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Biomedical subjects

A R Guimaraes

Publications and source records attributed to A R Guimaraes.

14 recordsLinked to original sources

Echoplanar chemical shift imaging.

A novel method of chemical shift imaging utilizing echoplanar imaging (EPI) has been developed for the purpose of improving the spatial resolution of metabolite images for the specific goal of high spatial resolution mapping of neuronal content. An EPI sequence was modified to allow temporal offsets of the 180 degree refocusing pulse that encode the chemical shift information into the phase of the signal. Implementation of this method on 1.5 and 3 T human imagers has resulted in images of N-acetyl aspartate in humans with spatial resolution of 360 microl and signal-to-noise ratio approximately 7:1 in less than 13 min.

Aspartic Acid↗

Imaging subcortical auditory activity in humans.

There is a lack of physiological data pertaining to how listening humans process auditory information. Functional magnetic resonance imaging (fMRI) has provided some data for the auditory cortex in awake humans, but there is still a paucity of comparable data for subcortical auditory areas where the early stages of processing take place, as amply demonstrated by single-unit studies in animals. It is unclear why fMRI has been unsuccessful in imaging auditory brain-stem activity, but one problem may be cardiac-related, pulsatile brain-stem motion. To examine this, a method eliminating such motion (using cardiac gating) was applied to map sound-related activity in the auditory cortices and inferior colliculi in the brain stem. Activation in both the colliculi and cortex became more discernible when gating was used. In contrast with the cortex, the improvement in the colliculi resulted from a reduction in signal variability, rather than from an increase in percent signal change. This reduction is consistent with the hypothesis that motion or pulsatile flow is a major factor in brain-stem imaging. The way now seems clear to studying activity throughout the human auditory pathway in listening humans.

Auditory Cortex↗

Increased cerebral blood volume in HIV-positive patients detected by functional MRI.

OBJECTIVE: To study changes in cerebral hemodynamics related to HIV infection. BACKGROUND: Cerebral injury is a well-known manifestation of HIV infection. Physiologic changes in the HIV brain may precede structural changes and may be detected by functional MRI (fMRI). METHODS: Dynamic contrast fMRI was used to measure the cerebral blood volume (CBV) in 13 patients infected with HIV and in 7 healthy control subjects. RESULTS: Significant increases in dynamic CBV were found in the deep (p < 0.001) and cortical gray matter (p < 0.05) of HIV-positive (HIV+) patients. Patients with definite cognitive impairment showed significantly greater increases in CBV in the deep gray matter (DGM) compared with those without impairment. In one patient with rapidly progressive cognitive impairment, these abnormalities reversed and paralleled clinical improvement after initiation of zidovudine monotherapy. CONCLUSIONS: This study supports the hypothesis that HIV infection is associated with significant cerebral hemodynamic changes, particularly in the DGM, that may contribute to cognitive dysfunction in AIDS. Functional MRI may be useful for early detection of cerebral injury and for the assessment of novel therapies.

Adult↗

The hippocampal formation participates in novel picture encoding: evidence from functional magnetic resonance imaging.

Considerable evidence exists to support the hypothesis that the hippocampus and related medial temporal lobe structures are crucial for the encoding and storage of information in long-term memory. Few human imaging studies, however, have successfully shown signal intensity changes in these areas during encoding or retrieval. Using functional magnetic resonance imaging (fMRI), we studied normal human subjects while they performed a novel picture encoding task. High-speed echo-planar imaging techniques evaluated fMRI signal changes throughout the brain. During the encoding of novel pictures, statistically significant increases in fMRI signal were observed bilaterally in the posterior hippocampal formation and parahippocampal gyrus and in the lingual and fusiform gyri. To our knowledge, this experiment is the first fMRI study to show robust signal changes in the human hippocampal region. It also provides evidence that the encoding of novel, complex pictures depends upon an interaction between ventral cortical regions, specialized for object vision, and the hippocampal formation and parahippocampal gyrus, specialized for long-term memory.

Adult↗

Brain choline-containing compounds are elevated in HIV-positive patients before the onset of AIDS dementia complex: A proton magnetic resonance spectroscopic study.

