# Wavefront Shaping and Its Application to Enhance Photoacoustic Imaging
## 1 Introduction
While promising, it must be noted that in PA imaging, only the detection of generated ultrasonic signals is \"transparent\" to tissue; the exciting photons experience the same strong scattering as in other optical microscopic techniques, and the optical fluence decays rapidly with tissue depth. This leads to limited practical depths of PA imaging: for optical resolution schemes, it is curbed to one transport mean free path (\(\sim\)1 mm) [36], beyond which diffusive light dominates and the imaging resolution is no longer determined by the light spot, but the ultrasonic focus; for acoustic resolution schemes, it is curbed to where the in situ optical fluence within the ultrasonic focus is too weak to generate reliable PA signals, usually being a couple of centimeters [13]. Therefore, it would be ideal if the diffusive light can be noninvasively refocused inside or behind thick scattering media. This actually has long been one of the holy grails in the community of biomedical optics. Traditional wisdom has treated multiple scattering of light a nuisance to be bypassed or eliminated. However, recently, researchers began to notice that the seemingly random scattering events and the resultant speckles are actually deterministic within a certain temporal window [37; 38], and it is possible to reverse [39; 40; 41] or compensate for [42] the scattering-induced phase scrambling. To do so, researchers have developed several wavefront shaping (sometimes also referred to wavefront engineering) techniques, such as iterative wavefront optimization [23; 24; 25; 26; 28; 29; 30; 31; 32; 33; 34; 35; 36; 37; 38; 39; 40; 41; 42; 43; 44; 45; 46; 47; 48; 49; 50; 51], measuring the transmission matrix of the scattering medium [21; 22; 52; 53; 54; 55; 56], and optical time reversal via phase conjugation [39; 40; 57; 58; 59; 60; 61; 62; 63; 64; 65]. Nevertheless, the goals of these implementations are identical, i.e., to make light wavelets traveling along different optical paths interfere coherently at a region of interest (ROI) and form a bright optical spot (focus) out of the much darker background. To create such an optical focus within or inside scattering media, which is more of biomedical interest, an internal guide star is needed to guide or provide a feedback for the wavefront shaping operations. For that purpose, researchers have proposed injected or embedded probes, such as small optical sensors [66; 67], fluorescence particles [68; 69], and nonlinear beads [57], ultrasound mediation [40; 58; 61; 70; 71], as well as absorption perturbation [22; 25; 46; 48; 72; 73; 74; 75; 76]. Among them, PA signal has been proved very attractive [22; 25; 28; 47; 48; 53; 57; 73; 74; 76], as it is noninvasive, relatively deeply-penetrating, and it can pinpoint the focal spot accurately (the acoustic and optical foci overlap). Furthermore, with linear [22; 25; 28; 53; 73; 74] or nonlinear [48] PA signals as the guide star, acoustic- and optical-diffraction limited optical focal spot can be achieved, respectively, benefiting from the nature of PA signal generation. In turn, during the process of such PA-guided wavefront optimization,the in situ optical fluence is gradually increased, and so is the strength of PA signals. Therefore, the signal-to-noise ratio (SNR) and the sensitivity of PA imaging can be greatly enhanced. Moreover, the formation of PA-guided optical focusing at depths in tissue paves the way to break the penetration depth limitation of current acoustic-resolution and optical-resolution PA imaging implementations. This technique, therefore, has the potential to impact the field. In this paper, we first briefly describe the propagation of light in tissue-like scattering media and the concept of wavefront shaping techniques. Then we discuss, in detail, how PA signals can be used as the guide star for wavefront shaping and how using wavefront shaping can enhance PA imaging in terms of sensitivity and resolution.