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The magnet system for rapid scan electron paramagnetic resonance imaging and spectroscopy
Abstract
The magnet and gradient systems suitable for electron paramagnetic resonance imaging experiments at RF range are presented. The air-core magnet based on the Helmholtz design in the article has a unique conical shape. A comprehensive study regarding the coils adjustment providing for the maximum field homogeneity is given. The z gradient is a four-coil system (seventh order), the transverse gradients are Golay coils (fifth order), and the scan system is the Helmholtz coil (fourth order). The magnet generates continuously a field of 37 mT (370 G), and the orthogonal gradient coils are designed to yield 100 mT/m (10 G/cm). The experimental tests have shown that the field generated is homogeneous to ±10 ppm in the 6 × 6 × 3 cm3 region (x/y/z), which is our field of interest, and to ±50 ppm in the 8 × 8 × 4 cm3 region (x/y/z). The system has the potential to monitor temporal changes of oxygen concentration in biological samples. © 2013 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 43B:22–31, 2013
... To obtain high spatial resolution in EPRI experiments large magnetic field gradient needs to be applied, which unfortunately causes signal broadening with simultaneous * corresponding author; e-mail: t.czechowski@novilet.eu amplitude decrease. Multiple attempts were made to increase the signal to noise ratio (SNR), which resulted in increasing the measurement speed [9,10], adjusting the detection method [1,11,12] and spectral-spatial imaging technique [13]. To overcome low SNR the amplitude of modulation higher than the 1/3 of the linewidth (referred to as an overmodulation) has been proposed. ...
... The measurements were carried out using a home built EPR imager [25] and a home written software. ...
... The measurements were carried out using a home built 280 MHz EPR imager [24] and a home written software. The Zeeman magnetic field was produced by the air-core magnet of a unique conical shape based on the Helmholtz principle powered by KEPCO power supply ATE 100-10M. ...
Design and construction of an electron paramagnetic resonance (EPR) spectrometer, operating in the continuous wave mode in the radio frequency (rf) region, and capable of performing spectroscopy and in vivo imaging of paramagnetic spin probes is described. A resonant frequency of 300 MHz was chosen to provide the required sensitivity at nontoxic levels of commonly used spin probes and penetration of the rf in small animals. Three major components, the magnet, the radio frequency signal detection bridge, and the data acquisition module are described in this article. Integration of a rapid scan capability to reduce imaging time is also described. Two- and three-dimensional EPR images of the spin probe distribution in phantom objects as well as from in vivo experiments are reported. From the EPR images, morphology of some internal organs could be recognized. EPR images of the spin probe distribution in mice suggest differences in perfusion of the spin probe between normal and tumor regions. Addition of a spectral dimension to spatial images should enable differentiation of oxygen status in normal and pathological conditions.
A time-domain radio frequency (rf) electron paramagnetic resonance (EPR) spectrometer/imager (EPRI) capable of detecting and imaging free radicals in biological objects is described. The magnetic field was 10 mT which corresponds to a resonance frequency of 300 MHz for paramagnetic species. Short pulses of 20–70 ns from the signal generator, with rise times of less than 4 ns, were generated using high speed gates, which after amplification to 283 Vpp, were deposited into a resonator containing the object of interest. Cylindrical resonators containing parallel loops at uniform spacing were used for imaging experiments. The resonators were maintained at the resonant frequency by tuning and matching capacitors. A parallel resistor and overcoupled circuit was used to achieve Q values in the range 20–30. The transmit and receive arms were isolated using a transmit/receive diplexer. The dead time following the trailing edge of the pulse was about 450 ns. The first stage of the receive arm contained a low noise, high gain and fast recovery amplifier, suitable for detection of spin probes with spin-spin relaxation times (T2) in the order of μs. Detection of the induction signal was carried out by mixing the signals in the receiver arm centered around 300 MHz with a local oscillator at a frequency of 350 MHz. The amplified signals were digitized and summed using a 1 GHz digitizer/summer to recover the signals and enhance the signal-to-noise ratio (SNR). The time-domain signals were transformed into frequency-domain spectra, using Fourier transformation (FT). With the resonators used, objects of size up to 5 cm3 could be studied in imaging experiments. Spatial encoding of the spins was accomplished by volume excitation of the sample in the presence of static field gradients in the range of 1.0–1.5 G/cm. The spin densities were produced in the form of plane integrals and images were reconstructed using standard back-projection methods. The image resolution of the phantom objects containing the spin probe surrounded by lossy biologic medium was better than 0.2 mm with the gradients used. To examine larger objects at local sites, surface coils were used to detect and image spin probes successfully. The results from this study indicate the potential of rf FT EPR for in vivo applications. In particular, rf FT EPR may provide a means to obtain physiologic information such as tissue oxygenation and redox status. © 1998 American Institute of Physics.
