A Low-cost Creatinine Biosensor by Differential Optical Signal Readout for the Whole Blood Analysis.

This study developed a low-cost paper-based biosensor for point-of-care (POC) detection of blood creatinine by using differential optical signal readout. Dual-channel photochemical paper-based test strips were fabricated with stackable multilayer films containing pre-immobilized enzymes and reagents for the identification and conversion of creatinine and creatine. Enzyme-linked reactions generated hydrogen peroxide (H2O2), which formed a blue oxidized condensate with aniline derivatives. The color depth was quantified via the differential optical signal of the two channels and positively correlated with the concentration of the analyte. This method was first proposed to address the issue of endogenous interferences in the enzymatic assay of creatinine, greatly improving the detection accuracy. The proposed biosensor was calibrated with spiked blood samples, and achieved a wide detection range of 31-1483 µmol/L, showing superior detection performance to general enzymatic methods, especially in the low concentration range. Creatine interference testing demonstrated that the biosensor could resist the interference of ≤ 300 µmol/L endogenous creatine. It is believed that the proposed optical differential biosensor for blood creatinine could enable to pave the way for a daily monitoring system for renal diseases.Clinical Relevance- This stackable multilayer paper-based biosensor provides an enzymatic colorimetric assay of creatinine in whole blood, which can be read out by the differential optical signal to exclude interference from endogenous creatine.

3T magnetic resonance spectroscopy as a powerful diagnostic modality for assessment of thyroid nodules.

OBJECTIVE: Magnetic resonance spectroscopy (MRS) is a powerful tool for structural studies of chemical compounds and biomolecules and also documented promising findings as a potential imaging technology in thyroid oncology. This prospective study was to ascertain the clinical significance of 3 Tesla MRS in the evaluation of patients with thyroid nodules (TNs) as an ancillary diagnostic technique for thyroid carcinoma. MATERIALS AND METHODS: Magnetic resonance spectroscopy at 3T at echo- times (TEs) 136 and 270 ms was carried out on 15 patients with total number of 32 TNs larger than 1 cm3, which all were surgically resected. Choline (Chol) to creatine (Cr) ratio was assessed at 136 and 270 TEs on each nodule and a receiver operating characteristic (ROC) curve was used to determine optimal cut-off point. The findings were compared with histopathology of thyroid specimens. RESULTS: There were 23 benign and 9 malignant lesions (7 papillary and 2 follicular thyroid carcinomas). The mean values of Chol/Cr at 136 and 270 TEs was 2.28 ± 3.65 and 1.52 ± 1.67 respectively and the difference between benign and malignant nodules was only significant at 136 TEs. The study revealed that Chol/ Cr ratio cut-off point of 2.5 best correlates with histopathology results (sensitivity = 75%; specificity = 100%; PPV = 100%; NPV= 92%). CONCLUSION: This preliminary study showed that 3T magnetic resonance spectroscopy might be a specific modality for the evaluation of thyroid nodules in differentiation of benign from malignant thyroid tissue. However, a larger series would give much greater confidence that this state-of-the-art technology will worth pursuing in clinical practice.

3T magnetic resonance spectroscopy as a powerful diagnostic modality for assessment of thyroid nodules

