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.

Figure 1. Principles

a, Illustration of dual-pulse excitation producing a nonlinear photoacoustic signal based on the Grueneisen relaxation effect. Two laser pulses with equal energy E are incident on an optical absorber. The first pulse causes a lingering change in the Grueneisen parameter (ΔΓ) due to an increase in temperature. Within the thermal confinement time, ΔΓ causes the amplitude from the second PA signal (V₂) to be stronger than that from the first (V₁). The difference ΔV is nonlinear—proportional to the square of the laser pulse energy (or fluence). b, Illustration of nonlinear photoacoustically guided wavefront shaping (PAWS) principle. When the same optical energy is concentrated to fewer speckle grains within an acoustic focus, the linear PA amplitude does not increase significantly, but the nonlinear PA amplitude approximately increases inversely proportionally with the number of bright speckle grains. The blue dashed circles represent the ultrasonic focal region.

Figure 2. Experimental setup and dual-stage optimization

a, Schematic of the photoacoustically guided wavefront shaping (PAWS) experimental setup. PBS, polarized beam splitter; SLM, spatial light modulator; λ/2, half-wave plate. b, Illustration of the two-stage optimization procedure (see Supplementary Movies 1 and 2 for more information). Stage 1, linear PAWS focuses light into the acoustic focal region. Stage 2, nonlinear PAWS focuses light onto a single-speckle grain. The blue dashed circles represent the acoustic focal region. A typical intensity distribution (green solid line) is shown above the speckle illustrations. The blue dashed envelopes represent the acoustic sensitivity.

Figure 3. Experimental results of Stage 1—using linear PA signal as feedback for wavefront shaping (linear PAWS)

a, PA signals before (blue dashed curve) and after (red solid curve) the linear PAWS (Stage 1) optimization. Note that all PA signals in this study were compensated for laser energy fluctuations, and normalized to the initial PA peak-to-peak amplitude shown here. b, Linear improvement factor (defined as the ratio of the PA amplitudes to the initial PA amplitude) versus iteration index. Linear PA amplitude improved ~60 times in Stage 1, indicating a peak enhancement factor of ~60 for optical fluence within the acoustic focus.

Figure 4. Experimental results of Stage 2—using nonlinear PA signal as feedback for wavefront shaping (nonlinear PAWS)

a, The initial PA signal pair (blue dashed curve for the first, and red solid curve for the second) from the paired laser pulses. The difference between the two PA signal amplitudes ΔV was used as feedback in nonlinear PAWS. b, The final PA signal pair (blue dashed curve for the first, and red solid curve for the second) after Stage 2 optimization. The inset shows the final optimized phase pattern displayed on the SLM. c, Nonlinear improvement factor versus iteration index. The normalized laser energy R = E/E_max is also shown, where E was the incident laser energy, and E_max the initial laser energy used before adjustment. The compensated nonlinear PA amplitudes are given by ΔV/R², and the nonlinear improvement factor is therefore given by $\frac{\mathrm{\Delta }V/R^2}{\mathrm{\Delta }{V}_{\mathit{\text{initial}}}}$, where ΔV_initial denotes the initial ΔV.

Figure 5. Visualization of single speckle grain focusing using nonlinear PAWS

a, Speckle pattern observed behind the diffuser when a randomized phase pattern was displayed on the SLM. b, Optical focus down to a single speckle grain observed behind the diffuser when the optimized phase pattern from Stage 2 (the inset of Figure 4b) was displayed on the SLM. The 1D profiles across the focus (green solid curves) measure 5.1 and 7.1 µm along x and y, respectively. The blue dashed circles show the measured acoustic focal region (50 MHz, −6 dB). Its lateral profiles (blue dashed curves) measure a FWHM of 65 µm. The intensity values in a and b are normalized to the peak value in a, after correction for the different camera settings for the two images.