Development of a hybrid EPR/NMR coimaging system.

Electron paramagnetic resonance imaging (EPRI) is a powerful technique that enables spatial mapping of free radicals or other paramagnetic compounds; however, it does not in itself provide anatomic visualization of the body. Proton magnetic resonance imaging (MRI) is well suited to provide anatomical visualization. A hybrid EPR/NMR coimaging instrument was constructed that utilizes the complementary capabilities of both techniques, superimposing EPR and proton-MR images to provide the distribution of paramagnetic species in the body. A common magnet and field gradient system is utilized along with a dual EPR and proton-NMR resonator assembly, enabling coimaging without the need to move the sample. EPRI is performed at approximately 1.2 GHz/ approximately 40 mT and proton MRI is performed at 16.18 MHz/ approximately 380 mT; hence the method is suitable for whole-body coimaging of living mice. The gradient system used is calibrated and controlled in such a manner that the spatial geometry of the two acquired images is matched, enabling their superposition without additional postprocessing or marker registration. The performance of the system was tested in a series of phantoms and in vivo applications by mapping the location of a paramagnetic probe in the gastrointestinal (GI) tract of mice. This hybrid EPR/NMR coimaging instrument enables imaging of paramagnetic molecules along with their anatomic localization in the body.     

EPR/NMR co-imaging for anatomic registration of free-radical images.

While electron paramagnetic resonance imaging (EPRI) enables spatial mapping of free radicals in the whole body of small animals, it solely visualizes the free-radical distribution and does not typically provide anatomic visualization of the body. However, anatomic registration is often required for meaningful interpretation of the EPRI-derived free-radical images. An approach is reported for whole-body, EPRI-based, free-radical imaging along with proton MRI in mice. EPRI instrumentation with a 750-MHz narrow band microwave bridge and transverse oriented electric field reentrant resonator, with automatic coupling control and automatic tuning control capability, was used to map the spatial distribution of nitroxide free radicals in phantoms and in living mice, while low-field proton MRI at 16 MHz was used to define the anatomic structure to register the EPR images. Small capillary tubes containing an aqueous radical label were used as markers to enable image superimposition. With this coregistration technique, the EPRI free-radical images were precisely registered, enabling assignment of the location of the observed free-radical distribution within the organs of the mice. This technique enabled differentiation of the distribution and metabolism of nitroxide radicals within the major organs and body sites of living mice.     

Correction of B1 inhomogeneities using echo-planar imaging of water

Reliable interpretation of the MR signal intensity over the FOV of an image must consider the spatial heterogeneity of instrumental sensitivity. A major source of such variation is the nonuniformity of the B₁ magnetic field of the radiofrequency coil. This heterogeneity can be minimized by coil design but is exaggerated by surface coils, which are used to maximize the signal-to-noise ratio for some applications. This paper describes a rapid method for mapping the B₁ field over the sample of interest, using ¹H echo-planar imaging, to correct for B₁ distortions. The method applies to ¹H imaging and has been extended to non-¹H imaging by using dual-frequency coils in which the B., distributions are matched for the ¹H frequency and the frequency of interest. The approach is demonstrated in phantoms, animals, and humans and for sodium imaging.     

Evaluation of the dose distribution gradient in the close vicinity of brachytherapy seeds using electron paramagnetic resonance imaging

Electron paramagnetic resonance (EPR) spectroscopy has been successfully employed to determine radiation dose using alanine. The EPR signal intensity reflects the number of stable free radicals produced, and provides a quantitative measurement of the absorbed dose. The aim of the present study was to explore whether this principle can be extended to provide information on spatial dose distribution using EPR imaging (EPRI). Lithium formate was selected because irradiation induces a single EPR line, a characteristic that is particularly convenient for imaging purposes. ¹²⁵I‐brachytherapy seeds were inserted in tablets made of lithium formate. Images were acquired at 1.1 GHz. Monte Carlo (MC) calculations were used for comparison. The dose gradient can be determined using two‐dimensional (2D) EPR images. Quantitative data correlated with the dose estimated by the MC simulations, although differences were observed. This study provides a first proof‐of‐concept that EPRI can be used to estimate the gradient dose distribution in phantoms after irradiation. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Fast gated EPR imaging of the beating heart: Spatiotemporally resolved 3D imaging of free‐radical distribution during the cardiac cycle

