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The goal of the FARSIGHT project is to develop and disseminate a next-generation toolkit to enable quantitative studies of complex & dynamic tissue microenvironments imaged by modern optical microscopes. Examples of such microenvironments of include brain tissue, stem cell niches, developing embryonic tissue, immune system components, and tumors. A better understanding of these living systems is critical for advancing human health. Our knowledge of these systems has been painstakingly “pieced together” from large numbers of fixed, 2-D images of specimens. The goal of this project is to help accelerate progress by harnessing the power of modern microscopy and computational image analysis and informatics tools.
The power of modern optical microscopy:We are experiencing the dawn of a new Golden Age of optical microscopy. It is now possible for modern microscopes to capture multi-dimensional images of these microenvironments. First of all, these microscopes can record three-dimensional (x,y,z) images of thick, intact slices that are more realistic compared to thin slices. Next, they can record multiple structures simultaneously in a manner that preserves their spatial inter-relationships. This allows us to make associative measurements in addition to traditional morphological measurements (we call them intrinsic measurements). Such four-dimensional imaging $(x, y, z, \lambda) $ usually accomplished using multiple fluorescent labels that tag the structures of interest with a high degree of molecular specificity. Finally, it is now possible to capture such 3-D multi-channel images of living systems in the form of a time-lapse movie (image sequence (x,y,z,t)) that reveals dynamic processes in the tissues. Using the all of the available imaging dimensions (x,y,z,λ,t), we can now observe living processes in their native tissue habitat. Ongoing progress in this field is producing microscopes that can resolve much finer structures, produce images much faster, and on a much larger scale.
But, can we make sense of these images? The images produced by modern microscopes are complex and voluminous. Increasingly, analyzing these images is beyond human ability. The FARSIGHT toolkit is developing automated computational tools that can extract meaningful measurements from the complex and voluminous data generated by modern optical microscopes. Automation is important, but not our sole motivating force. We are interested in advancing a systems oriented understanding of complex and dynamic tissue microenvironments. This calls for a particular emphasis on quantifying, representing, and analyzing associations among structural and functional tissue entities.
Supercomputing and Super Microscopy: Compared to the high-school microscopes that we all remember, it is fair to use the term super microscopy to describe modern microscopes. Analyzing their complex and voluminous data not only requires innovative algorithms, but also high-powered computers. the FARSIGHT toolkit will enable us to take advantage of multi-core, multi-processor, and cluster computers.