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D J Lurie

Publications and source records attributed to D J Lurie.

At least 19 recordsLinked to original sources

Continuous-wave magnetic resonance imaging of short T(2) materials.

There is growing interest in the use of magnetic resonance imaging (MRI) to examine solid materials where the restricted motion of the probed spins leads to broad lines and short T(2) values, rendering many interesting systems invisible to conventional 2DFT pulsed imaging methods. In EPR T(2) seldom exceeds 0.1 mus and continuous-wave methods are adopted for spectroscopy and imaging. In this paper we demonstrate the use of continuous-wave MRI to obtain 2-dimensional images of short T(2) samples. The prototype system can image samples up to 50 mm in diameter by 60 mm long and has been used to image polymers and water penetration in porous media. Typical acquisition times range between 10 and 40 min. Resolution of 1 to 2 mm has been achieved for samples with T(2) values ranging from 38 to 750 mus. There is the possibility of producing image contrast that is determined by the material properties of the sample.

Journal Article↗

Optimization of field-cycled PEDRI for in vivo imaging of free radicals.

A numerical model of the behaviour of the magnetization in a field-cycled dynamic nuclear polarization (DNP) experiment is presented, with the aim of optimizing pulse sequence parameters in field-cycled proton-electron double-resonance free radical imaging. The model is used to predict the observed enhancement of the NMR signal as a function of the magnetic field strength, EPR irradiation frequency and pulse sequence timing, as well as the properties of the sample including the NMR and EPR relaxation times. The model allowed optimization of parameters in the field-cycled DNP experiment, in particular the EPR irradiation frequency, to find the value which would give the largest difference between NMR signals recorded with and without EPR irradiation. Experiments to verify the model were carried out using aqueous solutions of TEMPOL, which exhibits three hyperfine lines in its EPR spectrum and triarylmethyl (TAM), which has a single, narrow line. It was found that the model predicted very well the variation in DNP enhancement with EPR irradiation power for both samples. The behaviour of the NMR signal with EPR irradiation frequency in studies using TEMPOL was also accurately modelled, with the optimum frequency lying between 60 and 80 MHz, depending on the EPR irradiation power. The optimum frequency obtained from the model also agreed with the experimental data obtained using the TAM free radical, but with this sample the theoretical curves tended to deviate from the experimental data at irradiation frequencies below 70 MHz.

Electron Spin Resonance Spectroscopy↗

Free radical imaging.

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Electron Spin Resonance Spectroscopy↗

Biological applications of spin pH probes.

The determination of pH is one of the most important problems in the biochemistry of living organisms, since many of the vital processes of cells and cellular organelles depend on the local pH value. Amongst currently used experimental approaches for the measurement of pH, the application of spin pH probes in combination with EPR spectroscopy is a comparatively new and rapidly developing field. In this article we describe the background, advantages and limitations of the method of spin pH probes, and discuss its recent applications. Availability of a wide variety of pH-sensitive nitroxides with different ranges of pH-sensitivity, labeling group and lipophilicity facilitates their application to a variety of biological systems from subcellular organelles to complex organisms. The recent progress in low-field EPR-based imaging and spectroscopy-based techniques allows spin pH probes to be used for non-invasive in vivo pH measurement and pH-sensitive imaging.

Animals↗

Low field (10 mT) pulsed dynamic nuclear polarization.

EPR irradiation by a train of inverting pulses has potential advantages over continuous-wave EPR irradiation in DNP applications; however, it has previously been used only at high field (5 T). This paper presents the design and testing of an apparatus for performing pulsed DNP experiments at 10 mT with large samples (17 ml). Experimental results using pulsed DNP with an aqueous solution of a narrow-linewidth paramagnetic probe are presented. A maximum DNP enhancement of about -36 with a train of inverting pulses (width 500 ns, repetition time 4 micros) was measured. A preliminary comparison showed that, when the same enhancement value is considered, the pulsed DNP technique requires an average power that is about three times higher than that required with the CW irradiation. However, for in vivo DNP applications it is very important to minimize the average power deposited in the sample. From the experimental results reported in this work, when considering the maximum enhancement, the pulsed technique requires only 2% of the average power necessary with the CW DNP technique. We believe that this reduction in the average power can be important for future DNP studies with large biological samples.

