Photoacoustically guided wavefront shaping for enhanced optical focusing in scattering media

Abstract

Non-invasively focusing light into strongly scattering media, such as biological tissue, is highly desirable but challenging. Recently, ultrasonically guided wavefront shaping technologies have been developed to address this limitation. So far, the focusing resolution of most implementations has been limited by acoustic diffraction. Here, we introduce nonlinear photoacoustically guided wavefront shaping (PAWS), which achieves optical diffraction-limited focusing in scattering media. We develop an efficient dual-pulse excitation approach to generate strong nonlinear photoacoustic (PA) signals based on the Grueneisen relaxation effect. These nonlinear PA signals are used as feedback to guide iterative wavefront optimization. As a result, light is effectively focused to a single optical speckle grain on the scale of 5–7 µm, which is ~10 times smaller than the acoustic focus with an enhancement factor of ~6,000 in peak fluence. This technology has the potential to benefit many applications that desire highly confined strong optical focus in tissue.

Wavefront Shaping and Its Application to Enhance Photoacoustic Imaging

“…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]:…”

“…For example, it has been demonstrated that subacoustic diffraction-limited optical focusing is possible when the detected PA signals (which are broadband) are spectrally filtered and then used as the feedback [26,45]. From the perspective of generation nonlinearity, Lai et al developed a dual-pulse excitation approach (Figure 3a), firing two consecutive, yet identical, optical pulses to generate two individual PA signals-the difference between them create a nonlinear PA response that can be used as a nonlinear feedback [48]. The hypothesis was built upon a so-called Grueneisen effect [49].…”

“…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,[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.…”

“…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 [22,25,28,47,48,53,55,73,74,76], 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, acousticand optical-diffraction limited optical focal spot can be achieved, respectively, benefiting from the nature of PA signal generation.…”

“…Among them, PA signal has been proved very attractive [22,25,28,47,48,53,55,73,74,76], 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, acousticand 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.…”