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The development of noninvasive methods capable of affording ever higher resolution images is an ongoing major objective of scientific investigation for the benefit of both clinical medicine and neuroscience. Since its development in the early 1970s, magnetic resonance imaging (MRI) has remained a technology of choice for medical imaging development because of the wide range of potential clinical applications. Although conventional systems with field strengths of 1.0-1.5 T rapidly popularized MRI in general clinical practice in the 1980s, research investigations have focused on imaging yielding much higher anatomical resolution using high (3.0-4.0 T) and ultra high-field (7.0-9.0 T) systems. The substantial clinical experience with high and ultra high-field systems has made evident that there is a definite limit to which higher spatial resolution in and of itself will improve information for clinical judgment, rather, it is essential to develop the entire study as a whole, which would allow for the selection of an optimal combination of all the study elements, especially the appropriate contrast mechanism. This process is analogous to the development of suitable stains for a given pathologic process in histological techniques. In MRI, the natural physico-chemical MR contrast properties of tissues can be taken advantage of to achieve this goal, thereby obviating the need for administering contrast material to individuals.

The potential of antiepileptic drugs (AEDs) to inhibit the water transport properties of aquaporin 4 (AQP4) was investigated using a combination of in silico and in vitro screening methods. Virtual docking studies on 14 AEDs indicated a range of docking energies that spanned approximately 40 kcal/mol, where the most stabilized energies were consistent with that of the previously identified AQP4 inhibitor acetazolamide. Nine AEDs and one bio-active metabolite were further investigated in a functional assay using AQP4 expressing Xenopus oocytes. Seven of the assayed compounds were found to inhibit AQP4 function, while three did not. A linear correlation was indicated between the in silico docking energies and the in vitro AQP4 inhibitory activity at 20 microM.

We investigated whether or not frame composition spontaneously selected by individuals exhibit a natural left shift in preference of luminosity, as previously suggested, by examining biases in luminosity imprinted in photographs taken under three different conditions: (i) daytime pictures taken outside without determination of frame composition (N=4153); (ii) daytime pictures taken outside with determination of frame composition (N=4035); and (iii) pictures taken inside with determination of frame composition (N=4045). As anticipated, there was a strong vertical gradient of luminance grayscale intensity, reflecting natural day light distribution, for pictures of categories (i) and (ii). Similarly, a minor vertical gradient was detected for pictures of category (iii), indicating common room lighting conditions. To our great interest, there was a consistent leftward tilt of ca. 2 and 9 degrees found in the vertical gradients for pictures of categories (ii) and (iii), respectively, but not for pictures of category (i). The result provides clear-cut evidence that there is indeed a natural preference for a leftward bias in luminosity for frame composition.

Object The authors of previous studies based on diffusion tensor imaging have indicated that there are two types of peritumoral edema—namely, edema with preserved structural integrity of the glial matrix and edema with compromised glial matrix. The authors of this study hypothesized that functionality of the glutamate (Glu)–glutamine shuttle, a vital neuron–glia interaction, may be differentially affected by peritumoral edema. They tested this hypothesis using proton magnetic resonance (MR) spectroscopy on a 3.0-tesla system that is capable of quantifying Glu without need of editing. Methods Twenty-three patients, each with a single brain tumor mass and peritumoral edema (nine high-grade gliomas, eight metastatic brain tumors, and six meningiomas), and nine healthy individuals participated in this study. Single-voxel proton MR imaging targeting the region of peritumoral edema was performed using a 3.0-tesla system. Glutamate levels in the peritumoral edema of nonglial tumors was significantly elevated (p < 0.01) compared with edema associated with glial tumors or normal white matter. The finding confirmed that peritumoral edema in nonglial tumors is distinct from that of glial tumors, as previously indicated in diffusion tensor imaging studies. The authors hypothesized that the former condition represents a compensatory increase in activities of the Glu–glutamine shuttle brought about by simple expansion of the extracellular space due to edema. Conclusions The assessment of Glu concentrations in peritumoral edema using 3.0-tesla proton MR spectroscopy may be developed into an objective index of the structural integrity of the glial matrix.

Hemispheric specialization is a prominent characteristic of the human brain. Should the ‘dominant’ hemisphere possess diierential neural organization for language production in the ‘higher order’ cortex, it would be rational to consider that the primary motor cortex may also show similar hemispheric specialization for speech production. In order to test this hypothesis, we investigated the spatial distribution of neural activities associated with phonation (M1p), silent tongue motion (M1t), and vocalization (M1v) within the primary motor cortex, utilizing independent component^ cross correlation^ sequential epoch analysis of high-¢eld functional magnetic resonance imaging time series. While M1t showed no signi¢cant diierences between the two hemispheres, M1p and M1v exhibited signi¢cant hemispheric diierences. The study demonstrated direct evidence that human primary motor cortex possesses clearcut hemispheric specialization similar to that observed for the higher order cortices. NeuroReport 17:1091^1095 � c 2006 Lippincott Williams & Wilkins.

