A divide and conquer strategy for the maximum likelihood localization of low intensity objects

In cell biology and other fields the automatic accurate localization of sub-resolution objects in images is an important tool. The signal is often corrupted by multiple forms of noise, including excess noise resulting from the amplification by an electron multiplying charge-coupled device (EMCCD). Here we present our novel Nested Maximum Likelihood Algorithm (NMLA), which solves the problem of localizing multiple overlapping emitters in a setting affected by excess noise, by repeatedly solving the task of independent localization for single emitters in an excess noise-free system. NMLA dramatically improves scalability and robustness, when compared to a general purpose optimization technique. Our method was successfully applied for in vivo localization of fluorescent proteins.