ABSTRACT Objective: Magnetic resonance spectroscopy (MRS) is a powerful tool for structural studies of chemical compounds and biomolecules and also documented promising findings as a potential imaging technology in thyroid oncology. This prospective study was to ascertain the clinical significance of 3 Tesla MRS in the evaluation of patients with thyroid nodules (TNs) as an ancillary diagnostic technique for thyroid carcinoma. Materials and methods: Magnetic resonance spectroscopy at 3T at echo- times (TEs) 136 and 270 ms was carried out on 15 patients with total number of 32 TNs larger than 1 cm3, which all were surgically resected. Choline (Chol) to creatine (Cr) ratio was assessed at 136 and 270 TEs on each nodule and a receiver operating characteristic (ROC) curve was used to determine optimal cut-off point. The findings were compared with histopathology of thyroid specimens. Results: There were 23 benign and 9 malignant lesions (7 papillary and 2 follicular thyroid carcinomas). The mean values of Chol/Cr at 136 and 270 TEs was 2.28 ± 3.65 and 1.52 ± 1.67 respectively and the difference between benign and malignant nodules was only significant at 136 TEs. The study revealed that Chol/ Cr ratio cut-off point of 2.5 best correlates with histopathology results (sensitivity = 75%; specificity = 100%; PPV = 100%; NPV= 92%). Conclusion: This preliminary study showed that 3T magnetic resonance spectroscopy might be a specific modality for the evaluation of thyroid nodules in differentiation of benign from malignant thyroid tissue. However, a larger series would give much greater confidence that this state-of-the-art technology will worth pursuing in clinical practice.

Study on the clinical application of the MRS in the cognitive assessment after stroke.

OBJECTIVE: To discuss the value of the application of the magnetic resonance spectroscopy (MRS) in the assessment of cognitive function impairment and the observation of therapeutic effect. PATIENTS AND METHODS: 30 patients with cognitive impairment after stroke (cognitive impairment group) and 30 patients with no apparent cognitive impairment (control group of the stroke) were selected through the screening of the mini-mental state examination (MMSE) scale, and another 30 healthy volunteers were selected (control group of the health). The general information of gender, age, education degree, disease duration and so on was matched among the 3 groups. MRS examined all the patients of the 3 groups at the time of enrollment, and the patients of both cognitive impairment and control groups received another assessment 2 months after treatment. RESULTS: The NAA/Cr (N-acetyl aspartate/creatine) of the bilateral hippocampus of the cognitive impairment group was lower than those of both control group of stroke and health (p < 0.05), while the Cho/Cr was higher (p < 0.05). After treatment, both patients of the cognitive impairment group and the control group of the stroke experienced an increase of NAA/Cr and a decrease of Cho/Cr (p < 0.05). CONCLUSIONS: MRS is applicative in the assessment of the cognitive impairment degree of the stroke patients and can also effectively identify the existence of the cognitive impairment, which makes it preferably valuable in the clinical application.

Simultaneous determination of metabolite concentrations, T1 and T2 relaxation times.

PURPOSE: To simultaneously measure concentration and T1 and T2 values of metabolites in the human brain in a single scan session. METHODS: A new pulse sequence with multiple variable acquisition parameters was proposed to encode metabolite T1 and T2 information into the acquired data. A linear combination-fitting algorithm was developed in-house to simultaneously determine metabolite concentrations and relaxation times. RESULTS: Concentration, T1 , and T2 values of N-acetyl-aspartate, total creatine, total choline, and glutamate were reliably measured in the frontal gray matter and white matter regions of nine healthy volunteers at 7 tesla in less than 10 minutes of scan time per voxel. T1 and T2 values of glutamine, as well as T1 of glutathione, were also measured in the frontal gray matter region with reasonable precision. CONCLUSION: The proposed technique allows multiparametric characterization of brain metabolites in a single scan session, making it possible to measure both levels and intracellular microenvironments of brain chemicals in clinical MR spectroscopy studies. Magn Reson Med 78:2072-2081, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Viability assessment of magnetic resonance spectroscopy for the detection of minimal hepatic encephalopathy severity.

