Funds are requested to purchase the Aperio VERSA 200 automated slide scanner, to introduce three new imaging modalities currently lacking from any of the service cores at Gladstone or either of the UCSF campuses: i) Design-based stereology (to ensure rigorous experimental design in analysis of three-dimensional morphologies) ii) Quantitative tissue FISH by whole slide imaging (WSI) and iii) Brain Connectivity Mapping (to trace inputs to specific circuits in whole brains). The slide scanner would be housed at the Gladstone Institutes Histology and Light Microscopy Core at UCSF, the principal histological service provider for Gladstone and UCSF. The instrument will be predominantly used by 8 investigators, 5 of whom are within Gladstone and 3 from other departments at UCSF. The Major Users identified in this request include NIH -funded researchers whose projects are focused on areas affecting human health including heart disease, Alzheimer?s disease, learning and memory, regenerative medicine, Parkinson?s disease, and obesity. In addition to the new experimental capabilities, the system will increase turn-around-time for WSI by at least 7- fold, as compared to the currently available acquisition methods. The Aperio VERSA 200 provides fully automated scanning of up to 200 1? x 3? slides at up to 63x magnification. The system includes brightfield and fluorescence cameras, 1.25x, 5x / 0.15, 10x / 0.32, 20x / 0.7, 40x / 0.85 (with correction collar), and 63x / 1.25 oil objectives, filter cubes for DAPI, GFP/FITC, Cy3, Cy5, and mCherry, a 12V 100W metal halide fluorescence illuminator and an automated oiling system for high resolution imaging. These combined features make it suitable for a wide range of experiments. To provide the specific experimental capabilities required, funds are requested for software modules enabling advanced stereological analysis, multi-channel segmentation and quantitation (IHC or IFA), and tissue FISH analysis modules. Together, this equipment will greatly expand the core capabilities and allow rapid, reproducible, and deep-reaching probing of the data on a large number of quantitative features. It is predicted that the Major Users identified in this request will account for approximately 80 % of the usage time; during the remaining Accessible User Time the slide scanner will be available for other area researchers. The slide scanner will be operated by the staff of the Histology and Light Microscopy Core at the Gladstone Institute and by trained users. This instrument will allow the core to offer versatile image acquisition and analysis modalities from slide-based samples to researchers at Gladstone and UCSF, thus significantly expanding this core?s utility for the local research community.

Public Health Relevance

This proposal requests funds to purchase an automated slide scanner capable of high resolution brightfield and fluorescence imaging, with additional modules for advanced stereological analysis , quantative analysis of cellular features, and tissue-based FISH. Introducing these transformative methodologies to the Gladstone Histology and Light Microscopy Core will benefit a broad range of biomedical research at Gladstone and UCSF, including Alzheimer's disease, end-stage heart failure, learning and memory, obesity, wound healing, Parkinson?s disease, and regenerative medicine. This proposal is highly relevant to the NIH?s mission to improve rigor and reproducibility in biomedical research, a responsibility shared by core research facilities.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
Biomedical Research Support Shared Instrumentation Grants (S10)
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Special Emphasis Panel (ZRG1-CB-T (30)I)
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Horska, Alena
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J. David Gladstone Institutes
Research Institutes
San Francisco
United States
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