Background Clinical magnetic resonance imaging (MRI) has recently entered the "high-field" era, and systems equipped with 3.0-4.0T superconductive magnets are becoming the gold standard for diagnostic imaging. While higher signal-to-noise ratio (S/N) is a definite advantage of higher field systems, higher susceptibility effect remains to be a significant trade-off. To take advantage of a higher field system in performing routine clinical images of higher anatomical resolution, we implemented a vector contrast image technique to 3.0T imaging, three-dimensional anisotropy contrast (3DAC), with a PROPELLER (Periodically Rotated Overlapping Parallel Lines with Enhanced Reconstruction) sequence, a method capable of effectively eliminating undesired artifacts on rapid diffusion imaging sequences. Methods One hundred subjects (20 normal volunteers and 80 volunteers with various central nervous system diseases) participated in the study. Anisotropic diffusion-weighted PROPELLER images were obtained on a General Electric (Waukesha, WI, USA) Signa 3.0T for each axis, with b-value of 1100 sec/mm(2). Subsequently, 3DAC images were constructed using in-house software written on MATLAB (MathWorks, Natick, MA, USA). Results The vector contrast allows for providing exquisite anatomical detail illustrated by clear identification of all major tracts through the entire brain. 3DAC images provide better anatomical resolution for brainstem glioma than higher-resolution T2 reversed images. Degenerative processes of disease-specific tracts were clearly identified as illustrated in cases of multiple system atrophy and Joseph-Machado disease. Conclusion Anatomical images of significantly higher resolution than the best current standard, T2 reversed images, were successfully obtained. As a technique readily applicable under routine clinical setting, 3DAC PROPELLER on a 3.0T system will be a powerful addition to diagnostic imaging.

Purpose The effectiveness of diffusion trace value analysis for non-invasive assessment of retinal ganglion cell (RGC) axonal degeneration at multiple anatomic levels along the human visual pathway under clinical setting was evaluated. Design Imaging study. Methods Ten patients with unilateral chronic optic neuropathy of varying cause and 16 age-matched normal subjects were studied. Trace, a tensor invariant that is considered to be a sensitive index for pathologic changes in axons, was analyzed at nine anatomic sites in each subject, namely, bilaterally at the level of the optic nerves, uncrossed chiasmal fibers, optic tracts and optic radiations, and crossed chiasmal fibers, using a 3.0 Tesla magnetic resonance imaging system. Results Trace values of the optic nerve and uncrossed chiasmal fibers ipsilateral to the affected eye, the crossed chiasmal fibers, and optic tracts bilaterally were significantly higher than those of the corresponding anatomic sites in normal subjects. The optic nerve and uncrossed chiasmal fibers ipsilateral to the unaffected side and optic radiations, bilaterally, had trace values which were not significantly different from the values of the corresponding anatomic levels in normal subjects. The increase in trace value in the optic nerve and uncrossed chiasmal fibers ipsilateral to the affected side was greater than those of the crossed chiasmal fibers and optic tracts. Conclusions Findings are highly consistent with a degenerative process of RGC axons and trace values are quantitatively well correlated to predicted pathology at the given anatomical sites. Trace value measurement at multiple sites along fiber pathways appears to be a powerful addition to clinical assessment of the functionality of components of the visual pathways during various stages of a pathologic process.

Dynamic contrast enhanced magnetic resonance imaging (dynamic MRI) represents a MRI version of non-diffusible tracer methods, the main clinical use of which is the physiological construction of what is conventionally referred to as perfusion images. The raw data utilized for constructing MRI perfusion images are time series of pixel signal alterations associated with the passage of a gadolinium containing contrast agent. Such time series are highly compatible with independent component analysis (ICA), a novel statistical signal processing technique capable of effectively separating a single mixture of multiple signals into their original independent source signals (blind separation). Accordingly, we applied ICA to dynamic MRI time series. The technique was found to be powerful, allowing for hitherto unobtainable assessment of regional cerebral hemodynamics in vivo.

Purpose: To evaluate the efficacy of a fully automatic, single-voxel, proton MR spectroscopy algorithm on a 3.0T MR system.Methods: The PROBE/SVQ algorithm (GE Medical Systems) was evaluated on a General Electric (GE) Signa LX-3T system. Ten normal volunteers (female, 21.1±2.0 years old) participated in the study. Nine representative regions of interest were examined, namely, right and left frontal white matter; right and left parietal white matter; right and left basal ganglia; right and left dentate nucleus; and pons.Results: The mean coefficients of variation in all regions for the N-acetyl-aspartate to creatine ratio (NAA/Cr), choline to creatine ratio (Cho/Cr), and choline to N-acetyl-aspartate ratio (Cho/NAA) were 10.2±2.4%, 11.4±3.2% and 12.6±1.4%, respectively.Conclusion: A fully automated spectroscopic examination under clinical setting utilizing the PROBE/SVQ algorithm appears to be a reliable method, extending the window of routine clinical assessment of brain metabolism.