Electron Spin Resonance Spectroscopy↗

Detection of nitrosyl-iron complexes by proton-electron-double-resonance imaging.

The nitrogen monoxide radical (NO*) forms paramagnetic mono- and dinitrosyl-iron complexes in biologic tissues. To establish a noninvasive technique for in vivo NO* imaging, we evaluated the suitability of these complexes as magnetic resonance (MR) contrast agents, making use of the ability of the unpaired electrons of the complexes to enter into dynamic nuclear polarization with water protons and hence produce enhancement on images generated by the technique of proton-electron-double-resonance imaging (PEDRI). Phantom solutions of synthetic nitrosyl-iron complexes (NICs) altered the signal intensity of PEDRI images. The dinitrosyl-iron complex (DNIC) with serum albumin induced a significantly larger signal alteration than the mononitrosyl-iron complex (MNIC) with dithiocarbamate. Exposure of rat liver to sodium nitroprusside (SNP) by ex vivo and in situ perfusion induced a composite X-band electron spin resonance (ESR) spectrum of the isolated liver characteristic of a MNIC and DNIC. On storage of the tissue, the MNIC signal disappeared and the DNIC signal intensity increased. Correspondingly, in cross-sectional PEDRI images taken at room temperature, the SNP-exposed livers initially exhibited a weak signal that strongly increased with time. In conclusion, NICs can be detected using PEDRI and could be exploited for in vivo NO* imaging.

Animals↗

Rapid imaging of free radicals in vivo using field cycled PEDRI.

Imaging of free radicals in vivo using an interleaved field-cycled proton-electron double-resonance imaging (FC-PEDRI) pulse sequence has recently been investigated. In this work, in order to reduce the EPR (electron paramagnetic resonance) irradiation power required and the imaging time, a centric reordered snapshot FC-PEDRI pulse sequence has been implemented. This is based on the FLASH pulse sequence with a very short repetition time and the use of centric reordering of the phase-encoding gradient, allowing the most significant free induction decay (FID) signals to be collected before the signal enhancement decays significantly. A new technique of signal phaseshift correction was required to eliminate ghost artefacts caused by the instability of the main magnetic field after field cycling. An FID amplitude correction scheme has also been implemented to reduce edge enhancement artefacts caused by the rapid change of magnetization population before reaching the steady state. Using the rapid pulse sequence, the time required for acquisition of a 64 x 64 pixel FC-PEDRI image was reduced to 6 s per image compared with about 2.5 min with the conventional pulse sequence. The EPR irradiation power applied to the sample was reduced by a factor of approximately 64. Although the resulting images obtained by the rapid pulse sequence have a lower signal to noise than those obtained by a normal interleaved FC-PEDRI pulse sequence, the results show that rapid imaging of free radicals in vivo using snapshot FC-PEDRI is possible.

Animals↗

Chemically induced analgesic nephropathy in the rat monitored by proton-electron double-resonance imaging (PEDRI).

Proton-electron double-resonance imaging (PEDRI) was used to assess renal function by monitoring the flow of the exogenous nitroxide free radical proxyl carboxylic acid (PCA) through normal and injured kidneys in the living rat. Kidney damage was induced by treatment with 2-bromoethylamine (BEA), which provides a well established model for human analgesic nephropathy. PCA clearance rates for liver, abdominal blood vessels, and renal tissues were determined from serial PEDRI images of normal rats (n = 6) and rats treated with BEA (n = 21). Different groups of BEA-treated animals were imaged on day 4 (n = 6), day 6 (n = 6), and day 9 (n = 9) after treatment. In BEA-treated rats, there was an increase in PCA half-life in all tissues studied. This increase was greatest in the kidney tissues and the effect progressed with time after treatment. The effect is probably due to BEA-induced damage to the tubules in the renal cortex and may not be related to the primary lesions in the renal medulla.

