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.

Dynamic fluorescence diffuse optical tomography (FDOT) is important in drug deliver research. In this letter, we first image the metabolic processes of micelles indocyanine green throughout the whole body of a nude mouse using the full-angle FDOT system with line illumination (L-FDOT). The resolution of L-FDOT is evaluated using phantom experiment. Next, in vivo dynamic tomographic images (100 frames; approximately 170 min) of mouse liver and abdomen are shown and cross-validated by planar fluorescence reflectance imaging in vitro. Results provide evidence on applicability of the tomographic image whole-body biological activities in vivo on minute timescale (approximately 1.7 min) using L-FDOT.

Accurate small animal surface reconstruction is important for full angle non-contact fluorescence molecular tomography (FMT) systems. In this letter, an optimal surface reconstruction method for FMT is proposed. The proposed method uses a line search method to minimize the mismatch between the reconstructed three-dimensional (3D) surface and the projected object silhouette at different angles. The results show that the mean mismatches of the 3D surfaces generated on three live anesthetized mice are all less than two charge coupled device (CCD) pixels (0.154 mm). With the accurately reconstructed 3D surface, in-vivo FMT is also performed.