The CNS is frequently involved in human immunodeficiency virus (HIV) infection. In recent studies using proton magnetic resonance spectroscopy, investigators found a significant reduction in N-acetyl aspartate, a metabolic marker of neurons, in late stages of dementia. To further understand the relationship between proton magnetic resonance spectroscopy changes and clinical disease and dementia, we compared 20 HIV-infected patients presenting at varying stages of acquired immunodeficiency syndrome (AIDS) dementia complex and infection to 10 age-matched controls. We found a significant reduction in N-acetyl aspartate/creatine only in patients who had advanced dementia and CD4 counts less that 200/microliter. By contrast, a significant elevation in compounds containing choline was present in patients in the early stages of HIV infection of who had CD4 counts greater than 200/microliter, in patients with normal MRI scans, and in all AIDS dementia complex groups, including subjects with no or minimal cognitive impairment. An elevated choline level also occurred in later stages of HIV infection (CD4 < 200/microliter). Our results suggest that an increase in choline occurs before N-acetyl aspartate decrements, MRI abnormalities, and the onset of dementia, and may therefore provide a useful marker for early detection of brain injury associated with HIV infection.

AIDS Dementia Complex↗

Quantitative in vivo 31P magnetic resonance spectroscopy of Alzheimer disease.

The purpose of this study was to determine whether, in Alzheimer disease (AD) patients, abnormalities in energy charge or phospholipid metabolism could be detected during life with quantitative phosphorus magnetic resonance spectroscopy (31P MRS). We performed in vivo 31P MRS in 16 patients with a clinical diagnosis of probable AD with mild to moderate dementia severity (mean Blessed Dementia Score = 17.5, range = 7-37) and in 8 healthy, nondemented, age-matched, control subjects. MR studies were performed on a commercial 1.5 T MR imager using a volume head coil. We acquired brain spectra by sampling a 6-cm-thick axial slice through the cerebrum (a region that includes approximately 900 ml of brain tissue); we measured beta-nucleoside triphosphate (beta-NTP), phosphocreatine (PCr), phosphomonoesters (PME), phosphodiesters (PDE), and inorganic phosphate (Pi) concentrations, then calculated ratios of these resonances. The beta-NTP, PCr, and Pi resonances in AD and control subjects were not significantly different. These data indicate that brain energy stores are not depleted in AD. No significant differences were detected in the absolute measurements of PME and PDE between the AD and control groups. However, among the calculated ratios, an increase in the PME/PDE ratio of approximately 50%, mostly due to a decrease in the PDE signal, was statistically significant (AD PME/PDE mean = 0.35, range 0.13-0.71; normal PME/PDE mean = 0.22, range 0.16-0.34). We speculate that the difference in PDE reflects changes in the biophysical state of membrane phospholipids in AD.

Aged↗

Quantitative in vivo 1H nuclear magnetic resonance spectroscopic imaging of neuronal loss in rat brain.

The aim of this research was to determine whether in vivo nuclear magnetic resonance spectroscopic measurement of N-acetyl aspartate, a neuron specific brain marker, provides a quantitative index of neuronal loss. Five rats were injected unilaterally in the corpus striatum with kainic acid, an analogue of glutamate that causes excitotoxic degeneration of intrinsic neurons, and were subjected to nuclear magnetic resonance imaging and spectroscopic imaging. Measurements of N-acetyl aspartate were determined in vivo and compared to post mortem nuclear magnetic resonance spectroscopic measures of N-acetyl aspartate and choline acetyl transferase and glutamate decarboxylase activities, biochemical markers for striatal intrinsic neuronal integrity. Mean per cent neuronal survival of hemispheres with lesion versus the contralateral hemispheres measured 72 for glutamate decarboxylase and 71 for N-acetyl aspartate (in vivo), 74 for N-acetyl aspartate (in vitro), and 62 for choline acetyl transferase, respectively. Our studies in rats have shown that estimates of neuronal loss through nuclear magnetic resonance spectroscopic measurements of N-acetyl aspartate are equivalent to traditional neuronal enzyme activity assays. The results unequivocally demonstrate that N-acetyl aspartate is a valid and sensitive neuronal marker with the capability of providing accurate assessments of neuronal loss in vivo.

Animals↗

Functional MR in the evaluation of dementia: correlation of abnormal dynamic cerebral blood volume measurements with changes in cerebral metabolism on positron emission tomography with fludeoxyglucose F 18.

