Shielded gradient coils and radio frequency probes for high-resolution imaging of rat brains.

A shielded gradient system and radio frequency probes for a 4.7-T/30-cm horizontal bore magnet are described. The systems were designed principally to obtain images and localized spectra from rat brains. The gradients can operate in either a shielded or non-shielded mode. The rf probe, which combines both highest sensitivity and highest resolution, consists of a large modified saddle type transmitter and a small surface reception coil, actively decoupled using diodes. The system performance is demonstrated on phantoms and on a rat brain, where an image with in plane resolution of 80 microns and a slice thickness of 150 microns is obtained.

The effects of caffeine on ischemic neuronal injury as determined by magnetic resonance imaging and histopathology.

The effects of caffeine on ischemic neuronal injury were determined in rats subjected to forebrain ischemia induced by bilateral carotid occlusion and controlled hypotension (50 mmHg for 10 min). High resolution (100 microns) multi-slice, multi-echo magnetic resonance images were obtained daily for three consecutive days post-operatively in sham-operated rats and in rats that received either saline vehicle (controls), a single i.v. injection of 10 mg/kg caffeine 30 min prior to an ischemic insult (acute caffeine group), or up to 90 mg/kg per day of caffeine for three consecutive weeks prior to an ischemic insult (chronic caffeine group). Rats in the control group exhibited enhanced magnetic resonance image intensity in the striatum 24 h after ischemia which increased in the striatum and also appeared in the hippocampus after 48 h, and which began to resolve in both regions by 72 h post-ischemia. Histopathological analysis of each rat following the final magnetic resonance examination showed that ischemic neuronal injury was strictly confined to the brain regions showing magnetic resonance image changes. Acute caffeine rats showed accelerated changes in the magnetic resonance images, with increased hippocampal intensity appearing at 24 h post-ischemia. Although there was magnetic resonance evidence of accelerated injury, quantitative analysis of the histopathological data at 72 h showed no significant difference in the extent of neuronal injury in any brain region between control-ischemic and acute caffeine rats. Nine out of 11 rats in the chronic caffeine group showed no magnetic resonance image changes over the three study days. Chronic caffeine rats had significantly less neuronal damage in all vulnerable brain regions than either of the other groups of ischemic rats. The accelerated ischemic injury in rats treated with an acute dose of caffeine may occur secondary to antagonism of adenosine receptors, whereas protection from ischemic injury following chronic administration of caffeine may be mediated by up-regulation of adenosine receptors.

Optimization of magnetization transfer measurements: statistical analysis by stochastic simulation. Application to creatine kinase kinetics.

A systematic study was performed to optimize the accuracy of kinetic parameters derived from magnetization transfer measurements. Three techniques were investigated: time-dependent saturation transfer (TDST), saturation recovery (SRS), and inversion recovery (IRS). In the last two methods, one of the resonances undergoing exchange is saturated throughout the experiment. The three techniques were compared with respect to the accuracy of the kinetic parameters derived from experiments performed in a given, fixed, amount of time. Stochastic simulation of magnetization transfer experiments was performed to optimize experimental design. General formulas for the relative accuracies of the unidirectional rate constant (k) were derived for each of the three experimental methods. It was calculated that for k values between 0.1 and 1.0 s-1, T1 values between 1 and 10 s, and relaxation delays appropriate for the creatine kinase reaction, the SRS method yields more accurate values of k than does the IRS method. The TDST method is more accurate than the SRS method for reactions where T1 is long and k is large, within the range of k and T1 values examined. Experimental verification of the method was carried out on a solution in which the forward (PCr----ATP) rate constant (kf) of the creatine kinase reaction was measured.

Selective, delayed increase in transfer constants for cerebrovascular permeation of blood-borne 3H-sucrose following forebrain ischaemia in the rat.

Experiments were conducted to explore the time course of changes in blood-brain barrier (BBB) permeability that may occur in the 2-vessel occlusion model of stroke in the rat. Anaesthetized Sprague-Dawley rats underwent 10 min of cerebral ischaemia produced by bilateral carotid occlusion plus haemorrhagic hypotension. After 6 min, or 3, 6, 18, 24, 48 h recovery and re-anaesthetization, an i.v. injection of 3H-sucrose was permitted to circulate for 30 min. Regional transfer constants (Ki) for BBB permeation of sucrose were calculated from the ratio of sucrose concentration in parenchyma relative to the time-integrated plasma concentration. In the 6-min group, all cerebral regions showed evidence of early BBB leakiness (increase in Ki above non-stroke baseline) which was maximal in forebrain cortex. This effect was diminished at subsequent time points, except in striatum and hippocampus which exhibited delayed intensification of opening, maximal in the 6 h group. Ki values had largely normalized by 24 h. Ki values were also determined 6 min, 6 h and 24 h after a 20-min stroke procedure. Early and regionally selective, delayed BBB openings were also seen, but recovery was not evident in cerebral regions at 24 h. Cortex exhibited a large increase in Ki indicating that a delayed, marked deterioration of BBB integrity had developed between the 6 h and 24 h time points. It is concluded that the combination of transfer constant measurements and the 2-vessel occlusion model could provide a sensitive means for investigating the cerebrovascular consequences and therapy of stroke.

Forebrain ischemia studied using magnetic resonance imaging and spectroscopy.

A combination of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) has been used to follow the time course of changes resulting from forebrain ischemia in the rat. The 31P MRS demonstrates that the level of high energy metabolites decreases significantly during the 10 min ischemic period but returns to normal after 1 h of reperfusion. MRI shows no change after 1 h of reperfusion but significant changes in the striatum after 24 h and in the hippocampus after 48 h. These changes correlate well with histopathology. Diabetic rats have shown the effect of hyperglycemia in accentuation of ischemic and post ischemic pH changes. Conversely, diabetic rats maintained severely hypoglycemic with insulin showed little variation in pH during or following the ischemic insult. The results emphasize the importance of both MRS and MRI in following the temporal profile and distribution of ischemic neuronal injury.

The use of immobilized ferrite to enhance the depth selectivity of in vivo surface coil NMR spectroscopy.

Ferrite particles immobilized on a flexible support and arranged in a specific pattern will produce localized gradients in the homogeneous B0 magnetic field. The screening gradients are strong enough to cause inhomogeneous broadening of the NMR signals arising from the region of a specimen which is adjacent to the ferrite particles. This technique allows improvement of the depth selectivity in non-invasive surface coil NMR spectroscopy while optimizing both the signal-to-noise ratio and the data acquisition time of in vivo NMR experiments. The ferrite screen method also facilitates the routine application of high resolution NMR pulse sequences to in vivo experiments. The technique is readily implemented without special hardware or software and displays a great versatility in the size, shape and depth of the screening effect.

1H-NMR relaxation studies of native and thermally denatured lysozyme solutions: an isotope dilution experiment.

1H-NMR relaxation times are reported for native and thermally denatured lysozyme aqueous solutions measured as the function of the proton mole fraction in the sample. A two-exponential character of proton longitudinal relaxation function was observed for native lysozyme solutions: the fast component was attributed to the non-exchangeable protein protons, the slow one to water protons. Purely exponential decay of longitudinal magnetization was observed for the thermally denatured samples. This has been explained in terms of a fast spin exchange model. The contributions of the protein protons to the water proton relaxation rate in native and thermally denatured samples were determined, too.