Near-Infrared Fluorescent Digital Pathology for the Automation of Disease Diagnosis and Biomarker Assessment
MOLECULAR IMAGING
Authors: Gibbs, Summer L.; Genega, Elizabeth; Salemi, Jeffery; Kianzad, Vida; Goodwill, Haley L.; Xie, Yang; Oketokoun, Rafiou; Khurd, Parmeshwar; Kamen, Ali; Frangioni, John V.
Abstract
Hematoxylin-eosin (H&E) staining of tissue has been the mainstay of pathology for more than a century. However, the learning curve for H&E tissue interpretation is long, whereas intra-and interobserver variability remain high. Computer-assisted image analysis of H&E sections holds promise for increased throughput and decreased variability but has yet to demonstrate significant improvement in diagnostic accuracy. Addition of biomarkers to H&E staining can improve diagnostic accuracy; however, coregistration of immunohistochemical staining with H&E is problematic as immunostaining is completed on slides that are at best 4 mm apart. Simultaneous H&E and immunostaining would alleviate coregistration problems; however, current opaque pigments used for immunostaining obscure H&E. In this study, we demonstrate that diagnostic information provided by two or more independent wavelengths of near-infrared (NIR) fluorescence leave the H&E stain unchanged while enabling computer-assisted diagnosis and assessment of human disease. Using prostate cancer as a model system, we introduce NIR digital pathology and demonstrate its utility along the spectrum from prostate biopsy to whole mount analysis of H&E-stained tissue.
Mutual inversion of flurbiprofen enantiomers in various rat and mouse strains
CHIRALITY
Authors: de Bruin, Natasja; Ferreiros, Nerea; Schmidt, Mike; Hofmann, Martine; Angioni, Carlo; Geisslinger, Gerd; Parnham, Michael John
Abstract
Flurbiprofen (F) is a nonsteroidal anti-inflammatory drug (NSAID) used therapeutically as the racemate of (R)-enantiomer and (S)-enantiomer. The inversion of RF to SF and vice versa was investigated in C57Bl/6 and SJL mice and Dark Agouti and Lewis rats. The enzyme -methylacyl-CoA racemase (AMACR) is involved in the chiral inversion pathway that converts members of the 2-arylpropionic acid NSAIDs from the R-enantiomer to the S-enantiomer. We studied C57Bl/6 mice deficient in AMACR postulating that they should show reduced inversion of RF to SF. In line with the data of others in mice, (R)-inversion to (S)-inversion was relatively high in both the C57Bl/6 and SJL mice (fraction inverted, F-I=37.7% and 24.7%, respectively). In contrast, in AMACR deficient mice, there was no measurable peak for SF after administration of RF. The results in both rat strains (Dark Agouti and Lewis rats, F-I=1.4% and 4.1%, respectively) confirm the low chiral inversion of the enantiomers of flurbiprofen in the rat, as observed by other authors in the Sprague-Dawley strain (<5%). From the present results, we conclude that for the study of flurbiprofen enantiomers, the rat is more suitable than the mouse as a model for the human in which (R)-inversion to (S)-inversion is negligible.