A case of acute thalamic hematoma not detected by computed tomography (CT) but unequivocally diagnosed by magnetic resonance imaging (MRI) is presented. A 79-year-old woman presented with acute left hemiparesis. The results of CT obtained on admission as well as on the seventh hospital day were negative for a hematoma. By contrast, serial MRIs exhibited chronological changes in the relaxation properties characteristics of acute hematoma in the thalamus. The case illustrates that contrary to widespread practice, CT cannot absolutely be relied on for the detection of acute intracerebral hematoma.

THE effects of diabetes mellitus on the kinetic constants of aldose reductase and sorbitol dehydrogenase in rat brain were investigated non-invasively in vivo using the 3-fluoro-3-deoxy-D-glucose (3-FDG) 19-fluorine ( 19 F) nuclear magnetic resonance (NMR) method. While forward flux for both aldose reductase and sorbitol dehydrogenase (k 1 and k 2 ) were significantly increased, there was no corresponding increase in reverse flux (k 3 and k 4 ), and leakage of fructose (k 5 ) was negligible. These findings indicate that the enzymatic kinetics of aldose reductase sorbitol (ARS) in diabetic brain undergo alteration favoring intracellular sorbitol and fructose accumulation, the frequently implicated biochemical basis of diabetic complications.

The absolute eigenvalues of the diffusion tensor of white matter in sixteen normal subjects in two groups representing the early developmental stage (ages 1–10 years, n = 8) and young adult stage (ages 18–34 years, n = 8) were assessed using a high-field (3.0 T) magnetic resonance (MR) system. All three eigenvalues, including the largest eigenvalue, decreased significantly with brain maturation. The rate of the decline in the two small eigenvalues was, however, much higher than that of the largest eigenvalue, resulting in an actual increase in fractional anisotropy, a commonly measured relative index. The data demonstrate that an increase in anisotropy associated with brain maturation represents a significant decline in the small eigenvalue components, rather than an increase in the largest eigenvalue. The observed pattern of eigenvalue changes is best explained by the simultaneous occurrence of two of several independent phenomena within the axonal microenvironment during the myelination process, namely, (1) decline in unrestricted water content in extra-axonal space, and (2) increase in apparent diffusivity within the axon. Copyright © 2003 John Wiley & Sons, Ltd.

Dorsolateral prefrontal cortex (DLPF) activation in response to cognitive paradigms engaging working memory was quantitatively evaluated using functional near infrared spectroscopy (fNIRS) in cognitively normal individuals across the age spectrum (20-90 years; 8 females, 52 males). DLPF activation score (DAS) demonstrated a significant decline (r(2) = -0561, p < 0.05) as a function of age. The study indicates that blood flow response associated with DLPF activation declines as a function of age in cognitively normal individuals and that fNIRS can be used as a convenient, portable tool for assessing such activation.

Background and Purpose. Cavities occasionally found within the hippocampus during routine clinical magnetic resonance imaging (MRI) studies are believed to be a normal variant reflecting fluid collection within the vestigial hippocampal sulcus. However, the lack of systematic studies defining objective criteria for such cavities has hampered further assessment of potential abnormalities within the hippocampus. This study assessed the detailed characteristics of hippocampal cavities in normal subjects using a new high-resolution MRI technique in an attempt to define objective criteria of normalcy. Methods. A new high-resolution imaging technique, T2-reversed MRI on a high-field (3.0-T) system was used to image the hippocampus in 74 normal volunteers in 3 age groups (28 young, 24 middle, and 22 senior). Results. Residual cavities in the vestigial hippocampal sulcus were resolved as single, crescent-shaped structures along the deep aspect of the vestigial hippocampal sulcus. The size of the cavities did not vary with age and never exceeded 1 mm in width and 3 mm in length. The frequency of detection, however, increased with age (21.4% [5/28] in the young, 25.0% [6/24] in the middle, and 36.4 [8/22] in the senior age group). Conclusion. The study established clear objective criteria for normal cavities within the hippocampus. These cavities likely represent physiological fluid collection within the vestigial hippocampal sulcus. Any cavity that does not meet these defined criteria should be considered potentially abnormal.

Functional magnetic resonance imaging studies on spoken versus written language processing were performed in 20 right-handed normal volunteers on a high-field (3.0-tesla) system. The areas activated in common by both auditory (listening) and visual (reading) language comprehension paradigms were mapped onto the planum temporale (20/20), primary auditory region (2/20), superior temporal sulcus area (2/20) and planum parietale (3/20). The study indicates that the planum temporale represents a common traffic area for cortical processing which needs to access the system of language comprehension. The destruction of this area can result in comprehension deficits in both spoken and written language, i.e. a classical case of Wernicke’s aphasia.