In vivo or ex vivo electron paramagnetic resonance imaging (EPRI) is a powerful technique for determining the spatial distribution of free radicals and other paramagnetic species in living organs and tissues. However, applications of EPRI have been limited by long projection acquisition times and the consequent fact that rapid gated EPRI was not possible. Hence in vivo EPRI typically provided only time‐averaged information. In order to achieve direct gated EPRI, a fast EPR acquisition scheme was developed to decrease EPR projection acquisition time down to 10–20 ms, along with corresponding software and instrumentation to achieve fast gated EPRI of the isolated beating heart with submillimeter spatial resolution in as little as 2–3 min. Reconstructed images display temporal and spatial variations of the free‐radical distribution, anatomical structure, and contractile function within the rat heart during the cardiac cycle. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Black body and transverse electromagnetic resonators operating at 340 MHz: volume RF coils for ultra high field MRI

PURPOSE: The purpose of this work was to describe the newly formulated black body (BB) resonator with historical perspective and to outline the construction and assembly of the transverse electromagnetic (TEM) RF coil for use in ultra high field MRI (UHFMRI) studies at 340 MHz. METHOD: TEM and BB resonators were machined from acrylic and Teflon tubing, copper foil, and brass connectors. Tuning was accomplished through adjustable TEM elements. Variable Teflon-based capacitors were utilized to provide matching to the 50 omega line. The TEM resonator operated in quadrature, and the BB resonator operated in linear mode. The final resonators were fully adjustable from 63 to 430 MHz. Quality (Q) values were measured using a network analyzer over this frequency range for the unloaded and loaded coils. Coil performance was also evaluated using gradient and spin echo imaging at 8 T. RESULTS: Both resonators yielded excellent images from mineral oil phantoms, with good homogeneity throughout the imaging volume. The BB resonator was characterized with enhanced signal-to-noise ratio and greatly reduced RF power requirements relative to the TEM resonator. Images obtained from the human head at 8 T with the TEM resonator were also excellent. Tuning remains a tedious process. CONCLUSION: The TEM resonator provides an excellent RF coil for imaging studies up to 340 MHz. Its homogeneity reliability remains to be improved. In part as a result of its inability to sustain radiative loses, the BB resonator has extremely low RF power requirements. The BB resonator may have important uses in limiting RF power requirements and enhancing signal-to-noise ratio at other frequencies. Larger slightly modified versions may also prove useful in human imaging, depending on tolerances and final quality factors.     

Imaging spin probe distribution in the tumor of a living mouse with 250 MHz EPR: correlation with BOLD MRI.

Electron paramagnetic resonance imaging (EPRI) promises to provide new insights into the physiology of tissues in health and disease. Understanding the in vivo imaging capability of this new modality requires comparison with other physiologically responsive techniques. Here, an initial comparison between 2D EPR spatial imaging of a narrow single line injectable paramagnetic trityl spin probe and 2D slice-selected carbogen subtraction BOLD MRI is presented. The images were obtained from the same FSa fibrosarcoma grown in the leg of a C3H mouse. This tumor was unusual in comparison with others imaged with subtraction BOLD MRI because of its peripheral distribution of intensity. The spatial distribution of the EPR spin probe showed the same peripheral distribution. The pixel resolutions of these images are comparable. These images provide an early in vivo comparison of EPRI with a well-established imaging modality. The comparison validates the in vivo distribution of spin probe as imaged with EPRI, and provides a proof of principle for the comparison of BOLD and EPRI.     

Radio frequency magnetic field mapping of a 3 Tesla birdcage coil: experimental and theoretical dependence on sample properties.

The RF B(1) distribution was studied, theoretically and experimentally, in phantoms and in the head of volunteers using a 3 T MRI system equipped with a birdcage coil. Agreement between numerical simulation and experiment demonstrates that B(1) distortion at high field can be explained with 3D full-Maxwell calculations. It was found that the B(1) distribution in the transverse plane is strongly dependent on the dielectric properties of the sample. We show that this is a consequence of RF penetration effects combined with RF standing wave effects. In contrast, along the birdcage coil z-axis the B(1) distribution is determined mainly by the coil geometry. In the transverse plane, the region of B(1) uniformity (within 10% of the maximum) was 15 cm with oil, 6 cm with distilled water, 11 cm with saline, and 10 cm in the head. Along z the B(1) uniformity was 9 cm with phantoms and 7 cm in the head.     

Direct magnetic resonance imaging of histological tissue samples at 3.0T.

