Neural bases of the foreign accent syndrome: a functional magnetic resonance imaging case study.

Foreign accent syndrome (FAS) is a rare disorder characterized by the emergence of a perceived foreign accent following brain damage. Despite decades of study, little is known about the neural substrates involved in this disorder. In this case study, MRI images of the brain were obtained during a speech task for an American English-speaking monolingual female who presented with FAS of unknown etiology and was thought to sound 'Swedish' or 'Eastern European'. On the basis of MR structural imaging, the patient was noted to have frontal lobe atrophy. An fMRI picture-naming task designed to broadly engage the speech motor network revealed predominantly left-hemisphere involvement, including activation of the (1) left superior temporal and medial frontal structures, (2) bilateral subcortical structures and thalamus, and (3) left cerebellum. The results suggest an instance of substantial brain reorganization for speech motor control.

Relation between work and phosphate metabolite in the in vivo paced mammalian heart.

Nuclear magnetic resonance (NMR) spectroscopy was used to monitor, on a beat-to-beat basis, the concentration of creatine phosphate and adenosine triphosphate during alterations in the work output of canine hearts in vivo. Over a wide range of rate-pressure products (5,000 to 25,000 mmHg/min), the relative amounts of creatine phosphate and adenosine triphosphate within the heart remained constant. The relative concentration of free adenosine diphosphate was calculated under the reasonable assumption that the creatine kinase-catalyzed reaction is near equilibrium in this tissue. The free concentration of adenosine diphosphate also did not change over this range of rate-pressure products. The data demonstrate that the concentration of these compounds is highly regulated in vivo and suggest that factors other than their concentration may be involved in the modulation of steady-state myocardial work output with oxygen consumption.

A comparison of in vivo catalysis by creatine kinase in avian skeletal muscles with different fibre composition.

The maximum activity of creatine kinase in vitro is similar in the pectoralis major muscle of the chicken and the duck. However, the flux (phosphocreatine to ATP) as measured by 31P saturation transfer NMR in vivo is almost 2-fold higher in the duck. This apparent discrepancy can be accounted for by the differences in the cytosolic free ADP concentrations in resting muscle.

Phosphorus-31 nuclear magnetic resonance studies of pig adrenal glands.

We have used phosphorus-31 nuclear magnetic resonance to study the secretion of adenosine 5'-triphosphate (ATP) from the medulla of perfused pig adrenal glands. The resonances of the nucleotide pools in the chromaffin granules and cytoplasm are clearly resolved and therefore the intragranular and cytoplasmic processes involving ATP can be monitored simultaneously in the gland during secretion. Secretion of nucleotide during a 3 h continuous stimulation by infusion of acetylcholine chloride was monitored by the decrease in intensity of the intragranular ATP resonances. Up to 40% of the total intragranular nucleotide was released under these conditions. The rate of secretion decreased with duration of stimulation. No significant changes in the steady-state levels of cytoplasmic ATP or in oxygen consumption were observed. The intragranular pH in ischaemic glands was 5.52 + 0.15, while in glands which had been perfused until their cytoplasmic nucleotide levels had recovered, the intragranular pH was 5.76 +/- 0.16. These results provide the first estimate of the internal pH of the chromaffin granules in intact perfused adrenal glands and show that no net acidification occurs in the presence of cytoplasmic ATP. However, the isolated chromaffin granule possesses a proton-pumping adenosine 5'-triphosphatase which, in the presence of a permeant counter-ion, such as chloride, acidifies the granule interior. It is, therefore, suggested that in the intact cell, the cytoplasmic concentration of permeant counter-ions is too low to allow electrically neutral proton accumulation in the granules.

Nuclear magnetic resonance study of free and bound water fractions in normal lenses.

Proton NMR relaxation times T1 and T2 were determined for normal lenses excised from sexually mature animals from seven different species. Lenses were immersed in physiological buffer during measurements, and suppression methods were employed to null the buffer signal. This enabled selective analysis of lenticular water. Observed relaxation times were correlated with protein and water content. At 37 degrees C and 1.89 Tesla, single-exponential spin-lattice relaxation was observed, but spin-spin relaxation was found to be double-exponential. It was shown that the short-T2 fraction is proportional to protein concentration; this fraction was attributed to water bound to protein. The long-T2 fraction was attributed to free lenticular water. The amounts of free and bound water thus obtained were used in the spin-lattice relaxation rate equation for rapid exchange in a two-component system to calculate the magnitudes of the two corresponding T1 relaxation components.

Left-hemisphere processing of emotional connotation during word generation.

Areas of the brain's left hemisphere involved in retrieving words with emotional connotations were studied with fMRI. Participants silently generated words from different semantic categories which evoked either words with emotional connotations or emotionally neutral words. Participants repeated emotionally neutral words as a control task. Compared with generation of emotionally neutral words, generation of words with emotional connotations engaged cortices near the left frontal and temporal poles which are connected to the limbic system. Thus, emotional connotations of words are processed in or near cortices with access to emotional experience.

