We describe a computationally efficient and robust, fully-automatic method for large-scale electron microscopy image registration. The proposed method is able to construct large image mosaics from thousands of smaller, overlapping tiles with unknown or uncertain positions, and to align sections from a serial section capture into a common coordinate system. The method also accounts for nonlinear deformations both in constructing sections and in aligning sections to each other. The underlying algorithms are based on the Fourier shift property which allows for a computationally efficient and robust method. We demonstrate results on two electron microscopy datasets. We also quantify the accuracy of the algorithm through a simulated image capture experiment. The publicly available software tools include the algorithms and a Graphical User Interface for easy access to the algorithms.
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