Optical technologies have been increasingly utilized in biomedicine, including diagnosis, therapy, and surgery. In almost all of these applications, photons need to propagate some distance in tissue. Therefore, the capability of focusing or demodulating light information plays an essential role, largely determining the sensitivity and spatial resolution of these techniques. This has always been desired yet considered challenging within or through thick biological tissues due to the strong scattering of light. However, research has shown that the seemingly random scattering and the resultant speckle patterns are indeed deterministic within a certain temporal window.

Despite the unique advantages of optical microscopy for molecular specific high resolution imaging of living structure in both space and time, current applications are mostly limited to research settings. This is due to the aberrations and multiple scattering that is induced by the inhomogeneous refractive boundaries that are inherent to biological systems. However, recent developments in adaptive optics and wavefront shaping have shown that high resolution optical imaging is not fundamentally limited only to the observation of single cells, but can be signifi- cantly enhanced to realize deep tissue imaging. To provide insight into how these two closely related fields can expand the limits of bio imaging, we review the recent progresses in their performance and applicable range of studies as well as potential future research directions to push the limits of deep tissue imaging.

Visual perception of humans penetrating turbid medium is hampered by scattering. Various techniques have been prompted recently to recover optical imaging through turbid materials. Among them, speckle correlation based on deconvolution is one of the most attractive methods taking advantage of high imaging quality, robustness, ease-of-use, and ease-of-integration. By exploiting the point spread function (PSF) of the scattering system, large Field-of-View, extended Depth-of-Field, noninvasiveness and spectral resoluation are now available as successful solutions for high quality and multifunctional image reconstruction. In this paper, we review the progress of imaging through a scattering medium based on deconvolution method, including the principle, the breakthrough of the limitation of the optical memory effect, the improvement of the deconvolution algorithm and innovative applications.

Coherent optical control within or through scattering media via wavefront shaping has seen broad applications since its invention around 2007. Wavefront shaping is aimed at overcoming the strong scattering, featured by random interference, namely speckle patterns. This randomness occurs due to the refractive index inhomogeneity in complex media like biological tissue or the modal dispersion in multimode fiber, yet this randomness is actually deterministic and potentially can be time reversal or precompensated. Various wavefront shaping approaches, such as optical phase conjugation, iterative optimization, and transmission matrix measurement, have been developed to generate tight and intense optical delivery or high-resolution image of an optical object behind or within a scattering medium. The performance of these modulations, however, is far from satisfaction. Most recently, artificial intelligence has brought new inspirations to this field, providing exciting hopes to tackle the challenges by mapping the input and output optical patterns and building a neuron network that inherently links them. In this paper, we survey the developments to date on this topic and briefly discuss our views on how to harness machine learning (deep learning in particular) for further advancements in the field.

While propagating inside the strongly scattering biological tissue, photons lose their incident directions beyond one transport mean free path (TMFP, ~1 millimeter (mm)), which makes it challenging to achieve optical focusing or clear imaging deep inside tissue. By manipulating many degrees of the incident optical wavefront, the latest optical wavefront engineering (WFE) technology compensates the wavefront distortions caused by the scattering media and thus is toward breaking this physical limit, bringing bright perspective to many applications deep inside tissue, e.g., high resolution functional/molecular imaging, optical excitation (optogenetics) and optical tweezers. However, inside the dynamic turbid media such as the biological tissue, the wavefront distortion is a fast and continuously changing process whose decorrelation rate is on timescales from milliseconds (ms) to microseconds (
s), or even faster. This requires that the WFE technology should be capable of beating this rapid process. In this review, we discuss the major challenges faced by the WFE technology due to the fast decorrelation of dynamic turbid media such as living tissue when achieving light focusing/imaging and summarize the research progress achieved to date to overcome these challenges.

We observed a phenomenon that different scattering components have different decorrelation time. Based on decorrelation time difference, we proposed a method to image an object hidden behind a turbid medium in a reflection mode. In order to suppress the big disturbance caused by reflection and back scattering, two frames of speckles are recorded in sequence, and their difference is used for image reconstruction. Our method is immune to both medium motions and object movements.

By manipulating the phase map of a wavefront of light using a spatial light modulator, the scattered light can be sharply focused on a specific target. Several iterative optimization algorithms for obtaining the optimum phase map have been explored. However, there has not been a comparative study on the performance of these algorithms. In this paper, six optimization algorithms for wavefront shaping including continuous sequential, partitioning algorithm, transmission matrix estimation method, particle swarm optimization, genetic algorithm (GA), and simulated annealing (SA) are discussed and compared based on their e±ciency when introduced with various measurement noise levels.

