Design and construction of an actively frequency-switchable RF coil for field-dependent Magnetisation Transfer Contrast MRI with fast field-cycling.

Magnetisation Transfer Contrast (MTC) is an important MR contrast-generating mechanism to characterise the MR-invisible macromolecular protons using an off-resonance pre-saturation RF irradiation pulse (or MT pulse). MTC MRI is normally implemented at a fixed magnetic field; however, it may be useful to evaluate changes of the MT effect as a function of external magnetic field strength (B0). In order to conduct field-dependent MTC experiments with a single MR system, two techniques are crucially needed. B0 should be able to be switched between levels during irradiation of the MT pulse. At the same time, the resonance frequency of the RF coil (f0) should also be able to be shifted to the corresponding value. Switching B0 is attained by the fast field-cycling technique, while in order to switch f0, a specially designed multi-tunable RF coil is required. Here, we designed and constructed an actively frequency-switchable RF coil for frequencies at and below 2.5 MHz. The design employed PIN diodes, and enabled switching f0 between five different values, with excellent impedance matching (approximately -37 dB S11 reflection) and Q-factor of about 100 at each configuration.

Cryogenic receive coil and low noise preamplifier for MRI at 0.01T.

We have investigated the design and construction of liquid nitrogen cooled surface coils made from stranded (litz) copper wire for low field MRI applications. If designed correctly, cooled litz coils can provide a competitive alternative to high temperature superconducting (HTS) coils without the complications associated with flux trapping. Litz coils can also be produced with a wider range of shapes and sizes, and at lower cost. Existing models were verified experimentally for flat spiral coils wound from solid and litz wires, operated at room temperature and 77K, and then used to design and optimise a cooled receive coil for MRI at 0.01T (425 kHz). The Q-factor reached 1022 when the coil was cooled to 77K, giving a bandwidth of just 0.42 kHz, so a low noise JFET preamplifier was developed to provide active damping of the coil resonance and thus minimise image intensity artefacts. The noise contribution of the preamplifier was determined using a method based on resistive sources and image noise analysis. The voltage and current noise were measured to be 1.25 nV/Hz(1/2) and 51 fA/Hz(1/2), respectively, and these values were used to estimate a noise figure of 0.32 dB at the resonant frequency of the cooled coil. The coil was used to acquire 0.01T spin echo images, first at room temperature and then cooled to 77K in a low noise liquid nitrogen cryostat. The measured SNR improvement on cooling, by a factor of 3.0, was found to correspond well with theoretical predictions.

Real-time monitoring of drug-induced changes in the stomach acidity of living rats using improved pH-sensitive nitroxides and low-field EPR techniques.

New improved pH-sensitive nitroxides were applied for in vivo studies. An increased stability of the probes towards reduction was achieved by the introduction of the bulky ethyl groups in the vicinity of the paramagnetic NO fragment. In addition, the range of pH sensitivity of the approach was extended by the synthesis of probes with two ionizable groups, and, therefore, with two pKa values. Stability towards reduction and spectral characteristics of the three new probes were determined in vitro using 290 MHz radiofrequency (RF)- and X-band electron paramagnetic resonance (EPR), longitudinally detected EPR (LODEPR), and field-cycled dynamic nuclear polarization (FC-DNP) techniques. The newly synthesized probe, 4-[bis(2-hydroxyethyl)amino]-2-pyridine-4-yl-2,5,5-triethyl-2,5-dihydro-1H-imidazol-oxyl, was found to be the most appropriate for the application in the stomach due to both higher stability and convenient pH sensitivity range from pH 1.8 to 6. LODEPR, FC-DNP and proton-electron double resonance imaging (PEDRI) techniques were used to detect the nitroxide localization and acidity in the rat stomach. Improved probe characteristics allowed us to follow in vivo the drug-induced perturbation in the stomach acidity and its normalization afterwards during 1 h or longer period of time. The results show the applicability of the techniques for monitoring drug pharmacology and disease in the living animals.

Development of a 3-D, multi-nuclear continuous wave NMR imaging system.

The development of a 3-D, multi-nuclear continuous wave NMR imaging (CW-NMRI) system is described and its imaging capability is demonstrated on a range of materials exhibiting extremely short T(2) relaxation values. A variety of radiofrequency resonators were constructed and incorporated into a new gradient and field offset coil assembly, while the overall system design was modified to minimise microphonic noise which was present in an earlier prototype system. The chemically combined (27)Al in a high temperature refractory cement was imaged, and the CW-NMRI system was found to be sensitive to small differences in (27)Al content in these samples. The penetration of (23)Na in salt water into samples of ordinary Portland cement (OPC) was investigated, with enhanced uptake observed for samples with larger pore size distributions. The solid (13)C component in a carbonated cement sample was also imaged, as were the (7)Li nuclei in a sample of powdered Li(2)CO(3). A spatial resolution of 1mm was measured in an image of a rigid polymeric material exhibiting a principal T( *)(2) value of 16.3 micros. Finally, a high-resolution 3-D image of this rigid polymer is presented.