Direct imaging of a histological slice is challenging. The vast difference in dimension between planar size and the thickness of histology slices would require an RF coil to produce a uniform RF magnetic (B1) field in a 2D plane with minimal thickness. In this work a novel RF coil designed specifically for imaging a histology slice was developed and tested. The experimental data demonstrate that the coil is highly sensitive and capable of producing a uniform B1 field distribution in a planar region of histological slides, allowing for the acquisition of high-resolution T2 images and T2 maps from a 60-microm-thick histological sample. The image intensity and T2 distributions were directly compared with histological staining of the relative iron concentration of the same slice. This work demonstrates the feasibility of using a microimaging histological coil to image thin slices of pathologically diseased tissue to obtain a precise one-to-one comparison between stained tissue and MR images.     

Proton electron double resonance imaging (PEDRI) of the isolated beating rat heart.

Proton electron double resonance imaging (PEDRI) is a double resonance technique where proton MRI is performed with irradiation of a paramagnetic solute. A low-field PEDRI system was developed at 20.1 mT suitable for imaging free radicals in biological samples. With a new small dual resonator, PEDRI was applied to image nitroxide free radicals in isolated beating rat hearts. Experiments with phantoms showed maximum image enhancement factors (IEF) of 42 or 28 with TEMPONE radical concentrations of 2-3 mM at EPR irradiation powers of 12W or 6W, respectively. In the latter case, image resolution better than 0.5 mm and radical sensitivity of 5 microM was obtained. For isolated heart studies, EPR irradiation power of 6W provided optimal compromise of modest sample heating with good SNR. Only a small increase in temperature of about 1 degrees C was observed, while cardiac function remained within 10% of control values. With infusion of 3 mM TEMPONE an IEF of 15 was observed enabling 2D or 3D images to be obtained in 27 sec or 4.5 min, respectively. These images visualized the change in radical distribution within the heart during infusion and clearance. Thus, PEDRI enables rapid and high-quality imaging of free radical uptake and clearance in perfused hearts and provides a useful technique for studying cardiac radical metabolism.     

Feasibility and assessment of non-invasive in vivo redox status using electron paramagnetic resonance imaging

Purpose:
To test the feasibility of electron paramagnetic resonance imaging (EPRI) to provide non-invasive images of tissue redox status using redox-sensitive paramagnetic contrast agents. Material and Methods:
Nitroxide free radicals were used as paramagnetic agents and a custom-built 300 MHz EPR spectrometer/imager was used for all studies. A phantom was constructed consisting of four tubes containing equal concentrations of a nitroxide. Varying concentrations of hypoxanthine/xanthine oxidase were added to each tube and reduction of the nitroxide was monitored by EPR as a function of time. Tumor-bearing mice were intravenously infused with a nitroxide and the corresponding reduction rate was monitored on a pixel-by-pixel basis using 2D EPR of the tumor-bearing leg and normal leg serving as control. For animal studies, nitroxides were injected intravenously (1.25 mmol/kg) and EPR projections were collected every 3 min after injection using a magnetic field gradient of 2.5 G/cm. The reduction rates of signal intensity on a pixel-by-pixel basis were calculated and plotted as a redox map. Redox maps were also collected from the mice treated with diethylmaleate (DEM), which depletes tissue thiols and alters the global redox status. Results:
Redox maps obtained from the phantoms were in agreement with the intensity change in each of the tubes where the signals were decreasing as a function of the enzymatic activity, validating the ability of EPRI to accurately access changes in nitroxide reduction. Redox imaging capability of EPR was next evaluated in vivo. EPR images of the nitroxide distribution and reduction rates in tumor-bearing leg of mice exhibited more heterogeneity than in the normal tissue. Reduction rates were found to be significantly decreased in tumors of mice treated with DEM, consistent with the depletion of thiols and the consequent alteration of the redox status. Conclusion:
Using redox-sensitive paramagnetic contrast agents, EPRI can non-invasively discriminate redox status differences between normal tissue and tumors.     

Eigenmode analysis of transmit coil array for tailored B1 mapping

In vivo radiofrequency (RF) field B₁ mapping represents an essential prerequisite for parallel transmit applications. However, the large dynamic range of the transmit fields of the individual coil elements challenges the accuracy of MR‐based B₁ mapping techniques. In the present work, the B₁ mapping error and its impact on the RF performance are studied based on a coil eigenmode analysis. Furthermore, the linear properties of the transmit chain are exploited to virtually adjust the weighting of the different coil eigenmodes in the B₁ mapping procedure, resulting in considerably reduced mapping errors. In addition, the weighting of the eigenmodes is tailored to potential target applications, e.g., specific absorption rate (SAR) reduced RF shimming or multidimensional RF pulses, resulting in improved RF performance. The basic theoretic principles of the concept are elaborated and validated by corresponding simulations. Furthermore, results on B₁ mapping and RF shimming experiments, performed on phantoms and in vivo using a 3‐T scanner equipped with an eight‐channel transmit/receive body coil, are presented to prove the feasibility of the approach. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Hexagonal zero mode TEM coil: a single-channel coil design for imaging multiple small animals.