Microimaging at 14 tesla using GESEPI for removal of magnetic susceptibility artifacts in T(2)(*)-weighted image contrast.

In magnetic resonance imaging (MRI), T(2)(*)-weighted contrast is significantly enhanced by extremely high magnetic field strength, offering broad potential applications. However, the T(2)(*)-weighted image contrast distortion and signal loss artifact arising from discontinuities of magnetic susceptibility within and around the sample are also increased, limiting utilization of high field systems for T(2)(*)-weighted contrast applications. Due to the B(0) dependence of the contrast distortions and signal losses, and the heterogeneity of magnetic susceptibility in biological samples, magnetic susceptibility artifacts worsen dramatically for in vivo microimaging at higher fields. Practical applications of T(2)(*)-sensitive techniques enhanced by higher magnetic fields are therefore challenged. This report shows that magnetic susceptibility artifacts dominate T(2)(*)-weighted image contrast at 14 T, and demonstrates that the GESEPI (gradient echo slice excitation profile imaging) technique effectively reduces or eliminates these artifacts at long TE in the highest field (14 T) currently available for (1)H imaging.

Brain metabolism after electroshock seizure in the neonatal dog: a [31P]NMR study.

In vivo [31P] nuclear magnetic resonance (NMR) spectroscopy disclosed that a 10 second electroshock seizure in oxygenated neonatal dogs produced prolonged alteration of brain phosphocreatine (PCr), inorganic phosphate (Pi), and lactate. The slow return of these metabolites to baseline may be related to lower endogenous stores of high energy phosphates, or less developed pathways for their regeneration.

31P-NMR evaluation of postischemia renal ATP and pH levels after ATP-MgCl2 treatment in rabbits.

Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy was used to measure adenosine triphosphate (ATP) concentration and pH in vivo in rabbits subjected to a 40-minute period of unilateral renal ischemia to determine the effect of infusing ATP-magnesium chloride (MgCl2, 100 mumol/kg) versus saline at the initiation of reperfusion. Data were compared initially by analysis of variance and then analyzed further using a general linear model with covariate adjustment. ATP-MgCl2-treated animals did not have higher ATP levels during recovery but did have significantly higher renal blood flow (p less than 0.05), a significantly decreased rate of recovery from acidosis (p less than 0.05), and significantly higher urinary output (p less than 0.01) than saline-treated animals during the recovery period. Therefore, treatment with ATP-MgCl2 improves postischemic functional parameters in this model of moderate injury without functioning as a direct source of ATP or its precursors. These data add support to the emerging concept that intracellular acidosis protects cells from reperfusion injury.

Use of a modified polysaccharide gel in developing a realistic breast phantom for MRI.

A polysaccharide material, TX-151, has been used together with water, NaCl, and Al powder to create a tissue equivalent gel to make a realistic, inexpensive, conveniently moldable, temporally stable tissue equivalent MRI phantom. Various phantom compositions were studied for variations in gelling time and relaxation times. Gd-DTPA added as a T1 (and T2) modifier and aluminum powder added to decrease T2 permitted phantoms to be made with a range of relaxation times comparable to human tissues. We have used this polysaccharide gel to create breast phantoms for testing breast coils and evaluating different MRI imaging sequences available for diagnosis. The breast phantoms consisted of a layer of Crisco, a good model for adipose tissue, surrounding the TX-151 gel. Some of these phantoms were created with a silicone implant encapsulated in the gel to simulate an augmented breast. More sophisticated phantoms can easily be developed by additions of other materials to this polysaccharide gel.

Mechanisms that contribute to the in vitro relaxation and signal intensity of water in barium sulfate suspensions used as MRI contrast agents.

The individual components of two commercially available barium sulfate (BaSO4) suspensions, Liquid HD and E-Z-paque (E-Z-EM Inc., Westbury, NY), were investigated to determine their contribution to relaxation. Longitudinal and transverse relaxation times of suspensions and solutions of the different BaSO4 particles and the vehicle used to keep them in suspension were measured separately at 2.0 T. A multiple echo Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence was used for T2 determinations with different values of the echo spacing 2 tau. Longer values of 2 tau resulted in significant shortening of the calculated T2 relaxation times, indicating that the major mechanism leading to signal loss in BaSO4 suspensions is the diffusion of water molecules through susceptibility gradients in the vicinity of suspended particles. At higher BaSO4 concentrations, decreased water proton density also produces significant signal loss. Viscosity has little effect on the relaxation. A combination of larger and smaller BaSO4 particle sizes was found to be more effective than smaller sizes only in enhancing signal decay.

In vivo animal tests of an artifact-free contrast agent for gastrointestinal MRI.