The purpose of this study was to determine whether regional differences in metabolites can be seen chronologically in permanent focal cerebral ischemia using 1H magnetic resonance spectroscopic imaging (MRSI), and whether these changes reflect pathological outcome. Regional variation in metabolites after permanent focal ischemia were investigated longitudinally in rats using 1H MRSI for a total of 7 days and then compared to histopathological findings. Four hours after the induction of ischemia, N-acetyl-L-aspartate (NAA) levels in the lateral caudo-putamen and the somatosensory cortex, core ischemic regions, decreased 22 and 40%, respectively. This reduction in NAA was coupled with a marked rise in lactate. In the medial caudo-putamen, the ischemic rim, however, NAA was preserved in spite of a marked increase in lactate. By 24 h post ischemia, the levels of NAA in medial caudo-putamen (ischemic rim in caudate) also decreased significantly. However NAA in cingulated cortex (ischemic rim in cortex) decreased more gradually between 24 and 48 h. This regional difference can reflect the severity of metabolic derangement in the acute stage. After 96 h following ischemia, the levels of all metabolites detected by 1H MRSI had decreased and the levels of NAA decline reflected the severity of histopathological damage. In conclusion, the regional metabolic differences could be assessed by 1H MRSI chronologically, and the depth of NAA decline reflected histopathological changes in the chronic stage.

31P and 3-fluoro-3-deoxy-D-glucose (3-FDG) 19F nuclear magnetic resonance (NMR) spectroscopic investigations were performed on aged rat brain in vivo. Phosphodiester (PDE) was found to be significantly higher (p less than 0.05) in aged brain (18 months, n = 10) than adult controls (6 months, n = 10) suggesting accelerated phospholipid catabolism in aged brain. Inorganic phosphate (Pi) levels were significantly lower (p less than 0.05) in aged brain (n = 5) than in normal adult controls (n = 5). The sorbitol index, a measure of aldose reductase activities in vivo, determined by the 3-FDG 19F NMR method, revealed that aldose reductase activities were significantly higher (p less than 0.05) in aged brain.

Article abstract Cortical activation associated with stereopsis was studied in eight right-handed neurosurgeons professionally trained in stereoscopic vision. The activation map associated with viewing three-dimensional images, as contrasted to viewing the corresponding two-dimensional images of identical contents (images of MR angiography), showed consistent activation in the cortex adjacent to the intraparietal sulcus. The study further demonstrated a dominant role of the right hemisphere in perceptual processing of stereopsis in humans.

The widely accepted method of blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) is a subtractive approach of state related analysis based on pictorial statistics, analogous to its predecessor, H2O(15) positron emission tomography (H2O(15)-PET). Although BOLD-fMRI has been shown to have several definite advantages over H2O(15)-PET, it has also been found to be much more artifact prone. This is primarily due to pixel misalignment of raw image data. Furthermore, similar to H2O(15)-PET, conventional means for pictorial analysis in BOLD-fMRI tends to be limited by the relatively low specificity of the observed activation. To overcome this limitation, we investigated a technique for BOLD-fMRI, sequential epoch analysis (SEA), on a high-field (3.0 T) system. The method allows for experimental designs comparable to neurophysiological techniques in primates and enables determination of activation of a selected cerebral cortical region of interest corresponding to a specific task. Utilizing SEA, we successfully identified a specific area within the premotor cortex which is activated complementary to the contralateral hand motion. The findings have strong implications regarding the neurological substrate responsible for the well described clinical phenomenon of physiological mirror movements in infants. The current study validated SEA BOLD-fMRI on a high-field system as a complementary method in the pictorial analysis of conventional fMRI, effectively offsetting the inherent problems of the conventional method, principally pixel misalignment and the relatively low specificity of the observed activation.

THE cortical areas subserving music literacy were investigated using high-field (3 Tesla) functional magnetic resonance imaging (fMRI). The activation pattern associated specifically with music score reading was compared with that associated with reading text in a subject's primary and secondary language. While the areas of activation were predominantly identical for all three reading modalities, there were areas within the occipital cortex activated exclusively by music score reading. Grand analysis of the activation patterns of eight pianists unequivocally identified that the principal cortical area needed for music literacy is the cortex flanking the right transverse occipital sulcus (musical brain).

The potential neuroprotective effects of guanidinoethane sulfate (GES) on delayed neuronal death of hippocampal CA1 neurons were investigated using a gerbil model of forebrain ischemia. Neuronal densities of CA1 neurons in the saline control group (255.1 +/- 11.7 cells/mm) and guanidinoethane sulfate pretreated control group (249.0 +/- 9.4 cells/mm) showed no significant differences. By contrast, in animals subjected to ischemia, CA1 neurons of the guanidinoethane sulfate pretreated group showed a significantly higher number of surviving neurons (61.1 +/- 55.11 cells/mm) compared to the saline group (17.75 +/- 12.73 cells/mm) (p0.05, t-test). The study indicated that although partial, guanidinoethane sulfate is neuroprotective towards gerbil hippocampal CA1 neurons against ischemic insult.