OBJECTIVE: To evaluate regional cerebral metabolic changes in minimal hepatic encephalopathy (MHE) patients using magnetic resonance spectroscopy (MRS) in 3T scanner. MATERIALS AND METHODS: This study comprised 30 cirrhotic patients with MHE, 29 cirrhotic patients without MHE and 30 healthy volunteers. Single-voxel proton MRS data in the anterior cingulate cortex (ACC) and basal ganglia were acquired using a 3-T scanner. The concentrations of N-acetylaspartate (NAA), mI (myo-inositol), glutamate (Glu), glutamine (Gln) and creatine (Cr) were obtained by LC-model software. Statistical analysis was performed to evaluate the differences between the three groups. RESULTS: There was a significant increase in Glu for the cirrhotic patients, particularly the MHE patients. There was an elevation of Gln in the cirrhotic patients, but not in all cirrhotic patients or controls. There was a significant decrease in mI for the cirrhotic patients, but no significant difference between the two cirrhosis groups. There was no significant difference in NAA between the three groups. CONCLUSIONS: MRS using a 3-T MR scanner could detect cerebral metabolic changes in cirrhotic patients with MHE. Glu levels were elevated in cirrhotic patients with MHE; Glu levels could be used as a sensitive indicator to evaluate the severity of MHE in patients with cirrhosis.

Low docosahexaenoic acid status is associated with reduced indices in cortical integrity in the anterior cingulate of healthy male children: a 1H MRS Study.

Docosahexaenoic acid (DHA, 22:6n-3) is the principal omega-3 fatty acid in mammalian brain gray matter, and emerging preclinical evidence suggests that DHA has neurotrophic and neuroprotective properties. This study investigated relationships among DHA status, neurocognitive performance, and cortical metabolism measured with proton magnetic resonance spectroscopy (1H MRS) in healthy developing male children (aged 8-10 years, n = 38). Subjects were segregated into low-DHA (n = 19) and high-DHA (n = 19) status groups by a median split of erythrocyte DHA levels. Group differences in 1H MRS indices of cortical metabolism, including choline (Cho), creatine (Cr), glutamine + glutamate + γ-aminobutyric acid (Glx), myo-inositol (mI), and n-acetyl aspartate (NAA), were determined in the right and left dorsolateral prefrontal cortex (R/L-DLPFC, BA9) and bilateral anterior cingulate cortex (ACC, BA32/33). Group differences in neurocognitive performance were evaluated with the Kaufman Brief Intelligence Test and identical-pairs version of the continuous performance task (CPT-IP). Subjects in the low-DHA group consumed fish less frequently (P = 0.02), had slower reaction times on the CPT-IP (P = 0.007), and exhibited lower mI (P = 0.007), NAA (P = 0.007), Cho (P = 0.009), and Cr (P = 0.01) concentrations in the ACC compared with the high-DHA group. There were no group differences in ACC Glx or any metabolite in the L-DLPFC and R-DLPFC. These data indicate that low-DHA status is associated with reduced indices of metabolic function in the ACC and slower reaction time during sustained attention in developing male children.

In vivo assessment of prostate cancer aggressiveness using magnetic resonance spectroscopic imaging at 3 T with an endorectal coil.

BACKGROUND: One of the most important clinical challenges in prostate cancer (PCa) management is an in vivo assessment of cancer aggressiveness. OBJECTIVE: To validate the performance of magnetic resonance (MR) spectroscopic imaging (MRSI) of the prostate at 3 T for the purpose of assessing tumour aggressiveness based on the ratio of choline plus creatine to citrate (Cho+Cr/Cit) and of choline to creatine (Cho/Cr), using the Gleason score of the radical prostatectomy (RP) specimen as the gold standard. DESIGN, SETTING, AND PARTICIPANTS: A total of 43 biopsy-proven PCa patients with 53 clinically relevant tumour foci were retrospectively included in this study. MEASUREMENTS: Patients underwent MR imaging and MRSI examination followed by RP. From MRSI, all spectroscopy voxels containing tumour were selected by a radiologist guided by the prostatectomy histopathology map only. For each tumour, two spectroscopists determined the maximum Cho+Cr/Cit, Cho/Cr, and malignancy rating using a standardised threshold approach, incorporating both metabolic ratios. The maximum Cho+Cr/Cit, Cho/Cr, and malignancy ratings showed a relation to tumour aggressiveness and so were used to differentiate among tumour aggressiveness classes. RESULTS AND LIMITATIONS: The maximum Cho+Cr/Cit ratio, maximum Cho/Cr ratio, and malignancy rating of a standardised threshold approach separated low-grade from higher-grade tumours, with areas under the receiver operating characteristic (ROC) curves of 0.70, 0.74, and 0.78, respectively. CONCLUSIONS: MRSI offers possibilities for an in vivo, noninvasive assessment of PCa aggressiveness. The combination of the different metabolite ratios was used with promising results for discrimination among different aggressiveness classes.

