Search

Chemical exchange saturation transfer (CEST) from taurine to water (TauCEST) can be used for in vivo mapping of taurine concentrations as well as for measurements of relative changes in intracellular pH (pH

Chemical exchange saturation transfer (CEST) from glutamate to water (GluCEST) is a powerful tool for mapping glutamate concentration and intracellular pH. GluCEST could also be helpful to understand the physiology of lower aquatic vertebrates and invertebrates. Therefore, this study aimed to investigate the GluCEST effect and the exchange rate ksw from amine protons of glutamate to water in a broad range of temperatures (1-37°C) and pH (5.5-8.0). Z-spectra were measured from glutamate solutions at different pH values and temperatures and analysed by numerically solving the Bloch-McConnell equation. As expected, a strong dependence of the GluCEST effect and the determined ksw values on pH and temperature was observed. In addition, a strong dependence of the GluCEST effect on phosphate buffer concentration was confirmed. The in vitro data show that GluCEST is detectable in the whole temperature range, even at 1°C. An interpolation function for the exchange rate ksw was determined for the considered range of temperatures and pH values, showing a bijective relation between the exchange rate and pH at a given temperature. To investigate the specificity of GluCEST imaging at low temperatures, the CEST effect was investigated for several metabolites relevant for CEST imaging of the brain. As an example, the contribution of GluCEST to the total CEST effect at 3 ppm was estimated for zebrafish (Danio rerio). It is shown that also at lower temperatures glutamate is the major contributor to the total CEST effect, particularly if the experimental parameters are optimized.

Chemical exchange saturation transfer (CEST) from glutamate to water (GluCEST) is a powerful tool for mapping glutamate concentration and intracellular pH. GluCEST could also be helpful to understand the physiology of lower aquatic vertebrates and invertebrates. Therefore, this study aimed to investigate the GluCEST effect and the exchange rate ksw from amine protons of glutamate to water in a broad range of temperatures (1-37°C) and pH (5.5-8.0). Z-spectra were measured from glutamate solutions at different pH values and temperatures and analysed by numerically solving the Bloch-McConnell equation. As expected, a strong dependence of the GluCEST effect and the determined ksw values on pH and temperature was observed. In addition, a strong dependence of the GluCEST effect on phosphate buffer concentration was confirmed. The in vitro data show that GluCEST is detectable in the whole temperature range, even at 1°C. An interpolation function for the exchange rate ksw was determined for the considered range of temperatures and pH values, showing a bijective relation between the exchange rate and pH at a given temperature. To investigate the specificity of GluCEST imaging at low temperatures, the CEST effect was investigated for several metabolites relevant for CEST imaging of the brain. As an example, the contribution of GluCEST to the total CEST effect at 3 ppm was estimated for zebrafish (Danio rerio). It is shown that also at lower temperatures glutamate is the major contributor to the total CEST effect, particularly if the experimental parameters are optimized.

High-resolution proton magnetic resonance spectroscopy was performed on tissue specimens from 33 patients with astrocytic tumors (22 astrocytomas, 11 glioblastomas) and 13 patients with meningiomas. For all patients, samples of primary tumors and their first recurrences were examined. Increased anaplasia, with respect to malignant transformation, resulting in a higher malignancy grade, was present in 11 recurrences of 22 astrocytoma patients. Spectroscopic features of tumor types, as determined on samples of the primary occurrences, were in good agreement with previous studies. Compared with the respective primary astrocytomas, characteristic features of glioblastomas were significantly increased concentrations of alanine (Ala) (p = 0.005), increased metabolite ratios of glycine (Gly)/total creatine (tCr) (p = 0.0001) and glutamate (Glu)/glutamine (Gln) (p = 0.004). Meningiomas showed increased Ala (p = 0.02) and metabolite ratios [Gly, total choline (tCho), Ala] over tCr (p = 0.001) relative to astrocytomas, and N-acetylaspartate and myo-inositol were absent. Metabolic changes of an evolving tumor were observed in recurrent astrocytomas: owing to their consecutive assessments, more indicators of malignant degeneration were detected in astrocytoma recurrences (e.g. Gly, p = 0.029; tCho, p = 0.034; Glu, p = 0.015; tCho/tCr, p = 0.001) in contrast to the comparison of primary astrocytomas with primary glioblastomas. The present investigation demonstrated a correlation of the tCho-signal with tumor progression. Significantly elevated concentrations of Ala (p = 0.037) and Glu (p = 0.003) and metabolite ratio tCho/tCr (p = 0.005) were even found in recurrent low-grade astrocytomas with unchanged histopathological grading (n = 11). This may be related to an early stage of malignant transformation, not yet detectable morphologically, and emphasizes the high sensitivity of 1H NMR spectroscopy in elucidating characteristics of brain tumor metabolism.

T2*-weighted imaging at 4.7 T was used to identify the cortical areas activated by electrical stimulation of the forepaw and hindpaw of alpha-chloralose anesthetized rats. Variation of the coronal slice position relative to the bregma, showed that the forepaw representation in the somatosensory cortex is more frontal and lateral than that of the hindpaw. Overlap between both activation areas was observed only in a small region in the slice at the level of the bregma. Documented localizations of both representations are in good agreement with earlier observations using invasive techniques. The determination of the separate areas of both paws indicates the feasibility of more complex activation studies in anesthetized animals, such as combined stimulations for the investigation of potentiation or depression effects on individual stimuli.

A fast version of the arterial spin tagging technique for the detection of cerebral perfusion is presented. Based on adiabatic spin inversion in combination with snapshot FLASH imaging our technique allows the recording of perfusion changes with a temporal resolution of about 3 s. Differences of cerebral perfusion dependent on the choice of anesthesia were observed in rat brain. Furthermore, with this arterial spin tagging method we demonstrated perfusion increases in the somatosensory cortex of anaesthetized rats during forepaw stimulation. Comparison of the activated areas in the T 2 * -weighted BOLD images and the perfusion-weighted images showed good spatial correspondence, but the sensitivity to the functional activation was more than ten times higher in the perfusion technique.