Biomedical subjects

Diana Cash

Publications and source records attributed to Diana Cash.

4 recordsLinked to original sources

PubMed2006

Using the BOLD MR signal to differentiate the stereoisomers of ketamine in the rat.

RATIONALE: Ketamine is a chiral molecule that is reported to model aspects of schizophrenia. OBJECTIVES: To investigate the stereospecificity of the isomers of ketamine using pharmacological magnetic resonance imaging (phMRI) in order to further understand ketamine's pharmacodynamic actions. METHOD: Responses to 25 mg kg-1S(+) isomer, R(-) isomer and racemic ketamine in independent groups of Sprague-Dawley rats were investigated using a prepulse inhibition paradigm, locomotor observations, MRI and 2-deoxyglucose techniques. RESULTS: Racemic ketamine and the S(+) isomer were both capable of disrupting sensorimotor gating as measured using prepulse inhibition and produced a longer period of hyperlocomotion comparative to the R(-) isomer. In contrast, large alterations in the BOLD MR signal were observed with R(-) isomer, whereas S(+) isomer and racemate precipitated more localized BOLD signal changes predominantly in cortical, hippocampal and hindbrain regions. Glucose utilization rates in conscious animals are in agreement with previously published data and verify the BOLD responses in the racemic group. However, no significant changes in glucose utilization were observed in the anesthetized cohort. CONCLUSIONS: Ketamine and its isomers have stereospecific effects on sensorimotor gating and locomotion that correlate with the enantiomer's affinity for the NMDA receptor. It would appear that anesthesia, as required for preclinical MRI procedures, may interact with and potentially attenuate the drug's response. Although analysis of the main effect of isomers in comparison to each other or the racemate offers an alternative analysis method that should be less susceptible to anesthetic interactions, only the R(-) isomer comparative to the racemate offers significant differences of interest.

Anesthetics, Dissociative↗

PubMed2004

Mapping transplanted stem cell migration after a stroke: a serial, in vivo magnetic resonance imaging study.

Preferential migration of stem cells toward the site of a lesion is a highly desirable property of stem cells that allows flexibility in the site of graft implantation in the damaged brain. In rats with unilateral stroke damage, neural stem cells transplanted into the contralateral hemisphere migrate across to the lesioned hemisphere and populate the area around the ischaemic infarct. To date, the migration of neural stem cells in the damaged brain has been mainly inferred from snapshot histological images. In this study, we demonstrate that by pre-labelling neural stem cells with the bimodal contrast agent Gadolinium-RhodamIne Dextran [GRID, detectable by both magnetic resonance imaging (MRI) and fluorescent microscopy], the transhemispheric migration of transplanted neural stem cells contralateral to a stroke lesion can be followed in vivo by serial MRI and corroborated by subsequent histological analyses. Our results indicate that neural stem cells migrated from the injection tract mainly along the corpus callosum within 7 days of transplantation and extensively re-populated the peri-lesion area by 14 days following implantation. In contrast, neural stem cells transplanted into sham controls did not show any substantial migration outside of the injection tract, suggesting that the transcallosal migration observed in the stroke-lesioned animals is due to neural stem cells being attracted by the lesion site. In vivo tracking of the migration of neural stem cells responding to damage will greatly enhance our understanding of optimal transplantation strategies as well as how neural stem cells promote functional and anatomical recovery in neurological disorders.

Animals↗

PubMed2002

Simultaneous PET and NMR.

There is currently great interest in combining data from different imaging modalities, either by image registration methods that are performed after the data has been acquired or using new devices that can acquire data from two modalities simultaneously, or near simultaneously. In this paper a small prototype NMR-compatible PET scanner capable of acquiring PET images simultaneously with either NMR images or NMR spectra is described. In an associated paper [1], Pamela Garlick describes some investigations of cardiac metabolism that have been made using this system. One of the main challenges in constructing an NMR-compatible PET scanner is that photomultiplier tubes, which are an essential element of nearly all current PET systems, will not function in a high magnetic field. In collaboration with Simon Cherry and the Crump Institute of Biomedical Imaging at UCLA Medical School, a small (5.4 cm diameter) NMR-compatible PET scanner that will operate within the bore of an NMR magnet has been developed. Long optical fibres are used to transport light from the scintillation crystals that form the detector head to photomultiplier tubes situated in a low magnetic field region several metres from the magnet. This system has been used to perform simultaneous PET and NMR spectroscopy measurements with a 9.4T spectroscopy system, and has also been used to obtain simultaneous PET and MR images in several MRI scanners including a 4.7T small bore animal imaging system. Current efforts in the development of this technology are directed at experimental studies on small animals, both because this is less demanding technically and because it is in this area that applications are likely to appear first. However, there is no reason in principle why human PET-MR would not be feasible. Below, work with the prototype system and the next stage in its development are described, and some of the future possibilities and challenges are discussed.

Animals↗

PubMed2002

Tracking transplanted stem cell migration using bifunctional, contrast agent-enhanced, magnetic resonance imaging.

The ability to track stem cell transplants in the brain by in vivo neuroimaging will undoubtedly aid our understanding of how these cells mediate functional recovery after neural transplantation. One major challenge for the development and refinement of stem cell transplantation is to map the spatial distribution and rate of migration in situ. Here we report a method for tracking transplanted stem cells in the ischemia-damaged rat hippocampus by magnetic resonance imaging (MRI). Before transplantation, stem cells were labeled in vitro either with a novel bifunctional contrast agent, gadolinium rhodamine dextran (GRID), identifiable by both MRI and fluorescence microscopy, or with PKH26, visible exclusively under fluorescence microscopy. At different time points following engraftment, the brains were evaluated by both histology and ex vivo MR imaging. Transplanted stem cells were identified by MRI only if prelabeled with GRID, whereas fluorescence microscopy detected transplanted cells using either label. The distribution of GRID-labeled stem cells identified by MRI corresponded to those detected using fluorescence microscopy. These results demonstrate that GRID-enhanced MRI can reliably identify transplanted stem cells and their migration in the brain.

Animals↗