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ABSTRACT: Uric acid (UA) has antioxidant properties yet when elevated is associated with vascular disease and stroke. Further, even high normal UA is associated with increased risk of mild cognitive dysfunction in elderly adults.
In this cross-sectional, observational study, we examined the relationship between serum UA and aggregate volume of white matter hyperintense (WMH) signals observed on proton density and T2-weighted brain MR images in a community sample of 177 adults ages 20 to 92. Using logistic regression, we tested whether participants with UA concentrations in the highest quartile of the sample--but still normal--would have increased WMH volumes.
Compared with those with low to moderate levels, participants with high normal serum UA were more likely to fall in the highest quartile of WMH volume. The odds ratios (95% CIs) of increased WMH were 2.6 (1.2 to 5.4) for total, 2.5 (1.2 to 5.1) for periventricular, and 2.8 (1.4 to 5.9) for subcortical WMH volume. After controlling for age, sex, race, education, body mass, hypertension, and diabetes, the multivariate-adjusted odds of large total and subcortical WMH volumes remained elevated. Finally, high normal UA increased the odds of having excessive ischemic burden four- to fivefold in adults ages 60 and older.
These findings demonstrate that mildly elevated serum uric acid is associated with increased burden of cerebral ischemic pathology, particularly in older adults. We outline the potential pathogenesis of this association. A clinical trial of antihyperuricemic medication to treat or prevent chronic brain ischemia might be warranted.
Neurology 11/2007; 69(14):1418-23. · 8.31 Impact Factor
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ABSTRACT: T(2) of cortical gray matter is generally assumed to be longer than that of white matter. It is shown here that this is not the case in the occipital lobe, but that this effect is often obscured at lower resolution and concealed in standard T(2)-weighted images. Using a high-resolution (1 x 1.3 x 2 mm(3)) segmented EPI Carr-Purcell-Meiboom-Gill sequence, T(2) relaxation times of the brain were measured at 1.5 T for eight healthy adult volunteers. The average T(2) values of cortical gray and white matter were found to be 88 +/- 2 and 84 +/- 3 msec in the frontal lobe, 84 +/- 2 and 83 +/- 3 msec in the parietal lobe, and 79 +/- 1 and 87 +/- 3 msec in the occipital lobe, respectively. This unexpected occipital T(2) contrast between gray and white matter is attributed to regional differences in iron concentration.
Magnetic Resonance in Medicine 09/2001; 46(2):401-6. · 2.96 Impact Factor
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ABSTRACT: A variety of surgical interventions have been recommended for patients with syringomyelia and Chiari malformation. To obtain a better understanding of currently used management strategies and surgical interventions, this study evaluates current opinions in the treatment of these entities.
Members of the Pediatric Section of the American Association of Neurological Surgeons (AANS) were surveyed in July of 1998. A questionnaire was designed to assess (1) management of asymptomatic and symptomatic cases; (2) signs and symptoms that warrant surgical intervention, and (3) surgical strategies. Seventy-seven of 234 surveys (33%) were returned. Responses were entered in a Microsoft Excel spreadsheet for data analysis.
Each year, respondents evaluated on average 10 patients with confirmed syringomyelia and operated on 7. There was substantial agreement to operate on patients with syringomyelia who had progressive scoliosis or progressive motor/sensory loss. For isolated syringomyelia without a Chiari malformation, the majority of respondents recommended shunting of the syrinx. Opinion was mixed concerning physical restrictions for asymptomatic patients with syringomyelia and Chiari malformations. For Chiari malformations, the majority of respondents recommended a minimum cervicomedullary decompression with dural patch grafting. No consensus was obtained on whether dural patch grafting should be done alone or in combination with intradural dissection or manipulation of the tonsils.
Although many respondents agreed on the management and surgical treatment of symptomatic patients with syringomyelia and/or Chiari malformations, there was disagreement with regard to the optimal surgical procedure. Respondents rejected prophylactic surgery for their asymptomatic patients, choosing to follow them conservatively with serial imaging and neurological examinations.