A new category of agents, brain pH alkaline shifters, is described. Using the prototype agent, guanidinoethane sulfate (GES), the actual alkaline shift in pH was demonstrated in adult mice brain by 31-phosphorus (31P) nuclear magnetic resonance (NMR) in vivo spectroscopy. This alkaline shift was also shown to effectively reduce the extent of brain intracellular lactic acidosis brought about by anoxic insult. These findings support the notion that a pH alkaline shift may protect the brain against the deleterious effects of lactic acidosis. Since higher pH has been shown to significantly reduce beta-amyloid deposition, alkaline shifters may also have therapeutic potential in Alzheimer's disease.

Noninvasive investigation of aldose reductase activities in rat testis was performed using 3-fluoro-3-deoxy-D-glucose (3-FDG) and nuclear magnetic resonance (NMR) spectroscopy/imaging. Quantitative determination of testis aldose reductase activities, expressed as the sorbitol index, showed a value similar to that of brain. Sorbitol imaging demonstrated aldose reductase activities in testis to be confined primarily to the central region of this organ. The 3-FDG 19F NMR method appears to have clinical potential in the evaluation of testicular function, especially that of spermatogenesis, noninvasively.

31-Phosphorus (31P) nuclear magnetic resonance (NMR) spectroscopy of fetal brain in utero was obtained entirely noninvasively in rat utilizing image selected in vivo spectroscopy (ISIS). The results were in excellent agreement with the data obtained using the surface coil method in the late stage fetus, namely, high phosphomonoester (PME), low phosphocreatine (PCr), and high intracellular pH. Localized spectroscopy provides unprecedented opportunities for the investigation of fetal brain metabolism in utero.

A quantitative analysis of taurine effect (facilitation of acid handling capacity of brain in response to anoxia/hypoxia by high levels of cytosolic taurine) was performed utilizing multinuclear (1H, 31P) in vivo nuclear magnetic resonance (NMR) spectroscopy and in vitro titration analysis. Taurine effects observed in vivo showed excellent quantitative agreement with the predicted values estimated based on brain taurine levels. The study confirmed that high levels of cytosolic taurine indeed facilitate acid buffering capacity of brain and this taurine effect can be readily explained by the physical, and need not involve metabolic, properties of taurine. Taurine appears to be a key component of the brain cytosol system in the fetus.

Control system engineering is a relatively newer field of engineering which is directly applicable to performance analysis of neuronal networks. Visuo-vestibular interaction (VVI) represents a neuronal control system which has most benefited from such analysis. In this paper, we present a new model of VVI derived from our previously reported model by adding cortical pursuit feedback. Mathematical analysis of abnormal eye oscillations and stability analysis of the VVI system provided us with a plausible hypothesis that the pathological ocular oscillations seen in oculopalatal myoclonus and see-saw nystagmus are indeed due to an unstable VVI control system. The former is due to degeneration of the inferior olivary nucleus resulting in loss of cerebellar learning effects, while the latter is due to disruption of the pathway conveying retinal error signals.

Transketolase (EC 2.2.1.1) is the enzyme that, together with aldolase, forms a reversible link between the glycolytic and pentose phosphate pathways. We have cloned and sequenced the transketolase gene from yeast (Saccharomyces cerevisiae). This is the first transketolase gene of the pentose phosphate shunt to be sequenced from any source. The molecular mass of the proposed translated protein is 73,976 daltons, in good agreement with the observed molecular mass of about 75,000 daltons. The 5'-nontranslated region of the gene is similar to other yeast genes. There is no evidence of 5'-splice junctions or branch points in the sequence. The 3'-nontranslated region contains the polyadenylation signal (AATAAA), 80 base pairs downstream from the termination codon. A high degree of homology is found between yeast transketolase and dihydroxyacetone synthase (formaldehyde transketolase) from the yeast Hansenula polymorpha. The overall sequence identity between these two proteins is 37%, with four regions of much greater similarity. The regions from amino acid residues 98-131, 157-182, 410-433, and 474-489 have sequence identities of 74%, 66%, 83%, and 82%, respectively. One of these regions (157-182) includes a possible thiamin pyrophosphate (TPP) binding domain, and another (410-433) may contain the catalytic domain.

The biochemical changes associated with brain maturation during the first 28 days postnatal were investigated utilizing proton and phosphorus-31 nuclear magnetic resonance spectroscopy in rat pups in vivo. Phosphocreatine was found to increase linearly during this period of development. Phosphomonoester was high at birth, peaked around the 10th day postnatal, and declined thereafter. N-Acetyl-aspartate was low at birth, increased in an approximately linear fashion, and reached adult levels by about Day 28 postnatal. Choline was high at birth and declined thereafter. Taurine, a sulfur amino acid abundant in fetal brain, was also present in high levels on the first day postnatal.

The pH controlling capability of brain of 1-day-old rat pups was investigated using proton (1H) and phosphorus-31 (31P) nuclear magnetic resonance (NMR) in vivo spectroscopy. Despite significantly high levels of lactate accumulation, brain of 1-day-old pups showed remarkable capability of maintaining brain pH virtually unchanged throughout 22 min of anoxia. The study supports the concepts that lactic acidosis is one of the important factors determining the outcome of cerebral anoxia and that the significantly higher pH controlling capability of immature brain plays a key role in the higher resistance toward anoxia.

