Human eye imaging

Optical coherence tomography (OCT) is an established method for retinal imaging. OCT provides high-resolution cross-sectional imaging (XZ images like in ultrasound) of the human retina at high speeds. Hence, OCT devices are used regularly to examine human eyes, even at the International Space Station. Classic OCT, however, does not provide high-resolution en face images (XY like in microscopy) of the outer retinal layers due to eye aberrations and the fundamental tradeoff between imaging depth and transverse resolution.

STOC imaging

To solve this problem, we developed a new way of controlling the optical phase called STOC (Spatio-Temporal Optical Coherence). In STOC imaging, we have extended FD-FF-OCT with a spatial phase modulator (SPM). The SPM dynamically modulates the phase of incident light by generating time-varying transverse mode (TEM) patterns. This is accomplished using active modulators or long multimode optical fiber. The resulting signals are processed and averaged to produce noise-free volume images of the sample. Application of STOC to Fourier-domain full-field optical coherence tomography (FD-FF-OCT) is called STOC tomography (STOC-T) or STOC imaging. It enables obtaining in vivo high-resolution, volumetric images of human skin, retina, and cornea at high speeds. A single volume is recorded in less than 10 milliseconds. For comparison, the eye blink lasts 10-40 times longer!

Brain sensing

Diffuse optics offers a noninvasive portable approach for examining biological tissues, including the human brain, in vivo. Near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) are the primary diffuse optical modalities. In both approaches, the light illuminates the tissue, and diffusively scattered photons are collected at some distance from the emitter (typically 2-3 cm). NIRS uses the detected signal to estimate optical properties (absorption and scattering), while DCS quantifies the blood flow from temporal changes of the remitted light intensity. Although these methods have been applied to monitor brain oxygenation and blood flow, their most widely adopted versions rely on continuous wavelength (CW) lasers, precluding absolute measures of the optical and dynamical tissue properties.

I developed interferometric near-infrared spectroscopy (iNIRS) during my post-doc at UC Davis to tackle this issue. The iNIRS approach uses interferometry based on a temporally coherent tunable laser to effectively combine NRIS and DCS into a single modality. Specifically, iNIRS supplements the conventional NIRS configuration with the tunable light source and the reference arm. The field remitted from the sample is recombined with the reference field. The beat frequency of the signal encodes photon path lengths (or times-of-flight). Short paths produce lower beat frequencies than long paths. Consequently, we can achieve the photon time-of-flight distribution by inverse-Fourier transforming the recorded signal.

However, iNIRS provides much more information through the reemitted optical field's two-dimensional autocorrelation function (ACF). In iNIRS, the ACF is measured as a function of time lag with TOF resolution. This two-dimensional measurement encodes information about the sample's absorption, scattering, and blood flow index (BFI). iNIRS was validated in liquid phantoms, mouse brain, and human brain in vivo. However, the original iNIRS (as DCS and TD-DCS) uses single-mode fibers for light collection, requiring integration times of 0.5-1 second. This time frame is too long, precluding the ability to detect rapid blood flow changes in the human brain that could be linked to neural signals.