Cyclic AMP (cAMP) is a continually produced nucleotide which is inactivated by hydrolysis to 5'AMP via phosphodiesterase 4 (PDE4) enzymes. Rolipram is a selective PDE4 inhibitor which exists in two enantiomeric forms, R(-) and S(+). Both of these enantiomers have previously been labelled with carbon-11 and used as positron emission tomography (PET) ligands for measuring PDE4 expression and function, and indirectly to explore the function of the cAMP second messenger, in vivo, using PET. The aim of these studies was to relate the in vitro affinities of the two rolipram enantiomers using standard pharmacological assays with the in vivo behaviour of the two enantiomers using PET. In vitro competition assays were performed using rat cortical membranes and [(3)H]R(-)- and [(3)H]S(+)-rolipram with increasing concentrations of either unlabelled R(-)- or S(+)-rolipram. In vivo, a series of PET studies were performed in the porcine brain using [(11)C]R(-)-rolipram with co-administration of increasing doses of either unlabelled R(-)- or S(+)-rolipram. Additional in vivo PET studies were performed using [(11)C]S(+)-rolipram with saturating doses of rolipram. In all studies, R(-)-rolipram exhibited a higher affinity for the PDE4 enzyme than S(+)-rolipram. The calculated affinity ratios were 7.97 from the in vitro studies; 12.5 from the in vivo studies using [(11)C]R(-)-rolipram; and 14.7 from the in vivo studies using [(11)C]S(+)-rolipram. To conclude, the in vitro affinities of R(-)- and S(+)-rolipram predict their apparent in vivo behaviour in the porcine brain, as measured by PET.
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SPONSOR/MONITOR'S ACRONYM(S)
HPW/RHCV
SPONSORING/MONITORING AGENCY REPORT NUMBER
AFRL-RH-WP-TR-2009-0015
DISTRIBUTION AVAILABILITY STATEMENTApproved for public release; distribution unlimited.
SUPPLEMENTARY NOTES88 ABW PA Cleared 02/17/09; 88ABW-09-0522.
ABSTRACTIt is believed that the fusion of multiple different images into a single image should be of great benefit to warfighters engaged in a search task. As such, more research has focused on the improvement of algorithms designed for image fusion. Many different fusion algorithms have already been developed; however, the majority of these algorithms have not been assessed in terms of their visual performance-enhancing effects using militarily relevant scenarios. The goal of this research is to apply a visual performance-based assessment methodology to assess four algorithms that are specifically designed for fusion of multispectral digital images. The image fusion algorithms used included a Principle Component Analysis based algorithm, a Shift-invariant Wavelet transform algorithm, a Contrast-based algorithm, and pixel averaging. The methodology used has been developed to acquire objective human visual performance data as a means of evaluating the image fusion algorithms. Standard objective performance metrics (response time and error rate), were used to compare the fused images vs. two baseline conditions comprising each individual image used in the fused test images. Observers searched images for a military target hidden among foliage and then indicated in which quadrant of the screen the target was located using a spatial-forced-choice paradigm. Response time and percent correct were measured for each observer.
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