The differential effects of high temperature on 9L rat gliosarcoma cells cultured in two distinctive forms, namely, anchored monolayer cells and multicellular spheroids, were investigated using 31P nuclear magnetic resonance spectroscopy. The critical temperatures resulting in irreversible changes in cellular energetics were found to be significantly different: 45°C for anchored cells and 43°C for multicellular spheroids, respectively. Phosphonionoester levels in multicellular spheroids were found to be consistently higher than those in anchored monolayer cells regardless of the temperature to which they were exposed. The study demonstrates that tissue derived from a single cell line may exhibit different metabolic properties depending on its growth pattern. © 1991 Academic Press, Inc.

Brain membrane phospholipid fatty acid composition is investigated in Alzheimer's disease using fresh pathologically proven autopsy material. The most striking abnormalities in Alzheimer brains compared to age-matched controls are found in the n - 6 line of polyunsaturated fatty acids (PUFA) showing an elevation of 18:2 (n - 6) associated with a reduction of 20:4 (n - 6) and 22:4 (n - 6). The findings strongly indicate abnormalities in delta 6-desaturation. The decrease in 22:6 (n - 3) also supports delta 6-desaturase abnormalities. Alteration in PUFA desaturation/elongation processes and resultant membrane abnormalities may play a key role in the pathogenesis of Alzheimer's disease.

✓ Serial proton (1H) and phosphorus-31 (31P) magnetic resonance (MR) spectroscopy of cerebral infarction was performed in rats to assess the sensitivity of these techniques for use in clinical cerebral infarction. In this experimental chronic infarction model, 31P spectroscopy tended to return to a “normal” pattern within 24 hours after induction of infarction in spite of pathologically proven completed infarction and, therefore, appeared not to be sensitive enough for clinical application. On the other hand, proton spectroscopy invariably showed persistent high lactate levels and was capable of distinguishing completed infarction from reperfused recovered brain. Persistent high lactate levels appear to be a good MR spectroscopic indicator of completed infarction.

Using 19-fluorine (19F) as nuclear magnetic resonance (NMR) signal probe and 2-fluoro-2-deoxy-D-glucose (2-FDG) as metabolic probe, one dimensional "imaging" (metabolite mapping) of pathway specific glucose metabolism in the pentose monophosphate shunt (PMS) and aldose reductase sorbitol (ARS) pathways were performed in situ in rat brain utilizing one dimensional rotating frame zeugmatography. Normal brain showed highest PMS activities in the brainstem consonant with known spatially heterogeneous concentration of glucose-6-phosphate dehydrogenase, the rate limiting enzyme for the PMS. The brain harboring sufficiently large gliosarcoma in the cerebrum showed a higher PMS/ARS area ratio indicating higher PMS activities in tumor which was localized by zeugmatography. The present study demonstrated the feasibility of studying regional glucose metabolism in the PMS and ARS utilizing 2-FDG.

We studied auditory and visual evoked potentials in D.W., a patient with congenital stenosis of the cerebral aqueduct. Head CT scans revealed marked hydrocephalus with expanded ventricles filling more than 80% of the cranium and compressing brain tissue to less than 1 cm in thickness. Despite the striking neuroanatomical abnormalities, however, the patient functioned well in daily life and was attending a local community college at the time of testing. Evoked potentials provided evidence of preserved sensory processing at cortical levels. Pattern reversal visual evoked potentials had normal latencies and amplitudes. Brain-stem auditory evoked potentials (BAEPs) showed normal wave V latencies. Na and Pa components of middle-latency AEP had normal amplitudes and latencies at the vertex, although amplitudes at lateral electrodes were larger than at the midline. In contrast to the normal sensory responses, long-latency auditory evoked potentials to standard and target tones showed abnormal P3 components. Standard tones (probability 85%), evoked NN1 components with normal amplitudes (−3.7 μV) and latencies (103 msec), but also elicited large P3 components (17 μV, latency 305 msec) that were never observed following frequent stimuli in control subjects. Target stimuli (probability 15%) elicited P3s in D.W. and controls, but P3 amplitudes were enhanced in D.W. (to more than 40 μV) and the P3 showed an unusual, frontal distribution. The results are consistent with a subcortical sources of the P300. Moreover, they suggest that the substitution of controlled for automatic processes may help high-functioning hydrocephalics compensate for abnormalities in cerebral structure.

It has been suggested that recovery from aphasia may depend on the ability of the nondominant hemisphere to subserve language functions. We describe a patient who illustrates a possible "transfer" of language dominance. The patients sustained two infarcts two years apart, one in each hemisphere, involving mirror image territories in the temporoparietal area. The clinical course of each infarct was almost identical, consisting of an initial Wernicke's aphasia which evolved into anomic aphasia during recovery.

Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, and ethanolamine plasmalogen represent the six most abundant phospholipids of brain cell membrane. The ratio of the phospholipid contents (phospholipid profile) of the brain is remarkably consistent under various metabolic conditions and alteration of the phospholipid profile is believed to reflect changes in the membrane system. We describe here a simple but sensitive method to analyze the phospholipid profile of the human brain utilizing the acidified chloroform-methanol lipid extraction method of Folch et al. and 31P nuclear magnetic resonance (NMR) spectroscopy. Unique regional phospholipid profiles were consistently obtained. Although the large chemical-shift anisotropy of the 31P confined to rigid structures such as the cell membrane precludes direct observation of phospholipid profiles in living tissue, a reflection of the membrane phospholipid profiles can nevertheless be obtained by studying "NMR visible" water soluble intermediate metabolites of membrane phospholipids in vivo.

Metabolic imaging reflecting glucose metabolism in the glycolytic and aldose reductase sorbitol (ARS) pathways was performed noninvasively in rat using fluorinated glucose analogs, 2-fluoro-2-deoxy-D-glucose (2-FDG) or 3-fluoro-3-deoxy-D-glucose (3-FDG), and fluorine-19 (19F) nuclear magnetic resonance (NMR) imaging. 19F images of 2-FDG-6-phosphate, a main metabolite of 2-FDG in the glycolytic pathway, showed high glucose utilization in the brain, spinal cord, and heart. Images of 3-fluoro-3-deoxy-D-sorbitol (3-FDSL), a main metabolite of 3-FDG in the ARS pathway, demonstrated the heterogeneous nature of the spatial distribution of aldose reductase activities, being highest in the brain and lens. The extremely low toxicity of 3-FDG indicates promise for clinical application of 3-FDG NMR imaging.

Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopic investigations of the rat stomach were performed utilizing a 1-cm2, three-turn, zig-zag coil. A zig-zag coil of this dimension produced an effective B1 field that extends only within a 4-mm distance from the plane of the surface coil, rendering it possible to obtain high-resolution 31P spectra localized to the stomach without contamination from surrounding tissues. Normal stomach showed a characteristic spectral pattern with resonances reflecting inorganic phosphate (Pi), phosphocreatine (PCr), and the alpha-, beta-, and gamma-phosphates of adenosine triphosphate (ATP). Ischemia-induced changes in Pi, PCr, and ATP resonances were readily followed in vivo with a time resolution of 2.13 min. Indomethacin-induced ulcer revealed a low intracellular pH and a decrease in the PCr to Pi ratio indicating the partially ischemic conditions of ulcerative lesions of the stomach as has been previously suggested. The present studies indicate that 31P NMR spectroscopy utilizing a zig-zag coil is a powerful tool to study local pathology of the gastrointestinal (GI) tract. Since zig-zag coils suitable for fiberscopic devices are easily constructed, clinical applications of the present technique are apparent.

The metabolism of 3-fluoro-3-deoxy-D-glucose (3-FDG) in rat brain in vivo was investigated noninvasively using 19F nuclear magnetic resonance (NMR) spectroscopy. Following an intravenous infusion of 3-FDG, 400 mg/kg, four resonances assigned to the alpha and beta anomers of 3-FDG, 3-fluoro-3-deoxy-D-sorbitol, and 3-fluoro-3-deoxy-D-fructose were clearly resolved in brain, a result indicating that 3-FDG is metabolized primarily into the aldose reductase sorbitol (ARS) pathway. An orally administered aldose reductase inhibitor, sorbinil, caused reduction of the flux of 3-FDG into the ARS, an observation suggesting that the method can be applied in quantitative studies of ARS pathway activities. Studies of 24-h urine specimens showed that in addition to the two metabolites observed in brain, F- was excreted into the urine. 3-FDG appears to be a suitable metabolic probe for assessing glucose metabolism in the ARS pathway by in vivo 19F NMR spectroscopy.

A method for obtaining nuclear magnetic resonance (NMR) spectroscopic signals confined to the cerebral cortex in rat using a cortical coil constructed based on the principles of the zig-zag coil is described. We obtained 31P NMR spectra of normal cerebral cortex and cold-induced injured cortex using this cortical coil. The cortical coil clearly demonstrated an increase in inorganic phosphate (Pi) confined to cerebral cortex which, by contrast, the conventional planar surface coil failed to detect. There are significant metabolic differences between cortex and subcortical tissues. The technique described here, capable of assessing cortical metabolism in vivo without contamination by the underlying tissue, has substantial application to studies of cerebral metabolism. © 1989 Academic Press, Inc.

The radiological appearance of prostate cancer metastasis to the central nervous system often mimics meningioma. The bony change of prostate cancer metastasis resembles the hyperostosis of meningioma because of its blastic rather than lytic nature. On computed tomographic (CT) scan, like meningioma, prostate cancer metastasis enhances homogeneously after the infusion of contrast material. Triple fossa (middle, temporal, and orbital fossae) involvement by a solitary mass without bony destruction is thought to be highly specific for meningiomas. We report a case demonstrating the CT findings typical for a triple fossa meningioma caused by prostate cancer metastasis.