A variety of shortcomings are associated with most currently used gastrointestinal contrast agents for magnetic resonance imaging (MRI). Artifacts resulting from peristalsis and other motions in the abdominal region are produced by many positive contrast agents (which increase signal intensity). Although this is not a problem for negative contrast agents (which decrease signal intensity), some negative contrast agents produce magnetic susceptibility artifacts that are especially pronounced at high field strength and with gradient echo pulse sequences. These susceptibility artifacts are produced by both paramagnetic and diamagnetic agents. It has been demonstrated in phantoms, however, that susceptibility matching can be used to produce contrast agents with desirable relaxation and contrast properties but without deleterious susceptibility artifacts. We now report results of animal tests of such an oral contrast agent, consisting of a suspension of superparamagnetic iron oxide particles and diamagnetic barium sulfate particles, compared to individual suspensions of the iron oxide and of the barium sulfate. Iron oxide was the least effective and the matched susceptibility mixture was the most effective for the intestine, which has traditionally been the most difficult region of the GI tract to visualize clearly. Matched susceptibility mixtures, which are inherently able to yield images free of susceptibility artifacts without compromising contrast, show promise of being improved oral negative contrast agents for use in gastrointestinal MRI.

Thallium-205 and proton nuclear magnetic resonance investigation of the complexation of thallium by the ionophores monensin and nigericin.

A thallium-205 and proton nuclear magnetic resonance study of the ionophores monensin and nigericin is reported. Evidence is presented for the simultaneous existence of two forms of monensin free acid in chloroform solution, one containing a water molecule in the central cavity and one with a water molecule on the periphery, linking the ends of the monensin molecule by hydrogen bonding. There appear to be three structurally different monensin complexes of thallium, two in the salt form and one in the acid form. In free nigericin acid, both terminal hydroxyl moieties hydrogen bond to the terminal carboxylic acid oxygens; in the Na+ salt, the binding of one of the carboxylate oxygens to the metal ion allows but one of the terminal OH's to hydrogen bond strongly. Thallium-205 chemical shifts and spin-lattice relaxation times in the title complexes are discussed and compared to those in ionophores studied previously.

Appearance of Pantopaque on MR images.

Pantopaque was shown to be both a radiographic and magnetic resonance (MR) contrast agent in two patients with suspected cord abnormalities who underwent MR examination following myelography. The Pantopaque appeared as a linear band of high signal intensity along the dependent portion of the spinal canal on MR images obtained with a repetition time of 500 msec and an echo time of 30 msec. MR images of two dogs--one injected with Pantopaque in the cervical subarachnoid space and the other with Amipaque--confirmed that the high signal arose from the Pantopaque. This high signal intensity is due to Pantopaque's short T1 relaxation time. Although Pantopaque will probably not be used as an MR contrast agent, it is important to recognize this property so that its high signal is not mistaken for fat or hemorrhage in the subarachnoid space on MR images.

Evidence for site-selective metal binding in calf liver metallothionein.

Two isoproteins of calf liver metallothionein (MT) have been isolated, purified, and characterized by atomic absorption, ultraviolet absorption, electron spin resonance, and 113Cd nuclear magnetic resonance spectroscopy. Native calf liver MT was found to contain both Cu+ and Zn2+ in a mole ratio of approximately 0.75. Selective replacement of the native Zn2+ with 113Cd2+ can be accomplished in vitro by adding 113CdCl2 to the homogenate before chromatography. Both isoproteins of metallothionein thus prepared contain approximately 3.9 g atoms of Cd2+ and 2.6 g atoms of Cu+/mol of protein. No ESR signal was found, indicating that either Cu+ or antiferromagnetically coupled Cu2+ is the form of copper present. Arguments in support of the former state are presented. Unlike the native 113Cd,Zn MT from rabbit liver, calf liver 113Cd,Cu MT exhibits a remarkably simple 113Cd NMR spectrum. Four major resonances were found for each isoprotein, in the same positions as the resonances assigned to the metals in the four-metal cluster A of rabbit liver metallothionein. This conclusion was confirmed by homonuclear decoupling experiments. This result in conjunction with the stoichiometry of bound metal ions found in the native protein suggests that Cu+ is bound selectively to the three-metal cluster B sites, and that one homogeneous protein fraction predominates. Three minor resonances to higher field are observed in the 113Cd NMR spectrum of calf liver MT-1 and one in calf liver MT-2, which may be attributed to a small fraction of cluster B with one Cu+ replaced by 113Cd2+. The possible biological significance of the different metal ion specificities of cluster A versus cluster B is discussed.

In vivo 31P nuclear magnetic resonance measurements in canine heart using a catheter-coil.

We have developed a new method of obtaining high resolution 31P nuclear magnetic resonance spectra from canine heart without the need for major surgery. This is done by passing an elliptical nuclear magnetic resonance receiver coil through a peripheral blood vessel into the right or left ventricle. This technique enables spectra to be obtained from a defined region of myocardium in less than 7 minutes (for the right ventricle) with a signal:noise ratio of greater than 9:1. With this catheter-coil, useful cardiac metabolic information will be obtainable, not only from specified regions of the heart, but also from various layers of myocardium.