Assessment of novel avian renal disease markers for the detection of experimental nephrotoxicosis in pigeons (Columba livia).

Renal disease is a major cause of illness in captive and wild avian species. Current renal disease markers (e.g., uric acid, blood urea nitrogen, and creatinine) are insensitive. Two endogenous markers, creatine and N-acetyl-beta-D-glucosaminidase (NAG), were selected for study in the pigeon (Columba livia). Representative organs from four pigeons were surveyed to determine those exhibiting the highest level of each marker. In a separate study, NAG and creatine from plasma and urine were assayed before and after gentamicin (50 mg/kg twice daily), administration for up to 9 days. Observer-blinded pathologic scoring (five saline solution controls, 17 treated birds) was used to verify the presence of renal disease that corresponded to marker increases. The first study revealed that kidney tissue had the highest NAG activity (by approximately six times), and pectoral muscle had the most creatine (>900 times). In response to gentamicin, plasma creatine (>five times) and NAG increased (approximately six times), which paralleled uric acid (>10 times). Urine creatine (approximately 60 times) and NAG increased dramatically (approximately 50 times) in response to gentamicin. In conclusion, NAG, especially in the urine, may be of value to noninvasively detect renal toxin exposures and to monitor potentially nephrotoxic drugs, and might be of value to screen free-ranging birds in large exhibits or in the wild by assaying fresh urate samples at feeding stations.

Assessment of Hg contamination and exposure to miners and schoolchildren at a small-scale gold mining and recovery operation in Thailand.

Gold extracted by Hg-amalgamation process, which can cause both health and environmental problems, is widespread in South East Asia including Myanmar, Laos, Cambodia, and Thailand. Small-scale gold mining operations have been carried out since the year 2000 in Phanom Pha District, Phichit Province, Thailand. Since no data is available for evaluating Hg exposure, an investigation of mercury (Hg) contamination and exposure assessment was carried out at this mine site. Environmental monitoring illustrated the total Hg in water was as high as 4 microg/l while Hg in sediment ranged between 102 to 325 microg/kg dry weight. Both Hg deposition from the air (1.28 microg/100 cm(2)/day) and concentration in surface soil (20,960 microg/kg dry weight) were elevated in the area of amalgamation. The potential of Hg exposure to miners as well as to schoolchildren was assessed. The concentrations of Hg in urine of 79 miners who were directly (group I) or indirectly (group II) involved in the gold recovery operation were 32.02 and 20.04 microg/g creatinine, respectively, which did not exceed regulatory limits (35 microg/g creatinine). Hair Hg levels in both groups (group I and group II) also were not significantly higher than the non-exposed group. In terms of risk factors, gender and nature of food preparation and consumption were the two significant variables influencing the concentration of Hg in urine of miners (P < 0.05). A hazard quotient (HQ) was estimated based on the inorganic Hg exposure of individual miners. The HQ values of group I were in a range 16 to 218 times higher than the safety level set as 1. By comparison the group II HQ index was very low (0.03-0.39). The miners in group I who worked and ate food from this area experienced potentially high exposure to Hg associated with the mining process. In a second Hg exposure assessment, a group of 59 schoolchildren who attended an elementary school near the gold mine site was evaluated for Hg exposure. A slightly higher Hg urine concentration was detected in group I and group II (involved and not involved in gold recovery) at average levels of 15.82 and 9.95 microg/g creatinine, respectively. The average Hg values for both groups were below the established levels indicating no risk from Hg intake. Average Hg hair level in all schoolchildren (0.93 microg/g) was not significantly higher than reference group. There were two variables (gender and personal hygiene) which affected the concentration of Hg in urine of schoolchildren (P < 0.05). The result (HQ) also suggested that schoolchildren were not at risk (< 1). Schoolchildren involved in gold mining activities showed some indirect exposure to Hg from the adults working in mining area.

