Research

Our lab has interdisciplinary biomedical engineering research programs focusing on the development of novel optical imaging methods for biomedical applications, including functional brain imaging, early cancer detection, cancer therapy monitoring and tissue engineering. Our optical imaging technologies include optical coherence tomography (OCT), multi-photon microscopy (MPM), fluorescence molecular imaging (FMI), fluorescence laminar optical tomography (FLOT), and endoscopy.

Technology Development

Early cancer detection

(A) 3D OCT image (X×Y×Z=5×3×0.5 mm3). (B) 3D FLOT image (X×Y×Z=3.8×3.3×2 mm3). (C) 3D OCT and FLOT fused image. (D) Cross-sectional OCT images. (E) Cross-sectional FLOT images. (F) 2D OCT and FLOT fused image. (G) Corresponding histology

We integrated OCT with depth-resolved fluorescence laminar optical tomography (FLOT), which enables mesoscopic (mm-scale) morphological and molecular tomography. The hybrid OCT/FLOT imaging holds great promise as a powerful tool for the diagnosis of early cancers.

Cancer Therapy Monitoring

(A) 3D OCT tumor image. The three-dimensional tumor volume is indicated by the blue dashed margin. (B) Cross-sectional OCT images from the green dashed line in Fig. 1(A). (C) Fused OCT/FLOT image (red-orange indicates the distribution of cancer drug). (D) Cross-sectional fused OCT/FLOT image. (E) Representative 3D FLOT images of the micro-distribution of drug in tumor at different time points during and after PIT Treatment (red-orange) superimposed with 3D tumor microstructure and corresponding 3D blood vessel on the tumor surface. PIT treatment starts at 0 min and lasts for 20 min as indicated by the red dashed line. Scale bar 1 mm.

We applied a multi-modal optical imaging approach including high-resolution optical coherence tomography (OCT) and high-sensitivity fluorescence laminar optical tomography (FLOT), to provide 3D tumor micro-structure and micro-distribution of mAb-IR700 in the tumor simultaneously during photo-immunotherapy (PIT) in situ and in vivo.

Deep Brain Functional Imaging

 

To access subcortical structures and image sensory-evoked neural activity, we designed a needle-based optical system using gradient-index (GRIN) rod lens. We performed voltage-sensitive dye imaging (VSDi) with GRIN rod lens to visualize neural activity evoked in the thalamic barreloids by deflection of whiskers in vivo.

3D Brain Functional Imaging in Mice Cortex

(A) Time-resolved FLOT. (B) 3D changes in fluorescence (ΔF/F(%), ordinate) in response to electrical stimulation reconstructed by FLOT system superimposed with OCT data. The two green rods in the 3D OCT image are the electrodes recorded by OCT and the orange ones are theFLOT-reconstructed changes in fluorescence (Δ F/F(%), ordinate) in response to electrical stimulation at different time points. (C) 3D changes in fluorescence(ΔF/F(%), ordinate) in response to the C2 whisker stimulation reconstructed by the FLOT system. (D) Coordinates of the strongest change in fluorescence (ΔF/F(%), ordinate) in response to the C2 whisker stimulation to study the signal trajectory.

We applied angled FLOT (aFLOT) to record 3D neural activities evoked in the whisker system of mice by deflection of a single whisker in vivo. The results show that it is possible to obtain 3D functional maps of the sensory periphery in the brain. This approach can be broadly applicable to functional imaging of other brain structures.

FLOT in Bone Tissue Engineering

It remains a challenge to image three-dimensional (3-D) structures and functions of the cell-seeded scaffold in mesoscopic scale (>2 ∼ 3mm). We utilized angled fluorescence laminar optical tomography (aFLOT), which allows depth-resolved molecular characterization of engineered tissues in 3-D to investigate cell viability, migration, and bone mineralization within bone tissue engineering scaffolds in situ.

OCT Probe for Surgical Guidance

 

(A) Schematic of the hand-held OCT needle imaging system; (B) hand-held part. (C) In vivo needle optical coherence tomography (OCT)-guided insertion in a piglet.

We developed a small hand-held optical coherence tomography (OCT) forward-imaging needle device for real-time epidural anesthesia surgery guidance and demonstrated its feasibility through exvivo and in vivo animal experiments. With tissue structures visualized and differentiated at the needle tip, OCT needle imaging device will enhance clinical outcomes with regards to complication rates, induced pain, and procedure failure when compared to standard practice.