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 signals based on the Grueneisen relaxation effect. These nonlinear photoacoustic 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 require a highly confined strong optical focus in tissue.

Focusing light deep inside living tissue has not been achieved despite its promise to play a central role in biomedical imaging, optical manipulation and therapy. To address this challenge, internal-guide-star-based wavefront engineering techniques—for example, time-reversed ultrasonically encoded (TRUE) optical focusing—were developed. The speeds of these techniques, however, were limited to no greater than 1 Hz, preventing them from in vivo applications. Here we improve the speed of optical focusing deep inside scattering media by two orders of magnitude, and focus diffuse light inside a dynamic scattering medium having a speckle correlation time as short as 5.6 ms, typical of living tissue. By imaging a target, we demonstrate the first focusing of diffuse light inside a dynamic scattering medium containing living tissue. Since the achieved focusing speed approaches the tissue decorrelation rate, this work is an important step towards in vivo deep tissue noninvasive optical imaging, optogenetics and photodynamic therapy.

Optical techniques offer a wide variety of applications as light-matter interactions provide extremely sensitive mechanisms to probe or treat target media. Most of these implementations rely on the usage of ballistic or quasi-ballistic photons to achieve high spatial resolution. However, the inherent scattering nature of light in biological tissues or tissue-like scattering media constitutes a critical obstacle that has restricted the penetration depth of non-scattered photons and hence limited the implementation of most optical techniques for wider applications. In addition, the components of an optical system are usually designed and manufactured for a fixed function or performance. Recent advances in wavefront shaping have demonstrated that scattering- or component-induced phase distortions can be compensated by optimizing the wavefront of the input light pattern through iteration or by conjugating the transmission matrix of the scattering medium. This offers unprecedented opportunities in many applications to achieve controllable optical delivery or detection at depths or dynamically configurable functionalities by using scattering media to substitute conventional optical components. In this article, the recent progress of wavefront shaping in multidisciplinary fields is reviewed, from optical focusing and imaging with scattering media, functionalized devices, modulation of mode coupling, and nonlinearity in multimode fiber to multimode fiber-based applications. Apart from insights into the underlying principles and recent advances in wavefront shaping implementations, practical limitations and roadmap for future development are discussed in depth. Looking back and looking forward, it is believed that wavefront shaping holds a bright future that will open new avenues for noninvasive or minimally invasive optical interactions and arbitrary control inside deep tissues. The high degree of freedom with multiple scattering will also provide unprecedented opportunities to develop novel optical devices based on a single scattering medium (generic or customized) that can outperform traditional optical components.

Artificial intelligence has gained significant attention for exploiting optical scattering for optical encryption. Conventional scattering media are inevitably influenced by instability or perturbations, and hence unsuitable for long-term scenarios. Additionally, the plaintext can be easily compromised due to the single channel within the medium and one-to-one mapping between input and output. To mitigate these issues, a stable spin-multiplexing disordered metasurface (DM) with numerous polarized transmission channels serves as the scattering medium, and a double-secure procedure with superposition of plaintext and security key achieves two-to-one mapping between input and output. In attack analysis, when the ciphertext, security key, and incident polarization are all correct, the plaintext can be decrypted. This system demonstrates excellent decryption efficiency over extended periods in noisy environments. The DM, functioning as an ultra-stable and active speckle generator, coupled with the double-secure approach, creates a highly secure speckle-based cryptosystem with immense potentials for practical applications.

The delineation of brain gliomas margins still poses challenges to precise imaging and targeted therapy, mainly due to strong light attenuation of the skull and high background interference. With deep penetration and high sensitivity, photoacoustic (PA) imaging (PAI) in the second near‐infrared (NIR II) window holds great potential for brain gliomas imaging. Herein, mesoionic dye A1094 encapsulated in Arg‐Gly‐Asp‐modified hepatitis B virus core protein (RGD‐HBc) is designed and synthesized for effective NIR II PAI of brain gliomas. An aggregation‐induced absorption enhancement mechanism is discovered in vitro and in vivo. It is also demonstrated that A1094@RGD‐HBc, with an enhanced absorption in the NIR II window, displays ninefold PA signal amplification in vivo, allowing for precise PAI of the brain gliomas at a depth up to 5.9 mm. In addition, with the application of abovementioned agent, high‐resolution PAI and ultrasensitive single photon emission computed tomography images of brain gliomas are acquired with accurate co‐localization. Collectively, the results suggest great promise of A1094@RGD‐HBc for diagnostic imaging and precise delineation of brain gliomas in clinical applications.

Intralipid is widely used as an optical scattering agent in tissue-mimicking phantoms. Accurate control when using Intralipid is critical to match the optical diffusivity of phantoms to the prescribed value. Currently, most protocols of Intralipid-based hydrogel phantom fabrication focus on factors such as Intralipid brand and concentration. In this note, for the first time to our knowledge, we explore the dependence of the optical reduced scattering coefficient (at 532 nm optical wavelength) on the temperature and the time of mixing Intralipid with gelatin-water solution. The studied samples contained 1% Intralipid and were measured with oblique-incidence reflectometry. It was found that the reduced scattering coefficient increased when the Intralipid-gelatin-water mixture began to solidify at room temperature. For phantoms that had already solidified completely, the diffusivity was shown to be significantly influenced by the temperature and the duration of the mixing course. The dependence of the measured diffusivity on the mixing conditions was confirmed by experimental observations. Moreover, the mechanism behind the dependence behavior is discussed.