Noncontact Speckle Contrast Diffuse Correlation Tomography of Blood Flow Distributions in Tissues with Arbitrary Geometries

A noncontact electron multiplying charge-coupled-device (EMCCD)-based speckle contrast diffuse correlation tomography (scDCT) technology has been recently developed in our laboratory, allowing for noninvasive three-dimensional measurement of tissue blood flow distributions. One major remaining constraint in the scDCT is the assumption of a semi-infinite tissue volume with a flat surface, which affects the image reconstruction accuracy for tissues with irregular geometries. An advanced photometric stereo technique (PST) was integrated into the scDCT system to obtain the surface geometry in real time for image reconstruction. Computer simulations demonstrated that a priori knowledge of tissue surface geometry is crucial for precisely reconstructing the anomaly with blood flow contrast. Importantly, the innovative integration design with one single-EMCCD camera for both PST and scDCT data collection obviates the need for offline alignment of sources and detectors on the tissue boundary. The in vivo imaging capability of the updated scDCT is demonstrated by imaging dynamic changes in forearm blood flow distribution during a cuff-occlusion procedure. The feasibility and safety in clinical use are evidenced by intraoperative imaging of mastectomy skin flaps and comparison with fluorescence angiography

Low-Cost Compact Diffuse Speckle Contrast Flowmeter Using Small Laser Diode and Bare Charge-Coupled-Device

We report a low-cost compact diffuse speckle contrast flowmeter (DSCF) consisting of a small laser diode and a bare charge-coupled-device (CCD) chip, which can be used for contact measurements of blood flow variations in relatively deep tissues (up to ∼8  mm). Measurements of large flow variations by the contact DSCF probe are compared to a noncontact CCD-based diffuse speckle contrast spectroscopy and a standard contact diffuse correlation spectroscopy in tissue phantoms and a human forearm. Bland–Altman analysis shows no significant bias with good limits of agreement among these measurements: 96.5% ± 2.2% (94.4% to 100.0%) in phantom experiments and 92.8% in the forearm test. The relatively lower limit of agreement observed in the in vivo measurements (92.8%) is likely due to heterogeneous reactive responses of blood flow in different regions/volumes of the forearm tissues measured by different probes. The low-cost compact DSCF device holds great potential to be broadly used for continuous and longitudinal monitoring of blood flow alterations in ischemic/hypoxic tissues, which are usually associated with various vascular diseases

Time-resolved laser speckle contrast imaging (TR-LSCI) of cerebral blood flow

To address many of the deficiencies in optical neuroimaging technologies such as poor spatial resolution, time-consuming reconstruction, low penetration depth, and contact-based measurement, a novel, noncontact, time-resolved laser speckle contrast imaging (TR-LSCI) technique has been developed for continuous, fast, and high-resolution 2D mapping of cerebral blood flow (CBF) at different depths of the head. TR-LSCI illuminates the head with picosecond-pulsed, coherent, widefield near-infrared light and synchronizes a newly developed, high-resolution, gated single-photon avalanche diode camera (SwissSPAD2) to capture CBF maps at different depths. By selectively collecting diffuse photons with longer pathlengths through the head, TR-LSCI reduces partial volume artifacts from the overlying tissues, thus improving the accuracy of CBF measurement in the deep brain. CBF map reconstruction was dramatically expedited by incorporating highly parallelized computation. The performance of TR-LSCI was evaluated using head-simulating phantoms with known properties and in-vivo rodents with varied hemodynamic challenges to the brain. Results from these pilot studies demonstrated that TR-LSCI enabled mapping CBF variations at different depths with a sampling rate of up to 1 Hz and spatial resolutions ranging from tens of micrometers on the head surface to 1-2 millimeters in the deep brain. With additional improvements and validation in larger populations against established methods, we anticipate offering a noncontact, fast, high-resolution, portable, and affordable brain imager for fundamental neuroscience research in animals and for translational studies in humans.Comment: 22 pages, 7 figures, 4 table

Noncontact Multiscale Diffuse Optical Imaging of Deep Tissue Hemodynamics in Animals and Humans

Blood flow (BF) impacts the delivery of oxygen and nutrients to tissues and the removal of metabolic byproducts from tissues. Imaging of BF distributions helps characterize many diseases associated with tissue hypoxia/ischemia. The purpose of this study was to develop and validate a novel, noninvasive, noncontact, high-density camera-based speckle contrast diffuse correlation tomography (scDCT) device for use in both animal and human studies. The scDCT uses a galvo-mirror to remotely deliver the focused point near-infrared light to source positions and a sensitive 2D camera to quantify spatial diffuse speckle fluctuations, resulting from the movement of red blood cells in deep tissue (i.e., BF). The scDCT provides many advanced unique features over other competitive technologies, which may impact basic neuroscience research and clinical applications. These features include a fully noncontact system, quick data acquisition, adjustable source-detector patterns/density, flexible field of view, and cost-effective instrument. One remaining limitation in the scDCT prototype is the assumption of a semi-infinite tissue volume with a flat surface (i.e., slab). This assumption affects image reconstruction accuracy for tissues with irregular geometries. A photometric stereo technique (PST) was integrated into the scDCT system to acquire subject-specific tissue surface geometry for image reconstruction. Innovative use of one single camera for both PST and scDCT data collections obviated the need for complex alignment of sources and detectors on the tissue boundary. The performance of the integrated scDCT system was evaluated using computer simulations and by imaging BF variations in human forearms during artery cuff occlusion on upper arms. The clinical safety and feasibility were demonstrated by intraoperative imaging of BF distributions in mastectomy skin flaps. Eleven (11) patients undergoing mastectomy and breast reconstruction were imaged by a fluorescence angiography system (SPY-PHI, Novadaq) after the injection of indocyanine green (ICG). Because the ischemic areas have irregular shapes, an innovative contour-based algorithm was used to compare 3D images of blood flow and 2D maps of ICG perfusion. Significant correlations were observed between the two measurements around the ischemic areas, suggesting that scDCT provides vital information for intraoperative assessment of mastectomy skin flaps. Compared to SPY-PHI, our scDCT is fully noninvasive (dye-free), time-independent, and provides both 2D and 3D images of BF distributions. Furthermore, scDCT system was downscaled and optimized for 2D/3D imaging of cerebral blood flow (CBF) distributions in small rats through intact scalp and skull. The scDCT was used to continuously image global CBF increases during 10% CO2 inhalations (n = 9) and regional CBF decreases across two hemispheres during sequential ipsilateral and bilateral common carotid artery ligations (n = 8). The longitudinal imaging capability was demonstrated over a recovery period of 14 days after an acute stroke. These pilot studies demonstrate the capability of the innovative scDCT for imaging of BF distributions in tissues/organs with different sizes and irregular geometries. After further optimization and validation in large populations, the scDCT is expected to provide vital information for the diagnosis and management of vulnerable, ischemic, and hypoxic tissues