A novel hexagonal coil design for simultaneous imaging of multiple small animals is presented. The design is based on a coaxial cavity and utilizes the magnetic field formed between two coaxial conductors with hexagonal cross-sections. An analytical solution describing the B(1) field between conductors of the hexagonal coil was found from the Biot-Savart law. Both experimental results and analytical calculations showed a variation in the B(1) field within the imaging region of less than 10%. Numerical calculations predicted approximately 35% improvement in B(1) field homogeneity with the hexagonal coil design compared to a cylindrical coaxial cavity design. The experimentally-measured signal-to-noise ratio (SNR) of the hexagonal coil loaded with six 50-mM phantoms was only 4-5% lower than that of a single parallel plate resonator loaded with one phantom. In vivo spin-echo (SE) images of six 7-day-old rat pups acquired simultaneously demonstrated sufficient SNR for microimaging. The construction scheme of the coil, simple methods for tuning and matching, and an anesthesia device and animal holder designed for the coil are described. The hexagonal coil design utilizes a single receiver and allows for simultaneous imaging of six small animals with no significant compromise in SNR.     

Development of a PEDRI free-radical imager using a 0.38 T clinical MRI system.

Proton electron double resonance imaging (PEDRI) uses the Overhauser effect to image the distribution of free-radicals in biological samples and animals. Standard MRI hardware and software is used, with the addition of hardware to irradiate the free-radical-of-interest's EPR resonance. For in vivo applications it must be implemented at a sufficiently low magnetic field to result in an EPR irradiation frequency that will penetrate the sample but will not cause excessive nonresonant power deposition therein. Many clinical MRI systems use resistive magnets that are capable of operating at 10-20 mT, and which could thus be used as PEDRI imagers with the addition of a small amount of extra hardware. This article describes the conversion of a 0.38 T whole-body MRI system for operation as a 20.1 mT small-animal PEDRI imager. The magnet power supply control electronics required a small modification to operate at the lower field strength, but no permanent hardware changes to the MRI console were necessary, and no software modification was required. Frequency down- and up-conversion was used on the NMR RF system, together with a new NMR/EPR dual-resonance RF coil assembly. The system was tested on phantoms containing free-radical solution, and was also used to image the distribution of a free-radical contrast agent injected intravenously into anesthetized mice.     

In vivo imaging of a stable paramagnetic probe by pulsed-radiofrequency electron paramagnetic resonance spectroscopy

Imaging of free radicals by electron paramagnetic resonance (EPR) spectroscopy using time domain acquisition as in nuclear magnetic resonance (NMR) has not been attempted because of the short spin-spin relaxation times, typically under 1 μs, of most biologically relevant paramagnetic species. Recent advances in radiofrequency (RF) electronics have enabled the generation of pulses of the order of 10–50 ns. Such short pulses provide adequate spectral coverage for EPR studies at 300 MHz resonant frequency. Acquisition of free induction decays (FID) of paramagnetic species possessing inhomogenously broadened narrow lines after pulsed excitation is feasible with an appropriate digitizer/averager. This report describes the use of time-domain RF EPR spectrometry and imaging for in vivo applications. FID responses were collected from a water-soluble, narrow line width spin probe within phantom samples in solution and also when infused intravenously in an anesthetized mouse. Using static magnetic field gradients and back-projection methods of image reconstruction, two-dimensional images of the spin-probe distribution were obtained in phantom samples as well as in a mouse. The resolution in the images was better than 0.7 mm and devoid of motional artifacts in the in vivo study. Results from this study suggest a potential use for pulsed RF EPR imaging (EPRI) for three-dimensional spatial and spectral-spatial imaging applications. In particular, pulsed EPRI may find use in in vivo studies to minimize motional artifacts from cardiac and lung motion that cause significant problems in frequency-domain spectral acquisition, such as in continuous wave (cw) EPR techniques.     