Pediatric Neurosurgery 01/2001; 33(6):311-7. · 0.70 Impact Factor
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ABSTRACT: The properties of the hemodynamic latencies in functional maps have been relatively unexplored. Accurate methods of estimating hemodynamic latencies are needed to take advantage of this feature of fMRI. A fully automated, weighted least-squares (WLS) method for estimating temporal latencies is reported. Using a weighted linear model, the optimal latency and amplitude of the fMRI response can be determined for those voxels that pass a detection threshold. There is evidence from previous studies that the hemodynamic response may be time-locked to the stimulus within certain limits, less variable earlier in its evolution, and able to resolve information about relative hemodynamic timing. This information can be used to test hypotheses about the sequence and spatial distribution of neural activity. The method can be used to weight the earliest evolution of the hemodynamic response more heavily and decrease bias resulting from the hemodynamic response function. Additionally, the WLS method can control for varying response shapes across the brain and improve latency comparisons between brain regions. The WLS method was developed to study the properties of hemodynamic latencies, which may be increasingly important as event-related fMRI continues to be advanced.
Magnetic Resonance in Medicine 01/2001; 44(6):947-54. · 2.96 Impact Factor
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ABSTRACT: Late life onset schizophrenia (sometimes termed "late paraphrenia") has been theorized to be due to neuro-degenerative processes affecting individuals with latent vulnerability to schizophrenia. However, neuro-imaging studies using computed tomography (CT) and magnetic resonance imaging (MRI) investigating possible degenerative anatomic correlates (atrophy, white matter disease, and strokes) to late onset psychoses have yielded conflicting findings. The variation in these findings may be due to differences in study design, case ascertainment, and measurement methods.
The present study compares a continuous measure of total volume of white matter hyperintensities (WMHs) in age, race, and gender-ratio matched groups of late-onset schizophrenic, elderly, early-onset schizophrenic and control subjects.
Our method of WMH measurement yielded an explicit volume and is an alternative to frequently used ordinal measures.
We found no significant differences in the WMH volumes between these three groups. This finding is consistent with a prior study (Symonds et al., 1997. J Neuropsychiat Clin Neurosci 9: 251 - 258), that used ordinal measures.
International Journal of Geriatric Psychiatry 01/2001; 15(12):1085-9. · 2.42 Impact Factor
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ABSTRACT: Chiari Type I malformation (CMI) is a congenital disorder recognized by caudal displacement of the cerebellar tonsils through the foramen magnum and into the cervical canal. Frequently, associated findings include abnormalities of nearby bony and neural elements as well as syringomyelia. Cerebellar tonsillar ectopia is generally considered pathological when greater than 5 mm below the foramen magnum. However, asymptomatic tonsillar ectopia is an increasingly recognized phenomenon, the significance of which is poorly understood.
The authors retrospectively reviewed the records of all brain magnetic resonance (MR) images obtained at our hospital over a 43-month period in an attempt to ascertain the relative prevalence and MR imaging characteristics of asymptomatic CMIs. Of 22,591 patients who underwent MR imaging of the head and cervical spine, 175 were found to have CMIs with tonsillar herniation extending more than 5 mm below the foramen magnum. Of these, 25 (14%) were found to be clinically asymptomatic. The average extent of ectopia in this population was 11.4 +/- 4.86 mm, and was significantly associated with a smaller cisterna magna. Syringomyelia and osseous anomalies were found in only one asymptomatic patient.
The authors suggest that the isolated finding of tonsillar herniation is of limited prognostic utility and must be considered in the context of all available clinical and radiographic data. Strategies for treating patients with asymptomatic CMIs are discussed.
Journal of Neurosurgery 07/2000; 92(6):920-6. · 2.96 Impact Factor
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ABSTRACT: The oxygen extraction ratio (OER) of a tissue describes the interplay between oxygen delivery and consumption and, as such, directly reflects the viability and activity of any organ. It is shown that OER can be quantified using a single magnetic resonance imaging observable, namely the relaxation time T2 of venous blood draining from the tissue. This principle is applied to study local OER changes in the brain on visual stimulation in humans, unambiguously demonstrating a mismatch between changes in blood flow and oxygen metabolism on activation.
