# Wavefront Shaping and Its Application to Enhance Photoacoustic Imaging
## 5 Discussion and Conclusions  
It has been shown that that using photoacoustic signals as feedback for optical wavefront shaping techniques open up a new road to focus scattering light within or behind tissue samples or optically-scattering media, which can in turn be used to increase the sensitivity, the resolution and, potentially, the penetration depth of photoacoustic imaging. The dissipation limit of PAT is several cm. By converging diffused energy into region of interest in deep tissue, wavefront shaping is able to break this limit, and eventually made suitable for whole-body imaging. For optical-resolution PAM (OR-PAM), wavefront shaping may be more attractive in that the diffusion limit can be surpassed, and the penetration depth can be up to several millimeters. Such integration may result in the critical impact to the diagnosis and treatment of diseases that exhibit direct or indirect optical contrast. To make it more practical towards biomedical applications in vivo, however, several challenges must be tackled. The first one is the speed of optical focusing. For example, the above-discussed nonlinear PAWS implementation [48] took several hours to complete a phase compensation optimization and produce the shown intense single speckle-scale optical focus. This time-consuming drawback is mainly due to the inherent requirement of many signal measurements and phase pattern update. Using an LCoS-type SLM whose refresh rate is 60 Hz, each iteration takes about one second, as reported [42; 48], which is mainly throttled by the refresh rate of the SLM, the inability of the Windows(r) operation system for parallel signal processing, as well as the communication speed between the PC and the SLM. Therefore, a fast substitute is in demand for practical applications, especially with living biological tissue, whose decorrelation time is typically a few milliseconds, or even shorter [40]. One straight-forward solution is to use DMD (refresh rate can be up to 23 kHz) in place of the LCoS-type SLM, and a field programmable gate array (FPGA) in place of the PC processor to significantly shorten the time needed to update the phase patterns, as well as data communication and processing for each iteration. Promising improvement of the iterative optimization speed has been confirmed [24; 56]. It should be noted, however, that the modulation from DMD relies on the tilting of the micro-mirror arrays, and only binary (i.e., either ON or OFF) intensity modulation is supported. Thus, usually a sacrificed enhancement ratio can be delivered compared to when an LCoS-type SLM serves as the wavefront modulator. Nevertheless, there is no doubt that a higher optimization speed, such as accomplishing thousands of iterations within one second, is critical to allow for practical applications of interest. With the abovementioned methods, generating one single optical focus with increased optimization speed is feasible. Yet, in many applications, including photoacoustic microscopy, a series of optical focal points are needed and rapid raster scanning of optical foci is required. Can the  
Figure 8: (**a**) Experimental setup for PAWS (transmission matrix measurement approach); (**b**) reference photograph of the absorbing leaf skeleton embedded in a transparent agarose gel block; (**c**) a standard photoacoustic image obtained by averaging different speckle illuminations and its envelope (**d**); and (**e**) enhanced photoacoustic imaging with PAWS optimization. PAWS-generated focal spot be translated sufficiently fast? Note that tissue constituents and the corresponding optimized phase compensation vary spatially, and a new cycle of iterations may be needed from one position to another. Using the so-called memory effect (a speckle correlation phenomenon) [37; 38], it is possible to tilt the obtained phase pattern by a small angle, which can translate the focus across the focal plane and is, thus, useful in eliminating the need for a new full optimization process at each point.