Optimized spectrally selective steady-state free precession sequences for cartilage imaging at ultra-high fields

OBJECT: Fat suppressed 3D steady-state free precession (SSFP) sequences are of special interest in cartilage imaging due to their short repetition time in combination with high signal-to-noise ratio. At low-to-high fields (1.5-3.0 T), spectral spatial (spsp) radio frequency (RF) pulses perform superiorly over conventional saturation of the fat signal (FATSAT pulses). However, ultra-high fields (7.0 T and more) may offer alternative fat suppression techniques as a result of the increased chemical shift. MATERIALS AND METHODS: Application of a single, frequency selective, RF pulse is compared to spsp excitation for water (or fat) selective imaging at 7.0 T. RESULTS: For SSFP, application of a single frequency selective RF pulse for selective water or fat excitation performs beneficially over the commonly applied spsp RF pulses. In addition to the overall improved fat suppression, the application of single RF pulses leads to decreased power depositions, still representing one of the major restrictions in the design and application of many pulse sequences at ultra-high fields. CONCLUSION: The ease of applicability and implementation of single frequency selective RF pulses at ultra-high-fields might be of great benefit for a vast number of applications where fat suppression is desirable or fat-water separation is needed for quantification purposes.

Optimized on-line enantioselective capillary electrophoretic method for kinetic and inhibition studies of drug metabolism mediated by cytochrome P450 enzymes.

Pharmacokinetic and pharmacodynamic properties of a chiral drug can significantly differ between application of the racemate and single enantiomers. During drug development, the characteristics of candidate compounds have to be assessed prior to clinical testing. Since biotransformation significantly influences drug actions in an organism, metabolism studies represent a crucial part of such tests. Hence, an optimized and economical capillary electrophoretic method for on-line studies of the enantioselective drug metabolism mediated by cytochrome P450 enzymes was developed. It comprises a diffusion-based procedure, which enables mixing of the enzyme with virtually any compound inside the nanoliter-scale capillary reactor and without the need of additional optimization of mixing conditions. For CYP3A4, ketamine as probe substrate and highly sulfated γ-cyclodextrin as chiral selector, improved separation conditions for ketamine and norketamine enantiomers compared to a previously published electrophoretically mediated microanalysis method were elucidated. The new approach was thoroughly validated for the CYP3A4-mediated N-demethylation pathway of ketamine and applied to the determination of its kinetic parameters and the inhibition characteristics in presence of ketoconazole and dexmedetomidine. The determined parameters were found to be comparable to literature data obtained with different techniques. The presented method constitutes a miniaturized and cost-effective tool, which should be suitable for the assessment of the stereoselective aspects of kinetic and inhibition studies of cytochrome P450-mediated metabolic steps within early stages of the development of a new drug.