Whole-brain fluorescence and brightfield imaging at single-cell level

DESCRIPTION (provided by applicant): The goal of this project is to develop an open and flexible imaging platform capable of rapid, 0.5- 5 m pixel resolution image capture of large-area histology sections (up to 125 mm by 175 mm), in brightfield and by epi-fluorescence optical sectioning. The project involves state-of-the- art instrumentation development coupled with application programming interfaces (APIs) to provide users with a reliable, multi-purpose research instrument. The development of a high speed large format imaging system will dramatically accelerate investigations such as amyloid protein studies for Alzheimer's disease or the expression of immediate-early genes (IEG) in understanding of the cellular basis of cognition. The number of digital-imaging system options decreases dramatically as the size of histology sections outgrows 1 W 3 glass slides. Further, because the current vendors are concentrating on digitizing anatomic pathology, their systems tend to be closed and inflexible to accommodate the regulatory constraints on medical devices. The market opportunity that DMetrix has identified is a robust and reliable commercial imaging platform with the flexibility and customization options valued by research groups. The project is divided into two Phases, punctuated by a demonstration of quantitative criteria, related to instrument and software performance. The primary goal of Phase I is the demonstration of feasibility of the large-area, rapid imaging instrument for brightfield and epi-fluorescence. A second goal is an image-viewer application that allows practical interaction with terabyte image data sets as will be generated by the instrument. The Specific Aims of Phase II are selected to lead to a product launch at the conclusion of the project. The Phase II Aims include the development of a V6, six-imaging-module slide scanner, image- management software, and an advanced image-viewer application. Further, the work in Phase II leverages the core expertise of DMetrix, namely the development of fast, parallel image-capture instruments. A significant part of the Phase II effort will be directed at making the proposed instrument manufacturable at a minimum cost of goods sold (COGS) and optimized for serviceability. DMetrix has teamed on thisproject with an interdisciplinary group of academic experts from the University of Arizona. The University team includes Dr. Carol Barnes from the McKnight Brain Institute, Dr. Ted Trouard, Department of Radiology and Biomedical Engineering, and Dr. GeneAlexander, Director of the Brain Imaging, Behavior and Aging Lab in the Department of Psychology. These University of Arizona scientists represent a diverse sampling of the broad impact of the proposed imaging platform on neuroscience research. PUBLICHEALTH RELEVANCE: Understanding the circuits in the brain responsible for cognition, emotion and action is a critical first step to developing treatments for important neurological disorders, such as Alzheimer's disease, Parkinson's disease, temporal lobeepilepsy, depression, and schizophrenia. Collectively, these disorders affect over 20 million Americans. Our long-range goal is to develop a system that has wide application across the field of neuroscience that will enable experiments impeded in the pastby technological limitations, to span mouse models of disease to rat and nonhuman primate models of normal aging. This knowledge may bring us closer to optimizing neural function in health, and developing new therapies for patients disabled by neurological disease.