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.

Relative shift in activity from medial to lateral frontal cortex during internally versus externally guided word generation.

Goldberg (1985) hypothesized that as language output changes from internally to externally guided production, activity shifts from supplementary motor area (SMA) to lateral premotor areas, including Broca's area. To test this hypothesis, 15 right-handed native English speakers performed three word generation tasks varying in the amount of internal guidance and a repetition task during functional magnetic resonance imaging (fMRI). Volumes of significant activity for each task versus a resting state were derived using voxel-by-voxel repeated-measures t tests (p <.001) across subjects. Changes in the size of activity volumes for left medial frontal regions (SMA and pre-SMA/BA 32) versus left lateral frontal regions (Broca's area, inferior frontal sulcus) were assessed as internal guidance of word generation decreased and external guidance increased. Comparing SMA to Broca's area, Goldberg's hypothesis was not verified. However, pre-SMA/BA 32 activity volumes decreased significantly and inferior frontal sulcus activity volumes increased significantly as word generation tasks moved from internally to externally guided.

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.

Activity in the paracingulate and cingulate sulci during word generation: an fMRI study of functional anatomy.

The supracallosal medial frontal cortex can be divided into three functional domains: a ventral region with connections to the limbic system, an anterior dorsal region with connections to lateral prefrontal systems, and a posterior dorsal region with connections to lateral motor systems. Lesion and functional imaging studies implicate this medial frontal cortex in speech and language generation. The current functional magnetic resonance imaging (fMRI) study of word generation was designed to determine which of these three functional domains was substantially involved by mapping individual subjects' functional activity onto structural images of their left medial frontal cortex. Of 28 neurologically normal right-handed participants, 21 demonstrated a prominent paracingu- late sulcus (PCS), which lies in the anterior dorsal region with connections to lateral prefrontal systems. Activity increases for word generation centered in the PCS in 18 of these 21 cases. The posterior dorsal region also demonstrated significant activity in a majority of participants (16/28 cases). Activity rarely extended into the cingulate sulcus (CS) (3/21 cases) when there was a prominent PCS. If there was no prominent PCS, however, activity did extend into the CS (6/7 cases). In no case was activity present on the crest of the cingulate gyrus, which is heavily connected to the limbic system. Thus, current findings suggest that medial frontal activity during word generation reflects cognitive and motor rather than limbic system participation. The current study demonstrates that suitably designed fMRI studies can be used to determine the functional significance of anatomic variants in human cortex.

Influence of speech stimuli intensity on the activation of auditory cortex investigated with functional magnetic resonance imaging.

Understanding the impact of variations in the acoustic signal is critical for the development of auditory and language fMRI as an experimental tool. We describe the dependence of the BOLD signal and speech intelligibility on the intensity of auditory stimuli. Eighteen subjects were imaged on a 1.5-T MRI scanner. Speech stimuli were English monosyllabic words played at five intensity levels. Intrasubject reproducibility was measured on one subject by presenting the stimulus five times at the same intensity level. Intelligibility was measured during data acquisition as subjects signaled when hearing two targets. Each functional trial consisted of four cycles (30 s off-30 s on). Five oblique slices covering primary and association auditory areas were imaged. Activated voxels were identified by cross-correlation analysis and their percent signal change (delta S) was measured. Intersubject differences in activation extent, asymmetry, and dependence on intensity were striking. Volume of activation was significantly greater in the left than in the right hemisphere. Intrasubject reproducibility for delta S was higher than for volume of activation. delta S and intelligibility showed a similar dependence on intensity suggesting that not only intensity but also intelligibility affect the fMRI signal.

Neurochemical changes in the cerebral cortex of treated and untreated hydrocephalic rat pups quantified with in vitro 1H-NMR spectroscopy.

The pathophysiology of infantile hydrocephalus is poorly understood, and shunt treatment does not always lead to a normal neurological outcome. To investigate some of the neurochemical changes in infantile hydrocephalus and the response to shunt treatment, we have used high-resolution 1H-NMR spectroscopy to analyze extracts of cerebral cortex from H-Tx rats, which have inherited hydrocephalus with an onset in late gestation. Hydrocephalic rats and rats with shunts placed at either 4 or 12 days after birth were studied at 21 days after birth, together with age-matched control littermates. In hydrocephalic rats there was a 46-62% reduction in the following compounds: myo-inositol, creatine, choline-containing compounds, N-acetyl aspartate, taurine, glutamine, glutamate, aspartate, and alanine. Phosphocreatine, glycine, GABA, and lactate were also reduced but not significantly. These changes are consistent with neuronal atrophy rather than ischemic damage. In hydrocephalic rats that received shunt treatment at 4 days, there were no significant reductions in any chemicals, indicating a normal complement of neurons. However, some compounds, particularly taurine, were elevated above control. After treatment at 12 days, N-acetyl aspartate and aspartate remained significantly reduced, suggesting continued neuronal deficiency.

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.

