Fluorescence tomography has become increasingly popular for detecting molecular targets for imaging gene expression and other cellular processes in vivo in small animal studies. In this imaging modality, multiple sets of data are acquired by illuminating the animal surface with different excitation patterns, each of which produces a distinct spatial pattern of fluorescence. This work addresses one of the most intriguing, yet unsolved, problems of fluorescence tomography, which is to determine how to optimally illuminate the animal surface so as to maximize the information content in the acquired data. The key idea of this work is to parameterize the illumination pattern and to maximize the information content in the data by improving the conditioning of the Fisher information matrix. We formulate our problem as a constrained optimization problem. We compare the performance of different geometric illumination schemes with those generated by this optimization approach using the Digimouse atlas.
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