Readout of fluorescence functional signals through highly scattering tissue

Fluorescence is a powerful means to probe information processing in the mammalian brain(1). However, neuronal tissues are highly heterogeneous and thus opaque to light. A wide set of non-invasive or invasive techniques for scattered light rejection, optical sectioning or localized excitation have been developed, but non-invasive optical recording of activity through a highly scattering layer beyond the ballistic regime is impossible as yet. Here, we show that functional signals from fluorescent time-varying sources located below a highly scattering bone tissue can be retrieved efficiently by exploiting matrix factorization algorithms to demix this information from temporal sequences of low-contrast fluorescence speckle patterns. By exploiting low-contrast fluctuating speckle patterns from extended fluorescence sources using an advanced signal-processing algorithm, functional signals through highly scattering tissues can be extracted.