Analgesics↗

Recent developments in combining LODESR imaging with proton NMR imaging.

We have designed and constructed RF coil assemblies and the appropriate instrumentation for combining proton NMR imaging with LODESR imaging. This has enabled us to collect sequential images from the same sample using both methods. The coil assembly consists of a crossed ellipse coil for LODESR and proton NMR signal detection and a saddle coil for excitation of the ESR resonance. Images have been collected of phantoms containing copper sulphate and Tempol solutions. NMR images were collected (4.3 min) and within 30 s LODESR data collection started (collection time 2.5 min). Only the Tempol solutions are visible in the LODESR images.

Animals↗

Multimodality magnetic resonance systems for studying free radicals in vivo.

The multimodality approach to in vivo detection of free radicals combines the relative benefits of three free radical detection modalities: conventional RF CW-ESR, LODESR and PEDRI. We have built apparatus capable of combining these modalities to allow sequential PEDRI and CW-ESR, sequential LODESR and proton NMR imaging and simultaneous LODESR and CW-ESR. These systems offer superior performance in terms of both the scope and quality of information over single-modality free radical detection systems.

Animals↗

Design, construction and use of a large-sample field-cycled PEDRI imager.

The design, construction and use of a large-scale field-cycled proton-electron double-resonance imaging (FC-PEDRI) imager is described. The imager is based on a whole-body sized, vertical field, 59 mT permanent magnet. Field cycling is accomplished by the field compensation method, and uses a secondary, resistive magnet with an internal diameter of 52 cm. The magnetic field can be switched from zero to 59 mT or vice versa in 40 ms. It is used with a double-resonance coil assembly (NMR/EPR) comprising a solenoidal NMR transmit/receive coil and a coaxial, external birdcage resonator for EPR irradiation. Experiments to image the distribution of an exogenous nitroxide free radical in anaesthetized rabbits are described.

Animals↗

The application of PEDRI to the study of free radicals in vivo.

Proton-electron double-resonance imaging (PEDRI) has considerable value for study of the distribution and elimination pathways of nitroxide free radicals (NFRs). This has been illustrated by its use in studies of kidney function in the living rat in which the NFR proxyl carboxylic acid (PCA) has been employed as a 'tracer'. The technique, at its present stage of development, can demonstrate location of PCA in enough detail to observe the passage through kidney cortex and medulla differentially, and to see the NFR within the major abdominal blood vessels. These studies are helping towards an understanding of the metabolic fate of PCA, as well as providing information about kidney performance after challenge with a nephrotoxin. In addition, nitric oxide complexes, formed in vivo by providing rats with a nitrite-rich diet, have been observed ex vivo using PEDRI and field-cycled DNP.

Animals↗

Nitroxide free radical clearance in the live rat monitored by radio-frequency CW-EPR and PEDRI.

The use of RF (100 to 300 MHz) PEDRI and CW-EPR techniques allows the in vivo study of large animals such as whole rats and rabbits. Recently a PEDRI instrument was modified to also allow CW-EPR spectroscopy with samples of similar size and under the same experimental conditions. In the present study, this CW-EPR and PEDRI apparatus was used to assess the feasibility of the detection of a pyrrolidine nitroxide free radical (2,2,5,5,-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid, PCA) in the abdomen of rats. In particular, we have shown that after the PCA administration (4 mmol kg(-1) b.w.): (i) the PCA EPR linewidth does not show line broadening due to concentration effects; (ii) a similar PCA up-take phase is observed by EPR and PEDRI; and (iii) the PCA half-lives in the whole abdomen of rats measured with the CW-EPR (T1/2=26+/-4 min, mean+/-sd, n=10) and PEDRI (T1/2=29+/-4 min, mean+/-sd, n=4) techniques were not significantly different (p > 0.05). These results show, for the first time, that information about PCA pharmacokinetics obtained by CW-EPR is the same as that from PEDRI under the same experimental conditions.