Journal of Cerebral Blood Flow & Metabolism 01/2000; 19(12):1289-95. · 5.01 Impact Factor
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ABSTRACT: The spin-echo response to visual activation was studied as a function of spatial resolution at a field of 1.5 T. The results showed that the increase in absolute T(2) upon activation was as large as 22.8 +/- 3.1% (P < 0.05) at the highest resolution (5.3 mm(3)), while it was as small as 3.5 +/- 0.2% (P < 0.05) at the lowest resolution (42.2 mm(3)). In addition, upon increasing resolution, the spin-echo signal decay as a function of echo time changed from monoexponential to nonexponential. These data indicate that, when using the standard resolution for fMRI studies at 1.5 T, the effects of spin-echo changes in the draining veins are of major contribution to the total blood oxygenation level-dependent (BOLD) signal changes measured in voxels encompassing the activated brain areas. The data can be quantitatively accounted for using a model based on the intravascular origin of the spin-echo effect including both macrovascular and microvascular effects. Existing theories for the spin-echo BOLD effect based on diffusion through field gradients predict negligible spin-echo effects inside the large vessels and are therefore incompatible with the data. Magn Reson Med 42:617-626, 1999.
Magnetic Resonance in Medicine 11/1999; 42(4):617-26. · 2.96 Impact Factor
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ABSTRACT: The impulse response function of a radioligand is the most fundamental way to describe its pharmacokinetics and to assess its tissue uptake and retention pattern. This study investigates the impulse response function of [11C](+)McN5652, a radioligand used for positron emission tomography (PET) imaging of the serotonin transporter (SERT) in the brain. Dynamic PET studies were performed in eight healthy volunteers injected with [11C](+)McN5652 and subsequently with its pharmacologically inactive enantiomer [11C](-)McN5652. The impulse response function was calculated by deconvolution analysis of regional time-activity curves, and its peak value (f(max)), its retention value at 75 minutes (fT), and its normalized retention (f(rel) = fT/f(max)) were obtained. Alternatively, compartmental models were applied to calculate the apparent total distribution volume (DV(T)) and its specific binding component (DV(S)). Both the noncompartmental (fT,f(rel)) and the compartmental parameters (DV) were investigated with and without correction for nonspecific binding by simple subtraction of the corresponding value obtained with [11C](-)McN5652. The impulse response function obtained by deconvolution analysis demonstrated high tracer extraction followed by a slow decline in the form of a monoexponential function. Statistical analysis revealed that the best compartmental model in terms of analysis of variance F and condition number of the parameter variance-covariance matrix was the one that was based on a single tissue compartment with parameters k1 and k2 and that also included the parameter of regional cerebral blood volume (BV). The parameter f(rel) demonstrated low between-subject variance (coefficient of variation [CV] = 19%), a midbrain to cerebellum ratio of 1.85, and high correlation with the known density of SERT (r = 0.787 where r is the coefficient of linear correlation between the parameter and the known density of SERT). After correction for nonspecific binding, f(rel) demonstrated further improvement in correlation (r = 0.814) and midbrain to cerebellum ratio (3.09). The variance of the distribution volumes was acceptable when the logarithmic transform lnDV was used instead of DV (17% for the three-parameter model), but correlation of this compartmental parameter was slightly less (r = 0.652 for the three-parameter model) than the correlation of the noncompartmental f(rel) with the known density of SERT, and the midbrain to cerebellum ratio was only 1.5 (uncorrected) and 1.8 (corrected). At the expense of increasing variance, the correlation was increased after correction for nonspecific binding using the inactive enantiomer (r = 0.694; CV = 22%). These results indicate that the kinetics of [11C](+)McN5652 can best be described by a one-tissue compartment model with three parameters (k1, k2, and BV), and that both the noncompartmental parameter f(rel) and the compartmental distribution volumes have the potential for quantitative estimation of the density of SERT. Further validation of the radioligand in experimental and clinical situations is warranted.
Journal of Cerebral Blood Flow & Metabolism 10/1999; 19(9):967-81. · 5.01 Impact Factor
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ABSTRACT: To define further the brain regions involved in tactile object recognition using functional MRI (fMRI) techniques.
The neural substrates involved in tactile object recognition (TOR) have not been elucidated. Studies of nonhuman primates and humans suggest that basic motor and somatosensory mechanisms are involved at a peripheral level; however, the mechanisms of higher order object recognition have not been determined.
The authors investigated 11 normal volunteers utilizing fMRI techniques in an attempt to determine the neural pathways involved in TOR. Each individual performed a behavioral paradigm with the activated condition involving identification of objects by touch, with identification of rough/smooth as the control.
