# Wavefront Shaping and Its Application to Enhance Photoacoustic Imaging
## 3 Photoacoustically-Guided Wavefront Shaping (PAWS)  
In wavefront shaping, to focus light within a scattering medium, a guide star must be created to produce a feedback signal that is proportional to the in situ optical flux. This could be an actual detector or source, such as a photodiode [27], CCD camera pixel [42], emitting fluorescence molecules [68], or optical nonlinear beads [57]. For biomedical applications, however, using these probes is usually undesired as physical access to the targeted position is required and the embedding procedure of the probes is invasive. Moreover, optical focusing enabled by these physical probes is restricted to fixed positions and cannot be freely moved within tissue. To overcome these limitations, researchers have developed virtual guide stars so that diffused photons emerging or propagating through the ROI can be specifically tagged or preferentially detected. An example is focused ultrasound modulation based on the acousto-optic effect [40; 71], where the ultrasonically frequency-shifted photons are phase conjugated and make their way back to the ultrasonic focus--it is, thus, also the optical focus. Similar ultrasonically determined optical focusing can also be achieved if the ultrasonically frequency-shifted photons are extracted and its strength is used as the feedback signal for iterative optimization [27; 82; 83]. These have inspired the use of photoacoustic signals as the virtual guide star. As discussed earlier, in photoacoustic effect, transient photon energy--no matter it is ballistic or diffusive--is absorbed by tissue molecules and converted into much less scattering ultrasonic waves, which can be detected using a single or a series of transducers. The detected signal can be generally expressed by [48]:  
\[\mathrm{PA}=k\iint A(x,y)\Gamma(\mathrm{T})\mu_{a}F(x,y)dxdy \tag{3}\]  
where \(k\) is a constant, \(A(x,y)\) is the ultrasound detection sensitivity distribution normalized as \(\iint A(x,y)dxdy=1\), \(\Gamma\) is the Grueneisen parameter (usually temperature- and material-dependent), \(\mu_{a}\) is the optical absorption coefficient of the local medium, and \(F(x,y)\) is the optical energy density (or fluence) within the ultrasonic focus. As seen, when the temperature and the absorption of the ROI remain relatively unchanged, the PA signal amplitude is linearly proportional to the optical fluence \(F\). Therefore, if PA signals are used as the feedback for wavefront shaping, maximizing PA signals' amplitude will lead to maximized optical fluence within the ultrasonic focus and, accordingly, an optical focus inside a highly-scattering medium. The idea of photoacoustically-guided wavefront shaping (PAWS) was first proposed by [PERSON] et al. in 2011 [25]. As illustrated in Figure 2, they used a 140-pixel deformable mirror (DM) to control the phase of green 1-ns pulses, which were converged by a lens and incident onto a scattering layer. Behind that layer, there were some graphite particles that absorbed diffused pulsed optical energy and generated PA signals, which were detected by a 75 MHz focused ultrasound transducer, amplified, and used as the feedback for optimizing the phase patterns on the DM. Different sizes of graphite absorbers were used to test the capability of optical focusing behind the scattering layer. As a result, a 41 \(\upmu\)m-diameter focus was created at the target plane, with an enhancement ratio of 5-10 for the PA signals as well as the focal optical intensity before and after wavefront optimization.