It has been hypothesized that free radical metabolism and oxygenation in living organs and tissues such as the heart may vary over the spatially defined tissue structure. In an effort to study these spatially defined differences, we have developed electron paramagnetic resonance imaging instrumentation enabling the performance of three-dimensional spectral-spatial images of free radicals infused into the heart and large vessels. Using this instrumentation, high-quality three-dimensional spectral-spatial images of isolated perfused rat hearts and rabbit aortas are obtained. In the isolated aorta, it is shown that spatially and spectrally accurate images of the vessel lumen and wall could be obtained in this living vascular tissue. In the isolated rat heart, imaging experiments were performed to determine the kinetics of radical clearance at different spatial locations within the heart during myocardial ischemia. The kinetic data show the existence of regional and transmural differences in myocardial free radical clearance. It is further demonstrated that EPR imaging can be used to noninvasively measure spatially localized oxygen concentrations in the heart. Thus, the technique of spectral-spatial EPR imaging is shown to be a powerful tool in providing spatial information regarding the free radical distribution, metabolism, and tissue oxygenation in living biological organs and tissues.
Proton-electron double-resonance imaging (PEDRI) is an alternative method to EPR for detecting and imaging free radicals in biological samples or animals. PEDRI uses the Overhauser effect, and involves collecting a proton NMR image while irradiating the EPR of the free radical under study. The spatial resolution in PEDRI is not affected by the linewidth of the free radical’s EPR resonance. An important development of the technique is field-cycled PEDRI (FC-PEDRI), in which the applied magnetic field is switched between two levels during the pulse sequence in order to decrease non-resonant RF power deposition and to increase sensitivity. A spectroscopic version of FC-PEDRI, called field-cycled dynamic nuclear polarization (FC-DNP) is useful for studying low concentrations of free radicals and enables EPR spectra to be obtained via the Overhauser effect. This Chapter describes the techniques and practical implementation of PEDRI and related techniques. Applications of the methods are described, and likely future uses of the techniques are discussed.
Designing a magnetically focused ribbon beam electron gun is totally dependent on one's ability to produce a highly homogeneous magnetic field. Such fields complying with different criteria of homogeneity were generated using four coils. The design parameters that minimised the RMS deviation of the field intensity from a constant value throughout the region of interest, were determined numerically. Electrons' trajectories from points along the source to a plane target, were calculated to evaluate the effect of the residual inhomogeneity of the optimal field. A four-coil system accurately implementing optimal design parameters, was built and successfully tested.
This paper describes the two-dimensional field generated by an M pole electromagnet of cylindrical symmetry. By individually controlling the currents on each pole, it is possible to rotate the direction of the field around the axis of the cylinder. Gradients of any order can also be generated. The dependence of the power on the physical dimensions of the whole magnet and on the gap region is also discussed.
A metallophthalocyanine radical, PcLi, was prepared by electrochemical oxidation of the corresponding dianion. The redox properties in solution show that PcLi is both easily reduced and easily oxidized (ΔE = Ered1/2-E1/2ox = 0.83 V). This property is of the utmost importance for obtaining intrinsic molecular semiconductors. The optical properties are similar to those for oxidized phthalocyanines and involve two low-lying π-π transitions at 430 and 810 nm. Despite the tendency to aggregation, the ESR spectrum of the isolated PcLi molecule has been obtained. It is consistent with an unpaired electron delocalized over the whole phthalocyanine ring.
A general method of designing magnetic field gradient coils for NMR imaging is suggested and developed. The method utilises a combination of exact calculations for infinite continuous current sheets with a series expansion method to analyse finite discrete models of the continuous case. The method is applied to two orientations for coils on a cylindrical form resulting in improvements of existing gradient coil designs.