PURPOSE: To determine whether magnetic susceptibility functional MR imaging of cerebral blood volumes provides information similar to fludeoxyglucose F 18 positron emission tomography (PET) brain images in patients undergoing evaluation for dementia. METHODS: Ten subjects were studied with both PET and functional MR. Clinical diagnoses included probable Alzheimer disease (n = 5), possible Alzheimer disease (n = 1), Pick disease (n = 2), and primary progressive aphasia (n = 2). The studies were quantitatively evaluated by coregistration of PET and functional MR images followed by regression analyses of corresponding regions of interest. Qualitatively, each brain was categorized into eight regions, and each was classified as normal or abnormal by visual inspection. RESULTS: Correlation coefficients between registered functional MR and PET images were excellent (mean, r = 0.58) in most of the cerebrum. Significant correlations were observed in 72 of 74 brain sections. Qualitatively, 16 brain regions were judged to be abnormal by both MR imaging and PET; 46 regions were normal by both; 10 regions were abnormal by PET only; and 8 regions were abnormal only by functional MR. The concordance between functional MR and PET was 78%, which was highly significant. CONCLUSION: Cerebral blood volumes images derived from magnetic susceptibility (functional MR) provide information similar to fludeoxyglucose F 18 PET images in demented patients undergoing evaluation for dementia.

Aged↗

Effect of fatty acid-rich diets on thymocyte proliferation and thymus involution during growing.

The effect of poly-unsaturated and saturated fatty acid-rich diet on the proliferation response of T and B lymphocytes in vitro was investigated. Also, a mitotic index of thymocytes and of thymus epithelial reticular-like cells and thymic involution coefficient were examined in vivo. w-6 PUFA-rich diet enhanced the rate of T (eightfold) and B (fourfold) lymphocyte proliferation, whereas saturated fatty acids did not show an important effect. However, both fat-rich diets increased the mitotic index of thymocytes and thymus involution index in vivo. These findings suggest that fat-rich diets may accelerate thymus involution during growing, possibly aggravating the impairment of the immune function which usually occurs under this condition.

Aging↗

Effects of various dietary fatty acids on enzyme activities of carbohydrate and glutamine metabolism and the metabolic response of lymphocytes and macrophages during Walker-256 ascites cell tumour growth in rats.

It was previously shown that polyunsaturated and saturated fatty acid rich diets affected metabolic and functional changes in macrophages and a variety of immune tissues (thymus, mesenteric lymph nodes and spleen). This study reports metabolic and functional changes in peritoneal macrophages and lymphocytes of Walker-256 ascites cell tumour-bearing rats which were fed (a) normal balanced diet (3% fat), (b) diet enriched (15% fat) with polyunsaturated fatty acids or (c) diet fortified (15% fat) with saturated fatty acids. Neither of the fatty acid enriched diets affected macrophage migration following tumour cell implantation and ascitic cell growth. However both of these fortified fatty acid regimes enhanced the production of H2O2 by macrophages and lymphocytes. The maximum catalytic capacities of hexokinase, glutaminase, glucose-6-phosphate dehydrogenase and glutathione peroxidase were measured in resident and tumour activated macrophages and lymphocytes obtained from rats fed the three fatty acid dietary regimes during seven days of tumour ascites cell growth. Tumour growth caused an increase in the activities of all of the above enzymes in macrophages irrespective of the fatty acid composition of the diet and notably decreased, independent of dietary fatty acid composition, the activities of the enzymes in lymphocytes. Only glutaminase activity in the lymphocytes of tumour bearing animals fed an unsaturated fatty acid-rich diet was not reduced, but was increased by 78%. Moreover macrophages from control rats fed an enriched polyunsaturated fatty acid diet had increased hexokinase activity (21%), decreased glutaminase (48%) and citrate synthase (decreased 41%) relative to the activities of these enzymes in macrophages of animals maintained on a balanced fatty acid diet. The feeding of both fatty acid rich diets did not modify the pattern of lymphocyte responses during the growth of tumour cells in these animals. None of the fatty acid diets modified the growth rate nor the yield of tumour cells in the peritoneal cavity.