Assessment of metabolite quantitation reproducibility in serial 3D-(1)H-MR spectroscopic imaging of human brain using stereotactic repositioning.

Intrasubject reproducibility of metabolite quantitation in three-dimensional proton magnetic resonance spectroscopic imaging (3D-MRSI) was investigated in 10 healthy volunteers over five separate sessions using two echo times (TEs): 144 and 30 ms. The use of a Gill-Thomas-Cosman (GTC) stereotactic head frame enabled precise subject repositioning and immobilization. Metabolite levels from each voxel in the volume of interest (VOI) were quantified using the Linear Combination of Model spectra (LCModel) analysis algorithm, and coefficients of variation (CVs) were calculated. Standard error estimates (%SD or Cramer-Rao lower bounds) generated by LCModel were used as a confidence filter. The 95% confidence interval (CI) was found for each metabolite, providing an indication of the normal fluctuation expected for 3D-MRSI. In vivo, median CVs at the %SD < or = 20 level were found to be (%CV for TE = 144 and 30 ms, respectively): N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (NAA): 10.2% and 13.5%; creatine plus phosphocreatine (Cr), 14.4% and 21.7%; and choline-containing compounds (Cho), 15.2% and 18.4%. Relaxing the statistical filtering criteria to %SD < or = 30 increased median CVs by less than 5% and permitted in vivo quantitation reproducibility to be evaluated for glutamine plus glutamate (Glx) and myoinositol (Ins) for TE = 30 ms, yielding CVs of 24.0% and 21.0%, respectively.

Assessment with magnetic resonance imaging and spectroscopy in Lhermitte-Duclos disease.

Lhermitte-Duclos disease (LDD) is a rare benign lesion of uncertain pathogenesis characterized by distortion of the normal cerebellar laminar cytoarchitecture. We report a 22-year-old man admitted for injury sustained in a traffic accident with the incidental finding of a cerebellar mass. Magnetic resonance imaging (MRI) revealed a mass lesion within the right cerebellar hemisphere. The final diagnosis of LDD was made by obtaining a surgical specimen and identifying the characteristic appearance of the lesion by MRI study. The images showed the typical striated pattern of hyperintensity on T2-weighted images and corresponding hypointensity on T1-weighted images, as well as the typical absence of enhancement following gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) administration. In addition, no disturbance of water diffusion on diffusion-weighted MRI, and associations of decreases in the N-acetylaspartate/creatine (NAA/Cr) and NAA/Choline (Cho) ratios with near normal values of Cho/Cr, as well as an obvious lactate peak gave supplemental information for diagnosis.

Multiparametric 3T MR approach to the assessment of cerebral gliomas: tumor extent and malignancy.

