Proton chemical shift imaging yielding separate water and lipid images was performed in a multisection mode on a clinical 1.5-T whole-body magnetic resonance imaging unit. Imaging was performed with a minor modification of the standard multisection spin-warp technique: that is, the addition of a sinc pulse or a soft square pulse and a homospoil gradient at the beginning of the pulse sequence. Phantom and human anatomic images are presented.

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Abstract:The acid-base dissociation constant (pK a ) of a drug is a key physicochemical parameter infl uencing many biopharmaceutical characteristics. While this has been well established, the overall proportion of non-ionizable and ionizable compounds for drug-like substances is not well known. Even less well known is the overall distribution of acid and base pK a values. The current study has reviewed the literature with regard to both the proportion of ionizable substances and pK a distributions. Further to this a set of 582 drugs with associated pK a data was thoroughly examined to provide a representative set of observations. This was further enhanced by delineating the compounds into CNS and non-CNS drugs to investigate where differences exist. Interestingly, the distribution of pK a values for single acids differed remarkably between CNS and non-CNS substances with only one CNS compound having an acid pK a below 6.1. The distribution of basic substances in the CNS set also showed a marked cut off with no compounds having a pK a above 10.5. The pK a distributions of drugs are infl uenced by two main drivers. The fi rst is related to the nature and frequency of occurrence of the functional groups that are commonly observed in pharmaceuticals and the typical range of pK a values they span. The other factor concerns the biological targets these compounds are designed to hit. For example, many CNS targets are based on seven transmembrane G protein-coupled receptors (7TM GPCR) which have a key aspartic acid residue known to interact with most ligands. As a consequence, amines are mostly present in the ligands that target 7TM GPCR's and this infl uences the pK a profi le of drugs containing basic groups. For larger screening collections of compounds, synthetic chemistry and the working practices of the chemists themselves can infl uence the proportion of ionizable compounds and consequent pK a distributions. The fi ndings from this study expand on current wisdom in pK a research and have implications for discovery research with regard to the composition of corporate databases and collections of screening compounds. Rough guidelines have been suggested for the profi le of compound collections and will evolve as this research area is expanded.

Magnetic resonance imaging was used ante mortem to confirm the anatomic location of an intracranial lesion in a dog with neurological signs. Necropsy revealed the lesion to be a choroid plexus carcinoma with thalamic invasion. A review of the literature on choroid plexus carcinomas in the dog is included.

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