High throughput object-based image analysis of β-amyloid plaques in human and transgenic mouse brain

• Published in: Journal of neuroscience methods Vol. 204; no. 1; pp. 179 - 188
• Main Authors: Samaroo, Harry D., Opsahl, Alan C., Schreiber, Jan, O’Neill, Sharon M., Marconi, Michael, Qian, Jessie, Carvajal-Gonzalez, Santos, Tate, Barbara, Milici, Anthony J., Bales, Kelly R., Stephenson, Diane T.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.02.2012
• Subjects: Aged; Aged, 80 and over; Algorithms; Alzheimer's disease; Animals; Brain - pathology; Female; High-throughput; Humans; Image Enhancement - methods; Image Interpretation, Computer-Assisted - methods; Imaging, Three-Dimensional - methods; Male; Mice; Mice, Transgenic; Microscopy, Confocal - methods; Object-based image analysis; Pattern Recognition, Automated - methods; Plaque, Amyloid - pathology; PS1APP; Reproducibility of Results; Sensitivity and Specificity; High-throughput; Alzheimer's disease; Object-based image analysis; PS1APP
• DOI: 10.1016/j.jneumeth.2011.10.003
• ISSN: 0165-0270; 1872-678X

► A high-throughput image analysis method was developed to measure amyloid plaques. ► Validation of method was achieved using both human AD and PS1APP brain tissues. ► Biochemical measures of brain Aβ levels confirmed with image analysis results. ► This method may improve consistency and reproducibility of amyloid quantification. Advances in imaging technology have enabled automated approaches for quantitative image analysis. In this study, a high content object based image analysis method was developed for quantification of β-amyloid (Aβ) plaques in postmortem brains of Alzheimer's disease (AD) subjects and in transgenic mice over overexpressing Aβ. Digital images acquired from immunohistochemically stained sections of the superior frontal gyrus were analyzed for Aβ plaque burden using a Definiens object-based segmentation approach. Blinded evaluation of Aβ stained sections from AD and aged matched human subjects accurately identified AD cases with one exception. Brains from transgenic mice overexpressing Aβ (PS1APP mice) were also evaluated by our Definiens object based image analysis approach. We observed an age-dependent increase in the amount of Aβ plaque load that we quantified in both the hippocampus and cortex. From the contralateral hemisphere, we measured the amount of Aβ in brain homogenates biochemically and observed a significant correlation between our biochemical measurements and those that we measured by our object based Definiens system in the hippocampus. Assessment of Aβ plaque load in PS1APP mice using a manual segmentation technique (Image-Pro Plus) confirmed the results of our object-based image analysis approach. Image acquisition and analysis of 32 stained human slides and 100 mouse slides were executed in 8h and 22h, respectively supporting the relatively high throughput features of the Definiens platform. The data show that digital imaging combined with object based image analysis is a reliable and efficient approach to quantifying Aβ plaques in human and mouse brain.