A unified framework for photoacoustic fluctuation imaging. Application to visibility enhancement with fluctuations induced by blood flow

Photoacoustic fluctuation imaging relies on exploiting some randomness in photoacoustic generation to provide fluctuation-based enhanced images, as compared to conventional photoacoustic images. While this approach has been successfully demonstrated experimentally for super-resolution imaging (induced either from multiple speckle illumination or from the flow of random distributions of absorbing particles) and for visibility enhancement (with multiple speckle illumination only), to date there is no comprehensive theoretical description of fluctuation photoacoustic imaging. In the first part of this work, we propose a unified theoretical framework relevant to both fluctuations induced by random illumination patterns and fluctuations induced by random distributions of absorbing particles. The theoretical predictions are then validated by Monte-Carlo finite-difference time-domain (FDTD) simulations of photoacoustic generation in a random medium. In particular, we explain why visibility artefacts are absent on 2nd-order fluctuation images. In the second part, we demonstrate experimentally that the flow of blood under physiological conditions can be exploited to produce photoacoustic fluctuation images free of the visibility artefacts of conventional photoacoustic imaging. Two-dimensional images of blood vessel phantoms flown with blood at physiological concentrations are obtained in vitro as a first proof-of-concept demonstration. Finally, the approach is applied in vivo to obtain 3D images of a chicken embryo.