INTRODUCTION: Contrast-enhanced MR imaging is the method of choice for routine assessment of brain tumors, but it has limited sensitivity and specificity. We verified if the addition of metabolic, diffusion and hemodynamic information improved the definition of glioma extent and grade. METHODS: Thirty-one patients with cerebral gliomas (21 high- and 10 low-grade) underwent conventional MR imaging, proton MR spectroscopic imaging ((1)H-MRSI), diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI) at 3 Tesla, before undergoing surgery and histological confirmation. Normalized metabolite signals, including choline (Cho), N-acetylaspartate (NAA), creatine and lactate/lipids, were obtained by (1)H-MRSI; apparent diffusion coefficient (ADC) by DWI; and relative cerebral blood volume (rCBV) by PWI. RESULTS: Perienhancing areas with abnormal MR signal showed 3 multiparametric patterns: "tumor", with abnormal Cho/NAA ratio, lower ADC and higher rCBV; "edema", with normal Cho/NAA ratio, higher ADC and lower rCBV; and "tumor/edema", with abnormal Cho/NAA ratio and intermediate ADC and rCBV. Perienhancing areas with normal MR signal showed 2 multiparametric patterns: "infiltrated", with high Cho and/or abnormal Cho/NAA ratio; and "normal", with normal spectra. Stepwise discriminant analysis showed that the better classification accuracy of perienhancing areas was achieved when regarding all MR variables, while (1)H-MRSI variables and rCBV better differentiated high- from low-grade gliomas. CONCLUSION: Multiparametric MR assessment of gliomas, based on (1)H-MRSI, PWI and DWI, discriminates infiltrating tumor from surrounding vasogenic edema or normal tissues, and high- from low-grade gliomas. This approach may provide useful information for guiding stereotactic biopsies, surgical resection and radiation treatment.

Assessment of adrenoleukodystrophy lesions by high field MRS in non-sedated pediatric patients.

BACKGROUND: Early detection of white matter lesions in childhood-onset cerebral adrenoleukodystrophy (ALD) is important as hematopoietic cell transplantation (HCT), currently the only effective treatment, is beneficial only if performed early in the disease course. OBJECTIVE: To establish reliable biochemical markers of cerebral disease progression in patients with ALD to aid in treatment planning. METHODS: The authors used proton magnetic resonance spectroscopy (MRS) in combination with LCModel analysis to quantify brain metabolites in small volumes (3 to 16 mL) in the occipital and frontal white matter and the splenium of the corpus callosum of 17 unsedated patients and 26 healthy volunteers (adult n = 21, age-matched n = 5) at 4 tesla. RESULTS: Absolute concentrations of 12 metabolites were reliably determined, seven of which were established as markers of lesion development. Among these, creatine and choline containing compounds were the weakest markers while N-acetylaspartate, glutamine, and lipids + lactate were the strongest. The large extent of changes in the markers enabled detection of early neurochemical changes in lesion formation prior to detection of abnormalities by conventional MRI. Concentrations of a number of metabolites were also significantly different between normal appearing white matter of patients and controls indicating biochemical alterations in the absence of cerebral disease. Neurochemical improvements following HCT were measured in six patients. CONCLUSIONS: The progression of adrenoleukodystrophy, as well as effectiveness of its treatment, can be assessed with high precision using high field 1H magnetic resonance spectroscopy in individual patients without the need for sedation.

Guanidinoacetate and creatine plus creatinine assessment in physiologic fluids: an effective diagnostic tool for the biochemical diagnosis of arginine:glycine amidinotransferase and guanidinoacetate methyltransferase deficiencies.

BACKGROUND: Disorders of creatine metabolism arise from genetic alterations of arginine:glycine amidinotransferase (AGAT), guanidinoacetate methyltransferase (GAMT), and the creatine transporter. We developed a strategy for the detection of AGAT and GAMT defects by measurement of guanidinoacetate (GAA) and creatine plus creatinine (Cr+Crn) in biological fluids. METHODS: Three patients with AGAT deficiency from the same pedigree and their eight relatives, as well as a patient affected by a GAMT defect and his parents were analyzed by a new HPLC procedure in comparison with 90 controls. The method, which uses precolumn derivatization with benzoin, separation with a reversed-phase column, and fluorescence detection, has shown good precision and sensitivity and requires minimal sample handling. RESULTS: In the three AGAT patients, plasma GAA was 0.01-0.04 micro mol/L [mean (SD) for neurologically normal controls was 1.16 (0.59) micromol/L], Cr+Crn was 15-29 micro mol/L [reference limit in our laboratory, 79 (38) micromol/L]. Urinary GAA was 2.4-5.8 micro mol/L [reference, 311 (191) micromol/L], and Cr+Crn was 2.1-3.3 mmol/L [reference, 9.9 (4.1) mmol/L]. We found a smaller decrease in GAA and Cr+Crn in some carriers of an AGAT defect. In the patient with GAMT deficiency, plasma and urine GAA was increased (18.6 and 1783 micromol/L, respectively), and Cr+Crn was decreased in plasma (10.7 micromol/L) and urine (2.1 mmol/L). GAA was increased in the parents' plasmas and in the mother's urine. CONCLUSION: The assessment of GAA is a new tool for the detection of both GAMT and AGAT deficiencies.