Achieving plane-wise uniform B1 amplitude in a 3D volume for high-field MRI: a computer simulation study

PURPOSE: To demonstrate the possibility of achieving plane-wise uniform B(1) field amplitude for human head imaging with an array coil configuration by using computer simulations. MATERIALS AND METHODS: We considered the use of an excitation array coil that employed composite excitation elements. Each composite excitation element consisted of three small current loops centered close to each other with axes along the x, y, and z directions, respectively. The excitation elements were distributed to surround a model human head. The vector B(1) field from each current loop was calculated using the FDTD numerical method at 170 MHz. Analytical target RF field patterns with plane-wise uniform B(1) field amplitude were derived and approximately constructed from the fields of individual current loops through a least-squares procedure. RESULTS: The RF field patterns generated by the computer simulations closely followed the target field patterns. Highly uniform B(1) field amplitude was obtained within parallel sagittal planes or parallel axial-to-coronal oblique planes in the brain with the expected plane-to-plane variations. CONCLUSION: In principle, patterns of B(1) amplitude distribution with a high degree of plane-wise homogeneity can be achieved simultaneously in multiple parallel planes in a 3D volume.     

A multipurpose MRI phantom based on a reverse micelle solution

Many chemical solutions for use in magnetic resonance imaging phantoms have been reported in the literature. Each of these solutions has its application-specific advantages and disadvantages. We propose a single reverse micelle phantom solution, which, although not a universal phantom solution, may find applications in testing of the radio frequency transmit and receive fields of an imaging coil, the homogeneity of the static magnetic field, and the suppression in a fat or water saturation imaging sequence. The solution is thermodynamically stable and biologically inert, it possesses a smaller standing wave artifact than water, and its overall spin lattice relaxation times may be adjusted.     

Advantageous application of a surface coil to EPR irradiation in overhauser‐enhanced MRI

The present study describes the advantageous application of a surface coil to electron paramagnetic resonance (EPR) irradiation in Overhauser‐enhanced MRI (OMRI). OMRI is a double‐resonance method for imaging free radicals based on the Overhauser effect. Proton NMR images are recorded without and with EPR irradiation of the free radical resonance, which results in a difference proton image that shows signal enhancement in spatial regions that contain the free radical. To obtain good signal enhancement in OMRI, very high RF power and a long EPR irradiation time are required. To improve sensitivity and shorten the image acquisition time, especially for localized (and topical) applications, we developed and tested a surface‐coil‐type EPR irradiation coil. Theoretical calculations and experimental data showed that EPR irradiation through the surface coil could ameliorate the localized Overhauser enhancement, which was related to the ratio of B₁ surface coil/B₁ volume coil in the region of interest (ROI), as expected. The increased sensitivity could also be converted into a shortened EPR irradiation time, resulting in fast data acquisition. For biomedical applications, the use of a surface coil (as opposed to a conventional volume coil) could decrease the total RF power deposition in the sample required to obtain the same Overhauser enhancement in the ROI. Magn Reson Med 57:806–811, 2007. © 2007 Wiley‐Liss, Inc.     

Saturated double-angle method for rapid B1+ mapping.

For in vivo magnetic resonance imaging at high field (> or =3 T) it is essential to consider the homogeneity of the active B(1) field (B(1)+), particularly if surface coils are used for RF transmission. A new method is presented for highly rapid B(1)+ magnitude mapping. It combines the double angle method with a B(1)-insensitive magnetization-reset sequence such that the choice of repetition time (TR) is independent of T(1) and with a multislice segmented (spiral) acquisition to achieve volumetric coverage with adequate spatial resolution in a few seconds. Phantom experiments confirmed the accuracy of this technique even when TR < T(1), with the side effect being lowered SNR. The speed of this method enabled B(1)+ mapping in the chest and abdomen within a single breath-hold. In human cardiac imaging, the method enabled whole-heart coverage within a single 16-s breath-hold. Results from phantoms and healthy volunteers at 1.5 T and 3 T are presented.     

High resolution electron paramagnetic resonance imaging of biological samples with a single line paramagnetic label

The application of electron paramagnetic resonance imaging (EPRI) to obtain information from biological samples has been limited by the lack of ideal single line radical labels. The commonly used nitroxides exhibit multiple lines causing either hyperfine-based limitations in the maximum obtainable image resolution or hyperfine-based artifacts in the reconstructed image. The use of a novel single-line triarylmethyl paramagnetic label that enables marked enhancement in image quality and resolution is reported. This label exhibits a single line EPR spectrum that is sharp (linewidth ～60 mG in the absence of oxygen) and relatively stable in tissues. The potential of this label in enabling high resolution EPR imaging of biological samples was demonstrated in a series of phantoms and isolated biological organs such as the rat kidney. The images demonstrate that resolutions better than 100 μm could be obtained at L-band on samples of up to 20 mm in size.