Two-photon microscopy normally suffers from the scattering of the tissue in biological imaging. Multidither coherent optical adaptive technique (COAT) can correct the scattered wavefront in parallel. However, the determination of the corrective phases may not be completely accurate using conventional method, which undermines the performance of this technique. In this paper, we theoretically demonstrate a method that can obtain more accurate corrective phases by determining the phase values from the square root of the fluorescence signal. A numerical simulation model is established to study the performance of adaptive optics in two-photon microscopy by combining scalar diffraction theory with vector diffraction theory. The results show that the distortion of the wavefront can be corrected more thoroughly with our method in two-photon imaging. In our simulation, with the scattering from a 450-μm-thick mouse brain tissue, excitation focal spots with higher peak-to-background ratio (PBR) and images with higher contrast can be obtained. Hence, further enhancement of the multidither COAT correction performance in two-photon imaging can be expected.

Feedback-based wavefront shaping focuses light through scattering media by employing phase optimization algorithms. Genetic algorithms (GAs), inspired by the process of natural selection, are well suited for phase optimization in wavefront shaping problems. In 2012, Conkey et al. first introduced a GA into feedback-based wavefront shaping to find the optimum phase map. Since then, due to its superior performance in noisy environment, the GA has been widely adopted by lots of implementations. However, there have been limited studies discussing and optimizing the detailed procedures of the GA. To fill this blank, in this study, we performed a thorough study on the performance of the GA for focusing light through scattering media. Using numerical tools, we evaluated certain procedures that can be potentially improved and provided guidance on how to choose certain parameters appropriately. This study is beneficial in improving the performance of wavefront shaping systems with GAs.

Melanoma, characterized by high mortality, rapid development and accompanied with angiogenesis is the most typical malignant tumor in skin cancer. Hence, the detection of blood vessels is of much significance. The early vascular network has small scale. If we remove the tumor early and biopsy it, it will increase the spread of the cancer cells and infection and bleeding. In this case, we presented a new angiography method. A high-resolution OCT system for noninvasive angiographic imaging of early skin melanoma — Swept Source Optical Coherence Tomography Angiography (SS-OCTA) is proposed. With a high lateral resolution of 10 μm in vivo tomographic angiography, SS-OCTA is used to image and identify the morphology of the early tumor blood vessels. In addition, a control group experiment is conducted to observe the growth of melanoma in the process of rupture, malformation of micro-vessels. The results of the analysis and statistical test (P < 0:05) are statistically significant.

Changes of the blood vessels and collagen are associated with the development of abnormal cervical cells. Recently, optical coherence tomography and Mueller polarization images were used to provide information regarding the presence of collagen fibers in the cervical tissue. However, most of these methods need a lot of time for image recording and are expensive. In addition, the general survey on the absorption and distribution characteristics of collagen and blood in the cervical is still lacking. In this study, we developed a colposcopy combining cross-polarized image and image processing algorithm with an e±cient analytical model to map the distribution of blood and collagen in the uterine. For this system's proof of concept, we captured and processed the case of cervical ectopy and Nabothian cyst. The results show that the distribution of blood and collagen maps matched with anatomical and physiological when compared with Lugol's iodine images. This technology has some advantages, such as low cost, real time, and can replace the use of acetic acid or Lugol's iodine in the future.

Wavefront shaping (WFS) techniques have been used as a powerful tool to control light propagation in complex media, including multimode fibers. In this paper, we propose a new application of WFS for multimode fiber-based sensors. The use of a single multimode fiber alone, without any special fabrication, as a sensor based on the light intensity variations is not an easy task. The twist effect on multimode fiber is used as an example herein. Experimental results show that light intensity through the multimode fiber shows no direct relationship with the twist angle, but the correlation coe±cient (CC) of speckle patterns does. Moreover, if WFS is applied to transform the spatially seemingly random light pattern at the exit of the multimode fiber into an optical focus. The focal pattern correlation and intensity both can serve to gauge the twist angle, with doubled measurement range and allowance of using a fast point detector to provide the feedback. With further development, WFS may find potentials to facilitate the development of multimode fiber-based sensors in a variety of scenarios.