Margaret A. Foster

Cyclic changes in composition and volume of the breast during the menstrual cycle, measured by magnetic resonance imaging

Summary. The volumes and spin‐lattice (T1) relaxation times of breast tissues and parenchymal water content were measured non‐invasively by magnetic resonance imaging (MRI) in eight healthy women during four to eight consecutive menstrual cycles. Total breast volume, and parenchymal volume, T1 relaxation time and water content were lowest between days 6 and 15. Between days 16 and 28, parenchymal volume, T1 relaxation time and water content rose sharply by 38·9%, 15·1% and 24·5%, respectively, and peaked after day 25. Within 5 days of the onset of menses, parenchymal volume fell sharply by 30·3%, while water content declined by 17·5%. Rising parenchymal volume in the second half of the menstrual cycle is not solely due to increased tissue water content and provides in vivo evidence for both growth and increased tissue fluid at this time.

Nuclear magnetic resonance pulse sequence and discrimination of high- and low-fat tissues

Abstract Signal size compared to independently measured T 1 is described for various pulse sequences on the Aberdeen Mk II nuclear magnetic resonance imager. The ability of these sequences to discriminate between certain tissue types, and in particular between adipose tissue and muscle, is discussed. Inversion recovery, with a t interval of 200 ms, gives the best discrimination for this purpose, with a contrast ratio of 6 between fat and muscle. Other image types, and especially T 1 , give better contrast for low-lipid soft tissues such as liver and spleen.

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.

Changes in NMR relaxation time associated with local inflammatory response

T1 and T2 relaxation values and water contents of rat and rabbit tissues have been measured during the course of local inflammatory reaction to turpentine. For rabbits, NMR transverse sectional images were also obtained by spin-warp imaging. Elevations in T1 values around the injection site occurred within 24 h. In rats, T1 values of fibrosed muscle at the centre of the reaction continued to rise as a cyst formed, encapsulating the turpentine. T1 values of the surrounding muscle decreased towards normal as the reaction progressed. Good correlation between relaxation rate and water content was observed. In the rabbits, T1 values measured in vitro around the injection site were compared with the values obtained from NMR images of living and dead rabbits. T1 values obtained immediately after death were consistently lower than values of the same tissues before death. Factors affecting a comparison of T1 values obtained by the different methods are discussed.

Free radicals imaged in vivo in the rat by using proton-electron double-resonance imaging

A new technique called proton—electron double-resonance imaging is described for imaging free radicals in aqueous samples. The method is a combination of proton NMR imaging with nuclear electron double resonance. The results of using this technique to image free radicals in vivo in the rat are presented. Rats were injected intravenously with a nitroxide free radical solution and a series of images was obtained from which the clearance of the free radical through the liver and kidneys could be observed.

Pulsed magnetic field exposure during pregnancy and implications for NMR foetal imaging: A study with mice

Following the recent progress in NMR imaging of the foetus in utero an investigation has been made of the effect of exposure to strong pulsed magnetic fields on the pregnancy of mice and the post natal development of their litters. 23 pregnant mice received exposures ranging from 3.5-12kT/s with pulse periods in the range 0.33-0.56ms at various times during gestation. A similar number of pregnant mice served as controls. No adverse effect was observed on the pregnancy. There was no significant difference between the litter numbers and growth rates of the exposed litters compared with controls. The implications of these results are discussed with regard to the safety of NMR imaging during pregnancy.

Comparison of NMR water proton T1 relaxation times of rabbit tissues at 24 MHz and 2.5 MHz.

The ratios between T1 relaxation times at 24 MHz and 2.5 MHz for most of the rabbit tissues lie in the range 1.9 to 2.2. However, among the rabbit tissues certain distinct types were found to have T1 ratios different from those of the general range. In particular this is true of muscle and nervous tissue. The ratios for most striated muscles lie in the range 2.7 to 3.1. However, the range for smooth muscle, 2.0 to 2.2, is very similar to that of the majority of other tissues, whilst the ratio for cardiac muscle, 2.5+or-0.11, lies between the extremes of the other major muscle types. For nervous tissues the ratios are, in general, considerably below 2.0. Spinal cord has a ratio of 1.43+or-0.1; medulla oblongata (1.66+or-0.16), cerebellum (1.75+or-0.02) and the white matter of the cerebral hemisphere (possibly with some contaminating grey matter) (1.77+or-0.08) lie intermediate between the values for spinal cord and the grey matter of the cerebral hemisphere, this latter being 2.00+or-0.01. Other variations were noticeable, for example, the difference in the ratio seen between bile and blood serum and the low ratio of the salivary gland.

In Vitro and In Vivo Measurement of pH and Thiols by EPR-Based Techniques

In vitro and in vivo measurements of pH and thiols provide critical information on physiology and pathophysiology of living organisms, particularly related to oxidative stress. Stable nitroxides of imidazoline and imidazolidine types provide the unique possibility of measuring local values of pH and glutathione content in various biological systems, including in vivo studies. The basis for these applications is the observation of specific chemical reactions of these nitroxides with protons or thiols, followed by significant changes in the electron paramagnetic resonance (EPR) spectra of these probes, measured by low-frequency EPR techniques. The applications of some newly developed pH and SH probes in model systems of pharmacological interest, biological fluids, tissues, and cells as well as in vivo studies in isolated hearts and in the gut of living animals are discussed.

Paramagnetic NMR Contrast Agents: Development and Evaluation

Paramagnetic ions could be theoretically used as NMR contrast agents because of their effect upon T1. However, the toxicity of these ions prevents their application. By the formation of appropriate chemical complexes with these ions, the toxicity of these agents can be substantially reduced while maintaining the paramagnetic effect. Two potential NMR contrast agents, one for oral use and one for intravenous administration, were developed and evaluated both in vitro and in vivo. The effect upon T1 in vitro of these paramagnetic compounds was determined using a JEOL FX-90Q NMR spectrometer. These agents were evaluated in vivo in dogs with a Technicare 0.3 tesla superconducting magnet system and in rabbits with the Aberdeen 0.04 tesla resistive NMR imager. Using calculated T1 NMR images, a nontoxic dose of gadolinium oxalate provided visualization of the gastrointestinal tract. Intravenous administration of chromium EDTA provided enhancement of the kidneys, ureters, and bladder, thereby potentially allowing for the evaluation of renal function with magnetic resonance imaging. Stable paramagnetic complexes can serve as effective, nontoxic, oral and intravenous NMR contrast agents.

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. Magn Reson Med 49:558–567, 2003.