Spectroscopic assessment of alterations in macromolecule and small-molecule metabolites in human brain after stroke.

BACKGROUND AND PURPOSE: We sought to measure the temporal evolution and spatial distribution of lesion macromolecules and small molecules (lactate, N-acetyl compounds, creatine, and choline) in stroke patients by using short echo time in vivo proton MR spectroscopy. METHODS: Single-voxel spectra with TE=22 ms were obtained with and without inversion recovery suppression of small-molecule resonances from 30 examinations of 24 patients 3 to 214 days after stroke. Subtraction of the suppressed from the unsuppressed spectra yielded metabolite spectra without overlap from macromolecules. Two-dimensional spectroscopic images were acquired with macromolecule and small-molecule suppression from 5 additional patients. RESULTS: Macromolecule signals were elevated in lesions relative to normal brain and tended to increase in the subacute period, even as lactate peaks declined. Regions of increased lactate, increased macromolecule signal at 1.3 ppm, and decreased N-acetyl compounds were closely correlated in the 2D spectroscopic images. CONCLUSIONS: Short echo time spectra can be acquired in vivo in a manner that improves signal-to-noise ratio over long echo experiments and resolves overlapping macromolecule and small-molecule signals. The prominent macromolecule signals seen in the subacute period in association with persistently elevated lactate may represent mobile lipids in macrophages or other cells.

Assessment of GABA concentration in human brain using two-dimensional proton magnetic resonance spectroscopy.

A quantitative method to assess in vivo brain gamma-aminobutyric acid (GABA) levels is proposed using a J-resolved, two-dimensional (2D) magnetic resonance spectroscopy (MRS) technique. Localized, J-resolved 2D MR spectra were obtained from a 12-cm(3) voxel in the occipital lobe of 36 healthy volunteers (18 male and 18 female, age: 25.1+/-4.8 years). Based on phantom measurements, a GABA resonance peak located at 2.94 ppm, 7.45 Hz, in J-resolved 2D MRS overlaps the least with other resonance peaks which arise from N-acetylaspartate, choline, creatine, glutamate and glutamine. Measurements of this resonance peak yield in vivo GABA concentrations of 1.01+/-0.36 micromol/cm(3) for male and 1.16+/-0.43 micromol/cm(3) for female volunteers, without correction for T1 and T2 relaxation effects. These results are in good agreement with previously reported data and suggest that, with further development, 2D MRS may provide a practical means to estimate the concentration of this important neurotransmitter.

Combined magnetization transfer and proton spectroscopic imaging in the assessment of pathologic brain lesions in multiple sclerosis.