Data suggest that in a majority of individuals, TOR involves the calcarine and extrastriatal cortex, inferior parietal lobule, inferior frontal gyrus, and superior frontal gyrus-polar region.
TOR may utilize visual systems to access an internal object representation. The parietal cortices and inferior frontal regions may be involved in a concomitant lexical strategy of naming the object being examined. Frontal polar activation likely serves a role in visuospatial working memory or in recognizing unusual representations of objects. Overall, these findings suggest that TOR could involve a network of cortical regions subserving somatosensory, motor, visual, and, at times, lexical processing. The primary finding suggests that in this normal study population, the visual cortices may be involved in the topographic spatial processing of TOR.
Neurology 05/1999; 52(7):1413-7. · 8.31 Impact Factor
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ABSTRACT: We used functional MRI (fMRI) to determine the cortical regions activated during processing of visual object shape in humans in six men and three women, using a paradigm with a baseline condition of simple shape detection and an activated condition of object/nonobject shape discrimination. Eight of the nine subjects studied showed significant signal changes. Seven of eight showed changes in the occipital lobes (five bilateral, two right only, one left only). All eight subjects with signal changes exhibited changes in the parietal lobes bilaterally. In the occipitotemporal gyri, there were signal changes bilaterally in seven subjects and unilaterally, on the right, in one. Activation-related fMRI signal increases were also present in the posterior superior and middle temporal gyri in seven of the subjects, with four showing bilateral signal changes, two showing signal changes on the left only, and one only on the right. The data strongly suggest that processing of object shape information in humans activates both the ventral and dorsal visual processing pathways ("what" and "where" pathways), described previously both in humans and in nonhuman primates.
Neurology 06/1997; 48(5):1416-20. · 8.31 Impact Factor
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ABSTRACT: The hypothesis that neuronal activation results in lactate accumulation due to mismatch between glucose and oxygen consumption was tested in the cat model of visual activation by monitoring cerebral metabolism with localized 1H nuclear magnetic resonance spectroscopy (MRS). Adult cats were anaesthetized with alpha-chloralose, paralysed and mechanically ventilated. Visual evoked potentials measured over the occipital cortex showed maximal amplitude at 2 Hz stimulation, but the latencies of the early cortical potentials, N1 and P1, were independent of stimulation frequency. High signal-to-noise ratio, short echo time volume-selected [1H]MRS was used to monitor cerebral lactate with a temporal resolution of 70 s. Difference proton spectroscopy unambiguously showed no lactate peak in the visual cortex during visual activation at stimulation frequencies ranging from 1 to 16 Hz. Absence of change in lactate concentration during visual stimulation was confirmed by averaging all the spectra acquired during activation and subtracting them from reference spectra collected in darkness, a procedure that had a calculated lactate detection limit of 0.17 mM. We also reduced the O2 in the inspired air to 13%, which decreased pO2 from 94.5 +/- 8.9 to 47.0 +/- 6.8 mmHg, during visual stimulation at 2 or 4 Hz. At this low PO2 level, visual stimulation did not cause lactate accumulation in the visual cortex, however. The present data show that neuronal activation to this degree in the cat brain is not associated with aerobic lactate production to an extent that can be detected with 1H MRS.
European Journal of Neuroscience 05/1997; 9(4):654-61. · 3.63 Impact Factor
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ABSTRACT: Functional MRI is a technique capable of providing spatial and temporal information about the brain's hemodynamics. It has been observed that the onset of observed signal changes can vary across regions exhibiting activation. The authors have developed a method for extracting information about these timing differences and for observing the temporal-spatial distribution of the blood response by, characterizing a typical hemodynamic response (HR) to a single flash of light repeated at 30 s intervals. They anatomically locate voxels in the primary visual cortex, a region located along the calcarine sulcus, which is the main terminus of the geniculocortical visual pathways. This average response profile is correlated with the data, producing a map of “active” voxels. Next, the authors explore the distribution of lags by shifting the HR, correlating this signal with the data, and producing another map. They observed increased activation in non-primary visual cortex as the lag was increased to 2-3 s. These results can be most effectively displayed in a time lapse movie. The described technique provides a way of determining varying hemodynamic lag times and partitioning “activated” regions in time. It also clearly demonstrates that these time lags do differ spatially
Engineering in Medicine and Biology Society, 1998. Proceedings of the 20th Annual International Conference of the IEEE;