Noninvasive metabolic magnetic resonance (MR) imaging reflecting glucose metabolism in the aldose-reductase-sorbitol (ARS) pathway was performed in the rabbit head; after administration of the fluorinated glucose analogue 3-fluoro-3-deoxy-D-glucose (3FD-glucose), fluorine-19 images were generated. Images of 3FD-glucose showed significant 3FD-glucose uptake by adipose tissue, indicating its buffering effects in case of excess loads of glucose. Images of 3-fluoro-3-deoxy-D-sorbitol (3FD-sorbitol) demonstrated the spatial distribution of aldose reductase activities and significant sorbitol accumulation in the lens. Images of 3-fluoro-3-deoxy-D-fructose (3FD-fructose) showed preferential uptake of fructose by muscle tissue. The extremely low toxicity of 3FD-glucose indicates promise for its clinical application in metabolic imaging.

One-dimensional chemical shift imaging reflecting local tissue contents of the fluorinated neuroleptics fluphenazine and trifluoperazine in rat brain was obtained noninvasively in vivo using one-dimensional 19-fluorine (19F) nuclear magnetic resonance (NMR) rotating frame zeugmatography. Activities of these fluorinated neuroleptics showed a differential distribution in the brain, maximal in the deep structures presumably within the basal ganglia. An additional resonance of an unidentified fluorinated metabolite was localized to the subcutaneous tissue. The present data indicate the feasibility of chemical shift imaging of fluorinated neuroleptics using a high field NMR system and the potential for future development of neurotransmitter imaging by NMR.

Fetal brain metabolism was investigated in utero noninvasively using multinuclear nuclear magnetic resonance spectroscopy in rats at two representative prenatal stages: early (17-18 days) and late (20-21 days) stages. Phosphorus-31 (31P) spectroscopy revealed that phosphocreatine is significantly lower in the early stage and increases to the level of early neonates by the late prenatal stage. Intracellular pH at the early stage was found to be strikingly high (7.52 +/- 0.21) and decreased to a level similar to that of neonates by the late stage (7.29 +/- 0.07). Phosphomonoester levels at both stages were similar to the values reported for early neonates. Water-suppressed proton (1H) spectroscopy demonstrated a distinctive in vivo fetal brain spectral pattern characterized by low levels of N-acetyl aspartate and high levels of taurine. High-resolution proton spectroscopy and homonuclear chemical-shift correlate spectroscopy of brain perchloric acid extracts confirmed these in vivo findings. In vitro 31P spectroscopy of acidified chloroform methanol extracts showed the characteristic membrane phospholipid profiles of fetal brain. The phosphatidylethanolamine (PE)-to-phosphatidylcholine (PC) ratio (PE/PC) did not show significant changes between the two stages at 0.40 +/- 0.11, a value similar to that of early neonates.

We report a case of congestive venous necrosis involving the diencephalon symmetrically, presumably precipitated by a dural arteriovenous malformation (AVM). The patient presented with a 1-month history of intermittent confusion and gait ataxia. The initial radiological work-up revealed a dural AVM. The patient's subsequent deterioration was accompanied by computed tomographic findings of diencephalic congestion. Pathological examination showed subacute necrosis of the diencephalon. We discuss the pathogenesis of this case of subacute diencephalic necorsis and its possible relationship to the entity of subacute diencephalic angioencephalopathy.

Sorbitol levels in heart were determined in streptozotocin-induced diabetic rats. Significantly higher levels were found in hearts of diabetic rats compared to normal rats. The findings are compatible with either significantly higher de novo synthesis of sorbitol in heart than is generally believed or uptake of circulating sorbitol by heart as previously indicated by nuclear magnetic resonance (NMR) in vivo metabolic imaging. Sorbitol accumulation in heart tissue may play a role in the pathogenesis of diabetic cardiomyopathy as has been implicated in cataract formation.

THE Wernicke–Korsakoff syndrome is a nutritional neurologic disorder that is due to thiamine deficiency. Although Wernicke's encephalopathy represents the acute phase of the syndrome, Korsakoff's psychosis represents its chronic continuum. Thiamine is a cofactor in glucose metabolism in the glycolytic and pentose phosphate pathways, and a state of thiamine deficiency is well known to be exacerbated or even precipitated by the administration of a glucose load in the patient with marginal thiamine reserves.1 , 2 The correction of hyperglycemia by hypoglycemic agents in diabetic patients increases short-term use of glucose in the tissues, which results in an obligatory demand for more thiamine. . . .

The demyelinating process in multiple sclerosis (MS) is only rarely a cause of central nervous system necrosis (Reder & Antel, 1984). This complication of MS is usually seen in association with massive, acute demyelination (Kohler et al, 1980; Lhermitte et al, 1981; Tominaga et al, 1982). We present a case of MS in which central spinal cord necrosis resulted in syrinx formation. Syrinx formation can result as a complication of a variety of disease processes, e.g. intramedullary tumours, trauma, or arachnoiditis (Aubin et al, 1981; Barnett et al, 1973). Review of the literature indicates our case to be the first in vivo demonstration of syrinx formation complicating MS.