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Caltech Optical Imaging Laboratory
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Time Reversal (TR)

Due to scattering, it is challenging to form an optical focus at depths much greater than ~1 mm in soft tissue (the optical diffusion limit). Time reversal aims to overcome the limits of optical diffusion by optimizing the optical wavefront to compensate for phase differences imparted as photons travel along differing optical paths in scattering media. By aligning the phase of the diffused light, a focus can be formed inside or beyond the scattering media through constructive interference. However, due to motion in biological tissue, such as blood flow, breathing, and Brownian motion, the optimal wavefront rapidly decorrelates as scatterers shift. Therefore, in order to utilize wavefront shaping in biomedical applications, it is vital for the optimal wavefront to be obtained and applied as quickly as possible.

To this end, our lab has explored numerous novel high-speed wavefront shaping techniques. Methods such as time-reversed ultrasonically encoded (TRUE) and time-reversed adapted-perturbation (TRAP) optical focusing use optical phase conjugation to "reverse" time and send light back along the optical paths that lead to the desired focus. This focus is generated by ultrasonic modulation of light as in TRUE or by natural or exogenous perturbations such as in TRAP and the corresponding optical wavefront is quickly captured using either a CMOS camera or photorefractive crystal. Using these methods, a focus can be formed in milliseconds.

In addition to speed, efficiency of focusing is important to ensure sufficient resolution and signal-to-noise ratio. In this area, we have pioneered non-linear photoacoustic wavefront shaping (PAWS), a technique in which iterative optimization is detected by non-linear photoacoustics (PA). While slower than direct measurement, iterative measurements permit PA to provide a guide star. In turn, PA enjoys a much greater penetration depth than other optical detection methods, while non-linear PA drastically improves focusing efficiency.

Wavefront shaping has the potential to focus at depths of tens of cm in soft tissue. By over coming the limits of optical diffusion, wavefront shaping therefore holds promise in non-invasive whole body optical imaging, optogenetics, optical tweezers, and phototherapy.

Selected Publications

  1. Cheng, Z.; Li, C.; Khadria, A.; Zhang, Y.; Wang, L. V.; "High-gain and high-speed wavefront shaping through scattering media," Nature Photonics 17 299-305 (2023) [PDF]
  2. [Wei, X.; Shen, Y.; Jing, J. C.]; Hemphill, A. S.; Yang, C.; Xu, S.; Yang, Z.; Wang, L. V.; "Real-time frequency-encoded spatiotemporal focusing through scattering media using a programmable 2D ultrafine optical frequency comb," Science Advances 6(8) EAAY1192 (2020) [PDF]
  3. [Yang, J. M.; Li, L.]; Shemetov, A. A.; Lee, S.; Zhao, Y.; Liu, Y.; Shen, Y. C.; Li, J. W.; Oka, Y.; Verkhusha, V. V.; Wang, L. V.; "Focusing light inside live tissue using reversibly switchable bacterial phytochrome as a genetically encoded photochromic guide star," Science Advances 5(12) (2019) [PDF]
  4. Yang, J.; Gong, L.; Xu, X.; Hai, P.; Shen, Y.; Suzuki, Y.; Wang, L. V.; "Motionless volumetric photoacoustic microscopy with spatially invariant resolution," Nature Communications 8(1) 780 (2017) [PDF]
  5. Liu, Y.; Ma, C.; Shen, Y. C.; Shi, J. H.; Wang, L. V.; "Focusing light inside dynamic scattering media with millisecond digital optical phase conjugation," Optica 4(2) 280-288 (2017) [PDF]
  6. [Shen, Y.; Liu, Y.]; Ma, C.; Wang, L. V.; "Sub-Nyquist sampling boosts targeted light transport through opaque scattering media," Optica 4(1) 97-102 (2017) [PDF]
  7. Hemphill, A. S.; Tay, J. W.; Wang, L. V.; "Hybridized wavefront shaping for high-speed, high-efficiency focusing through dynamic diffusive media," Journal of Biomedical Optics 21(12) 121502 (2016) [PDF]
  8. [Shen, Y.; Liu, Y.]; Ma, C.; Wang, L.V.; "Focusing light through biological tissue and tissue-mimicking phantoms up to 9.6 centimeters in thickness with digital optical phase conjugation," Journal of Biomedical Optics 21(8) 085001 (2016) [PDF]
  9. Lai, P.; Wang, L.; Tay, J. W.; Wang, L. V.; "Photoacoustically guided wavefront shaping for enhanced optical focusing in scattering media," Nature Photonics 9 126-132 (2015) [PDF]
  10. Liu, Y.; Lai, P.; Ma, C.; Xu, X.; Grabar, A. A.; Wang, L. V.; "Optical focusing deep inside dynamic scattering media with near-infrared time-reversed ultrasonically encoded (TRUE) light," Nature Communications 6 5409 (2015) [PDF]
  11. Ma, C.; Xu, X.; Liu, Y.; Wang, L. V.; "Time-reversed adapted-perturbation (TRAP) optical focusing onto dynamic objects inside scattering media," Nature Photonics 8(12) 931-936 (2014) [PDF]
  12. [Tay, J. W.; Lai, P.]; Suzuki, Y.; Wang, L. V.; "Ultrasonically encoded wavefront shaping for focusing into random media," Scientific Reports 4 3918 (2014) [PDF]
  13. [Xu, X.; Liu, H.]; Wang, L. V.; "Time-reversed ultrasonically encoded optical focusing into scattering media," Nature Photonics 5(3) 154-157 (2011) [PDF]