A new method of obtaining a very homogeneous magnetic field compensated to the sixth order is suggested. This is achieved by lowering the current density in the central part of a simple cylindrical coil. The optimum volume of the necessary conductor for such a coil is smaller than for a so called outer notch coil compensated to the sixth order. The new type of homogeneous coils could be very advantageous for high field superconducting solenoids. An example is given of a 6 T superconducting solenoid with an inner diameter of 3.2 cm with a field homogeneity better than 10-6 throughout a spherical volume of 1 cm diameter, which requires 10% less superconductor than a notched coil.
Air-core coils are more practical than iron-core magnets for producing the required magnetic field distribution for electron paramagnetic resonance imaging at frequencies of a few hundred megahertz. An air-core, air-cooled magnet/gradient coil system is presented in this paper, which is optimum in the sense that mathematically it produces fields, which for the number of coils specified, are as uniform (for the magnet) and as linear (for the gradient coils) as is possible over a spherical volume. The magnet is four-coil (eighth-order), the z-coordinate gradient coil system is two-coil, Maxwell (fifth order), and the transverse gradient coils are four-coil, Anderson (fifth order). The design tradeoffs included homogeneity and linearity specifications, compatibility with access needed for physiological studies, power requirements, and provisions for rapid scanning. Incremental adjustments of the positions of the magnet coils, based on uniformity measurements, facilitated the meeting of design specifications at a reasonable cost. The 81 cm magnet can operate continuously at 90 G and can scan to 140 G. A 15 cm diameter working volume has a homogeneity of about 40 ppm. Three-dimensional gradient coils are designed for 10 G/cm. © 2002 Wiley Periodicals, Inc. Concepts in Magnetic Resonance (Magn Reson Engineering) 15: 51–58, 2002.
We have previously reported a high-spatial-resolution multisite electron paramagnetic resonance (EPR) oximetry method that
is based on consecutive applications of magnetic field gradients with the same direction but different magnitudes. This method
that could be called also two-gradient convolution EPR oximetry has no restrictions for the shape of solid paramagnetic materials
implanted in tissue and is applicable for any particulate EPR oxygen-sensitive matieral with a Lorentzian line shape. To enhance
the utilization of this method, a previously described algorithm was used to develop user-friendly Windows-based software.
Practical conditions of application of the method were established using several different model systems. It has been shown
that the spectral overlap from the adjacent sites can be neglected if the splitting between the corresponding lines exceeds
the largest line width by at least a factor of 1.3. An additional requirement of the method is that the second field gradient
should exceed by at least 30% the value of the first gradient. It was confirmed that the error in line width determination
at L-band is proportional to the noise-to-signal ratio, and does not exceed 1% a noise-to-signal ratio of 0.1 in a typical
in vivo experiment. We demonstrate that the line widths of up to 10 different sites can be determined.
To be able to perform a two-dimensional study of free radical distribution by the continuous-wave electron paramagnetic resonance
method in the X-band, special coils producing a magnetic gradient of 8 G/mm have been designed and constructed. The EPR spectra
recorded for this gradient were subjected to the procedure of deconvolution in order to elicit information on the concentration
of the radical distribution. The data obtained were used as the source file of the program reconstructing the image. The reconstruction
was based on the iterative simultaneous algebraic reconstruction technique (Andersen A.H., Kak A.C.: Ultrason. Imag. 6, 81–94,
1984). The quality of the generated images depends on the angle of the sample axis to the gradient direction set by a goniometer
and on the deconvolution procedures applied. The first tests on artificially generated phantoms indicated a dependence of
the obtained images on the magnetic field gradients applied. The determined spatial distribution of radicals has confirmed
their uniform distribution in the sample. The preliminary tests were performed for diphenyl-picrylhydrazyl. Having proved
the reliability of the method, analogous measurements were also performed for plyphenylene sulphide PPS-V1 and indicated a
homogeneous distribution of radicals in the whole volume of the sample. The images obtained confirmed the uniform distribution
of the radicals.