BACKGROUND AND PURPOSE: Conventional MR imaging of multiple sclerosis (MS) provides relatively poor pathologic specificity, which has led to the investigation of more sophisticated MR techniques. The purpose of this study was to combine magnetization transfer (MT) imaging and proton MR spectroscopic imaging (MRSI) to evaluate the specific pathologic features of myelination and neuronal integrity in patients with MS and to determine the relationship between these measures within plaques. METHODS: We acquired conventional MR, MT, and proton MRSI data and evaluated clinical disability in 30 patients with MS, whose conditions were categorized as relapsing-remitting, primary progressive, or secondary progressive. The lesions were classified, using a semiautomated edge-following technique, on T2-weighted MR images, and an analysis of MT and proton MRSI data was conducted for lesion regions as well as for tissue that was categorized as normal. RESULTS: The MT ratio (MTR) of normal-appearing white matter in the patients with MS was significantly lower than in the healthy participants, whereas gray matter values were unchanged. MS lesions showed a large reduction in MTR, with old lesions exhibiting a lower MTR than new lesions. The average lesion MTR and the MR spectroscopic imaging-measured relative concentration of N-acetylaspartate, a marker of neuronal integrity, was positively correlated in patients with relapsing-remitting MS. This relationship was strengthened in regions containing new lesions. CONCLUSION: The integrated use of MT and MR spectroscopic imaging provides a more complete description of the pathologic features of MS than does conventional MR imaging alone, and our data suggest that axonal damage occurs in step with new demyelination and is not a late feature of the disease.

Avaliaçäo da necessidade da dosagem rotineira de hematócrito, hemoglobina, uréia e creatinina séricos durante a avaliaçäo pré-anestésica / Assessment of the need for routine dosage of hematocrits, hemoglobin, blood urea nitrogen and serum creatinine during preoperative evaluation

Justificativa e objetivos - Muitas dúvidas e opiniöes existem quanto à realizaçäo de exames pré-operatórios de maneira rotineira, como parte integrante da avaliaçäo pré-anestésica. As tendências atuais apontam para a realizaçäo desses exames fundamentada em avaliaçäo clínica e exame físico detalhados, que säo as bases da avaliaçäo pré-anestésica. Como esses testes laboratoriais continuam sendo realizados indiscriminadamente e as dúvidas quanto a seu real valor também persistem, idealizamos este trabalho com o objetivo de avaliar os resultados de hematócrito, de hemoglobina, de uréia e de creatinina séricos, testes solicitados rotineiramente na avaliaçäo pré-operatória de pacientes candidatos a cirurgias eletivas, determinando sua necessidade e possivelmente esclarecer essas dúvidas. Método - foram estudados 1065 pacientes com idade a partir de 12 anos, estado físico ASA I, II e III, internados para realizaçäo de procedimento cirúrgico eletivo, divididos em sete grupos de diferentes faixas etárias, com distribuiçäo aleatória em relaçäo ao sexo. Foram observados e analisados os resultados dos exames laboratoriais de hematócrito, hemoglobina, uréia e creatinina séricos, que fazem parte da rotina de avaliaçäo pré-operatória da maioria das clínicas cirúrgicas de nosso hospital. A análise estatística realizada para cada variável estudada foi a Análise de Variância e, para a comparaçäo grupo a grupo, o Teste de Comparaçäo Múltipla de Benferroni. As diferenças foram consideradas significativas quando p < 0,05 ou 5 por cento. Resultados - Para os 1065 pacientes estudados, obtivemos um total de 4025 exames laboratoriais solicitados, sendo semelhante o número de exames realizados em cada grupo. Para os resultados de hematócrito e hemoglobina näo houve diferença entre os grupos e os valores situaram-se dentro de limites da normalidade. Considerando-se a uréia e a creatinina séricas, houve diferença entre os grupos de pacientes mais novos e aqueles de pacientes mais idosos e os resultados näo mostraram anormalidades significativas em todos os grupos. Conclusöes - concluímos que os valores médios obtidos, tanto de hematócrito e hemoglobina, quanto de uréia e creatinina séricos, em todos os grupos etários, säo aceitáveis para pacientes cirúrgicos, de uma maneira geral. Todavia, sua utilidade é mínima se realizados independentemente da avaliaçäo clínica. Assim, esses exames pré-operatórios de rotina devem ser abandonados e a boa prática clínica e o bom senso é que...