High Sensitivity of T-Ray for Thrombus Sensing.

Atherosclerotic plaque rupture or erosion and subsequent development of platelet-containing thrombus formation is the fundamental cause of cardiovascular disease, which is the most common cause of death and disability worldwide. Here we show the high sensitivity of 200-270 GHz T-ray to distinguish thrombus formation at its early stage from uncoagulated blood. A clinical observational study was conducted to longitudinally monitor the T-ray absorption constant of ex-vivo human blood during the thrombus formation from 29 subjects. Compared with the control group (28 subjects) with uncoagulated blood samples, our analysis indicates the high sensitivity of 200-270 GHz T-Ray to detect thrombus with a low p-value < 10-5. Further analysis supports the significant role of platelet-activated thrombotic cascade, which modified the solvation dynamics of blood and occurred during the early coagulation stage, on the measured T-Ray absorption change. The ability to sense the thrombus formation at its early stage would hold promise for timely identification of patients at risk of various atherothrombotic disorders and save billions of lives.

In vivo sub-femtoliter resolution photoacoustic microscopy with higher frame rates.

Microscopy based on non-fluorescent absorption dye staining is widely used in various fields of biomedicine for 400 years. Unlike its fluorescent counterpart, non-fluorescent absorption microscopy lacks proper methodologies to realize its in vivo applications with a sub-femtoliter 3D resolution. Regardless of the most advanced high-resolution photoacoustic microscopy, sub-femtoliter spatial resolution is still unattainable, and the imaging speed is relatively slow. In this paper, based on the two-photon photoacoustic mechanism, we demonstrated a in vivo label free laser-scanning photoacoustic imaging modality featuring high frame rates and sub-femtoliter 3D resolution simultaneously, which stands as a perfect solution to 3D high resolution non-fluorescent absorption microscopy. Furthermore, we first demonstrated in vivo label-free two-photon acoustic microscopy on the observation of non-fluorescent melanin distribution within mouse skin.

Near-field sub-THz transmission-type image system for vessel imaging in-vivo.

A THz near-field transmission imaging system was successfully demonstrated to image the vessels inside the ears of nude mice in vivo. Wave-guided illumination and near-field scanning detection with a sub-wavelength aperture were applied. An operating frequency of 340 GHz was chosen to achieve a higher penetration depth in tissues with a reasonable signal-to-noise ratio. The near-field pattern of the power transmittance through the vessel was also numerically simulated and showed good correspondence to the measured results. The capability of the system for long-term monitoring in vivo was also demonstrated.

Pilot clinical study to investigate the human whole blood spectrum characteristics in the sub-THz region.

We have conducted a pilot clinical study to not only investigate the sub-THz spectra of ex-vivo fresh human whole blood of 28 patients following 8-hours fasting guideline, but also to find out the critical blood ingredients of which the concentration dominantly affects those sub-THz spectra. A great difference between the sub-THz absorption properties of human blood among different people was observed, while the difference can be up to ~15% of the averaged absorption coefficient of the 28 samples. Our pilot clinical study indicates that triglycerides and the number of red blood cells were two dominant factors to have significant negative correlation to the sub-THz absorption coefficients.

High-depth-resolution 3-dimensional radar-imaging system based on a few-cycle W-band photonic millimeter-wave pulse generator.

We demonstrate that a near-single-cycle photonic millimeter-wave short-pulse generator at W-band is capable to provide high spatial resolution three-dimensional (3-D) radar imaging. A preliminary study indicates that 3-D radar images with a state-of-the-art ranging resolution of around 1.2 cm at the W-band can be achieved.

Terahertz polarization-sensitive rectangular pipe waveguides.

We propose square and rectangular pipe waveguides for low-loss THz waveguiding and polarization control. Different from common circular-symmetric THz fibers and waveguides, the proposed rectangular pipe waveguides successfully remove the transmission degeneracy of two orthogonal polarizations and possess polarization sensitivity to the guided THz waves. By measuring the attenuation spectra, we find that the polarization sensitivity depends on the structure of the pipe waveguides. With butt coupling method, it is easy to combine circular pipe waveguides and the rectangular ones.

High-sensitivity in vivo THz transmission imaging of early human breast cancer in a subcutaneous xenograft mouse model.

We performed in vivo THz transmission imaging study on a subcutaneous xenograft mouse model for early human breast cancer detection. With a THz-fiber-scanning transmission imaging system, we continuously monitored the growth of human breast cancer in mice. Our in vivo study not only indicates that THz transmission imaging can distinguish cancer from the surrounding fatty tissue, but also with a high sensitivity. Our in vivo study on the subcutaneous xenograft mouse model will encourage broad and further investigations for future early cancer screening by using THz imaging system.

Performance of THz fiber-scanning near-field microscopy to diagnose breast tumors.

Based on tissues from 20 female patients (mean age: 53 years; rang: 36-72 years), we examine the performance of a room-temperature-operated terahertz (THz) fiber-scanning near-field microscopy to diagnose slices of breast tissues. The specimens were frozen sliced and then measured in a thawed state without dehydration. We performed the imaging at 320 GHz. Our study indicates that images acquired in the THz transmission-illumination mode can all clearly distinguish breast tumor tissues from normal tissues without H&E staining. Due to its capability to perform quantitative analysis and to allow follow-up staining and traditional pathohistological analysis, our study indicates great potential of the THz fiber-scanning near-field microscopy for future automation, which is critical for fast and complete pre-screening on breast tumor pathological examinations and for assisting quick definition of the tumor margins during the surgical procedure such as breast-conserving surgery.

Terahertz pipe-waveguide-based directional couplers.

We experimentally demonstrate a terahertz (THz) leaky mode directional coupler for future THz applications. The proposed directional coupler comprises two square pipe waveguides. The coupling efficiency is investigated for different frequencies, polarizations, and core sizes. Rectangular pipe-waveguide-based directional couplers and the issue of insertion loss are also discussed. It is found that the THz directional coupler works most efficiently in the minimal-attenuation wavelength regime.

Fiber-based swept-source terahertz radar.

We demonstrate an all-terahertz swept-source imaging radar operated at room temperature by using terahertz fibers for radiation delivery and with a terahertz-fiber directional coupler acting as a Michelson interferometer. By taking advantage of the high water reflection contrast in the low terahertz regime and by electrically sweeping at a high speed a terahertz source combined with a fast rotating mirror, we obtained the living object's distance information with a high image frame rate. Our experiment showed that this fiber-based swept-source terahertz radar could be used in real time to locate concealed moving live objects with high stability.