Metabolite changes in the cerebral cortex of treated and untreated infant hydrocephalic rats studied using in vitro 31P-NMR spectroscopy.

The effect of hydrocephalus on cerebral energy metabolites and on intermediates of membrane phospholipid metabolism has been studied in H-Tx rats with inherited infantile hydrocephalus. Hydrocephalic rats and rats with shunts placed at 4-5 days or at 10 days after birth were subjected to magnetic resonance imaging in vivo before 21 days of age to determine the dimensions of the ventricles and cortex. At 21 days, the brains from the three groups of rats, together with age-matched control littermates, were frozen in situ, and chloroform/methanol extracts of cerebral cortex were prepared for high-resolution 31P-NMR spectroscopy. Hydrocephalus resulted in modest decreases in most metabolites quantified. Levels of phosphocreatine, ATP, and diphosphodiesters plus NAD were significantly reduced by 23-32%, and inorganic phosphate content was reduced but not significantly. Levels of the membrane phospholipid intermediates phosphorylethanolamine, glycerophosphorylethanolamine, and glycerophosphorylcholine were also significantly reduced by 30-33%, indicating changes in membrane metabolism. These general decreases are consistent with a loss of cell contents, possibly due to changes in dendrite structure in hydrocephalus. Rats shunt-treated at 4-5 days were similar to control rats for all energy metabolites, but those treated later at 10 days had reduced phosphocreatine and ATP levels. Shunt-treated rats also had reductions in levels of membrane phospholipids, some of which occurred in sham-operated rats. It is concluded that hydrocephalus leads to reductions in levels of energy metabolites and in levels of membrane phospholipids and that the changes in energy metabolites can be reversed by early, but not by later, shunt treatment.

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.

Diagnosis of renal artery stenosis: feasibility of combining MR angiography, MR renography, and gadopentetate-based measurements of glomerular filtration rate.

OBJECTIVE: Our aim was to evaluate the feasibility of combining in a single test (1) structural evaluation of renal arteries with MR angiography, (2) functional evaluation of global glomerular filtration rates calculated on the basis of plasma disappearance of gadopentetate dimeglumine, and (3) renographic analysis of individual kidneys based on the dynamic changes in signal intensity that occur after administration of gadopentetate dimeglumine. SUBJECTS AND METHODS: We used unenhanced MR angiography to measure patency of the renal arteries in 10 healthy volunteers and in 10 patients with renal artery stenosis. Calculations of global glomerular filtration rate were based on measurements of plasma disappearance of gadopentetate dimeglumine as shown by MR relaxometry. For renography with gadopentetate dimeglumine, we generated curves that showed changes in signal intensity in both kidneys over time; intrarenal kinetics were studied by measuring the time of arrival of gadopentetate dimeglumine in the cortex and outer medulla of the kidney. Conventional angiograms, measurements of global glomerular filtration rate based on plasma disappearance of 99mTc-DTPA, and 99mTc-DTPA renograms were used as reference standards. We compared the two different methods of determining global glomerular filtration rates by computing the correlation coefficient of the linear regression of rates derived from studies with gadopentetate dimeglumine versus rates derived from studies with 99mTc-DTPA. RESULTS: In all volunteers, renal arteries were well visualized, and global glomerular filtration rates based on plasma clearance of gadopentetate dimeglumine were normal. In nine of 10 patients, correlation was good between findings on MR angiograms and findings on conventional arteriograms. Finding were discordant in one patient because the patient moved during the MR angiography. For all six patients studied, correlation was good between measurements of global glomerular filtration rates based on plasma clearance of gadopentetate dimeglumine and those based on clearance of 99mTc-DTPA (r = 98%). CONCLUSION: Our results suggest the potential of magnetic resonance for a comprehensive approach for detection of renal artery stenosis. This novel approach provides structural evaluation of renal arteries with unenhanced MR angiography. MR renography is done and global glomerular filtration rates are determined by using MR relaxometry after injection of contrast material. Corticomedullary transit times can be determined on the basis of the dynamic changes in signal intensity that occur after administration of gadopentetate dimeglumine.

Shunt treatment at two postnatal ages in hydrocephalic H-Tx rats quantified using MR imaging.

The H-Tx rat has inherited hydrocephalus with an onset in late gestation. Ventriculosubcutaneous shunts were placed in a group of hydrocephalic pups at 3-6 days after birth and in another group at 8-12 days after birth. Multislice proton magnetic resonance (MR) images were taken of shunt-treated pups at 7, 14, or 21 days and of age-matched control and untreated hydrocephalic rats and were subjected to quantitative analysis. Some rats were also imaged before surgery. The volume of the ventricles of untreated hydrocephalic pups increased linearly with age at a rate of 52 microliters/day. The ventricles of shunted pups were reduced from the preshunt condition and were around 20% of age-matched hydrocephalic rats. There was no significant difference in the post-shunt volume between early and late shunt groups. The cortical mantle thickness in both groups of shunt-treated rats was significantly thicker than in untreated pups and close to that of control rats. It is concluded that shunt treatment at both ages reversed the hydrocephalus as measured from MR images, although other evidence from fixed brains suggests that normal morphology may not be achieved at the cellular level even for early shunts.

