alpha lambda, was determined with a double crystal acoustic interferometer, as a function of temperature and frequency for LUVs in the vicinity of their phospholipid phase transition. Differential scanning calorimetry (DSC) and electron spin resonance (ESR) were also employed to probe the thermodynamics and molecular environment of the hydrocarbon side chains. With increasing A23187 content, the phase transition temperature (Tm) of the LUV suspensions remained near 42.0 degrees C, while the amplitude of alpha lambda at the phase transition increased dramatically. At Tm the relaxation frequency, where alpha lambda max occurs, decreased with A23187 content, suggesting that the relaxation rate of the event responsible for the absorption of ultrasound decreased. The ESR studies showed no change in the fluidity of the bilayer with the inclusion of 2 and 5 mol% A23187 in the C-12 region of the bilayer. Therefore, A23187 in LUV membranes slows the structural relaxation of the hydrocarbon side chains of the phospholipid bilayer at the phase transition.

Calcimycin

NMR and ESR study of liposome delivery of Mn2+ to murine liver.

The mechanism of tissue relaxation of liposome-delivered Mn2+ as a contrast agent for magnetic resonance imaging (MRI) was examined using magnetic resonance and electron spin resonance (ESR) techniques. It is known that liposomes of the size and composition used in this study are taken up by fixed liver macrophages (Kupffer cells). It was determined that Mn2+ must be released from the liposomes in order to affect the water proton relaxation rate in the liver. As long as the Mn2+ was confined to the Kupffer cells, no substantial changes in the relaxation of the majority of the liver water were observed. Unlike other contrast agents delivered to the Kupffer cells (for example, Gd-starch microspheres or magnetite), once the Mn2+ is delivered and released into the Kupffer cells, it can diffuse from the Kupffer cells and be rapidly taken up by the hepatocytes. This seems to be the mechanism for selective relaxation enhancement in the liver. A consequence of this behavior is that the time at which maximum contrast enhancement occurs for MRI can be varied by the choice of liposome phospholipid composition. ESR techniques were used to directly determine the state of Mn2+ and the integrity of liposomes in various stages of processing.

Animals

Kinetics of the lamellar and hexagonal phase transitions in phosphatidylethanolamine. Time-resolved x-ray diffraction study using a microwave-induced temperature jump.

The kinetics of the thermotropic lamellar gel (L beta')/lamellar liquid crystal (L alpha) and L alpha/inverted hexagonal (HII) phase transitions in fully hydrated dihexadecylphosphatidylethanolamine (DHPE) have been studied. Measurements were made by using time-resolved x-ray diffraction (TRXRD) to monitor progress of the transitions. In these studies microwave energy at 2.5 GHz was used to increase the sample temperature rapidly and uniformly through the phase transition regions. The L beta'/L alpha and L alpha/HII transitions of DHPE were examined under active microwave heating and passive cooling. The transitions were found to be repeatable and reversible, and to have an upper bound on the time required to complete the transition of less than 3 s. Regardless of the direction of the transition, both phase transitions appeared to be two-state with no accumulation of intermediates to within the sensitivity limits of the TRXRD method. The rate and amplitude of the temperature jump can be controlled by regulating microwave radiation input power. A temperature jump rate of 29 degrees C/s was obtained at a final microwave power setting of 120 W. Comparisons between previously reported fluid flow (Caffrey, M. 1985. Biochemistry. 24:4826-4844) and microwave heating studies suggest that the determination of limiting transit times will require faster heating.

Kinetics

Kinetics of the premelting (L beta'-P beta') and main transition (P beta'-L alpha) in hydrated dipalmitoylphosphatidylcholine. A time-resolved x-ray diffraction study using microwave-induced temperature-jumps.

The dynamics and mechanism of the premelting (L beta'-P beta') and main transitions (P beta'-L alpha) in fully hydrated dipalmitoylphosphatidylcholine were examined by low-angle time-resolved x-ray diffraction (TRXRD) using microwave radiation to effect uniform, internal sample heating. Equilibrium and dynamic aspects of the transitions were investigated. The dynamic studies involved applying a temperature jump of sufficient amplitude to effect the two transitions sequentially. Our findings are as follows. (a) Microwave radiation has proven useful as a means for implementing rapid and uniform internal heating in temperature-jump studies of lipid-phase transition kinetics. (b) Heating rate can be controlled by adjusting microwave power setting. (c) The thermal expansion coefficient of the three lyotropic phases follows the sequence L beta' not equal to O greater than P beta' much greater than L alpha. (d) Regardless of temperature-jump amplitude and sample heating rate the P beta' phase was always in evidence as an intermediate between the L beta' and L alpha phases. (e) The degree of development of the P beta' phase was inversely proportional to temperature-jump amplitude and heating rate. (f) The shortest transit time recorded for the combined L beta'-P beta', and P beta'-L alpha transitions was less than 1 s. (g) Upon cooling from the L alpha phase the onset of the chain disorder/order transition was apparent as a dramatic change of slope in the scattering angle vs. time plot which is interpreted as arising from sample heating by the latent heat of the transition. (h) Based on the shape of the low-angle diffraction pattern of the P beta' phase the P beta'-L alpha transition appears to be reversible with no evidence of metastability as was observed in the slow scan TRXRD measurements of Tenchov et al. (1989. Biophys. J. 56:757-768).

1,2-Dipalmitoylphosphatidylcholine