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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: (i) harnessing the power of modern microscopy to help see the microenvironments in a much more detailed, direct, and comprehensive manner; and (ii) computational tools to analyze the data produced by these microscopes.
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,λ) 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.
Toolkits vs. Software Packages: We draw a distinction between these two words. A software package is a self-contained and tightly integrated software system that provides a defined set of services. A toolkit, on the other hand, is a collection of software modules with a set of standardized interfaces. To solve a given image analysis task, you can choose the right set of modules, and stitch them together using a scripting language (Python in our case). Toolkits are easier to build and maintain (especially for academic laboratories like us), and more versatile since we cannot foresee all possible applications that FARSIGHT will encounter in the future.
Open Source Toolkit: When completed, FARSIGHT will be an open source toolkit. It draws upon major open source toolkits especially the [Insight Toolkit (ITK)], the [Visualization Toolkit (VTK)], [Open Microscopy Environment (OME]), and various others. We plan to foster a community composed of users in the life sciences and developers in the computational sciences (many colleagues seem at ease in both categories!). We hope that our developer colleagues will leverage FARSIGHT and contribute code. At the same time, we hope that our life sciences colleagues will open our eyes to new problems and grand opportunities. In the end, we want to foster a cross-disciplinary sharing of knowledge across the communities. We're all in this together.
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.
Making it Practical: The FARSIGHT Framework serves as a practical guide to users and developers alike. The toolkit can be used to implement the framework.
