# Wavefront Shaping and Its Application to Enhance Photoacoustic Imaging
## 3 Photoacoustically-Guided Wavefront Shaping (PAWS)
Therefore, optimization based on such a nonlinear feedback signal strongly  
Figure 2: Left: experimental schematic of the first photoacoustically guided optical focusing system. DM, deformable mirror; UT, ultrasound transducer. Right: optical spot behind the scattering layer (**a**) before and (**b**) after being guided to the ultrasonic focal spot (marked by the arrows) via wavefront shaping; (**c**) a photo of graphite particle (marked by wide arrow) after being shifted to 10 \(\upmu\)m from the optical beam; and (**d**) the refocused optical beam centered at the graphite particle after wavefront shaping. The narrow arrows mark the locations of the center of ultrasonic focus. The diameter of the ultrasound focus is 90 \(\upmu\)m (Figure from ref. [25]). favors energy focusing towards fewer and fewer--eventually a single--optical speckle grain rather than distribution relatively evenly over all speckle grains within the ultrasonic focus. Experimentally, as shown in Figure 3b, regular single-pulse PA signals were first used as the feedback to increase the optical fluence within the ultrasonic focal region, increasing the optical fluence from the initial 0.1 to 6 mJ/cm\({}^{2}\). After that, two optical pulses separated by 40 us (well within the thermal confinement time of 189 us under the experimental conditions) were fired every 20 ms. The difference between the two PA signals (\(\Delta\)PA) was used as the feedback for optimization. Eventually, after iterative optimization a single-speckle grain optical focus, dimensioned at 5-7 um, was formed around the center of the ultrasonic focal region (Figure 3d), which is about 10 times smaller than the size of the ultrasonic focus. In comparison, before wavefront optimization, or when a random phase pattern was displayed on the SLM, a random speckle pattern was seen, with many speckle grains (~169 through computation) within the ultrasonic focus (Figure 3c). Moreover, the peak optical fluence  
Figure 3: (**a**) Schematic of the two-stage PAWS experimental set-up. \(\lambda/2\): half-wave plate; PBS: polarizing beam splitter; SLM: LCoS-type spatial light modulator; PAWS, photoacoustically-guided wavefront shaping. (**b**) a representative demonstration for optimization procedure with two stages: linear PAWS focuses light into the acoustic resolution (within the acoustic focal region denoted by blue dashed line); nonlinear PAWS focuses light down to optical resolution (observed as a single-speckle grain); (**c**) the observation upon speckle pattern behind the diffuser without phase modulation (a randomized phase pattern uploaded on the SLM); and (**d**) the optical focus down to optical resolution observed behind the diffuser with phase modulation by nonlinear PAWS (Figure from [48]). improvement ratio from both the linear and nonlinear optimization stages was 60 \(\times\) 100 = 6000 times, and the peak fluence reached \(\sim\)600 mJ/cm\({}^{2}\) at the end, which is a really exciting achievement. Such an intensive and tightly focused optical focus within scattering media may benefit many biomedical applications that desire high resolution at depths. For example, a 6000-times improvement in the SNR would make an imaging system much more sensitive and potentially able to image much deeper. Or, if you are doing laser surgery, you could damage targeted tissue much more efficiently, even in deep regions. Surely, this could potentially enable super-resolution photoacoustic imaging in deep tissue. It needs to be pointed out that the PAWS implementations discussed above all rely on iterative optimization of the feedback signal. In addition to that, there is another version of PAWS to reach the optimum wavefront compensation, i.e., through measuring the optical transmission matrix (TM) of the complex medium. The TM implementation of wavefront shaping was first introduced by [PERSON] et al. [PERSON] et al. (2016), where a CCD camera was used to measure the speckle patterns behind a scattering sample as the output matrix corresponding to specific input modes (SLM modes) (Figure 4).