New technology noninvasively monitors cerebral blood flow index and brain function in adult humans.

Diffuse optics (DO) is a light-based technique used to study the human brain, but it suffers from low brain specificity. Interferometric diffuse optics (iDO) promises to improve the quantitative accuracy and depth specificity of DO, and particularly, coherent light fluctuations (CLFs) arising from blood flow. iDO techniques have alternatively achieved either time-of-flight (TOF) discrimination or highly parallel detection, but not both at once. Here, we break this barrier with a single iDO instrument. Specifically, we show that rapid tuning of a temporally coherent laser during the sensor integration time increases the effective linewidth seen by a highly parallel interferometer. Using this concept to create a continuously variable and user-specified TOF filter, we demonstrate a solution to the canonical problem of DO, measuring optical properties. Then, with a deep TOF filter, we reduce scalp sensitivity of CLFs by 2.7 times at 1 cm source-collector separation. With this unique combination of desirable features, i.e., TOF-discrimination, spatial localization, and highly parallel CLF detection, we perform multiparametric imaging of light intensities and CLFs via the human forehead.

We present multi-exposure interferometric diffusing wave spectroscopy (MiDWS), which measures brain blood flow index (BFI) continuously and non-invasively. MiDWS employs interferometry to detect low light levels, probing the optical field autocorrelation indirectly by varying the sensor exposure time. Here MiDWS is compared with conventional interferometric diffusing wave spectroscopy and speckle contrast optical spectroscopy in phantoms. Notably, the MiDWS approach enables the use of low frame rate, two-dimensional complementary metal–oxide semiconductor cameras in a short exposure time regime, where detector noise greatly exceeds the sample photon count. Finally, we show that MiDWS can monitor the BFI simultaneously at two source-collector separations (1 and 3 cm) on the adult human head on a single camera, enabling the use of superficial signal regression techniques to improve brain specificity.

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.

Oxygen is a critical component of the microenvironment required for supporting cellular activities. Tissue oxygen alteration is a vital sign for the assessment of cardiovascular diseases such as heart failure, septic shock, and cerebral hypoxia.^{1 – 3} Tissue oxygenation level reflects the balance between oxygen supply and consumption.⁴ Blood flow affects the efficiency of oxygen delivery to and waste removal from tissues. Blood flow is highly sensitive to pathophysiological alterations,⁵ thus could be an indicator for the detection of diseases that are associated with tissue ischemia such as peripheral artery disease, cerebral vascular disease, neurological disorders, and cancers.^{6 – 11} There are also growing interests in simultaneous measurements of blood flow and oxygenation alterations as more comprehensive biomarkers for tissue health/injury than one single parameter alone.^{12 – 14} Furthermore, a combination of tissue blood flow and oxygenation allows to estimate the metabolic rate of tissue oxygen consumption,^12,15 another important functional parameter highly associated with tissue pathology.

Diffuse optics seeks to characterize and image biological tissue with multiply scattered near-infrared light. From the inception of this scientific field, the potential of near-infrared light to probe brain physiology was recognized.¹ Diffuse optics is divided according to the measured signals, with light absorption and scattering for near-infrared spectroscopy (NIRS)² or coherent light fluctuations (CLFs) for diffuse correlation spectroscopy (DCS),³ and according to detection methodology, with continuous wave (CW),⁴ time domain (TD),⁵ frequency domain (FD),⁶ or spatial frequency domain.⁷ CW NIRS was first demonstrated around 45 years ago (Fig. 1)¹ and remains widely used for functional brain measurements.^16,17 In the 1980s, researchers recognized the inherent ambiguities of CW measurements and explored novel dimensions, by resolving tissue responses in the TD¹⁸ and FD.¹⁹ These measurements are now considered to be quantitative benchmarks to disambiguate absorption and scattering and to achieve depth sensitivity.