For strong homogeneous fields the ideal loop and solenoid elements of a prototype system may be expanded into thick cylindrical coils whose current density is (a) uniform or (b) inversely proportional to the cylindrical radius. Error coefficients of the zonal harmonic series for field or gradient that are cancelled in any given prototype continue to vanish as the elements are expanded, even to fusion, if at each stage the coil boundaries are adjusted by an iterative method. This involves the use of (a) the harmonic source functions Un* or (b) the Legendre functions Pn; either set is best computed by a recursion formula. An alternative method based on Lyle's principle requires no iterations and only trivial calculations. Though it also is valid for systems of any order, it can only expand a set of loops into coils with square cross sections of limited area. Also, the true null coefficients are replaced by small residues proportional to 4th and higher powers of the section dimensions when the second method is used.
The number of tabulated prototype systems of the 6th and 8th orders is increased to more than 200. Since multiply infinite sets of prototypes can be computed for every order higher than the 8th, univariate tables would be inadequate and only a few illustrative examples of such systems are given. Some 150 thick-walled systems of the 6th or 8th order are listed in several tables, but such a selection can only suggest the wide range of possibilities. These systems have more degrees of freedom than do the corresponding prototypes, and even the 6th order is multivariant. At the 8th order and beyond, the growing redundancy of variables permits the design of systems with a common current density in all coils and with all section dimensions proportional to a set of small integers. Systems of order 4n have paired coils with gaps for lateral access, an advantage that is lacking in the 6th-order designs.
Efficient computer programs have been written to design systems of all the types so far enumerated, including multiple sets of both prototypes and fully adjusted systems of thick coils for orders from 8 to 20 in steps of 4. Since adequate tabulation of results is ruled out by their diversity and sheer bulk, in view of the wide range of potential applications the programs themselves must be considered the basic research tool. They will be described in detail elsewhere.
As a measure of field inhomogeneity, including contributions from all orders and from both axial and radial field components, the concept of total vector error is developed. The tables include error limits for all systems, and some 40 systems or their error contours are shown in the figures.
We report the development of a novel radio frequency electron‐spin‐resonance spectrometer designed to provide measurements with high molar sensitivity and resolution in vivo. Radio frequency (250 MHz) is chosen to obtain good penetration in animal tissue and large aqueous samples with modest sacrifice of sensitivity. The spectrometer has a lumped component resonator and operates in continuous‐wave mode. The spectrometer is capable of two‐dimensional imaging, and with a modest addition should be capable of three‐dimensional imaging. We demonstrate 3‐mm spatial resolution for DPPH samples. For 10‐ml samples of aqueous nitroxide, we demonstrate sensitivity (normalized to spectral width of 1 G) to 3×10<sup>-</sup><sup>8</sup>‐M concentrations and spectral resolution of 0.1 G. Spectra from nitroxide spin label injected into a live mouse are shown.
The generation of uniform magnetic fields over extended regions of space by means of circular coils of large cross‐sectional area is analyzed. It is shown by an extension of Garrett's theory of axially symmetric magnetic fields that the optimum shape of the coil cross section can be found analytically without numerical integration over the winding area. The theory is illustrated by application to Helmholtz coils and double Helmholtz coils of rectangular cross section. Choice of the optimum dimensions makes it possible to generate very uniform fields of great intensity.
The coils described in this paper are assembled in two relatively thin flat stacks which are placed on each pole piece of a nuclear spin resonance magnet. One coil of each coil pair is in each of the two stacks, and each coil pair is so designed that the current circulating in it produces, in the airgap center, a correcting magnetic field describable by one of a set of spherical harmonics. The orthogonal properties of the spherical harmonics render possible substantially independent adjustments of the currents in the several coil pairs, when some spin resonance parameter such as line width is utilized to determine that individual optima are reached.
Experimental coil stacks with 13 coil pairs, for the second, third, and zonal fourth harmonics, have been constructed, and preliminary results obtained by Rex Richards (Oxford) indicate that when a 4-mm spin sample is used, this method can serve to reduce field inhomogeneities to less than 1 part in 108 with few sets of 13 current adjustments.
Design possibilities of single and double Helmholtz coils of rectangular cross section have been investigated for the purpose of generating magnetic fields which have the same or even better uniformity as compared to that achieved with the idealized coils of negligible winding cross section. It is shown that the optimum dimensions of coil configuration can be determined by means of numerical analysis, even under such practical conditions that the ratio of thickness to width of winding cross section and the turn ratio of the coil pairs should be ratios of relatively small integers. It is also suggested that the balancing method provides a possible means of extending the uniform region one and a half times as much as that achieved with the idealized coils of negligible winding cross section.
