Author:       2014-05-09

Laser speckle contrast imaging (LSCI), a full-field optical imaging technique, can provide a two-dimensional map of blood flow at high spatiotemporal resolution. It has played

an important role in studying cerebral blood flow, mesentery microcirculation, and angiogenesis in the chick chorioallantoic membrane, but is still limited to transparenttissues. This is because the static speckle caused by turbid tissue conceals dynamic information on blood flow and reduces the imaging resolution and contrast of LSCI.To overcome this problem, window models have been developed through surgical operation, but causes side effects. The tissue optical clearing technique may be an available way, but the most researches are limited to in vitro.

During the past years, Prof. Dan Zhu’s group is focusing on developing in vivo tissue optical clearing. After topical treated the skin with their optical clearing agents, the skin will become transparent within minutes, which makes the LSCI imaging the subcutaneous blood flow with high resolution and contrast. In addition, they first invented a skull optical clearing method, which is able to imaging the cortical blood flow without removing skull or thinned skull. The above researches are attracted more attention. In 2012, Prof. Dan Zhu was invited to write a review for Laser & Photonics Reviewers (Dan Zhu, Kirill Larin, Qingming Luo, Valery Tuchin, Recent progress in tissue optical clearing, Laser & Photonics Reviewers, 7(5), 732-757, 2013, (IF=7.976)). Last year, she was invited to write another review to report her group’s progress in tissue optical clearing window for blood flow monitoring using LSCI. The LSCI is an innovative technique developed by his colleagues, Prof. Qingming Luo and Pengcheng Li, which is paly significant role in cortical blood flow, and vascular disease diagnosis and evaluation of curative effect. However, the turbid tissues reduce the resolution and contrast, Prof. Dan Zhu’s group developed skin/skull optical clearing methods resolved the problem. This paper gives an overview of recent progress in the use of TOC for vascular visualization with LSCI. First, the principle of TOC-induced improvement of LSCI and a quantitative analysis method for evaluating the improvement are described briefly. Second, the paper introduces transparent windows, including various skin windows and a cranial window, that permit LSCI to monitor dermal or cortical blood flow, respectively, with high resolution and contrast. Third, preliminary investigations of the safety of TOC demonstrate that the transparent skin window is switchable, which enables LSCI to repeatedly image blood flow. However, research on in vivo TOC is currently less advanced than that on in vitro TOC. Future work should focus on developing a highly effective, safe method and extending its applications.

 Fig. 1 Typical visual photographs (first and third rows) and corresponding laser speckle temporal contrast images (second and fourth rows) of in vivo rat skin before and after treatment with PT and saline

Fig. 2 (Top row) White-light images, (middle row) laser speckle temporal contrast images, and profiles of speckle temporal contrast values along horizontal line for in vivo mouse skull in initial state, after SOCS treatment of skull, and without skull. Numbers 1–4 indicate cortical blood vessels of interest. Arrows indicate locations of vessels 1 and 3

 

This work was supported in part by the National Major Scientific Research Program of China under Grant 2011CB910401, in part by the Science Fund for Creative Research Group of

China under Grant 61121004, in part by the National Nature Science Foundation of China under Grants 81171376, 91232710, 812111313, and in part by the Research Fund for the

Doctoral Program of Higher Education of China (No. 20110142110073).

Jing Wang, Yang Zhang, Pengcheng Li, Qingming Luo, Dan Zhu*, Review: Tissue Optical Clearing Window for Blood Flow Monitoring Using Laser Speckle Contrast Imaging, IEEE Journal

of Selected Topics in Quantum Electronics, 20(2): 6801112, 2014(Invited��/p>

Separately, Prof. Dan Zhu’s group also reported an original paper. They used a molecular dynamics simulation and in vitro experiments to evaluate the optical clearing efficacy of three sugars, fructose, glucose, and ribose. The simulated results revealed that fructose and ribose have the highest and lowest optical clearing potential, respectively, according to their propensity to form hydrogen bonds and bridges. The resolutions through skin samples after 24 min of immersion in fructose, glucose, or ribose solutions were quantitatively calculated using a USAF target and reached 14.3±1.2μm, 27.3±2.4μm, and 39.6±4.1μm, respectively, which are in accordance with the theoretical prediction. Unfortunately, topical fructose treatment of in vivo rat skin could not induce excellent optical clearing. Thus, a chemical penetration enhancer was used for in vivo studies. A comparison of laser speckle imaging of dermal blood flow after topical treatment with fructose, a penetration enhancer, and a mixture of the two to rat skin in vivo demonstrated that the mixture causes the largest increase in the resolution and contrast. This study, from an MD simulation to experiments, not only finds an optimal optical clearing agent, but also provides a way to develop innovative skin OCAs. It is hoped that the developed FPT will play important roles in optical-based diagnosis and treatment.

Fig. 3 Typical white-light images (top row) and laser speckle temporal contrast images (bottom row) of rat skinin vivobefore and after topical application of (a) fructose, (b) the mixture of PEG-400 and thiazone, and (c) the mixture of fructose, PEG-400 and thiazone.
 

This work was supported in part by the Science Fund for Creative Research Group of China under Grant 61121004, in part by the National Nature Science Foundation of China under Grants 81171376, 91232710, 812111313, and in part by the Research Fund for the Doctoral Program of Higher Education of China (No. 20110142110073).
 

Jing Wang, Ning Ma, Rui Shi, Yang Zhang, Tingting Yu and Dan Zhu*, Sugar-induced Skin Optical Clearing: From Molecular Dynamics Simulation to Experimental Demonstration, IEEEJournal of Selected Topics in Quantum Electronics, 20(2): 7101007, 2014