Transmissive-detected laser speckle imaging for blood flow monitoring in thick tissue

Blood flow velocity is an important parameter reflecting vascular function. Abnormal vascular function is closely related to the occurrence and development of many diseases, such as diabetes, arteriosclerosis, thrombosis and so on. Therefore, the monitoring of flow velocity is not only an important research target, but also an important clinical indicator.

Laser speckle contrast imaging (LSCI) is a wide-field, noninvasive imaging technique with high temporal and spatial resolution, which is based on the analysis of light signals after scattering and random interference, and therefore obtains the velocity information of scattering particles in biological tissues (e.g., red blood cells). It has been widely used in the research of vascular functions. However, the deep signals are hardly detectable for a conventional windowless model because it works on the reflective-detected mode; therefore the strength of static speckle in the upper layer is much greater than that of dynamic speckle signal in the deep targeted blood vessels, leading to a low signal-to-background ratio (SBR).

In a new paper published in Light Science & Application, Dan Zhu’s group from Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, China, have greatly improved the imaging ability of laser speckle imaging on thick tissue by changing the detection methods of laser speckle imaging. Using the transmission detection method, the dynamic speckle signals from the vascular layer become stronger than the static speckle information from the upper tissue layer, thus improving the SBR of thick-tissue blood flow detection.

In previous studies, conventional reflective-detected LSCI could obtain high-resolution images of blood flow distribution in experimental animals only when combined with “surgical windows” or “tissue optical clearing windows.” However, in the human experiment, the image resolution is extremely low because a “tissue window” cannot be performed. On the contrary, the authors of this paper used TR-LSCI to perform cutaneous/subcutaneous blood flow mapping and tracking in various mouse body parts, including the ear, hindlimb, back and paw, without any skin window. More importantly, TR-LSCI was capable of monitoring adult human blood flow changes in fingers or palms with individual-vessel resolution, and the imaging procedure didn’t need much laser irradiation (6 mJ/cm²), “which was much lower than that used in low-level-laser therapy,” the scientists said.

Using their system, the scientists studied the difference of the response between blood flow in deep tissue and perfusion in the superficial layer and found that “compared to the perfusion in the superficial layer, where there was almost microvasculature, blood flow in the deep larger vessels was more affected by pressure and recovered more slowly after pressure was released.”

Thanks to its noninvasiveness, low cost, and high temporal-spatial resolution, TR-LSCI holds great potential in the field of microcirculation research. These scientists envision the future applications for the technology:

“Our systematical in vivo results also suggested that TR-LSCI could perform blood flow mapping with promising resolution in thick tissue without the assistance of tissue windows, those conventional LSCI needs for the research of tumor vasculature, wound healing, therapeutic effect of thrombolytic drugs, photodynamic therapy of malformed blood vessels and so on,” they observed.

“The successful acquirement of blood flow signal in human hand implied that TR-LSCI might be further applied in other human body parts whose thickness is feasible for light to penetrate, such as ear, lip, toe, and instep etc. Thus, the development of TR-LSCI might accelerate the clinical research of microcirculation and related diseases, such as diabetic foot ulcer, rheumatoid arthritis and dermatitis,” they added.

In the future, the TR-LSCI can be further optimized by using longer wavelength laser to obtain greater imaging depth and quality, or by using algorithms to improve the quality of the final image. This low-cost, high-resolution and complete non-invasive technique holds great potential to be widely used in clinical applications.