A potentially artifact-free oral contrast agent for gastrointestinal MRI.

The combination of diamagnetic barium sulfate and superparamagnetic iron oxide (SPIO) in one suspension produces a macroscopic cancellation of positive and negative magnetic susceptibility components that can potentially eliminate susceptibility artifacts even with gradient echo pulse sequences. The relaxation properties that make the SPIO suspension a useful negative contrast agent are retained.

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.

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.

Specific MR imaging of human lymphocytes by monoclonal antibody-guided dextran-magnetite particles.

Human lymphocytes were labeled with biotinylated anti-lymphocyte-directed monoclonal antibodies, to which streptavidin and subsequently biotinylated dextran-magnetite particles were coupled. This labeling resulted in a strong and selective negative contrast enhancement of lymphocyte suspensions at 2.0 T, caused predominantly by the specific increase of R2 with a small but significant specific increase of R1. The R1 was found to decrease with increasing field strength. The immunolabeling procedure described here may be used for the selective signal depletion of target cells in MR imaging.

A 31P NMR study of mitochondrial inorganic phosphate visibility: effects of Ca2+, Mn2+, and the pH gradient.

The effects of external pH, temperature, and Ca2+ and Mn2+ concentrations on the compartmentation and NMR visibility of inorganic phosphate (Pi) were studied in isolated rat liver mitochondria respiring on succinate and glutamate. Mitochondrial matrix Pi is totally visible by NMR at 8 degrees C and at low external concentrations of Pi. However, when the external Pi concentration is increased above 7 mM, the pH gradient decreases, the amount of matrix Pi increases, and the fraction not observed by NMR increases. Raising the temperature to 25 degrees C also decreases the pH gradient and the Pi fraction observed by NMR. At physiologically relevant concentrations, Ca2+ and Mn2+ do not seem to play a major role in matrix Pi NMR invisibility. For Ca2+ concentrations above 30 nmol/mg of protein, formation of insoluble complexes will cause loss of Pi signal intensity. For Mn2+ concentrations above 2 nmol/mg of protein, the Pi peak can be broadened sufficiently to preclude detection of a high-resolution signal. The results indicate that mitochondrial matrix Pi should be mostly observable up to 25 degrees C by high-resolution NMR. While the exact nature of the NMR-invisible phosphate in perfused or in vivo liver is yet to be determined, better success at detecting and resolving both Pi pools by NMR is indicated at high field, low temperature, and optimized pulsing conditions.

Spatial mapping of 23Na NMR signals by two-dimensional rotating frame imaging.

The reconstruction of two-dimensional spatial images with 0.5-mm resolution using radiofrequency gradients generated by an NMR coil system rotated about the sample is demonstrated for 23Na. The method retains chemical shift, should be capable of mapping T1 and T2 information, and might offer sensitivity advantages for nuclides with short T2.

Genetic and biochemical characterization of corn inbred lines tolerant to the sulfonylurea herbicide primisulfuron.

Inbred lines of corn (Zea mays L.) have been characterized, which exhibit differential sensitivity to the sulfonylurea herbicide primisulfuron (2-[3-(4,6-bis(di-fluoromethoxy) pyrimidin-2-yl)-ureidosulfonyl]-benzoic acid methylester). When treated postemergence with 160 g a.i. per hectare, inbred 4CO exhibited complete tolerance while inbred 4N5 was killed. The F1 hybrid 4C0 x 4N5 was uniformly tolerant indicating dominance of the tolerance trait. The field observations correlated with laboratory tests in which seedling root growth was measured. Based on IC50, inbred 4CO was more than ten times more tolerant than inbred 4N5. In the F2 and F3 generations, a 3∶1 segregation of tolerant and sensitive individuals was observed, consistent with tolerance being inherited as a single dominant trait. Backcrosses of heterozygous F1 plants with the sensitive parent (4N5) yielded progeny that segreated at the expected 1∶1 ratio. Backcrosses with 4C0 yielded tolerant offspring only. Inhibition characteristics of acetohydroxyacid synthase (AHAS; E.C. 4.1.3.18) were determined. The enzymes from both inbreds and their F1 hybrid were equally sensitive and strongly inhibited by primisulfuron (IC50: 7 nM). The fate of (14)C-labeled primisulfuron in seedling tissues of inbred 4C0 and the hybrid, 4C0 x 4N5, indicated rapid metabolism with a half-life (t 1/2) of approximately 3 h. On the other hand, the herbicide-sensitive inbred 4N5 was considerably slower to metabolize primisulfuron (t 1/2 >24 h). These data indicate that differential metabolism is the mechanism of tolerance to the sulfonylurea herbicide primisulfuron in tolerant corn.