Electron paramagnetic resonance (EPR) imaging in the continuous wave (CW) and time-domain modes, as well as Overhauser-enhanced magnetic resonance imaging in vivo is described. The review is based mainly on the CW and time-domain EPR instrumentation at 300 MHz developed in our laboratory, and the relative merits of these methods for functional in vivo imaging of small animals to assess hypoxia and tissue redox status are described. Overhauser imaging of small animals at magnetic fields in the range 10-15 mT that is being carried out in our laboratory for tumor imaging and the evaluation of tumor hypoxia based on quantitative evaluation of Overhauser enhancement is also described. Alternate approaches to spectral-spatial imaging using the transverse decay constants to infer in situ line widths and hence in vivo pO2 using CW and time-domain EPR imaging are also discussed. The nature of the spin probes used, the quality of the images obtained in all the three methods, the achievable resolution, limitations and possible future directions in small animal functional imaging with these modalities are summarized.
The CW-EPR method of image reconstruction is based on sample rotation in a magnetic field with a constant gradient (50 G/cm). In order to obtain a projection (radical density distribution) along a given direction, the EPR spectra are recorded with and without the gradient. Deconvolution, then gives the distribution of the spin density. Projection at 36 different angles gives the information that is necessary for reconstruction of the radical distribution. The problem becomes more complex when there are at least two types of radicals in the sample, because the deconvolution procedure does not give satisfactory results. We propose a method to calculate the projections for each radical, based on iterative procedures. The images of density distribution for each radical obtained by our procedure have proved that the method of deconvolution, in combination with iterative fitting, provides correct results. The test was performed on a sample of polymer PPS Br 111 (p-phenylene sulphide) with glass fibres and minerals. The results indicated a heterogeneous distribution of radicals in the sample volume. The images obtained were in agreement with the known shape of the sample.
The authors define ordered subset processing for standard algorithms (such as expectation maximization, EM) for image restoration from projections. Ordered subsets methods group projection data into an ordered sequence of subsets (or blocks). An iteration of ordered subsets EM is defined as a single pass through all the subsets, in each subset using the current estimate to initialize application of EM with that data subset. This approach is similar in concept to block-Kaczmarz methods introduced by Eggermont et al. (1981) for iterative reconstruction. Simultaneous iterative reconstruction (SIRT) and multiplicative algebraic reconstruction (MART) techniques are well known special cases. Ordered subsets EM (OS-EM) provides a restoration imposing a natural positivity condition and with close links to the EM algorithm. OS-EM is applicable in both single photon (SPECT) and positron emission tomography (PET). In simulation studies in SPECT, the OS-EM algorithm provides an order-of-magnitude acceleration over EM, with restoration quality maintained.
Continuous wave (CW) electron paramagnetic resonance (EPR) imaging can be used to obtain slice-selective images of free radicals without measuring three-dimensional (3D) projection data. A method that incorporated a modulated magnetic field gradient (MFG) was combined with polar field gradients to select a slice in the subject noninvasively. The slice-selective in vivo EPR imaging of triarylmethyl radicals in the heads of live mice is reported. 3D surface-rendered images were successfully obtained from slice-selective images. In the experiment in mice, a slice thickness of 1.8 mm was achieved.
This article describes a method for reducing the acquisition time in three-dimensional (3D) continuous-wave electron paramagnetic resonance (CW-EPR) imaging. To visualize nitroxyl spin probes, which have a short lifetime in living organisms, the acquisition time for a data set of spectral projections should be shorter than the lifetime of the spin probes. To decrease the total time required for data acquisition, the duration of magnetic field scanning was reduced to 0.5s. Moreover, the number of projections was decreased by using the concept of a uniform distribution. To demonstrate this faster data acquisition, two kinds of nitroxyl radicals with different decay rates were measured in mice. 3D EPR imaging of 4-hydroxy-2,2,6,6-tetramethylpiperidine-d17-1-15N-1-oxyl in mouse head was successfully carried out. 3D EPR imaging of nitroxyl spin probes with a half-life of a few minutes was achieved for the first time in live animals.