Animals↗

The excretion mechanism of the spin label proxyl carboxylic acid (PCA) from the rat monitored by X-band ESR and PEDRI.

Proton electron double resonance imaging (PEDRI) was used for monitoring in vivo the distribution, metabolism and, in particular, the excretion mechanism of the exogenous nitroxide free radical proxyl carboxylic acid (PCA) in the rat. PCA clearance half-lives through liver, abdominal vessels, and renal tissues were determined from a series of PEDRI images for normal rats (n = 5) and rats treated with probenecid (n = 5), a competitive inhibitor of the tubular secretion process. The approximately doubled renal half-lives of the treated animals suggest that tubular secretion accounts for about 50% of PCA renal loss in the normal rat and reabsorption is insignificant. PCA binding to bovine serum albumin was investigated by X-band ESR and the bound fraction was found to be less than 10% of the total PCA. Most probably, PCA binds to hydrophilic sites. Blood PCA concentration investigated by X-band ESR exhibited biphasic behavior and PEDRI results confirmed the in vivo metabolic reduction of PCA by rat liver cells.

Animals↗

Continuous-wave NMR imaging of solids.

Current pulsed nuclear magnetic resonance methods of imaging samples such as solids with short spin-spin relaxation times are restricted to use with T2 values longer than approximately 10 microseconds. In the present study a method of imaging ultra-short T2 samples using continuous- wave, swept-field NMR is presented that, in principle, will be able to overcome this restriction. The technique is identical to that used in continuous-wave electron paramagnetic resonance imaging of paramagnetic species and involves irradiating the sample continuously with a radiofrequency excitation in the presence of a strong stationary magnetic field gradient. When the main magnetic field is swept over a suitable range, the variation of the NMR absorption signal with applied magnetic field yields a one-dimensional projection of the object under study along the gradient direction. Two- or three-dimensional image data sets may be reconstructed from projections that are obtained by applying the gradient in different directions. Signal-to-noise ratio can be improved by modulating the magnetic field and employing a lock-in amplifier to recover signal variations at the audio modulation frequency. Preliminary experiments were performed using a 7 Tesla magnet and a 300 MHz continuous-wave radiofrequency bridge with lock-in detection. The apparatus is described and the results of pilot experiments that employed vulcanized rubber samples are presented. The ability of the technique to detect short T2 samples was demonstrated by the presence of a background signal from the Perspex former of the birdcage resonator used for signal reception.

Magnetic Resonance Spectroscopy↗

The dissociation of some 111In chelates in the presence of transferrin and haemoglobin studied by PAC.

The interaction of [111In]Tris-chelates with protein molecules in aqueous solution at room temperature has been studied using time-integral and time-differential PAC. Increasing amounts of apo-transferrin were added to solutions of [111In]tropolonate, -acetylacetonate, -oxinate and -oxine sulphate, and of haemoglobin to [111In]tropolonate. The transfer of 111In from chelate to protein was monitored by time-integral PAC measurements. Analysis of these data in erms of stability constants showed that with added transferrin complete dissociation of each 111In chelate occurred with increasing protein concentration, the radiolabel being sequestered by the protein molecules. Confirmation of this was provided by time-differential PAC measurements at four tropolone:transferrin relative concentrations, and in the pure systems. A value for the first stability constant of transferrin is presented. Analysis of time-integral PAC data showed that added haemoglobin did not cause complete dissociation of [111In]tropolonate, a [111In]tropolone-haemoglobin complex being formed. Time-differential PAC studies of the [111In]tropolonate:haemoglobin and [111In]haemoglobin systems at 77 K and 295 K supported this conclusion, revealing quadrupole frequencies of 14.0 +/- 0.6 MHz in [111In]haemoglobin and 9.1 +/- 1.1 MHz in the mixed system.

Drug Stability↗