Field-cycled PEDRI imaging of free radicals with detection at 450 mT.

This paper describes the design, construction and use of a field-cycled proton-electron double-resonance imaging (FC-PEDRI) system for the detection and imaging of free radicals. The unique feature of this imager is its use of a 450-mT detection magnetic field in order to achieve good image quality and sensitivity. The detection magnetic field is provided by a superconducting magnet, giving high stability and homogeneity. Field cycling is implemented by switching on and off the current in an internal, coaxial, resistive secondary magnet that partially cancels the superconducting magnet's field at the sample; the secondary magnet is actively shielded to avoid eddy currents. EPR irradiation takes place at approximately 5 mT, following which the field is switched to 450 mT in 40 ms for NMR signal detection. Full details of the imager's subsystems are given, and experiments to image the distribution of stable free radical contrast agents in phantoms and in anesthetized rats are described.

Evaluation of MRI for in vivo monitoring of retinal damage and detachment in experimental ocular inflammation.

Two quantitative methods were developed for investigation of the potential of MRI for in vivo monitoring of retinal damage and detachment in experimental autoimmune uveitis (EAU). Measurements of retinal thickness and detachment area were performed on matched MR and histologic (HIST) images of rat eyes at different stages of EAU. In vivo MR images of rat eyes were acquired at 4.7 T using a figure-of-eight surface coil and a spin echo pulse sequence. Ex vivo measurements were performed on HIST images acquired using a digital camera attached to a microscope. MR images mirrored the HIST appearance of inflamed eyes at each stage of disease. Retinal detachments as small as 0.1 mm(2) were measured in vivo by MRI and confirmed in the same eye ex vivo by histology. Measurements performed on corresponding MR and HIST images demonstrated a good agreement between the two techniques. The potential of MRI for in vivo visualization and for monitoring changes in the eye during development of EAU was demonstrated in this study.

Continuous wave MRI of heterogeneous materials.

A prototype continuous wave MRI system operating at 7T has been used successfully to study a variety of heterogeneous materials exhibiting T2 relaxation values ranging from 10 micros to 50 ms. Two-dimensional images of a poly(methly methacrylate) (PMMA) resolution phantom (T2=38 micros) exhibited a spatial resolution of approximately 1mm at a magnetic field gradient strength of 200 mT/m. The technique was used to study the hydration, drying, and subsequent water penetration properties of cement samples made from ordinary Portland cement, and revealed inhomogeneities arising from the cure conditions. Sandstone samples from an oil reservoir in the North Sea were also studied; structure within these materials, arising from the sedimentary bed layering in the reservoir, was found to have an effect on their water transport properties. A section from a confectionery bar (T2* approximately 50-60 ms) was also imaged, and its internal structure could be clearly discerned.

In vivo detection of a pH-sensitive nitroxide in the rat stomach by low-field ESR-based techniques.

A study was made of the in vivo detectability of a pH-sensitive, imidazolidine spin probe, and the efficacy of low-frequency electron spin resonance (ESR)-based techniques for pH measurement in vitro and in vivo in rats. The techniques used were longitudinally-detected ESR (LODESR) and field-cycled dynamic nuclear polarization (FC-DNP) for in vitro and in vivo measurements, and radiofrequency (RF)- and X-band ESR for comparisons in vitro. The spin probe was hexamethyl imidazolidine (HMI) with a pK of 4.6. All techniques detected HMI. Detection by FC-DNP implies coupling between the free radical and solvent water spins. Separations between the three spectral lines of the nitroxide radical, relative to measurement frequency, were consistent with theory. The overall spectrum width from unprotonated HMI (pH > pK) was greater than that from protonated agent (pH < pK). This was observed in vitro and in vivo. Longer-term studies showed that HMI is detectable and has the same spectral width (i.e., is at the same pH) up to 2 hr after gavage into the stomach, although the magnitude of the signal decreases rapidly during the first hour. These findings demonstrate the suitability of LODESR and FC-DNP for monitoring HMI and measuring pH in vivo. These techniques would be useful for monitoring disease and drug pharmacology in the living system.