First introduced in the 1980s, laser speckle contrast imaging is a powerful tool for full-field imaging of blood flow. Recently laser speckle contrast imaging has gained increased attention, in part due to its rapid adoption for blood flow studies in the brain. We review the underlying physics of speckle contrast imaging and discuss recent developments to improve the quantitative accuracy of blood flow measures. We also review applications of laser speckle contrast imaging in neuroscience, dermatology and ophthalmology.

Laser Speckle Contrast Imaging (LSCI) is a minimally invasive full field optical technique used to generate blood flow maps with high spatial and temporal resolution. The lack of quantitative accuracy and the inability to predict flows in the presence of static scatterers such as an intact or thinned skull have been the primary limitation of LSCI. We present a new Multi-Exposure Speckle Imaging (MESI) instrument that has potential to obtain quantitative baseline flow measures. We show that the MESI instrument extends the range over which relative flow measurements are linear. We also present a new speckle model which can discriminate flows in the presence of static scatters. We show that in the presence of static scatterers the new model used along with the new MESI instrument can predict correlation times of flow consistently to within 10% of the value without static scatterers compared to an average deviation of more than 100% from the value without static scatterers using traditional LSCI. We also show that the new speckle model used with the MESI instrument can maintain the linearity of relative flow measurements in the presence of static scatterers.

Gold nanoshells (dielectric silica core/gold shell) are a novel class of hybrid metal nanoparticles whose unique optical properties have spawned new applications including more sensitive molecular assays and cancer therapy. We report a new photo-physical property of nanoshells (NS) whereby these particles glow brightly when excited by near-infrared light. We characterized the luminescence brightness of NS, comparing to that of gold nanorods (NR) and fluorescent beads (FB). We find that NS are as bright as NR and 140 times brighter than FB. To demonstrate the potential application of this bright two-photon-induced photoluminescence (TPIP) signal for biological imaging, we imaged the 3D distribution of gold nanoshells targeted to murine tumors.

Monitoring cerebral blood flow (CBF) during surgery is important during a variety of surgical procedures. In procedures such as clipping of aneurysms or vessel bypass, CBF measurements can help assess if blood flow has returned to presurgical baseline levels. In other procedures such as tumor resections, CBF measurements can help assess postsurgical tissue viability. CBF measures can also be used to identify motor, sensory, and speech activation centers in the cortex in procedures that require functional localization. Although the importance of imaging CBF during surgery is well known, there are not many techniques that can produce real-time CBF images with minimum interference to the surgery. For this reason, in vivo measurements of blood flow during surgeries have been underutilized as a surgical tool.