Animals↗

The human brain resonance of choline-containing compounds is similar in patients receiving lithium treatment and controls: an in vivo proton magnetic resonance spectroscopy study.

Lithium specifically and potentially inhibits membrane transport of choline. However, the effect of lithium on human neuronal choline content is unknown. This study was performed to determine if lithium alters the human brain choline concentration in vivo. In vivo proton magnetic resonance spectroscopy was used to compare the relative brain concentration of choline-containing compounds in seven lithium-treated patients and six lithium-free controls. No significant difference was observed in the mean relative choline resonance between the patient and control groups. Lithium treatment did not appear to alter the overall brain content of choline-containing compounds. It remains possible that a component of these compounds, particularly free choline, is elevated during lithium treatment.

Adult↗

Accumulation of fluoxetine and norfluoxetine in human brain during therapeutic administration.

In vivo 19fluorine nuclear magnetic resonance spectroscopy was used to measure the brain concentration of fluoxetine and norfluoxetine in five patients with obsessive-compulsive disorder and three with major depression. The mean brain:plasma ratio of the parent drug plus the metabolite was significantly elevated to 2.6 (SD = 1.0) (95% confidence interval = 1.9-3.3). This accumulation may have implications for understanding both the therapeutic and the toxic effects of fluoxetine.

Adult↗

Overall body fat and regional fat distribution in young women: quantification with MR imaging.

Overall body fat and its distribution in different regions are important predispositions to known aberrations in lipid and glucose metabolism. The accuracy of MR imaging in estimating overall body fatness and regional fat distribution at individual landmarks was determined by comparing it with well-accepted measures by deuterium-oxide (D2O) dilution and bioimpedance analysis. Fourteen normal young women (athletes and control subjects) were studied. A total of 308 axial, T1-weighted, spin-echo MR images over a specific region in the trunk (21-24 scans per subject) were obtained. Morphometric computer image analysis was performed to determine the subcutaneous, internal, and total fat volumes in each image. The data were analyzed in two ways: data from all slices were summed to assess overall body fatness, and six anatomic landmarks were chosen for regional comparisons. MR-determined estimates of overall body fatness strongly correlated with total body fat measures by D2O dilution in both total fat (r = .91) and subcutaneous fat (r = .92) determinations. Athletes in both the low- and high-intensity training phases had significantly lower values of MR-determined total body fatness than did control subjects. Parallel to total body fatness, athletes had significantly lower MR-determined ratios of total fat/total volume in four of six individual landmarks compared with control subjects. Our experience suggests that MR is an accurate method to quantify overall body fatness, when compared with D2O dilution and bioimpedance analysis. MR could also discriminate regional components of subcutaneous and internal body fat at individual landmarks.

Adipose Tissue↗

Measurement of human brain lithium in vivo by MR spectroscopy.

PURPOSE: To quantify lithium in the human brain. METHODS: A 7Li MR spectroscopy method was developed with special features for high precision including: a) sampling a large cerebral volume to maximize the signal-to-noise ratio; b) adiabatic excitation pulses to ensure uniform spin mutation; c) morphometric analysis of the MR images of the sampled cerebrum; d) a mathematical model derived from empirical data to correct for receiver inhomogeneity effects; and e) a long interpulse delay, to eliminate errors arising from uncertain T1 values. RESULTS: A theoretical precision of 5.2% and an accuracy of better than 7.2% in someone with a brain lithium level of 1.0 mEq per liter of cerebral volume and precision and accuracy of 6.8 and 8.6%, respectively, in someone with 0.5 mEq/L brain lithium was calculated. This level of precision was surpassed in phantoms and patients. Brain lithium in 10 patients treated with lithium carbonate varied from 0.52 to 0.87 mEq/L (mean = 0.58 mEq/L; SD = 0.17 mEq/L). Brain-to-serum lithium ratios varied from 0.50 to 0.97 mEq/L (mean = 0.77 mEq/L; SD = 0.14 mEq/L). Substantial variation in brain lithium was observed in patients with similar serum lithium. CONCLUSIONS: A highly reliable method to quantify human brain lithium by 7Li MR spectroscopy has been implemented. Unexpected variability in brain versus serum levels of lithium was detected in patients with bipolar disease.

Brain Chemistry↗