Computational Methods for the Analysis of Cerebral Vasculature

Interpreting the genome, with the goal of identifying the roles and functions of all the individual genes and regulatory elements that encode the construction and development of the human body, is a major challenge in science that has the potential to completely reshape our understanding of both health and disease. Experimental mice are playing a central role in the international effort to identify the functions of genes whereby the physical embodiment, in this case a mouse, that corresponds to a particular genetic sequence is created under well-controlled laboratory conditions. Thousands of strains of mice have been created where the genetic code is minutely varied so as to identify the changes in the mouse that associate with these individual codes. A particularly powerful way to assess the resulting changes in the mouse is based on three-dimensional images.

In this project, we propose to develop technology based on 3D imaging to detect subtle changes in the organization of the fine blood vessel network that permeates the brain. Recent advances in microscopic imaging technology mean that the whole network of blood vessels for a given mouse's brain can be captured in a single very-large 3D image. The organization of this complex vessel network is thought to play a critical role in how the brain functions. A challenge for identifying organizational changes in these networks is that some amount of natural variation is observed, even when the genes are kept the same. The major effort of the present proposal is therefore to develop computer methods that can systematically analyze the 3D images of the brains of different groups of mice so as to isolate those organizational changes that are associated genetic changes. These tools will provide a completely new way to pries apart the construction plan for the cerebral blood circulation.

Research is funded by the Natural Sciences and Engineering Research Council of Canada